bluuebunny/crossref_metadata_2025_split huggingface dataset:
Emotional Awareness and Expression Therapy Achieves Greater Pain Reduction than Cognitive Behavioral Therapy in Older Adults with Chronic Musculoskeletal Pain: A Preliminary Randomized Comparison Trial
Authors: Yarns Brandon C , Lumley Mark A , Cassidy Justina T , Steers W Neil , Osato Sheryl , Schubiner Howard , Sultzer David L 
Published: April 2020

Abstract

Objective
Emotional awareness and expression therapy (EAET) emphasizes the importance of the central nervous system and emotional processing in the etiology and treatment of chronic pain. Prior trials suggest EAET can substantially reduce pain; however, only one has compared EAET with an established alternative, demonstrating some small advantages over cognitive behavioral therapy (CBT) for fibromyalgia. The current trial compared EAET with CBT in older, predominately male, ethnically diverse veterans with chronic musculoskeletal pain.

Design
Randomized comparison trial.

Setting
Outpatient clinics at the West Los Angeles VA Medical Center.

Subjects
Fifty-three veterans (mean age = 73.5 years, 92.4% male) with chronic musculoskeletal pain.

Methods
Patients were randomized to EAET or CBT, each delivered as one 90-minute individual session and eight 90-minute group sessions. Pain severity (primary outcome), pain interference, anxiety, and other secondary outcomes were assessed at baseline, post-treatment, and three-month follow-up.

Results
EAET produced significantly lower pain severity than CBT at post-treatment and follow-up; differences were large (partial η2 = 0.129 and 0.157, respectively). At post-treatment, 41.7% of EAET patients had &gt;30% pain reduction, one-third had &gt;50%, and 12.5% had &gt;70%. Only one CBT patient achieved at least 30% pain reduction. Secondary outcomes demonstrated small to medium effect size advantages of EAET over CBT, although only post-treatment anxiety reached statistical significance.

Conclusions
This trial, although preliminary, supports prior research suggesting that EAET may be a treatment of choice for many patients with chronic musculoskeletal pain. Psychotherapy may achieve substantial pain reduction if pain neuroscience principles are emphasized and avoided emotions are processed.
Improved ligand-binding- and signaling-competent human NK2R yields in yeast using a chimera with the rat NK2R C-terminus enable NK2R-G protein signaling platform
Authors: Jain Abhinav R , Britton Zachary T , Markwalter Chester E , Robinson Anne S 
Published: April 2020

AbstractThe tachykinin 2 receptor (NK2R) plays critical roles in gastrointestinal, respiratory and mental disorders and is a well-recognized target for therapeutic intervention. To date, therapeutics targeting NK2R have failed to meet regulatory agency approval due in large part to the limited characterization of the receptor-ligand interaction and downstream signaling. Herein, we report a protein engineering strategy to improve ligand-binding- and signaling-competent human NK2R that enables a yeast-based NK2R signaling platform by creating chimeras utilizing sequences from rat NK2R. We demonstrate that NK2R chimeras incorporating the rat NK2R C-terminus exhibited improved ligand-binding yields and downstream signaling in engineered yeast strains and mammalian cells, where observed yields were better than 4-fold over wild type. This work builds on our previous studies that suggest exchanging the C-termini of related and well-expressed family members may be a general protein engineering strategy to overcome limitations to ligand-binding and signaling-competent G protein-coupled receptor yields in yeast. We expect these efforts to result in NK2R drug candidates with better characterized signaling properties.
Immune responses after influenza vaccination in patients of primary Sjögren’s syndrome
Authors: Zhou Xingyu , Liu Yisi , Jin Yuebo , Wang Yifan , Miao Miao , Chen Jiali , Cheng Yaobin , Liu Yudong , He Jing , Li Zhanguo 
Published: April 2020

AbstractObjectivesInfluenza vaccination is effective in preventing infections in most people. This study aimed to assess the changes of immune responses in primary Sjögren’s Syndrome (pSS) patients after influenza vaccination and determine the safety of influenza vaccination.MethodsA total of 17 patients with pSS and 16 healthy controls (HCs) were included. Peripheral mononuclear cells were analysed by flow cytometry. Vaccine-specific antibodies were determined by ELISA. Clinical features and serological responses were monitored.ResultsThe percentages of T follicular helper cell (Tfh) were significantly elevated in HCs after vaccination (P=0.0005), while no significant differences in the levels of Tfh in pSS patients were identified (P=0.1748). The proportions of Th2 cells were significantly decreased after vaccination in both pSS patients and HCs (P&lt;0.05). In contrast, the percentages of Th1 cells and Th17 cells were significantly increased after vaccination in pSS patients (P&lt;0.05), while no significant differences in the percentages of Th1 and Th17 cells were identified in HCs (P&gt;0.05), although a trend towards higher levels of Th1 cells was observed (P=0.0830). No significant changes in the proportions of memory B cells and plasmablasts were observed after vaccination. Patients with pSS developed higher levels of vaccine-specific IgGs compared with HCs (P=0.001). No significant changes in disease manifestations and laboratory parameters were observed after vaccination. No increased vaccination related adverse effect was observed in pSS.ConclusionOur findings suggest the feasibility of applying influenza vaccines to patients with pSS, raising awareness for vaccination among the rheumatology community and involved healthcare professionals.
Combating antibiotic resistance using plant‐derived compounds
Authors: Jones Emily Marie , Lopper Matthew 
Published: April 2020

Bacteria have steadily developed defenses against antibiotics since the world’s first fleet of antibacterial drugs was introduced. One strategy that bacteria can use to become multi‐drug resistant involves the overexpression of large, membrane‐embedded efflux pumps, such as the AcrAB‐TolC pump found in Escherichia coli (E. coli) and other Gram‐negative bacteria. This large efflux pump gives the bacterium the capability of transporting a wide variety of compounds out of the cell, including antibiotics that we use to combat bacterial infections. Overexpression of efflux pumps has been shown to lead to multidrug resistance in clinically important bacterial pathogens. Here, I have sought to identify novel inhibitors of bacterial efflux pumps by screening methanolic plant extracts for efflux pump inhibitory activity using an ethidium bromide‐based fluorescence assay. I have determined that yerba maté extract causes accumulation of ethidium bromide in live E. coli bacterial cells. To determine the ability of yerba maté extract to cause accumulation of clinically relevant antibiotics, I used growth curve analysis of E. coli in the presence of the plant extract with levofloxacin and carbenicillin. I have concluded that the combination of yerba maté and antibiotics enhances the susceptibility of bacteria. This research could open up a new avenue in the treatment of multi‐drug resistant bacterial infections.Support or Funding InformationClare Boothe Luce Research Scholars Program
The Association between Epidermal Growth Factor Receptor (EGFR) Gene Polymorphisms and Lung Cancer Risk
Authors: Bashir Nabil , Ragab Entesar , Khabour Omar , Alfaqih Mahmoud , Khassawneh Basheer , Momani Jafar 
Published: April 2020

Lung cancer is the leading cause of cancer death globally. The epidermal growth factor receptor (EGFR) plays an important role in cell proliferation and signaling. In this study, we examined the association between EGFR gene polymorphisms and lung cancer risk among the Jordanian population. A total of 129 patients with primary lung cancer and 129 matched healthy controls were recruited into this study. EGFR rs712829, rs712830, rs2072454, and rs11543848 single nucleotide polymorphisms (SNPs) were genotyped to test for their association with lung cancer risk. A significant association was observed between the rs712829 SNP and lung cancer risk (p < 0.05) where the GG + GT genotypes were higher in lung cancer patients when compared to controls. In addition, no association was detected between rs712830, rs2072454, and rs11543848 SNPs and lung cancer risk. When patients were stratified according to the lung cancer type, a significant association was detected between both rs712829 and rs2072454 and adenocarcinoma lung cancer (p < 0.05). Haplotype analysis of all four SNPs showed a significant association between the TCCG haplotype and both lung cancer and the adenocarcinoma subtype (p < 0.001). In conclusion, EGFR rs712829, rs2072454 SNPs, and TCCG haplotypes are associated with a risk of lung cancer among Jordanians. Since genetic associations are affected by the genetic background of populations, more studies in other Arab populations are required to confirm the present findings.Support or Funding InformationThe study was supported by funding provided by the Ministry of Higher Education—Scientific Research Fund (SRF) grant number JUST‐1‐2016.

Genotypes/Allele Pattern

Patients

Controls

p‐Value

For rs712829

GG

12 (28%)

29 (22%)

0.020

TT

4 (9%)

35 (27%)

GT

27 (63%)

65 (50%)

For rs712830

CC

41 (95%)

121 (94%)

0.670

CA

2 (5%)

8 (6%)

For rs2072454

CC

6 (14%)

15 (12%)

0.027

TT

26 (60%)

57 (44%)

CT

11 (26%)

57 (44%)

For rs11543848

AA

8 (19%)

26 (20%)

0.073

GG

2 (5%)

18 (14%)

GA

33 (77%)

85 (66%)

Note: Rs29: rs712829, Rs30: rs712830, Rs54: rs2072454 and Rs48: rs11543848.

Haplotype

Rs29

Rs30

Rs54

Rs48

Frequency

Odd Ratio (95% CI)

p‐Value

1

T

C

T

A

0.2118

1.00

—

2

G

C

T

A

0.1748

1.00 (0.31–3.24)

1

3

G

C

T

G

0.1552

0.93 (0.34–2.55)

0.9

4

T

C

T

G

0.1228

1.38 (0.32–5.96)

0.66

5

G

C

C

G

0.0953

1.08 (0.31–3.67)

0.91

6

T

C

C

A

0.0794

1.46 (0.33–6.43)

0.62

7

G

C

C

A

0.0681

0.69 (0.15–3.15)

0.63

8

T

C

C

G

0.0629

168,507 (168,498–168,517)

<0.001

9

G

A

T

G

0.0156

0.71 (0.08–6.39)

0.76

Note: Rs29: rs712829, Rs30: rs712830, Rs54: rs2072454 and Rs48: rs11543848.
The Expression of MRPL42 in Glioma and Its Prognostic Analysis
Authors: Duan Hubin , Hao Chunyan , Qiao Xiaohong , Wang Hongqin , Xue Wen , Lu Jian , Zhang Jinbao , Zhang Huaping , Zhang Ce 
Published: April 2020

ObjectiveTo determine the correlation between mitochondrial ribosomal protein MRPL42 expression levels in glioma and its association with clinicopathological parameters and prognosis.Methodsimmunohistochemistry assays were performed to explore the MRPL42 levels among diverse World Health Organization (WHO) grade of glioma, and its correlation with clinicopathological characteristics and survival prognosis of patients was also analyzed.ResultsThe results of immunohistochemistry analysis indicated that the expression of MRPL42 was positively correlated with glioma WHO grade(P<0.05) and several malignant clinicopathological index including Ki67 and P53mut. Besides, Kaplan‐Meier survival analysis also illustrated that patients with high expression of MRPL42 had significantly shorter overall survival than those with low expression of MRPL42(P<0.05).ConclusionThe expression of MRPL42 not only showed a tumor grade and clinicopathological factors‐dependent pattern, but also existed a positive correlation between them and distinguished glioma with poor prognosis, which may serve as prognostic biomarkers and potential therapeutic targets in glioma.Support or Funding Information• This study was supported by the National Natural Science Foundation Youth Fund (30600637), China Postdoctoral Science Foundation Grant (2019T120195), China Postdoctoral Science Foundation Grant (2014M561207), the Shanxi Province Basic Research Program ( 2010021034‐4, 201601D011119), the Shanxi Scholarship Council of China (2011‐096 and Key Projects No. 4), Department of Human Resources and Social Security of Shanxi province, The science and technology research projects of health department of Shanxi Province (2016D011119), The Teaching Reform Program of Shanxi Higher Education, The Education Reform Project of Postgraduate Students in Shanxi Province. The Project of “131” Leading Talents of Shanxi Higher Education, The Education Reform Project of Shanxi Medical University.
The Interplay between O‐GlcNAc And Phosphorylation on Tyrosine Hydroxylase Activity And Cathecolamine Synthesis in PC12 Cells
Authors: da Costa Rodrigues Bruno , Lucena Miguel , Rego Anna , Oliveira Isadora , Beckman Danielle , Ferreira Sergio Teixeira , de Mello Fernando Garcia , Todeschini Adriane Regina , Reis Ricardo , Dias Wagner Barbosa 
Published: April 2020

About 2% to 5% of all glucose that enters the cell is directed to the Hexosamine Biosynthetic Pathway (HBP), which has glutamine fructose‐6‐phosphate aminotransferase (GFAT) as the rate‐limiting step enzyme. HBP has UDP‐N‐acetylglucosamine (UDP‐GlcNAc) as a final product, which can be used as substrate for intracellular O‐GlcNAc; a post‐translational modification (PTM) resulting from the covalent attachment of a GlcNAc to the hydroxyl groups on serine and threonine residues in proteins. This reaction is catalyzed by O‐GlcNAc transferase (OGT), and the removal reaction of this monosaccharide is made by O‐GlcNAcase (OGA). The balance of the activity of such enzymes and UDP‐GlcNAc availability will regulate the levels of O‐GlcNAcylated proteins, with an O‐GlcNAcylation, similarly to phosphorylation, highly inducible, dynamic and active in many cellular processes. Tyrosine hydroxylase (TH) is the rate‐limiting step enzyme in catecholamine synthesis, responsible for hydroxylate L‐tyrosine at meta‐position to obtain L‐DOPA, the precursor of dopamine, which has a physiological role as a neurotransmitter. There are several supports on the literature that phosphorylation on serine 40 of TH increases its activity on a dynamical way, however, the mechanism of how O‐GlcNAc plays a role on this modulation remains unknown. We showed in PC12 cells treated with the pharmacological inhibitor of OGA Thiamet G (TMG); and nerve growth factor (NGF), a compound that induces these cells in a process of neuritogenesis, that O‐GlcNAcylation acts on the control of the phosphorylation levels of serine 40 in TH, where stimulation by 28% on the increase in phosphorylation at serine 40 decreases the levels of O‐GlcNAc in 26% compared to control; while the increase of intracellular O‐GlcNAc in 19% reduces the phosphorylation at serine 40 by 16%. In addition, HPLC analysis shows that the increase of intracellular O‐GlcNAc reduces the levels of L‐DOPA and dopamine by 80%. Finally, TH’s immunoprecipitation analysis reveals that it is O‐GlcNacylated, and this PTM regulates its activity. These data suggest a cellular mechanism that integrates carbohydrate metabolism (by HBP) with the catecholamine biosynthetic pathway in a neuritogenesis process; where competition between O‐GlcNAc and phosphate at serine 40 tyrosine hydroxylase site modulates its activity, controlling the synthesis of dopamine levels in PC12 cells.Support or Funding InformationFunding: CNPq, CAPES, FAPERJ
A time‐resolved fluorescence resonance energy transfer‐based screen for identification of a novel claudin‐4 binder that modulates the epithelial tight junction barrier
Authors: Kondoh Masuo , Watari Akihiro , Yagi Kiyohito 
Published: April 2020

Claudins, a 27‐member family of proteins with four transmembrane domains each, play a pivotal role in maintaining tight junction (TJ) seals in epithelial and endothelial tissue. The C‐terminal fragment of Clostridium perfringens enterotoxin (C‐CPE) binds to claudin‐4, which is a key functional and structural component of the TJ in mucosal epithelial cells. Upon binding, C‐CPE reversibly modulates TJ seals, yielding an enhancement of the paracellular transport of solutes. However, the use of C‐CPE as an absorption enhancer is limited by the molecule’s immunogenicity and manufacturing cost. In the present study, we developed a high‐throughput screening system using Time‐Resolved Fluorescence Resonance Energy Transfer (TR‐FRET) to identify small‐molecule compounds that bind to claudin‐4. Using this system, we performed a claudin‐4 binding screen of a library containing 2642 biologically active small molecules, and identified thiostrepton as a novel claudin‐4 binder. Thiostrepton decreased the transepithelial electrical resistance and increased flux of 4‐kDa FITC‐dextran in Caco‐2 cell monolayers without cell toxicity. Immunoblotting analysis revealed that thiostrepton changed the level of claudin‐4 in the Triton‐X soluble fraction, which contains TJ components, without altering the localization of claudin‐4. Furthermore, treatment of isolated rat jejunum with thiostrepton increased absorption of 4‐kDa FITC‐dextran. The TR‐FRET‐based screening system described here is expected to be of use in identifying compounds that modulate the permeability of the intestinal epithelial cell barrier; these compounds might serve as novel absorption enhancers in the intestine.Support or Funding InformationThis study was supported in part by Grants‐in‐Aid for Scientific Research from the Ministry of Education, Culture, Sports, Science and Technology of Japan (19H04468, 18K19400); a grant for Research on Development of New Drugs from the Japan Agency for Medical Research and Development (AMED); and grants from the Platform Project for Supporting Drug Discovery and Life Science Research (Basis for Supporting Innovative Drug Discovery and Life Science Research [BINDS]) of AMED (JP19am0101077, JP19am0101084, JP19am0101090).
Stain pleiotropy: direct regulation of arterial contractility by simvastatin
Authors: Zerin Farzana , Hasan Ahasanul , Hasan Raquibul 
Published: April 2020

Long‐term use of simvastatin, an inhibitor HMG‐CoA reductase and cholesterol synthesis, has been reported to influence vascular function secondary to the reduction of cholesterol. However, direct effects of simvastatin application on fresh isolated arteries and its relevance for arterial contractility regulation are unclear. Here, we investigated direct regulation of vascular reactivity by therapeutic concentrations of simvastatin in an ex‐vivo preparation of rat thoracic aorta using a combination of wire myography, Western blotting, and arterial biotinylation techniques. Our wire myography data revealed that simvastatin stimulates reversible contraction of aorta at therapeutic concentrations (0.0001–0.1 μM), with 0.01 μM producing maximum response that is equivalent to ~60% of depolarization‐mediated aorta contraction induced by 60mM K+. Endothelium removal or co‐application of mevalonate with simvastatin did not alter simvastatin‐induced vasocontraction. In contrast, removing extracellular Ca2+ with EGTA or co‐application of nimodipine, a blocker of CaV1.2, each abolished simvastatin‐evoked contraction of aorta. Ryanodine, a blocker of ryanodine receptor‐mediated Ca2+ release from intracellular Ca2+ stores, did not alter aorta contraction by simvastatin. Arterial biotinylation data showed that CaV1.2 channel protein expression and relative cellular distribution remain unchanged by simvastatin for the time points covering duration of simvastatin application. In summary, our data suggest that simvastatin directly controls arterial smooth muscle cell [Ca2+]i and arterial contractility primarily by stimulating Ca2+ entry via CaV1.2 ion channel in arterial smooth muscle cells, which is independent of HMG‐CoA reductase inhibition by simvastatin. Our future studies will examine if simvastatin and other statins can alter arterial contractility and blood pressure in normotensive and hypertensive animals in which CaV1.2 is upregulated.Support or Funding InformationThis work was supported by a start‐up grant from the Mercer University College of Pharmacy to Dr. Raquibul Hasan
Redox Signaling in Human Brain Vascular Smooth Muscle Cells
Authors: Rybka Vladyslava , Marcocci Lucia , Sariipek Nurefsan E. , Shults Nataliia V. , Gychka Sergiy G. , Suzuki Yuichiro 
Published: April 2020

BackgroundStroke is a leading cause of death in the U.S. and worldwide. Ischemic stroke is the major type of stroke, in which blood vessels in the brain become blocked. Thickening of the vascular wall narrows the lumen of the brain vessel and increases the incidence of ischemic stroke. Smooth muscle cell (SMC) growth contributes to the thickening of the vascular wall. Therapeutic strategies to inhibit and/or reverse brain vascular SMC growth, therefore, should reduce the incidence of ischemic stroke. However, the mechanism of brain vascular SMC growth is not well understood. Redox processes through the generation of reactive oxygen species (ROS) regulate cell signaling in various biological processes. The present study examined redox signaling, in particular, iron‐dependent protein carbonylation signaling in brain vascular SMCs.Methods & ResultsTreatment of cultured human brain vascular SMCs with deferoxamine (an iron chelator) resulted in a dose‐dependent reduction of cell growth induced by serum or by platelet‐derived growth factor (PDGF) as monitored by CCK8 colorimetric cell viability assay. As our laboratory previously discovered that iron‐catalyzed protein carbonylation mediates cell signaling in other cell types, we tested the effects of PDGF on protein carbonylation in human brain vascular SMCs. Treatment with PDGF promoted transient carbonylation of various proteins with a peak at 10 min. U0126, an inhibitor of the MEK/ERK pathway suppressed PDGF‐induced growth of human brain vascular SMCs and deferoxamine reduced ERK phosphorylation and activation in response to PDGF, suggesting that redox signaling occurs upstream from the ERK activation. The immunohistochemistry detection of malondialdehyde in brain tissues from human patients who died of stroke indicated the production of ROS in the vascular smooth muscle layer.ConclusionsWe demonstrate that redox signaling mediates the growth of brain vascular SMCs, opening up the possibility for targeting redox processes to improve therapeutic strategies to reduce the incidence of ischemic stroke.Support or Funding InformationSupported by NIH
Effects of Lycopene on Growth Factor Response in Prostate Cancer Cells
Authors: Nivison Mary , VanderWilde Allegra , Balijepalli Pravita , Meier Kathryn E. 
Published: April 2020

Dietary and nutritional factors are considered critical modulating factors in prostate cancer development. Epidemiological data have suggested to the idea that dietary consumption of lycopene, found in tomatoes, may prevent prostate cancer. This study examined the mechanism by which lycopene interacts with prostate cancer cells, with the goal of discovering less toxic treatment and prevention options. The hypothesis that was addressed was that lycopene interferes with growth factor‐mediated signal transduction in prostate cancer cells. The effects of lycopene on PC‐3, a human prostate cancer cell line, were analyzed using proliferation assays, immunoblot analysis, and confocal microscopy. The growth factors used were lysophosphatidic acid (LPA) and epidermal growth factor (EGF). Lycopene (10 μM) inhibited LPA and EGF‐induced proliferation of PC‐3 cells, confirming previous unpublished results. Lycopene also inhibited activation of Akt in response to LPA and EGF as assessed by immunoblotting. Confocal immunofluorescence microscopy showed that the decrease in activated Akt was most prominent in the cell nucleus. These results confirm the ability of lycopene to inhibit growth factor response in human prostate cancer cells, and suggest new directions for future studies.Support or Funding InformationSupported by the ASPET Summer Undergraduate Research Program, College of Pharmacy and Pharmaceutical Sciences, Sue Harriet Monroe Mullen Innovative Cancer Prevention Research Fund, and the ASPET David Lehr Award.