bluuebunny/crossref_metadata_2025 huggingface dataset:
pH‐Dependent Interactions between Keggin Heteropolyanions in Dilute Solutions
Authors: Antonio Mark R. , Bera Mrinal K.
Published: December 2018

Keggin phosphotungstate heteropolyanions (HPA), PW12O403–, are known to interact via short‐range attraction and long‐range repulsion (SALR) at moderate and high solution concentrations and low‐pH (pH = 1). These interactions were identified through the observation of structure factor peaks in small‐angle X‐ray scattering (SAXS) data reported previously (J. Phys. Chem. C 2016, 120, 1317). Here we describe the interactions between the same heteropolyanions with extremely low concentrations at low (pH = 0) and high pH (pH = 4.7) conditions. The solution chemistry of Keggin heteropolyanions at these two pH values provides a unique way to change the charge of the cluster anions without changing the structure (from the perspective of SAXS) and, at the same time, changing the hydrogen bonding interactions. The structure factors obtained from concentration dependent SAXS data reveal that the change in pH changes the nature of SALR interactions, consistent with the presence of the plenary PW12O403− anion at pH = 0 and the monovacant lacunary PW11O397– anion at pH = 4.7. At the low pH condition, the attractive interactions dominate to provide a peak near Q = 0 Å−1 momentum transfer in the structure factors, whereas at pH = 4.7 the repulsive interactions dominate, thereby eliminating the peak near Q = 0 Å−1. The experimental results presented here are in agreement with the recent liquid state theory and computer simulation predictions on SALR interactions.
Salicylic acid‐enhanced biosynthesis of pharmacologically important lignans and neo lignans in cell suspension culture of Linum ussitatsimum L
Authors: Nadeem Muhammad , Ahmad Waqar , Zahir Adnan , Hano Christophe , Abbasi Bilal Haider
Published: December 2018

Linum usitatsimum L. (flax) is a perennial herb with magnitude of medicinal and commercial applications. In the present study, we investigated the effects of salicylic acid (SA) on biosynthesis of lignans (secoisolariciresinol diglucoside (SDG) and lariciresinol diglucoside (LDG)) and neolignans (dehydrodiconiferyl alcohol glucoside (DCG) and guaiacylglycerol‐β‐coniferyl alcohol ether glucoside (GGCG)) in cell cultures of flax. Moderate concentration of SA (50 μM) enhanced biomass accumulation (10.98 g/L dry weight (DW)), total phenolic content (37.81 mg/g DW), and antioxidant potential (87.23%) to two‐fold than their respective controls after 72 h of exposure. However, higher levels of total flavonoid content (5.32 mg/g DW) were noted after 48 h of exposure to 50 μM of SA. HPLC analyses revealed that 50 μM SA, significantly enhanced biosynthesis of SDG (7.95 mg/g DW), LDG (7.52 mg/g DW), DCG (54.90 mg/g DW), and GGCG (16.78 mg/g DW), which was almost 2.7, 1.8, 3.88, and 3.98 fold higher than their respective controls after 72 h of exposure time, respectively. These results indicated that moderate concentrations of SA had significant effects on biosynthesis and productivity of lignans and neolignans in cell culture of L. usitatissimum.
Dry Reforming of Methane in DBD Plasma over Ni‐Based Catalysts: Influence of Process Conditions and Support on Performance and Durability
Authors: Ray Debjyoti , Nepak Devadutta , Janampelli Sagar , Goshal Partha , Subrahmanyam Ch.
Published: December 2018

The conversion of greenhouse gases, H2 and CO selectivity, H2/CO ratio, and carbon formation in the dry reforming reaction over Ni‐supported ZSM‐5, Al2O3, and TiO2 are tested under thermal, plasma, and plasma–thermal conditions. It is observed that the dielectric nature, specific surface area, and acid‐base properties of the support influence the performance during the DRM reaction. Typical results indicate that the best activity and syngas yield are achieved with 15Ni/Al2O3 under plasma conditions, possibly due to the high dielectric constant and surface area of Al2O3 and nanosize of Ni. In the thermal condition, the highest conversion of 73% and 68% for CH4 and CO2, respectively, is achieved over 15Ni/ZSM‐5 at 500 °C. Plasma‐assisted thermal conditions provide the highest conversion due to the activation of reactants and their partial conversion in the plasma zone before entering into the catalytic zone. The plasma‐assisted thermocatalytic conversions of CH4 and CO2 reach the best values of 76% and 71%, respectively, on 15Ni/ZSM‐5. Under the same conditions, 68% and 65% conversion of CH4 and CO2, respectively, is achieved with 15Ni/Al2O3 where the selectivity for H2 and CO is 45% and 58%, respectively.
Experiment study of the effect of salt on the stability of solar ponds
Authors: Ines Mahfoudh , Jomâa Safi Mohamed
Published: December 2018

The sun is the largest source of renewable energy and this energy is abundantly available in all part of the earth. One way to trap solar energy is through the use of salt‐gradient solar ponds (SGSP). Collecting and storing of energy for this device is in one system, so the heat in summer can be utilized in winter. A typical SGSP consists of a pond containing three density stratified layers. The stability duration and the efficiency of a SGSP depend closely on the self‐maintenance of the NCZ layer, which itself depends on the type of the used salt. This article reviews nonconvective solar ponds, the problems encountered in their operations and the effect of the used salts. Three salts: NaCl, MgCl, and CaCl2 were tested in a laboratory set‐up under different operating conditions. Temperature and concentration gradients were developed by heating the pond from the bottom. The results showed that MgCl and CaCl2 stratification remains stable until the temperature reaches around 70 °C while NaCl layers were mixed at 55 °C. © 2018 American Institute of Chemical Engineers Environ Prog, 38: 699–705, 2019
In‐plane–out‐of‐plane non‐linear model of masonry infills in the seismic analysis of r.c.‐framed buildings
Authors: Mazza Fabio
Published: December 2018

The out‐of‐plane (OOP) behaviour of masonry infills (MIs), inserted in reinforced concrete (r.c.)–framed buildings, is recognized as one of the most important failure modes of this nonstructural element during an earthquake, which may be a consequence of simultaneous or prior in‐plane (IP) damage. A five‐element macro‐model, with four diagonal OOP non‐linear beams and one horizontal IP non‐linear truss, with an equivalent mass of the infill panel divided between two central nodes, takes into account the IP and OOP failure modes occurring in the event of seismic loading. Pivot hysteretic models predict the non‐linear IP and OOP force‐displacement laws of the infill panel, based on geometrical rules defining loading and unloading branches. Firstly, a calibration of the proposed IP‐OOP interaction model of MIs is carried out considering full‐scale experimental results of traditional masonry typologies. Each specimen is initially subjected to in‐plane quasi‐static cyclic loading, until a maximum drift is reached, and then one‐sided OOP cycles are imposed pushing in the horizontal direction and back to zero force. Then a numerical investigation considers masonry infills of an existing six‐storey r.c.‐framed building designed in compliance with a former Italian seismic code. To evaluate the interaction, the results of simultaneous IP and OOP cyclic tests on MIs at the top, intermediate, and lowest levels of the test structure are presented, assuming different displacement histories: (1) OOP loading faster than IP, at the sixth storey; (2) equal IP and OOP loading, at the third storey; (3) IP loading faster than OOP, at the first storey. Finally, attention is focused on the contribution of masonry infills to the IP and OOP energy dissipation of r.c.‐framed structures.
Semistatic hedging and pricing American floating strike lookback options
Authors: Chung San‐Lin , Huang Yi‐Ta , Shih Pai‐Ta , Wang Jr‐Yan
Published: December 2018

We price an American floating strike lookback option under the Black–Scholes model with a hypothetic static hedging portfolio (HSHP) composed of nontradable European options. Our approach is more efficient than the tree methods because recalculating the option prices is much quicker. Applying put–call duality to an HSHP yields a tradable semistatic hedging portfolio (SSHP). Numerical results indicate that an SSHP has better hedging performance than a delta‐hedged portfolio. Finally, we investigate the model risk for SSHP under a stochastic volatility assumption and find that the model risk is related to the correlation between asset price and volatility.
Geochemistry of siltstones of the Early Cretaceous Laiyang Group in Taolin area, Shandong Province, Eastern China: Implications for provenance, source weathering, palaeo‐environment, and tectonic setting
Authors: Zhang Zhenkai , Zhou Yaoqi , Zhou Tengfei , Yu Shanshan , He Yuanfang , Gao Feng
Published: December 2018

The depositional environment and tectonic setting of the newly identified Ri‐Qing‐Wei Basin are the focus of controversy. In order to solve these questions, the geochemical characteristics of siltstones from Laiyang Group in Taolin area are analysed in detail. The siltstones present similar contents of SiO2 and Al2O3 compared with upper continental crust (UCC) and post‐Archean Australian Shale (PAAS) and are classified as wacke on chemical classification plot of clastic rocks. The trace elements are characterized by the depletion of transition elements (Sc, V, Cr, Ni, and Cu). The chondrite‐normalized REE patterns exhibit the enrichment of LREE and depletion of HREE, as well as significant negative Eu anomalies. Relative high Index of Compositional Variability (ICV) values suggest the siltstones are compositionally immature and the sediments of first‐cycle. The low Chemical Index of Alteration (CIA) and Plagioclase Index of Alteration (PIA) values of the samples indicate the weak source weathering condition. Moreover, the characteristics of A‐CN‐K plot suggest K‐metasomatism occurred after burial. A series of palaeo‐environment indexes imply that the Laiyang Group were deposited in a reducing marine environment with hot and arid climate. Major‐ and trace‐based tectonic setting discriminant diagrams all indicate that the Ri‐Qing‐Wei Basin was formed in an active continental margin setting; this conclusion is also supported by the analysis of the coeval igneous rocks. Based on the investigations of the subduction of the Palaeo‐Pacific plate and the development of Cretaceous basins on the eastern Eurasia, we propose that Ri‐Qing‐Wei Basin was formed in response to the delamination of the North China Craton and the subduction of Izanagi plate.
Multidelay multiparametric arterial spin labeling perfusion MRI and mild cognitive impairment in early stage Parkinson's disease
Authors: Suo Xueling , Lei Du , Cheng Lan , Li Nannan , Zuo Panli , Wang Danny J. J. , Huang Xiaoqi , Lui Su , Kemp Graham J. , Peng Rong , Gong Qiyong
Published: December 2018

Mild cognitive impairment (MCI), a well‐defined nonmotor manifestation of Parkinson's disease (PD), greatly impairs functioning and quality of life. However, the contribution of cerebral perfusion, quantified by arterial spin labeling (ASL), to MCI in PD remains poorly understood. The selection of an optimal delay time is difficult for single‐delay ASL, a problem which is avoided by multidelay ASL. This study uses a multidelay multiparametric ASL to investigate cerebral perfusion including cerebral blood flow (CBF) and arterial transit time (ATT) in early stage PD patients exhibiting MCI using a voxel‐based brain analysis. Magnetic resonance imaging data were acquired on a 3.0 T system at rest in 39 early stage PD patients either with MCI (PD‐MCI, N = 22) or with normal cognition (PD‐N, N = 17), and 36 age‐ and gender‐matched healthy controls (HCs). CBF and ATT were compared among the three groups with SPM using analysis of variance followed by post hoc analyses to define regional differences and examine their relationship to clinical data. PD‐MCI showed prolonged ATT in right thalamus compared to both PD‐N and HC, and in right supramarginal gyrus compared to HC. PD‐N showed shorter ATT in left superior frontal cortex compared to HC. Prolonged ATT in right thalamus was negatively correlated with the category fluency test (p = .027, r = −0.495) in the PD‐MCI group. This study shows that ATT may be a more sensitive marker than CBF for the MCI, and highlights the potential role of thalamus and inferior parietal region for MCI in early stage PD.
Reply to Chen et al.: Parametric methods for cluster inference perform worse for two‐sided t‐tests
Authors: Eklund Anders , Knutsson Hans , Nichols Thomas E.
Published: December 2018

One‐sided t‐tests are commonly used in the neuroimaging field, but two‐sided tests should be the default unless a researcher has a strong reason for using a one‐sided test. Here we extend our previous work on cluster false positive rates, which used one‐sided tests, to two‐sided tests. Briefly, we found that parametric methods perform worse for two‐sided t‐tests, and that nonparametric methods perform equally well for one‐sided and two‐sided tests.
Oscillatory dynamics of cortical functional connections in semantic prediction
Authors: Mamashli Fahimeh , Khan Sheraz , Obleser Jonas , Friederici Angela D. , Maess Burkhard
Published: December 2018

An event related potential, known as the N400, has been particularly useful in investigating language processing as it serves as a neural index for semantic prediction. There are numerous studies on the functional segregation of N400 neural sources; however, the oscillatory dynamics of functional connections among the relevant sources has remained elusive. In this study we acquired magnetoencephalography data during a classic N400 paradigm, where the semantic predictability of a fixed target noun was manipulated in simple German sentences. We conducted inter‐regional functional connectivity (FC) and time–frequency analysis on known regions of the semantic network, encompassing bilateral temporal, and prefrontal cortices. Increased FC was found in less predicted (LP) nouns compared with highly predicted (HP) nouns in three connections: (a) right inferior frontal gyrus (IFG) and right middle temporal gyrus (MTG) from 0 to 300 ms mainly within the alpha band, (b) left lateral orbitofrontal (LOF) and right IFG around 400 ms within the beta band, and (c) left superior temporal gyrus (STG) and left LOF from 300 to 700 ms in the beta and low gamma bands. Furthermore, gamma spectral power (31–70 Hz) was stronger in HP nouns than in LP nouns in left anterior temporal cortices in earlier time windows (0–200 ms). Our findings support recent theories in language comprehension, suggesting fronto‐temporal top–down connections are mainly mediated through beta oscillations while gamma band frequencies are involved in matching between prediction and input.
From catechol‐tocopherol to catechol‐hydroquinone polyphenolic antioxidant hybrids
Authors: Viglianisi Caterina , Menichetti Stefano , Morelli Paola , Baschieri Andrea , Amorati Riccardo
Published: December 2018

Multidefence antioxidants represent a valuable solution for the protection against oxidative stress. From the planned synthesis of a catechol‐tocopherol hybrid, we isolated a catechol‐hydroquinone hybrid through a BBr3‐mediated benzochromene‐fluoren‐1‐ol transposition. The compound prepared showed a remarkable chain‐breaking antioxidant in the catechol portion, while the very sensitive hydroquinone moiety revealed to be an efficient generator of hydroperoxyl radicals.
Venous thromboembolism in head and neck surgery: Risk, outcome, and burden at the national level
Authors: Al‐Qurayshi Zaid , Walsh Jarrett , Rodrigo Bayon , Kandil Emad
Published: December 2018

Background

Venous thromboembolism (VTE) can complicate major surgeries. This study examines the risk and outcomes of VTE in patients who underwent head and neck surgeries.

Methods

Retrospective cross‐sectional analysis utilizing the Nationwide Readmissions Database (2010‐2014). Study population included adults (≥18 year) patients who underwent head and neck surgeries.

Results

A total 386 VTE patients and 116 450 controls included. VTE risk was 0.37%, postoperative mortality was 4.87%. Of VTE, 57.02% identified within the initial admission for surgery, while the rest required readmission within 90 days. VTE high‐risk surgeries included: major ear/skull base surgeries, major nose/paranasal sinuses surgeries, major mouth/tonsil surgeries, major salivary glands/ducts surgeries, major maxillofacial bones/mandible surgeries, and major and nonmajor pharynx and larynx surgeries (P < .05). Those same surgeries were also associated with a high risk of readmission (P < .05).

Conclusions

VTE is associated with a significant mortality risk. Surgeries that involve the pharynx and larynx have the highest risk of VTE and readmission.
Cutaneous malignant melanoma of the oral cavity following skin graft reconstruction: Case report
Authors: Mayo Zachary , Seyedin Steven , Marquardt Michael , Mohiuddin Imran , Milhem Mohammed , Liu Vincent , Pagedar Nitin , Anderson Carryn
Published: December 2018

Background

Malignant melanomas on skin graft recipient sites are rare, with few cases reported in the literature.

Methods

We present a case report of a patient with recurrent cutaneous melanoma in the grafted anterolateral thigh flap of the tongue.

Results

A patient underwent hemiglossectomy with free flap reconstruction for squamous cell carcinoma of the tongue. Five years later the patient was seen with a 1‐cm nodule and surrounding erythroplakia at the recipient site of the graft. Analysis revealed cutaneous malignant melanoma. Patient then related a remote history of a suspected skin melanoma of the donor leg that had been treated with excision, with unknown histology.

Conclusion

This may be the first reported case of a cutaneous malignant melanoma in the oral cavity following an anterolateral thigh free flap reconstruction, emphasizing the importance of obtaining a comprehensive history of skin cancers and closely inspecting the donor site prior to graft harvesting.
Synthesis and characterization of novel substituted thiophene derivatives and discovery of their carbonic anhydrase and acetylcholinesterase inhibition effects
Authors: Cetin Adnan , Türkan Fikret , Taslimi Parham , Gulçin İlhami
Published: December 2018

Novel substituted thiophene derivatives (1, 2a‐e, 3, and
4) were synthesized and their structures were characterized by infrared radiation, nuclear magnetic resonance, and mass analysis. These novel substituted thiophene derivatives were effective inhibitor compounds of the carbonic anhydrase I and II isozymes (hCA I and II), and acetylcholinesterase (AChE) enzyme with
K
i values in the range of 447.28 to 1004.65 nM for hCA I, 309.44 to 935.93 nM for hCA II, and 0.28 to 4.01 nM for AChE, respectively. Novel substituted thiophene derivatives can be good candidate drugs for the treatment of some diseases like neurological disorders, epilepsy, glaucoma, gastric and duodenal ulcers, mountain sickness, or osteoporosis as carbonic anhydrase isozymes inhibitors, and for the treatment of Alzheimer’s and Parkinson’s diseases as acetylcholinesterase inhibitors.
Expression and characterization of Flavikunin: A Kunitz‐type serine protease inhibitor identified in the venom gland cDNA library of Bungarus flaviceps
Authors: Kaur Simran , Devi Arpita , Saikia Bhaskarjyoti , Doley Robin
Published: December 2018

Trancriptomic analysis of the venom gland cDNA library of Bungarus flaviceps revealed Kunitz‐type serine protease inhibitor as one of the major venom protein families with three groups A, B, C. One of the group B isoforms named Flavikunin, which lacked an extra cysteine residue involved in disulfide bond formation in
β‐bungarotoxin, was synthesized, cloned, and overexpressed in
Escherichia coli. To decipher the structure‐function relationship, the P1 residue of Flavikunin, histidine, was mutated to alanine and arginine. Purified wild‐type and mutant Flavikunins were screened against serine proteases‐thrombin, factor Xa, trypsin, chymotrypsin, plasmin, and elastase. The wild‐type and mutant Flavikunin (H∆R) inhibited plasmin with an IC
50 of 0.48 and 0.35 µM, respectively. The in‐silico study showed that P1 residue of wild‐type and mutant (H∆R) Flavikunin interacted with S1′ and S1 site of plasmin, respectively. Thus, histidine at the P1 position was found to be involved in plasmin inhibition with mild anticoagulant activity.
Clopidogrel reduces lipopolysaccharide‐induced inflammation and neutrophil‐platelet aggregates in an experimental endotoxemic model
Authors: Wang Xiao‐Li , Deng Hua‐Fei , Li Ting , Miao Shu‐Ying , Xiao Zi‐Hui , Liu Mei‐Dong , Liu Ke , Xiao Xian‐Zhong
Published: December 2018

Platelet activation contributes to organs failure in inflammation and plays an important role in endotoxemia. Clopidogrel inhibits platelet aggregation and activation. However, the role of clopidogrel in modulating inflammatory progression of endotoxemia remains largely unexplored. Therefore, we investigated the role of clopidogrel on the activation of platelet and leukocytes in lipopolysaccharide (LPS)‐induced inflammation in mice. Animals were treated with clopidogrel or vehicle before LPS induction. The expression of neutrophil‐platelet aggregates and platelet activation and tissue factor was determined. Immunofluorescence was used to analyze platelet‐leukocyte interactions and tissue factor (TF) expression on leukocytes. Clopidogrel pretreatment markedly decreased lung damage, inhibited platelet‐neutrophil aggregates and TF expression. In addition, clopidogrel reduced thrombocytopenia and affected the number of circulating white blood cell in endotoxemia mice. Moreover, clopidogrel also reduced platelet shedding of CD40L and CD62P in endotoxemic mice. Taken together, clopidogrel played an important role through reducing platelet activation and inflammatory process in endotoxemia.
MiR‐34c/SOX9 axis regulates the chemoresistance of ovarian cancer cell to cisplatin‐based chemotherapy
Authors: Xiao Songshu , Li Yueran , Pan Qiong , Ye Mingzhu , He Sili , Tian Qi , Xue Min
Published: December 2018

Cisplatin (DDP)‐based chemotherapy is a standard strategy for ovarian cancer (OC), while chemoresistance remains a major therapeutic challenge. Transcription factor SOX9 has been reported to be associated with tumor cell proliferation, metastasis, and chemoresistance. In the current study, we observed a higher SOX9 expression in OC cell lines; SOX9 overexpression might aggravate the chemoresistance of the OC cell to DDP, whereas its knockdown enhanced the chemoresistance. We screened for candidate microRNAs (miRNAs) which might target SOX9 using online tools and further verified the effect of miR‐34c, one of the candidate miRNA that significantly inhibited SOX9 expression, in the regulation of OC cell proliferation and chemoresistance to DDP. Further, we verified the interaction between SOX9 and miR‐34c, as well as the involvement of β‐catenin signaling in this process. Through the analysis of the correlation between miR‐34c expression and the clinical features of patients with OC, we revealed that miR‐34c might inhibit OC cell proliferation and chemoresistance to improve the prognosis of patients with OC. Further, the expression of SOX9, β‐catenin, and c‐Myc in OC tissues was upregulated and inversely correlated with miR‐34c expression, indicating that rescuing miR‐34c expression, thus to inhibit SOX9, β‐catenin, and c‐Myc expression presents a promising strategy of reducing the chemoresistance of the OC cell to DDP.
Role of miR‐486‐5p in regulating renal cell carcinoma cell proliferation and apoptosis via TGF‐β–activated kinase 1
Authors: He Yanfa , Liu Jianzhen , Wang Yongjun , Zhu Xiaoli , Fan Zhengchao , Li Chongbin , Yin Hang , Liu Ying
Published: December 2018

Renal cell carcinoma (RCC) is a common kidney tumor in adults. The role of miR‐486‐5p in RCC is unknown. The aim of our study was to identify new targets regulated by miR‐486‐5p in RCC, to obtain a deeper insight into the network and to better understand the role of these microRNAs and their targets in carcinogenesis of RCC. We performed a series of tests and found consistently lower expression levels of miR‐486‐5p in kidney cancer cells. Restoration of miR‐486‐5p expression in RCC cells could lead to the suppression of cell proliferation and the increase of cell apoptosis. Further studies demonstrated that TGF‐β–activated kinase 1 was a target gene of miR‐486‐5p in kidney cancer cells. It was also shown that C‐C motif chemokine ligand 2 (CCL2) from tumor‐associated macrophages downregulated miR‐486‐5p expression, and miR‐486‐5p inhibited RCC cell proliferation and apoptosis resistance induced by CCL2. The study demonstrates that there are potential diagnosis and therapy values of miR‐486‐5p in RCC.
RETRACTED: Downregulation of microRNA‐23b protects against ischemia‐reperfusion injury via p53 signaling pathway by upregulating MDM4 in rats
Authors: Zhao Zhi , Guan Jian‐Zhong , Wu Min , Lai Gui‐Hua , Zhu Zhong‐Lian
Published: December 2018

Total knee arthroplasty is a commonly performed safe procedure and typically executed in severe knee arthritis, but it also triggers ischemia‐reperfusion injury (IRI). More recently, microRNAs (miRs) have been reported to play a contributory role in IRI through the key signaling pathway. Hence, the current study aimed to investigate the effect and specific mechanism of microRNA‐23b (miR‐23b), murine double minute 4 (MDM4), and the p53 signaling pathway in IRI rat models. First, the IRI model was established, and the expression pattern of miR‐23b, MDM4, and the p53 signaling pathway‐related genes was characterized in cartilaginous tissues. Then, miR‐23b mimics or inhibitors were applied for the elevation or the depletion of the miR‐23b expression and siRNA‐MDM4 for the depletion of the MDM4 expression in the articular chondrocytes. By means of immunohistochemistry, quantitative real‐time polymerase chain reaction, and Western blot analysis, IRI rats exhibited increased miR‐23b expression, activated p53 signaling pathway, and decreased MDM4 expression. MDM4 was verified as a target gene of miR‐23b through. Downregulated miR‐23b increased the expression of MDM4, AKT, and Bcl‐2, but decreased the expression of p53, p21, and Bax. In addition, a series of cell experiments demonstrated that downregulated miR‐23b promoted articular chondrocyte proliferation and cell cycle entry, but inhibited articular chondrocyte apoptosis. The absence of the effects of miR‐23b was observed after MDM4 knocked down. Our results indicate that silencing miR‐23b could act to attenuate IRI and reduce the apoptosis of articular chondrocytes through inactivation of the p53 signaling pathway by upregulating MDM4, which provide basic therapeutic considerations for a novel target against IRI.
Extension of lymphocyte viability for radiation biodosimetry: Potential implications for radiological/nuclear mass casualty incidents
Authors: Smith Tammy , Escalona Maria , Ryan Terri , Livingston Gordon K. , Sanders Jacob T. , Balajee Adayabalam S.
Published: December 2018

Dicentric chromosome assay (DCA) is routinely used for estimating the absorbed radiation dose in exposed humans. Optimal lymphocyte viability is crucial for reliable dose estimation and most cytogenetic laboratories prefer the receipt of blood samples within 24 to 36 hours after collection. Delays in the shipment/receipt of samples can occur sometimes under certain unforeseen circumstances: (1) Adverse weather conditions, (2) distant location of blood collection sites, and (3) shipping and handling of a large number of samples after radiological/nuclear mass casualty incident(s). To circumvent some of these limitations, we evaluated the suitability of ex vivo irradiated blood samples stored in the presence of phytohemagglutinin (PHA) for 7 days at ambient temperature (22‐24°C) for radiation biodosimetry. Blood samples stored in the presence of PHA for up to 7 days showed a higher mitotic index than blood samples stored without PHA. To verify the use of stored blood samples for DCA, frequencies of X‐rays induced dicentric chromosomes were analyzed in the blood samples that were cultured either 24 hours after exposure or 7 days later after storage. Our results indicate that storage of ex vivo irradiated blood samples in the presence of PHA at ambient temperature was found optimal for DCA and that the radiation doses estimated by dicentric chromosome frequencies were grossly similar between the fresh and stored blood samples. Our study suggests that reliable and accurate biodosimetry results can be obtained for triage using blood samples stored for up to a week at ambient temperature in the presence of PHA.
A three microRNA‐based prognostic signature for small cell lung cancer overall survival
Authors: Yan Hao , Xin Shaobin , Ma Jing , Wang Hui , Zhang Heng , Liu Jindong
Published: December 2018

Background

Small‐cell lung cancer (SCLC) is one of the most aggressive cancers with mechanisms far from understood.

Objective

We proposed to identify valuable prognostic signature for SCLC prognosis prediction.

Methods

microRNA (miRNA) expression profiles of 42 SCLC patients were acquired from the Gene Expression Omnibus. miRNAs that significantly associated with SCLC overall survival (OS‐relevant) were identified through univariate Cox regression analysis followed by random survival forest analysis for identification of more reliable miRNA signature.

Results

Eleven OS‐relevant miRNAs were obtained, and hsa‐miR‐194, hsa‐miR‐608, and hsa‐miR‐9 were further refined through RFS. A formula composed of the three miRNAs’ expression values weighted by their multivariate Cox regression coefficients was constructed, and based on which, SCLC patients with longer OS could be well distinguished from those with shorter OS.

Conclusions

This study should provide a valuable clue for SCLC prognosis evaluation.
Effects of catalpol on bronchial asthma and its relationship with cytokines
Authors: Li Yanlin , Wang Hai , Yang Xu
Published: December 2018

An animal (BALB/c mice) model of catalpol associated with bronchial asthma in vivo was established, and the effects of catalpol and its relationship with cytokines were investigated. A total of 30 adult BALB/c mice were randomly divided into a positive control group, a model group, and a catalpol group, with 10 mice in each group. The lung function of mice, the cell count, and the cytokine concentrations in bronchoalveolar lavage fluid (BALF) were detected. The levels of cytokines [interleukin 4 (IL‐4), interleukin 5 (IL5), and interferon gamma (IFN‐γ)] in BALF were measured with enzyme‐linked immunosorbent assay methods. The total number of cells in the BALF of the group treated with catalpol was significantly lower than the model group. After treatment with catalpol, the eosinophils and neutrophils of the mice were remarkably reduced compared with the model group. The malondialdehyde content in the lung tissue homogenate of the mice was also decreased in the catalpol group. The cytokines IL‐5 and IL‐4 exhibited a similar tendency: the concentrations of IL‐4 and IL‐5 for the catalpol group were dramatically decreased compared with the model group. However, the IFN‐γ concentration for the catalpol group was higher than the model group. The results indicated that IL‐5 may involve in the pathologic process of asthma‐like IL‐4, and an inflammatory reaction may still exist in the airway during the remission stage of asthma. The imbalances of the cytokine network might be an important molecular basis in the asthma pathogenesis. It is suggested that catalpol may be a potential drug for the clinical treatment of asthma.
Vaccines for colorectal cancer: an update
Authors: Sarvizadeh Mostafa , Ghasemi Faezeh , Tavakoli Fatemeh , Sadat Khatami Sara , Razi Ebrahim , Sharifi Hossein , Biouki Nousin Moussavi , Taghizadeh Mohsen
Published: December 2018

Colorectal cancer (CRC) is known as the third most common and fourth leading cancer associated death worldwide. The occurrence of metastasis has remained as a critical challenge in CRC, so that distant metastasis (mostly to the liver) has been manifested in about 20%‐25% of patients. Several screening approaches have introduced for detecting CRC in different stages particularly in early stages. The standard treatments for CRC are surgery, chemotherapy and radiotherapy, in alone or combination. Immunotherapy is a set of novel approaches with the aim of remodeling the immune system battle with metastatic cancer cells, such as immunomodulatory monoclonal antibodies (immune checkpoint inhibitors), adoptive cell transfer (ACT) and cancer vaccine. Cancer vaccines are designed to trigger the intense response of immune system to tumor‐specific antigens. In two last decades, introduction of new cancer vaccines and designing several clinical trials with vaccine therapy, have been taken into consideration in colon cancer patients. This review will describe the treatment approaches with the special attention to vaccines applied to treat colorectal cancer.
Astrocytic insulin‐like growth factor‐1 prevents excitotoxic downregulation of adenosine deaminase acting on RNA in calcium dynamics
Authors: Chen Wei , He Bin , Zheng Ping
Published: December 2018

Background

A‐to‐I RNA editing catalyzed by the adenosine deaminase acting on RNA (ADAR) 1 represents an RNA‐based recoding mechanism implicated in a variety of cellular processes like intracellular homeostasis. Previous studies have demonstrated that the expression of ADAR1 is increased in glioma, and ADAR1 short hairpin RNA affects regulated cellular exocytosis. This indicates that ADAR1 might be involved in cellular proliferation and/or apoptosis.

Method

To investigate the molecular mechanism by which ADAR1 is activity dependent, we applied the primary neuron culture and coculture with astrocytes and the RNA chipset to explore the underlying mechanism.

Results

We found that in primary cultured neurons, the excitotoxicity induced by kainic acid (KA) increased the cellular calcium concentration determined by flow cytometry, and cocultured astrocyte could decrease the calcium concentration in KA‐treated neurons. In addition, we applied RNA chipset and found KA decreased the ADAR1 and signal transducer and activator of transcription 2 (STAT2) expression and cocultured astrocytes could increase the insulin‐like growth factor (IGF)‐1 expression and reverse the reduced ADAR1 and STAT2. This effect can be abolished by the astrocytic IGF‐1 with AG1024.

Conclusion

Astrocytic IGF‐1 has a neuroprotective role in preventing excitotoxic downregulation of ADAR1 in mediating calcium dynamics via STAT2.
RhoB antibody alters retinal vascularization in models of murine retinopathy
Authors: Almonte‐Baldonado Rowena , Bravo‐Nuevo Arturo , Gerald Damien , Benjamin Laura E. , Prendergast George C. , Laury‐Kleintop Lisa D.
Published: December 2018

Neovascularization in cancer or retinopathy is driven by pathological changes that foster abnormal sprouting of endothelial cells. Mouse genetic studies indicate that the stress‐induced small GTPase RhoB is dispensable for normal physiology but required for pathogenic angiogenesis. In diabetic retinopathy, retinopathy of prematurity (ROP) or age‐related wet macular degeneration (AMD), progressive pathologic anatomic changes and ischemia foster neovascularization are characterized by abnormal sprouting of endothelial cells. This process is driven by the angiogenic growth factor VEGF, which induces and supports the formation of new blood vessels. While injectable biologics targeting VEGF have been used to treat these pathological conditions, many patients respond poorly, prompting interest in other types of mechanism‐based therapy. Here we report the preclinical efficacy of a monoclonal antibody that specifically targets RhoB, a signaling molecule that is genetically dispensable for normal physiology but required for pathogenic retinal angiogenesis. In murine models of proliferative retinal angiogenesis or oxygen‐induced retinopathy, administering a monoclonal RhoB antibody (7F7) was sufficient to block neoangiogenesis or avascular pathology, respectively. Our findings offer preclinical proof of concept for antibody targeting of RhoB to limit diabetic retinopathy, ROP or wet AMD and perhaps other diseases of neovasculogenesis such as hemangioma or hemangiosarcoma nonresponsive to existing therapies.
Propofol partially attenuates complete freund's adjuvant‐induced neuroinflammation through inhibition of the ERK1/2/NF‐κB pathway
Authors: Cheng Lijian , Chen Zhenhong , Wang Lihua , Lan Yunping , Zheng Lihua , Wu Fangpu
Published: December 2018

Peripheral inflammation in male C57BL/6 mice was induced by intraplantar injection of 20 μL complete freund's adjuvant (CFA) in the left hind paw. Mice were randomly divided into three groups: Sham, CFA, and propofol+CFA. Mechanical allodynia was assessed by von Frey analysis, and heat hyperalgesia was detected by exposure of the plantar surface to a beam of radiant heat. Propofol significantly attenuated the severity and duration of CFA‐induced pain hypersensitivity, heat hyperalgesia, and paw edema. Propofol inhibited CFA‐induced microglia activation, and markedly decreased CFA‐induced ionized calcium binding adapter molecule 1 (IBA‐1) expression. Propofol inhibited CFA‐induced expression of p‐extracellular signal‐regulated kinase1/2 (p‐ERK1/2) and nuclear factor kappa‐light‐chain‐enhancer of activated B cells (NF‐κB) p65, as demonstrated by Western blot analysis. In addition, 3‐(4,5‐dimethyl‐2‐thiazolyl)‐2,5‐diphenyl‐2‐H‐tetrazolium bromide assays indicated that propofol had no cytotoxic effect on BV2 microglia cells. Reverse transcription‐quantitative‐polymerase chain reaction and enzyme‐linked immunosorbent assay results demonstrated that propofol attenuates CFA‐induced tumor necrosis factor‐α (TNF‐α), interleukin (IL)‐6, and IL‐1β production in the spinal cord as well as in BV2 cells. Taken together, these results demonstrate that propofol attenuates CFA‐induced neuroinflammation (TNF‐α, IL‐6, and IL‐1β expression) through a mechanism that involves activation of ERK1/2/NF‐κB signaling pathway.
Plumbagin induces autophagy and apoptosis of SMMC‐7721 cells in vitro and in vivo
Authors: Lin Yuning , Chen Yongxin , Wang Shengshan , Ma Jing , Peng Yue , Yuan Xianling , Lv Beibei , Chen Wanjun , Wei Yanfei
Published: December 2018

Plumbagin (PL), an active naphthoquinone compound, has been demonstrated to be a potential anticancer agent. However, the underlying anticancer mechanism is not fully understood. In this study, the human hepatocellular carcinoma (HCC) SMMC‐7721 cell line was studied in an in vitro model. The cell proliferation was inhibited by PL in a dose‐ and time‐dependent manner. Electron microscopy, acridine orange staining, and immunofluorescence were used to evaluate autophagosome formation and LC3 protein expression in PL‐treated SMMC‐7721 cells. Real‐time polymerase chain reaction and Western blot showed that PL treatment suppressed the expression of apoptosis and autophagy factors (LC3, Beclin1, Atg7, and Atg5), which are associated with tumor apoptosis and autophagy in SMMC‐7721 cells. In the study of in vitro tumor nude mouse models, PL can inhibit tumor growth. Cell apoptosis and autophagy of the transplanted tumors were evaluated by hematoxylin and eosin staining, terminal deoxynucleotidyl transferase‐mediated dUTP nick end‐labeling staining, and Western blot. In addition, in the in vivo studies of HCC cells, we found that pretreatment with the autophagy inhibitor 3‐methyladenine blocked the formation of apoptosis induced by PL. In contrast, administration of the apoptosis inhibitor Z‐VAD did not affect PL‐induced autophagy. Taken together, our findings strongly suggest that PL is a promising drug with significant antitumor activity in HCC.
A correlational study between serum asymmetric dimethylarginine level and impaired glucose tolerance patients associated with obesity
Authors: Huang Shan , Xu Yong , Peng Wen‐Fang , Cheng Jie , Li Hui‐Hua , Shen Li‐Sha , Xia Li‐Li
Published: December 2018

Asymmetric dimethylarginine (ADMA) plays a vital role in the regulation of insulin sensitivity and has been shown as a potential marker for various disease, including type 2 diabetes mellitus (DM2). However, the correlation between ADMA and impaired glucose tolerance (IGT) and obesity has not been studied. A total of 195 subjects were involved in our study. The characteristics of the subjects in the study cohort were measured and analyzed. We found that the serum ADMA and C‐reactive protein levels were significantly increased in IGT and diabetic patients, whereas the levels of lipoprotein A and adiponectin were decreased, especially in diabetic patients with obesity. The serum ADMA level was positively correlated to a homeostatic model assessment for insulin resistance, and multivariate regression analysis further indicated that ADMA was an independent factor for DM patients with obesity. Our study expands the understanding of the complicated relationship between obesity, insulin resistance, IGT, and ADMA. In addition, we demonstrated that the serum ADMA level could serve as a diagnositic biomarker of the early signs for IGT patients with obesity.
Preventive effect of omega‐3 fatty acids in a rat model of stress‐induced liver injury
Authors: Ali Fatma Farrag , Rifaai Rehab Ahmed
Published: December 2018

Omega‐3 fatty acids are gaining attention as a therapeutic agent of many diseases. Their protective effect in a variety of diseases has been demonstrated. To the best of our knowledge, this is the first study on omega‐3 fatty acids related to acute cold‐restraint stress (CRS) induced hepatic dysfunction in rats. Forty adult male Sprague–Dawley albino rats were used and classified into: control, omega‐3 group, each rat was pretreated with omega‐3 fatty acids; CRS group, rats were subjected to acute CRS for 6 hr; and CRS group pretreated with omega‐3 fatty acids. Serum was obtained to determine corticosterone (CORT), alanine aminotransferase (ALT), aspartate aminotransferase (AST), and tumor necrosis factor‐α (TNF‐α) levels. Hepatic malondialdehyde (MDA) and total antioxidant capacity (TAC) levels were measured. Also, liver tissues were taken for histological examination and immunohistochemical assessment of the apoptotic marker, caspase‐3. Results showed that pretreatment of stressed rats with omega‐3 fatty acids led to significant decrease in hepatic MDA and increase in TAC levels. They reduced serum levels of CORT, ALT, AST, and TNF‐α. Also, they improved liver damage and suppressed hepatic caspase‐3 expression. In conclusion, pretreatment of stressed rats with omega‐3 fatty acids has ameliorated stress‐induced liver damage due to their antioxidant, anti‐inflammatory, and antiapoptotic effects. So, they can be used to minimize stress complications on the liver.
Activation of TGF‐β1/Smad3 signaling pathway inhibits the development of ovarian follicle in polycystic ovary syndrome by promoting apoptosis of granulosa cells
Authors: Shen Haoran , Wang Yao
Published: December 2018

Objective: To investigate the role of the transforming growth factor‐β1 (TGF‐β1)/Smad3 signaling pathway in development of ovarian follicle by promoting apoptosis of granulosa cells in polycystic ovary syndrome (PCOS).

Methods

A total of 54 female rats were obtained and randomly assigned into the PCOS (n = 27) and control groups (
n = 27). PCOS rat models were constructed using the dehydroepi‐androsterone method to observe ovarian morphology and ultrastructure. Chemiluminescence immunoassay was performed to detect the levels of luteinizing hormone, follicle stimulating hormone, estradiol, progesterone, and testosterone. The release of TGF‐β1 in follicular fluid and serum was tested by the enzyme‐linked immunosorbent assay.

Results

Expression of p‐Smad3 significantly increased in granulosa cells of PCOS group. In terms of the Smad2 protein, there was no significant difference between the PCOS and control group. In comparison to the control group, the number of normal secondary follicles and normal antral follicles were significantly decreased, whereas the number of hypogenetic secondary follicles undergoing atresia and antral follicles were significantly elevated in the PCOS group. Furthermore, the thickness of granulosa cells decreased and the apoptosis of granulosa cells increased in the PCOS group compared with the control one.

Conclusion

These results indicate that p‐Smad3 may have a close relationship with apoptosis of granulosa cells, the mechanism is that the TGF‐β1/Smad3 signaling pathway may inhibit development of ovarian follicle of PCOS by regulating the apoptosis of granulosa cells.
Strategies toward rheumatoid arthritis therapy; the old and the new
Authors: Abbasi Mojtaba , Mousavi Mohammad Javad , Jamalzehi Sirous , Alimohammadi Reza , Bezvan Maryam Hasanzadeh , Mohammadi Hamed , Aslani Saeed
Published: December 2018

Currently, medications used to treat rheumatoid arthritis (RA) are glucocorticoids (GCs) and nonsteroidal anti‐inflammatory drugs (NSAIDs), predominantly used for controlling the pain and inflammation, disease‐modifying antirheumatic drugs (DMARDs), administered as first‐line medication for newly diagnosed RA cases, and biological therapies, used to target and inhibit specific molecules of the immune and inflammatory responses. NSAIDs and other GCs are effective in alleviating the pain, inflammation, and stiffness due to RA. DMARDs that are used for RA therapy are hydroxychloroquine, methotrexate, leflunomide, and sulfasalazine. The biological therapies, on the contrary, are chimeric anti‐CD20 monoclonal antibody, rituximab, inhibitors of tumor necrosis factor‐α (TNF‐α) like etanercept, infliximab, and adalimumab, a recombinant inhibitor of interleukin‐1 (IL‐1), anakinra, and costimulation blocker, abatacept. Moreover, newly under evaluation biological therapies include new TNF‐α inhibitors, JAK inhibitors, anti‐interleukin‐6‐receptor monoclonal antibodies (mABs), and antibodies against vital molecules involved in the survival and development of functional B cells. The new strategies to treat RA has improved the course of the disease and most of the patients are successful in remission of the clinical manifestations if the diagnosis of the disease occur early. The probability of remission increase if the diagnosis happens rapidly and treat‐to‐target approach are implemented. In this review article, we have attempted to go through the treatment strategies for RA therapy both the routine ones and those which have been developed over the past few years and currently under investigation.