bluuebunny/crossref_metadata_2025 huggingface dataset:
The effects of transient receptor potential channel (TRPC) on airway smooth muscle cell isolated from asthma model mice
Authors: Zhang Xiaoyu , Zhao Zhixin , Ma Lijun , Guo Yali , Li Xiaosu , Zhao Limin , Tian Cuijie , Tang Xueyi , Cheng Dongjun , Chen Zhuochang , Zhang Luoxian
Published: March 2018

This study aimed to validate whether transient receptor potential channel1 (TRPC1) and TRPC3 participate in the regulation the proliferation of airway smooth muscle cells (ASMCs) through modulating calcium ion (Ca2+) influx in vitro. Chronic model of murine asthma was induced and ASMCs isolated from asthmatic mice were used in this whole study. TRPC1 and TRPC3 were upregulated in asthmatic mouse ASMCs and selected for further investigation. Ca2+ concentration and the cell viability of asthmatic mouse ASMCs were significantly higher than that from non‐ asthma mice, however, TRPC channels blocker SKF96365 alleviated these effects. Furthermore, TRPC1 or TRPC3 overexpression markedly increased Ca2+ concentration and significantly induced the viability of ASMCs; whereas TRPC1 or TRPC3 knockdown exerted the completely conversed effects. Moreover, knockdown of TRPC1 and TRPC3 also exerted different effects on the protein expression of growth‐related proteins p‐p38, p‐JNK, cleaved caspase‐3 and Bcl‐2, as well as on cell cycle. Finally, we found Ca2+ chelator EGTA or BAPTA‐AM significantly diminished the effects of si‐TRPC1 and si‐TRPC3 on the cell viability, cell cycle, and the protein expression of p‐p38, p‐JNK, cleaved caspase‐3, and Bcl‐2 in asthmatic mouse ASMCs. Our findings demonstrated that the effects of TRPC1 and TRPC3 on the cell viability and cell cycle of ASMCs were, at least partially, through regulating Ca2+ influx.
LncRNA FLVCR1‐AS1 acts as miR‐513c sponge to modulate cancer cell proliferation, migration, and invasion in hepatocellular carcinoma
Authors: Zhang Kunsong , Zhao Zhenxian , Yu Junfeng , Chen Wei , Xu Qiongcong , Chen Liuhua
Published: March 2018

In the present study, we aimed to search for dysregulated lnRNAs in Hepatocellular carcinoma (HCC) tissues, and analyze the relationship of its expression level with the clinicopathological feature and patient prognosis. The biological function of FLVCR1‐AS1, the identified lncRNA, in the process of HCC development, and progression was investigated in vitro and in vivo. The underlying molecular mechanism was further explored. We determined FLVCR1‐AS1 expression in HCC tissues and peri‐tumor tissues by bioinformatic analysis, qRT‐PCR, Northern blot and in situ hybridization. The relationship between FLVCR1‐AS1 expression level and prognosis was determined by analyzing clinical samples. The effects of FLVCR1‐AS1 knockdown on HCC cell proliferation, apoptosis, migration, and invasion were investigated by CCK8, FACS, and tanswell assay, respectively. Tumor xenograft model was used to determine the influence of down‐regulated FLVCR1‐AS1 on tumor growth and metastasis. lncRNA FLVCR1‐AS1 was extremely up‐regulated in HCC tissues and cell lines. FLVCR1‐AS1 expression level was positively correlated with tumor severity. FLVCR1‐AS1 knockdown remarkably inhibited HCC cell proliferation, migration, and invasion in vitro and in vivo while induced cell apoptosis. In mechanism, FLVCR1‐AS1 acted as a competitive endogenous RNAs to sponge miR‐513c which targeted the mRNA of MET for degradation. By directly sponging miR‐513c, FLVCR1‐AS1 increased MET expression in HCC, and then promoted HCC progression. It was demonstrated that FLVCR1‐AS1 played a positive role in HCC development and progression according to the study in its mechanism, function and clinical manifestation, so that it could be expected to become a new target in HCC prevention and treatment.
DMC is not better than TMZ on intracranial anti‐glioma effects
Authors: Shi Lei , Sun Guan
Published: March 2018

Previous studies showed Demethoxycurcumin (DMC) has stronger anti‐glioma and anti‐GSCs effects both in vitro and in vivo. In addition, DMC seems to be lower toxicity than TMZ on nude mice. However, this conclusion was confirmed to be wrong in this study. We have evaluated the antitumor efficacy of DMC or TMZ treatment by an orthotopic glioblastoma xenograft model. Nude mice were injected with U87MG‐luc cells in the caudate nucleus of the brain and treated with DMC (30 mg/kg q.d.) or TMZ (10 mg/kg q.d.) by intraperitoneal injection. Bioluminescence imaging (BLI) was used to monitoring tumor growth and response to therapy. Western blot was used to detect the expression of p‐Akt, cleaved‐caspase‐3 and Bax. The average value of BLI showed TMZ determined a significant tumor regression while DMC had a mild regression effect on tumor growth compared with control group. Immunohistochemistry for Ki67, proliferating cell nuclear antigen (PCNA), and TUNEL demonstrated that TMZ more effectively inhibited the expression of Ki67 and PCNA, and increased the ratio of TUNEL‐positive cells in in situ tumor tissue. Western blot analysis also indicated that TMZ but not DMC more significantly decreased p‐Akt and increased cleaved‐caspase‐3 and Bax expression.These findings suggested a fact that TMZ appear to be more effective in controlling the growth of glioblastoma than DMC in an orthotopic glioblastoma xenograft model.
Crocin improves renal function by declining Nox‐4, IL‐18, and p53 expression levels in an experimental model of diabetic nephropathy
Authors: Yaribeygi Habib , Mohammadi Mohammad T. , Rezaee Ramin , Sahebkar Amirhossein
Published: March 2018

Oxidative damage, inflammation and apoptosis play significant roles in diabetic nephropathy. Previous studies demonstrated anti‐inflammatory and anti‐oxidative effects of crocin, but there is no evidence about its effects on IL‐18, NOX‐4, and p53 expression in diabetic kidneys. The aim of this study was to evaluate possible effects of crocin on improving main mechanisms underlying diabetic nephropathy. Male Wistar rats were randomly divided into four separate groups as normal (C), normal treated (CC), diabetic (D), and diabetic treated (DC) (n = 6). Diabetes was induced by a single dose of streptozotocin (40 mg/kg/intravenous). Treated groups received crocin (40 mg/kg, intraperitoneal) for 8 weeks. At the end of the 8th week of the study, all rats were sacrificed and urine, blood and tissue were collected. Levels of urea, uric acid, creatinine and glucose were determined collected sera, and proteinuria was measured in urine samples. Moreover, the contents of malondialdehyde (MDA), nitrate, and glutathione (GLT) as well as catalase (CAT) and superoxide dismutase (SOD) enzymes activities were measured. The expression of NOX‐4, IL‐18, and p53 at both mRNA and protein levels were also assessed. Hyperglycemia significantly increased proteinuria in diabetic rats (D). Also, depressed antioxidant defense system potency, but increased NOX‐4 expression and free radicals production resulting in oxidative stress, were observed. Moreover, expressions of IL‐18 (as a marker of inflammation) and p53 (as a marker of apoptosis) were increased. These outcomes were accompanied by enhanced histological damages and renal failure but, treatment with crocin improved these deteriorations, and ameliorated renal function. It potentiated renal cells antioxidant defense system and declined inflammation. Also, crocin lowered apoptosis and improved histological damages in renal cells. Oxidative stress, inflammation and apoptosis are considered three main mechanisms underlying diabetic nephropathy. Treatment with crocin prevented these deleterious effects and improved renal function under diabetic conditions.
Cucurbitacin I induces pro‐death autophagy in A549 cells via the ERK‐mTOR‐STAT3 signaling pathway
Authors: Ni Yinyun , Wu Sisi , Wang Xiangxiu , Zhu Guonian , Chen Xuemei , Ding Yu , Jiang Wei
Published: March 2018

Natural products are a great source of cancer chemotherapeutic agents. In the present study, the anticancer effects of cucurbitacin I on A549 cells were investigated. Cucurbitacin I decreased cell viability, inhibited colony formation, and induced apoptosis in A549 cells. Cucurbitacin I caused accumulation of autophagosome and dose‐dependent expression of LC3II protein. Autophagy inhibitors 3‐methyladenine (3‐MA) inhibited autophagy induced by cucurbitacin I and relieved cucurbitacin I‐triggered cell death and apoptosis in A549 Cells. Cucurbitacin I treatment inhibits the ERK activation and the downstream phosphorylation level of mTOR and STAT3, but not the PI3K/Akt pathway. Furthermore, treatment with the mTOR activator MHY‐1485, which also suppressed cucurbitacin I‐induced LC3II expression, and also reversed cucurbitacin I‐induced cell death and apoptosis. Taken together, these results suggest that cucurbitacin I induced pro‐death autophagy through ERK/mTOR/STAT3 signaling cascade in A549 cells.
Variation in proteomics and metabolomics of chicken hepatocytes exposed to medium with or without folic acid
Authors: Liu Yanli , Wu Shengru , Sun Wenqiang , Chen Si , Yang Xin , Yang Xiaojun
Published: March 2018

Hepatocytes are suitable models for metabolism study. Combined proteomics and metabolomics approaches should provide a comprehensive understanding for the effect of folic acid on hepatic metabolism in vitro. Primary chicken liver cells were exposed to medium with or without folic acid. The combined analyses uncovered 61 differential proteins and 43 differential metabolites between groups with or without folic acid in culture medium. Further pathway annotations revealed that RNA transport, protein processing, TCA cycle, glycolysis, pyruvate metabolism, and so on were significantly enriched. Meanwhile, lipid metabolism was enhanced in no folic acid group along with higher adipose triglyceride lipase, and 2‐hydroxybutyric acid level. Concomitantly, amino acid, and carbohydrates metabolism were disturbed. Some amino acids level were changed as well as sugar‐acids and sugar‐alcohols. In addition, antioxidant function was altered resulting from perturbation of glutathione metabolism, glutamate, and cysteine metabolism. In conclusion, our results indicated that folic acid might affect antioxidant function and metabolism of lipid, amino acid, and carbohydrates in primary chicken hepatocytes via integrating proteomics, and metabolomics analyses method. These results may provide an insight into the effect of folic acid on hepatic metabolism in future research direction.
Aqueous leaves extract of Madhuca longifolia attenuate diclofenac‐induced hepatotoxicity: Impact on oxidative stress, inflammation, and cytokines
Authors: Simon Jerine Peter , Evan Prince Sabina
Published: March 2018

Diclofenac is a Non‐Steroidal Anti‐inflammatory drug which is used as an analgesic. It is known to cause heptotoxicity on over dose and long term usage. Madhuca longifolia is an evergreen tree found widely in India that is known to have several ethnomedical uses. The aim of our study is to evaluate the beneficial effect of the aqueous leaf extract of M. longifolia against diclofenac‐induced toxicity. Rats were dived into five groups of six rats each. Group‐I was normal control. Group‐II was administered with diclofenac (50 mg/kg. b.w./day, i.p) on 4th and 5th day. Group‐III rats were treated with aqueous leaf extract of M. longifolia (500 mg/kg b.w./day, oral) for 5 consecutive days and diclofenac (50 mg/kg. b.w./day, i.p) was given on 4th and 5th day. Silymarin (25 mg/kg. b.w./day, oral) was used as standard drug which was given to the rats of group‐IV along with diclofenac on 4th and 5th day. Aqueous leaf extract of M. longifolia (500 mg/kg b.w./day, oral) alone was administered in group‐V. After the study period, the rats were evaluated for liver enzyme markers, antioxidant parameters, histopathological changes, and cytokines levels. The hepatic proinflammatory mediator cytokines like TNF‐α, IL‐6, and IL‐1β were evaluated through ELISA. The protein expression of Caspase‐3, COX‐2, and NF‐κB were analysed through Western blotting techniques. Aqueous leaves extract of M. longifolia was able to normalize the changes caused by diclofenac. Current study indicatesthe protective effect of the aqueous leaves extract of M. longifolia against diclofenac‐induced toxicity.
Mitochondrial inhibitory factor protein 1 attenuates coupling factor 6‐induced aging signal
Authors: Osanai Tomohiro , Tanaka Makoto , Mikami Kasumi , Kitajima Maiko , Magota Koji , Tomita Hirofumi , Okumura Ken
Published: March 2018

Coupling factor 6 (CF6) forces a counter‐clockwise rotation of plasma membrane F1Fo complex, resulting in proton import and accelerated aging. Inhibitory factor peptide 1 (IF1) suppresses a unidirectional counter‐clockwise rotation of F1Fo complex without affecting ATP synthesis. We tested the hypothesis that IF1 may attenuate CF6‐induced aging signaling in CF6‐overexpressing transgenic (TG) cells. In IF1‐GFP overexpressing wild type (WT) cells, the diffuse peripheral staining of tubular mitochondria was observed with a dense widely distributed network around the nucleus. In TG cells, however, the only peri‐nuclear network of fragmented mitochondria was observed at 24 h, but it was developed to a widely distributed mitochondrial network of tubular mitochondria at 72 h. TG cells displayed aging hallmarks of telomere attrition, epigenetic alterations, defective proteostasis, and genomic instability with a decrease in emerin and lamin and loss of heterochromatin. IF1 induction rescued TG cells from telomere attrition, expression of genomic instability with the increase in emerin and lamin, and that of epigenetic alterations with recovery of heterochromatin. In defective proteostasis, IF1 induction restored a potent peri‐nuclear staining of autolysosomes compared with the baseline weak staining. The decrease in Atg7 was restored, whereas the increase in P62 was abolished. We conclude that genetic disruption of proton signals by IF1 induction suppressed CF6‐induced expression of aging hallmarks such as telomere attrition, epigenetic alterations, defective proteostasis, and genomic instability. Given the widespread biological actions of CF6, the physiological and pathological actions of IF1 may be complex.
MicroRNA expression profiles of neural stem cells following valproate inducement
Authors: He Hui , Li Wen , Peng Min , Qin Jianbing , Shi Jinhong , Li Haoming , Tian Meiling , Zhang Xinhua , Lv Guangming , Jin Guohua
Published: March 2018

Neural stem cells (NSCs) possess self‐renewal and multilineage differentiation ability, thus are considered to be a potential source for cell replacement therapy of many nervous system diseases, such as neurodegenerative diseases. Valproate (VPA), a member of histone deacetylase inhibitor family, is an epigenetic regulator and can promote NSCs to differentiate into neurons, nevertheless, the underlying mechanisms of the process remain unclear. MicroRNAs (miRNAs) exert a crucial part in the posttranscriptional regulation of gene expression. Epigenetic mechanisms involve in the regulation of miRNAs expression. Therefore we speculated that miRNAs may be important factors during the promotion of neuronal differentiation by VPA. Here, after selecting appropriate concentration and treatment time of VPA, we conducted microRNA arrays at 24 h on the treatment of 1 mM VPA or vehicle. After validation, we obtained 5 significantly upregulated miRNAs (miR‐29a‐5p, miR‐674‐5p, miR‐155‐5p, miR‐652‐3p, and miR‐210‐3p) in VPA group compared with control. We predicted the target genes of these miRNAs on the website. Through gene ontology (GO) and pathway analyses, we obtained preliminary comprehension of the function of these genes. The bioinformatics analyses indicated the involvement of them during neurogenesis. In addition, we observed high expression of miR‐210‐3p, miR‐29a‐5p, and miR‐674‐5p in central nervous system, which suggested that they were likely to play crucial roles in neuronal differentiation. We then defined the upregulation of Map2 by transfecting mimic of miR‐674‐5p, which indicated the promotion of miR‐674‐5p on NSCs differentiation. The present study explored the miRNAs potentially mediated the function of VPA on promoting NSCs to differentiate into neurons.
Synthesis, structural analysis, spectral investigations, and DFT calculations of 1‐(3‐amino‐4‐thia‐1,2‐diazaspiro[4.11]hexadec‐2‐en‐1‐yl)ethan‐1‐one
Authors: Barut Celepci Duygu , Yıldırım Ayhan , Şen Betül
Published: March 2018

1‐(3‐amino‐4‐thia‐1,2‐diazaspiro[4.11]hexadec‐2‐en‐1‐yl)ethan‐1‐one was synthesized and experimentally characterized by using FT‐IR, 1H NMR, 13C NMR, and UV–Vis spectroscopy. The structure of the compound was confirmed by single‐crystal X‐ray diffraction. In the crystal structure, the molecules are linked by pairs of N‐H⋯N hydrogen bonds, forming centrosymmetric dimers with the graph‐set motif. The water molecule also plays an important role in the stabilization of the crystal structure, bridging the dimers to form a two‐dimensional supramolecular network. The molecular geometry, frontier molecular orbitals, vibrational frequencies, electronic properties, and molecular electrostatic potential were calculated using density functional theory (DFT) with the B3LYP/6‐311G(d,p) basis set. Geometric parameters, vibrational assignments, and electronic properties such as calculated energies, excitation energies, and oscillator strengths were compared with the experimental data, and it was seen that the theoretical results support the experimental parameters.
Palladium nanoparticles supported on modified hollow Fe3O4@TiO2: Preparation, characterization, and catalytic activity in Suzuki cross‐coupling reactions
Authors: Elhampour Ali , Mirhosseyni Marzie Sadat , Nemati Firouzeh
Published: March 2018

Hollow Fe3O4@TiO2‐NH2/Pd as a light‐weight, magnetically heterogeneous catalyst was successfully prepared, and characterized by using different techniques including X‐ray powder diffraction (XRD), Fourier transform infrared spectroscopy (FT‐IR), field‐emission scanning electron microscopy (FE‐SEM), transmission electron microscopy (TEM), energy‐dispersive X‐ray spectroscopy (EDX), vibrating sample magnetometer (VSM) measurements, and thermogravimetric analysis (TGA). Then this heterogeneous catalyst was tested in the Suzuki cross‐coupling reaction, and the results confirmed the success of this method. The catalyst could be separated easily using an external magnet and reused at least in five runs successfully without any appreciable loss in its catalytic activity.
Clinical application of endothelial injury marker in hypertensive patients
Authors: Guo Xiao Qian , Ren Wei , Peng Rui , Liu Yan Hong , Li Yan
Published: March 2018

Purpose

Endothelial damages are one of the most important causes of persistent hypertensive complications. The aim of our study was to discuss the relationship between the molecular markers of endothelial damage, thrombomodulin, and complications in hypertension.

Methods

A total 132 cases of hypertensive patients, including 13 patients with damage of target organs, were selected as research subjects. And grouping was based on different levels of blood pressure. The blood pressure and thrombomodulin levels were detected among all cases, and their drinking, smoking, and other medical records were tracked.

Results

Higher plasma concentration of thrombomodulin was demonstrated in subjects with hypertensive complications compared with without complications [24.5 (18.1,37.55) vs 12.1 (9.1,22.3) TU/mL, P = .001, respectively]. The optimum thrombomodulin cutoff value was determined to be more than 15.5 TU/mL, with a sensitivity of 92.3% and a specificity of 63%. With the increase in blood pressure level, thrombomodulin levels in three groups gradually raised [6.15(5.475,12.75) vs 9.75(7.725,13.35) vs 16.45 (10.125,23.725) TU/mL, P = .007, respectively].

Conclusion

With the increase in blood pressure and the occurrence of complications, thrombomodulin showed an increasing trend, which was caused by an increase in the degree of endothelial injury. So, thrombomodulin may serve as a clinically meaningful marker of the progression of hypertension.
Safety and efficacy of enhanced recovery after surgery (ERAS) programs in patients undergoing hepatectomy: A prospective randomized controlled trial
Authors: Qi Shuo , Chen Guodong , Cao Peng , Hu Jiangping , He Gengsheng , Luo Jiaxing , He Jun , Peng Xiuda
Published: March 2018

Background and aim

Enhanced recovery after surgery (ERAS) programs, following a variety of perioperative treatments with evidence‐based medical evidence, has indicated its validity to accelerate rehabilitation in a wide variety of surgical procedures. This randomized controlled trial (RCT) study was implemented to verify the safety and efficacy of the perioperative effects in patients undergoing hepatectomy with ERAS or with conventional surgery (CS).

Methods

From August 2016 to November 2017, according to the inclusion criteria, 160 patients with liver diseases were suitable for participating in this experiment. Patients before liver resection were randomized into ERAS group (n = 80) and CS group (n = 80), and then the outcome measures were compared between the two groups.

Results

Enhanced recovery after surgery group had significantly less complications than CS group (P = .009). Compared with CS group, patients in ERAS group had low peak of WBCs in postoperative day (POD1), ALT in POD1 and POD3 (P < .05), high value of ALB in POD3 and POD5 (P < .05), less pain and higher patient satisfaction (P < .001), earlier exhaust, oral feeding, ambulation and extubation time (P < .05),and also had less hospital stay and cost (P < .001). There were no significant differences in readmission rate (<30 days) between two groups (P = .772).

Conclusions

Enhanced recovery after surgery programs applied to patients undergoing hepatectomy can safely and effectively relieve stress response, reduce the incidence of complications, improve patient satisfaction, accelerate patient recovery, reduce financial burden, and bring economic benefits.
Correlation between neutrophil/lymphocyte ratio and Ranson score in acute pancreatitis
Authors: Abaylı Bahri , Gençdal Genco , Değirmencioğlu Şerife
Published: March 2018

Background

Acute pancreatitis (AP) is characterized by inflammation of the pancreas, elevated pancreatic enzymes, and abdominal pain. The neutrophil to lymphocyte ratio (NLR) is used as a marker of inflammation. In this retrospective study, we aimed to investigate novel early prognostic predictors of AP, such as NLR and its correlation with the Ranson score.

Methods

A total 435 patients (Male: 152; 34.9%, Age: 63.53 ± 17.22 years) were included in the study. Data were collected by two clinicians scanning the registered hospital records.

Results

Classification of the patients according to the aetiologies revealed gallstone(s) 58.6% (n = 255), hyperlipidaemia 2.2% (n = 9), viruses 0.7% (n = 3), malignancies 0.5% (n = 2), and alcohol 0.2% (n = 1). No reason was discovered in 37.9% (n = 165) of patients. Age, duration in the intensive care unit, serum aspartate aminotransferase (AST) levels, alanine aminotransferase (ALT), alkaline phosphatase (ALP), gamma‐glutamyl transferase (GGT), total bilirubin, direct bilirubin, lactate dehydrogenase (LDH), white blood cell (WBC) count, neutrophil count, lymphocyte count, and the NLR were greater in the group with a Ranson score ≥3 than the group with a Ranson score <3.

Discussion

Quick diagnosis is essential in AP. Current scoring systems for AP diagnosis are complicated, whereas NLP is a simple, practical, and effective marker.
Personal risk factors associated with burnout among psychotherapists: A systematic review of the literature
Authors: Simionato Gabrielle K. , Simpson Susan
Published: March 2018

Objectives

Emotionally taxing job demands place psychotherapists at risk for burnout, often to the detriment of the therapist, clients, and the profession of psychotherapy (Maslach, 2007). The aim of the present systematic review was to (a) explore the levels of both burnout and job stress in psychotherapists, (b) identify tools used to measure work‐related stress and burnout, and (c) identify personal risk factors for developing burnout among psychotherapists.

Method

Databases PsycINFO, Medline, EMBASE, ASSIA, and CINHAL were searched. Forty articles met inclusion criteria.

Results

Over half of sampled psychotherapists reported moderate‐high levels of burnout, with the majority of results based on quantitative cross‐sectional self‐report surveys. Younger age, having less work experience, and being overinvolved in client problems were the most common personal risk factors for moderate‐high levels of stress and burnout among psychotherapists.

Conclusion

It appears that psychotherapists commonly experience some burnout, and personal factors influence burnout development.
Cross‐validation of PAI scales for the detection of suspected ADHD in adults
Authors: Lancaster Amber , Liljequist Laura
Published: March 2018

The purpose of this study was to cross‐validate scales and subscales of the Personality Assessment Inventory (PAI) identified in previously published research against criterion variables for the identification of Attention Deficit/Hyperactivity Disorder (ADHD) in adults. Performance‐based indicators of attention deficits from the Wechsler Adult Intelligence Scale—Fourth Edition were used as criterion variables. In a hierarchical logistic regression analysis, the addition of the PAI scales to the criterion variables did significantly improve the fit of the model, with an overall classification accuracy of 75%. Limitations of this study and implications for future research are discussed.
Citizen participation in the police domain: The role of citizens’ attitude and morality
Authors: Schreurs Wendy , Kerstholt José H. , de Vries Peter W. , Giebels Ellen
Published: March 2018

Although there is a large potential of citizen capital in fighting crime and creating safer neighborhoods, in reality, only a small fraction of citizens is actively participating. This study examines the relationship between different types of actual participation behavior in the police domain from a citizen's stance and 3 different but interconnected psychological drivers: the attitude toward citizen participation, moral values, and moral emotions. A total of 217 Dutch citizens filled out an online questionnaire, assessing these drivers and the actual participatory actions they engaged in over the past year. The results show that 4 broad categories of participation behavior can be distinguished: social control (e.g., correcting others regarding their behavior); responsive participation (e.g., calling the police); collaborative participation (e.g., meeting with a police officer); and detection (e.g., joining a neighborhood watch). As expected, moral values had an indirect influence on participation via attitude and moral emotions. The attitude toward citizen participation was positively related to all four types of reported behavior, while the influence of moral emotions only related to social control and responsive behavior. These results can be used in the design and testing of interventions to stimulate citizen participation.
“Humbling experiences”: A photovoice project with sexual and gender‐expansive youth experiencing homelessness
Authors: Forge Nicholas , Lewinson Terri , Garner Brittany M. , Braxton Charlayna , Greenwald Lindsay , Maley Olivia
Published: March 2018

While experiencing homelessness, queer youth are subject to stereotyping, discrimination, and violence that affect their ability to achieve independent living and actualize goals. Lesbian, gay, bisexual, transgender, and queer (LGBTQ)‐identified youth of color are at greater risk for homelessness when compared to heterosexual counterparts. This study explores lived experiences of queer‐identified youth of color who are currently experiencing homelessness. Using photovoice methodology, a group of 4 participants drawn from an Atlanta‐based service provider for LGBTQ youth were engaged in a series of focus groups to discuss meaningful photographic images and give voice to shared homelessness experiences. From their individual and collective narratives, three key themes were identified: becoming aware, managing inner struggles, and recognizing personal strengths. The participating youth marked the conclusion of the project by presenting to youth service practitioners a poster board display of photos that visually represented areas of concern and opportunities for ongoing advocacy to benefit this underserved and often misunderstood population. This study also reports on this poster board display and the outcomes identified by the participating young people for better supporting homeless LGBTQ young people.
Rab9‐dependent autophagy is required for the IGF‐IIR triggering mitophagy to eliminate damaged mitochondria
Authors: Huang Chih‐Yang , Kuo Wei‐Wen , Ho Tsung‐Jung , Chiang Shu‐Fen , Pai Pei‐Ying , Lin Jing‐Ying , Lin Ding‐Yu , Kuo Chia‐Hua , Huang Chih‐Yang
Published: March 2018

Mitochondria dysfunction is the major characteristic of mitophagy, which is essential in mitochondrial quality control. However, excessive mitophagy contributes to cell death in a number of diseases, including ischemic stroke and hepatotoxicity. Insulin‐like growth factor II (IGF‐II) and its receptor (IGF‐IIR) play vital roles in the development of heart failure during hypertension. We found that IGF‐II triggers IGF‐IIR receptor activation, causing mitochondria dysfunction, resulting in mitophagy, and cardiomyocyte cell death. These results indicated that IGF‐IIR activation triggers mitochondria fragmentation, leading to autophagosome formation, and loss of mitochondria content. These results are associated with Parkin‐dependent mitophagy. Additionally, autophagic proteins Atg5, and Atg7 deficiency did not suppress IGF‐IIR‐induced mitophagy. However, Rab9 knockdown reduced mitophagy and maintained mitochondrial function. These constitutive mitophagies through IGF‐IIR activation trigger mitochondria loss and mitochondrial ROS accumulation for cardiomyocyte viability decrease. Together, our results indicate that IGF‐IIR predominantly induces mitophagy through the Rab9‐dependent alternative autophagy.
Histone methylation and acetylation in macrophages as a mechanism for regulation of inflammatory responses
Authors: Daskalaki Maria G. , Tsatsanis Christos , Kampranis Sotirios C.
Published: March 2018

Macrophages respond to noxious stimuli and contribute to inflammatory responses by eliminating pathogens or damaged tissue and maintaining homeostasis. Response to activation signals and maintenance of homeostasis require tight regulation of genes involved in macrophage activation and inactivation processes, as well as genes involved in determining their polarization state. Recent evidence has revealed that such regulation occurs through histone modifications that render inflammatory or polarizing gene promoters accessible to transcriptional complexes. Thus, inflammatory and anti‐inflammatory genes are regulated by histone acetylation and methylation, determining their activation state. Herein, we review the current knowledge on the role of histone modifying enzymes (acetyltransferases, deacetylases, methyltransferases, and demethylases) in determining the responsiveness and M1 or M2 polarization of macrophages. The contribution of these enzymes in the development of inflammatory diseases is also presented.
Analysis of tumoral spheres growing in a multichamber microfluidic device
Authors: Belgorosky Denise , Fernández‐Cabada Tamara , Peñaherrera‐Pazmiño Ana Belén , Langle Yanina , Booth Ross , Bhansali Shekhar , Pérez Maximiliano S. , Eiján Ana María , Lerner Betiana
Published: March 2018

Lab on a Chip (LOC) farming systems have emerged as a powerful tool for single cell studies combined with a non‐adherent cell culture substrate and single cell capture chips for the study of single cell derived tumor spheres. Cancer is characterized by its cellular heterogeneity where only a small population of cancer stem cells (CSCs) are responsible for tumor metastases and recurrences. Thus, the in vitro strategy to the formation of a single cell‐derived sphere is an attractive alternative to identify CSCs. In this study, we test the effectiveness of microdevices for analysis of heterogeneity within CSC populations and its interaction with different components of the extracellular matrix. CSC could be identify using specific markers related to its pluripotency and self‐renewal characteristics such as the transcription factor Oct‐4 or the surface protein CD44. The results confirm the usefulness of LOC as an effective method for quantification of CSC, through the formation of spheres under conditions of low adhesion or growing on components of the extracellular matrix. The device used is also a good alternative for evaluating the individual growth of each sphere and further identification of these CSC markers by immunofluorescence. In conclusion, LOC devices have not only the already known advantages, but they are also a promising tool since they use small amounts of reagents and are under specific culture parameters. LOC devices could be considered as a novel technology to be used as a complement or replacement of traditional studies on culture plates.
Biological effects of interleukin‐6 on Gingival Fibroblasts: Cytokine regulation in periodontitis
Authors: Naruishi Koji , Nagata Toshihiko
Published: March 2018

Periodontitis is a bacterial infectious disease, and many inflammatory cytokines regulate periodontitis pathophysiology through a crosstalk between tissue cells and immune cells. Interleukin (IL)‐6 is an important cytokine involved in the regulation of host response to bacterial infection. Human Gingival Fibroblasts (HGFs) are the most abundant cells in gingival connective tissues. Various HGF responses to periodontal pathogens or inflammatory cytokines contribute to the development of periodontitis. Lipopolysaccharide derived from Porphyromonas gingivalis (Pg LPS) and IL‐1β significantly increase IL‐6 production in HGFs. However, IL‐6 cannot function in HGFs without the soluble form of the IL‐6 receptor (sIL‐6R), because HGFs do not express sufficient cell surface IL‐6R to bind appreciable levels of IL‐6. Importantly, sIL‐6R is essential for IL‐6 signaling in HGFs, and the sIL‐6R is produced by differentiated THP‐1 cells treated with IL‐6. Calprotectin, a heterodimer of S100A8 and S100A9, is released during inflammation and significantly induces IL‐6 production in HGFs via toll‐like receptor 4 (TLR4)/nuclear factor‐kappa B (NF‐κB) signals. Calprotectin also induces sIL‐6R production in differentiated THP‐1 cells. IL‐6 induces vascular endothelial growth factor (VEGF), matrix‐metalloproteinase‐1 (MMP‐1), and cathepsin L production in HGFs in the presence of sIL‐6R. Taken together, calprotectin‐induced IL‐6 production in HGFs may cause periodontitis progression through a crosstalk of fibroblasts and macrophages. There are many reports that examine how cytokines are released from HGFs to cause beneficial or harmful effects in inflamed periodontal lesions. This review explores the pathophysiology of periodontitis by focusing IL‐6‐mediated crosstalk of HGFs and macrophages.
Whole body ARHGAP21 reduction improves glucose homeostasis in high‐fat diet obese mice
Authors: Soares Gabriela M. , Zangerolamo Lucas , Azevedo Elis G. , Costa‐Júnior Jose M. , Carneiro Everardo M. , Saad Sara T. , Boschero Antonio C. , Barbosa‐Sampaio Helena C.
Published: March 2018

GTPase activating proteins (GAPs) are ubiquitously expressed, and their role in cellular adhesion and membrane traffic processes have been well described. TBC1D1, which is a Rab‐GAP, is necessary for adequate glucose uptake by muscle cells, whereas increased TCGAP, which is a Rho‐GAP, decreases GLUT4 translocation, and consequently glucose uptake in adipocytes. Here, we assessed the possible involvement of ARHGAP21, a Rho‐GAP protein, in glucose homeostasis. For this purpose, wild type mice and ARHGAP21 transgenic whole‐body gene‐deficiency mice (heterozygous mice, expressing approximately 50% of ARHGAP21) were fed either chow (Ctl and Het) or high‐fat diet (Ctl‐HFD and Het‐HFD). Het‐HFD mice showed a reduction in white fat storage, reflected in a lower body weight gain. These mice also displayed an improvement in insulin sensitivity and glucose tolerance, which likely contributed to reduced insulin secretion and pancreatic beta cell area. The reduction of body weight was also observed in Het mice and this phenomenon was associated with an increase in brown adipose tissue and reduced muscle weight, without alteration in glucose‐insulin homeostasis. In conclusion, the whole body ARHGAP21 reduction improved glucose homeostasis and protected against diet‐induced obesity specifically in Het‐HFD mice. However, the mechanism by which ARHGAP21 leads to these outcomes requires further investigation.
High salt‐induced excess reactive oxygen species production resulted in heart tube malformation during gastrulation
Authors: Gao Lin‐rui , Wang Guang , Zhang Jing , Li Shuai , Chuai Manli , Bao Yongping , Hocher Berthold , Yang Xuesong
Published: March 2018

An association has been proved between high salt consumption and cardiovascular mortality. In vertebrates, the heart is the first functional organ to be formed. However, it is not clear whether high‐salt exposure has an adverse impact on cardiogenesis. Here we report high‐salt exposure inhibited basement membrane breakdown by affecting RhoA, thus disturbing the expression of Slug/E‐cadherin/N‐cadherin/Laminin and interfering with mesoderm formation during the epithelial‐mesenchymal transition(EMT). Furthermore, the DiI+ cell migration trajectory in vivo and scratch wound assays in vitro indicated that high‐salt exposure restricted cell migration of cardiac progenitors, which was caused by the weaker cytoskeleton structure and unaltered corresponding adhesion junctions at HH7. Besides, down‐regulation of GATA4/5/6, Nkx2.5, TBX5, and Mef2c and up‐regulation of Wnt3a/β‐catenin caused aberrant cardiomyocyte differentiation at HH7 and HH10. High‐salt exposure also inhibited cell proliferation and promoted apoptosis. Most importantly, our study revealed that excessive reactive oxygen species(ROS)generated by high salt disturbed the expression of cardiac‐related genes, detrimentally affecting the above process including EMT, cell migration, differentiation, cell proliferation and apoptosis, which is the major cause of malformation of heart tubes.
Fisetin mediated apoptotic cell death in parental and Oxaliplatin/irinotecan resistant colorectal cancer cells in vitro and in vivo
Authors: Jeng Long‐Bin , Kumar Velmurugan Bharath , Chen Ming‐Cheng , Hsu Hsi‐Hsien , Ho Tsung‐Jung , Day Cecilia‐Hsuan , Lin Yueh‐Min , Padma V. Vijaya , Tu Chuan‐Chou , Huang Chih‐Yang
Published: March 2018

Irinotecan (CPT11) and Oxaliplatin have been used in combination with fluorouracil and leucovorin for treating colorectal cancer. However, the efficacy of these drugs is reduced due to various side effects and drug resistance. Fisetin, a hydroxyflavone possess anti‐proliferative, anti‐cancer, anti‐inflammatory, and antioxidant activity against various types of cancers. Apart from that, fisetin has been shown to induce cytotoxic effects when combined with other known chemotherapeutic drugs. In this study, we aimed to investigate whether Fisetin was capable of sensitizing both Irinotecan and Oxaliplatin resistance colon cancer cells and explored the possible signaling pathways involved using In vitro and In vivo models. The results showed that Fisetin treatment effectively inhibited cell viability and apoptosis of CPT11‐LoVo cells than Oxaliplatin (OR) and parental LoVo cancer cells. Western blot assays suggested that apoptosis was induced by fisetin administration, promoting Caspase‐8, and Cytochrome‐C expressions possibly by inhibiting aberrant activation of IGF1R and AKT proteins. Furthermore, fisetin inhibited tumor growth in athymic nude mouse xenograft model. Overall, our results provided a basis for Fisetin as a promising agent to treat parental as well as chemoresistance colon cancer.
Omega‐3 fatty acids modulate the lipid profile, membrane architecture, and gene expression of leiomyoma cells
Authors: Islam Md Soriful , Castellucci Clara , Fiorini Rosamaria , Greco Stefania , Gagliardi Riccardo , Zannotti Alessandro , Giannubilo Stefano R. , Ciavattini Andrea , Frega Natale G. , Pacetti Deborah , Ciarmela Pasquapina
Published: March 2018

Uterine leiomyomas (fibroids or myomas) are the most common benign tumors of premenopausal women and new medical treatments are needed. This study aimed to determine the effects of omega‐3 fatty acids on the lipid profile, membrane architecture and gene expression patterns of extracellular matrix components (collagen1A1, fibronectin, versican, or activin A), mechanical signaling (integrin β1, FAK, and AKAP13), sterol regulatory molecules (ABCG1, ABCA1, CAV1, and SREBF2), and mitochondrial enzyme (CYP11A1) in myometrial and leiomyoma cells. Myometrial tissues had a higher amount of arachidonic acid than leiomyoma tissues while leiomyoma tissues had a higher level of linoleic acid than myometrial tissues. Treatment of primary myometrial and leiomyoma cells with eicosapentaenoic acid (EPA) or docosahexaenoic acid (DHA) reduced the monounsaturated fatty acid (MUFA) content and increased the polyunsaturated fatty acid (PUFA) content in both cell types. Myometrial and leiomyoma cell membranes were in the liquid‐crystalline phase, but EPA‐ and DHA‐treated cells had decreased membrane fluidity. While we found no changes in the mRNA expression of ECM components, EPA and DHA treatment reduced levels of ABCG1, ABCA1, and AKAP13 in both cell types. EPA and DHA also reduced FAK and CYP11A1 expression in myometrial cells. The ability of omega‐3 fatty acids to remodel membrane architecture and downregulate the expression of genes involved in mechanical signaling and lipid accumulation in leiomyoma cells offers to further investigate this compound as preventive and/or therapeutic option.
SIRT1 regulates nuclear number and domain size in skeletal muscle fibers
Authors: Ross Jacob A. , Levy Yotam , Svensson Kristoffer , Philp Andrew , Schenk Simon , Ochala Julien
Published: March 2018

Skeletal muscle fibers are giant multinucleated cells wherein individual nuclei govern the protein synthesis in a finite volume of cytoplasm; this is termed the myonuclear domain (MND). The factors that control MND size remain to be defined. In the present study, we studied the contribution of the NAD+‐dependent deacetylase, sirtuin 1 (SIRT1), to the regulation of nuclear number and MND size. For this, we isolated myofibers from mice with tissue‐specific inactivation (mKO) or inducible overexpression (imOX) of SIRT1 and analyzed the 3D organisation of myonuclei. In imOX mice, the number of nuclei was increased whilst the average MND size was decreased as compared to littermate controls. Our findings were the opposite in mKO mice. Muscle stem cell (satellite cell) numbers were reduced in mKO muscles, a possible explanation for the lower density of myonuclei in these mice; however, no change was observed in imOX mice, suggesting that other factors might also be involved, such as the functional regulation of stem cells/muscle precursors. Interestingly, however, the changes in the MND volume did not impact the force‐generating capacity of muscle fibers. Taken together, our results demonstrate that SIRT1 is a key regulator of MND sizes, although the underlying molecular mechanisms and the cause‐effect relationship between MND and muscle function remain to be fully defined.
TUSC7: A novel tumor suppressor long non‐coding RNA in human cancers
Authors: Li Na , Shi Ke , Li Wei
Published: March 2018

Accumulating evidences has shown that tumor suppressor candidate 7 (TUSC7) as a putatively tumor suppressor gene in various tumors. The low‐expression of TUSC7 is related to poor prognosis, and increased the proliferation rate of tumor cells. Over‐expression of TUSC7 could suppress tumor cell proliferation, migration, invasion, and colony formation, suggesting that TUSC7 might be a diagnostic and prognostic biomarker, as well as therapeutic target. In this review, we summarized the molecular mechanism and clinical significance of TUSC7 in tumorigenesis, tumor progression, and prognosis.
The role of enhancer of zeste homolog 2: From viral epigenetics to the carcinogenesis of hepatocellular carcinoma
Authors: Sanna Luca , Marchesi Irene , Melone Mariarosa A. B. , Bagella Luigi
Published: March 2018

Nowadays, epigenetics covers a crucial role in different fields of science. The enhancer of zeste homolog 2 (EZH2), the catalytic subunit of the Polycomb Repressive Complex 2 (PRC2), is a big proponent of how epigenetic changes can affect the initiation and progression of several diseases. Through its catalytic activity, responsible for the tri‐methylation of lysine 27 of the histone H3 (H3K27me3), EZH2 is a good target for both diagnosis and therapy of different pathologies. A large number of studies have demonstrated its crucial role in cancer initiation and progression. Nevertheless, only recently its function in virus diseases has been uncovered; therefore, EZH2 can be an important promoter of viral carcinogenesis. This review explores the role of EZH2 in viral epigenetics based on recent progress that demonstrated the role of this protein in virus environment. In particular, the review focuses on EZH2 behavior in Hepatitis B Virus, analyzing its role in the rise of Hepatocellular Carcinoma.
IL‐6 increases podocyte motility via MLC‐mediated focal adhesion impairment and cytoskeleton disassembly
Authors: He Fang‐Fang , Bao Dian , Su Hua , Wang Yu‐Mei , Lei Chun‐Tao , Zhang Chun‐Yun , Ye Chen , Tang Hui , Wan Cheng , You Chao‐Qun , Zhang Jiao , Xiong Jing , Zhang Chun
Published: March 2018

The disturbance of podocyte motility is an essential pathogenic mechanisms of foot process effacement during proteinuric diseases, and myosin light chain (MLC) is a pivotal component in regulating the motility of podocytes. Inflammatory cytokine interleukin‐6 (IL‐6) has been reported to induce podocyte abnormalities by various mechanisms, however, whether aberrant cell motility contributes to the IL‐6‐induced podocyte injury remains unknown. Here, by wound healing, transwell, and cell migration assays, we confirmed that IL‐6 accelerates the motility of podocyte. Simultaneously, the phosphorylation of MLC is elevated along with perturbed focal adhesion (FAs) and cytoskeleton. Next, via genetic and pharmacologic interruption of MLC or its phosphorylation we revealed that the activation of MLC is implicated in IL‐6‐mediated podocyte hypermotility as well as the disassembly of FAs and F‐actin. By using stattic, an inhibitor for STAT3 phosphorylation, we uncovered that STAT3 activation is the upstream event for MLC phosphorylation and the following aberrant motility of podocytes. Additionally, we found that calcitriol markedly attenuates podocyte hypermotility via blocking STAT3‐MLC. In conclusion, our study demonstrated that IL‐6 interrupts FAs dynamic, cytoskeleton organization, and eventually leads to podocyte hypermotility via STAT3/MLC, whereas calcitriol exerts its protective role by inhibiting this pathway. These findings enrich the mechanisms accounting for IL‐6‐mediated podocyte injury from the standpoint of cell motility and provide a novel therapeutic target for podocyte disorders.