bluuebunny/crossref_metadata_2025_split huggingface dataset:
Association of excision repair cross‐complimentary group 1 gene polymorphisms with breast and ovarian cancer susceptibility
Authors: Yang Fan , Mu Xiyan , Bian Ce , Zhang Huan , Yi Tao , Zhao Xia , Lin Xiaojuan 
Published: May 2019

AbstractThe role of excision repair cross‐complimentary group 1 (ERCC1) gene polymorphisms in breast and ovarian cancer development has long been controversial and existing data were inconsistent. Here, we conducted a comprehensive meta‐analysis to better clarify the association. Case‐control studies published from December 2008 to November 2018 were assessed. The statistical analyses of the pooled odds ratios (ORs) and the corresponding 95% confidence intervals (CIs) were calculated. Fifteen articles with 24 case‐control studies and 3 ERCC1 polymorphisms were enrolled. A total of 20 923 participants including 9896 cases and 11 027 controls were analyzed. The results showed that C to T variation in the ERCC1 rs11615 (C/T) polymorphisms was correlated with breast cancer susceptibility (T vs C: OR = 1.19, 95% CI = 1.02‐1.38; TT + CT vs CC: OR = 1.24, 95% CI = 1.12‐1.36). ERCC1 rs3212986 (C/A) polymorphisms posed an increased risk for breast and ovarian cancer as whole (A vs C: OR = 1.12, 95% CI = 1.01‐1.25; AA + CA vs CC: OR = 1.11, 95% CI = 1.02‐1.22), and presented especially higher risk for ovarian cancer (A vs C: OR = 1.31, 95% CI = 1.05‐1.63; AA vs CA + CC: OR = 1.66, 95% CI = 1.12‐2.47; AA vs CC: OR = 1.72, 95% CI = 1.12‐2.64). Meanwhile, neither overall group analyses nor stratified analyses displayed any association of ERCC1 rs2298881 (A/C) polymorphisms in breast and ovarian cancer susceptibility. This meta‐analysis suggested that ERCC1 rs11615 (C/T) polymorphisms were associated with breast cancer susceptibility and rs3212986 (C/A) polymorphisms were especially correlated with ovarian cancer risk. More case‐control studies with well‐adjusted data and diverse populations are essential for validation of our conclusion.
Pancreatic β‐cell regeneration: From molecular mechanisms to therapy
Authors: Motlagh Roozbeh Akbari , Mohebbi Shabnam , Moslemi Maryam , Jabbari Parnia , Alizadeh Arezoo , Mardani Rajab , Gheibi hayat Seyed Mohammad 
Published: May 2019

AbstractPancreatic β cells are a type of cells that are present in the islets of Langerhans. These cells are highly specialized for the secretion of insulin in response to low increasing of blood glucose levels. Hence, pancreatic β cells could contribute to maintaining systemic glucose homeostasis. Increasing evidence has revealed that a variety of internal (ie, genetic and epigenetic factors) and external factors (ie, radical‐oxidative stress) are involved in the protection and/or regeneration of pancreatic β cells. The pathways regulating β‐cell replication have been intensely investigated. Glucose has an important role in cell cycle entry of quiescent β cells, which exerts its effect via glucose metabolism and unfolded proteins. A variety of growth factors, hormones, and signaling pathways (ie, calcium‐calcineurin nuclear factor of activated T cells) are others factors that could affect β‐cell replication under different conditions. Therefore, a greater understanding of the underlying pathways involved in the regeneration and protection of pancreatic β cells could lead to finding and developing new therapeutic approaches. Utilization of stem cells and various phytochemical agents have provided new aspects for preventing β‐cell degeneration and stimulating the endogenous regeneration of islets. Thus, these therapeutic platforms could be used as potential therapies in the treatment of insulin‐dependent diabetes mellitus. Here, we summarized the various mechanisms involved in pancreatic β‐cell regeneration. Moreover, we highlighted different therapeutic approaches which could be used for the regeneration of pancreatic β cells.
Phosphorylated mTORC1 represses autophagic‐related mRNA translation in neurons exposed to ischemia‐reperfusion injury
Authors: Hua Rongrong , Wei Haiping , Liu Chunyan , Shi Zhe , Xing Yan 
Published: May 2019

AbstractObjectivesThe sequential reactivation of mechanistic target of rapamycin (mTOR) inhibited autophagic flux in neurons exposed to oxygen‐glucose deprivation/reperfusion (OGD/R), which was characterized by reduction of autophagosome formation and restriction of autolysosome degradation. However, its detailed molecular mechanism was still unknown. In this study, we further explore the existing form of mTOR and its suppression on the transcriptional levels of related mRNA from neurons exposed to ischemia‐reperfusion injury.MethodsThe OGD/R or middle cerebral artery occlusion/reperfusion (MCAO/R)‐treated neurons was used to simulate ischemia/reperfusion injury
. Autophagy flux was monitored by means of microtubule‐associated protein 1 light chain 3 (LC3) and p62. The reactivation of mTOR was determined by phosphorylation of ribosomal protein S6 kinase 1 (S6K1). Then the inhibitors of mTOR were used to confirm its existence form. Finally, the mRNA transcription levels were analyzed to observe the negative regulation of mTOR.ResultsThe sequential phosphorylation of mTOR contributed to the neuronal autophagy flux blocking. mTOR was re‐phosphorylated and existed as mTOR complex 1 (mTORC1), which was supported by phosphorylation of S6K1 at Thr 389 in neurons. In addition, the phosphorylation of S6K1 was decreased roughly by applying mTORC1 inhibitors, rapamycin and torin 1. However, the administration of mTORC1/2 inhibitor PP242 could recover the phosphorylation of S6K1, which suggested that mTORC2 was involved in the regulation of mTORC1 activity. In paralleling with reactivation of mTORC1, related mRNA transcription was repressed in neurons under ischemia‐reperfusion exposure in vivo and in vitro. The mRNA expression levels of LC3, Stx17, Vamp8, Snap29, Lamp2a, and Lamp2b were decreased in neurons after reperfusion, comparing with ischemia‐treated neurons.ConclusionsThe reactivated mTORC1 could suppress the transcription levels of related mRNA, such as LC3, Stx17, Vamp8, Snap29, Lamp2a, and Lamp2b. The research will expand the horizons that mTOR would negatively regulate autophagy at transcription and post‐translation levels in neurons suffering ischemia‐reperfusion injury.
Osthole inhibits osteoclasts formation and bone resorption by regulating NF‐κB signaling and NFATc1 activations stimulated by RANKL
Authors: Ma Yong , Wang Lining , Zheng Suyang , Xu Jiake , Pan Yalan , Tu Pengcheng , Sun Jie , Guo Yang 
Published: May 2019

AbstractChinese herbal medicine Fructus Cnidii has an outstanding effect on chronic lumbar pain and impotence, also has been used against osteoporosis with high frequency. Yet, the mechanisms of osthole, a derivative of Fructus Cnidii, on osteoclasts remains barely known. In this study, it was found out that osthole (10−6mol/L, 10−5mol/L) had the influence of inhibiting osteoclast formation and bone resorptive activities induced by receptor activator of nuclear factor κB ligand (RANKL), rather than affecting the viability of osteoclast‐like cells. Furthermore, osthole could also inhibit the messenger RNA expressions of c‐Src, tartrate‐resistant acid phosphatase, β3‐Integrin, matrix metallopeptidase 9, and cathepsin K. The results of the mechanistic study indicated that osthole regulated the nuclear factor of activated T‐cells cytoplasmic 1 (NFATc1) and nuclear factor‐κB (NF‐κB) activations following the RANKL stimulation.These findings suggested that the inhibitory effects of osthole were associated with restraining the activations of NFATc1 and NF‐κB induced by RANKL. Thus osthole can be used as a potential treatment for abnormal bone‐resorption related diseases.
Biochemical evidence on the potential role of methyl mercury in hepatic glucose metabolism through inflammatory signaling and free radical pathways
Authors: Maqbool Faheem , Bahadar Haji , Hassani Shokoufeh , Niaz Kamal , Baeeri Maryam , Rahimifard Mahban , Ghasemi‐Niri Seyedeh Farnaz , Abdollahi Mohammad 
Published: May 2019

AbstractMethylmercury (MeHg) is an extremely important environmental toxicant posing serious health risks to human health and a big source of environmental pollutant. Numerous evidence available showing a link between nervous system toxicity and MeHg exposure. Other forms of mercury are reason of metabolic toxic effects and alteration of DNA in the human body. The sources of exposure could be occupational or other environmental settings. In the present study MeHg was orally gavaged to mice, at doses of 2.5, 5, and 10 mg/kg for 4 weeks. Fasting hyperglycemia, activity of hepatic phoshphoenolpyruvate carboxykinase and glucose 6‐phoshphate were reported high as compared to control group. Inflammatory markers like, tumor necrosis factor α, the actual end product of inflammatory mediators’ cascade pathway was also raised in comparison to control group. Hyperinsulinemia observed in serum showed clear understanding of mercury induced insulin resistance. Moreover, tissue damage due to increased oxidative stress markers like, hepatic lipid peroxidation, 8‐deoxygunosine, reactive oxygen species, and carbonyl groups was significantly higher as compared to control group. MeHg caused a significant reduction in antioxidant markers like ferric reducing antioxidant power and total thiol molecules. The present study highlighted that activity of key enzymes involved in glucose metabolism is changed, owing to MeHg induced toxicity in the liver. Induction of similar toxic effects assumed to be stimulated by the production of high quantity free radicals.
The effects of delta‐9‐tetrahydrocannabinol on Krüppel‐like factor‐4 expression, redox homeostasis, and inflammation in the kidney of diabetic rat
Authors: Yanar Karolin , Coskun Zeynep Mine , Beydogan Alisa Bahar , Aydin Seval , Bolkent Sema 
Published: May 2019

AbstractDiabetes mellitus is a complex, multifactorial disorder that is attributed to pancreatic β cell dysfunction. Pancreatic β cell dysfunction results in declining utilization of glucose by peripheral tissues as kidney and it leads to nephropathy. Excessive production and accumulation of free radicals and incapable antioxidant defense system lead to impaired redox status. Macromolecular damage may occur due to impaired redox status and also immune imbalance. Δ9‐Tetrahydrocannabinol (THC) is the main active ingredient in cannabis. THC acts as an immunomodulator and an antioxidant agent. Our aim was to evaluate the effects of THC in the diabetic kidney. We analyzed macromolecular damage biomarkers as protein carbonyl (PCO), lipid hydroperoxide (LHP), malondialdehyde (MDA), 8‐hydroxy‐2′‐deoxyguanosine (8‐OHdG), and antioxidant defense system biomarkers as thiol fractions (T‐SH, NP‐SH, P‐SH) and Cu/Zn‐superoxide dismutase activity for the antioxidative effects of THC. Furthermore, mRNA expression of Krüppel‐like factor‐4, secreted immunopositive cell number changes of interleukin‐6, nuclear factor κβ (NF‐κβ), and peroxisome proliferator‐activated receptor‐γ and tumor necrosis factor α (TNF‐α) levels were analyzed for the immunomodulatory activity of THC. Diabetic rats showed significantly increased levels of PCO, LHP, MDA, and 8‐OHdG when compared with controls (P < 0.05 for each parameter). THC significantly reduced the elevated levels of PCO and 8‐OHdG (P < 0.05 for both parameters) and also LHP and MDA levels were insignificantly reduced by THC. Also, thiol fractions insignificantly increased in THC administered diabetic kidney when compared with diabetic rats. The NF‐κβ cell number significantly decreased in the diabetic rats treated with THC compared with the diabetic group. According to our data, THC has ameliorative effects on the impaired redox status of diabetic kidney and also it acts as an immunomodulator. Therefore, THC might be used as a therapeutic agent for diabetic kidneys but its usage in the healthy kidney may show adverse effects.
The molecular mechanism study of insulin in promoting wound healing under high‐glucose conditions
Authors: Wang Lin , Yang Bai , Jiang Hua , Yu Guo , Feng Mi , Lu Xingmei , Luo Qiang , Wu Hao , Zhang Shuo , Liu Hongchen 
Published: May 2019

AbstractBackgroundWound healing is a complex process in bone development. The aim of this study was to explore the molecular mechanism study of insulin in promoting wound healing.MethodsFirstly, the acute human monocyte leukemia cell lines were induced to differentiate into macrophages. Secondly, the porphyromonas gingivalis was applied to mix with the differentiated macrophages. Thirdly, the effect of different concentrations of insulin (0 ng/mL, 5 ng/mL, 50 ng/mL, 100 ng/mL, 200 ng/mL, 500 ng/mL, and 1,000 ng/mL) on the phagocytosis of macrophages and production of reactive oxygen species was investigated. Depending on these experiments, the optimal insulin concentration was used to treat the macrophages at different time points (0 hours and 0.5 hours) to identify the differentially expressed mRNAs. Finally, functional analysis including gene ontology (GO) and the Kyoto Encyclopedia of Genes and Genomes (KEGG) and protein‐protein interaction (PPI) analysis was carried out to explore the biological function of these differentially expressed mRNAs.ResultsThe test of phagocytosis function and production of reactive oxygen species showed that 200 ng/mL insulin treatment had a significant influence on antibacterial and production of reactive oxygen species. In RNA sequencing, a total of 415 (245 upregulated and 170 downregulated) differentially expressed mRNAs were identified between different time points. Two important signaling pathways including endocytosis and systemic lupus erythematosus were found in the KEGG enrichment analysis. In the PPI network, several hub proteins encoded by differentially expressed mRNA including ALB, HIP1R, RAB5A, HIST1H2BJ, HIST1H3G, and HIST1H2BO were identified.ConclusionOur work demonstrated that several differentially expressed mRNAs, such as EGR1, RAB34, ALB, HIP1R, RAB5A, HIST1H2BJ, HIST1H3G, and HIST1H2BO and two important signaling pathways including endocytosis and systemic lupus erythematosus may play important roles in the bone wound healing.
Prenatal liver stromal cells: Favorable feeder cells for long‐term culture of hepatic progenitor cells
Authors: Feizi Zahra , Zahmatkesh Ensieh , Farzaneh Zahra , Piryaei Abbas , Gramignoli Roberto , Nussler Andreas K. , Baharvand Hossein , Vosough Massoud 
Published: May 2019

AbstractClinical and pharmaceutical applications of primary hepatocytes (PHs) are limited due to inadequate number of donated livers and potential challenges in successful maintenance of PHs in culture. Freshly isolated hepatocytes lose their specific features and rapidly de‐differentiate in culture. Bipotent hepatoblasts, as liver precursor cells that can differentiate into both hepatocytes and cholangiocytes (Alb‐ and Ck19‐positive cells, respectively), could be used as an alternative and reliable cell source to produce enough PHs for drug discovery or possible clinical applications. In this study, growth factor‐free coculture systems of prenatal or postnatal murine liver stromal cells (pre‐LSCs or post‐LSCs, respectively) were used as feeder cells to support freshly isolated mice hepatoblasts. DLK1‐positive hepatoblasts were isolated from mouse fetuses (E14.5) and cocultured with feeder cells under adherent conditions. The hepatoblasts' bipotent features, proliferation rate, and colony formation capacity were assessed on day 5 and 7 post‐seeding. Immunoﬂuorescence staining showed that the hepatoblasts remained double positive for Alb and Ck19 on both Pre‐ and Post‐LSCs, after 5 and 7 days of coculture. Moreover, application of pre‐LSCs as feeder cells significantly increased the number of DLK1‐positive cells and their proliferation rate (ie, increased the number of Ki‐67 positive cells) on day 7, compared to Post‐LSCs group. Finally, to address our ultimate goal, which was an extension of hepatoblasts ex vivo maintenance, 3D spheres of isolated hepatoblasts were, cultured in conditioned medium (CM) derived from pre‐LSCs until day 30. It was observed that the CM derived from Pre‐LSCs could successfully prolong the maintenance of hepatic progenitor cells (HPCs) in 3D suspension culture.
Novel key genes in triple‐negative breast cancer identified by weighted gene co‐expression network analysis
Authors: Chen Jian , Qian Xiaojun , He Yifu , Han Xinghua , Pan Yueyin 
Published: May 2019

AbstractTriple‐negative breast cancer (TNBC) is a special subtype of breast cancer (BC) with poor prognosis. Although some molecular mechanisms of TNBC have been elucidated, the efficacy of current treatments is limited. Therefore, it is urgently demanded to screen for novel biomarkers and drug targets for TNBC. In this study, we obtained four independent data sets (GSE76250, GSE31448, GSE43358, and METABRIC) from the Gene Expression Omnibus (GEO) database and the cBioPortal website. In the GSE76250 data set, 890 differentially expressed genes were identified and weighted gene co‐expression network analysis was performed based on them. Then, two preserved modules associated with the KI67 score were detected. Gene ontology and pathway enrichment analyses showed genes in the modules participated in some cancer‐related biological processes or pathways. Non‐SMC condensin I complex subunit G (NCAPG) and ATP‐binding cassette subfamily A member 9 (ABCA9) were identified as hub genes of the modules, and the significance of hub genes was validated in the GSE43358 data set. Finally, their prognostic value was assessed by survival analysis. These findings suggested that NCAPG and ABCA9 may be the key genes of TNBC. Moreover, ABCA9 was first reported in TNBC. They deserved further studies.
Long intergenic noncoding RNA p21 suppresses the apoptosis of hippocampus neurons in streptozotocin‐diabetic mice by sponging microRNA‐221 through upregulation of FOS
Authors: Sun Qin , Zeng Qing‐Cui , Chen Yan‐Qiu , Zhang Min , Wei Ling‐Ling , Chen Ping 
Published: May 2019

AbstractDiabetes is associated with neurological complications, and accumulated evidence shows that biological pathways in diabetes are targeted by noncoding RNA transcripts. In this study, the role of long intergenic noncoding RNA (lincRNA) p21/microRNA‐221 (miR‐221)/fructooligosaccharide (FOS) axis was investigated in the mice with diabetes treatment. The streptozotocin‐induced diabetic mouse model was established. The learning ability and the pathological changes in mice were analyzed. After that, the interaction among miR‐221, lincRNA p21, and FOS was explored and verified. The subcellular location of lincRNA p21 was identified. Finally, the cell cycle and apoptosis of the hippocampus neurons were measured. In the diabetic mice, the levels of blood glucose were higher and the leaning abilities were inhibited. miR‐221 was highly expressed in the diabetic mice whereas lincRNA p21 and FOS were poorly expressed. miR‐221 could bind with both lincRNA p21 and FOS. miR‐221 silencing or lincRNA p21 overexpression in the diabetes mice reduced the cell apoptosis rate, and the expression of Bax and cleaved Caspase‐3, whereas increase the Bcl‐2 expression. Overexpression of lincRNA p21 promotes FOS expression by binding to miR‐221, thereby, inhibiting hippocampal neuron apoptosis in diabetic mice. This may offer potential targets for diabetes.
Naloxone reversed cognitive impairments induced by repeated morphine under heavy perceptual load in the 5‐choice serial reaction time task
Authors: Guo Hao , Xie Qiaoli , Cui Jingjing , Xu Dan , Deji Cuola , Chen Yuanyuan , Wang Yunpeng , Lai Jianghua 
Published: May 2019

AbstractRepeated opioids abuse may produce long‐lasting and complicated cognitive deficits in individuals. Naloxone is a typical mu‐opioid receptor antagonist widely used in clinical treatment for opioid overdose and opioid abuse. However, it remains unclear whether naloxone affects morphine‐induced cognitive deficits. Using the 5‐choice serial reaction time task (5‐CSRTT), the present study investigated cognitive profiles including attention, impulsivity, compulsivity, and processing speed in repeated morphine‐treated mice. Repeated morphine administration (10 mg/kg, i.p.) induced complex cognitive changes including decreased attention and increased impulsivity, compulsivity, processing speed. Systemic naloxone administration (5 mg/kg, i.p.) reversed these cognitive changes under the heavy perceptual load in 5‐CSRTT. Using the novel object recognition (NOR), Y‐maze and open‐field test (OFT), the present study investigated the memory ability and locomotor activity. Naloxone reversed the effect of morphine on recognition memory and locomotion but had no effect on working memory. In addition, repeated morphine administration decreased the expression of postsynaptic density protein 95 (PSD95) and cAMP response element binding protein (CREB) phosphorylation in the prefrontal cortex (PFC) and hippocampus (HIP), and these effects were significantly reversed by naloxone in PFC. Our study suggests that repeated exposure to morphine affects multiple cognitive aspects and impairs synaptic functions. Systemic naloxone treatment reverses the mu‐opioids‐induced cognitive changes, especially under the heavy perceptual load, possibly by restoring the synaptic dysfunctions.
Evaluation of Heat Generation in Unidirectional Versus Oscillatory Modes During K‐Wire Insertion in Bone
Authors: Luo Yuanqiang , Chen Lei , Finney Fred T. , Park Dae Woo , Talusan Paul G. , Holmes James R. , Shih Albert J. 
Published: May 2019

ABSTRACTHeat generation during insertion of Kirschner wires (K‐wires) may lead to thermal osteonecrosis and can affect the construct fixation. Unidirectional and oscillatory drilling modes are options for K‐wire insertion, but understanding of the difference in heat generation between the two modes is lacking. The goal of this study was to compare the temperature rise during K‐wire insertion under these two modes and provide technical guidelines for K‐wire placement to minimize thermal injury. Ten orthopedic surgeons were instructed to drill holes on hydrated ex vivo bovine bones under two modes. The drilling trials were evaluated in terms of temperature, thrust force, torque, drilling time, and tool wear. The analysis of variance showed that the oscillatory mode generated significantly lowered peak bone temperature rise (13% lower mean value, p = 0.036) over significantly longer drilling time (46% higher mean time, p < 0.001) than the unidirectional mode. Drilling time had significant effect on peak bone temperature rise under both modes (p < 0.001) and impact of peak thrust force was significant under oscillatory mode (p < 0.001). These findings suggest that the drilling mode choice is a compromise between peak temperature and bone exposure time. Shortening the drilling time was the key under both modes to minimize temperature rise and thermal necrosis risk. To achieve faster drilling, technique analysis found that “shaky” and intermittent drilling with moderate thrust force are preferred techniques by small vibration of the drill about the K‐wire axis and slight lift‐up of the K‐wire once or twice during drilling. © 2019 Orthopaedic Research Society. Published by Wiley Periodicals, Inc. J Orthop Res 37:1903–1909, 2019