bluuebunny/crossref_metadata_2025_split huggingface dataset:
Acute physical exercise increases leptin‐induced hypothalamic extracellular signal‐regulated kinase1/2 phosphorylation and thermogenesis of obese mice
Authors: Gaspar Rafael Calais , Muñoz Vitor Rosetto , Kuga Gabriel Keine , Nakandakari Susana Castelo Branco Ramos , Minuzzi Luciele Guerra , Botezelli José Diego , da Silva Adelino S.R. , Cintra Dennys Esper , de Moura Leandro Pereira , Ropelle Eduardo Rochete , Pauli José Rodrigo 
Published: September 2018

AbstractThe obesity is a result of energy imbalance and the increase in thermogenesis seems an interesting alternative for the treatment of this disease. The mechanism of energy expenditure through thermogenesis is tightly articulated in the hypothalamus by leptin. The hypothalamic extracellular signal‐regulated kinase‐1/2 (ERK1/2) is a key mediator of the thermoregulatory effect of leptin and mediates the sympathetic signal to the brown adipose tissue (BAT). In this context, physical exercise is one of the main interventions for the treatment of obesity. Thus, this study aimed to verify the effects of acute physical exercise on leptin‐induced hypothalamic ERK1/2 phosphorylation and thermogenesis in obese mice. Here we showed that acute physical exercise reduced the fasting glucose of obese mice and increased leptin‐induced hypothalamic p‐ERK1/2 and uncoupling protein 1 (UCP1) content in BAT (
P < 0.05). These molecular changes are accompanied by an increased oxygen uptake (VO
2) and heat production in obese exercised mice (
P < 0.05). The increased energy expenditure in the obese exercised animals occurred independently of changes in spontaneous activity. Thus, this is the first study demonstrating that acute physical exercise can increase leptin‐induced hypothalamic ERK1/2 phosphorylation and energy expenditure of obese mice.
Inhibiting role of rosiglitazone in the regulation of inflammatory response and protective effects for severe acute pancreatitis in mice
Authors: Nie Shen , Cui Xiaoya , Guo Jinping , Ma Xiaohua , Zhi Haijun , Li Shilei , Li Yong 
Published: September 2018

AbstractObjectivesOur study aimed to probe the effects of rosiglitazone treatment on a severe acute pancreatitis (SAP) model induced by caerulein and investigate the underlying mechanism.MethodsDifferentially expressed messenger RNAs (mRNAs) in the mice of a SAP group were screened out by microarray analysis. The inflammatory response pathway was obtained from the online website DAVID Bioinformatics Resources 6.8. The interactions of caerulein and its target proteins were shown by search tool for interactions of chemicals (STITCH). Functional interactions of the genes associated with pancreatitis and the target proteins of caerulein were obtained with search tool for interactions of chemicals (STRING). SAP mice were established by hourly intraperitoneal injection of caerulein. Rosiglitazone was used as treatment drug, and pancreatic inflammation was assessed. The expression of Socs3 was studied by reverse transcriptase‐polymerase chain reaction (RT‐PCR) and Western blot analysis. The expression of interleukin (IL)‐6, IL‐1b, and Egr1 were studied by RT‐PCR and Western blot analysis.ResultsThe GSE77983 data were analyzed, and the results showed that Socs3 was overexpressed in SAP tissues. The inflammation response pathway in pancreas was selected by DAVID, STITCH, and STRING. After injection of rosiglitazone in mice, the serum levels of amylase and lipase were decreased. Furthermore, the mRNA and protein levels of Socs3 and inflammatory cytokines in pancreatic tissues were downregulated.ConclusionsRosiglitazone could protect mice with SAP from injury by downregulating Socs3 and inhibiting the inflammatory response pathway.
New N‐benzhydrylpiperazine/1,3,4‐oxadiazoles conjugates inhibit the proliferation, migration, and induce apoptosis in HeLa cancer cells via oxidative stress–mediated mitochondrial pathway
Authors: khanam Rashmin , kumar Raj , Hejazi Iram Iqbal , Shahabuddin Syed , Meena Ramovatar , Rajamani Paulraj , Yadav Nitin , Bhat Asif Iqbal , Athar Fareeda 
Published: September 2018

AbstractN‐benzhydrylpiperazine and 1,3,4‐oxadiazoles are pharmacologically active scaffolds which exhibits significant inhibitory growth effects against various cancer cells, however, antiproliferation effects and the underlying mechanism for inducing apoptosis for aforementioned scaffolds addressing HeLa cancer cells remains uncertain. In this study,
N‐benzhydrylpiperazine clubbed with 1,3,4‐oxadiazoles (4a–4h) were synthesized, subsequently characterized using high resolution spectroscopic techniques and eventually evaluated for their antiproliferation potential by inducing apoptosis in HeLa cancer cells. The MTT assay screening results revealed that among all, compound
4d (
N‐benzhydryl‐4‐((5‐(4‐aminophenyl)‐1,3,4‐oxadiazol‐2‐yl)methyl)piperazine) in particular, exhibited IC
50 value of 28.13 ± 0.21 μg/mL and significantly inhibited the proliferation of HeLa cancer cells in concentration‐dependent manner. The in vitro anticancer assays for treated HeLa cells resulted in alterations in the cell morphology, reduction in colony formation, and inhibition of cell migration in concentration‐dependent treatment. Furthermore, G2/M phase arrest, variations in the nuclear morphology, degradation of chromosomal DNA confirmed the ongoing apoptosis in treated HeLa cells. Increase in the expression of cytochrome
C and caspase‐3 confirmed the involvement of intrinsic mitochondrial pathway regulating the cell death. Also, elevation in reactive oxygen species level and loss of mitochondrial membrane potential signified that compound
4d induced apoptosis in HeLa cells by generating the oxidative stress. Therefore, compound
4d may act as a potent chemotherapeutic agent against human cervical cancer.
Comparison of large‐scale deletions of the sperm mitochondrial DNA in normozoospermic and asthenoteratozoospermic men
Authors: Gholinezhad Maryam , Yousefnia‐pasha Yousefreza , Hosseinzadeh Colagar Abasalt , Mohammadoo‐Khorasani Milad , Bidmeshkipour Ali 
Published: September 2018

AbstractBackground and objectiveMitochondria play a crucial role in energy metabolism for the survival and motility of sperm during fertilization. The aim of this study was to determine the association of large‐scale mitochondrial DNA deletions with abnormal sperm motility and morphology in asthenoteratozoospermic patients.Materials and methodsIn this case‐control study, 41 semen samples were collected from 18 normozoospermic healthy men and 23 asthenoteratozoospermic patients, according to the WHO guidelines. The swim‐up technique was used for separation of spermatozoa on the basis of their motility. Long‐range polymerase chain reaction (PCR) was used for screening of mitochondrial DNA (mtDNA) large‐scale deletions, and primer shift PCR was used for confirmation of deletions.ResultsThe mean sperm motility, normal morphology, and progressive motility in asthenoteratozoospermic patients were significantly lower than in the normozoospermic group (P < 0.0001). There was a positive significant correlation between motility and normal sperm morphology (
P < 0.0001,
r = 0.741). The results of long‐range PCR revealed the existence of 4866‐bp deletion along with the two common 4977‐bp and 7436‐bp deleted mtDNA in both groups. However, the frequency of multiple mtDNA deletions in the asthenoteratozoospermic group (15/23, 65.22%) was significantly higher than that in the normozoospermic group (7/18, 38.89%). Direct sequencing of the 534‐bp PCR product revealed that it was amplified from the mtDNA with a 4866‐bp deletion flanked by a seven‐nucleotide direct repeat (5′‐ACCCCCT‐3′).ConclusionsOur findings suggested that these large‐scale deletions of mtDNA may be genetic risk factors for poor sperm quality in asthenoteratozoospermia‐induced male infertility. Thus, it is necessary to understand the mechanisms behind the generation of these deletions.
Focal adhesion kinase, RhoA, and p38 mitogen‐activated protein kinase modulates apoptosis mediated by angiotensin II AT2 receptors
Authors: Manzur María J. , Aguilera Milton O. , Kotler Mónica L. , Berón Walter , Ciuffo Gladys M. 
Published: September 2018

AbstractApoptosis plays an important role in cellular processes such as development, differentiation, and homeostasis. Although the participation of angiotensin II (Ang II) AT2 receptors (AT
2R) in cellular apoptosis is well accepted, the signaling pathway involved in this process is not well established. We evaluated the participation of signaling proteins focal adhesion kinase (FAK), RhoA, and p38 mitogen‐activated protein kinase (p38MAPK) in apoptosis induced by Ang II via AT
2R overexpressed in HeLa cells. Following a short stimulation time (120 to 240 minutes) with Ang II, HeLa‐AT
2 cells showed nuclear condensation, stress fibers disassembly and membrane blebbing. FAK, classically involved in cytoskeleton reorganization, has been postulated as an early marker of cellular apoptosis. Thus, we evaluated FAK cleavage, detected at early stimulation times (15 to 30 minutes). Apoptosis was confirmed by increased caspase‐3 cleavage and enzymatic activity of caspase‐3/7. Participation of RhoA was evaluated. HeLa‐AT
2 cells overexpressing RhoA wild‐type (WT) or their mutants, RhoA V14 (constitutively active form) or RhoA N19 (dominant‐negative form) were used to explore RhoA participation. HeLa‐AT
2 cells expressing the constitutively active variant RhoA V14 showed enhanced apoptotic features at earlier times as compared with cells expressing the WT variant. RhoA N19 expression prevented nuclear condensation/caspase activation. Inhibition of p38MAPK caused an increase in nuclear condensation and caspase‐3/7 activation, suggesting a protective role of p38MAPK. Our results clearly demonstrated that stimulation of AT
2R induce apoptosis with participation of FAK and RhoA while p38MAPK seems to play a prosurvival role.
Distal‐less homeobox 3, a negative regulator of myogenesis, is downregulated by microRNA‐133
Authors: Qadir Abdul S. , Lee Jeeyong , Lee Yun‐Sil , Woo Kyung Mi , Ryoo Hyun‐Mo , Baek Jeong‐Hwa 
Published: September 2018

AbstractDistal‐less homeobox 3 (Dlx3), a member of the Dlx family of homeobox proteins, is a transcriptional activator of runt‐related transcription factor 2 (Runx2) during osteogenic differentiation. It has been demonstrated that forced expression of Runx2 induces an osteogenic program and ectopic calcification in muscles. Therefore, it would be reasonable to predict that Dlx3 also affects myogenic differentiation. The relationship between Dlx3 and myogenesis, however, remains poorly understood. Therefore, in this study, the role and regulation of Dlx3 during myogenic differentiation were investigated. Expression level of Dlx3 was downregulated in human mesenchymal stem cells (MSCs), mouse MSCs, and C2C12 cells cultured in myogenic medium. Dlx3 level was inversely correlated with myogenic differentiation 1 and the muscle‐specific microRNA, microRNA‐133 (miR‐133). The expression level of Runx2 was closely regulated by Dlx3 even under myogenic conditions. Overexpression of Dlx3 markedly downregulated expression levels of myogenic transcription factors and myotube formation in C2C12 cells, whereas Dlx3 knockdown enhanced myogenic differentiation. The Dlx3 3′‐untranslated region (3′‐UTR) has two potential binding sites for miR‐133. Luciferase reporter assays demonstrated that Dlx3 is a direct target of miR‐133a and miR‐133b, and that the two target sites are redundantly active. Taken together, these results suggest that Dlx3 is a negative regulator of myogenic differentiation and that miR‐133a and miR‐133b enhance myogenic differentiation, partly through inhibition of Dlx3 expression via direct targeting of the Dlx3 3′‐UTR.
Effect of simvastatin in different concentrations on free radicals in A‐2058 human melanoma malignum cells—EPR studies
Authors: Zdybel Magdalena , Chodurek Ewa , Pilawa Barbara 
Published: September 2018

AbstractThe influence of concentration of simvastatin (SIM) on free radicals in A‐2058 human melanoma malignum cells was studied. The proliferation assay for melanoma A‐2058 cells with SIM in concentration range from 0.1 to 20 µM was performed. SIM in the concentrations of 0.1, 0.3, and 1 μM only slightly changed the growth of A‐2058 cells, but the growth of the cells considerably decreased for higher concentrations of SIM. Free radicals in the cells were examined by an X‐band (9.3 GHz) electron paramagnetic resonance (EPR) spectroscopy. o‐Semiquinone free radicals with g‐factors in the range of 2.0060 to 2.0065 were found in A‐2058 cells. The asymmetric broad EPR spectra with linewidths (ΔBpp) from 0.87 to 1.25 mT were measured. The fast spin‐lattice relaxation processes characterized all the tested cells. The free radical concentrations in the all A‐2058 cells cultured with SIM were lower than in the control cells. The quenching of free radicals in A‐2058 cells depended on concentration of SIM. This effect was the weakest for concentration of SIM of 3 μM. The strongest decrease of free radical concentration caused SIM in concentration of 1 μM.
Tissue protein and lipid alterations in response to metallic impaction
Authors: Seidman Shari A. , Johnson Natasha A. , Arbelo Ulises , Aribindi Katyayini , Bhattacharya Sanjoy K 
Published: September 2018

AbstractTissue response to metallic contact and injury remains poorly understood at the level of proteins and lipid changes. We used corneas as a model system (bovine, porcine [n = 300 each], and human corneas [n = 6]) to characterize proteomic and lipidomic reactions to metallic exposure (impaction with iron). We also made a limited investigation into protein extractability and profile changes due to copper, and lead exposure as well. We identified selected proteins after trypsin digestion using an LCQ Deca XP and lipids using a TSQ Quantum Access Max mass spectrometer, respectively. Our findings indicate that iron impaction to corneal tissue results in cleavage of 1‐phosphatidylinositol‐4,5‐bisphosphate phosphodiesterase beta‐2 variant (PLCB2; 134 kDa) into a 36 kDa species and presence of the epithelial layer is necessary for this cleavage. Penetration of the cornea with other metals (copper and lead) resulted in lower protein extractability from corneal tissue compared with controls but not distinct changes in PLCB2. The changes in protein profiles were unique to the type of metal used for impaction. The depth of injury negatively affected protein extractability and profile compared with controls. These changes were also dependent on several other factors in a complex manner. Iron impaction of corneal tissue for 24 hours results in cleavage of PLCB2 commensurate with significant changes in phosphatidylinositols but not phosphatidylcholines or other phospholipids.
Inhibition of miR146b‐5p suppresses CT‐guided renal cell carcinoma by targeting TRAF6
Authors: Meng Gaopei , Li Guoce , Yang Xue , Xiao Na 
Published: September 2018

AbstractRenal cell carcinoma (RCC) is one of the most common malignancies in the urinary system. Due to the lack of early symptoms, diagnosis of RCC usually occurs at late stages or after cancer metastasis leading to poor prognosis. Therefore, it is crucial to study early molecular mechanisms and biomarkers. Previous studies have suggested that microRNAs are involved in RCC initiation and development, making them a good candidate for early diagnosis and therapy. MiR146b‐5P plays important roles in the progression of multiple cancers including thyroid cancer, pancreatic cancer, cervical cancer. However, it is not clear whether and how miR146b‐5P is involved in RCC. In this study, we aimed to investigate the function of miR146b‐5P in RCC. We examined the expression levels of miR146b‐5p in renal cancer tissue and cell lines. We also explored the effects of blocking miR146b‐5p in renal tumor growth and inflammatory signaling. Finally, we determined if miR146b‐5p regulates tumorigenesis through TRAF6. We found that miR146b‐5p levels were significantly increased in renal cancer tissue and renal cancer cells. Blocking miR146b‐5p suppressed renal tumor growth and enhanced inflammatory response through increased TRAF6 expression. These effects were eliminated in TRAF6 knockout mice. Our results suggest that enhanced miR146b‐5p expression may be a biomarker for RCC and modulating miR146b‐5p and TRAF6 levels represent a potential therapeutic strategy for RCC.
MiR‐125b suppresses the carcinogenesis of osteosarcoma cells via the MAPK‐STAT3 pathway
Authors: Xiao Tao , Zhou You , Li Hui , Xiong Liang , Wang Jing , Wang Zhi‐Hua , Liu Li‐Hong 
Published: September 2018

AbstractThe microRNA (miRNA) miR‐125b is abnormally expressed in many different types of tumors, including osteosarcoma (OS). How aberrantly expressed miR‐125b participates in regulating the initiation and progression of OS is still poorly understood. In the current study, we found that in OS, miR‐125b can suppress the expression of MAP kinase kinase 7 (MKK7), which can dephosphorylate and inactivate signal transducer and activator of transcription 3 (STAT3). We also identified an elevated expression level of MKK7 in OS and an association between MKK7 expression and poor prognosis. Further, miR‐125b inhibited OS cell proliferation and invasion by targeting and downregulating MKK7 in vitro and suppressed tumor formation in vivo. Moreover, using Western blot analysis, we preliminarily proved that the activation (phosphorylation) of STAT3 was regulated by MKK7 at the epigenetic level. MKK7 was overexpressed in OS and associated with poor clinical results. The miR‐125b‐MAPK‐STAT3 axis may be one of the mechanisms of OS oncogenesis and a potential target for the treatment of OS.
Bisphenol A stimulates steroidogenic acute regulatory protein expression via an unknown mechanism in adrenal cortical cells
Authors: Medwid Samantha , Guan Haiyan , Yang Kaiping 
Published: September 2018

AbstractBisphenol A (BPA) is one of the most widespread endocrine disrupting chemicals in the environment. Exposure to BPA is known to be associated with disruption of steroidogenesis in reproductive tissues, but little is known about its effects on the adrenal gland. We previously showed that prenatal BPA exposure resulted in elevated plasma corticosterone levels concomitant with increased adrenal levels of steroidogenic acute regulatory protein (StAR), the rate‐limiting step in steroidogenesis, in adult female mouse offspring. However, the molecular mechanisms underlying the BPA‐induced StAR protein expression in the adrenal gland remain unknown. Therefore, the current study was designed to address this important question using the human cortical cell line, H295A cells, as an in vitro model system. We found that: (1) BPA increased StAR protein levels in a dose‐dependent manner; (2) both estrogen receptor alpha (ERα)‐ and ERβ‐specific agonists mimicked while the ER antagonist ICI abrogated the stimulatory effects of BPA on StAR protein levels; and (3) BPA did not alter StAR messenger RNA, 37kDa preprotein or protein half‐life. Taken together, these findings demonstrate that BPA increases StAR protein levels through an unknown mechanism independent of StAR gene transcription, translation, and protein half‐life. Furthermore, such effects are likely mediated by ERα and/or ERβ.
Increasing maternal age of blastocyst affects on efficient derivation and behavior of mouse embryonic stem cells
Authors: Assadollahi Vahideh , Fathi Fardin , Abdi Mohammad , Khadem Erfan Mohamad Bager , Soleimani Farzad , Banafshi Omid 
Published: September 2018

AbstractMouse embryonic stem cells (mESCs) have the capability to undergo unlimited cell division and differentiate into derivatives of all three embryonic germ layers. These fundamental features enable mESCs to potentially be appropriate, efficient models for biological and medical research. Therefore, it is essential to produce high‐performance mESCs. In the current study, we have produced mESCs from blastocysts that developed from fertilized oocytes of 2 (2‐C57)‐, 4 (4‐C57)‐, and 6 (6‐C57)‐month‐old C57BL/6 mice. A comparison of isolated stem cells was done from the viewpoint of the efficiency of mESC derivation, self‐renewal, and their differentiation capacity. All generated mESCs showed a similar expression of the molecular markers protein of pluripotency and AP activity. In the 3i medium, there was a significant decrease in undifferentiated marker genes expression in the 2‐C57 cells compared with the other two groups (
P < 0.05) but developmental genes significantly increased in the 4‐C57 and 6‐C57 cells compared with the 2‐C57 cells (
P < 0.05). The differentiation capacity into three germ layers through the embryoid body formation and percentage of cell lines with normal numbers of chromosomes reduced with increased maternal age. The highest DT and highest percentage of cells in the S phase belonged to 2‐C57 cells. These data demonstrated that blastocysts which developed from fertilized oocytes of 2‐, 4‐, and 6‐month‐old C57BL/6 mice can generate pluripotent stem cells, and suggested that both the efficiency of mESC isolation and the behavior of these isolated mESCs including pluripotency, self‐renewal, cell cycle, and DT changed with increasing maternal age.
Retracted: MicroRNA‐520a‐3p suppresses epithelial–mesenchymal transition, invasion, and migration of papillary thyroid carcinoma cells via the JAK1‐mediated JAK/STAT signaling pathway
Authors: Bi Chang‐Long , Zhang Ying‐Qi , Li Bo , Guo Min , Fu Yi‐Li 
Published: September 2018

AbstractPapillary thyroid cancer (PTC) is a kind of thyroid cancer and frequently presents with epithelial–mesenchymal transition (EMT). MicroRNAs (miRNAs) were previously reported to be associated with PTC. Thus, this study aims to define the role of microRNA‐520a‐3p (miR‐520a‐3p) in PTC through the JAK/STAT signaling pathway by targeting
JAK1. The PTC and normal thyroid tissues of 137 PTC patients were collected. First of all, the expression pattern of miR‐520a‐3p, JAK1, JAK2, STAT3, E‐cadherin, and vimentin in PTC was identified. The relationship between miR‐520a‐3p and
JAK1 was predicted and analyzed. And a series of miR‐520a‐3p mimic or inhibitor, or siRNA
JAK1 introduced into PTC cells were applied to examine the effect of miR‐520a‐3p on PTC cell viability, migration, invasion, cell cycle, apoptosis, and EMT. Meanwhile, the regulatory effect of miR‐520a‐3p and
JAK1 on the JAK/STAT signaling pathway was also determined. The expression of
JAK1,
JAK2,
STAT3, and vimentin increased yet miR‐520a‐3p and E‐cadherin decreased in PTC tissue.
JAK1 was negatively regulated by miR‐520a‐3p. Functionally, EMT induction was prevented by miR‐520a‐3p upregulation through downregulating
JAK1. When upregulating miR‐520a‐3p or silencing
JAK1 in PTC cells, PTC cell viability, migration, and invasion were inhibited yet cell apoptosis promoted with cells arrested at G1 phase, indicating that miR‐520a‐3p prevented PTC progression by downregulating
JAK1. Moreover, miR‐520a‐3p elevation or
JAK1 inhibition inactivated the JAK/STAT signaling pathway. Collectively, miR‐520a‐3p prevents cancer progression through inactivating the JAK/STAT signaling pathway by downregulating
JAK1 in PTC.