bluuebunny/crossref_metadata_2025 huggingface dataset:
Resting heart rate and risk of type 2 diabetes: A prospective cohort study and meta‐analysis
Authors: Lee Dong Hoon , de Rezende Leandro Fórnias Machado , Hu Frank B. , Jeon Justin Y. , Giovannucci Edward L.
Published: October 2018

Background

Positive association between resting heart rate (RHR) and risk of type 2 diabetes (T2D) has been documented in several studies. However, whether RHR is an independent predictor of T2D and its potential interaction with other risk factors of T2D remain unclear.

Methods

We conducted a prospective cohort study of 31 156 men from the Health Professionals Follow‐up Study (1992‐2012). Cox proportional hazard model was used to examine the association between RHR and T2D risk. We further examined whether this association is modified by known risk factors. Lastly, we conducted a meta‐analysis of prospective cohort studies.

Results

During 505 380 person‐years of follow‐up, we identified 2338 incident T2D cases. The multivariable‐adjusted hazard ratio (HR) comparing the highest vs lowest categories of RHR was 1.69 (95% confidence interval [CI], 1.43‐2.01). Increase in 10 bpm of RHR was associated with 19% increased risk of T2D in the fully adjusted model (HR, 1.19; 95% CI, 1.14‐1.24). The HRs of T2D associated with RHR were stronger among those with normal weight or without hypertension (P interaction < 0.001). Moreover, RHR with other known risk factors cumulatively increased T2D risk. A meta‐analysis consistently showed a positive association between RHR and T2D risk (the summary relative risk [RR] for highest vs lowest RHR, 1.53; 95% CI, 1.26‐1.86, n = 12, the summary RR per 10 bpm increase, 1.17; 95% CI, 1.09‐1.26, n = 13).

Conclusions

High RHR was independently associated with increased risk of T2D. Our findings suggest that RHR, with other known risk factors, could be a useful tool to predict T2D risk.
Combining Bayesian genetic clustering and ecological niche modeling: Insights into wolf intraspecific genetic structure
Authors: Milanesi Pietro , Caniglia Romolo , Fabbri Elena , Puopolo Felice , Galaverni Marco , Holderegger Rolf
Published: October 2018

The distribution of intraspecific genetic variation and how it relates to environmental factors is of increasing interest to researchers in macroecology and biogeography. Recent studies investigated the relationships between the environment and patterns of intraspecific genetic variation across species ranges but only few rigorously tested the relation between genetic groups and their ecological niches. We quantified the relationship of genetic differentiation (FST) and the overlap of ecological niches (as measured by n‐dimensional hypervolumes) among genetic groups resulting from spatial Bayesian genetic clustering in the wolf (Canis lupus) in the Italian peninsula. Within the Italian wolf population, four genetic clusters were detected, and these clusters showed different ecological niches. Moreover, different wolf clusters were significantly related to differences in land cover and human disturbance features. Such differences in the ecological niches of genetic clusters should be interpreted in light of neutral processes that hinder movement, dispersal, and gene flow among the genetic clusters, in order to not prematurely assume any selective or adaptive processes. In the present study, we found that both the plasticity of wolves—a habitat generalist—to cope with different environmental conditions and the occurrence of barriers that limit gene flow lead to the formation of genetic intraspecific genetic clusters and their distinct ecological niches.
Atlantic butterflies: a data set of fruit‐feeding butterfly communities from the Atlantic forests
Authors: Santos Jessie Pereira dos , Freitas André Victor Lucci , Brown Keith Spalding , Carreira Junia Yasmin Oliveira , Gueratto Patrícia Eyng , Rosa Augusto Henrique Batista , Lourenço Giselle Martins , Accacio Gustavo Mattos , Uehara‐Prado Márcio , Iserhard Cristiano Agra , Richter Aline , Gawlinski Karine , Romanowski Helena Piccoli , Mega Nicolás Oliveira , Teixeira Melissa Oliveira , Moser Alfred , Ribeiro Danilo Bandini , Araujo Poliana Felix , Filgueiras Bruno Karol Cordeiro , Melo Douglas Henrique Alves , Leal Inara Roberta , Beirão Marina do Vale , Ribeiro Sérvio Pontes , Cambuí Elaine Cristina Barbosa , Vasconcelos Rodrigo Nogueira , Cardoso Márcio Zikán , Paluch Marlon , Greve Roberto Rezende , Voltolini Júlio Cesar , Galetti Mauro , Regolin André Luis , Sobral‐Souza Thadeu , Ribeiro Milton Cezar
Published: October 2018

Butterflies are one of the best‐known insect groups, and they have been the subject of numerous studies in ecology and evolution, especially in the tropics. Much attention has been given to the fruit‐feeding butterfly guild in biodiversity conservation studies, due to the relative ease with which taxa may be identified and specimens sampled using bait traps. However, there remain many uncertainties about the macroecological and biogeographical patterns of butterflies in tropical ecosystems. In the present study, we gathered information about fruit‐feeding butterfly species in local communities from the Atlantic Forests of South America. The ATLANTIC BUTTERFLIES data set, which is part of ATLANTIC SERIES data papers, results from a compilation of 145 unpublished inventories and 64 other references, including articles, theses, and book chapters published from 1949 to 2018. In total, the data set contains 7,062 records (presence) of 279 species of fruit‐feeding butterflies identified with taxonomic certainty, from 122 study locations. The Satyrini is the tribe with highest number of species (45%) and records (30%), followed by Brassolini, with 13% of species and 12.5% of records. The 10 most common species correspond to 14.2% of all records. This data set represents a major effort to compile inventories of fruit‐feeding butterfly communities, filling a knowledge gap about the diversity and distribution of these butterflies in the Atlantic Forest. We hope that the present data set can provide guidelines for future studies and planning of new inventories of fruit‐feeding butterflies in this biome. The information presented here also has potential use in studies across a great variety of spatial scales, from local and landscape levels to macroecological research and biogeographical research. We expect that such studies be very important for the better implementation of conservation initiatives, and for understanding the multiple ecological processes that involve fruit‐feeding butterflies as biological indicators. No copyright restrictions apply to the use of this data set. Please cite this Data paper when using the current data in publications or teaching events.
Actor perceptions of polycentricity in wind power governance
Authors: Juerges Nataly , Leahy Jessica , Newig Jens
Published: October 2018

Wind power development as an alternative to fossil fuels or nuclear energy is currently a challenge for many countries. Wind power development often leads to conflicts between different actors. This case study examines conflict about wind power projects in forested landscapes in Rhineland‐Palatinate, Germany, and Maine, USA. Specifically, actor perspectives on polycentric governance and its legitimacy to manage such complex conflicts were evaluated based on 40 qualitative, semistructured interviews with actors engaged in wind power decisions from various sectors. Polycentric governance has been advocated by many to alleviate conflicts and arrive at sustainable solutions in complex resource management settings. Polycentric governance systems of wind power issues were regarded positively and considered as having high legitimacy by interview participants. Even though individuals had varied perceptions, the combined perceptions of the two polycentric systems in Rhineland‐Palatinate and Maine and the factors that constitute legitimacy in wind power governance were similar in both cases.
Management and outcomes of cardiac sarcoidosis: a 20‐year experience in two tertiary care centres
Authors: Fussner Lynn A. , Karlstedt Erin , Hodge David O. , Fine Nowell M. , Kalra Sanjay , Carmona Eva M. , Utz James P. , Isaac Debra L. , Cooper Leslie T.
Published: October 2018

Aims

Cardiac sarcoidosis (CS) often presents with ventricular arrhythmias, heart block, and cardiomyopathy. The prognosis of CS with contemporary management is uncertain. We estimated the impact of baseline and treatment variables on left ventricular ejection fraction (LVEF), ventricular assist device placement, heart transplant, and death.

Methods and results

We identified patients with CS seen from 1994–2014 at two large academic medical centres. All met the 2014 Heart Rhythm Society expert consensus criteria for diagnosis. From the 574 patients identified, 91 met inclusion criteria. Twenty‐two (24.2%) were diagnosed by endomyocardial biopsy. Cardiomyopathy was the primary presentation in 47 patients (51.6%). Within 90 days of diagnosis, 41 patients (45.0%) received prednisone alone, 29 (31.9%) received alternative immunosuppression with or without prednisone, and 21 (23.1%) received no immunosuppression. During follow‐up, 31 of 47 cardiomyopathy patients experienced improvement in LVEF, while 23 experienced decline in LVEF or clinical exacerbation, and 15 of 22 patients presenting with ventricular arrhythmia had recurrence. These results did not differ by treatment group. During a median follow‐up of 44 months for our cohort, 14 patients reached the composite endpoint of ventricular assist device placement, heart transplant, or death. Survival without the composite outcome did not differ by treatment group, but was worse among patients presenting with cardiomyopathy (log‐rank = 0.005).

Conclusion

In a large series of CS subjects, rates of ventricular arrhythmia and heart failure events remain high with no treatment regimen clearly associated with better outcome. Patients with cardiomyopathy at diagnosis were more likely to reach the composite endpoint.
Novel Selective Approach to Terminally Substituted [n]Dendralenes
Authors: Polák Peter , Tobrman Tomáš
Published: October 2018

Dendralenes are simple alkenes with cross‐conjugated double bonds that are frequently synthesized due to being potentially valuable building blocks for the synthesis of more complex structures. The synthetic approaches to dendralenes are based on the cross‐coupling reactions of electrophilic and nucleophilic synthons derived from geminally substituted ethylene. Our novel methodology for the synthesis of only terminally substituted [3]‐ and [4]dendralenes, as well as 2,3‐disubstituted buta‐1,3‐dienes, involves the preparation of 1,2‐disubstituted cyclobutenes from readily available 2‐bromocyclobutanone and the subsequent thermal ring‐opening reactions.
Economic evaluation of a healthy lifestyle intervention for chronic low back pain: A randomized controlled trial
Authors: Williams Amanda , van Dongen Johanna M. , Kamper Steven J. , O'Brien Kate M. , Wolfenden Luke , Yoong Sze L. , Hodder Rebecca K. , Lee Hopin , Robson Emma K. , Haskins Robin , Rissel Chris , Wiggers John , Williams Christopher M.
Published: October 2018

Background

Economic evaluations which estimate cost‐effectiveness of potential treatments can guide decisions about real‐world healthcare services. We performed an economic evaluation of a healthy lifestyle intervention targeting weight loss, physical activity and diet for patients with chronic low back pain, who are overweight or obese.

Methods

Eligible patients with chronic low back pain (n = 160) were randomized to an intervention or usual care control group. The intervention included brief advice, a clinical consultation and referral to a 6‐month telephone‐based healthy lifestyle coaching service. The primary outcome was quality‐adjusted life years (QALYs). Secondary outcomes were pain intensity, disability, weight and body mass index. Costs included intervention costs, healthcare utilization costs and work absenteeism costs. An economic analysis was performed from the societal perspective.

Results

Mean total costs were lower in the intervention group than the control group (‐$614; 95%CI: −3133 to 255). The intervention group had significantly lower healthcare costs (‐$292; 95%CI: −872 to −33), medication costs (−$30; 95%CI: −65 to −4) and absenteeism costs (‐$1,000; 95%CI: −3573 to −210). For all outcomes, the intervention was on average less expensive and more effective than usual care, and the probability of the intervention being cost‐effective compared to usual care was relatively high (i.e., 0.81) at a willingness‐to‐pay of $0/unit of effect. However, the probability of cost‐effectiveness was not as favourable among sensitivity analyses.

Conclusions

The healthy lifestyle intervention seems to be cost‐effective from the societal perspective. However, variability in the sensitivity analyses indicates caution is needed when interpreting these findings.

Significance

This is an economic evaluation of a randomized controlled trial of a healthy lifestyle intervention for chronic low back pain. The findings suggest that a healthy lifestyle intervention may be cost‐effective relative to usual care.
The type of sport matters: Pain perception of endurance athletes versus strength athletes
Authors: Assa Tal , Geva Nirit , Zarkh Yoni , Defrin Ruth
Published: October 2018

Background

Studies assessing athletes’ pain sensitivity yield inconsistent data, which demonstrate either increased pain threshold and tolerance in athletes than controls or similar thresholds. This inconsistency may result from the variability in the type of sport practiced by the athletes and its effect on pain perception. For example, endurance athletes perform continuous intense exercise for prolonged durations, whereas strength athletes perform short bouts of extreme efforts. Consequently, endurance athletes may tolerate and modulate pain better than strength athletes. This hypothesis was tested by comparing pain perception of endurance athletes with that of strength athletes.

Methods

Subjects were 19 endurance athletes (triathletes), 17 strength athletes (weightlifters and throwers) and 17 non‐athlete controls. Quantitative measurements included heat‐pain threshold, heat‐pain tolerance, cold pressor pain ratings, temporal summation of pain (TSP) and conditioned pain modulation (CPM). Fear of pain and pain catastrophizing were also assessed.

Results

The two athlete groups had lower pain ratings than non‐athletes. However, strength athletes had higher heat‐pain threshold than endurance athletes, whereas endurance athletes had higher heat‐pain tolerance and stronger CPM than strength athletes and lower fear of pain levels. Longer training time correlated with TSP in endurance athletes but with CPM and heat‐pain tolerance in strength athletes.

Conclusions

Although athletes in general seem less responsive to noxious stimuli than non‐athletes, the type of sport differentially affects pain perception; whereas endurance‐based sport is associated with improved pain inhibition, strength‐based sport is associated with reduced pain sensitivity. These characteristics may be considered when sport is recommended for pain management.

Significance

This study shows that different sport types are associated with different characteristics of pain perception and modulation, as well as of thoughts towards pain.
Freestanding RGO—Co3O4—PPy Composite Films as Electrodes for Supercapacitors
Authors: Jiang Lili , Li Youjian , Luo Dan , Zhang Qinyong , Cai Fanggong , Wan Guojiang , Xiong Lu , Ren Zhifeng
Published: October 2018

Supercapacitors are of great importance for energy storage and have been the subject of intensive research in recent years, in which conductive polymers are used to make flexible and freestanding electrodes. However, their insufficient access to the electrolytes and the low chemical stability of these conductive polymers lead to their poor performance. To solve these issues, a facile method that can be used to synthesize freestanding composite film electrodes of reduced graphene oxide–cobalt oxide–polypyrrole (RGO—Co3O4—PPy) as supercapacitors is demonstrated. They exhibit a high specific capacitance of 532.8 F g−1 and nearly no degradation after 700 cycles of charging and discharging. The synergistic effect of Co3O4, RGO, and PPy is responsible for the superior property. The three‐phase composite electrode utilizes the RGO nanosheet as a substrate to provide a large surface area for loading Co3O4 nanoparticles and also to enhance the electron transfer. Furthermore, the deposition of PPy largely reduces the resistivity of RGO—Co3O4—PPy, and the introduction of Co3O4 nanoparticles significantly improves cycle stability.
A Novel Method of Synthesizing Boron‐doped Carbon Catalysts
Authors: Suo N. , Huang H. , Wu A. M. , Cao G. Z. , Zhang G. F.
Published: October 2018

Boron‐doped carbon catalysts are prepared by a novel method combining hot filament chemical vapor deposition technique with high temperature annealing treatment. Nano‐boron powders are coated by thin diamond layers and then the coated nano‐boron powders are annealed for different times at 1,300 °C in vacuum. The morphology, microstructure, and chemical bonding states of the synthetized materials have been investigated by scanning electron microscope (SEM), X‐ray diffraction (XRD), Raman spectroscopy, Fourier transform infrared spectroscopy (FT‐IR), and X‐ray photoelectron spectroscopy (XPS), respectively. The results indicate that boron atoms have diffused into the carbon lattice and the content of doping boron rises gradually with the increase of annealing time. The characteristic signal of the B‐C bond will vanish and of the signal B4C will appear, if the annealing time is too long. The experimental results of rotating disk electrode (RDE) voltammetry illustrate that the catalyst obtained after annealing for 2 h has the highest electrocatalytic oxygen reduction reaction (ORR) activity. The response current characterized by chronoamperometry exhibits that the deposits with a higher catalytic activity have a poorer stability and methanol tolerance.
Why and how do foreign institutional investors outperform domestic investors in futures trading: Evidence from Taiwan
Authors: Chuang Yi‐Wei , Lin Yu‐Fen , Weng Pei‐Shih
Published: October 2018

A unique data set containing all transactions from the Taiwan Futures Exchange allows us to dissect the long‐lasting outperformance of foreign institutional investors in this emerging market. We show that foreign institutional investors comprehensively outperform domestic investors in trade directions, submission types, trading counterparties, order sizes, and order aggressiveness. Although submitting passive orders increases the trading profits of each investor group significantly, particularly for foreign institutions, the most passive domestic trades still lose to the most aggressive foreign institutional trades. We suggest that information advantage plays a more important role than order submission strategy in foreign institutional investors’ superior performance.
Traumatic brain injury‐induced neuronal damage in the somatosensory cortex causes formation of rod‐shaped microglia that promote astrogliosis and persistent neuroinflammation
Authors: Witcher Kristina G. , Bray Chelsea E. , Dziabis Julia E. , McKim Daniel B. , Benner Brooke N. , Rowe Rachel K. , Kokiko‐Cochran Olga N. , Popovich Phillip G. , Lifshitz Jonathan , Eiferman Daniel S. , Godbout Jonathan P.
Published: October 2018

Microglia undergo dynamic structural and transcriptional changes during the immune response to traumatic brain injury (TBI). For example, TBI causes microglia to form rod‐shaped trains in the cerebral cortex, but their contribution to inflammation and pathophysiology is unclear. The purpose of this study was to determine the origin and alignment of rod microglia and to determine the role of microglia in propagating persistent cortical inflammation. Here, diffuse TBI in mice was modeled by midline fluid percussion injury (FPI). Bone marrow chimerism and BrdU pulse‐chase experiments revealed that rod microglia derived from resident microglia with limited proliferation. Novel data also show that TBI‐induced rod microglia were proximal to axotomized neurons, spatially overlapped with dense astrogliosis, and aligned with apical pyramidal dendrites. Furthermore, rod microglia formed adjacent to hypertrophied microglia, which clustered among layer V pyramidal neurons. To better understand the contribution of microglia to cortical inflammation and injury, microglia were eliminated prior to TBI by CSF1R antagonism (PLX5622). Microglial elimination did not affect cortical neuron axotomy induced by TBI, but attenuated rod microglial formation and astrogliosis. Analysis of 262 immune genes revealed that TBI caused profound cortical inflammation acutely (8 hr) that progressed in nature and complexity by 7 dpi. For instance, gene expression related to complement, phagocytosis, toll‐like receptor signaling, and interferon response were increased 7 dpi. Critically, these acute and chronic inflammatory responses were prevented by microglial elimination. Taken together, TBI‐induced neuronal injury causes microglia to structurally associate with neurons, augment astrogliosis, and propagate diverse and persistent inflammatory/immune signaling pathways.
Factors affecting the choice of health care utilisation between private and public services among the elderly population in India
Authors: Chatterjee Chandrima , Nayak Narayan Chandra , Mahakud Jitendra , Chatterjee Suhita Chopra
Published: October 2018

India is experiencing rapid population ageing in recent years. One of the most concomitant issues is the choice of health care services among the elderly, leading to its impact on the magnitude of health expenditure. Applying Andersen's Health Behavioural Model, this study identifies the predictors of the choice of inpatient health care services among the Indian elderly between private and public services. It also examines the nature of interregional disparity in the choice of health care services. Using NSSO data, the results suggest that the elderly belonging to upper caste and having higher levels of education, higher incomes, larger family size, and needing surgery are likely to choose private health care, while those experiencing higher economic dependence, chronic diseases, and higher duration of hospitalisation tend to prefer public inpatient services. The magnitude and significance of these factors, however, vary across regions. The findings of the study provide an understanding of the preferences of the India's geriatric population over hospital services, which may help policymakers better understand their health care needs.
Evolution of quality of life and health‐related behaviors among Spanish university students
Authors: Faílde Garrido José María , Ruiz Soriano Laura , Pérez Fernández María Reyes , Lameiras Fernández María , Rodríguez Castro Yolanda
Published: October 2018

At the beginning of their academic studies (testing phase), the quality of life and certain health‐related behaviors were evaluated. Four years later (retest phase), they were reevaluated. Between the two evaluation periods, a health promotion (HP) program was applied. The battery of instruments included measures: health‐related quality of life (HRQOL), alcoholic and nicotine dependence, eating habits, physical activity, and sexual behaviors. It also included a number of sociodemographic data. The results show that, in general, the students reported adequate levels of HRQOL, and there were no important differences between the two evaluation moments. Regarding dietary behavior, no significant changes were detected in the pattern of adherence to the Mediterranean diet, which remained at an average level of adequacy. On the contrary, significant decreases were detected in relation to alcohol and tobacco dependence as well as significant increases in physical activity levels. Lastly, with regard to sexual behavior, although certain aspects of improvement were perceived, there is a need to increase awareness of the systematic use of condoms. In conclusion, this study provides relevant information that will serve as a starting point for monitoring changes in health behaviors and for the design and implementation of HP actions directed at university students.
MHD boundary layer flow of SWCNT‐water and MWCNT‐water nanofluid over a vertical cone with heat generation/absorption
Authors: Reddy Y. Raja Obula , Reddy M. Suryanarayana , Reddy P. Sudarsana
Published: October 2018

The analysis is carried out to investigate the magneto hydro dynamics (MHD) boundary layer flow, heat and mass transfer characteristics of two carbon nanotubes, namely, single‐wall carbon nanotubes (SWCNTs) and multiwall carbon nanotubes (MWCNTs), with water as the base fluid by taking thermal radiation and chemical reaction into consideration. Suitable similarity conversions are employed to reduce nonlinear partial differential equations into the system of ordinary differential equations, and these equations together with boundary conditions are solved numerically using the finite element method. Velocity, temperature, and concentration distributions as well as skin friction coefficient, Nusselt number, and Sherwood number for diverse values of influencing parameters are examined in detail, and the results are displayed graphically and in tabular form. It is found that the rate of heat transfer is remarkably higher in water‐based MWCNTs than the SWCNTs as the value of the nanoparticle volume fraction parameter rises in the boundary layer regime.
Optimizing C2C12 myoblast differentiation using polycaprolactone–polypyrrole copolymer scaffolds
Authors: Browe Daniel , Freeman Joseph
Published: October 2018

Advancements in tissue engineering and biomaterial development have the potential to provide a scalable solution to the problem of large‐volume skeletal muscle defects. Previous research on the development of scaffolds for skeletal muscle regeneration has focused on strategies for increasing conductivity, which has improved satellite cell attachment and differentiation. However, these strategies usually increase scaffold stiffness, which some studies suggest may be detrimental to myoblast development. In this study, the polymers polypyrrole (PPy) and polycaprolactone (PCL) were synthesized together into a copolymer (PPy–PCL) designed to increase scaffold conductivity without significantly influencing stiffness. Different scaffold groups were fabricated via electrospinning, characterized, and assessed for their suitability for myoblast proliferation and differentiation. The groups included an aligned and random iteration of pure PCL, 10% PPy–PCL, 20% PPy–PCL, and 40% PPy–PCL. Only the 40% PPy–PCL group had a measureable conductivity, and the addition of PPy–PCL had no significant effect on the stiffness of the scaffolds. The PPy–PCL copolymer significantly increased the attachment of C2C12 myoblasts as compared to pure PCL scaffolds, but the concentration of PPy–PCL did not significantly alter cell attachment. In addition, scaffolds with PPy–PCL promoted myoblast differentiation to a greater extent than scaffolds made of PCL as measured by fusion index and number of nuclei per myotube. Aligned scaffolds were superior to random scaffolds in almost all measures. These results suggest that conductivity may not be the key factor in improving skeletal muscle scaffolds. Instead, cell attachment and aligned guidance cues may have a greater impact on myoblast differentiation. © 2018 Wiley Periodicals, Inc. J Biomed Mater Res Part A: 107A: 220–231, 2019.
Synergistic antitumor effects of rhein and doxorubicin in hepatocellular carcinoma cells
Authors: Wu Li , Liu Xiao , Cao Ke Xin , Ni Zi hui , Li Wei Dong , Chen Zhi Peng
Published: October 2018

The aim of this study was to investigate the synergistic antitumor activity of rhein and doxorubicin (DOX) and to elucidate the underlying mechanisms in hepatocellular SMMC‐7721 and HepG2 cells. Cell growth curves, caspase‐3 activity, and intracellular DOX accumulation were observed using an IncuCyte real‐time video imaging system. Combination index was used to calculate synergistic potential of rhein and DOX. Cell apoptosis was detected by the Annexin V‐FITC/PI apoptosis kit. Lactate dehydrogenase and adenosine triphosphate (ATP) levels were assessed using an assay kit. Oxygen consumption rates (OCR) and extracellular acidification rates were assessed by the Seahorse XFe96 Extracellular Flux Analyzer. Mitochondrial inner membrane potential (ΔΨm) was monitored with JC‐1 fluorescence. Western blot analysis was used to detect the level of P‐glycoprotein. Synergistic antiproliferative and proapoptotic effects were exerted by the combination of rhein at 10 μM and DOX at 2 μM in SMMC‐7721 and HepG2 cells. Rhein could influenced the accumulation of DOX in both cells, which was associated with remarkably decreased mitochondrial energy metabolism and ATP levels. Rhein could reduce ΔΨm in both cells. mPTP, opener atractyloside (ATR) could accelerate the loss of ΔΨm, and further suppress the OCR induced by rhein. In contrast, the mPTP blocker cyclosporin A (Cs A) inhibited the loss of ΔΨm and the OCR induced by rhein. Our data indicate that a decline in mitochondrial energy metabolism was responsible for the synergistic antitumor effects of rhein and DOX in hepatocellular carcinoma cells. Reduction of ΔΨm and opening of mPTP inhibited the exchange of ATP/adenosine diphosphate between mitochondrial matrix and cytoplasm is the important mechanism.
Expression and the potential functions of TRIM32 in lung cancer tumorigenesis
Authors: Yin Hongmei , Li Zhen , Chen Jia , Hu Xiaobo
Published: October 2018

TRIM32 is a member of the tripartite motif (TRIM) family, which has been associated with tumorigenesis. However, its expression and potential functional role(s) in lung cancer progression have not been fully understood. To evaluate the relationship between the expression of TRIM32 and the prognosis of patients with lung cancer, an independent data set (The Human Protein Atlas website) was introduced. The expression and function analysis of TRIM32 in lung cancer cell lines were also performed by using cell counting kit‐8, flow cytometry, transwell, real‐time polymerase chain reaction and Western blot analysis. Our data showed that TRIM32 was overexpressed in lung cancer tissues and cell lines and was associated with a poor prognosis. TRIM32 silencing inhibited cell proliferation, migration, invasion, adhesion, and the activation of janus kinase 2 (JAK2)/signal transducer and activator of transcription 3 (STAT3) signaling. The results showed knockdown of TRIM32 in NCI‐H446 cells also inhibited cell growth in nude mice in the xenograft model. Additionally, TRIM32 overexpression promoted lung cancer cell proliferation and motility and mediated the expression of Bax, Bcl‐2, cleaved caspase‐3, matrix metalloproteinase‐2 (MMP‐2) and MMP‐9 were inhibited by JAK2/STAT3 signaling inhibitor (AG490). Taken together, our findings suggest that TRIM32 may regulate lung cancer cell proliferation, apoptosis, and motility through activating the JAK2/STAT3‐signaling pathway and may be a novel and promising target for lung cancer.
Therapeutic potential of RAS prenylation pharmacological inhibitors in the treatment of breast cancer, recent progress, and prospective
Authors: Soleimani Atena , Amirinejad Mostafa , Rahsepar Sara , Vazirian Fatemeh , Bahrami Afsane , Ferns Gordon A. , Khazaei Majid , Avan Amir , Hassanian Seyed Mahdi
Published: October 2018

Breast cancer is one of the most prevalent malignancies among women around the world. RAS proteins require posttranslational modifications, including protein prenylation for proper membrane localization and signaling. Regulation of RAS signaling via specific and novel pharmacological inhibitors is a potentially novel therapeutic approach in breast cancer therapy. This review summarizes the recent knowledge about the clinical value of RAS prenylation pharmacological inhibitors in breast cancer treatment.
Identification of a universal 6‐lncRNA prognostic signature for three pathologic subtypes of renal cell carcinoma
Authors: Zuo Shuguang , Wang Liping , Wen Yuqing , Dai Gongpeng
Published: October 2018

Renal cell carcinoma (RCC) is the most common adult renal epithelial cancer susceptible to metastasis and patients with irresectable RCC always have a poor prognosis. Long noncoding RNAs (lncRNAs) have recently been documented as having critical roles in the etiology of RCC. Nevertheless, the prognostic significance of lncRNA‐based signature for outcome prediction in patients with RCC has not been well investigated. Therefore, it is essential to identify a lncRNA‐based signature for predicting RCC prognosis. In the current study, we comprehensively analyzed the RNA sequencing data of the three main pathological subtypes of RCC (kidney renal clear cell carcinoma [KIRC], kidney renal papillary cell carcinoma [KIRP], and kidney chromophobe carcinoma [KICH]) from The Cancer Genome Atlas (TCGA) database, and identified a 6‐lncRNA prognostic signature with the help of a step‐wise multivariate Cox regression model. The 6‐lncRNA signature stratified the patients into low‐ and high‐risk groups with significantly different prognosis. Multivariate Cox regression analysis showed that predictive value of the 6‐lncRNA signature was independent of other clinical or pathological factors in the entire cohort and in each cohort of RCC subtypes. In addition, the three independent prognostic clinical factors (including age, pathologic stage III, and stage IV) was also stratified into low‐ and high‐risk groups basis on the risk score, and the stratification analyses demonstrated that the high‐risk score was a poor prognostic factor. In conclusion, these findings indicate that the 6‐lncRNA signature is a novel prognostic biomarker for all three subtypes of RCC, and can increase the accuracy of predicting overall survival.
Accurate heats of formation of polycyclic saturated hydrocarbons predicted by using the XYG3 type of doubly hybrid functionals
Authors: Zhang Igor Ying , Wu Jianming , Xu Xin
Published: October 2018

Polycyclic saturated hydrocarbons (PSHs) are attractive candidates as hydrocarbon propellants. To assess their potential values, one of the key factors is to determine their energy contents, such as to calculate their heats of formation (HOF). In this work, we have calculated HOFs for a set of 36 PSHs including exo‐Tricyclo[5.2.1.0(2,6)] decane, the principal component of the high‐energy density hydrocarbon fuel commonly identified as JP‐10. The results from B3LYP, B3LYP‐D3BJ, M06‐2X, B2PLYP, B2PLYP‐D3BJ, and the XYG3 type of doubly hybrid (xDH) functionals are presented. It is demonstrated here that the xDH functionals yield accurate HOFs in good agreement with those from experiments or the G4 theory. In particular, XYGJ‐OS, a low scaling xDH functional, is shown to hold the promise for accurate prediction of HOFs for PSHs of larger sizes. © 2018 Wiley Periodicals, Inc.
Tumor microenvironment: Interactions and therapy
Authors: Najafi Masoud , Goradel Nasser Hashemi , Farhood Bagher , Salehi Eniseh , Solhjoo Somaye , Toolee Heidar , Kharazinejad Ebrahim , Mortezaee Keywan
Published: October 2018

Tumor microenvironment (TME) is a host for a complex network of heterogeneous stromal cells with overlapping or opposing functions depending on the dominant signals within this milieu. Reciprocal paracrine interactions between cancer cells with cells within the tumor stroma often reshape the TME in favor of the promotion of tumor. These complex interactions require more sophisticated approaches for cancer therapy, and, therefore, advancing knowledge about dominant drivers of cancer within the TME is critical for designing therapeutic schemes. This review will provide knowledge about TME architecture, multiple signaling, and cross communications between cells within this milieu, and its targeting for immunotherapy of cancer.
Tubulin–Na+,K+‐ATPase interaction: Involvement in enzymatic regulation and cellular function
Authors: Santander Veronica S. , Campetelli Alexis N. , Monesterolo Noelia E. , Rivelli Juan F. , Nigra Ayelen D. , Arce Carlos A. , Casale César H.
Published: October 2018

A new function for tubulin was described by our laboratory: acetylated tubulin forms a complex with Na+,K
+‐ATPase (NKA) and inhibits its activity. This process was shown to be a regulatory factor of physiological importance in cultured cells, human erythrocytes, and several rat tissues. Formation of the acetylated tubulin–NKA complex is reversible. We demonstrated that in cultured cells, high concentrations of glucose induce translocation of acetylated tubulin from cytoplasm to plasma membrane with a consequent inhibition of NKA activity. This effect is reversed by adding glutamate, which is coctransported to the cell with Na
+. Another posttranslational modification of tubulin, detyrosinated tubulin, is also involved in the regulation of NKA activity: it enhances the NKA inhibition induced by acetylated tubulin. Manipulation of the content of these modifications of tubulin could work as a new strategy to maintain homeostasis of Na
+ and K
+, and to regulate a variety of functions in which NKA is involved, such as osmotic fragility and deformability of human erythrocytes. The results summarized in this review show that the interaction between tubulin and NKA plays an important role in cellular physiology, both in the regulation of Na
+/K
+ homeostasis and in the rheological properties of the cells, which is mechanically different from other roles reported up to now.
VEGF‐C attenuates renal damage in salt‐sensitive hypertension
Authors: Beaini Shadia , Saliba Youakim , Hajal Joelle , Smayra Viviane , Bakhos Jules‐Joel , Joubran Najat , Chelala Dania , Fares Nassim
Published: October 2018

Salt‐sensitive hypertension is a major risk factor for renal impairment leading to chronic kidney disease. High‐salt diet leads to hypertonic skin interstitial volume retention enhancing the activation of the tonicity‐responsive enhancer‐binding protein (TonEBP) within macrophages leading to vascular endothelial growth factor C (VEGF‐C) secretion and NOS3 modulation. This promotes skin lymphangiogenesis and blood pressure regulation. Whether VEGF‐C administration enhances renal and skin lymphangiogenesis and attenuates renal damage in salt‐sensitive hypertension remains to be elucidated. Hypertension was induced in BALB/c mice by a high‐salt diet. VEGF‐C was administered subcutaneously to high‐salt‐treated mice as well as control animals. Analyses of kidney injury, inflammation, fibrosis, and biochemical markers were performed in vivo. VEGF‐C reduced plasma inflammatory markers in salt‐treated mice. In addition, VEGF‐C exhibited a renal anti‐inflammatory effect with the induction of macrophage M2 phenotype, followed by reductions in interstitial fibrosis. Antioxidant enzymes within the kidney as well as urinary RNA/DNA damage markers were all revelatory of abolished oxidative stress under VEGF‐C. Furthermore, VEGF‐C decreased the urinary albumin/creatinine ratio and blood pressure as well as glomerular and tubular damages. These improvements were associated with enhanced TonEBP, NOS3, and lymphangiogenesis within the kidney and skin. Our data show that VEGF‐C administration plays a major role in preserving renal histology and reducing blood pressure. VEGF‐C might constitute an interesting potential therapeutic target for improving renal remodeling in salt‐sensitive hypertension.
Allicin attenuates calcium oxalate crystal deposition in the rat kidney by regulating gap junction function
Authors: Lai Yongchang , Liang Xiongfa , Zhong Fangling , Wu Weizhou , Zeng Tao , Huang Jian , Duan Xiaolu , Li Shujue , Zeng Guohua , Wu Wenqi
Published: October 2018

Renal calculus is a global common urological disease that is closely related to crystal adhesion and renal tubular epithelial cell impairment. Gap junctions (GJs) and their components (connexins and Cxs) are involved in various pathophysiology processes, but their roles in renal calculi progression are not well defined. Our previous RNA microarray analysis suggests that GJs are one of the key predicted pathways involved in the renal calcium oxalate (CaOx) crystal rat model. In the current study, we found that the Cx43 and Cx32 expression and the GJ function decreased significantly after stimulation with CaOx or sodium oxalate (NaOx) in NRK‐52E, MDCK, and HK‐2 cells, and Cx43 expression also decreased in renal tissues in renal CaOx crystal model rats. Inhibition of Cx43 in NRK‐52E cells by small interference RNA significantly increased the CD44 and androgen receptor expression, and the adhesion between CaOx crystals and cells, which were consistent with the function of GJ inhibitors. On the other hand, after GJ function and Cx43 expression were increased by allicin, diallyl disulfide, or diallyl trisulfide, the impairment of NRK‐52E cells by NaOx or other GJ inhibitors and the adhesion between CaOx crystals and renal cells decreased significantly. Furthermore, allicin also increased Cx43 expression and inhibited crystal deposition in rat kidneys. Taken together, our results provide a basis that GJs and Cx43 may participate in renal CaOx stone progression and that allicin, together with its analogues, could be potential drugs for renal calculus precaution.
Myostatin induces tumor necrosis factor‐α expression in rheumatoid arthritis synovial fibroblasts through the PI3K–Akt signaling pathway
Authors: Su Chen‐Ming , Hu Sung‐Lin , Sun Yi , Zhao Jin , Dai Chengqian , Wang Lihong , Xu Guohong , Tang Chih‐Hsin
Published: October 2018

In rheumatoid arthritis (RA), a chronic inflammatory disease, loss of muscle mass is an important contributor to the loss of muscle strength in RA patients. Myostatin, a myokine involved in the process of muscle hypertrophy and myogenesis, enhances osteoclast differentiation and inflammation. Here, we investigated the mechanisms of myostatin in RA synovial inflammation. We found a positive correlation between myostatin and tumor necrosis factor‐α (TNF‐α), a well‐known proinflammatory cytokine, in RA synovial tissue. Our in vitro results also showed that myostatin dose‐dependently induced TNF‐α expression through the phosphatidylinositol 3‐kinase (PI3K)–Akt–AP‐1 signaling pathway. Myostatin treatment of human MH7A cells stimulated AP‐1‐induced luciferase activity and activation of the c‐Jun binding site on the TNF‐α promoter. Our results indicated that myostatin increases TNF‐α expression via the PI3K–Akt–AP‐1 signaling pathway in human RA synovial fibroblasts. Myostatin appears to be a promising target in RA therapy.
Interaction between mesenchymal stromal cell‐derived extracellular vesicles and immune cells by distinct protein content
Authors: Mardpour Soura , Hamidieh Amir Ali , Taleahmad Sara , Sharifzad Farzaneh , Taghikhani Adeleh , Baharvand Hossein
Published: October 2018

Mesenchymal stromal cells (MSCs) can effectively contribute to tissue regeneration inside the inflammatory microenvironment mostly through modulating immune responses. MSC‐derived extracellular vesicles (MSC‐EVs) display immunoregulatory functions similar to parent cells. Interactions between MSC‐EVs and immune cells make them an ideal therapeutic candidate for infectious, inflammatory, and autoimmune diseases. These properties of MSC‐EVs have encouraged researchers to perform extensive studies on multiple factors that mediate MSC‐EVs immunomodulatory effects. Investigation of proteins involved in the complex interplay of MSC‐EVs and immune cells may help us to better understand their functions. Here, we performed a comprehensive proteomic analysis of MSC‐EVs that was previously reported by ExoCarta database. A total of 938 proteins were identified as MSC‐EV proteome using quantitative proteomics techniques. Kyoto Encyclopedia of Genes and Genomes analysis demonstrates that ECM–receptor interaction, focal adhesion, and disease‐specific pathways are enriched in MSC‐EVs. By detail analysis of proteins presence in immune system process, we found that expression of some cytokines, chemokines, and chemokine receptors such as IL10, HGF, LIF, CCL2, VEGFC, and CCL20, which leads to migration of MSC‐EVs to injured sites, suppression of inflammation and promotion of regeneration in inflammatory and autoimmune diseases. Also, some chemoattractant proteins such as CXCL2, CXCL8, CXCL16, DEFA1, HERC5, and IFITM2 were found in MSC‐EV proteome. They may actively recruit immune cells to the proximity of MSC or MSC‐EVs, may result in boosting immune response under specific circumstances, and may have protective role in infectious diseases. In this review, we summarize available information about immunomodulation of MSC‐EVs with particular emphasis on their proteomics analysis.
Stromal‐induced downregulation of miR‐1247 promotes prostate cancer malignancy
Authors: Taddei Maria Letizia , Cavallini Lorenzo , Ramazzotti Matteo , Comito Giuseppina , Pietrovito Laura , Morandi Andrea , Giannoni Elisa , Raugei Giovanni , Chiarugi Paola
Published: October 2018

Cancer progression is strictly dependent on the relationship between tumor cells and the surrounding stroma, which supports cancer malignancy promoting several crucial steps of tumor progression, including the execution of the epithelial to mesenchymal transition (EMT) associated with enhancement in cell invasion, resistance to both anoikis and chemotherapeutic treatments. Recently it has been highlighted the central role of microRNAs (miRNAs) as regulators of tumor progression. Notably, in several tumors a strong deregulation of miRNAs is observed, supporting proliferation, invasion, and metabolic reprogramming of tumor cells. Here we demonstrated that cancer‐associated fibroblasts induce a downregulation of miR‐1247 in prostate cancer (PCa) cells. We proved that miR‐1247 repression is functional for the achievement of EMT and increased cell invasion as well as stemness traits. These phenomena contribute to promote the metastatic potential of PCa cells as demonstrated by increased lung colonization in in vivo experiments. Moreover, as a consequence of miR‐1247 downregulation, we observed a correlated increased expression level of neuropilin‐1, a miR‐1247 target involved as a coreceptor in the epidermal growth factor receptor signaling. Taken together, our data highlight miR‐1247 as a potential target for molecular therapies aimed to block the progression and diffusion of PCa.