bluuebunny/crossref_metadata_2025 huggingface dataset:
Knockdown of lncRNA H19 inhibits abnormal differentiation of small intestinal epithelial cells in diabetic mice
Authors: Shan Ti‐Dong , Lv Shao‐Yan , Tian Zi‐Bin , Liu Xi‐Shuang , Liu Fu‐Guo , Sun Xu‐Guo
Published: August 2018

Diabetes mellitus (DM) comprises a group of metabolic diseases characterized by insulin deficiency or resistance and hyperglycemia. We previously reported the presence of abnormal differentiation of small intestinal epithelial cells (IECs) in diabetic mice, but the exact mechanism of this phenomenon has not been thoroughly elucidated to date. In this study, we found that H19 was markedly upregulated in IECs of DM mice. H19 knockdown significantly inhibited abnormal differentiation of IECs in DM mice. Bioinformatics analysis identified miR‐141‐3p as a candidate for H19. Based on luciferase reporter assays, we found that miR‐141‐3p directly targeted H19. Luciferase reporter assays also showed that miR‐141‐3p could directly target β‐catenin. Furthermore, H19 might act as an endogenous “sponge” by competing for miR‐141‐3p binding to regulate miRNA targets in vitro and in vivo. In summary, our findings provide the first evidence supporting the role of H19 in IECs of DM mice, and miR‐141‐3p targets not only protein‐coding genes but also the lncRNA H19.
How to influence the mesenchymal stem cells fate? Emerging role of ectoenzymes metabolizing nucleotides
Authors: Roszek Katarzyna , Wujak Magdalena
Published: August 2018

Extracellular purines, principally adenosine triphosphate and adenosine, are among the oldest evolutionary and widespread chemical messengers. The integrative view of purinergic signaling as a multistage coordinated cascade involves the participation of nucleotides/nucleosides, their receptors, enzymes metabolizing extracellular nucleosides and nucleotides as well as several membrane transporters taking part in the release and/or uptake of these molecules. In view of the emerging data, it is evident and widely accepted that an extensive network of diverse enzymatic activities exists in the extracellular space. The enzymes regulate the availability of nucleotide and adenosine receptor agonists, and consequently, the course of signaling events. The current data indicate that mesenchymal stem cells (MSCs) and cells induced to differentiate exhibit different sensitivity to purinergic ligands as well as a distinct activity and expression profiles of ectonucleotidases than mature cells. In the proposed review, we postulate for a critical role of these enzymatic players which, by orchestrating a fine‐tune regulation of nucleotides concentrations, are integrally involved in modulation and diversification of purinergic signals. This specific hallmark of the MSC purinome should be linked with cell‐specific biological potential and capacity for tissue regeneration. We anticipate this publication to be a starting point for scientific discussion and novel approach to the in vitro and in vivo regulation of the MSC properties.
LncRNA PVT1 regulates VEGFC through inhibiting miR‐128 in bladder cancer cells
Authors: Yu Cui , Longfei Liu , Long Wang , Feng Zeng , Chen Jinbo , Chao Li , Peihua Liu , Xiongbing Zu , Hequn Chen
Published: August 2018

Long noncoding RNA PVT1 is considered to be an oncogene in multiple cancers. Our previous studies indicated that PVT1 levels were higher in bladder cancer tissue and correlated with clinical progression and poor prognosis in bladder cancer patients. A bioinformatics analysis showed that PVT1 may regulate VEGFC expression through miR‐128 as a competing endogenous RNA (ceRNA). In this study, we demonstrated that PVT1 expression levels affect the proliferation and migration ability of bladder cancer cells. Moreover, PVT1 knockdown significantly decreased the proliferation capacity of bladder cancer cells in nude mice. Luciferase assays and RNA‐binding protein immunoprecipitation were performed to investigate the potential mechanism of ceRNAs in the regulation of PVT1 and VEGFC. The results showed that the increased number of PVT1 transcripts interacted directly with miR‐128 to decrease miR‐128 binding to the VEGFC 3′‐untranslated region. This effect suppressed VEGFC mRNA degradation by miR‐128. In conclusion, these results indicated that PVT1 might play a critical role in bladder cancer tumorigenesis via miR‐218 and VEGFC. Therefore, PVT1 could be a new biomarker for bladder cancer diagnosis and therapy.
MicroRNA‐638 inhibits human airway smooth muscle cell proliferation and migration through targeting cyclin D1 and NOR1
Authors: Wang Hongyu , Yao Huijuan , Yi Bing , Kazama Kyosuke , Liu Yan , Deshpande Deepak , Zhang Jian , Sun Jianxin
Published: August 2018

Abnormal airway smooth muscle cell (ASMC) proliferation and migration contribute significantly to increased ASM mass associated with asthma. MicroRNA (miR)‐638 is a primate‐specific miRNA that plays important roles in development, DNA damage repair, hematopoiesis, and tumorigenesis. Although it is highly expressed in ASMCs, its function in ASM remodeling remains unknown. In the current study, we found that in response to various mitogenic stimuli, including platelet‐derived growth factor‐two B chains (PDGF‐BB), transforming growth factor β1, and fetal bovine serum, the expression of miR‐638, as determined by quantitative real‐time polymerase chain reaction (qRT‐PCR), was significantly downregulated in the proliferative human ASMCs. Both gain‐ and loss‐of‐function studies were performed to study the role of miR‐638 in ASMC proliferation and migration. We found that adenovirus‐mediated miR‐638 overexpression markedly inhibits ASMC proliferation and migration, while ablation of miR‐638 by anti‐miR‐638 markedly increases cell proliferation and migration, as determined by WST‐8 proliferation and scratch wound assays. Dual‐luciferase reporter assay, qRT‐PCR, and immunoblot analysis were used to investigate the effects of miR‐638 on the expression of the downstream target genes in ASMCs. Our results demonstrated that miR‐638 overexpression significantly reduced the expression of downstream target cyclin D1 and NOR1, both of which have been shown to be essential for cell proliferation and migration. Together, our study provides the first in vitro evidence highlighting the antiproliferative and antimigratory roles of miR‐638 in human ASMC remodeling and suggests that targeted overexpression of miR‐638 in ASMCs may provide a novel therapeutic strategy for preventing ASM hyperplasia associated with asthma.
Role of STAT signaling and autocrine action of chemokines during H2O2 induced HTR‐8/SVneo trophoblastic cells invasion
Authors: Banerjee Priyanka , Malik Ankita , Malhotra Sudha Saryu , Gupta Satish Kumar
Published: August 2018

During pregnancy, regulated generation of reactive oxygen species (ROS) is important for activation of signaling pathways and placentation. In the current study, the effect of H2O2 on invasion of HTR‐8/SVneo cells, a human extravillous trophoblast cell line, is investigated. Treatment of HTR‐8/SVneo cells for 24 hr with H
2O2 (25 µM) leads to a significant increase in invasion without affecting cell proliferation, viability, and apoptosis. Concomitantly, a significant increase in the matrix metalloproteinase‐9 (MMP‐9)/tissue inhibitor of metalloproteinases‐1 (TIMP‐1) ratio is observed. Further, significant increase in phosphorylation of signal transducer and activator of transcription 1 (STAT‐1) and STAT‐3 (both at ser727 residue) is observed on treating HTR‐8/SVneo cells with 25 µM of H2O2 accompanied by an increase in the secretion of interleukin‐8 (IL‐8) and macrophage inflammatory protein‐1β (MIP‐1β). A significant decrease in H2O2‐mediated invasion of HTR‐8/SVneo cells and reduced expression of IL‐8 and MIP‐1β accompanied by decrease in MMP‐9/TIMP‐1 ratio are observed on inhibiting STAT‐1 and STAT‐3 by small interfering RNA (siRNA). Inhibition of STAT‐1 activity by fludarabine and STAT‐3 activity by Stattic also leads to a decrease in H2O2‐mediated increase in HTR‐8/SVneo cell invasion. Inhibition of IL‐8 and MIP‐1β by siRNA also leads to a significant decrease in both basal and H2O2‐mediated invasion. Interestingly, inhibition of MIP‐1β by siRNA leads to a significant reduction in H2O2‐mediated increase in IL‐8. However, no significant effect of IL‐8 silencing on H2O2‐mediated MIP‐1β expression was observed. From the above results, it can be concluded that H2O2 activates STAT signaling, MIP‐1β & IL‐8 secretion and increases MMP‐9/TIMP‐1 ratio leading to an increased invasion of HTR‐8/SVneo cells without affecting their viability.
Berberine attenuates pulmonary arterial hypertension via protein phosphatase 2A signaling pathway both in vivo and in vitro
Authors: Luo Jie , Gu Yue , Liu Pengfei , Jiang Xiaomin , Yu Wande , Ye Peng , Chao Yuelin , Yang Hongfeng , Zhu Linlin , Zhou Ling , Chen Shaoliang
Published: August 2018

Excessive proliferation, migration, and antiapoptosis of pulmonary artery (PA) smooth muscle cells (PASMCs) underlies the development of pulmonary vascular remodeling. The innervation of the PA is predominantly sympathetic, and increased levels of circulating catecholamines have been detected in pulmonary arterial hypertension (PAH), suggesting that neurotransmitters released by sympathetic overactivation may play an essential role in PAH. However, the responsible mechanism remains unclear. Here, to investigate the effects of norepinephrine (NE) on PASMCs and the related mechanism, we used 3‐(4,5‐dimethyl‐2‐thiazolyl)‐2,5‐diphenyl‐2‐H‐tetrazolium bromide, the proliferating cell nuclear antigen and the cell counting kit‐8 assay to evaluate the proliferation of PASMCs, Boyden chamber migration, and wound‐healing assays to assess migration and western blot analysis to investigate protein expression. We demonstrated that the phosphorylation level of the protein phosphatase 2A (PP2A) catalytic subunit (Y307) was higher in PAH patients and PAH models than in controls, both in vivo and in vitro. In addition, NE induced the proliferation and migration of PASMCs, which was attenuated by berberine (BBR), a Chinese herbal medicine, and/or PP2A overexpression. PP2A inhibition worsened NE‐induced PAH and could not be reversed by BBR. Thus, PP2A is critical in driving PAH, and BBR may alleviate PAH via PP2A signaling pathways, thereby offering a potential therapeutic option for PAH.
Establishment and characterization of a telomerase‐immortalized porcine bronchial epithelial cell line
Authors: Xie Xing , Gan Yuan , Pang Maoda , Shao Guoqing , Zhang Lei , Liu Beibei , Xu Qi , Wang Haiyan , Feng Yanyan , Yu Yanfei , Chen Rong , Wu Meng , Zhang Zhenzhen , Hua Lizhong , Xiong Qiyan , Liu Maojun , Feng Zhixin
Published: August 2018

Primary porcine bronchial epithelial cells (PBECs) are an ideal model to study the molecular and pathogenic mechanisms of various porcine respiratory pathogens. However, the short lifespan of primary PBECs greatly limit their application. Here, we isolated and cultured primary PBECs and established immortalized PBECs by transfecting primary PBECs with the pEGFP‐hTERT recombinant plasmid containing human telomerase reverse transcriptase (hTERT). Immortalized PBECs (hTERT‐PBECs) retained the morphological and functional features of primary PBECs as indicated by cytokeratin 18 expression, telomerase activity assay, proliferation assays, karyotype analysis, and quantitative reverse‐transcriptase polymerase chain reaction. Compared to primary PBECs, hTERT‐PBECs had higher telomerase activity, extended replicative lifespan, and displayed enhanced proliferative activity. Moreover, this cell line is not transformed in vitro and does not exhibit a malignant phenotype in vivo, suggesting that it can be safely used in further studies. Besides, hTERT‐PBECs were susceptible to swine influenza virus of H3N2 subtype and porcine circovirus type 2. In conclusion, the immortalized hTERT‐PBECs represent a valuable in vitro model, which can be widely used in the study of porcine respiratory pathogenic infections.
Exogenous hydrogen sulfide attenuates the development of diabetic cardiomyopathy via the FoxO1 pathway
Authors: Ye Peng , Gu Yue , Zhu Yan‐Rong , Chao Yue‐Lin , Kong Xiang‐Quan , Luo Jie , Ren Xiao‐Min , Zuo Guang‐Feng , Zhang Dai‐Min , Chen Shao‐Liang
Published: August 2018

Background

Previous studies have suggested that exogenous hydrogen sulfide can alleviate the development of diabetic cardiomyopathy (DCM) by inhibiting oxidative stress, inflammation, and apoptosis. However, the underlying mechanism is not fully understood. Nuclear expression and function of the transcription factor Forkhead box protein O (FoxO1) have been associated with cardiovascular diseases, and thus, the importance of FoxO1 in DCM has gained increasing attention. This study was designed to investigate the interactions between hydrogen sulfide (H2S) and nuclear FoxO1 in DCM.

Methods

Diabetes was induced in adult male C57BL/6J mice by intraperitoneal injection of streptozotocin and was treated with H2S donor sodium hydrosulfide for 12 weeks. The H9C2 cardiomyoblast cell line and neonatal rat cardiomyocytes (NRCMs) were treated with the slow‐releasing H2S donor GYY4137 before high‐glucose (HG) exposure with or without pretreatment with the Akt inhibitor MK‐2206 2HCl. Changes in FoxO1 protein phosphorylation and subcellular localization were determined in H9C2 cells, NRCMs, and cardiac tissues from normal and diabetic mice. Cardiac structure and function in the diabetic mice were evaluated by echocardiography and histological analysis and compared with those in control animals.

Results

The echocardiographic and histopathological data indicated that exogenous H2S improved cardiac function and attenuated cardiac hypertrophy and myocardial fibrosis in diabetic mice. H2S also improved HG‐induced oxidative stress and apoptosis in cardiac tissue and NRCMs. In addition, H2S induced FoxO1 phosphorylation and nuclear exclusion in vitro and in vivo, and this function was not inhibited by MK‐2206 2HCl. Alanine substitution mutation of three sites in FoxO1‐enhanced FoxO1 transcriptional activity, and subsequent treatment with exogenous H2S could not prevent HG‐induced nuclear retention.

Conclusions

Our data indicate that H2S is a novel regulator of FoxO1 in cardiac cells and provide evidence supporting the potential of H2S in inhibiting the progression of DCM.
Sex differences in murine cardiac pathophysiology with hyperoxia exposure
Authors: Rodgers Jennifer L. , Rodgers Lydia E. , Tian Zhi , Allen‐Gipson Diane , Panguluri Siva K.
Published: August 2018

Hyperoxia (>90% oxygen) is commonly implemented in mechanically ventilated patients. Reports suggest that hyperoxia is directly associated with in‐hospital mortality in ventilated patients. Certain studies also show that mortality in women undergoing mechanical ventilation is significantly higher than that in men. Additionally, females are predisposed to certain cardiac electrophysiological risks, including QTc prolongation. In this study, we assessed the impact of hyperoxia in male and female mice (C57BL/6J) at age 8–10 weeks. On completion of either hyperoxia or normoxia exposures, physical, hemodynamic, biochemical, functional, electrophysiological, and molecular assessments were conducted. Hyperoxia‐exposed mice lost a significant amount of body mass, compared with normoxia controls, in both sexes. However, while both genders developed brady‐arrhythmia after hyperoxia exposure, female mice exhibited significantly reduced heart rates compared with males, with significantly elevated RR intervals. Additionally, 50% mortality was observed in females, whereas no mortality was reported in males. Furthermore, unlike in male mice, we observed no hypertrophy upon hyperoxia exposure in female mice. We reported that both hyperoxia‐treated male and female mice exhibit significant hyperdynamic left ventricular ejection fraction, which is marked by % ejection fraction > 70 compared with the normoxia controls. We also noted significant reductions in stroke volume and cardiac output in both mice with hyperoxia. Surface ECG also demonstrated that hyperoxia exposure significantly augments RR, PR, QRS, QTc, and JT intervals in both sexes. Molecular analysis of left ventricular tissue demonstrated dysregulation of potassium ion channels in hyperoxia‐treated males and females. In summary, we determined that sex differences are present with 72 hr hyperoxia exposure.
Hippo pathway functions as a downstream effector of AKT signaling to regulate the activation of primordial follicles in mice
Authors: Hu Liao‐Liao , Su Tie , Luo Rui‐Chen , Zheng Yue‐Hui , Huang Jian , Zhong Zhi‐Sheng , Nie Jing , Zheng Li‐Ping
Published: August 2018

Clarifying the molecular mechanisms by which primordial follicles are initiated is crucial for the prevention and treatment of female infertility and ovarian dysfunction. The Hippo pathway has been proven to have a spatiotemporal correlation with the size of the primordial follicle pool in mice in our previous work. But the role and underlying mechanisms of the Hippo pathway in primordial follicle activation remain unclear. Here, the localization and expression of the core components were examined in primordial follicles before and after activation. And the effects of the Hippo pathway on primordial follicle activation were determined by genetically manipulating yes‐associated protein 1 (Yap1), the key transcriptional effector. Furthermore, an AKT specific inhibitor (MK2206) was added to determine the interaction between the Hippo pathway and AKT, an important signaling regulator of ovarian function. Results showed that the core components of the Hippo pathway were localized in both primordial and primary follicles and the expression levels of them changed significantly during the initiation of primordial follicles. Yap1 knockdown suppressed primordial follicle activation, while its overexpression led to the opposite trend. MK2206 downregulated the ratio of P‐MST/MST1 and upregulated the ratio of P‐YAP1/YAP1 significantly, whereas Yap1‐treatment had no influence on AKT. In addition, YAP1 upregulation partially rescued the suppression of the primordial follicle activation induced by MK2206. Our findings revealed that the Hippo‐YAP1 regulates primordial follicular activation, which is mediated by AKT signaling in mice, thus providing direct and new evidence to highlight the role of Hippo signaling in regulating ovarian follicles development.
Effects of carnitine palmitoyltransferases on cancer cellular senescence
Authors: Guan Lihuan , Chen Yixin , Wang Yongtao , Zhang Huizhen , Fan Shicheng , Gao Yue , Jiao Tingying , Fu Kaili , Sun Jiahong , Yu Aiming , Huang Min , Bi Huichang
Published: August 2018

The carnitine palmitoyltransferase (CPT) family is essential for fatty acid oxidation. Recently, we found that CPT1C, one of the CPT1 isoforms, plays a vital role in cancer cellular senescence. However, it is unclear whether other isoforms (CPT1A, CPT1B, and CPT2) have the same effect on cellular senescence. This study illustrates the different effects of CPT knockdown on PANC‐1 cell proliferation and senescence and MDA‐MB‐231 cell proliferation and senescence, as demonstrated by cell cycle kinetics, Bromodeoxyuridine incorporation, senescence‐associated β‐galactosidase activity, colony formation, and messenger RNA (mRNA) expression of key senescence‐associated secretory phenotype factors. CPT1C exhibits the most substantial effect on cell senescence. Lipidomics analysis was performed to further reveal that the knockdown of CPTs changed the contents of lipids involved in mitochondrial function, and lipid accumulation was induced. Moreover, the different effects of the isoform deficiencies on mitochondrial function were measured and compared by the level of radical oxygen species, mitochondrial transmembrane potential, and the respiratory capacity, and the expression of the genes involved in mitochondrial function were determined at the mRNA level. In summary, CPT1C exerts the most significant effect on mitochondrial dysfunction‐associated tumor cellular senescence among the members of the CPT family, which further supports the crucial role of CPT1C in cellular senescence and suggests that inhibition of CPT1C may represent as a new strategy for cancer treatment through the induction of tumor senescence.
Targeting drugs to APJ receptor: From signaling to pathophysiological effects
Authors: Huang Zhen , He Lu , Chen Zhe , Chen Linxi
Published: August 2018

G‐protein‐coupled receptors (GPCRs) are recognized as the largest protein receptor superfamily, which are widely distributed in various tissues and organs. In addition, GPCRs are involved in many physiological and pathological longitudinal responses. Studies have indicated that putative receptor protein related to AT1 (APJ receptor) is an orphan GPCRs until its endogenous ligand apelin is found. Recently, Elabela, a new APJ receptor endogenous ligand was also found. Some evidence showed that the APJ receptor is distributed in the central nervous and cardiovascular systems. Moreover, the APJ receptor and its ligand are involved in many physiological functions and pathophysiological effects, making it a promising drug target for future treatment of diseases such as ischemic heart disease, hypertension, heart failure, and others. Although APJ is closely associated with many diseases, there are no drugs that can activate or inhibit APJ directly. In the current review, we try our best to summarize all agonists and antagonists targeting APJ, including peptides and small molecules. Given the role of apelin/APJ and Elabela/APJ in cardiovascular and other diseases, we believe that the combination of these agonists and antagonists with apelin and Elabela will play a corresponding role in various pathophysiological effects with further development of research.
Licochalcone D directly targets JAK2 to induced apoptosis in human oral squamous cell carcinoma
Authors: Seo Ji‐Hye , Choi Hyun Woo , Oh Ha‐Na , Lee Mee‐Hyun , Kim Eunae , Yoon Goo , Cho Seung‐Sik , Park Seon‐Min , Cho Young Sik , Chae Jung‐Il , Shim Jung‐Hyun
Published: August 2018

Licochalcone (LC) families have been reported to have a wide range of biological function such as antioxidant, antibacterial, antiviral, and anticancer effects. Although various beneficial effects of LCD were revealed, its anticancer effect in human oral squamous cancer has not been identified. To examine the signaling pathway of LCD’s anticancer effect, we determined whether LCD has physical interaction with Janus kinase (JAK2)/signal transducer and activator of transcription‐3 (STAT3) signaling, which is critical in promoting cancer cell survival and proliferation. Our results demonstrated that LCD inhibited the kinase activity of JAK2, soft agar colony formation, and the proliferation of HN22 and HSC4 cells. LCD also induced mitochondrial apoptotic events such as altered mitochondrial membrane potential and reactive oxygen species production. LCD increased the expression of apoptosis‐associated proteins in oral squamous cell carcinoma (OSCC) cells. Finally, the xenograft study showed that LCD significantly inhibited HN22 tumor growth. Immunohistochemical data supported that LCD suppressed p‐JAK2 and p‐STAT3 expression and induced cleaved‐caspase‐3 expression. These results indicate that the anticancer effect of LCD is due to the direct targeting of JAK2 kinase. Therefore, LCD can be used for therapeutic application against OSCC.
Regulation of human mitogen‐activated protein kinase 15 (extracellular signal‐regulated kinase 7/8) and its functions: A recent update
Authors: Lau Andy T. Y. , Xu Yan‐Ming
Published: August 2018

Mitogen‐activated protein kinase 15 (MAPK15), originally also known as extracellular signal‐regulated kinase 7/8, is the most recently identified atypical MAPK and the least studied so far. Examinations of the role of MAPK15 in various cell lines and model systems indicate that MAPK15 participates in a variety of cellular activities such as promoting cell proliferation, cell transformation, and apoptosis; stimulating autophagy; regulating cell division, ciliogenesis, and protein secretion; and maintaining genome stability. As multiple roles of MAPK15 were observed among these studies, therefore, it remains unclear whether MAPK15 acts as a proto‐oncogene or tumor suppressor. Here, the recent literature on human MAPK15 and the resulting functions will be discussed.
Carvacrol induces mitochondria‐mediated apoptosis via disruption of calcium homeostasis in human choriocarcinoma cells
Authors: Lim Whasun , Ham Jiyeon , Bazer Fuller W. , Song Gwonhwa
Published: August 2018

Carvacrol is a monoterpenoid phenol present in the oils of various plants including Origanum vulgare (oregano) or Origanum majorana (marjoram). For a long time, it has been used as spice in foods because of its antimicrobial properties. Additionally, it appears to have anticancer effects against some cancer but this has not been well studied. Therefore, we conducted various assays to confirm the effects of carvacrol on choriocarcinoma cell lines (JAR and JEG3). Our results indicate that carvacrol has antiproliferative properties and induces apoptosis, resulting in increased expression of proapoptotic proteins. Additionally, carvacrol disrupted the mitochondrial membrane potential and induced calcium ion overload in the mitochondrial matrix in both JAR and JEG3 cells. Furthermore, carvacrol generated oxidative stress and lipid peroxidation in both JAR and JEG3 cells. Moreover, carvacrol‐suppressed phosphoinositide 3‐kinase–protein kinase B and extracellular signal–regulated kinase 1/2 mitogen‐activated protein kinase (MAPK) signal transduction whereas expression of phosphor‐P38 and c‐Jun N‐terminal kinase MAPK was increased. Together, our results indicate that carvacrol may be a possible new therapeutic agent or supplement for the control of human choriocarcinomas.
Deguelin inhibits RANKL‐induced osteoclastogenesis in vitro and prevents inflammation‐mediated bone loss in vivo
Authors: Zhang Tan , Zhao Kangxian , Han Weiqi , Yang Wanlei , Lu Xuanyuan , Liu Qian , Li Xiucheng , Qian Yu
Published: August 2018

Excessive bone resorption by osteoclasts (OCs) plays an important role in lytic bone diseases, such as osteoporosis. Although the pharmacological treatment of osteoporosis has been extensively developed, alternative treatments are still needed. Deguelin, a rotenoid isolated from several plant species, is a strong antitumor agent; however, its effect on OCs remains unclear. To the best of our knowledge, this is the first study to report that deguelin inhibits the receptor activator of nuclear factor‐κB (NF‐κB) ligand (RANKL)‐induced osteoclastogenesis, messenger RNA expression of osteoclastic‐specific genes, and osteoclastic bone resorption, in primary bone marrow‐derived macrophages. At the molecular level, deguelin markedly blocked RANKL‐induced osteoclastogenesis by attenuating the phosphorylation of NF‐κB p65 and inhibiting p65 nuclear translocation. In addition, deguelin suppressed the downstream expression of nuclear factor of activated T‐cell cytoplasmic 1, which is a crucial transcription factor in OC differentiation. Consistent with the in vitro results, deguelin inhibited lipopolysaccharide‐induced bone resorption by suppressing osteoclastogenesis. Taken together, our findings reveal that deguelin has antiosteoclastic effects in vitro and in vivo and possesses potential as a new therapeutic option for osteolytic bone diseases.
Action mechanisms of n‐3 polyunsaturated fatty acids on the oocyte maturation and developmental competence: Potential advantages and disadvantages
Authors: Zarezadeh Reza , Mehdizadeh Amir , Leroy Jo L. M. R. , Nouri Mohammad , Fayezi Shabnam , Darabi Masoud
Published: August 2018

Infertility is a growing problem worldwide. Currently, in vitro fertilization (IVF) is widely performed to treat infertility. However, a high percentage of IVF cycles fails, due to the poor developmental potential of the retrieved oocyte to generate viable embryos. Fatty acid content of the follicular microenvironment can affect oocyte maturation and the subsequent developmental competence. Saturated and monounsaturated fatty acids are mainly used by follicle components as primary energy sources whereas polyunsaturated fatty acids (PUFAs) play a wide range of roles. A large body of evidence supports the beneficial effects of n‐3 PUFAs in prevention, treatment, and amelioration of some pathophysiological conditions including heart diseases, cancer, diabetes, and psychological disorders. Nevertheless, current findings regarding the effects of n‐3 PUFAs on reproductive outcomes in general and on oocyte quality more specifically are inconsistent. This review attempts to provide a comprehensive overview of potential molecular mechanisms by which n‐3 PUFAs affect oocyte maturation and developmental competence, particularly in the setting of IVF and thereby aims to elucidate the reasons behind current discrepancies around this topic.
Relationship between endothelial function and skeletal muscle strength in community dwelling elderly women
Authors: Yoo Jun‐Il , Kim Mi‐Ji , Na Jae‐Bum , Chun Yun‐Hong , Park Young‐Jin , Park Yongwhi , Hah Young‐Sool , Ha Yong‐Chan , Park Ki Soo
Published: August 2018

Background

The aim of this study is to determine whether there is correlation between endothelial function and skeletal muscle function measured by hand grip strength in elderly women.

Methods

This cross‐sectional study used data of NAMGARAM‐2 cohort. The NAMGARAM‐2 cohort consisted of a group of people living in three rural communities. They were enrolled for studies on activity limitation due to age‐related musculoskeletal disorders including knee osteoarthritis, osteoporosis, and sarcopenia. They were residents aged 40 years or older. They agreed to participate in this cohort from March 2016 to May 2017. Peripheral endothelial function was assessed by reactive hyperaemia‐peripheral arterial tonometry using EndoPAT2000 system. Hand grip strength was measured using a digital hand dynamometer.

Results

Endothelial function index assessed by EndoPAT was worse in the low grip strength group than that in the normal group of elderly women (1.54 ± 0.51 in the low grip strength group vs. 1.77 ± 0.67 in the normal group, P = 0.003). There was a positive correlation between hand grip strength and endothelial function (r = 0.176, P = 0.007). On stepwise multivariate analysis, endothelial dysfunction (reactive hyperaemia‐peripheral arterial tonometry index < 1.67) significantly increased the risk of low hand grip strength (odds ratio = 2.019; 95% confidence interval = 1.107–3.682; P = 0.022).

Conclusions

Endothelial function and skeletal muscle strength had a significant correlation in elderly women, providing additional support for the relevant role of vascular system in sarcopenia.
Behavioral control by the response–reinforcer correlation
Authors: Kuroda Toshikazu , Lattal Kennon A.
Published: August 2018

Using a discrete‐trials procedure, two experiments examined the effects of response–reinforcer correlations on responding while controlling molecular variables that operated at the moment of reinforcer delivery (e.g., response–reinforcer temporal contiguity, interresponse times preceding reinforcement). Each trial consisted of three successive components: Response, Timeout, and Reinforcement, with the duration of each component held constant. The correlation between the number of responses in the Response component and reinforcer deliveries in the Reinforcement component was varied. In the Positive‐correlation condition, a larger number of responses in the Response component programmed a higher reinforcement rate (Experiment 1) or a shorter time to reinforcement (Experiment 2) in the Reinforcement component. Although programmed in this way, the actual reinforcer delivery was dependent on, and occurred immediately after, a response in the Reinforcement component. In the Zero‐correlation condition, the programmed rates of reinforcement (Experiment 1) or the times to reinforcement (Experiment 2) in the Reinforcement component of each trial were yoked to those in the preceding Positive‐correlation condition. Responding in the Response component was higher in the Positive‐ than in the Zero‐correlation condition, without systematic changes in molecular variables. The results suggest that the response–reinforcer correlation can be a controlling variable of behavior.
The effect of vitamin D deficiency on eradication rates of Helicobacter pylori infection
Authors: El Shahawy Mohamed S , Hemida Mahmoud H , El Metwaly Ibrahim , Shady Zakarya M
Published: August 2018

Background/Aim

Many studies have investigated risk factors other than antibiotic resistance linked to Helicobacter pylori (H. pylori) eradication failure. The aim of this study was to study the effect of serum levels of 25‐hydroxy‐vitamin D (25[OH]D) on eradication rates of H. pylori infection.

Methods

This study included 150 patients diagnosed with H. pylori gastritis using magnifying narrow‐band imaging endoscopy supported by stool antigen test. Serum 25‐OH vitamin D levels were measured via the Enzyme‐Linked Immune Sorbent assay (ELISA) method before starting eradication therapy of H. pylori infection. All patients were treated with clarithromycin‐based triple therapy for 14 days. H. pylori eradication was determined via a stool antigen test performed 4 weeks after the end of therapy. According to the serum level of 25‐OH vitamin D levels, the patients were divided into two groups: group I (sufficient) had a vitamin D level of ≥20 ng/mL, while group II (deficient) had a vitamin D level of <20 ng/mL.

Results

Our results revealed that eradication was successful in 105 (70%) patients and failed in 45 (30%) patients. The mean 25[OH]D level was significantly lower in the eradication failure group compared to the successful treatment group (14.7 ± 4.5 vs 27.41 ± 7.1; P < 0.001). Furthermore, there were significantly more patients with deficient 25[OH]D levels in the failed treatment group, 30 (66.6%), compared to the successful group, 10 (9.5%) (P < 0.001).

Conclusions

Our results demonstrated that 25‐OH vitamin D deficiency may be considered a risk factor related to eradication failure of H. pylori infection. In addition, a further randomized trial to evaluate the effect of vitamin D supplementation in H. pylori eradication is mandatory.
Enabling graduation for whom? Identifying and explaining heterogeneity in livelihood trajectories post‐cash transfer exposure
Authors: Sabates‐Wheeler Rachel , Sabates Ricardo , Devereux Stephen
Published: August 2018

We use a data set from a graduation programme in Rwanda to explore the heterogeneous livelihood pathways that programme participants follow during and after the programme period. We show that household characteristics, such as gender of household head and labour availability, will affect trajectories of change; yet, the impact of initial resources will depend on what outcomes are being measured and possible complementarities between them. This reinforces the importance of a multi‐sectoral strategy for supporting livelihoods. We conclude that certain types of households need longer on a programme, as well as additional support to local enabling factors to support graduation. Copyright © 2018 John Wiley & Sons, Ltd.
How Do High and Low Levels of Social Trust Affect the Long‐run Performance of Poor Economies?
Authors: Gundlach Erich , Svendsen Gert Tinggaard
Published: August 2018

Poor countries with high levels of social trust are shown to experience a hump‐shaped pattern of long‐run growth. With social trust modelled as a human capital externality, a calibrated two‐sector model replicates the observed hump‐shaped growth path. The simulation results imply that a hypothetical poor economy with ahighlevel of social trust, when beginning at a relative income level of 16 per cent, may need about 160 years to reach 50 per cent of the income level of the leading countries. For a hypothetical poor country with alowlevel of social trust, the process of catching up may only begin after more than 150 years of relative stagnation. © 2018 John Wiley & Sons, Ltd.
Improved perfusion pattern score association with type 2 diabetes severity using machine learning pipeline: Pilot study
Authors: Chen Yuheng , Duan Wenna , Sehrawat Parshant , Chauhan Vaibhav , Alfaro Freddy J , Gavrieli Anna , Qiao Xingye , Novak Vera , Dai Weiying
Published: August 2018

Background

Type 2 diabetes mellitus (T2DM) is associated with alterations in the blood–brain barrier, neuronal damage, and arterial stiffness, thus affecting cerebral metabolism and perfusion. There is a need to implement machine‐learning methodologies to identify a T2DM‐related perfusion pattern and possible relationship between the pattern and cognitive performance/disease severity.

Purpose

To develop a machine‐learning pipeline to investigate the method's discriminative value between T2DM patients and normal controls, the T2DM‐related network pattern, and association of the pattern with cognitive performance/disease severity.

Study Type

A cross‐sectional study and prospective longitudinal study with a 2‐year time interval.

Population

Seventy‐three subjects (41 T2DM patients and 32 controls) aged 50–85 years old at baseline, and 42 subjects (19 T2DM and 23 controls) aged 53–88 years old at 2‐year follow‐up.

Field Strength/Sequence

3T pseudocontinuous arterial spin‐labeling MRI.

Assessment

Machine‐learning‐based pipeline (principal component analysis, feature selection, and logistic regression classifier) to generate the T2DM‐related network pattern and the individual scores associated with the pattern.

Statistical Tests

Linear regression analysis with gray matter volume and education years as covariates.

Results

The machine‐learning‐based method is superior to the widely used univariate group comparison method with increased test accuracy, test area under the curve, test positive predictive value, adjusted McFadden's R square of 4%, 12%, 7%, and 24%, respectively. The pattern‐related individual scores are associated with diabetes severity variables, mobility, and cognitive performance at baseline (P < 0.05, |r| > 0.3). More important, the longitudinal change of individual pattern scores is associated with the longitudinal change of HbA1c (P = 0.0053, r = 0.64), and baseline cholesterol (P = 0.037, r = 0.51).

Data Conclusion

The individual perfusion diabetes pattern score is a highly promising perfusion imaging biomarker for tracing the disease progression of individual T2DM patients. Further validation is needed from a larger study.

Level of Evidence: 1

Technical Efficacy: Stage 1

J. Magn. Reson. Imaging 2019;49:834–844.
Upscaling impact of wind/sea surface temperature mesoscale interactions on southern Africa austral summer climate
Authors: Desbiolles Fabien , Blamey Ross , Illig Serena , James Rachel , Barimalala Rondrotiana , Renault Lionel , Reason Chris
Published: August 2018

Mesoscale sea surface temperature (SST) variability plays an important role in shaping local atmospheric boundary layers through thermodynamic processes. This study focuses on the upscaling effects of mesoscale SST gradients in sensitive areas on the southern Africa regional atmospheric circulation. Using regional atmospheric model sensitivity experiments which differ only in the mesoscale SST forcing characteristics (either the full spectrum of SST variability or only its large‐scale components are included), we first quantify the importance of SST gradients on regional atmospheric conditions. Agulhas eddies and meanders influence the vertical air column up to the troposphere, and mesoscale ocean patterns significantly modify incoming landwards moisture fluxes. The austral summer mean state is then modified in terms of air temperature, cloud cover and mean rainfall, with notable differences in tropical rainbands over southwestern Africa. Mesoscale SST variability favours tropical–extra‐tropical interactions and cloudband development over the continent. These results stress the importance of high‐resolution ocean forcing for accurate atmospheric simulations.
Biomechanics of the knee extensor mechanism and its relationship to patella tendinopathy: A review
Authors: Dan Michael , Parr William , Broe David , Cross Mervyn , Walsh William R.
Published: August 2018

The term jumpers knee for patella tendinitis, as coined by Dr. Martin Blazina, is now commonly referred to as tendinopathy. He believed it was associated with patella alta. Since then multiple studies have failed to reliably show an association between patella tendinopathy and associated intrinsic risk factors. There is, unfortunately, a well‐established doctrine that the extensor mechanism is simply a pulley. The goal of the review is to examine the biomechanics of the extensor mechanism and apply this to studies investigating intrinsic risk factors for patella tendinopathy. A better understanding of the biomechanics of the extensor mechanism may stimulate the discovery of intrinsic risk factors for developing patella tendinopathy, and subsequent surgical options to address them. Clinical significance: The aim of this review is to direct future research into biomechanical risk factors for developing patella tendinopathy and subsequently, possible treatments. © 2018 Orthopaedic Research Society. Published by Wiley Periodicals, Inc. J Orthop Res 36:3105–3112, 2018.
Investigation of carbon in the Allan Hills A77278 meteorite via 2D and 3D Raman microspectroscopy
Authors: Yesiltas Mehmet
Published: August 2018

This paper reports the first Raman spectral and imaging data on the ordinary chondrite Allan Hills A77278 (ALHA77278) in two and three dimensions. Mineralogy in the ALHA77278 meteorite appears to be mainly silicates (olivine and pyroxene) with some carbonaceous material in the matrix. Metal phases are also present in the studied sample. Two‐dimensional Raman spectral distribution maps show the locations of these chemical constituents. Several diamond grains are observed to be buried in olivine and extend down to a ~7‐μm depth in the sample, which might be contamination captured during the sample preparation. Raman spectral peak parameters for D and G carbon bands are presented and trends among these parameters are discussed. These spectral parameters, when compared with those of other meteorites reported in the literature, show similarity with unequilibrated ordinary chondrites and primitive carbonaceous chondrites. Estimated peak metamorphic temperature for the parent asteroid is calculated to be around ~260°C, which is comparable with lower metamorphic grade ordinary chondrites, indicating that the metamorphic grade of ALHA77278 might be less than 3.7, as it has been officially assigned. Three‐dimensional Raman tomographic measurements present visualizations of the identified chemical components in high resolution as well as the epoxy used during the preparation of the sample. Spatial distribution of epoxy is used to avoid these regions during the Raman spectral data extraction from the carbonaceous matter from a depth of the sample, which could otherwise complicate the datasets used to infer the thermal history of the ALHA77278 meteorite.
Reducing the cooking water‐to‐dried pasta ratio and environmental impact of pasta cooking
Authors: Cimini Alessio , Cibelli Matteo , Moresi Mauro
Published: August 2018

BACKGROUND

During daily pasta cooking, the general consumer pays little attention to water and energy issues. The present study aimed to measure the cooking quality and environmental impact of a standard format of dry pasta by varying the water‐to‐dried pasta ratio (WPR) from 12 to 2 L kg−1.

RESULTS

In the above WPR range, the cooked pasta water uptake (1.3 ± 0.1 g g−1), cooking loss (0.037 ± 0.009 g g−1) and degree of starch gelatinization (11.2 ± 0.8%) were approximately constant, whereas the main Texture Analysis parameters (eg, cooked pasta hardness at 30% and 90% deformation, and resilience) showed no statistically significant difference. As the WPR was reduced from 12 to 2 L kg−1, the specific electric energy consumption linearly decreased from 1.93 to 0.39 Wh g−1 and the carbon footprint and eutrophication potential of pasta cooking lessened by approximately 80% and 50%, respectively.

CONCLUSION

Cooking dry pasta in a large excess of water (ie, 10 L kg−1), as commonly suggested by the great majority of pasta manufacturers, might be pointless. Such a great mitigation with respect to the environmental impact of pasta cooking should be checked further for other commercial pasta formats and would highlight the need for novel and more suitable pasta cookers than those currently in use. © 2018 Society of Chemical Industry
Composition and physicochemical properties of dried berry pomace
Authors: Reißner Anne‐Marie , Al‐Hamimi Said , Quiles Amparo , Schmidt Carolin , Struck Susanne , Hernando Isabel , Turner Charlotta , Rohm Harald
Published: August 2018

BACKGROUND

Berry pomace is a valuable but little used by‐product of juice manufacturing. When processed to a stable fruit powder, the composition differs from that of the whole fruit. To facilitate application in foods, a detailed knowledge of its composition and physicochemical properties is essential.

RESULTS

Blackcurrant, redcurrant, chokeberry, rowanberry and gooseberry were selected for analysis. All pomace powders had a high fibre content (> 550 g kg−1) and a fat content of up to 200 g kg−1. Despite identical milling conditions, the particle sizes of the pomace powders varied. This can be traced back to seed content and brittleness, which also becomes apparent with respect to surface characteristics. Blackcurrant pomace powder differed from other varieties in terms of its low water‐binding capacity (3.2 g g−1) and a moderate moisture uptake, whereas chokeberry pomace powder showed the highest polyphenol content and rowanberry pomace powder was rich in flavonols.

CONCLUSION

The results obtained in the present study provide a comprehensive overview of the properties of berry pomace powder and allow conclusions to be made regarding their applicability for use in complex food systems. © 2018 Society of Chemical Industry
Advantages of patient‐derived orthotopic mouse models and genetic reporters for developing fluorescence‐guided surgery
Authors: Lwin Thinzar M , Hoffman Robert M , Bouvet Michael
Published: August 2018

Fluorescence‐guided surgery can enhance the surgeon’s ability to achieve a complete oncologic resection. There are a number of tumor‐specific probes being developed with many preclinical mouse models to evaluate their efficacy. The current review discusses the different preclinical mouse models in the setting of probe evaluation and highlights the advantages of patient‐derived orthotopic xenografts (PDOX) mouse models and genetic reporters to develop fluorescence‐guided surgery.
Resection of abdominal inferior vena cava without graft interposition: Considerations in preserving renal function
Authors: Theodoraki Kassiani , Kostopanagiotou Konstantinos , Theodosopoulos Theodosios , Vassiliu Pantelis , Kizgala Polyxeni , Parasyris Stavros , Bouzalas Dionysios , Arkadopoulos Nikolaos , Smyrniotis Vassilios
Published: August 2018

The management of tumors involving or infiltrating the inferior vena cava (IVC) constitutes a great surgical challenge, since radical resection affords patients the only possibility for long‐term survival. These tumors can be resected without graft interposition, provided that there is adequate collateral circulation and that the renal function can be secured. Meanwhile, ligation of the left renal vein may be possible due to the existence of collateral circulation through the adrenal and gonadal veins. We briefly present our experience on renal outflow preservation through implantation of the right renal vein into the IVC stump or through diversion of the left renal vein into the inferior mesenteric vein.