bluuebunny/crossref_metadata_2025 huggingface dataset:
Nephrolithiasis (Hisat-E-Kulyah) and Its Management: An Overview
Authors: Asif Khan Mohammad , Fatimah Mehjabeen , Alam Saiyad Shah
Published: October 2018

Nephrolithiasis is one of the most common health problems that affect approximately 15 % population worldwide and about 2.3% population of India. Most (75% to 80%) kidney stones are calcium stones, composed of calcium oxalate and/or calcium phosphate. These stones are generally associated with high concentration of calcium in the blood or urine. The classical features of renal colic are sudden severe pain. It is usually caused by the stones in the kidney, renal pelvis or ureter, causing dilatation, stretching and spasm of the ureter. Pain starts in the loin about the level of the costovertebral angle. Typical symptoms of acute renal colic are intermittent colicky flank pain that may radiate to the lower abdomen or groin, often associated with nausea and vomiting. Many stones are asymptomatic and discovered during investigations for other conditions. Small urinary calculi pass out of the body without any clinical intervention. According to Jaleenoos (Galen) renal stones are formed when rooh (gaseous matter) is trapped in the spaces of the kidney and consolidates to form hard substances. Another cause of renal calculi is ulceration of the kidney, in which pus accumulates and solidifies, thereby forming renal stones or at least establishing a nidus for the formation of stones. Avicenna contends that the persistence of “morbid matter” in the urinary tract is instrumental in the formation of ghaliz madda (viscid matter). In Unani system of medicine the main aim of management for nephrolithiasis is to make morbid and abnormal humors easily extractible from the body through the excretory system.
This paper will deal with the literature, clinical aspect and management of the Nephrolithiasis in Unani System of Medicine
Estudio comparativo de disociación de iones moleculares inducida por absorción secuencial de fotones infrarrojos
Authors: Giroldo Tatiana , M. Riveros José
Published: October 2018

La disociación de iones moleculares de acetofenonas sustituidas inducidas por absorción multifotónica secuencial de fotones infrarrojos ha sido estudiada en un espectrómetro de resonancia ciclotrónica de iones por transformada de Fourier con el objetivo de obtener datos termoquímicos. Dos métodos diferentes se han usado para este fin: 1) la radiación emitida por un filamento de tungsteno incandescente situado en la propia celda del espectrómetro, y 2) un láser continuo de CO2. En el primer caso, es posible obtener una pseudo energía de activación a partir de los valores de la constante de disociación en función de la temperatura. En el segundo caso, el estudio de la constante de disociación en función de la intensidad de la radiación del láser ofrece una alternativa para obtener la energía de activación. El uso de una ecuación cinética maestra se ha utilizado para obtener valores aproximados de las energías de disociación y se discuten las limitaciones de los métodos.
Análisis de la precipitación en la microcuenca del Arroyo Itay durante el período 1982-2012
Authors: Martin Etchegaray Alan José , Díaz Domínguez Raúl Enrique , Méndez Gaona Fernando
Published: October 2018

Recientemente se han registrado cambios significativos en eventos climatológicos que generan una serie de problemas ecológicos y sociales. El análisis de tendencias de precipitaciones constituye una herramienta básica y elemental para estudiar estos cambios. En esta investigación, se analizaron datos de precipitaciones durante el período 1982 – 2012 provenientes del pluviómetro del Aeropuerto Silvio Petirossi con el objeto de analizar las tendencias y los picos de precipitación registrados en el período de estudio. Se calculó la precipitación acumulada para cada año de estudio y se determinaron los totales de precipitación para los meses y estaciones climatológicas de cada año. También, se calcularon los componentes de tendencia (T), cíclico (C) y estacional (S) de modelo aditivo para análisis de series temporales. Para el período estudiado los años 1996, 1997 y 1998 fueron los más lluviosos. En cambio, el año más seco ha sido el 1985. El 22 de diciembre del 1997 fue el día que registró mayor valor de precipitación. Por otra parte, se detectó una leve tendencia creciente de 1,817 mm/año. En cuanto a las estaciones: el verano es la estación con mayor precipitación acumulada (13356,3 mm) seguido del otoño (12725,9 mm) y de la primavera (12635,9 mm); finalmente, el invierno registró la menor precipitación acumulada (5372,9 mm). Se registraron tendencias crecientes en el verano (0,63 mm/año) y la primavera (3,76 mm/año), sin embargo, se observaron tendencias decrecientes en el otoño (-0,58 mm/año) y el invierno (-1,36 mm/año).
Experimental Analysis of the Source and Sink Relationship in a Meandering Bend
Authors: HE Li
Published: October 2018

The source-sink-relationships in natural rivers are compound results of various influencing factors, and correlated fitted equations are kind of qualitative description. Experiment analyses was conducted in a laboratory flume to reach a quantitative description, whose center line follows a sine-generated curve with deflection angle of 30 degree. Three-dimensional velocities, bed deformation and composition of the pool-bar complexes in the meander bend are analyzed. The comparison of deformed bed and the depth-averaged velocities founds that, the maximum depth-averaged velocities of sections around the transition reach occurred at the edge of pool with smaller transverse slope, and the maximum depth-averaged velocities for sections around the apex section occurred at the edge of pool with larger transverse slope. Quantitative analysis of the composition of pool-bar complexes revealed the source-sink relation of moved particles. It shows that, moved particles sourced from the concave bank are mainly come from area down the apex section, and moved particles sourced from the convex bank are mainly come from area upper the apex section. Besides, there exit an area with strong sediment exchange, namely the bar around the convex-side of the apex section.
Fatigue Strength Assessment of Semi-Submersible Floating Wind Turbine Foundation under Turbulent Wind
Authors: SANG Song , CHU Zhaofei , CAO Aixia , DONG Zixin , DONG Jinqi
Published: October 2018

Under the complex marine environment load and the role of the upper wind turbine load, deep sea floating wind turbine support structure would suffer fatigue damage, which often endangers the safety of the wind turbine system. This paper chose the "5 MW baseline" wind turbine model which published by the US National Renewable Energy Laboratory (NREL) as the design basis. The paper uses the OC4-DeepC wind semi-submersible offshore wind turbine model for the verification of offshore floating wind turbines. According to the characteristics of stress and the distribution of stress, the paper selects seven key parts which are prone to fatigue damage are screened, respectively established local finite element models and carried out grid encryption. Based on the SESAM hydrodynamic analysis software and FAST wind motor dynamic load calculation procedure, the fatigue damage of the target node under the action of wind turbine load is studied. The results show that the structural fatigue damage occurs mainly at the horizontal connection of the upper part of the neutral column and the diagonal connection of the lower part of the neutral column. The fatigue damage degree of the crown and the saddle point is relatively large at the connecting rod position.
Effects of marble, timber, and glass powder as partial replacements for cement
Authors: Tayeh Bassam A.
Published: October 2018

Waste materials, such as glass, marble, and timber, are pressing environmental problems worldwide, and their environmental impact can be best overcome by reusing them. This research mainly aims to determine the impact of using waste materials, such as crushed glass, crushed marble, and burned wood in powder form, as partial replacements for cement on the compressive strength of concrete. Mechanical properties (e.g., compressive strength) and physical properties (e.g., workability and unit weight) were investigated. The powdered waste materials (after passing through sieve #200) were partially replaced with cement by ratios of 10%, 20%, and 30%. Compressive strength was tested on the 7th, 28th, and 56th days. Results showed that workability decreased as the partial replacement level of glass powder, marble powder, and timber ash increased. The results also showed a decrease in the compressive strength of concrete when the replacement level was increased from 10% to 30% for each waste material.
Numerical Simulation of Three Phase Displacement Characteristics of Foam Fluid In Homogeneous Porous Media
Authors: Du D.X , Zhang D.
Published: October 2018

Foam technology has found wide applications in enhanced oil recovery and greenhouse geological storage. In this paper, a numerical simulate is carried out with the stochastic bubble population balance model on the foam three phase displacement process in a homogeneous oil/water/gas coexistence porous media of liquid. The effects of the maximum equilibrium bubble density nmax and the foam generation rate Kg on foam displacement process is mainly discussed. Numerical results indicate that the oil phase can be displaced well by foam fluid. Larger nmax values lead to higher apparent viscosity of foam and higher the pressure difference, and with the increase of Kg, the number of foam can reach a balance in a short distance, so it has better displacement effect on the oil phase components. The results obtained in this paper have a certain guiding role in understanding the enhanced oil recovery mechanism of foam fluid.
Een en ander oor die ontwikkeling van die nuwe testamentiese wetenskap die afgelope vyftig jaar
Authors: Van Rensburg S.P.J.J.
Published: October 2018

No abstract available.
Karl Barth se beskouing ten opsigte van die leer van die parthenogenesis met 'n verwysing na die etiese ideaal van die ongehude lewensstaat
Authors: Koekemoer P.J.T.
Published: October 2018

No abstract available.
Die draagkrag van die geloftes van 1838 en 1880
Authors: Mans C.J.
Published: October 2018

No abstract available.
Die gehalte en gestalte van Praktiese Teologie sedert die begin van die twintigste eeu
Authors: De Wet J.I.
Published: October 2018

No abstract available.
In memoriam: Prof. dr. S. F. H. J. Berkelbach v.d. Sprenkel
Authors: Koekemoer P.J. Theo
Published: October 2018

No abstract available.
Hedendaagse krisispunte in die teologie*
Authors: Engelbrecht B.J.
Published: October 2018

No abstract available.
The Relationship between Student Science Teachers’ Views on Nature of Science and Classroom Practice: Is There Any?
Authors: Stefanidou Constantina , Skordoulis Constantine , Kechagias Christos
Published: October 2018

The present study investigated the relationship between student science teachers’ views on Nature of Science and their views on the importance of teaching Nature of Science. It is a case study in which qualitative methods and descriptive statistics are used. The sample consisted of 23 student science teachers who attended a faculty course on Didactics of Physics and participated voluntarily. Preliminary findings showed a moderate relationship between students’ views on Nature of Science issues and their classroom practice, particularly regarding “tenets” such as the tentative character of science and sociocultural milieu. When it comes to more epistemological issues, such as the difference between a theory and a law, then student teachers have considerable conceptual difficulties and they also find the particular “tenets” less important for a school science context.
Analysis of residents' travel characteristics along Beijing rail transit line based on binary choice model
Authors: Cai Zhaoyang , Yan Jianwei
Published: October 2018

From ancient to modern times, in the historical process of urban development, urban transportation has been developing along with the development of the city's political, economic and cultural industries, and the relationship between each other has always been a topic constantly discussed by planning scholars. The development of urban transportation promotes the urban population gathering and industrial development, and promotes the development of urban geographical space. At the same time, it also brings endless convenience to urban residents, so that they can complete the displacement from the beginning to the destination with relatively low cost. However, with the rapid development of urban scale and the rapid growth of urban population, the problems of traffic congestion and land resource shortage in big cities of China seriously restrict the improvement of the quality of life of residents and the further development of the city. In this context, compact city is the inevitable choice for future urban development, while the transportation system supporting compact city form can only be public transportation. As a high-volume, efficient and rapid public transport mode, rail transit can not only solve the traffic congestion problem in high-density areas of cities, but also optimize the development and utilization of urban land and adjust the urban spatial layout, which is of great significance for the sustainable development of cities. The network of rail transit in Beijing becomes the backbone of public passenger transport system, and play an irreplaceable role in guiding the urban space layout adjustment, population migration and the transformation of traffic structure. The study of travel characteristics of the residents who live along the rail transit, in-depth analysis the relationship of the rail transit, the population migration and commuter travel, it is of great significance providing decision support for urban planning. Based on binary choice model, establishing the residents' travel choice model, rail transit impact model of different crowds. Study the relationship between rail transit and residents' travel characteristics, predict the rail transit to guide the trend of population migration.
Designing seryl‐tRNA synthetase for improved serylation of selenocysteine tRNAs
Authors: Fu Xian , Crnković Ana , Sevostyanova Anastasia , Söll Dieter
Published: October 2018

Selenocysteine (Sec) lacks a cognate aminoacyl‐tRNA synthetase. Instead, seryl‐tRNA synthetase (SerRS) produces Ser‐tRNASec, which is subsequently converted by selenocysteine synthase to Sec‐tRNASec. Escherichia coli SerRS serylates tRNASec poorly; this may hinder efficient production of designer selenoproteins in vivo. Guided by structural modelling and selection for chloramphenicol acetyltransferase activity, we evolved three SerRS variants capable of improved Ser‐tRNASec synthesis. They display 10‐, 8‐, and 4‐fold increased kcat/KM values compared to wild‐type SerRS using synthetic tRNASec species as substrates. The enzyme variants also facilitate in vivo read‐through of a UAG codon in the position of the critical serine146 of chloramphenicol acetyltransferase. These results indicate that the naturally evolved SerRS is capable of further evolution for increased recognition of a specific tRNA isoacceptor.
Concordance with NCCN treatment guidelines: Relations with health care utilization, cost, and mortality in breast cancer patients with secondary metastasis
Authors: Rocque Gabrielle B. , Williams Courtney P. , Kenzik Kelly M. , Jackson Bradford E. , Azuero Andres , Halilova Karina I. , Ingram Stacey A. , Pisu Maria , Forero Andres , Bhatia Smita
Published: October 2018

Background

The impact of National Comprehensive Cancer Network (NCCN) treatment guideline concordance on costs, health care utilization, and mortality for patients with breast cancer and secondary metastases is unknown.

Methods

From 2007 to 2013, women with early‐stage breast cancer who received treatment for secondary metastases (n = 5651) were evaluated for first recorded systemic therapy concordance with NCCN guidelines within the Surveillance, Epidemiology, and End Results Program–Medicare linked database. Generalized linear and mixed effects models evaluated factors associated with nonconcordance and the relation between concordance status and health care utilization and costs. Mortality risk was estimated with Cox regression.

Results

Eighteen percent of the patients received nonconcordant therapy, with the most common being single‐agent, human epidermal growth factor receptor 2 (HER2)–targeted therapy (36%), therapy mismatched with the estrogen receptor/HER2 status (11%), unapproved bevacizumab regimens (10%), and adjuvant regimens in a metastatic setting (6%). A younger age, a hormone receptor–negative status, and a HER2‐positive status were associated with nonconcordance (P < .05). Nonconcordance was associated with 22% and 21% increased rates of emergency department visits and hospitalizations, respectively, and $1765 higher average monthly Medicare costs. Differences in adjusted mortality risk were noted by the category of nonconcordance; single‐agent, HER2‐targeted therapy was associated with decreased mortality risk (hazard ratio [HR], 0.66; 95% confidence limit [CL], 0.57‐0.76), and increased mortality risk was observed with unapproved bevacizumab use (HR, 1.40; 95% CL, 1.13‐1.74).

Conclusions

Most patients (82%) received treatment consistent with NCCN guidelines. Nonconcordant treatment was associated with higher health care utilization and costs, with mortality differences observed by the type of guideline deviation. Consideration of both patient and financial outcomes will be important as health systems increase the emphasis on guideline‐based care.
A call to action: Why sarcoma surgery needs to be centralized
Authors: Raut Chandrajit P. , Bonvalot Sylvie , Gronchi Alessandro
Published: October 2018

Although experts agree that complex surgeries or those that are performed for patients with rare conditions should be performed at high‐volume centers, the majority of patients with primary retroperitoneal sarcoma undergo surgical resection at centers with relatively low volumes. This has implications for both immediate patient outcome and long‐term clinical trial success, and highlights the importance of centralizing care for patients with such rare cancers.
Prey exploitation and dispersal strategies vary among natural populations of a predatory mite
Authors: Revynthi Alexandra M. , Egas Martijn , Janssen Arne , Sabelis Maurice W.
Published: October 2018

When predators commonly overexploit local prey populations, dispersal drives the dynamics in local patches, which together form a metapopulation. Two extremes in a continuum of dispersal strategies are distinguished: the “Killer” strategy, where predators only start dispersing when all prey are eliminated, and the “Milker” strategy, in which predator dispersal occurs irrespective of prey availability. Theory shows that the Milker strategy is not evolutionarily stable if local populations are well connected by dispersal. Using strains of the predatory mitePhytoseiulus persimilis, collected from 11 native populations from coastal areas in Turkey and Sicily, we investigated whether these two strategies occur in nature. In small wind tunnels, we measured dispersal rates and population dynamics of all populations in a system consisting of detached rose leaves, spider mites (Tetranychus urticae) as prey, andP. persimilis. We found significant variation in the exploitation and dispersal strategies among predator populations, but none of the collected strains showed the extreme Killer or Milker strategy. The results suggest that there is genetic variation for prey exploitation and dispersal strategies. Thus, different dispersal strategies in the Milker–Killer continuum may be selected for under natural conditions. This may affect the predator–prey dynamics in local populations and is likely to determine persistence of predator–prey systems at the metapopulation level.
Microdroplet monitoring using microfluid circuit combined quartz oscillator based capacitive sensor
Authors: Ebata Ryo , Sakai Ryo , Sohgawa Masayuki , Abe Takashi
Published: October 2018

In this article, we developed a compact microdroplet monitoring sensor. This sensor is capacitive sensor combined a microfluidic circuit and a crystal oscillator. We succeeded in the generation and monitoring of microdroplets with this sensor. We optimized the sensing capacitor to improve the sensitivity of the sensor. With optimized the sensing capacitor, the frequency response can be increased. We measured NaCl aqueous solution concentration with the optimized sensing capacitor. From the measurement result, the high dynamic range measurement can be made by using two frequencies.
Effects of HMGA2 gene downregulation by siRNA on lung carcinoma cell migration in A549 cell lines
Authors: Naghizadeh Sanaz , Mansoori Behzad , Mohammadi Ali , Kafil Hossein Samadi , Mousavi Zohreh , Sakhinia Ebrahim , Baradaran Behzad
Published: October 2018

Background

Although there are multiple treatments for lung cancer, the death rate of this cancer remains high because of metastasis in earlier stages. So a novel treatment for overcoming metastasis is urgently needed. Overexpression of high‐mobility group AT‐hook 2 (HMGA2), a nonhistone chromosomal protein has been observed in metastatic cancers. So, we suggested that HMGA2 upregulation may play a critical role in treating lung cancer.

Methods

The A549 cells were transfected with specific HMGA2 small interfering RNA (siRNA) using transfection reagent. Relative HMGA2 and matrix metallopeptidase 1 (MMP1), C‐X‐C chemokine receptor type 4 (CXCR4), vimentin, and E‐cadherin messenger RNA expression levels were measured by quantitative real‐time polymerase chain reaction. To diagnose cytotoxic effect of HMGA2 siRNA and other components of transfection process, 3‐(4,5‐dimethylthiazol‐2‐yl)‐2,5‐diphenyltetrazolium bromide assay was applied. The migration capacity after transfection with HMGA2 siRNA was detected by wound‐healing assay.

Results

HMGA2 siRNA significantly reduced HMGA2 expression in a dose‐dependent manner 48 hours after transfection. Expression levels of MMP1, vimentin, and CXCR4 were reduced, but E‐cadherin level was not changed meaningfully. HMGA2 knockdown significantly reduced cell survival rate and also led to the inhibition of cell migration.

Conclusions

Our results indicated that RNA interference by downregulation of HMGA2 gene expression and affecting downstream genes led to the inhibition of cell migration and proliferation. Therefore, HMGA2 siRNA might be an alternative treatment option for metastatic lung cancer.
Arctigenin inhibits RANKL‐induced osteoclastogenesis and hydroxyapatite resorption in vitro and prevents titanium particle–induced bone loss in vivo
Authors: Wei Gejin , Liang Tihong , Wei Chengming , Nong Xiaolian , Lu Qiteng , Zhao Jinmin
Published: October 2018

Wear particle–induced bone resorption leads to prosthesis loosening, which is a major complication associated with total joint arthroplasty. Although the exact mechanism remains unclear, wear particle–induced extensive osteoclastogenesis plays a critical role in this process. Thus, a potential treatment of prosthetic loosening is focused on suppressing extensive osteoclast formation and bone resorption, which prevents wear particle–induced osteolysis. Arctigenin isolated from Arctium lappa has numerous beneficial pharmacologic effects, including anti‐inflammatory, antiviral, and anticancer activities. Here, we explored the potential impact of arctigenin on titanium (Ti) particle–induced osteolysis in vivo. Our data showed that arctigenin significantly suppressed Ti particle–induced osteolysis and prevented bone destruction compared with Ti group. In addition, the number of osteoclasts reduced after treatment with arctigenin in vivo, indicating osteoclastogenesis might be inhibited by arctigenin. Next, bone marrow–derived macrophages were used to examine osteoclast differentiation, bone resorption, and activation of osteoclast‐related signaling pathways. The results showed that arctigenin inhibited RANKL‐induced osteoclastogenesis without any cytotoxicity and suppressed osteoclastic marker genes expression and hydroxyapatite resorption activity in a dose‐dependent manner. Additionally, arctigenin suppressed receptor activator of nuclear factor κΒ (NF‐κB) ligand–induced NF‐κB activation, concomitant with retarded IκBɑ degradation and inhibition of p65 nuclear translocation, leading to impaired osteoclastogenesis. Collectively, our results suggest that arctigenin is a promising candidate for the treatment of osteoclast‐related osteolytic diseases caused by excessive osteoclast formation.
The relationship between homeobox B7 expression and the clinical characteristics of patient with prostate cancer
Authors: Song Zhangxing , Liao Zhaolin , Cui Yingdong , Yang Chao
Published: October 2018

Background

The prognosis of patients with prostate cancer (PCa) remains poor.

Methods

GSE16560, GSE32448, GSE79957, GSE17951, and TCGA‐PRAD were reanalyzed to evaluate the expression of homeobox B7 (HOXB7) between PCa tissues and normal prostate tissues and to characterize the correlation between the expression of HOXB7 and the clinicopathological features of patients with PCa. Gene set enrichment analysis was conducted to investigate the mechanisms.

Results

HOXB7 was upregulated in PCa tissues (P = 0.0005). Both the univariate and multivariate analyses demonstrated that the expression of HOXB7 was correlated with the Gleason score and TNM staging of patients with PCa. The Gleason score and TNM staging were higher in the HOXB7 high expression group. The overall survival (hazard ratio [HR] = 0.632; 95% confidence interval [CI]: 0.4773‐0.8369;
P = 0.0014) and progression‐free survival (HR = 0.544; 95% CI: 0.3157‐0.9373;
P = 0.0283) favored patients with PCa in HOXB7 low expression group over those in HOXB7 high expression group. PCa samples in HOXB7 low expression group were enriched in gene sets associated with the epithelial mesenchymal transition, apical junction, angiogenesis, ultraviolet response, and hypoxia.

Conclusions

HOXB7 might be an independent prognostic factor of patients with PCa.
SEMA3B‐AS1‐inhibited osteogenic differentiation of human mesenchymal stem cells revealed by quantitative proteomics analysis
Authors: Zhang Chen , Zhu Yun , Liu Yugang , Zhang Xiguang , Yue Qiaoning , Li Li , Chen Yatang , Lu Sheng , Teng Zhaowei
Published: October 2018

Human mesenchymal stem cells (hMSCs) are fibroblastoid multipotent adult stem cells with capacities of differentiation into osteoblasts and chondrocytes and show great potential in new bone formation and bone repair‐related clinical settings, such as osteoporosis. Long noncoding RNAs (lncRNAs) have been demonstrated to play important roles in various biological processes. Here, we report an antisense lncRNA SEMA3B‐AS1 regulating hMSCs osteogenesis. SEMA3B‐AS1 is proximal to a member of the semaphorin family Sema3b. Overexpression of SEMA3B‐AS1 using the lentivirus system markedly inhibits the proliferation of hMSCs and meanwhile reduces osteogenic differentiation. Using a comprehensive proteomic technique named isobaric tag for relative and absolute quantitation, we found that SEMA3B‐AS1 significantly alters the process of osteogenesis through downregulating the expression of proteins involved in actin cytoskeleton, focal adhesion, and extracellular matrix–receptor interaction, while increasing the expression of proteins in the spliceosome. Collectively, we find that SEMA3B‐AS1 is a target for controlling osteogenesis of hMSCs.
Identification of a crucial amino acid responsible for the loss of specifying FGFR1–KLB affinity of the iodinated FGF21
Authors: Luo Wu , Lin Xiao‐Mian , Wang Tian‐Xiang , Cai Jia‐Long , Zeng Xiang‐Feng , Zhu Cai‐Rong , Li Rong‐Zhen , Wang Heng , Wu Xiao‐Ping
Published: October 2018

Previous studies suggest that specific binding to the complex consisting of fibroblast growth factor receptor‐1 (FGFR1) and the coreceptor beta‐Klotho (KLB) is the premise for human FGF19 and FGF21 activating the downstream signaling cascades, and regulating the metabolic homeostasis. However, it was found that human FGF21 loses its ability to bind to FGFR1–KLB after iodination with Na125I and chloramine T, whereas human FGF19 retained its affinity for FGFR1–KLB even after iodination. The molecular mechanisms underlying these differences remained elusive. In this study, we first demonstrated that an intramolecular disulfide bond was formed between cysteine‐102 and cysteine‐121 in FGF21, implying that the oxidation of the cysteine to cysteic acid, which may interfere with the active conformation of FGF21, did not occur during the iodination procedures, and thus ruled out the possibility of the two conserved cysteine residues mediating the loss of FGF21 binding affinity to FGFR1–KLB upon iodination. Site‐directed mutagenesis and molecular modeling were further applied to determine the residue(s) responsible for the loss of FGFR1–KLB affinity. The results showed that mutation of a single tyrosine‐207, but not the other five tyrosine residues in FGF21, to a phenylalanine retained the FGFR1–KLB affinity of FGF21 even after iodination, whereas replacing the corresponding phenylalanine residue with tyrosine in FGF19 did not alter its binding affinity to FGFR1–KLB, but decreased the receptor binding ability of the iodinated protein, suggesting that tyrosine‐207 is the crucial amino acid responsible for the loss of specifying FGFR1–KLB affinity of the iodinated FGF21.
MiR‐208b regulates cell cycle and promotes skeletal muscle cell proliferation by targeting CDKN1A
Authors: Wang Jian , Song Chengchuang , Cao Xiukai , Li Hui , Cai Hanfang , Ma Yilei , Huang Yongzhen , Lan Xianyong , Lei Chuzhao , Ma Yun , Bai Yueyu , Lin Fengpeng , Chen Hong
Published: October 2018

Skeletal muscle is the most abundant tissue in the body. The development of skeletal muscle cell is complex and affected by many factors. A sea of microRNAs (miRNAs) have been identified as critical regulators of myogenesis. MiR‐208b, a muscle‐specific miRNA, was reported to have a connection with fiber type determination. However, whether miR‐208b has effect on proliferation of muscle cell was under ascertained. In our study, cyclin‐dependent kinase inhibitor 1A (CDKN1A), which participates in cell cycle regulation, was predicted and then validated as one target gene of miR‐208b. We found that overexpression of miR‐208b increased the expression of cyclin D1, cyclin E1, and cyclin‐dependent kinase 2 at the levels of messenger RNA and protein in cattle primary myoblasts in vivo and in vitro. Flow cytometry showed that forced expression of miR‐208b increased the percentage of cells at the S phase and decreased the percentage of cells at the G0/G1 phase. These results indicated that miR‐208b participates in the cell cycle regulation of cattle primary myoblast cells. 5‐Ethynyl‐20‐deoxyuridine and 3‐(4,5‐dimethylthiazol‐2‐yl)‐2,5‐diphenyltetrazolium bromide assays showed that overexpression of miR‐208b promoted the proliferation of cattle primary myoblasts. Therefore, we conclude that miR‐208b participates in the cell cycle and proliferation regulation of cattle primary skeletal muscle cell through the posttranscriptional downregulation of CDKN1A.
Disturbed Th17/Treg balance, cytokines, and miRNAs in peripheral blood of patients with Behcet’s disease
Authors: Ahmadi Majid , Yousefi Mehdi , Abbaspour‐Aghdam Sanaz , Dolati Sanam , Aghebati-Maleki Leili , Eghbal‐Fard Shadi , Khabbazi Alireza , Rostamzadeh Davood , Alipour Shahriar , Shabani Mahdi , Nouri Mohammad , Babaloo Zohreh
Published: October 2018

Impaired inflammatory immune cells have been implicated in the pathogenesis of Behcet’s disease (BD). In the current study, we aimed to evaluate the frequency of T helper (Th) 17 and regulatory T (Treg) cells, cytokine secretion, the expression of transcription factors related to Th17 and Treg cells, and microRNAs (miRNAs) targeting these transcription factors in BD patients. Blood samples from 47 BD patients and 58 healthy subjects were drawn, and the peripheral blood mononuclear cells (PBMCs) were separated and isolated. The frequency of Th17 and Treg cells was assessed using flow cytometry. Transcription factors related to these cells and miRNAs targeting these transcription factors were quantified using real‐time polymerase chain reaction. Finally, the levels of associated cytokines were measured using enzyme‐linked immunosorbent assay. A significant reduction in the percentage of Treg cell frequency and the levels of interleukin (IL)‐10 and forkhead box P3 messenger RNA (mRNA) expressions were observed. The proportion of Th17 cells was notably increased, which was accompanied by a increased levels of IL‐17, IL‐23, and retinoic acid‐related orphan receptor ɣ (RORɣt) mRNA expressions in BD patients. The level of Th17‐associated cytokines in the supernatant was found to be elevated in BD patients. T‐cell‐associated miRNA expression levels, miR‐25, miR‐106b, miR‐326, and miR‐93 were significantly upregulated, while miR‐146a and miR‐155 levels were lower in PBMCs of patients with BD when compared with the controls. The increase in the proportion of Th17 cells alongside the decrease in Treg cells are possibly the involving factors in the pathogenesis of BD. Therefore, the evaluation of immune cells and related miRNA profile may serve as both prognostic biomarker and therapeutic approach in treating patients with BD.
Cinnamaldehyde regulates H2O2‐induced skeletal muscle atrophy by ameliorating the proteolytic and antioxidant defense systems
Authors: Kaur Nirmaljeet , Gupta Prachi , Saini Vikram , Sherawat Sandeep , Gupta Sanjeev , Dua Anita , Kumar Vinod , Injeti Elisha , Mittal Ashwani
Published: October 2018

Skeletal muscle atrophy/wasting is associated with impaired protein metabolism in diverse physiological and pathophysiological conditions. Elevated levels of reactive oxygen species (ROS), disturbed redox status, and weakened antioxidant defense system are the major contributing factors toward atrophy. Regulation of protein metabolism by controlling ROS levels and its associated catabolic pathways may help in treating atrophy and related clinical conditions. Although cinnamaldehyde (CNA) enjoys the established status of antioxidant and its role in ROS management is reported, impact of CNA on skeletal muscle atrophy and related pathways is still unexplored. In the current study, the impact of CNA on C2C12 myotubes and the possible protection of cultured cells from H
2O
2‐induced atrophy is examined. Myotubes were treated with H
2O
2 in the presence and absence of CNA and the changes in the antioxidative, proteolytic systems, and mitochondrial functions were scored. Morphological analysis showed significant protective effects of CNA on length, diameter, and nuclei fusion index of myotubes. The evaluation of biochemical markers of atrophy; creatine kinase, lactate dehydrogenase, succinate dehydrogenase along with the study of muscle‐specific structural protein (i.e., myosin heavy chain‐fast [MHCf] type) showed significant protection of proteins by CNA. CNA pretreatment not only checked the activation of proteolytic systems (ubiquitin‐proteasome E3‐ligases [MuRF1/Atrogin1]), autophagy [Beclin1/LC3B], cathepsin L, calpain, caspase), but also prevented any alteration in the activities of antioxidative defense enzymes (catalase, glutathione‐
S‐transferase, glutathione‐peroxidase, superoxide dismutase, glutathione reductase). The results suggest that CNA protects myotubes from H
2O
2‐induced atrophy by inhibiting/resisting the amendments in proteolytic systems and maintains cellular redox‐balance.
The mechanisms of DIRAS family members in role of tumor suppressor
Authors: Li Xueli , Liu Shuiping , Fang Xiao , He Chao , Hu Xiaotong
Published: October 2018

DIRAS family is a group of GTPases belonging to the RAS superfamily and shares homology with the pro‐oncogenic Ras GTPases. Currently, accumulating evidence show that DIRAS family members could be identified as putative tumor suppressors in various cancers. The either lost or reduced expression of DIRAS proteins play an important role in cancer development, including cell growth, migration, apoptosis, autophagic cell death, and tumor dormancy. This review focuses on the latest research regarding the roles and mechanisms of the DIRAS family members in regulating Ras function, cancer development, assessing potential challenges, and providing insights into the possibility of targeting them for therapeutic use.
Tyrosine phosphorylation of HDAC3 by Src kinase mediates proliferation of HER2‐positive breast cancer cells
Authors: Seo Jaesung , Guk Garam , Park Seung‐Ho , Jeong Mi‐Hyeon , Jeong Ji‐Hoon , Yoon Ho‐Geun , Choi Kyung‐Chul
Published: October 2018

The role of histone deacetylase 3 (HDAC3) is to repress the expression of various genes by eliminating acetyl group from histone. Thus, the regulation of HDAC3 activity is essential to maintain cellular homeostasis. In this study, we found that HDAC3 interacts with c‐Src kinase. However, the interaction between HDAC3 and c‐Src was previously reported, it has still been ambiguous whether c‐Src phosphorylates HDAC3 and affects the function of HDAC3. First, we confirmed that HDAC3 directly binds to c‐Src, and c‐Src identified to interact with C‐terminal domain (277–428 a.a.) of HDAC3. c‐Src also phosphorylated three tyrosine sites of HDAC3 at tyrosine 325, 328, and 331. Importantly, wild‐type c‐Src increases HDAC3 activity, but not mutant c‐SrcK298M (kinase inactive form). When these tyrosine residues are all substituted for alanine residues, the deacetylase activity of mutant HDAC3 was abolished. In addition, a proliferation of HER2‐positive breast cancer cells expressing phosphorylation deficient mutant HDAC3 is decreased in comparison with control cells. Thus, our findings suggested that phosphorylation of HDAC3 by c‐Src kinase regulates the HDAC3 activity and the proliferation of breast cancer cells.
Differentiation of microfluidic‐encapsulated trabecular meshwork mesenchymal stem cells into insulin producing cells and their impact on diabetic rats
Authors: Barati Ghasem , Nadri Samad , Hajian Ramin , Rahmani Ali , Mostafavi Hossein , Mortazavi Yousef , Taromchi Amir Hossein
Published: October 2018

Tissue and stem cell encapsulation andtransplantation were considered as promising tools in the treatment of patients with diabetes mellitus. The aim of this study was to evaluate the effect of microfluidic encapsulation on the differentiation of trabecular meshwork mesenchymal stem cells (TM‐MSC), into insulin‐producing cells (IPCs) both in vitro and in vivo. The presence of differentiated cells in microfibers (three dimensional [3D]) and tissue culture plates (TCPS; two dimensional [2D]) culture was evaluated by detecting mRNA and protein expression of pancreatic islet‐specific markers as well as measuring insulin release of cells in response to glucose challenges. Finally, semi‐differentiated cells in microfibers (3D) and 2D cultures were used to control the glucose level in diabetic rats. The results of this study showed that MSCs differentiated in alginate microfibers (fabricated by microfluidic device) express more Pdx‐1 mRNA (1.938‐fold, p‐value: 0.0425) and Insulin mRNA (2.841‐fold,
p‐value: 0.0001) compared with those cultured on TCPS. Furthermore, cell encapsulation in microfluidic derived microfibers decreased the level of blood glucose in diabetic rats. The approach used in this study showed the possibility of alginate microfibers as a matrix for differentiation of TM‐MSCs (as a new source) into IPCs. In addition, it could minimize different steps in stem cell differentiation, handling, and encapsulation, which lead to loss of an unlimited number of cells.
Glucose intolerance in monosodium glutamate obesity is linked to hyperglucagonemia and insulin resistance in α cells
Authors: Araujo Thiago R. , da Silva Joel A. , Vettorazzi Jean F. , Freitas Israelle N. , Lubaczeuski Camila , Magalhães Emily A. , Silva Juliana N. , Ribeiro Elane S. , Boschero Antonio C. , Carneiro Everardo M. , Bonfleur Maria L. , Ribeiro Rosane Aparecida
Published: October 2018

Obesity predisposes to glucose intolerance and type 2 diabetes (T2D). This disease is often characterized by insulin resistance, changes in insulin clearance, and β‐cell dysfunction. However, studies indicate that, for T2D development, disruptions in glucagon physiology also occur. Herein, we investigated the involvement of glucagon in impaired glycemia control in monosodium glutamate (MSG)‐obese mice. Male Swiss mice were subcutaneously injected daily, during the first 5 days after birth, with MSG (4 mg/g body weight [BW]) or saline (1.25 mg/g BW). At 90 days of age, MSG‐obese mice were hyperglycemic, hyperinsulinemic, and hyperglucagonemic and had lost the capacity to increase their insulin/glucagon ratio when transitioning from the fasting to fed state, exacerbating hepatic glucose output. Furthermore, hepatic protein expressions of phosphorylated (p)‐protein kinase A (PKA) and cAMP response element‐binding protein (pCREB), and of phosphoenolpyruvate carboxykinase (PEPCK) enzyme were higher in fed MSG, before and after glucagon stimulation. Increased pPKA and phosphorylated hormone‐sensitive lipase content were also observed in white fat of MSG. MSG islets hypersecreted glucagon in response to 11.1 and 0.5 mmol/L glucose, a phenomenon that persisted in the presence of insulin. Additionally, MSG α cells were hypertrophic displaying increased α‐cell mass and immunoreactivity to phosphorylated mammalian target of rapamycin (pmTOR) protein. Therefore, severe glucose intolerance in MSG‐obese mice was associated with increased hepatic glucose output, in association with hyperglucagonemia, caused by the refractory actions of glucose and insulin in α cells and via an effect that may be due to enhanced mTOR activation.
DGCR5 attenuates neuropathic pain through sponging miR‐330‐3p and regulating PDCD4 in CCI rat models
Authors: Peng Chengwei , Zhang Chuanqing , Su Zhe , Lin Dongyang
Published: October 2018

Neuropathic pain caused by somatosensory nervous system dysfunction is a serious public health problem. Some long noncoding RNAs (lncRNAs) can participate in physiological processes involved in neuropathic pain. However, the effects of lncRNA DGCR5 in neuropathic pain have not been explored. Therefore, in our current study, we concentrated on the biological roles of DGCR5 in neuropathic pain. Here, it was observed that DGCR5 was significantly decreased in chronic sciatic nerve injury (CCI) rat models. DGCR5 overexpression was able to alleviate neuropathic pain development including mechanical and thermal hyperalgesia. In addition, the current understanding of miR‐330‐3p function in neuropathic pain remains largely incomplete. Here, we found that miR‐330‐3p was greatly increased in CCI rats and DGCR5 can modulate miR‐330‐3p expression negatively. Upregulation of DGCR5 repressed inflammation‐correlated biomarkers including interleukin 6 (IL‐6), tumor necrosis factor α, and IL‐1β in CCI rats by sponging miR‐330‐3p. The negative correlation between DGCR5 and miR‐330‐3p was confirmed in our current study. Inhibition of miR‐330‐3p suppressed neuropathic pain progression by restraining neuroinflammation in vivo. In addition, PDCD4 was predicted as a downstream target of miR‐330‐3p. Furthermore, PDCD4 was significantly increased in CCI rats and DGCR5 regulated PDCD4 expression through sponging miR‐330‐3p in CCI rat models. Taken these together, it was implied that DGCR5/miR‐330‐3p/PDCD4 axis participated in neuropathic pain treatment.
Romina: A powerful strawberry with in vitro efficacy against uterine leiomyoma cells
Authors: Giampieri Francesca , Islam Md Soriful , Greco Stefania , Gasparrini Massimiliano , Forbes Hernandez Tamara Y. , Delli Carpini Giovanni , Giannubilo Stefano Raffaele , Ciavattini Andrea , Mezzetti Bruno , Mazzoni Luca , Capocasa Franco , Castellucci Mario , Battino Maurizio , Ciarmela Pasquapina
Published: October 2018

Uterine leiom yomas are benign tumors highly prevalent in reproductive women. In thecurrent study, initially, we aimed to screen five different strawberry cultivars (Alba, Clery, Portola, Tecla, and Romina) to identify efficient cultivars in terms of phytochemical characterization and biological properties by measuring phenolic and anthocyanin content as well as antioxidant capacity, and by measuring apoptotic rate and reactive oxygen species (ROS) production in uterine leiomyoma cells. Next, we focused on the most efficient ones, cultivar Alba (A) and Romina (R) as well as Romina anthocyanin (RA) fraction for their ability to regulate oxidative phosphorylation (oxygen consumption rate [OCR]) glycolysis (extracellular acidification rate [ECAR]), and also fibrosis. Leiomyoma and myometrial cells were treated with a methanolic extract of A and R (250 μg/ml) or with RA (50 μg/ml) for 48 hr to measure OCR and ECAR, as well as gene expression associated with fibrosis. In the leiomyoma cells, RA was more effective in inducing apoptosis and increasing intracellular ROS levels, followed by R and A. In myometrial cells, all strawberry treatments increased the cellular viability and decreased ROS concentrations. Leiomyoma cells showed also a significant decrease in ECAR, especially after RA treatment, while OCR was slightly increased in both myometrial and leiomyoma cells. R and RA treatment significantly decreased collagen 1A1, fibronectin, versican, and activin A messenger RNA expression in leiomyoma cells. In conclusion, this study suggests that Romina, or its anthocyanin fraction, can be developed as a therapeutic and/or preventive agent for uterine leiomyomas, confirming the healthy effects exerted by these fruits and their bioactive compounds.
EA15, MIR22, LINC00472 as diagnostic markers for diabetic kidney disease
Authors: Wang Yan‐Zhe , Zhu Ding‐Yu , Xie Xin‐Miao , Ding Miao , Wang Yong‐Lan , Sun Lin‐Lin , Zhang Nan , Shen E. , Wang Xiao‐Xia
Published: October 2018

This study aimed to investigate the molecular mechanisms of diabetic kidney disease (DKD) and to explore new potential therapeutic strategies and biomarkers for DKD. First we analyzed the differentially expressed changes between patients with DKD and the control group using the chip data in Gene Expression Omnibus (GEO) database. Then the gene chip was subjected to be annotated again, so as to screen long noncoding RNAs (lncRNAs) and study expression differences of these lncRNAs in DKD and controlled samples. At last, the function of the differential lncRNAs was analyzed. A total of 252 lncRNAs were identified, and 14 were differentially expressed. In addition, there were 1,629 differentially expressed messenger RNAs (mRNAs) genes, and proliferation and apoptosis adapter protein 15 (PEA15),
MIR22, and long intergenic nonprotein coding RNA 472 (
LINC00472) were significantly differentially expressed in DKD samples. Through functional analysis of the encoding genes coexpressed by the three lncRNAs, we found these genes were mainly enriched in type 1 diabetes and autoimmune thyroid disease pathways, whereas in Gene Ontology (GO) function classification, they were also mainly enriched in the immune response, type I interferon signaling pathways, interferon‐γ mediated signaling pathways, and so forth. To summary, we identified
EA15,
MIR22, and
LINC00472 may serve as the potential diagnostic markers of DKD.