bluuebunny/crossref_metadata_2025 huggingface dataset:
Breath Figures decorated silicon oxinitride ceramic surfaces with controlled Si ions release for enhanced osteoinduction
Authors: Carlomagno Cristiano , Motta Antonella , Sorarù Giandomenico , Aswath Pranesh , Migliaresi Claudio , Maniglio Devid
Published: October 2018

Bioactive coatings are usually applied to bone and dental prostheses to enhance the integration and their stability in the bone. Recently, silicon (Si) oxynitride ceramics have been demonstrated to possess osteoconductive properties due to the release of Si ions, particularly important in the early stage of bone formation. In addition, the pattern of the bone contacting surface has been reported to affect cells’ differentiation and metabolic activity. In this work, we propose the Breath Figure (BF) process combined with a pyrolysis step, starting from a photo‐crosslinkable alkoxy silicone precursor, as a method to realize bioactive patterned coating on metal bone and dental prostheses. Four different surface patterned coatings were applied to Ti4Al6V disks starting from solutions with different precursor concentrations. Morphology, chemical composition, and Si ions’ release were evaluated and compared. Moreover, all samples underwent to biological in vitro testing with human mesenchymal stem cells (hMSCs) in comparison with the uncoated titanium alloy. The results indicated that the Si released from the coatings determined an increase in the cellular activity with the BF pattern influencing the hMSCs’ initial adhesion and proliferation. © 2018 Wiley Periodicals, Inc. J Biomed Mater Res Part B: Appl Biomater 107B: 1284–1294, 2019.
HOXD‐AS1 is a predictor of clinical progression and functions as an oncogenic lncRNAs in papillary thyroid cancer
Authors: Xu Kai , Feng Ying
Published: October 2018

Long noncoding RNA HOXD cluster antisense RNA 1 (HOXD‐AS1) has been found to play a crucial role in the tumorigenesis and progression of human cancer. However, the role of HOXD‐AS1 in papillary thyroid cancer is still unknown. The purpose of this study was to investigate the clinical value and biological function of HOXD‐AS1 in papillary thyroid cancer. The results showed HOXD‐AS1 is overexpressed in papillary thyroid cancer tissues and cell lines compared with matching nontumor tissue specimens and normal thyroid cell line, respectively. High expression of HOXD‐AS1 was associated with elderly people, advanced clinical stage, large tumor size, present lymph node metastasis, and distant metastasis. There was no significant correlation between HOXD‐AS1 expression and disease‐free survival or overall survival in this cohort from the TCGA database. The study in vitro suggested reduced HOXD‐AS1 expression inhibited papillary thyroid cancer cell proliferation, migration, and invasion, and promoted cell‐cycle arrest. In conclusion, HOXD‐AS1 is a biomarker for predicting clinical progression in papillary thyroid cancer.
Eriodictyol inhibits high glucose‐induced oxidative stress and inflammation in retinal ganglial cells
Authors: Lv Peilin , Yu Jingni , Xu Xiayu , Lu Tianjian , Xu Feng
Published: October 2018

Diabetic retinopathy (DR) is one of the most common microvascular complications of diabetes mellitus and is considered as a leading cause of blindness. Oxidative stress and inflammation are significant drivers for the development of DR. Eriodictyol, a flavonoid compound, was proved to possess anti‐inflammatory, antioxidative, and antidiabetic activities. However, the role of eriodictyol in DR has not been unveiled. In the current study, we explored the protective effects of eriodictyol on high glucose (HG)‐induced rat retinal ganglial cells (RGCs). The results suggested that eriodictyol improved cell viability of HG‐induced rat RGC‐5 cells in a dose‐dependent manner. Eriodictyol reduced the reactive oxygen species production and increased the activities of superoxide dismutase, glutathione peroxidase and catalase in rat RGC‐5 cells in response to HG stimulation. The production of proinflammatory cytokines including tumor necrosis factor alpha and interleukin‐8 was diminished after eriodictyol treatment. Eriodictyol also suppressed cell apoptosis induced HG in rat RGC‐5 cells. Furthermore, eriodictyol enhanced the nuclear translocation of nuclear factor erythroid‐2 (E2)‐related factor 2 (Nrf2) and elevated the expression of antioxidant enzyme heme‐oxygenase‐1 (HO‐1). These findings suggested that eriodictyol protects the RGC‐5 cells from HG‐induced oxidative stress, inflammation, and cell apoptosis through regulating the activation of Nrf2/HO‐1 pathway.
Retracted: MicroRNA‐105 promotes epithelial‐mesenchymal transition of nonsmall lung cancer cells through upregulating Mcl‐1
Authors: Jin Xiangfeng , Yu Yi , Zou Qiang , Wang Mingzhao , Cui Yaojie , Xie Jing , Wang Zizong
Published: October 2018

Background

A growing number of microRNAs have been proved to play significant roles in limiting tumor growth and the epithelial‐mesenchymal transition (EMT) process of nonsmall cell lung cancer (NSCLC). Present work aims to study the function of microRNA (miR)‐105 in EMT of NSCLC cells, which is unrevealed yet.

Methods

Two NSCLC cell lines A549 and Calu‐3 were transfected with miR‐105 mimic, inhibitor, or scrambled control. And then the effects of miR‐105 were evaluated by performing trypan blue staining, transwell assay, ANNEXIN‐FITC/propidium iodide (PI) double staining and Western blot analysis. The expression levels of myeloid cell leukemia‐1 (Mcl‐1) after transfection were tested by real‐time quantitative polymerase chain reaction and Western blot analysis. Whether Mcl‐1 was a downstream effector of miR‐105, and the involvement of mammalian target of Rapamycin (mTOR) and p38 mitogen‐activated protein kinase (p38MAPK) signaling pathways were assessed.

Results

The overexpression of miR‐105 significantly increased the viability and migration of A549 and Calu‐3, but had no impacts on cell apoptosis. Meanwhile, E‐cadherin was remarkably downregulated, and N‐cadherin, Vimentin, ZEB1, and Snail were upregulated by miR‐105 overexpression. Mcl‐1 was positively regulated by miR‐105, and the effects of miR‐105 overexpression on A549 and Calu‐3 cells viability, migration and EMT were all flattened by Mcl‐1 silence. Both mTOR and p38MAPK pathways were activated in miR‐105‐overexpressing and Mcl‐1‐overexpressing cells. Besides, inhibition of mTOR and p38MAPK pathways by using Rapamycin and VX‐702 abolished the regulatory effects of Mcl‐1 on EMT.

Conclusion

Our study underlines the importance of miR‐105 in modulating NSCLC cells EMT. miR‐105 promoted the EMT of NSCLC cells possibly via upregulation of Mcl‐1 and thereby activation of mTOR and p38MAPK signaling.
Long noncoding RNA growth arrest‐specific 5 facilitates glioma cell sensitivity to cisplatin by suppressing excessive autophagy in an mTOR‐dependent manner
Authors: Huo Jun‐Feng , Chen Xiao‐Bing
Published: October 2018

Malignant glioma is a severe type of brain tumor with a grim prognosis. The occurrence of resistance compromises the efficacy of chemotherapy for glioma. Long noncoding RNA growth arrest‐specific 5 (GAS5) has recently become an attractive target for cancer therapy by regulating cell growth, invasion, and migration. Nevertheless, its role in glioma chemoresistance remains elusive. In the current study, the expression of GAS5 was decreased in glioma cell lines, and lower levels of GAS5 were observed in U138 and LN18 glioma cells that had low sensitivity to cisplatin. Functional assay confirmed that knockdown of GAS5 enhanced cell resistance to cisplatin in U87 cells, which had a relatively high expression of GAS5. Conversely, elevation of GAS5 increased cell sensitivity to cisplatin in U138 cells that had a relatively low expression of GAS5. Mechanistically, cisplatin exposure evoked excessive autophagy concomitant with an increase in autophagy‐related LC3II expression and a decrease in autophagy substrate p62 expression, which was reversely muted after GAS5 overexpression. In addition, GAS5 restored cisplatin‐inhibited mammalian target of rapamycin (mTOR) activation. Preconditioning with mTOR antagonist rapamycin engendered not only mTOR inhibition but also abrogated GAS5‐mediated depression in cisplatin‐evoked autophagy. Notably, blocking the mTOR pathway also attenuated GAS5‐increased sensitivity to cisplatin in U138 cells. Cumulatively, these findings indicate that GAS5 may blunt the resistance of glioma cells to cisplatin by suppressing excessive autophagy through the activation of mTOR signaling, implying a promising therapeutic strategy against chemoresistance in glioma.
Retracted: Downregulated microRNA‐224 aggravates vulnerable atherosclerotic plaques and vascular remodeling in acute coronary syndrome through activation of the TGF‐β/Smad pathway
Authors: Xu Hai‐Ming , Sui Feng‐Hua , Sun Mei‐Hua , Guo Gong‐Liang
Published: October 2018

Recent studies have shown that circulating microRNAs (miRNA) play a critical role in diagnosing acute coronary syndrome (ACS). This study aims to investigate the effect of miR‐224 on atherosclerotic plaques forming and vascular remodeling in ACS and its relationship with TGF‐β/Smad pathway. Myocardial infarction (MI) rat model was established and lentivirus vector of miR‐224 inhibitor was prepared for investigating the effect of downregulated miR‐224 on the contents of nitric oxide (NO) and endothelin‐1 (ET‐1), blood lipid levels and inflammatory factor levels in serum as well as the TGF‐β/Smad pathway. The rats suffering from MI had decreased survival rates and exhibited reduced levels of NO, high‐density lipoprotein cholesterol, and lumen diameter, and Smad7 messenger RNA (mRNA) and protein expression; while had significantly increased ratio of heart weight or body weight, levels of ET‐1, inflammatory factors, blood lipid indexes, vascular remodeling indexes, collagen volume fraction, vulnerable atherosclerotic plaque area, VCAM‐1 and MMP‐2 protein expression, TGF‐β, Smad2, Smad3, and Smad4 mRNA and protein expression. After inhibiting the TGF‐β/Smad pathway, the rats suffering from MI showed notably opposite trend. In conclusion, downregulation of miR‐224 expression promotes the formation of vulnerable atherosclerotic plaques and vascular remodeling in ACS through activation of the TGF‐β/Smad pathway. Therefore, this study provides a new therapeutic target for ACS.
Alteration of cellular and immune‐related properties of bone marrow mesenchymal stem cells and macrophages by K562 chronic myeloid leukemia cell derived exosomes
Authors: Jafarzadeh Nazli , Safari Zohreh , Pornour Majid , Amirizadeh Naser , Forouzandeh Moghadam Mehdi , Sadeghizadeh Majid
Published: October 2018

Leukemic cells can impact the bone marrow niche to create a tumor‐favorable microenvironment using their secreted factors. Little knowledge is available about immunosuppressive and tumor‐promoting properties of chronic myeloid leukemia derived exosomes in bone marrow stromal components. We report here that K562‐derived exosomes can affect the gene expression, cytokine secretion, nitric oxide (NO) production, and redox potential of bone marrow mesenchymal stem cells (BM‐MSCs) and macrophages. Human BM‐MSCs and mouse macrophages were treated with K562‐derived exosomes. Our results demonstrated that the expression of the genes involved in hematopoietic developmental pathways and immune responses, including C‐X‐C motif chemokine 12 (Cxcl12), Dickkopf‐related protein 1 (DKK1), wnt5a, interleukin 6 (IL‐6), transforming growth factor‐beta, and tumor necrosis factor‐alpha (TNF‐alpha), changed with respect to time and exosome concentration in BM‐MSCs. The TNF‐alpha level was higher in exosome‐treated BM‐MSCs compared with the control. Exosome treatment of BM‐MSCs led to an increased production of NO and a decreased production of reactive oxygen species (ROS) in a time‐ and concentration‐dependent manner. We have shown that K562‐derived exosomes induce overexpression of IL‐10 and TNF‐alpha and downregulation of iNOS transcript levels in macrophages. The enzyme‐linked immunosorbent assay results showed that TNF‐alpha and IL‐10 secretions increased in macrophages. Treatment of macrophages with purified exosomes led to reduced NO and ROS levels. These results suggest that K562‐derived exosomes may alter the local bone marrow niche toward a leukemia‐reinforcing microenvironment. They can modulate the inflammatory molecules (TNF‐alpha and NO) and the redox potential of BM‐MSCs and macrophages and direct the polarization of macrophages toward tumor‐associated macrophages.
Induction of apoptotic but not autophagic cell death by Cinnamomum cassia extracts on human oral cancer cells
Authors: Yu Ching‐Han , Chu Shu‐Chen , Yang Shun‐Fa , Hsieh Yih‐Shou , Lee Chih‐Yi , Chen Pei‐Ni
Published: October 2018

Cinnamomum cassia has been widely studied in different fields to reveal its antidiabetic, antidepressive, antiviral, anti‐inflammatory, antiosteoporotic, and anticancer effects. Its antimalignant activities have been explored in lung cancer, breast cancer, colorectal cancer, and even oral cancer, but the detailed signaling mechanism and effects of this plant on animal models need to be clarified. In the current study,
C. cassia extract (CCE) was used to investigate the antitumorigenesis mechanism in vitro and in vivo. The major constituents of CCE used in this study were coumarin, cinnamic acid, and cinnamic aldehyde. CCE reduced the viability, number, and colony formation of human oral cancer cells, and induced their apoptosis. Caspase‐3 activation, Bcl‐2 reduction, and phosphatidylserine inversion were involved in CCE‐stimulated apoptosis. CCE also enhanced the expression of autophagic markers, including acidic vesicular organelle, microtubule‐associated protein 1 light chain 3‐I, autophagy‐related protein 14, rubicon, and p62. The combined treatment of CCE and caspase inhibitor significantly restored mitochondrial membrane potential (Δ
ψ
m) and cell viability. However, the combined treatment of CCE and autophagy inhibitor further reduced the cell viability indicating that autophagy might be a survival pathway of CCE‐treated SASVO3 cells. In contrast, CCE treatment for 12 days did not adversely affect SASVO3 tumor‐bearing nude mice. CCE also elicited dose‐dependent effects on the decrease in tumor volume, tumor weight, and Ki‐67 expression. These results suggested that CCE showed the potential for the complementary treatment of oral caner.
Interferon‐stimulated gene 15 enters posttranslational modifications of p53
Authors: Wang Yang , Ding Qi , Lu Yu‐Chen , Cao Shi‐Yang , Liu Qing‐Xue , Zhang Lei
Published: October 2018

The tumor suppressor protein p53 is a central governor of various cellular signals. It is well accepted that ubiquitination as well as ubiquitin‐like (UBL) modifications of p53 protein is critical in the control of its activity. Interferon‐stimulated gene 15 (ISG15) is a well‐known UBL protein with pleiotropic functions, serving both as a free intracellular molecule and as a modifier by conjugating to target proteins. Initially, attentions have historically focused on the antiviral effects of ISG15 pathway. Remarkably, a significant role in the processes of autophagy, DNA repair, and protein translation provided considerable insight into the new functions of ISG15 pathway. Despite the deterministic revelation of the relation between ISG15 and p53, the functional consequence of p53 ISGylation appears somewhat confused. More important, more recent studies have hinted p53 ubiquitination or other UBL modifications that might interconnect with its ISGylation. Here, we aim to summarize the current knowledge of p53 ISGylation and the differences in other significant modifications, which would be beneficial for the development of p53‐based cancer therapy.
Melatonin defends mouse oocyte quality from benzo[ghi]perylene‐induced deterioration
Authors: Li Wei‐Dong , Yu Shuai , Luo Shi‐Ming , Shen Wei , Yin Shen , Sun Qing‐Yuan
Published: October 2018

Benzo[ghi]perylene (B[ghi]P) is a polycyclic aromatic hydrocarbon widely found in haze. Long‐term exposure to humans or animals can cause serious damage to the respiratory system. Melatonin is an endogenous natural hormone synthesized and released by the pineal gland. In this study, we investigated the effects of melatonin on in vitro cultured B[ghi]P‐exposed mouse oocytes and the protective roles of melatonin. Our data indicate that B[ghi]P exposure leads to meiotic maturation arrest and reduced ability of sperm binding and parthenogenetic activation. Also, B[ghi]P exposure disrupts actin filament dynamics, spindle assembly, and kinetochore–microtubule attachment stability, which results in oocyte aneuploidy. Simultaneously, B[ghi]P exposure disturbs the distribution of mitochondria, increases the level of oxidative stress, and induces apoptosis of oocytes. Whereas all of these toxic effects of B[ghi]P can be restored after melatonin supplement. In conclusion, our findings validate that melatonin has a certain protective effect on preventing the reduced oocyte quality caused by B[ghi]P exposure during meiotic maturation in mouse oocytes.
LINC01433 promotes hepatocellular carcinoma progression via modulating the miR‐1301/STAT3 axis
Authors: Huang Haijin , Bu Yan‐Zhi , Zhang Xiao‐Yu , Liu Juan , Zhu Li‐Yao , Fang Yong
Published: October 2018

Long noncoding RNAs (lncRNAs) have been demonstrated to play significant roles in hepatocellular carcinoma (HCC) tumor progression. LINC01433 has been implicated in the progression of lung cancer. However, its biological role in HCC remains poorly understood. In our current study, we focused on the detailed mechanism of LINC01433 in HCC development. First, it was exhibited that LINC01433 was remarkably elevated in HCC cells, which indicated that LINC01433 was involved in HCC. Then, knockdown of LINC01433 was able to restrain HCC cell proliferation and cell colony formation and greatly induced cell apoptosis. On the contrary, overexpression of LINC01433 promoted HCC cell proliferation, increased cell colony formation, and enhanced cell invasion capacity. Subsequently, we found that miR‐1301 was remarkably decreased in HCC cells, and it can serve as a target of LINC01433 according to bioinformatics analysis. In addition, the binding correlation between them was validated by performing RNA pull‐down experiments and RIP assay. Moreover, STAT3 was predicted and validated as a target of miR‐1301, and it was shown that miR‐1301 mimics significantly suppressed STAT3 in HCC cells. Finally, in vivo models were established, and the results demonstrated that silencing of LINC01433 could repress HCC development through modulating miR‐1301 and STAT3. Taken together, these results indicated in our study that LINC01433 participated in HCC progression through modulating the miR‐1301/STAT3 axis and it might act as a novel biomarker in HCC diagnosis and treatment.
Snake venoms promote stress‐induced senescence in human fibroblasts
Authors: Lewinska Anna , Bocian Aleksandra , Petrilla Vladimir , Adamczyk‐Grochala Jagoda , Szymura Karolina , Hendzel Wiktoria , Kaleniuk Edyta , Hus Konrad K. , Petrillova Monika , Wnuk Maciej
Published: October 2018

Snake venoms are widely studied in terms of their systemic toxicity and proteolytic, hemotoxic, neurotoxic, and cytotoxic activities. However, little is known about snake‐venom‐mediated effects when used at low, noncytotoxic concentrations. In the current study, two human fibroblast cell lines of different origin, namely WI‐38 fetal lung fibroblasts and BJ foreskin fibroblasts were used to investigate snake‐venom‐induced adaptive response at a relatively noncytotoxic concentration (0.01 µg/ml). The venoms of Indochinese spitting cobra (
Naja siamensis), western green mamba (
Dendroaspis viridis), forest cobra (
Naja melanoleuca), and southern copperhead (
Agkistrodon contortrix) were considered. Snake venoms promoted FOXO3a‐mediated oxidative stress response and to a lesser extent DNA damage response, which lead to changes in cell cycle regulators both at messenger RNA and protein levels, limited cell proliferation and migration, and induced cellular senescence. Taken together, we have shown for the first time that selected snake venoms may also exert adverse effects when used at relatively noncytotoxic concentrations.
Chronic kidney disease after 5/6 nephrectomy disturbs the intestinal microbiota and alters intestinal motility
Authors: Nishiyama Kazuhiro , Aono Kimiya , Fujimoto Yasuyuki , Kuwamura Mitsuru , Okada Toshiya , Tokumoto Hayato , Izawa Takeshi , Okano Ryoichi , Nakajima Hidemitsu , Takeuchi Tadayoshi , Azuma Yasu‐Taka
Published: October 2018

Organ–organ crosstalk is involved in homeostasis. Gastrointestinal symptoms are common in patients with renal failure. The aim of this study was to elucidate the relationship between gastrointestinal motility and gastrointestinal symptoms in chronic kidney disease. We performed studies in C57BL/6 mice with chronic kidney disease after 5/6 nephrectomy. Gastrointestinal motility was evaluated by assessing the ex vivo responses of ileum and distal colon strips to electrical field stimulation. Feces were collected from mice, and the composition of the gut microbiota was analyzed using 16S ribosomal RNA sequencing. Mice with chronic kidney disease after 5/6 nephrectomy showed a decreased amount of stool, and this constipation was correlated with a suppressed contraction response in ileum motility and decreased relaxation response in distal colon motility. Spermine, one of the uremic toxins, inhibited the contraction response in ileum motility, but four types of uremic toxins showed no effect on the relaxation response in distal colon motility. The 5/6 nephrectomy procedure disturbed the balance of the gut microbiota in the mice. The motility dysregulation and constipation were resolved by antibiotic treatments. The expression levels of interleukin 6, tumor necrosis factor‐α, and iNOS in 5/6 nephrectomy mice were increased in the distal colon but not in the ileum. In addition, macrophage infiltration in 5/6 nephrectomy mice was increased in the distal colon but not in the ileum. We found that 5/6 nephrectomy altered gastrointestinal motility and caused constipation by changing the gut microbiota and causing colonic inflammation. These findings indicate that renal failure was remarkably associated with gastrointestinal dysregulation.
Aberrant expression of long noncoding RNA SNHG15 correlates with liver metastasis and poor survival in colorectal cancer
Authors: Huang Liang , Lin Hongcheng , Kang Liang , Huang Pinzhu , Huang Jun , Cai Jinlin , Xian Zhenyu , Zhu Peixuan , Huang Meijin , Wang Liping , Xian Cory J. , Wang Jianping , Dong Jianghui
Published: October 2018

Long noncoding RNAs (lncRNAs) play a critical role in the initiation and progression of colorectal cancer (CRC), but little is known about the function of lncRNAs in the colorectal liver metastasis (CLM). This study was designed to identify specific lncRNAs correlating to liver metastasis of CRC, and to further assess their clinical value. Seventeen patients with primary CRC lesions, adjacent normal mucosa, and synchronous liver metastases lesions were divided into discovery set (six patients) and test set (11 patients). Transcriptome sequencing (RNAseq) was used to screen differential expression of lncRNAs in the discovery set. Based on bioinformatics data, quantitative reverse‐transcription polymerase chain reaction (qRT‐PCR) was used to verify the target lncRNA in test set. The relationships between target lncRNA and clinical values were analysed in an expanded validation set of additional 91 patients. 23 upregulated and 14 downregulated lncRNAs were detected for distinguishing synchronous liver metastases, primary CRC lesions from adjacent normal mucosa in the RNAseq set. The expression levels of four lncRNAs in the 37 lncRNA signature were verified by qRT‐PCR in the test set. Compared with the paired normal mucosa, high expression levels of lnc‐small‐nucleolar RNA host gene 15 (SNHG15) were detected not only in primary CRC lesions but also in liver metastases lesions in the test set. Furthermore, in the expanded validation set, high expression of lnc‐SNHG15 was significantly associated with lymph‐node metastasis and liver metastasis (p < 0.05), and patients displaying high lncRNA‐SNHG15 expression exhibited a shorter median overall survival duration than those displaying low expression (30.7 vs. 35.2 months; p = 0.003). Multivariate analyses demonstrated that lncRNA‐SNHG15 overexpression may serve as a poor prognostic biomarker for CRC patients (p = 0.049; Cox's regression: 2.731). Lnc‐SNHG15 overexpression was significantly associated with CLM and high‐expression of lnc‐SNHG15 in CRC was an independent predictor of poor survival.
A pH‐sensitive luminal His‐cluster promotes interaction of PAM with V‐ATPase along the secretory and endocytic pathways of peptidergic cells
Authors: Rao Vishwanatha K. , Zavala Gerardo , Deb Roy Abhijit , Mains Richard E. , Eipper Betty A.
Published: October 2018

The biosynthetic and endocytic pathways of secretory cells are characterized by progressive luminal acidification, a process which is crucial for posttranslational modifications and membrane trafficking. This progressive fall in luminal pH is mainly achieved by the vacuolar‐type‐H+ ATPase (V‐ATPase). V‐ATPases are large, evolutionarily ancient rotary proton pumps that consist of a peripheral V1 complex, which hydrolyzes ATP, and an integral membrane V0 complex, which transports protons from the cytosol into the lumen. Upon sensing the desired luminal pH, V‐ATPase activity is regulated by reversible dissociation of the complex into its V1 and V0 components. Molecular details of how intraluminal pH is sensed and transmitted to the cytosol are not fully understood. Peptidylglycine α‐amidating mono‐oxygenase (PAM; EC 1.14.17.3), a secretory pathway membrane enzyme which shares similar topology with two V‐ATPase accessory proteins (Ac45 and prorenin receptor), has a pH‐sensitive luminal linker region. Immunofluorescence and sucrose gradient analysis of peptidergic cells (AtT‐20) identified distinct subcellular compartments exhibiting spatial co‐occurrence of PAM and V‐ATPase. In vitro binding assays demonstrated direct binding of the cytosolic domain of PAM to V1H. Blue native PAGE identified heterogeneous high‐molecular weight complexes of PAM and V‐ATPase. A PAM‐1 mutant (PAM‐1/H3A) with altered pH sensitivity had diminished ability to form high‐molecular weight complexes. In addition, V‐ATPase assembly status was altered in PAM‐1/H3A expressing cells. Our analysis of the secretory and endocytic pathways of peptidergic cells supports the hypothesis that PAM serves as a luminal pH‐sensor, regulating V‐ATPase action by altering its assembly status.
MGF E peptide improves anterior cruciate ligament repair by inhibiting hypoxia‐induced cell apoptosis and accelerating angiogenesis
Authors: Sha Yongqiang , Yang Li , Lv Yonggang
Published: October 2018

Severe hypoxic microenvironment endangers cell survival of anterior cruciate ligament (ACL) fibroblasts and is harmful to ACL repair and regeneration. In the current study, we explored the effects of mechanogrowth factor (MGF) E peptide on the hypoxia‐induced apoptosis of ACL fibroblasts and relevant mechanisms. It demonstrated that severe hypoxia promoted hypoxia‐inducible factor‐1α (HIF‐1α) expression and caused cell apoptosis of ACL fibroblasts through increasing caspase 3/7/9 messenger RNA (mRNA), cleaved caspase 3 and proapoptotic proteins expression levels but decreasing antiapoptotic proteins expression levels. Fortunately, MGF E peptide effectively protected ACL fibroblasts against hypoxia‐induced apoptosis through regulating caspase 3/7/9 mRNA, cleaved caspase 3 and apoptosis‐relevant proteins expression levels. Simultaneously, mitochondrial, @@@MEK‐ERK1/2 (extracellular‐signal‐regulated kinase 1/2), and phosphoinositide‐3‐kinase‐protein kinase B (PI3K‐Akt) pathways were involved in MGF E peptide regulating hypoxia‐induced apoptosis of ACL fibroblasts. In rabbit ACL rupture model, MGF E peptide also decreased HIF‐1α expression levels, cell apoptosis, and facilitated cell proliferation. In addition, MGF could accelerate angiogenesis after ACL injury probably owing to its recruitment of proangiogenesis cells by stromal cell‐derived factor 1α/CXCR4 axis and stimulation of vascular endothelial growth factor α expression level. In conclusion, our findings suggested that MGF E peptide could be utilized for ACL repair and regeneration and supplied experimental support for its application in clinical ACL treatment as a potential strategy.
Muon disrupts AKT hydrogen bond network in cancer
Authors: Radisavljevic Ziv
Published: October 2018

A cancer microenvironment generates strong hydrogen bond network system by the positive feedback loops supporting cancer complexity and robustness. Such network functions through the AKT locus generating high entropic energy supporting cancer metastatic robustness. Charged lepton particle muon follows the rule of Bragg effect during a collision with hydrogen network in cancer cells. Muon beam dismantles hydrogen bond network in cancer by the muon‐catalyzed fusion, leading to apoptosis of cancer cells. Muon induces cumulative energy appearance on the hydrogen bond network in a cancer cell with its fast decay to an electron and two neutrinos. Thus, muon beam, muonic atom, muon neutrino shower, and electrons simultaneously cause fast neutralization of the AKT hydrogen bond network by the conversion of hydrogen into deuterium or helium, inactivating the hydrogen bond networks and inducing failure of cancer complexity and robustness with the disappearance of a malignant phenotype.
LncRNA ENST00000453774.1 contributes to oxidative stress defense dependent on autophagy mediation to reduce extracellular matrix and alleviate renal fibrosis
Authors: Xiao Xiangcheng , Yuan Qiongjing , Chen Yusa , Huang Zhihua , Fang Xi , Zhang Haixia , Peng Ling , Xiao Ping
Published: October 2018

Although long noncoding RNA (LncRNA) are important players in the initiation and progression of many pathological processes, the role of LncRNAENST00000453774.1 (LncRNA 74.1) in renal fibrosis still remains unclear. Lentivirus mediated LncRNA 74.1 overexpressing HK2 cells and overexpression mice models were constructed. HK2 cells induced by transforming growth factor‐β (TGF‐β) in vitro, and the mice UUO model in vivo were used to simulate renal fibrosis. The expression of LncRNA 74.1 was significantly downregulated in the TGF‐β‐induced HK‐2 cell fibrosis and clinical renal fibrosis specimens. LncRNA 74.1 overexpression obviously attenuated renal fibrosis in vitro and unilateral ureteral obstruction‐induced renal fibrosis in vivo. LncRNA 74.1 promoted reactive oxygen species defense by activating prosurvival autophagy then decreased ECM‐related proteins fibronectin and collagen I involved in renal fibrosis. We also found that Nrf2‐keap1 signaling played important roles in the remission of ECM mediated by LncRNA 74.1. This study indicates that LncRNA 74.1 downregulation would contribute to renal fibrosis and its overexpression might represent a novel anti‐fibrotic treatment in renal diseases.
Hepatic stellate cells regulate hepatic progenitor cells differentiation via the TGF‐β1/Jagged1 signaling axis
Authors: Aimaiti Yasen , Jin Xin , Shao Yue , Wang Wei , Li Dewei
Published: October 2018

Hepatic stellate cells (HSCs) play an important microenvironmental role in hepatic progenitor cells (HPCs) differentiation fate. To reveal the specific mechanism of HSCs induced by transforming growth factor β1 (TGF‐β1) signaling in HPCs differentiation process, we used Knockin and knockdown technologies induced by lentivirus to upregulate or downregulate TGF‐β1 level in mouse HSCs (mHSCs) (mHSCs‐TGF‐β1 or mHSCs‐TGF‐βR1sih3). Primary mouse HPCs (mHPCs) were isolated and were cocultured with mHSCs‐TGF‐β1 and mHSCs‐TGF‐βR1sih3 for 7 days. Differentiation of mHPCs was detected by quantitative reverse transcriptase polymerase chain reaction analysis and immunofluorence in vitro. mHPCs‐E14.5 cell lines and differently treated mHSCs were cotransplanted into mice spleens immediately after establishment of acute liver injury model for animal studies. Engraftment and differentiation of transplanted cells as well as liver function recovery were measured at the seventh day via different methods. mHSCs‐TGF‐β1 were transformed into myofibroblasts and highly expressed Jagged1, but that expression was reduced after blockage of TGF‐β1 signaling. mHPCs highly expressed downstream markers of Jagged1/Notch signaling and cholangiocyte markers (CK19, SOX9, and Hes1) after coculture with mHSCs‐TGF‐β1 in vitro. In contrast, mature hepatocyte marker (ALB) was upregulated in mHPCs in coculture conditions with mHSCs‐TGF‐βR1sih3. At the seventh day of cell transplantation assay, mHPCs‐E
14.5 engrafted and differentiated into cholangiocytes after cotransplanting with TGF‐β1‐knockin mHSCs, but the cells had a tendency to differentiate into hepatocytes when transplanted with TGF‐βR1‐knockdown mHSCs, which corresponded to in vitro studies. HSCs play an important role in regulating HPCs differentiation into cholangiocytes via the TGF‐β1/Jagged1 signaling axis. However, HPCs have a tendency to differentiate into hepatocytes after blockage of TGF‐β1 signaling in HSCs.
CCN2 promotes drug resistance in osteosarcoma by enhancing ABCG2 expression
Authors: Tsai Hsiao‐Chi , Chang An‐Chen , Tsai Chun‐Hao , Huang Yuan‐Li , Gan Lijun , Chen Chi‐Kuan , Liu Shih‐Chia , Huang Te‐Yang , Fong Yi‐Chin , Tang Chih‐Hsin
Published: October 2018

In recent years, osteosarcoma survival rates have failed to improve significantly with conventional treatment modalities because of the development of chemotherapeutic resistance. The human breast cancer resistance protein/ATP binding cassette subfamily G member 2 (BCRP/ABCG2), a member of the ATP‐binding cassette family, uses ATP hydrolysis to expel xenobiotics and chemotherapeutics from cells. CCN family member 2 (CCN2) is a secreted protein that modulates the biological function of cancer cells, enhanced ABCG2 protein expression and activation in this study via the α6β1 integrin receptor and increased osteosarcoma cell viability. CCN2 treatment downregulated miR‐519d expression, which promoted ABCG2 expression. In a mouse xenograft model, knockdown of CCN2 expression increased the therapeutic effect of doxorubicin, which was reversed by ABCG2 overexpression. Our data show that CCN2 increases ABCG2 expression and promotes drug resistance through the α6β1 integrin receptor, whereas CCN2 downregulates miR‐519d. CCN2 inhibition may represent a new therapeutic concept in osteosarcoma.
A dual role of cholesterol in osteogenic differentiation of bone marrow stromal cells
Authors: Li Kun , Xiu Chunmei , Zhou Qiang , Ni Li , Du Jun , Gong Tingting , Li Meng , Saijilafu  , Yang Huilin , Chen Jianquan
Published: October 2018

Osteoblasts, the chief bone‐forming cells, are differentiated from mesenchymal stromal/stem cells. Disruption of this differentiation process can cause osteoporosis, a bone disease characterized by low bone mass and deteriorated bone structure. Cholesterol has been implicated in pathogenesis of osteoporosis, and was recently identified as an endogenous activator of Hedgehog (Hh) signaling. However, its pathological and physiological roles in osteoblast differentiation are still poorly understood. Moreover, it is unclear whether these potential roles played by cholesterol are related to its capability to modulate Hh pathway. In this study, we investigated the role of exogenous versus endogenous cholesterol in osteogenesis and Hh pathway activation using ST2 cells, a bone marrow stromal cell line. We found that exogenous cholesterol significantly inhibited alkaline phosphatase (ALP) activity and messenger RNA expression of osteoblast markers genes (Alpl, Sp7, and Ibsp) while modestly activating expression of Gli1 (a readout of Hh signaling) under both basal osteogenic culture condition and Wnt3a treatment. Similarly, exogenous cholesterol suppressed osteogenic response of ST2 cells to sonic Hh (Shh) or purmorphamine (Purmo) treatment, which, however, was accompanied by diminished induction of Gli1, indicating the involvement of a Hh‐dependent mechanism. Interestingly, depletion of endogenous cholesterol also reduced Shh‐induced ALP activity and Gli1 expression. Likewise, cholesterol depletion inhibited osteogenic response to Purmo, although it did not affect Gli1 induction. Taken together, our findings have demonstrated that cholesterol plays a dual role in osteoblast differentiation likely through both Hh‐dependent and ‐independent mechanisms.
Tolerance of Hydrolyzed Liquid Protein Fortified Human Milk and Effect on Growth in Premature Infants
Authors: Shakeel Fauzia , Newkirk Melanie , Altoubah Taymeyah , Martinez Denise , Amankwah Ernest K
Published: October 2018

Background

We evaluated tolerance of hydrolyzed liquid protein (LP) supplement added to fortified human milk (HM) to optimize protein intake in preterm infants.

Methods

A prospective observational study of 31 subjects compared with 31 historic controls, receiving mothers own milk (MOM) and/or donor milk (DM) to assess LP tolerance, growth, and risk for morbidities was conducted. Milk was analyzed for nutrient content. Feeding intolerance, defined as cessation of feedings for ≥48 hours, abdominal distension and/or residuals, necrotizing enterocolitis (NEC), and metabolic acidosis were used to assess safety, while weight and head circumference (HC) were used to evaluate growth.

Results

LP added to powder‐fortified HM had no impact on feeding intolerance and NEC. Biochemical parameters showed no metabolic acidosis: blood urea nitrogen levels (first week: median, 13 mg/dL; interquartile range [IQR], 9–16; last week: median, 13 mg/dL; IQR, 10.3–14; P = .94), bicarbonate levels (first week: median, 26.3 mEq/L; IQR, 24–28; last week: median, 28 mEq/L; IQR, 26.3–29.8; P = .10), and pH levels (first week: median, 7.4; IQR, 7.3–7.4; last week: median, 7.4; IQR, 7.37–7.40; P = .5). Weight and HC were not statistically significant. HM analysis showed lower protein and caloric content, respectively (MOM: 0.88 vs DM: 0.77 g/100 mL; P < .0001 and MOM: 18.68 vs DM: 17.96 kcal/oz; P = .02).

Conclusions

Hydrolyzed LP is well tolerated in preterm infants with no difference in growth rates. Clinicians should focus on the need to maximize both protein and energy to optimize growth.
Synthesis and characterization of antimicrobial polylactide via ring‐opening polymerization and click chemistry methods
Authors: Aynali Figen , Doganci Erdinc , Doruk Tugrul , Sadikoglu Hasan
Published: October 2018

Novel biodegradable polylactide (PLA) copolymers bearing pendant antimicrobial agent groups were successfully fabricated with a combination of ring‐opening copolymerization and copper(I)‐catalysed azide–alkyne cycloaddition click reaction in a two‐step reaction procedure. First, biodegradable PLA copolymers bearing azido groups were synthesized by the ring‐opening copolymerization ofl‐lactide and 2,2‐ bis(azidomethyl)trimethylene carbonate in the presence of 1‐dodecanol as protic co‐initiator and tin(II) 2‐ethylhexanoate (Sn(Oct)2) as the catalyst. Then, alkyne functionalized quaternary ammonium salts were attached onto the azido groups of the copolymers via a Huisgen 1,3‐dipolar cycloaddition reaction to give PLA imparting antimicrobial activity. The chemical structure and composition of the copolymers were clearly confirmed using1H NMR and Fourier transform infrared spectroscopies and gel permeation chromatography. Thermal phase transition temperatures (TmandTg) and the thermal stability of the polymers were investigated by DSC and TGA experiments, respectively. The antimicrobial activity tests were carried out against Gram‐negative (Escherichia coli) and Gram‐positive (Staphylococcus aureus) bacteria by the drop plate method. It was observed that antimicrobial agents are more active in the polymeric form than in the monomeric form. Also, the activity depends on the compositional ratio and the length of the alkyl group on the ammonium salts. © 2018 Society of Chemical Industry
Beyond HAZOP: Analyzing common cause and system scenarios
Authors: Roche Eloise , Dupont Watson , Summers Angela
Published: October 2018

A production operation often consists of multiple unit operations, supported by plant‐wide services such as instrument air, power, electronic communications, and cooling water. The production operation can be covered by multiple risk studies, which divide up the production operation based on nontechnical reasons, such as unit management, study length, and convenience. The use of multiple studies is particularly common with large production units or with integrated packaged equipment. The “divide and conquer” approach to the studies is good for planning and execution, but the resulting “pieces and parts” analysis can allow significant common cause scenarios to get lost in the clutter. Traditional HAZOP approaches generally focus on pairing individual causes with deviations and consequences. This traditional approach can result in inadequate consideration of more complex scenarios, such as those involving:

Multiple automated system actions

Global loss of service

Transference of risk

These complex scenarios are often interrelated and thus are not well suited for analysis by HAZOP procedures that mandate a single cause‐consequence relationship. This article will propose extensions to the typical HAZOP process to address these challenges in a more holistic manner. © 2018 American Institute of Chemical Engineers Process Saf Prog 38: e11997, 2019
Electronic Structure and Optical Absorption in Gd‐Implanted Silica Glasses
Authors: Zatsepin Anatoly , Kuznetsova Yulia , Zatsepin Dmitry , Boukhvalov Danil , Gavrilov Nikolay , Koubisy Mohamed
Published: October 2018

The electronic structure and optical properties of silica glass implanted with Gd‐ions by the pulsed implantation technique are studied. Experimental XPS data combined with the theoretical density functional theory (DFT)‐modeling establish the most probable scenarios for Gd‐embedding at the interstitial and substitutional positions in silica before and after thermal annealing. The optical absorption spectra are analyzed within two spectral regions of direct interband transitions and exponential Urbach tails. The influence of both radiation and thermal treatment on the overall structural disorder of host‐matrix is determined using fundamental optical parameters (band gap, phonon energy). The local atomic displacements caused by the implantation damage and thermal recovery of host‐structure for as‐implanted and annealed samples are quantitatively estimated.
pH‐Driven Precise Control of Hybridization Reaction Kinetics for Rapid DNA Assay
Authors: Yan Yishu , Lu Yuan , Liu Xiaoni , Zhang Yan , Chen Jinghua
Published: October 2018

The development of DNA assays based on gold nanoparticles (AuNPs) holds great promise for point‐of‐care diagnosis at molecular level; nevertheless, how to accelerate the hybridization reaction rates, and design rapid DNA assay in aqueous solution remains challenging. Herein, a pH switchable AuNP aggregation system, functionalized with compound Y1, was set up. This method provided an elegant strategy for the precise control of DNA hybridization reaction kinetics when Y1 was co‐functionalized with ssDNA on the AuNPs. Using this strategy, real‐time DNA detection was realized by simply adjusting the pH value of the solution without affecting the sensitivity. Particularly worth mentioning, this system maintained high specificity, and were capable of accurately discriminating against single‐based mismatched sequences. In total, this system significantly improved the rapidity and robustness of ssDNA modified AuNPs, providing sound basis for the low‐cost, and disposable molecular diagnosis design.
Organic Cross‐Linker Enabling a 3D Porous Skeleton–Supported Na3V2(PO4)3/Carbon Composite for High Power Sodium‐Ion Battery Cathode
Authors: Wang Enhui , Chen Mingzhe , Liu Xiaohong , Liu Yumei , Guo Haipeng , Wu Zhenguo , Xiang Wei , Zhong Benhe , Guo Xiaodong , Chou Shulei , Dou Shi‐Xue
Published: October 2018

Cathodes with high energy density and good structural stability are needed for sodium‐ion batteries (SIBs) to be applied in energy storage field. Herein, a 3D porous skeleton–supported Na3V2(PO4)3/carbon composite (NVP@C‐3DPS) is synthesized via a simple sol–gel method by introducing an appropriate amount of citric acid as organic cross‐linker. The generated interlinking gel provides extensive support that orients the NVP crystal growth along the ductile carbon framework, directly exposing the active material to electrolyte. Field‐emission scanning electron microscopy results reveal that the hierarchical pores (macro and meso) are interconnected by the gel skeleton, with their thickness ranging from 50 to 300 nm. Thus, advantages are achieved, including a highly conductive continuous network, effective electrolyte contact surface areas, and short Na‐ion transfer distance. Moreover, the cross‐linking and porous property on the nanoscale gives very superior barrier‐free Na‐ion diffusion. Consequently, the NVP@C‐3DPS electrode exhibits excellent electrochemical performance, including superior high‐rate capacity (78 mA h g−1 at 192 C, approaching 76.9% of the initial capability of 98.6 mA h g−1 at 0.5 C), remarkable cycling stability (98.4% retention after 800 cycles at 1 C, 91.4% retention after 2000 cycles at 10 C), and outstanding high‐rate endurance (76.0% capacity retentions after 3000 cycles at 100 C).
Synergy of Hydrophobic Surface Capping and Lattice Contraction for Stable and High‐Efficiency Inorganic CsPbI2Br Perovskite Solar Cells
Authors: Wang Haoran , Bian Hui , Jin Zhiwen , Liang Lei , Bai Dongliang , Wang Qian , Liu Shengzhong F.
Published: October 2018

CsPbI2Br has been recognized as a promising material for photovoltaic applications due to its excellent optoelectronic properties and compositional stability. Unfortunately, its desired perovskite phase is not stable in humid environments as it is spontaneously transformed into a yellow non‐perovskite phase. Herein, we present our strategy to use phenylethylammonium chlorine (PEACl) treatment to significantly improve the moisture‐resistance of the CsPbI2Br film without compromising its high solar cell efficiency. It is found that: 1) small‐sized hydrophobic aromatic group PEA+ forms in the edge‐on orientation on the CsPbI2Br surface and 2) smaller halide Cl− is doped into the CsPbI2Br lattice during post‐annealing, leading to a smaller lattice structure with beneficial crystallization quality. Compared with the reference sample without the PEACl treatment, the present device achieves a comparable power‐conversion efficiency of 14.05% and much improved moisture resistance.
Tunnel Oxide – Magnesium as Electron‐Selective Passivated Contact for n‐type Silicon Solar Cell
Authors: Zhang Zhi , Liao Mingdun , Tong Hui , Wang Dan , Quan Cheng , Gao Pingqi , Sheng Jiang , Guo Wei , Yang Jie , Zhang Yanhe , Gong Xinxin , Zhang Xinyu , Yan Baojie , Zhou Xiaoling , Zeng Yuheng , Ye Jichun
Published: October 2018

A tunnel silicon oxide (SiOx) and magnesium (Mg) electron‐selective structure and its application for n‐type c‐Si solar cell are carefully studied in this work. The fabrication, reflectance, passivation quality, contact resistivity, and thermal stability of the SiOx/Mg contact are investigated. The optimized thermally annealed SiOx at 700 °C leads to the best surface passivation and acceptable contact resistivity for the SiOx/Mg contact on an n‐type c‐Si wafer, i.e., the lowest single‐side surface saturated dark current (J0) of about 100 fA cm−2 and the contact resistivity of less than 30 mΩ cm−2 are achieved. In general, the SiOx/Mg structure exhibits robust performances to be used as an electron‐selective passivated contact for n‐type c‐Si solar cells.