bluuebunny/crossref_metadata_2025_split huggingface dataset:
Return of the lysergamides. Part V: Analytical and behavioural characterization of 1‐butanoyl‐d‐lysergic acid diethylamide (1B‐LSD)
Authors: Brandt Simon D. , Kavanagh Pierce V. , Westphal Folker , Stratford Alexander , Elliott Simon P. , Dowling Geraldine , Wallach Jason , Halberstadt Adam L. 
Published: May 2019

AbstractThe psychedelic properties of lysergic acid diethylamide (LSD) have captured the imagination of researchers for many years and its rediscovery as an important research tool is evidenced by its clinical use within neuroscientific and therapeutic settings. At the same time, a number of novel LSD analogs have recently emerged as recreational drugs, which makes it necessary to study their analytical and pharmacological properties. One recent addition to this series of LSD analogs is 1‐butanoyl‐LSD (1B‐LSD), a constitutional isomer of 1‐propanoyl‐6‐ethyl‐6‐nor‐lysergic acid diethylamide (1P‐ETH‐LAD), another LSD analog that was described previously. This study presents a comprehensive analytical characterization of 1B‐LSD employing nuclear magnetic resonance spectroscopy (NMR), low‐ and high‐resolution mass spectrometry platforms, gas‐ and liquid chromatography (GC and LC), and GC‐condensed phase and attenuated total reflection infrared spectroscopy analyses. Analytical differentiation of 1B‐LSD from 1P‐ETH‐LAD was straightforward. LSD and other serotonergic hallucinogens induce the head‐twitch response (HTR) in rats and mice, which is believed to be mediated largely by 5‐HT2A receptor activation. HTR studies were conducted in C57BL/6J mice to assess whether 1B‐LSD has LSD‐like behavioral effects. 1B‐LSD produced a dose‐dependent increase in HTR counts, acting with ~14% (ED50 = 976.7 nmol/kg) of the potency of LSD (ED50 = 132.8 nmol/kg). This finding suggests that the behavioral effects of 1B‐LSD are reminiscent of LSD and other serotonergic hallucinogens. The possibility exists that 1B‐LSD serves as a pro‐drug for LSD. Further investigations are warranted to confirm whether 1B‐LSD produces LSD‐like psychoactive effects in humans.
Vase‐Kite Equilibrium of Resorcin[4]arene Cavitands Investigated Using Molecular Dynamics Simulations with Ball‐and‐Stick Local Elevation Umbrella Sampling
Authors: Hahn David F. , Milić Jovana V. , Hünenberger Philippe H. 
Published: May 2019

AbstractA key feature of resorcin[4]arene cavitands is their ability to switch between a closed/contracted (Vase) and an open/expanded (Kite) conformation. The mechanism and dynamics of this interconversion remains, however, elusive. In the present study, the Vase‐Kite transitions of a quinoxaline‐based and of a dinitrobenzene‐based resorcin[4]arene are investigated using molecular dynamics (MD) simulations in three environments (vacuum, chloroform, and toluene) and at three temperatures (198.15, 248.15, and 298.15 K). The challenge of sampling the Vase‐Kite transition, which occurs experimentally on the millisecond time scale, is overcome by calculating relative free energies using ball‐and stick local elevation umbrella sampling (B&S‐LEUS) to enhance the statistics on the relevant states and to promote interconversion transitions. Associated unbiased MD simulations also evidence for the first time a complete Vase‐to‐Kite transition, as well as transitions between degenerate Kite1 and Kite2 forms and solvent‐exchange events. The calculated Vase‐to‐Kite free‐energy changes ΔG are in qualitative agreement with the experimental magnitudes and trends. The level of quantitative agreement is, however, limited by the force‐field accuracy and, in particular, by the approximate treatment of intramolecular interactions at the classical level. The results are in line with a less stable Vase state for the dinitrobenzene compared to the quinoxaline compound, and a negative entropy change ΔS for the Vase‐to‐Kite transition of the latter compound. Relative free energies calculated for intermediates also suggest that the Vase‐Kite transition does not follow a concerted mechanism, but an asynchronous one with sequential opening of the flaps. In particular, the conformation involving two adjacent flaps open in a parallel direction (cis‐p) represents a likely intermediate, which has not been observed experimentally to date.
Label‐free bioanalysis of Leishmania infantum using refractive index tomography with partially coherent illumination
Authors: Soto Juan M. , Mas Alicia , Rodrigo José A. , Alieva Tatiana , Domínguez‐Bernal Gustavo 
Published: May 2019

AbstractIn this work, we report the use of refractive index (RI) tomography for quantitative analysis of unstained DH82 cell line infected with Leishmania infantum. The cell RI is reconstructed by using a modality of optical diffraction tomography technique that employs partially coherent illumination, thus enabling inherent compatibility with conventional wide‐field microscopes. The experimental results demonstrate that the cell dry mass concentration (DMC) obtained from the RI allows for reliable detection and quantitative characterization of the infection and its temporal evolution. The RI provides important insight for studying morphological changes, particularly membrane blebbing linked to an apoptosis (cell death) process induced by the disease. Moreover, the results evidence that infected DH82 cells exhibit a higher DMC than healthy samples. These findings open up promising perspectives for clinical diagnosis of Leishmania.
Retracted: Baicalein retards proliferation and collagen deposition by activating p38MAPK‐JNK via microRNA‐29
Authors: Yang Xiaoliang , Zhang Chunyan , Jiang Jinjie , Li Yinghao 
Published: May 2019

AbstractImmoderate proliferation and deposition of collagen generally result in hypertrophic scars and even keloids. microRNA‐29 (miR‐29) has been proved as a crucial regulator in these pathological processes. Although mounting evidence have proved baicalein (BAI) impairs scar formation, it is still incompletely understood whether miR‐29 participated in the underlying mechanism. In the present study, NIH‐3T3 cells were stimulated with BAI, and then cell viability was analyzed by cell counting kit‐8 (CCK‐8) and Western blot. We further analyzed total soluble collagen, collagen 1, and alpha‐smooth muscle actin (α‐SMA) in NIH‐3T3 cells, which were exposed to transforming growth factor beta 1 (TGF‐β1)/BAI, using a Sircol assay kit, quantitative reverse transcription‐PCR (qRT‐PCR) and Western blot, respectively. Besides, the miR‐29 inhibitor was transduced and its transfection efficiency was verified by qRT‐PCR. Finally, the phosphorylated p38 mitogen‐activated protein kinase (p38MAPK) and c‐Jun N‐terminal kinase (JNK) were examined by Western blot. BAI effectively retarded NIH‐3T3 proliferation in a dose‐dependent manner. Besides, TGF‐β1‐induced deposition of total soluble collagen and synthesis of collagen 1 and α‐SMA were repressed by BAI at mRNA and protein levels. However, miR‐29 inhibitor reversed the effects of BAI. Remarkably, BAI promoted phosphorylated expression of p38MAPK and JNK while miR‐29 inhibitor reversed its effects on the phosphorylated expression of p38MAPK and JNK. BAI effectively weakened the cell viability and repressed TGF‐β1‐induced total soluble collagen as well as collagen 1 and α‐SMA by upregulating miR‐29. Mechanically, BAI activates the p38MAPK/JNK pathway by promoting miR‐29.
Trifluoperazine as an alternative strategy for the inhibition of tumor growth of colorectal cancer
Authors: Qian Kun , Sun Laiyu , Zhou Guoqing , Ge Haixia , Meng Yue , Li Jingfen , Li Xiao , Fang Xinqiang 
Published: May 2019

AbstractThe development of cancer in patients with schizophrenia is affected by genetic and environmental factors and antipsychotic medication. Several studies found that schizophrenia was associated with decreased risk of some cancers, and the neuroleptic medication might help to reduce the risk of colorectal cancer (CRC). Phenothiazine drugs including trifluoperazine (TFP) are widely used antipsychotic drugs and showed some antitumor effects, we here investigated the potential application of TFP in the treatment of colon cancer. A series doses of TFP were treated to the colon cancer cell line HCT116 and the inhibitory concentration (IC50) of TFP for HCT116 was determined by cell counting kit‐8. The results indicated that the treatment of TFP impaired the cell vitality of HCT116 in a dose‐ and time‐dependent manner. Meanwhile, the Edu assay demonstrated that the proliferation was also inhibited by TFP, which was accompanied with the induction of apoptosis and autophagy. The expression of CCNE1, CDK4, and antiapoptosis factor BCL‐2 was downregulated but the proapoptosis factor BAX was upregulated. The autophagy inhibitor chloroquine could significantly reverse the TFP‐induced apoptosis. Moreover, the ability of migration and invasion of HCT116 was found to be suppressed by TFP, which was associated with the inhibition of epithelial‐mesenchymal transition (EMT). The function of TFP in vivo was further confirmed. The results showed that the administration of TFP remarkably abrogated the tumor growth with decreased tumor volume and proliferation index Ki‐67 level in tumor tissues. The EMT phenotype was also confirmed to be inhibited by TFP in vivo, suggesting the promising antitumor effects of TFP in CRC.
Peimine inhibits the growth and motility of prostate cancer cells and induces apoptosis by disruption of intracellular calcium homeostasis through Ca2+/CaMKII/JNK pathway
Authors: Tan Hailin , Zhang Guiming , Yang Xuecheng , Jing Tao , Shen Daqing , Wang Xinsheng 
Published: May 2019

AbstractProstate cancer (PC) is one of the most common malignant tumors in man. Peimine (PM) is a bioactive substance isolated from Fritillaria. Previous studies have shown that PM could inhibit the occurrence of a variety of cancers. However, the roles of PM in PC and its related mechanism have not been elucidated. Calcium (Ca2+) is an important intracellular messenger involved in a variety of cell processes. In this study, we found that the appropriate doses of PM (2.5, 5, and 10 μM) significantly inhibited the growth of PC cells (DU‐145, LNCap, and PC‐3), but has no significant effect on normal prostate cells (RWPE‐1). In addition, PM treatment inhibited the invasion and migration of PC‐3 cells and blocked the epithelial‐mesenchymal transition process. These effects were exhibited a dose‐dependent manner. Furthermore, the current results also showed that PM treatment significantly increased the Ca2+ concentration, the increased Ca2+ promoted the phosphorylation of Ca2+/calmodulin‐dependent protein kinase II (CaMKII) and c‐Jun N‐terminal kinase (JNK), further inhibited the growth and invasion of PC‐3 cells, and induced its apoptosis. Ca2+ chelator BAPTA‐AM (1 μM) could counteract the increase of intracellular Ca2+ concentration. Similarly, JNK pathway inhibitor SP600125 (10 μM) also inhibited cell growth and invasion and induced apoptosis. In addition, experiments in nude mice showed that PM inhibited tumor formation through Ca2+/CaMKII/JNK signaling pathway. In conclusion, our results show that PM inhibits the growth and motility of prostate cancer cells and induces apoptosis by disruption of intracellular calcium homeostasis through Ca2+/CaMKII/JNK pathway.
An ego network analysis approach identified important biomarkers with an association to progression and metastasis of gastric cancer
Authors: Tian Xiaofeng , Ju Haiying , Yang Wei 
Published: May 2019

AbstractBackgroundGastric cancer (GC) is the fifth most common cancer type worldwide. The aim of this study was to identify gastric‐related therapeutic indicators on the basis of the ego network analysis.Material and methodsThe microarray data related to GC was downloaded from ArrayExpress database. All human protein‐protein interaction (PPI) networks were downloaded from the STRING database. Ego genes were identified on the basis of PPI networks and the gene expression in GC, and then co‐expression networks (ego networks) were constructed using these ego genes. On the basis of ego networks, the optimal GO terms and genes were predicted by affinity predictions and cold read predictions. Finally, the predicted genes as effective biomarkers for GC were verified by the bioinformatics analysis.ResultsThe differential expression networks were conducted and comprised of 365 edges and 232 nodes, which resulted in 218 ego genes. Although there was no significant difference in the expression of top ten ego genes among different groups of GC samples, it was eventually confirmed that top three optimal GO terms with highest cool read values were translational termination (cool read value = 0.987), translational elongation (cool read value = 0.986), and macromolecular complex disassembly (cool read value = 0.985) and top five optimal genes were UBA52, RPS27A, MAPK1, UBC, and UBB. UBA52, RPS27A, and MAPK1 were verified by the bioinformatics analysis to be related to the progression and metastasis of GC.ConclusionsAn ego network analysis approach is a very effective method for screening GC and the screened genes might be biomarkers for GC diagnosis and treatment.
Research on the roles of genes coding ATP‐binding cassette transporters in Porphyromonas gingivalis pathogenicity
Authors: Gao Li , Ma Yuanyuan , Li Xiting , Zhang Liping , Zhang Chi , Chen Qianying , Zhao Chuanjiang 
Published: May 2019

AbstractPorphyromonas gingivalis, as a major pathogen of periodontitis, could rapidly adhere to and invade host gingival epithelial cells (GECs) for the induction of infection. One ATP‐binding cassette (ABC) transporter gene was found to be upregulated during this infection process, however, the molecular mechanisms remain unclear. In this study, we systemically investigated the messenger RNA level changes of all ABC transporter family genes in P. gingivalis while being internalized within GECs by real‐time polymerase chain reaction. We identified that two ABC transporter genes, PG_RS04465 (PG1010) and PG_RS07320 (PG1665), were significantly increased in P. gingivalis after coculturing with GECs. Mutant strains with knockout (KO) of these two genes were generated by homogenous recombination. PG_RS04465 and PG_RS07320 KO mutants showed no change in the growth of bacteria per se. Knockdown of PG_RS07320, but not PG_RS04465, caused decreased endotoxin level in the bacteria. In contrast, both mutant strains showed decreased Arg‐ and Lys‐gingipains activities, with significantly reduced adhesion and invasion capabilities. Secreted interleukin‐1β (IL‐1β) and IL‐6 levels in GECs cocultured with PG_RS04465 or PG_RS07320 KO mutants were also decreased, whereas, only the cells cocultured with PG_RS07320 KO mutants showed significant decrease. In addition, virulence study using mouse revealed that both KO mutant strains infection caused less mouse death than wild‐type strains, showing reduced virulence of two KO strains. These results indicated that ABC transporter genes PG_RS04465 and PG_RS07320 are positive regulators of the virulence of P. gingivalis.
MicroRNAs and response to therapy in leukemia
Authors: Sharifi Hossein , Jafari Najaf Abadi Mohammad Hassan , Razi Ebrahim , Mousavi Nousin , Morovati Hamid , Sarvizadeh Mostafa , Taghizadeh Mohsen 
Published: May 2019

AbstractA variety of epigenetic factors involved in leukemia pathogenesis. Among various epigenetic factors, microRNAs (miRNAs) have emerged as important players, which affect a sequence of cellular and molecular signaling pathways. Leukemia is known as progressive cancer, which is related to many health problems in the world. It has been shown that the destruction of the blood‐forming organs could lead to abnormal effects on the proliferation and development of leukocytes and their precursors. Despite many attempts for approved effective and powerful therapies for patients with leukemia, finding and developing new therapeutic approaches are required. One of the important aspects of leukemia therapy, identification of underlying cellular and molecular mechanisms involved in the pathogenesis of leukemia. Several miRNAs (ie, miR‐103, miR‐101, mit‐7, let‐7i, miR‐424, miR‐27a, and miR‐29c) and play major roles in response to therapy in patients with leukemia. miRNAs exert their effects by targeting a variety of targets, which are associated with response to therapy in patients with leukemia. It seems that more understanding about the roles of miRNAs in response to therapy in patients with leukemia could contribute to better treatment of patients with leukemia. Here, for the first time, we summarized various miRNAs, which are involved in response to therapy in the treatment patients with leukemia.
Comparative assessment of the therapeutic drug targets of C. botulinum ATCC 3502 and C. difficile str. 630 using in silico subtractive proteomics approach
Authors: Bhardwaj Tulika , Haque Shafiul , Somvanshi Pallavi 
Published: May 2019

AbstractGrowing antimicrobial resistance of the pathogens against multiple drugs posed a serious threat to the human health worldwide. This fueled the need of identifying the novel therapeutic targets that can be used for developing new class of the drugs. Recently, there is a substantial rise in the rate of Clostridium infections as well as in the emergence of virulent and antibiotic resistant strains. Hence, there is an urgent need for the identification of potential therapeutic targets and the development of new drugs for the treatment and prevention of Clostridium infections. In the present study, a combinatorial approach involving systems biology and comparative genomics strategy was tested against Clostridium botulinum ATCC 3502 and Clostridium difficile str. 630 pathogens, to render potential therapeutic target at qualitative and quantitative level. This resulted in the identification of five common (present in both the pathogens, 34 in C. botulinum ATCC 3502 and 42 in C. difficile str. 630) drug targets followed by virtual screening–based identification of potential inhibitors employing molecular docking and molecular dynamics simulations. The identified targets will provide a solid platform for the designing of novel wide‐spectrum lead compounds capable of inhibiting their catalytic activities against multidrug‐resistant Clostridium in the near future.
TLR4 and nucleolin influence cell injury, apoptosis and inflammatory factor expression in respiratory syncytial virus‐infected N2a neuronal cells
Authors: Hu Tao , Yu Haiyang , Lu Min , Yuan Xiaoling , Wu Xuan , Qiu Huan , Chen Jason , Huang Shenghai 
Published: May 2019

AbstractRespiratory syncytial virus (RSV) infection was recently reported to be associated with central nervous system (CNS) symptoms and neurological complications; however, related studies are very limited. Moreover, the molecular mechanism underlying RSV neuropathogenesis is still unclear. Our previous study revealed that toll‐like receptor 4 (TLR4) and nucleolin (C23) could be modulated and that they played a role during RSV infection in mouse neuronal‐2a (N2a) cells. In the present study, the effects of silencing of TLR4 and C23 on RSV propagation and N2a cellular responses were examined by using RNA interference technology. Four N2a cell treatment groups were established, namely, a normal control group, RSV control group, TLR4 siRNA + RSV group, and C23 siRNA + RSV group. Expression changes in NeuN protein and colocalization of C23 and TLR4 with RSV F protein were assessed using confocal microscopy. Changes in TLR4 and C23 mRNA expression, TLR4, C23, TLR3, TLR7, and p‐NF‐κB protein expression, and interleukin (IL)‐8, IL‐6, and tumor necrosis factor (TNF‐α) cytokine secretion was measured using quantitative real‐time reverse‐transcription polymerase chain reaction, Western blot analysis, and enzyme‐linked immunosorbent assay, respectively. RSV titers and the apoptotic status of N2a cells were monitored using plaque formation assays and flow cytometry, respectively. The results indicated that TLR4 and C23 gene knockdown decreased the amount of F protein in RSV‐infected N2a cells, inhibited RSV propagation, attenuated N2a neuronal injury, diminished cell apoptosis levels, downregulated TLR3 and TLR7 protein expression, and reduced inflammatory protein expression. Therefore, TLR4 and C23 knockdown influences cell injury, apoptosis and inflammatory protein expression in RSV‐infected N2a cells.
Retracted: Elevation of circular RNA circ‐POSTN facilitates cell growth and invasion by sponging miR‐1205 in glioma
Authors: Yang Yimin , Zhang Ying , Chen Bin , Ding Lili , Mu Zhuang , Li Yanhua 
Published: May 2019

AbstractGlioma is the most common type of primary intracranial tumor. Dysregulation of circular RNAs (circRNAs) plays a critical role in multiple solid tumors. However, the expression profiles of circRNAs and their functions in glioma have been rarely studied. The current work aims to investigate the clinical significance of a novel circRNA, circ‐POSTN, in glioma and explore its biological functions and mechanisms in the progression of glioma. We found that circ‐POSTN was highly expressed in glioma tissue samples and cells. High circ‐POSTN expression was significantly linked to larger tumor size, higher World Health Organization grades, and shorter overall survival. Furthermore, silencing of circ‐POSTN in glioma cells could decrease cell growth, migratory and invasive potential, and induce cell apoptosis in LN229 cells. On the contrary, ectopically expressed circ‐POSTN induced the opposite effects in the U251 cell line. By bioinformatic prediction and luciferase reporter assay, we identified that miR‐1205 could be sponged by circ‐POSTN. Further rescue assays demonstrated that the oncogenic functions of circ‐POSTN are partly attributed to its regulation of miR‐1205 in glioma cells. Taken together, our data suggest that circ‐POSTN plays an oncogenic role in glioma progression and may serve as a novel therapeutic target in this deadly disease.
Identification of an adaptor protein‐2 mu gene (AccAP2m) in Apis cerana cerana and its role in oxidative stress responses
Authors: Wang Xinxin , Chao Yuzhen , Wang Ying , Xu Baohua , Wang Chen , Li Han 
Published: May 2019

AbstractThe adaptor protein‐2 (AP‐2) complex refers to a class of proteins that play an important role in cargo recognition and are involved in clathrin‐mediated endocytosis of cargo proteins from the plasma membrane in animal cells. However, there have been few studies of AP‐2 in insects. Here, we isolated an AP‐2 gene from Apis cerana cerana (A. cerana cerana) and explored the function of this gene, named AccAP2m. The obtained amino acid sequence of AccAP2m is highly conserved across species and contains conserved features of the AP‐2 family. Quantitative real‐time PCR analysis showed that AccAP2m mRNA levels were high in newly emerged workers, and the expression levels were higher in muscle than in other tissues. The expression of AccAP2m was altered in response to various environmental stress factors. Moreover, overexpression of recombinant AccAP2m protein enhanced the resistance of the bacteria to HgCl2, CdCl2, and cumyl hydroperoxide. In addition, after knockdown of AccAP2m in A. cerana cerana by RNA interference (RNAi), the transcription of some antioxidant genes was downregulated, and the activities of some antioxidant enzymes decreased. Taken together, these results indicate that AccAP2m may play an indispensable role in response to oxidative stresses.