bluuebunny/crossref_metadata_2025 huggingface dataset:
Early childhood development in Iran and its provinces: Inequality versus average
Authors: Rarani Mostafa Amini , Nosratabadi Mehdi , Moeeni Maryam
Published: August 2018

Background

Early childhood development is influenced by family socioeconomic status in such a way that socioeconomic deprivation might be accompanied with adverse outcomes in early development of a child. This study aimed to assess early childhood development based on average and also based on the distribution of socioeconomic inequality in Iran and its provinces.

Methods

Using data from provincially representative Multiple Indicator Demographic and Health Survey (2010), we developed a suitable latent class approach to construct a proxy of socioeconomic status. A composite index of early childhood development was used. We assessed inequality in early childhood development using the concentration index method.

Results

At province level (n = 30), the highest and lowest averages of early childhood development were 13.60 (SD = 2.99) and 5.81 (SD = 3.29), respectively. Concentration indices indicated pro‐rich inequality in early childhood development at national and provincial level. The concentration index of early childhood development was 0.087 (95% CI = 0.085‐0.0098) in Iran. Moreover, the consistent positive values of the concentration indices revealed that early childhood development inequality favored best‐off children in all provinces. However, early childhood development was disproportionally distributed among provinces and rated 0.016 to 0.149.

Conclusions

Iranian children in more prosperous households reported higher early childhood development compared with those in poor households at national and provincial level. It is vital to consider inequality in addition to average level of childhood development across Iranian provinces to reach a more comprehensive understanding of childhood development for public policy action in the country.
Moderating healthcare costs through an assisted physical activity programme
Authors: Vagnoni Emidia , Biavati Giulia Rita , Felisatti Michele , Pomidori Luca
Published: August 2018

Background

During the last decades, physical inactivity has become increasingly important due to its effects on health; in the medical field, it has been highlighted that physical inactivity is one of the leading cause of death. Moreover, the increasing trend in a sedentary lifestyle has also led to economic concerns; for this reason, the need to develop healthcare programmes to raise awareness of the benefits of physical exercise among the global population has arisen.

Objective

This paper analyses the relationship between moderate physical activity, cost of pharmaceuticals and health services utilization with regard to a primary care community programme based on moderate exercise intervention. The study highlights the effect of an exercise programme for people in sheltered accommodation in terms of effects on their quality of life and in terms of economic sustainability.

Methodology

A randomized controlled trial of an exercise programme was designed. A total of 150 patients were randomized in two groups. The intervention group was recruited from Centro Esercizio Vita whereas the participants of the control group were recruited from general practitioners.

Results

At 9 months after randomization, the exercise‐based group presented a lower average cost for drugs (p‐value 0.039), an overall better health status perception (p‐value 0.0019) and accessed general practitioners less frequently (p‐value 0.058).

Conclusions

Our study shows that assisted physical activity practiced on the basis of an exercise programme, over a period of nine months, has overall positive consequences in terms of reduction in health expenditure and quality of life.
A critical analysis of health care purchasing arrangements in Kenya: A case study of the county departments of health
Authors: Mbau Rahab , Barasa Edwine , Munge Kenneth , Mulupi Stephen , Nguhiu Peter K. , Chuma Jane
Published: August 2018

Background

Purchasing in health care financing refers to the transfer of pooled funds to health care providers for the provision of health care services. There is limited empirical work on purchasing arrangements and what is required for strategic purchasing in low‐ and middle‐income countries. We conducted this study to critically assess the purchasing arrangements of the county departments of health (CDOH) who are the largest purchasers of health care in Kenya.

Methods

We used a qualitative case study approach to assess the extent to which the purchasing actions of the CDOH in Kenya were strategic. We purposively sampled 10 counties and collected data using in‐depth interviews (n = 81), focus group discussions (n = 4), and documents review. We analyzed data using a framework approach.

Results

County departments of health did not practice strategic purchasing. The government's (national and county) role as a steward for the purchasing function was characterized by poor accountability and inadequate budgetary allocations for service delivery. The absence of a purchaser‐provider split between the CDOH and public health care providers undermined provider selection based on performance and quality. Poor public participation and ineffective complaints and feedback mechanisms limited public accountability and responsiveness to the needs of the people.

Conclusion

Our findings show that while there are frameworks that could promote strategic purchasing of the CDOH, strategic purchasing is impaired by poor implementation of these frameworks and the inherent weaknesses of a public integrated purchasing system that lacks purchaser‐provider split.
Challenges toward achieving universal health coverage in Ghana, Kenya, Nigeria, and Tanzania
Authors: Umeh Chukwuemeka A.
Published: August 2018

Although many sub‐Saharan African countries have made efforts to provide universal health coverage (UHC) for their citizens, several of these initiatives have achieved little success. This study aims to review the challenges facing UHC in Ghana, Kenya, Nigeria, and Tanzania, and to suggest program or policy changes that might bolster UHC.

Routine data reported by the World Bank and World Health Organization, as well as annual reports of the national health insurance schemes of Ghana, Kenya, Nigeria, and Tanzania, were analyzed. The data were supplemented by a review of published and gray literature on health insurance coverage in these four countries.

The analysis showed that some of the challenges facing UHC in these countries include (1) large proportion of the population living in extreme poverty and unable to pay premiums, (2) large informal sector whose members are mostly uninsured, (3) high dropout rate from insurance schemes, (4) poorly funded primary health care system, and (5) segmented health insurance fund pool.

In order to achieve UHC by 2030, it will be important for these countries to (1) raise sufficient revenue to finance their health systems, (2) improve the efficiency of revenue utilization, (3) identify and provide coverage for the very poor, (4) reduce the proportion of the population that is underinsured, and (5) improve access to quality health care in rural areas.
Controls on stream hydrochemistry dynamics in a high Arctic snow‐covered watershed
Authors: Docherty Catherine L. , Riis Tenna , Milner Alexander M. , Christoffersen Kirsten Seestern , Hannah David M.
Published: August 2018

Arctic streams are highly sensitive to climate change due to warmer air temperature and increased precipitation associated with an encroaching low Arctic climatic zone into currently high‐Arctic coastal areas. Increases in nivation processes and permafrost degradation will lead to potential changes in stream physicochemical habitat, although these impacts are poorly understood. To address this gap, physicochemical habitat characteristics in streams around Zackenberg in Northeast Greenland National Park were investigated during the summers of 2013 to 2016. Streams with different sized snowpacks represented both low and high snowfall conditions leading to different nivation processes. Streams with larger snowpacks displayed lower channel stability, with higher channel mobility, suspended sediment and solute concentrations. Suspended sediment concentration was identified as a key driver of stream solute concentrations, and varying snowpack levels caused high interannual variability in solute concentrations. Winter snowpack size was confirmed to be an important driver of stream physicochemical habitat in an Arctic region with low glacial cover. We predict climate change will strongly impact stream hydrochemistry in this region through increased nivation processes alongside active layer thickening and solifluction, thereby increasing stream suspended sediment and solute concentrations. These findings indicate that hydrochemistry was principally a function of erosion, with variation being determined by spatial and temporal patterns in erosional processes, and as such, alternative methods to fingerprint water sources should be considered in this region.
Comparison of the INTERGROWTH‐21st, National Institute of Child Health and Human Development, and WHO fetal growth standards
Authors: Hua Xiaolin , Shen Minxue , Reddy Uma M. , Buck Louis Germaine , Souza Joao Paulo , Gülmezoglu A. Metin , Zhang Jun
Published: August 2018

Objective

To compare the ability of the INTERGROWTH‐21st, National Institute of Child Health and Human Development, and WHO fetal growth standards to identify fetuses at risk of adverse perinatal outcomes.

Methods

A retrospective analysis was performed among women enrolled in a multicenter randomized controlled trial (Routine Antenatal Diagnostic Imaging with Ultrasound) that was conducted in six states in the USA between November 1987 and May 1991. The predictive capability of various biometric indicators (biparietal diameter, femur length, abdominal circumference, head circumference, estimated fetal weight, and birthweight) was evaluated. Adverse outcomes included severe morbidity and perinatal death.

Results

There were 9409 women included. Biometric indicators measured at a gestational age of 18–24 weeks had insufficient predictive sensitivity (range, 4%–47%). By contrast, measurements taken at 28–34 weeks predicted statistically significant relative risk (range 1.5–10.2; P<0.05 for 27/30 relative risk values) and area under the receiver operating characteristic curve (range, 0.50–0.59; P<0.05 for 8/15 curves). Nonetheless, differences in accuracy between standards for predicting adverse perinatal outcomes were subtle (P>0.05 for differences in area under the curve values).

Conclusion

Although useful to monitor fetal growth trajectory and the level of risk, all three fetal growth standards provided limited accuracy for identifying fetuses at risk of adverse perinatal outcomes.
Effects of prophylactic uterine artery embolization on second‐trimester induced abortions in patients with placenta previa
Authors: Wang Ning , Li Xing‐Miao , Fei Yi‐Lin , Liu Yan‐Min , Lin Jun , Jiang Xiu‐Xiu
Published: August 2018

Objective

To evaluate the effects of prophylactic uterine artery embolization (UAE) on second‐trimester induced abortions in patients with placenta previa.

Methods

The present study was a retrospective review of second‐trimester induced abortions in the presence of placenta previa that conducted between January 1, 2008, and October 31, 2017, at a university hospital in Hangzhou, China. Pregnancy outcomes including intraoperative blood loss, transfusion, dilatation and evacuation, hysterotomy delivery, and hysterectomy were compared between patients with and without prophylactic UAE.

Results

There were 54 patients included in the study. In patients with partial placenta previa (n=15), the volume of intraoperative blood loss and the frequency of dilatation and evacuation were not significantly different between the UAE and non‐UAE groups (P>0.05). No patient had a transfusion, hysterotomy delivery, or hysterectomy. Among patients with complete placenta previa (n=39), the volumes of intraoperative blood loss (P=0.014) and transfusion (P=0.046) were significantly lower in the UAE group compared with the non‐UAE group. The rates of dilatation and evacuation, and hysterotomy delivery did not differ between the groups (P>0.05), but were numerically higher in the non‐UAE group. No patient was treated with hysterectomy.

Conclusion

Prophylactic UAE before a second‐trimester induced abortion had significant advantages in women with complete placenta previa, but it did not improve the pregnancy outcome in patients with partial placenta previa.

Chinese Clinical Trial Registry

ChiCTR‐OPC‐14005334.
Obsessive and harmonious passion in physically active Spanish and Hungarian men and women: A brief report on cultural and gender differences
Authors: Szabo Attila , Griffiths Mark D. , Demetrovics Zsolt , de la Vega Ricardo , Ruíz‐Barquín Roberto , Soós István , Kovacsik Rita
Published: August 2018

Increased research on passion in exercise calls for direct examination of possible moderating variables, such as culture and gender, that could influence the interpretation of the research results. This study using a nation by gender between‐participants design, examined differences in obsessive‐ and harmonious passion in Spanish and Hungarian physically active individuals. Participants (n = 1002) completed the Passion Scale, reported their gender, age and weekly hours of physical activity. Multivariate analysis of covariance revealed that the experiencing of physical activity‐related obsessive‐ and harmonious passion differed between the 2 countries and Hungarian women scored significantly higher on harmonious and obsessive passion than Spanish women. However, Hungarian men only scored significantly higher on obsessive passion, but not harmonious passion compared to Spanish men. These results suggest that gender and cultural differences are likely to affect the interpretation and generalisation of research on passion and exercise.
COGNITIVE AND SOCIOEMOTIONAL FUNCTIONING AT 4½ YEARS IN CHILDREN BORN TO MOTHERS WHO HAVE RECEIVED TREATMENT FOR SUBSTANCE‐ABUSE PROBLEMS WHILE PREGNANT
Authors: Haabrekke Kristin , Siqveland Torill , Nygaaard Egil , Bjornebekk Astrid , Slinning Kari , Wentzel‐Larsen Tore , Walhovd Kristine B. , Smith Lars , Moe Vibeke
Published: August 2018

Cognitive and socioemotional functioning at 4½ years of age were examined in children born to mothers with substance‐abuse problems (n = 22) recruited from residential treatment institutions while pregnant, and then compared to children born to mothers with mental health problems (n = 18) and children from a low‐risk group (n = 26). No significant group differences in cognitive functioning were found, but the children born to mothers with substance‐abuse problems showed more caregiver‐reported socioemotional problems than did the low‐risk children, like the children born to mothers with mental health problems. Birth weight had an effect on internalizing problems at 4½ years and mediated the relation between group and socioemotional problems, although not when controlling for caregiver education, single parenthood, and anxiety and depression. At 4½ years, 7 children born to mothers with substance‐abuse problems were placed in foster care. These children had lower birth weight and higher caregiver‐rated internalizing problems. In addition to emphasizing the importance of the quality of the prenatal environment, this study suggests that families with previous substance abuse are in need of long‐term follow‐up to address socioemotional problems and enhance further positive child cognitive development. The foster‐placed children may be in particular need of long‐term follow‐up.
#NeverthelessMemesPersisted: Building Critical Memetic Literacy in the Classroom
Authors: Harvey Lauren , Palese Emily
Published: August 2018

As our students’ consumption of internet memes through social media increases, a critical perspective toward these memes becomes increasingly important. Memes present teachers with a powerful and relevant way to approach critical analysis and discussion in the 21st‐century classroom. In this article, the authors present a framework for incorporating critical discussion and creation of memes into classrooms. Harnessing the power and prevalence of memes, the authors explore how internet memes can be used as a vehicle for critically engaging students. When they understand the characteristics that make memes an effective vector of cultural transmission, students can more critically recognize, consume, and produce these tools for humor and social and political critique.
Graphene oxide severely inhibits DNase activity
Authors: Huo Da , Zhang Bing , Peng Qi , Li Hongyue , Wang Hui , Yu Qilin , Li Mingchun
Published: August 2018

Graphene oxide (GO) is an important type of 2D nanomaterial and widely used in biomedicine, sensors, photocatalysis and electronic materials. With the extensive exposure of GO, its biological effect is debatable. In this study, we found a novel biological effect of GO, ie, suppression of deoxyribonuclease (DNase). GO inhibited DNA degradation when DNA or the DNA/RNA mixture was exposed to DNase. Moreover, GO suppressed nuclear fragmentation when the nuclei were treated with DNase. Interestingly, GO neither interacted with DNA nor influenced the interaction between DNase and DNA. Further investigation revealed that GO had a strong activity of adsorbing l‐phenylalanine and l‐histidine, key amino acid residues in the active site of DNase. These results suggest that GO could suppress the activity of DNase by interaction with the active site of DNase, and have an impact on DNase‐related cellular processes (eg, apoptosis), implying its potential application in treating diseases associated with disorderly DNase function.
Reflection‐mode switchable subwavelength Bessel‐beam and Gaussian‐beam photoacoustic microscopy in vivo
Authors: Park Byullee , Lee Hoyong , Jeon Seungwan , Ahn Joongho , Kim Hyung H. , Kim Chulhong
Published: August 2018

We have developed a reflection‐mode switchable subwavelength Bessel‐beam (BB) and Gaussian‐beam (GB) photoacoustic microscopy (PAM) system. To achieve both reflection‐mode and high resolution, we tightly attached a very small ultrasound transducer to an optical objective lens with numerical aperture of 1.0 and working distance of 2.5 mm. We used axicon and an achromatic doublet in our system to obtain the extended depth of field (DOF) of the BB. To compare the DOF performance achieved with our BB‐PAM system against GB‐PAM system, we designed our system so that the GB can be easily generated by simply removing the lenses. Using a 532 nm pulse laser, we achieved the lateral resolutions of 300 and 270 nm for BB‐PAM and GB‐PAM, respectively. The measured DOF of BB‐PAM was approximately 229 μm, which was about 7× better than that of GB‐PAM. We imaged the vasculature of a mouse ear using BB‐PAM and GB‐PAM and confirmed that the DOF of BB‐PAM is much better than the DOF of GB‐PAM. Thus, we believe that the high resolution achieved at the extended DOF by our system is very practical for wide range of biomedical research including red blood cell (RBC) migration in blood vessels at various depths and observation of cell migration or cell culture.
Chronic Kidney Disease Is Associated With Greater Bone Marrow Adiposity
Authors: Woods Gina N , Ewing Susan K , Sigurdsson Sigurdur , Kado Deborah M , Ix Joachim H , Hue Trisha F , Eiriksdottir Gudny , Xu Kaipin , Gudnason Vilmundur , Lang Thomas F , Vittinghoff Eric , Harris Tamara B , Rosen Clifford J , Li Xiaojuan , Schwartz Ann V
Published: August 2018

Bone marrow adiposity is associated with aging, osteoporosis, and reduced hematopoiesis, as well as anorexia nervosa, but little is known about the underlying mechanisms that affect marrow adiposity. Chronic kidney disease (CKD) may influence bone marrow adipose tissue (BMAT), possibly through loss of lean mass or higher circulating levels of sclerostin. To test these hypotheses, we investigated the cross-sectional association between estimated glomerular filtration rate (eGFR) as a measure of kidney function and 1H-MRS-based measurement of vertebral BMAT (L1 to L4) in 475 older adults from the Age Gene/Environment Susceptibility (AGES)-Reykjavik study. Mean BMAT was compared in those with eGFR >60 (n = 297) versus those with eGFR 45 to 60 (n = 120) or eGFR <45 (n = 58) using linear regression models. Participants had a mean age of 81.5 (SD 4.1) years, mean eGFR of 64.3 (SD 16.1) mL/min/1.734 cm2, mean BMAT of 54.5% (SD 8.5); 48.2% were women. In unadjusted and adjusted models (age, visit window, gender, diabetes and visceral adipose tissue), BMAT was higher in those with eGFR <45 (adjusted mean 58.5%; 95% CI, 56.2 to 60.7) compared with those with eGFR >60 (adjusted mean 53.8%; 95% CI, 52.8 to 54.8) (p = 0.0002). BMAT did not differ in those with eGFR 45 to 60 (adjusted mean 54.3%; 95% CI, 52.8 to 55.9) compared with those with eGFR >60 (p = 0.58). In a subgroup of participants with serum sclerostin available (n = 253), additional adjustment for sclerostin attenuated the difference in adjusted mean vertebral BMAT between those with eGFR <45 versus >60 from 3.7% (p = 0.04) to 2.4% (p = 0.20). CKD stage 3b or worse was associated with greater bone marrow adiposity; this association may be partially mediated by sclerostin. © 2018 American Society for Bone and Mineral Research.
The Spectrum of Fundamental Basic Science Discoveries Contributing to Organismal Aging
Authors: Farr Joshua N , Almeida Maria
Published: August 2018

Aging research has undergone unprecedented advances at an accelerating rate in recent years, leading to excitement in the field as well as opportunities for imagination and innovation. Novel insights indicate that, rather than resulting from a preprogrammed series of events, the aging process is predominantly driven by fundamental non-adaptive mechanisms that are interconnected, linked, and overlap. To varying degrees, these mechanisms also manifest with aging in bone where they cause skeletal fragility. Because these mechanisms of aging can be manipulated, it might be possible to slow, delay, or alleviate multiple age-related diseases and their complications by targeting conserved genetic signaling pathways, controlled functional networks, and basic biochemical processes. Indeed, findings in various mammalian species suggest that targeting fundamental aging mechanisms (eg, via either loss-of-function or gain-of-function mutations or administration of pharmacological therapies) can extend healthspan; ie, the healthy period of life free of chronic diseases. In this review, we summarize the evidence supporting the role of the spectrum of fundamental basic science discoveries contributing to organismal aging, with emphasis on mammalian studies and in particular aging mechanisms in bone that drive skeletal fragility. These mechanisms or aging hallmarks include: genomic instability, telomere attrition, epigenetic alterations, loss of proteostasis, deregulated nutrient sensing, mitochondrial dysfunction, cellular senescence, stem cell exhaustion, and altered intercellular communication. Because these mechanisms are linked, interventions that ameliorate one hallmark can in theory ameliorate others. In the field of bone and mineral research, current challenges include defining the relative contributions of each aging hallmark to the natural skeletal aging process, better understanding the complex interconnections among the hallmarks, and identifying the most effective therapeutic strategies to safely target multiple hallmarks. Based on their interconnections, it may be feasible to simultaneously interfere with several fundamental aging mechanisms to alleviate a wide spectrum of age-related chronic diseases, including osteoporosis. © 2018 American Society for Bone and Mineral Research.
Reversibly immortalized human umbilical cord–derived mesenchymal stem cells (UC‐MSCs) are responsive to BMP9‐induced osteogenic and adipogenic differentiation
Authors: Shu Yi , Yang Chao , Ji Xiaojuan , Zhang Linghuan , Bi Yang , Yang Ke , Gong Mengjia , Liu Xing , Guo Qi , Su Yuxi , Qu Xiangyang , Nan Guoxin , Zhao Chen , Zeng Zongyue , Yu Xinyi , Zhang Ruyi , Yan Shujuan , Lei Jiayan , Wu Ke , Wu Ying , An Liping , Huang Shifeng , Gong Cheng , Yuan Chengfu , Liu Wei , Huang Bo , Feng Yixiao , Zhang Bo , Dai Zhengyu , Shen Yi , Luo Wenping , Wang Xi , Haydon Rex C. , Luu Hue H. , Reid Russell R. , Wolf Jennifer Moriatis , Lee Michael J. , He Tong‐Chuan , Li Yasha
Published: August 2018

Human mesenchymal stem cells (MSCs) are a heterogeneous subset of nonhematopoietic multipotent stromal stem cells and can differentiate into mesodermal lineage, such as adipocytes, osteocytes, and chondrocytes, as well as ectodermal and endodermal lineages. Human umbilical cord (UC) is one of the most promising sources of MSCs. However, the molecular and cellular characteristics of UC‐derived MSCs (UC‐MSCs) require extensive investigations, which are hampered by the limited lifespan and the diminished potency over passages. Here, we used the piggyBac transposon–based simian virus 40 T antigen (SV40T) immortalization system and effectively immortalized UC‐MSCs, yielding the iUC‐MSCs. A vast majority of the immortalized lines are positive for MSC markers but not for hematopoietic markers. The immortalization phenotype of the iUC‐MSCs can be effectively reversed by flippase recombinase–induced the removal of SV40T antigen. While possessing long‐term proliferation capability, the iUC‐MSCs are not tumorigenic in vivo. Upon bone morphogenetic protein 9 (BMP9) stimulation, the iUC‐MSC cells effectively differentiate into osteogenic, chondrogenic, and adipogenic lineages both in vitro and in vivo, which is indistinguishable from that of primary UC‐MSCs, indicating that the immortalized UC‐MSCs possess the characteristics similar to that of their primary counterparts and retain trilineage differentiation potential upon BMP9 stimulation. Therefore, the engineered iUC‐MSCs should be a valuable alternative cell source for studying UC‐MSC biology and their potential utilities in immunotherapies and regenerative medicine.
MFG‐E8/integrin β3 signaling contributes to airway inflammation response and airway remodeling in an ovalbumin‐induced murine model of asthma
Authors: Zhi Yueli , Huang Han , Liang Lihong
Published: August 2018

Asthma is the most common chronic childhood disease worldwide, characterized by airway remodeling and chronic inflammation, orchestrated primarily by Th2 cytokines. The aim of the current study was to explore the influences of milk fat globule epidermal growth factor 8 (MFG‐E8)/integrin β3 signaling involved in airway inflammation and remodeling in asthma. BALB/c mice were sensitized by intraperitoneal injection of ovalbumin (OVA), followed by OVA nebulization. The levels of MFG‐E8 expression were declined markedly in the OVA‐induced allergy murine model. In addition, administration of MFG‐E8 strongly reduced the accumulation of T‐helper type 2 (Th2)‐associated cytokines (such as interleukin‐4, ‐5, and ‐13) as well as chemokine CCL11 (eotaxin) in bronchoalveolar lavage fluid and tissues in the OVA‐sensitized mice. Moreover, MFG‐E8 remarkably repressed the total immunoglobulin E and OVA‐specific immunoglobulin E in serum in OVA‐challenged mice. Meanwhile, treatment with recombinant murine MFG‐E8 noticeably prevented inflammatory cell infiltration into the airways, as showed by a marked decrease in the numbers of total immune cells, eosinophils, neutrophils, macrophages, and lymphocytes in the bronchoalveolar lavage fluid in response to OVA challenge. Importantly, MFG‐E8 apparently alleviated OVA‐driven airway remodeling, which were evidenced by declined secretion of important mediators of airway remodeling, including transforming growth factor‐β1, matrix metalloproteinase 9, ADAM8, and vascular endothelial growth factor, and reduced airway collagen deposition and inhibited goblet cell hyperplasia in OVA‐induced asthma in mice. Mechanistically, integrin 3 contributes to the protective effect of MFG‐E8 in inhibiting airway inflammation and remodeling in OVA‐driven features of allergic asthma. Overall, MFG‐E8, as a candidate molecule to evaluate airway inflammation and remodeling, could be a potential target for the management and prevention of asthma exacerbations, suggesting that MFG‐E8/integrin β3 signaling may serve as a promising therapeutic agent for childhood asthma.
RETRACTED: (2R,3R)Dihydromyricetin inhibits osteoclastogenesis and bone loss through scavenging LPS‐induced oxidative stress and NF‐κB and MAPKs pathways activating
Authors: Zhang Xuejun , Li Xin , Fang Jianguo , Hou Xiaolong , Fang Huang , Guo Fengjing , Li Feng , Chen Anmin , Huang Shilong
Published: August 2018

Osteolysis is a serious complication of several chronic inflammatory diseases and is closely associated with a local chronic inflammatory reaction with a variety of causes. However, similarities exist in the mechanisms of their pathological processes. Inflammatory factors and oxidative stress–induced nuclear factor κB (NF‐κB) and mitogen‐activated protein kinases (MAPKs) signaling pathways play a center role in bone erosion. Dihydromyricetin (DMY) is a natural compound with anti‐inflammatory and antioxidative effect, which are commonly used in chronic pharyngitis and alcohol use disorders. In the current study, we identified that DMY attenuated lipopolysaccharide (LPS)–induced oxidative stress through inhibiting the production of reactive oxygen species (ROS) and nitric oxide (NO), downregulated COX‐2 and iNOS, and promoted the activity of the antioxidative system by activating superoxide dismutase (SOD) and Nrf2/HO‐1 pathway. To further investigate the underlying mechanism, we found that DMY inhibits osteoclast (OC) differentiation and bone resorption activity through blocking the RANKL‐induced activation of the NF‐κB and MAPKs signaling pathways and then downregulated c‐Fos and NFATc1, which is essential for OC differentiation. Furthermore, DMY inhibited LPS‐induced osteolysis in vivo. Collectively, these results indicate that DMY might be a promising prophylactic antiosteoclastic/resorptive agent in preventing or treating bone lysis diseases.
ERO1L promotes pancreatic cancer cell progression through activating the Wnt/catenin pathway
Authors: Han Fei , Xu Qianqian , Zhao Jianguo , Xiong Peng , Liu Jun
Published: August 2018

Pancreatic cancer is a lethal malignancy with an extremely poor prognosis. Although many genes and noncoding RNAs have been found to regulate its progression, more regulators are needed to be understood to resolve its high lethality. Endoplasmic reticulum oxidoreductase 1 alpha (ERO1L) plays crucial roles in the progression of various tumors, but its role in pancreatic cancer progression has not been studied. In this study, we found that ERO1L was significantly upregulated in pancreatic cancer cells and patients; its overexpression significantly promoted pancreatic cancer migration, invasion, and growth, while its knockdown significantly inhibited pancreatic cancer migration, invasion, and growth. Mechanism analysis suggested that ERO1L promoted many tumor‐associated signaling pathways, especially the Wnt/catenin pathway; it could activate the Wnt/catenin pathway and upregulate the targets of the Wnt/catenin pathway. We further analyzed the correlation between ERO1L expression and the prognosis of patients, suggesting that patients with high ERO1L expression had short survival time; it is an independent prognosis factor for patients' prognosis. Together, we found that ERO1L was an oncogene for pancreatic cancer.
The in vivo and in vitro approaches for establishing a link between advanced glycation end products and lung cancer
Authors: Khan Hamda , Khan Mohd. Sajid , Ahmad Saheem
Published: August 2018

Advanced glycation end products (AGEs) are directly related to third aging‐associated diseases, such as cardiovascular diseases, arteriosclerosis, and neurodegeneration. Likewise, these irreversible and nonenzymatic products have been reported to be involved in the progression of malignant cancers. In general, aging‐associated diseases and the initiation of cancer have been subjects of interest for several years. Few studies on the role of AGEs in cancer have been performed on cell lines. Moreover, past investigations in the field of glycation biology still lack the knowledge of in vivo and in vitro approaches for cancer cells. Accordingly, we aimed to focus on and establish a link between cancer and glycation with respect to all the possible AGEs. In our study, the levels of carboxymethyllysine (CML) increased by 50.94% in an animal model of glycation, whereas in an animal model of cancer, the contents of CML increased by 45.94% compared with their negative controls. Similarly, fluorescent AGEs were also examined and were found to be increased by 65.3% and 58.63% in the animal models of glycation and cancer, respectively, compared with the control subjects. The protein carbonyl contents were also found to be enhanced in the animal models of glycation and cancer. In our study, the levels of reactive oxygen species were also found to be significantly increased in the in vitro model of cancer cells as compared with the controls. Such an initial breakthrough indicated that AGEs were present in the serum of the animal models of cancer and glycation.
Molecular insights into the interactions of GF‐17 with the gram‐negative and gram‐positive bacterial lipid bilayers
Authors: Jahangiri Samira , Jafari Majid , Arjomand Mehdi , Mehrnejad Faramarz
Published: August 2018

The cationic antimicrobial peptide GF‐17, a 17‐mer‐derived peptide from human cathelicidin LL‐37, has a significant strength in the killing of the methicillin‐resistant Staphylococcus aureus and Escherichia coli strains. Herein, we conducted a series of all‐atom molecular dynamics simulations to investigate the ability of GF‐17 in perturbing the model membranes of the gram‐positive, S. aureus, and gram‐negative, E. coli, bacteria. We also explored the contributions of the specific residues in the peptide activity. The molecular dynamics results indicated that the peptide is stabilized on the membrane surface and rapidly binds to the phosphate headgroups of the model membranes through the electrostatic interactions and hydrogen bonds. Furthermore, both polar and nonpolar interactions are energetically favored for the binding with the membrane surface. The research also revealed the important roles of the phenylalanine residues in the early insertion of the peptide into the bacterial model membranes. In addition, the results demonstrated that the central residues Arg23 and Lys25 played a critical role in the binding of GF‐17 to both gram‐negative and gram‐positive model membranes, in excellent agreement with experimental studies. This study emphasizes on the pivotal role of basic residues in prompt association of the peptide on the model membrane surface and on the significance of residues Phe17, Ile24, Phe27, and Val32 in hydrophobic interactions. Therefore, our observations provide insights into the membrane‐GF‐17 interactions at atomic details that are useful to develop potent antimicrobial peptides targeting multidrug‐resistant bacteria.
Melatonin reduces two‐cell block via nonreceptor pathway in mice
Authors: Shi Feifei , Li Hua , Wang Enling , Chen Zi‐Jiang , Zhang Cong
Published: August 2018

Embryo development block seriously limits the success of in vitro embryo production and assisted reproductive technology. Although numerous researchers have explored this problem, it remains to be solved. In this study, we found that melatonin supplementation at 10−8 and 10−9 M in M16 significantly reduced two‐cell block of mouse embryos. When those melatonin‐treated four‐cell embryos were transplanted into the oviducts of female recipient mice, the litter sizes were significantly increased compared with those of the controls. Mechanism study discovered that melatonin treatment markedly reduced reactive oxygen species and mitochondrial superoxide. Quantitative polymerase chain reaction revealed that melatonin significantly upregulated the transcription of catalase, superoxide dismutase 2, glutathione peroxidase, and the antiapoptotic factors Bcl‐2 and Bcl‐x while downregulated the transcription of pro‐apoptotic genes p53 and Bax. In addition, we found Dux, an important gene which promotes zygotic genome activation, and zygotic genes (zinc finger and SCAN4B and eukaryotic translation initiation factor 1A) were all increased after melatonin treatment. Melatonin membrane receptors have two isoforms, melatonin receptor 1 and 2 (MT1, MT2). Further studies with luzindole (a nonselective MT1 and MT2 antagonist) demonstrated that the beneficial effects of melatonin on reducing two‐cell block were not mediated by the melatonin membrane receptors. This study shows that melatonin can be used for improving the embryo quality and production efficiency cultured in vitro and also identifies the underlying mechanism by which melatonin decreases two‐cell block.
Protein kinase Cε targets respiratory chain and mitochondrial membrane potential but not F0F1‐ATPase in renal cells injured by oxidant
Authors: Nowak Grazyna , Bakajsova‐Takacsova Diana
Published: August 2018

We have previously shown that protein kinase Cε (PKCε) is involved in mitochondrial dysfunction in renal proximal tubular cells (RPTC). This study examined mitochondrial targets of active PKCε in RPTC injured by the model oxidant tert‐butyl hydroperoxide (TBHP). TBHP exposure augmented the levels of phosphorylated (active) PKCε in mitochondria, which suggested translocation of PKCε to mitochondria after oxidant exposure. Oxidant injury decreased state 3 respiration, adenosine triphosphate (ATP) production, ATP content, and complex I activity. Further, TBHP exposure increased ΔΨm and production of reactive oxygen species (ROS), and induced mitochondrial fragmentation and RPTC death. PKCε activation by overexpressing constitutively active PKCε exacerbated decreases in state 3 respiration, complex I activity, ATP content, and augmented RPTC death. In contrast, inhibition of PKCε by overexpressing dnPKCε mutant restored state 3 respiration, respiratory control ratio, complex I activity, ΔΨm, and ATP production and content, but did not prevent decreases in F0F1‐ATPase activity. Inhibition of PKCε prevented oxidant‐induced production of ROS and mitochondrial fragmentation, and reduced RPTC death. We conclude that activation of PKCε mediates: (a) oxidant‐induced changes in ΔΨm, decreases in mitochondrial respiration, complex I activity, and ATP content; (b) mitochondrial fragmentation; and (c) RPTC death. In contrast, oxidant‐induced inhibition of F0F1‐ATPase activity is not mediated by PKCε. These results show that, in contrast to the protective effects of PKCε in the heart, PKCε activation is detrimental to mitochondrial function and viability in RPTC and mediates oxidant‐induced injury.
FABP5 is a critical regulator of methionine‐ and estrogen‐induced SREBP‐1c gene expression in bovine mammary epithelial cells
Authors: Li Ping , Yu Mengmeng , Zhou Chengjian , Qi Hao , Wen Xuepeng , Hou Xiaoming , Li Meng , Gao Xuejun
Published: August 2018

The intracellular fatty acid‐binding proteins (FABPs) are a well‐conserved family that function as lipid chaperones. Ongoing studies are focused on identification of the mechanistic complexity and vast biological diversity of different isoforms of FABPs. However, the molecular mechanism of FABP5 in the regulation of milk fat synthesis in the mammary gland of dairy cows is still largely unknown. Here, we report that FABP5 acts as a critical regulator of terol response element‐binding protein‐1c (SREBP‐1c) gene expression induced by methionine (Met) and estrogen (E2) in bovine mammary epithelial cells (BMECs). We observed that the expression of FABP5 was markedly higher in dairy cow mammary tissue during the lactating period than the puberty period and the dry period. FABP5 is located in the cytoplasm, and Met and E2 significantly increase the protein levels of FABP5 in BMECs. Using gene function study approaches, we revealed that FABP5 positively regulates SREBP‐1c gene expression and promotes milk fat synthesis. We confirmed that FABP5 is required for Met‐ and E2‐induced SREBP‐1c gene expression and milk fat synthesis. We further uncovered that fatty acids are needed for FABP5‐mediated SREBP‐1c gene expression. Thus, our study demonstrates that FABP5 is a critical regulator of Met‐ and E2‐induced SREBP‐1c gene expression leading to milk fat synthesis.
Adipose tissue dysfunction in cancer cachexia
Authors: Daas Sahar I. , Rizeq Balsam R. , Nasrallah Gheyath K.
Published: August 2018

Cancer cachexia is a complex disorder that is driven by inflammation and metabolic imbalances, resulting in extreme weight loss. Adipose tissue, a main player in cancer cachexia, is an essential metabolic and secretory organ consisting of both white adipose tissue (WAT) and brown adipose tissue. Its secretory products, including adipokines and cytokines, affect a wide variety of central and peripheral organs, such as the skeletal muscle, brain, pancreas, and liver. Therefore, a combination of metabolic alterations, and systemic inflammation dysregulation of both anti‐inflammatory and proinflammatory modulators contribute toward adipose tissue wasting in cancer cachexia. Growing evidence suggests that, during cancer cachexia, WAT undergoes a browning process, resulting in increased lipid mobilization and energy expenditure. In this review, we have summarized the characteristics of cancer cachexia and WAT browning. Furthermore, this review describes how adipose tissue becomes inflamed in cancer, shedding light on the combinatorial action of multiple secreted macromolecules, cytokines, hormones, and tumor mediators on adipose tissue dysfunction. We also highlight the inflammatory responses, energy utilization defects, and molecular mechanisms underlying the WAT dysfunction and browning in cancer cachexia. Further, the actual mechanisms behind the loss of adipose tissue are unknown, but have been attributed to increased adipocyte lipolysis, systemic inflammation, and apoptosis or reduced lipogenesis. The understanding of adipose tissue dysfunction in cancer cachexia will hopefully promote the development of new therapeutic approaches to prevent or treat this wasting syndrome.
MiR‐214 is an important regulator of the musculoskeletal metabolism and disease
Authors: Sun Youqiang , Kuek Vincent , Liu Yuhao , Tickner Jennifer , Yuan Yu , Chen Leilei , Zeng Zhikui , Shao Min , He Wei , Xu Jiake
Published: August 2018

MiR‐214 belongs to a family of microRNA (small, highly conserved noncoding RNA molecules) precursors that play a pivotal role in biological functions, such as cellular function, tissue development, tissue homeostasis, and pathogenesis of diseases. Recently, miR‐214 emerged as a critical regulator of musculoskeletal metabolism. Specifically, miR‐214 can mediate skeletal muscle myogenesis and vascular smooth muscle cell proliferation, migration, and differentiation. MiR‐214 also modulates osteoblast function by targeting specific molecular pathways and the expression of various osteoblast‐related genes; promotes osteoclast activity by targeting phosphatase and tensin homolog (Pten); and mediates osteoclast‐osteoblast intercellular crosstalk via an exosomal miRNA paracrine mechanism. Importantly, dysregulation in miR‐214 expression is associated with pathological bone conditions such as osteoporosis, osteosarcoma, multiple myeloma, and osteolytic bone metastasis of breast cancer. This review discusses the cellular targets of miR‐214 in bone, the molecular mechanisms governing the activities of miR‐214 in the musculoskeletal system, and the putative role of miR‐214 in skeletal diseases. Understanding the biology of miR‐214 could potentially lead to the development of miR‐214 as a possible biomarker and a therapeutic target for musculoskeletal diseases.
Modulating calcium‐mediated NFATc1 and mitogen‐activated protein kinase deactivation underlies the inhibitory effects of kavain on osteoclastogenesis and bone resorption
Authors: Guo Qiang , Cao Zhen , Wu Bo , Chen Fangxiao , Tickner Jennifer , Wang Ziyi , Qiu Heng , Wang Chao , Chen Kai , Tan Renxiang , Gao Qile , Xu Jiake
Published: August 2018

Osteoclasts are responsible for bone resorption during the process of bone remodeling. Increased osteoclast numbers and bone resorption activity are the main factors contributing to bone loss–related diseases such as osteoporosis. Therefore, modulating the formation and function of osteoclasts is critical for the effective treatment of osteolysis and osteoporosis. Kavain is the active ingredient extracted from the root of the kava plant, which possesses known anti‐inflammatory properties. However, the effects of kavain on osteoclastogenesis and bone resorption remain unclear. In this study, we found that kavain inhibits receptor activator of nuclear factor‐κB ligand (RANKL)–induced osteoclast differentiation and fusion using tartrate‐resistant acid phosphatase staining and immunofluorescence. Furthermore, kavain inhibited bone resorption performed by osteoclasts. Using reverse transcription‐polymerase chain reaction and western blot analysis, we found that kavain downregulates the expression of osteoclast marker genes, such as nuclear factor of activated T cells, cytoplasmic 1 (Nfatc1), v‐atpase d2 (Atp6v0d2), dendrocyte expressed seven transmembrane protein (Dcstamp), matrix metallopeptidase 9 (Mmp9), cathepsin K (Ctsk), and Acp5. Additionally, kavain repressed RANKL‐induced calcium oscillations, nuclear factor of activated T cells activation, and mitogen‐activated protein kinase phosphorylation, while leaving NF‐κB unaffected. We found no effects of kavain on either osteoblast proliferation or differentiation. Besides, kavain inhibited bone loss in ovariectomized mice by suppressing osteoclastogenesis. Collectively, these data suggest a potential use for kavain as a candidate drug for the treatment of osteolytic diseases.
The effects of expression of different microRNAs on insulin secretion and diabetic nephropathy progression
Authors: Mafi Alireza , Aghadavod Esmat , Mirhosseini Naghmeh , Mobini Moein , Asemi Zatollah
Published: August 2018

MicroRNAs (miRNAs) have recently become well‐known efficacious biomarkers for the diagnosis of diabetic nephropathy (DN). MiRNAs, short noncoding RNAs, are posttranscriptional regulators of gene expression, which regulate several biological cell functions, including insulin production and secretion, as well as insulin resistance in tissues. Today, the focus of the medical world is centered on the role of miRNAs as mediators for different diseases, such as DN and end‐stage renal diseases (ESRD). MiRNAs are stable and detectable in human biological fluids, so their detection for early diagnosis of different diseases is highly sensitive and specific. Previous reports have shown that the alteration of miRNA profiles significantly correlates with specific stages of DN, kidney fibrosis, and renal dysfunction. This review was aimed at assessing the pathway of different miRNA expressions responsible for insulin secretion disorder and DN progression.