bluuebunny/crossref_metadata_2025_split huggingface dataset:
Coumarins as potential antidiabetic agents
Authors: Li Hanbing , Yao Yuanfa , Li Linghuan 
Published: July 2017

Abstract

Objectives
Even with great advances in modern medicine and therapeutic agent development, the search for effective antidiabetic drugs remains challenging. Coumarins are secondary metabolites found widely in nature plants and used mainly in anticoagulation and antithrombotic therapy. Over the past two decades, however, there has been an increasing body of literatures related to the effects of coumarins and their derivatives on diabetes and its complications. This review aimed to focus on research findings concerning the effects of coumarins against diabetes and its complications using in-vitro and in-vivo animal models, and also to discuss cellular and molecular mechanisms underlying these effects.

Key findings
The search for new coumarins against diabetes and it complications, either isolated from traditional medicine or chemically synthesized, has been constantly expanding. The cellular and molecular mechanisms involved include protecting pancreatic beta cells from damage, improving abnormal insulin signalling, reducing oxidative stress/inflammation, activating AMP-activated protein kinase (AMPK), inhibiting α-glucosidases and ameliorating diabetic complications.

Conclusions
The effects and mechanisms of coumarins and their derivatives upon diabetes and its complications are discussed in current review. Further investigations remain to be carried out to develop a promising antidiabetic agent based on coumarin cores.
A comprehensive review on anticancer mechanisms of the main carotenoid of saffron, crocin
Authors: Hoshyar Reyhane , Mollaei Homa 
Published: July 2017

Abstract

Objectives
Crocin is derived from dried stigmas of Crocus sativus L. (saffron). It has long been used to prevent and treat various diseases. Although crocin is suggested as one of the most effective cancer therapeutic constituents of saffron stigma, its exact molecular mechanisms are not fully understood. In this study, we reviewed anticancer effects of crocin and its underlying molecular mechanisms.

Key findings
While several mechanisms may account for the antitumour activity of crocin, alteration of expression/activity of the genes and also epigenetic changes may be considered as necessary phenomena. These alternations may lead to inhibition of cancer cells' proliferation or/and induction of apoptosis through various mechanism including inhibition of synthesis of DNA and RNA, interaction with cellular topoisomerase, suppression of the telomerase activity and active STAT3, and targeting of microtubules. Moreover, this carotenoid could reverse the epithelial–mesenchymal transition and inhibit metastasis.

Conclusions
Knowing molecular mechanisms of antitumoral agents could guide us to choose the best chemotherapeutic compound especially for targeted therapy and also provide insights about possible side effects.
Adaptive maintenance of European alleles in the Brazilian Africanized honeybee
Authors: Harpur Brock A. 
Published: July 2017

The Anthropocene is an epoch hallmarked by intensified human intrusion across ecosystems. One such intrusion is the movement and re‐introduction of long‐separated populations. By facilitating introgression – intraspecific genetic admixture – secondary contact can facilitate range expansion and the establishment of invasive species. The proximate mechanisms through which introgression facilitates expansion are rarely known (Bock et al., ; Rius & Darling, ), but managed species provide a useful avenue for exploration. Bee‐keepers have been interbreeding highly diverged honeybee clades for centuries, often to introduce “useful” phenotypic variation to their stocks. Across the Western honeybee's (Apis mellifera) European range, this practice has not resulted in range expansion (Moritz, Härtel, & Neumann, ). In the Americas, however, introgression of European with African subspecies resulted in a widely publicized invasive population: The Africanized honeybee (AHB). In this issue of Molecular Ecology, Nelson, Wallberg, Simões, Lawson, and Webster () have made the first step towards understanding how this invasive species successfully spread across the Americas.
Two proteases with caspase‐3‐like activity, cathepsin B and proteasome, antagonistically control ER‐stress‐induced programmed cell death in Arabidopsis
Authors: Cai Yao‐Min , Yu Jia , Ge Yuan , Mironov Aleksandr , Gallois Patrick 
Published: July 2017

Summary

Programmed cell death (PCD) induced by endoplasmic reticulum (ER) stress is implicated in various plant physiological processes, yet its mechanism is still elusive. An activation of caspase‐3‐like enzymatic activity was clearly demonstrated but the role of the two known plant proteases with caspase‐3‐like activity, cathepsin B and proteasome subunit PBA1, remains to be established.

Both genetic downregulation and chemical inhibition were used to investigate the function of cathepsin B and PBA1 in ER‐stress‐induced PCD (ERSID). Transcript level and activity labelling of cathepsin B were used to assess activation. To study tonoplast rupture, a plant PCD feature, both confocal and electronic microscopies were used.

Cathepsin B downregulation reduced reactive oxygen species (ROS) accumulation and ERSID without affecting the induction of the unfolded protein response (UPR), but downregulation of PBA1 increased UPR and ERSID. Tonoplast rupture was not altered in the cathepsin B mutant and cathepsin B activation was independent of vacuolar processing enzyme (VPE). VPE activity was independent of cathepsin B.

ERSID is regulated positively by cathepsin B and negatively by PBA1, revealing a complex picture behind caspase‐3‐like activity in plants. Cathepsin B may execute its function after tonoplast rupture and works in parallel with VPE.
On the factors inducing the inhibition of diapause in the progeny of diapause females of Trichogramma telengai
Authors: Voinovich Natalia D. , Reznik Sergey Ya. 
Published: July 2017

AbstractThe ability to enter diapause in the progeny of Trichogramma Westw. (Hymenoptera: Trichogrammatidae) females that have undergone diapause is markedly reduced or even completely absent. This maternal inhibition of diapause can result from three types of factors: (i) environmental factors that induce maternal diapause; (ii) maternal diapause itself; and (iii) diapause‐terminating environmental factors. The present study aims to determine the factors that prevent diapause in the progeny of a Trichogramma telengai Sor. generation that has undergone diapause. Different tendencies to enter diapause in the maternal generation are induced by different photoperiods (LD 12 : 12 h, 16 : 8 h and 18 : 6 h) during development of the grandmaternal generation and different temperatures (from 10 to 15 °C) during larval development of the maternal generation. To terminate diapause, prepupae of the maternal generation are kept at 4–5 °C in the dark. To estimate the ability to enter diapause, the progeny generation is incubated at 14 °C. The results suggest that the inhibition of the tendency to enter diapause in the progeny of T. telengai females that have undergone diapause is caused by diapause itself rather than by diapause‐inducing or diapause‐terminating environmental factors. This result can be used to clarify the mechanism of the inhibition of diapause in the progeny of females that have undergone diapause.
Understanding the health of veterans who are homeless: A review of the literature
Authors: Weber Jillian , Lee Rebecca C. , Martsolf Donna 
Published: July 2017

AbstractThe United States Department of Housing and Urban Development estimates that almost 50,000 veterans are homeless on any given night. Homeless veterans are at greater risk of health disparities than their housed counterparts due to the multifactorial nature of their health and social needs. The Department of Veterans Affairs, in collaboration with more than a dozen other federal agencies, has concentrated efforts to improve the health of this vulnerable population while enacting a plan to eliminate veteran homelessness within the near future. Understanding the unique health needs of veterans who are homeless allows the profession of nursing to better support these efforts. The purpose of this literature review was to provide comprehensive knowledge to nurses about the health of homeless veterans for their use in clinical practice, research, and in contributing to the positive health outcomes for this vulnerable population.
How did investor‐state dispute settlement get a bad rap? Blame it onNAFTA, of course
Authors: Anderson Greg 
Published: July 2017

AbstractIn the short history of the US bilateral investment treaty (BIT) programme, there have been no instances of dispute settlement cases initiated against the United States by firms fromBITcountries. TheNAFTAexperience changed that. Where other studies have only hinted at the reasons forNAFTAcontroversies, this paper makes clear three causal factors: (i) changing patterns and intensity ofFDI, (ii) the application of those rules to developed countries amid those changingFDIpatterns and (iii) ambiguities inISDSrules themselves. The paper explores these and traces the ways in which lessons of theNAFTAhave been instrumental in changing the pursuit of investment protection agreements.BITs used to be uncontroversial, but theNAFTAfocused attention on reforms toISDSthat maintain the utility ofBITs in the governance ofFDI, without creating a legal structure for simply challenging the state.
Screening the Medicines for Malaria Venture Pathogen Box across Multiple Pathogens Reclassifies Starting Points for Open-Source Drug Discovery
Authors: Duffy Sandra , Sykes Melissa L. , Jones Amy J. , Shelper Todd B. , Simpson Moana , Lang Rebecca , Poulsen Sally-Ann , Sleebs Brad E. , Avery Vicky M. 
Published: July 2017

ABSTRACT

Open-access drug discovery provides a substantial resource for diseases primarily affecting the poor and disadvantaged. The open-access Pathogen Box collection is comprised of compounds with demonstrated biological activity against specific pathogenic organisms. The supply of this resource by the Medicines for Malaria Venture has the potential to provide new chemical starting points for a number of tropical and neglected diseases, through repurposing of these compounds for use in drug discovery campaigns for these additional pathogens. We tested the Pathogen Box against kinetoplastid parasites and malaria life cycle stages
in vitro
. Consequently, chemical starting points for malaria, human African trypanosomiasis, Chagas disease, and leishmaniasis drug discovery efforts have been identified. Inclusive of this
in vitro
biological evaluation, outcomes from extensive literature reviews and database searches are provided. This information encompasses commercial availability, literature reference citations, other aliases and ChEMBL number with associated biological activity, where available. The release of this new data for the Pathogen Box collection into the public domain will aid the open-source model of drug discovery. Importantly, this will provide novel chemical starting points for drug discovery and target identification in tropical disease research.
In Vitro
Activity of Ceftolozane-Tazobactam and Other Antimicrobial Agents against Burkholderia cepacia Complex and Burkholderia gladioli
Authors: Mazer Dale M. , Young Carol , Kalikin Linda M. , Spilker Theodore , LiPuma John J. 
Published: July 2017

ABSTRACT

We tested the activities of ceftolozane-tazobactam and 13 other antimicrobial agents against 221 strains of
Burkholderia cepacia
complex and
Burkholderia gladioli
. Most strains (82%) were cultured from persons with cystic fibrosis, and most (85%) were recovered since 2011. The ceftolozane-tazobactam MIC was ≤8 μg/ml for 77% of the strains. However, the MIC range was broad (≤0.5 to >64 μg/ml; MIC
50/90
, 2/32 μg/ml). Significant differences in susceptibility to some antimicrobial agents were observed between species.
Plasmids of Diverse Inc Groups Disseminate the Fosfomycin Resistance Gene
fosA3
among Escherichia coli Isolates from Pigs, Chickens, and Dairy Cows in Northeast China
Authors: Wang Xiu-Mei , Dong Zhimin , Schwarz Stefan , Zhu Yao , Hua Xin , Zhang Yanhe , Liu Siguo , Zhang Wan-Jiang 
Published: July 2017

ABSTRACT

Thirty-nine fosfomycin-resistant
Escherichia coli
isolates carrying
fosA3
were obtained from pigs, chickens, dairy cows, and staff in four northeastern provinces of China between June 2015 and April 2016. The
fosA3
gene was colocated with
bla
CTX-M
genes on conjugative plasmids of the incompatibility groups IncN (
n
= 12), IncN-F33:A
−
:B
−
(
n
= 2), IncF33:A
−
:B
−
(
n
= 14), IncF14:A
−
:B
−
(
n
= 2), and IncI1/sequence type 136 (ST136) (
n
= 9). Four different genetic contexts of
fosA3
were detected among the 39
E. coli
isolates. Three potential epidemic plasmids circulated among
E. coli
strains from this region.
Repurposing Thiram and Disulfiram as Antibacterial Agents for Multidrug-Resistant Staphylococcus aureus Infections
Authors: Long Timothy E. 
Published: July 2017

ABSTRACT

Thiram and disulfiram were evaluated as antibacterial agents against multidrug-resistant
Staphylococcus aureus
. Against a 30-member panel comprised of vancomycin-susceptible, vancomycin-intermediate, and vancomycin-resistant
S. aureus
strains, the MIC
90
values of the respective test agents were 4 and 16 μg/ml. Additional analyses revealed that thiram and disulfiram are rapid-acting bacteriostatic agents with narrow, Gram-positive-bacterium spectrum activity. Synergy studies further determined that disulfiram increases the vancomycin susceptibility of three clinical vancomycin-resistant
S. aureus
strains
in vitro
, thus establishing a potential use in combination therapy.
Multicenter Study of Clinical Features of Breakthrough Acinetobacter Bacteremia during Carbapenem Therapy
Authors: Lee Yi-Tzu , Wang Yung-Chih , Kuo Shu-Chen , Chen Chung-Ting , Liu Chang-Pan , Liu Yuag-Meng , Chen Te-Li , Yang Ya-Sung 
Published: July 2017

ABSTRACT

Breakthrough
Acinetobacter
bacteremia during carbapenem therapy is not uncommon, and it creates therapeutic dilemmas for clinicians. This study was conducted to evaluate the clinical and microbiological characteristics of breakthrough
Acinetobacter
bacteremia during carbapenem therapy and to assess the efficacy of various antimicrobial therapies. We analyzed 100 adults who developed breakthrough
Acinetobacter
bacteremia during carbapenem therapy at 4 medical centers over a 6-year period. Their 30-day mortality rate was 57.0%, and the carbapenem resistance rate of their isolates was 87.0%. Among patients with carbapenem-resistant
Acinetobacter
bacteremia, breakthrough bacteremia during carbapenem therapy was associated with a significantly higher 14-day mortality (51.7% versus 37.4%, respectively;
P
= 0.025 by bivariate analysis) and a higher 30-day mortality (
P
= 0.037 by log rank test of survival analysis) than in the nonbreakthrough group. For the treatment of breakthrough
Acinetobacter
bacteremia during carbapenem therapy, tigecycline-based therapy was associated with a significantly higher 30-day mortality (80.0%) than those with continued carbapenem therapy (52.5%) and colistin-based therapy (57.9%) by survival analysis (
P
= 0.047 and 0.045 by log rank test, respectively). Cox regression controlling for confounders, including severity of illness indices, demonstrated that treatment with tigecycline-based therapy for breakthrough
Acinetobacter
bacteremia was an independent predictor of 30-day mortality (hazard ratio, 3.659; 95% confidence interval, 1.794 to 7.465;
P
< 0.001). Patients with breakthrough
Acinetobacter
bacteremia during carbapenem therapy posed a high mortality rate. Tigecycline should be used cautiously for the treatment of breakthrough
Acinetobacter
bacteremia that develops during carbapenem therapy.
Characterization of a Large Antibiotic Resistance Plasmid Found in Enteropathogenic Escherichia coli Strain B171 and Its Relatedness to Plasmids of Diverse E. coli and Shigella Strains
Authors: Hazen Tracy H. , Michalski Jane , Nagaraj Sushma , Okeke Iruka N. , Rasko David A. 
Published: July 2017

ABSTRACT

Enteropathogenic
Escherichia coli
(EPEC) is a leading cause of severe infantile diarrhea in developing countries. Previous research has focused on the diversity of the EPEC virulence plasmid, whereas less is known regarding the genetic content and distribution of antibiotic resistance plasmids carried by EPEC. A previous study demonstrated that in addition to the virulence plasmid, reference EPEC strain B171 harbors a second, larger plasmid that confers antibiotic resistance. To further understand the genetic diversity and dissemination of antibiotic resistance plasmids among EPEC strains, we describe the complete sequence of an antibiotic resistance plasmid from EPEC strain B171. The resistance plasmid, pB171_90, has a completed sequence length of 90,229 bp, a GC content of 54.55%, and carries protein-encoding genes involved in conjugative transfer, resistance to tetracycline (
tetA
), sulfonamides (
sulI
), and mercury, as well as several virulence-associated genes, including the transcriptional regulator
hha
and the putative calcium sequestration inhibitor (
csi
).
In silico
detection of the pB171_90 genes among 4,798 publicly available
E. coli
genome assemblies indicates that the unique genes of pB171_90 (
csi
and
traI
) are primarily restricted to genomes identified as EPEC or enterotoxigenic
E. coli
. However, conserved regions of the pB171_90 plasmid containing genes involved in replication, stability, and antibiotic resistance were identified among diverse
E. coli
pathotypes. Interestingly, pB171_90 also exhibited significant similarity with a sequenced plasmid from
Shigella dysenteriae
type I. Our findings demonstrate the mosaic nature of EPEC antibiotic resistance plasmids and highlight the need for additional sequence-based characterization of antibiotic resistance plasmids harbored by pathogenic
E. coli
.
In Vivo
Emergence of Resistance to Novel Cephalosporin–β-Lactamase Inhibitor Combinations through the Duplication of Amino Acid D149 from OXA-2 β-Lactamase (OXA-539) in Sequence Type 235 Pseudomonas aeruginosa
Authors: Fraile-Ribot Pablo A. , Mulet Xavier , Cabot Gabriel , del Barrio-Tofiño Ester , Juan Carlos , Pérez José L. , Oliver Antonio 
Published: July 2017

ABSTRACT

Resistance development to novel cephalosporin–β-lactamase inhibitor combinations during ceftazidime treatment of a surgical infection by
Pseudomonas aeruginosa
was investigated. Both initial (97C2) and final (98G1) isolates belonged to the high-risk clone sequence type (ST) 235 and were resistant to carbapenems (
oprD
), fluoroquinolones (GyrA-T83I, ParC-S87L), and aminoglycosides (
aacA7/aacA8/aadA6
). 98G1 also showed resistance to ceftazidime, ceftazidime-avibactam, and ceftolozane-tazobactam. Sequencing identified
bla
OXA-2
in 97C2, but 98G1 contained a 3-bp insertion leading to the duplication of the key residue D149 (designated OXA-539). Evaluation of PAO1 transformants producing cloned OXA-2 or OXA-539 confirmed that D149 duplication was the cause of resistance. Active surveillance of the emergence of resistance to these new valuable agents is warranted.
Genetic Adjuvantation of a Cell-Based Therapeutic Vaccine for Amelioration of Chagasic Cardiomyopathy
Authors: Konduri Vanaja , Halpert Matthew M. , Liang Dan , Levitt Jonathan M. , Cruz-Chan Julio Vladimir , Zhan Bin , Bottazzi Maria Elena , Hotez Peter J. , Jones Kathryn M. , Decker William K. 
Published: July 2017

ABSTRACT

Chagas disease, caused by infection with the protozoan parasite
Trypanosoma cruzi
, is a leading cause of heart disease (“chagasic cardiomyopathy”) in Latin America, disproportionately affecting people in resource-poor areas. The efficacy of currently approved pharmaceutical treatments is limited mainly to acute infection, and there are no effective treatments for the chronic phase of the disease. Preclinical models of Chagas disease have demonstrated that antigen-specific CD8
+
gamma interferon (IFN-γ)-positive T-cell responses are essential for reducing parasite burdens, increasing survival, and decreasing cardiac pathology in both the acute and chronic phases of Chagas disease. In the present study, we developed a genetically adjuvanted, dendritic cell-based immunotherapeutic for acute Chagas disease in an attempt to delay or prevent the cardiac complications that eventually result from chronic
T. cruzi
infection. Dendritic cells transduced with the adjuvant, an adenoviral vector encoding a dominant negative isoform of Src homology region 2 domain-containing tyrosine phosphatase 1 (SHP-1) along with the
T. cruzi
Tc24 antigen and
trans
-sialidase antigen 1 (TSA1), induced significant numbers of antigen-specific CD8
+
IFN-γ-positive cells following injection into BALB/c mice. A vaccine platform transduced with the adenoviral vector and loaded in tandem with the recombinant protein reduced parasite burdens by 76% to >99% in comparison to a variety of different controls and significantly reduced cardiac pathology in a BALB/c mouse model of live Chagas disease. Although no statistical differences in overall survival rates among cohorts were observed, the data suggest that immunotherapeutic strategies for the treatment of acute Chagas disease are feasible and that this approach may warrant further study.
S-Nitrosoglutathione Reductase Deficiency Confers Improved Survival and Neurological Outcome in Experimental Cerebral Malaria
Authors: Elphinstone Robyn E. , Besla Rickvinder , Shikatani Eric A. , Lu Ziyue , Hausladen Alfred , Davies Matthew , Robbins Clinton S. , Husain Mansoor , Stamler Jonathan S. , Kain Kevin C. 
Published: July 2017

ABSTRACTArtesunate remains the mainstay of treatment for cerebral malaria, but it is less effective in later stages of disease when the host inflammatory response and blood-brain barrier integrity dictate clinical outcomes. Nitric oxide (NO) is an important regulator of inflammation and microvascular integrity, and impaired NO bioactivity is associated with fatal outcomes in malaria. Endogenous NO bioactivity in mammals is largely mediated byS-nitrosothiols (SNOs). Based on these observations, we hypothesized that animals deficient in the SNO-metabolizing enzyme,S-nitrosoglutathione reductase (GSNOR), which exhibit enhancedS-nitrosylation, would have improved outcomes in a preclinical model of cerebral malaria. GSNOR knockout (KO) mice infected withPlasmodium bergheiANKA had significantly delayed mortality compared to WT animals (P< 0.0001), despite higher parasite burdens (P< 0.01), and displayed markedly enhanced survival versus the wild type (WT) when treated with the antimalarial drug artesunate (77% versus 38%;P< 0.001). Improved survival was associated with higher levels of protein-bound NO, decreased levels of CD4+and CD8+T cells in the brain, improved blood-brain barrier integrity, and improved coma scores, as well as higher levels of gamma interferon. GSNOR KO animals receiving WT bone marrow had significantly reduced survival followingP. bergheiANKA infection compared to those receiving KO bone barrow (P< 0.001). Reciprocal transplants established that survival benefits of GSNOR deletion were attributable primarily to the T cell compartment. These data indicate a role for GSNOR in the host response to malaria infection and suggest that strategies to disrupt its activity will improve clinical outcomes by enhancing microvascular integrity and modulating T cell tissue tropism.