bluuebunny/crossref_metadata_2025_split huggingface dataset:
Metabolic Activation of Retrorsine may Disrupt Bile Acid Homeostasis in Mice through the Nrf2 Pathway
Authors: Pang Xiaoyan , Tang Chongzhuang , Cao Peng , Zhou Lei , Chen Xiaoyan 
Published: April 2021

Background:
The hepatotoxic pyrrolizidine alkaloids (PAs) were reported to increase bile acid (BA)
levels in the rat. However, it is still unclear whether the production of highly reactive dehydropyrrolizidine through
CYP450s is directly relevant to BA changes.

Objective:
To further explore the mechanism by which metabolic activation of PAs induced BA changes, the effect
of impaired or enhanced metabolic activation on the BA profiling and BA-related synthesis and to investigate transport
genes, and explore the involvement of the Nrf2 pathway.

Methods:
Blood and liver samples were collected after intragastrical administration of 35 mg/kg retrorsine or saline
for seven days in wild-type (WT) and Nrf2 KO mice. CYP450 inhibitor, 1-aminobenzotriazole (ABT), or gammaglutamylcysteine
synthetase inhibitor, L-buthionine-sulfoximine (BSO) were employed in WT mice. Retrorsineinduced
hepatotoxicity was evaluated by a biochemical method and H&E staining method. Serum BAs were quantified
by high-performance liquid chromatography/triple quadrupole mass spectrometry. Blood pyrrole-protein adducts
were semi quantified by high-performance liquid chromatography/quadrupole time-of-flight mass spectrometry. The
gene and protein expression of BA-related transporters and enzymes in the liver were measured by a quantitative
real-time PCR method and western blotting method.

Results:
The BA concentrations in serum were increased in the retrorsine-treated WT mice, along with the upregulation
of BA transporters, Ostβ, Mrp3, Mrp4, and Mrp2. When ABT was co-administered, the altered BA levels
and Mrp4 mRNA and protein levels were reversed, accompanied by a 50% reduction of 6,7-dihydro-7-hydroxy-1-
hydroxymethyl-5H-pyrrolizine (DHP) formation. When BSO was co-administered, serum BAs were not further
increased, but Ostβ, Mrp3, Mrp4 mRNA, and Mrp4 protein levels continuously increased. The induction of Mrp4 by
retrorsine among the tested BA transporters was the only one that was abolished or enhanced in the presence of ABT
or BSO. The Nrf2 protein levels in the nucleus increased in the retrorsine-treated WT mice, which were remarkably
repressed by co-administration of ABT and enhanced by co-administration of BSO. In Nrf2 KO mice receiving retrorsine,
the bile acids and the mRNA and protein levels of Mrp2, Mrp3, Mrp4, and Ostβ were hardly changed, indicating
the direct role of Nrf2 in retrorsine-induced BA changes in WT mice.

Conclusion:
The activation of Nrf2 translocation by forming the reactive metabolite of PAs induced the expressions
of BA transporters and changed serum BA levels. Mrp4 was a sensitive biomarker for the perturbation of redox
status caused by the formation of dehydropyrrolizidine.
Synthesis of 2-Hydroxynaphthyl Pyrazolines Containing Isoniazid Moiety:
A Potential Antitubercular Agent
Authors: Kottapalle Gajanan , Deshmukh Nagesh , Shinde Avinash 
Published: April 2021

Abstract:
The new series of pyrazolines derivatives containing isoniazid moiety were synthesized from
2-hydroxynaphthyl functionalized chalcones and isoniazid using sodium hydroxide as a base in 2-
ethoxy ethanol. We evaluated their antitubercular activity against Mycobacterium tuberculosis strain
(H37Rv) by Microplate Alamar Blue Assay (MABA). Some of the tested compounds 3a, 3b, and 3c,
were found to have higher antitubercular activity than the selected standard drugs, whereas compounds
3d, 3e, 3i and 3j were found to have higher antitubercular activity than Streptomycin and same as that
of Pyrazinamide and Ciprofloxacin, while remaining compound showed moderate activity. Whereas it
is found that the disubstituted halogen compound and electron-withdrawing group on the phenyl ring
are important substitutions for an increase in antitubercular activity.
Antioxidant and ROS Inhibitory Activities of Heterocyclic 2-Aryl-4(3H)-quinazolinone Derivatives
Authors: Perveen Shahida , Saad Syed Muhammad , Khan Khalid Mohammed , Choudhary Muhammad Iqbal 
Published: April 2021

Background:
Antioxidants are small molecules that prevent or delay the process of
oxidations caused by highly reactive free radicals. These molecules are known for their ability to
protect various cellular architecture and other biomolecules from oxidative stress and free radicals.
Thus, antioxidants play a key role in the prevention of oxidative damages caused by highly reactive
free radicals.

Methods:
In the present study, a series of previously synthesized heterocyclic 2-aryl-4(3H)-
quinazolinone derivatives 1-25 were screened for antioxidant activity by employing in vitro DPPH
and superoxide anion radical scavenging activities. ROS inhibitory activities were also evaluated
by serum-opsonized zymosan activated whole blood phagocytes and isolated neutrophils.
Cytotoxicity studies were carried out by employing an MTT assay against the 3T3 cell line.

Results:
Most of the 2-aryl-4(3H)-quinazolinone derivatives showed potent antioxidant activities in
superoxide anion radical scavenging assay with IC50 value ranging between 0.57 μM - 48.93 μM,
as compared to positive control quercetin dihydrate (IC50 = 94.1 ± 1.1 μM ). Compounds 5, 6, and
14 showed excellent activity in DPPH assay. Compounds 5-8, 12-15, 17, and 20 showed promising
activities in the ROS inhibition assay. All compounds were found to be non-cytotoxic against the
3T3 cell line. Structure antioxidant activity has been established.

Conclusion:
It can be concluded that most of the heterocyclic 2-aryl-4(3H)-quinazolinone
derivatives 1-25 are identified as promising antioxidant agents that are capable of fighting against
free radicals and oxidative stress. Thus, they can serve as a lead towards treating oxidative stress and
related pathologies.
Design, Synthesis, Computational and Biological Evaluation of Two New Series of 1, 3- and 1,6-dihydroxy Xanthone Derivatives as Selective COX-2 Inhibitors
Authors: Gogoi Urvashee , Das Aparoop , Pathak Manash Pratim , Chattopadhyay Pronobesh , Johari Surabhi 
Published: April 2021

Background:
Over the years, the xanthone nucleus has been serving as an interesting
scaffold for the design of derivatives aiming at anti-inflammatory drug development.

Objective:
The objective of the current work was to design and synthesize two series of novel 3-
(5'-substituted pentyloxy)-1-hydroxy xanthone & 6-(5'-substituted pentyloxy)-1-hydroxy xanthone
derivatives. The designed compounds were examined in vivo for anti-inflammatory activity. The
effect of the synthesized xanthone derivatives on the serum expression of IL-10 and TNF-α was
evaluated to understand the underlying molecular mechanisms.

Method:
The title compounds were virtually designed and screened for ADME/T properties and
docked onto the COX-2 protein. The synthesis of the xanthone derivatives was achieved by the
condensation of salicylic acid derivatives and a suitable phenol in the presence of a mixture of
phosphorus pentoxide–methanesulfonic acid as an acylation catalyst. The compounds were
evaluated for in vivo anti-inflammatory activity by carrageenan induced paw edema method and
serum expression of cytokines was evaluated using ELISA assays.

Results:
The selected compounds exhibited docking scores ranging between -10.7 to -6.8
(Kcal/mol), respectively, as compared with standard Celecoxib (-7.9 Kcal/mol) and the nonselective
COX inhibitor Indomethacin (-6.4 Kcal/mol). Among the tested compounds, 9u has
shown the highest activity with 65.6 % reduction in edema (69.8% for Celecoxib). Immunoassay
results showed a significant drop in serum TNF-α and an elevation in serum IL-10.

Conclusion:
The findings highlight that some of the synthesized xanthone derivatives displayed
marked anti-inflammatory activity, which can be further investigated to render efficient and novel
non-ulcerogenic anti-inflammatory agents.
Biological Evaluation, Isolation, and Characterization of Novel Polyphenol
Derivatives fromSchleichera oleosa (Lour) Oken as Anti-diabetic Agents
Authors: Muthukrishnan Soundararajan , Sivakkumar Thillai , Anbiah Vigil 
Published: April 2021

Background:
The treatment of diabetes involves insulin and many different oral hypoglycemic
drugs. In chronic disease conditions, medications potentially lose viability. Therefore,
searching for more effective and safer natural anti-diabetic agents has continued to be an important
area of investigation

Objective:
The present study aims to investigate the effect of ethanolic and aqueous extracts of Schleichera
oleosa (S. oleosa) on diabetic rats and isolate and characterize the active compound from
an effective extract.

Method:
The ethanolic and aqueous extracts were administered orally (200 and 400 mg/kg, for 28
days) to streptozotocin-nicotinamide-induced diabetic rats. Hypoglycemic effects, OGTT, alteration
in body weight, lipid profile, biochemical parameters, hepatic enzymes, and histopathological
examination were assessed. Afterwards, the active constituents of the effective extract were isolated
using column chromatography, and the preliminary structural features were investigated by FTIR,
1H NMR, 13C NMR, and LC/MS.

Results:
The extracts treated rats showed a significant reduction in the fasting blood glucose level
(FBGL), total cholesterol, triglycerides, LDL, VLDL, and stress markers (MDA, SGOT, SGPT),
and a significant increase was observed in the concentrations of HDL and bodyweight when compared
to the diabetic rat. Furthermore, the extract restored the altered level of antioxidant enzymes
and glucose metabolizing hepatic key enzymes. Histopathological evaluation of the pancreas revealed
the regeneration of the β-cells in diabetic rats, which was earlier necrosed by streptozotocin.
In this study, an active constituent SMK/SO/01 was isolated from the effective ethanolic extract,
and further spectral studies confirmed it as belonging to the polyphenolic category.

Conclusion:
These findings provide scientific evidence that SMK/SO/01 has the potential to be a
potential drug candidate for diabetes mellitus and complications induced by the disease. Also, these
results prove that ethanolic extract of S. oleosa leaves exerts effective anti-diabetic activity,
which provides scientific backing for folklore medicine.
Significance of Inorganic Nitrate Supplement in Cardiovascular Health
Authors: Dudhe Rupesh , Dudhe Anshu C. , Raut Shravan D. 
Published: April 2021

Background & Objectives:
Nitric Oxide (NO) is frequently produced by the enzyme nitric
oxide synthase (NOS) and is crucial for the control and effectiveness of the cardiovascular system.
However, there is a substantial reduction in NOS activity with aging that can lead to the development
of hypertension and other cardiovascular obstacles. Fortunately, NO can also be produced
by sequential reduction of inorganic nitrates supplementation. This proves that NO from inorganic
nitrate supplements can compensate for inadequate NOS activity, thus providing cardio protective
benefits.

Discussion:
This review focuses on the general information about nitrous oxide, its types and
mechanism of action and the fact that overview of inadequate NOS activity for cardio protective
benefits was often studied for cardiovascular treatments.

Conclusion:
We concluded that the natural plant NO is essential for cardiovascular activity to target
site with desired concentration. Moreover, the researchers focused on evidence that suggested
that nitrate supplementation could help regulate blood pressure, limit progression of atherosclerosis,
and improve myocardial contractility in both healthy individuals and those with cardiovascular
diseases.
Editorial
Authors: Koga Natalia Massako , Machado Raphael Amorim , Gomide Alexandre de Avila , Filgueiras Fernando , Ramesh M 
Published: April 2021

This special issue of the Public Service Journal (RSP) brings together papers on building policy capacity for development within the Brazilian context. Starting from a broad and integrated understanding of development, which is not restricted to the context of the economic sphere, this compilation presents analyses that discuss issues relevant to the current national agenda. The accumulated imbalance of 'capacities' in various policy areas, the challenges of implementing the Sustainable Development Goals, the peculiarities of capacity mobilization in the local context, and the intersection between capacities and governance are some of the topics debated in this publication.
It is worth mentioning that this publication is a result of the debate promoted during the International Workshop on Building Capable States for Development in Latin America, held in São Paulo in December 2018 - an event promoted in a partnership between the National University of Singapore (NUS), the Getulio Vargas Foundation (FGV/EAESP), and the Institute of Applied Economic Research (IPEA). Thus, the papers presented in this special issue have been examined and discussed previously among Brazilian and international academics dedicated to the study of state capacities. The aim of publishing these papers in English is to continue to promote this sort of dialogue in international debates on the field of public policy.
On the origin of low angle normal faulting in the Southern Rio Grande Rift
Authors: Carciumaru Dana , Ortega Roberto 
Published: April 2021

La parte sur del Rift Rio Grande está definida por una serie de fallas normales de alto ángulo que separan bloques elevados de grandes cuencas de depósitos del Cenozoico. Una serie de fallas normales de bajo ángulo se encuentran en los bloques elevados y sus relaciones con la cuenca y con las estructuras montañosas es controversial. Estudios preliminares concluyeron que las fallas de bajo ángulo se formaron en una fase previa de extensión y después fueron inclinadas sobre la orientación actual de fallas más recientes. Otros estudios concluyeron que estas fallas son el resultado de un fallamiento reciente y son un factor clave en el desarrollo de las cuncas actuales y de la topografía montañosa. Por esta razón, en esta parte de la dorsal de Rift Rio Grande el análisis de esfuerzos es una tarea difícil. Fechar la edad geológica de las estructuras y el basculamiento extensivo del área son las principales fuentes de error. En este artículo reconstruimos el régimen de esfuerzos usando técnicas numéricas basadas en estadística para dos montañas del Rift del Rio Grande: East Potrillo Mountains Y Franklin Mountains. El campo de esfuerzos y la historia tectónica también se discuten. Las direcciones de las venas extensionales fueron comparadas con el campo general de esfuerzos. Se encontró que la mayoría de las fallas fueron reactivadas en la primera etapa de extensión de Rio Grande, además con la ocurrencia de un basculamiento extensivo con rotaciones. En Potrillo Mountains se requiere un proceso de corrección angular por basculamiento de W25 SE y W45 SE orientado N30W para obtener dos campos de esfuerzos homogéneos. El plano de falla corregido muestra un componente oblicuo en estos dos campos de esfuerzos; el primero corresponde a la reactivación de las fallas con el	Ïƒ1 y el	Ïƒ3 orientados N78E y N69E respectivamente mientras el segundo campo de esfuerzos es relacionado con las fallas más actuales y es orientado N64W y N61E respectivamente. En Franklin Mountains el basculamiento es menos importante sin embargo dos campos de esfuerzos con orientaciones similares pero valores de phi diferentes fueron detectados (reconocidos). La historia de esfuerzos post - Laramidica de la región es controlada de diferentes eventos extensionales que influenciaron las estructucturas pre - existentes y también generaron un sistema de falla nueva.
Alternatives to Improve Operational Traffic in Roundabouts Using Microsimulation
Authors: Rincón-Numpaque Nelson , Moreno-Anselmi Luis Ángel , Rodríguez-Polo Kelly Andrea , Gaviria-Mendoza Carlos Andrés 
Published: April 2021

Roundabout in urban arterials are likely to block roads or generate long queues of vehicles due to the constant changes on urban dynamics near to the interception. Several alternatives to modify the flow pattern or geometry and infrastructure need to be study previously to propose a final design solution of roundabout with traffic issues. In this study, a review of three alternatives to improve the operational traffic are discussed; signalized intersection, turbo-roundabouts and overpass/underpass. In addition, the application of these alternatives is evaluated in a “classic” roundabout located at Tunja city that has a maximum of 3691 Veh/h counted and it is operated in saturated condition. Microsimulation is used from a calibrated model with volume counted, vehicle composition and speeds in the VISSIM software. Results show that signalize the roundabout does not improve the operational traffic (with a reduction on 38% of approach speed) and, the turbo-roundabouts are a mid-term solution that meet the traffic demand on 15 years with a progressively loss of service (with a mean approach speed of 6.4 Km/h at 15 years). The constructions of underpass and overpass show to be the only solution that increase four times the travel speed throw the roundabout and keep acceptable speed at the end of cyclic live of intersection (18.7 Km/h at 20 years).
Technical-economic analysis of [Bmim][BF4] for the post-combustion CO2 capture at ”Termocentro” thermoelectric plant, Colombia
Authors: Amado-González Eliseo , Sánchez-Peinado Walter David , Fuentes-Ordoñez Edwin Gustavo 
Published: April 2021

In the present work, steady-state simulations of the natural gas combined cycle (NGCC) and the post-combustion CO2 capture (PCC) processes have been modelled in Aspen Plus® environment. The capture plan model was validated with data from the Colombian power plant "Termocentro" at 300MWe. A techno-economical evaluation study has been performed for both a combined cycle (gas and steam) and the PCC process. The PCC process was based on the solvent 30% (w/w) MEA-H2O and on the solvent H2O-30% (w/w)-MEA-5% (w/w))-[Bmim][Bf4]. Sensitivity analysis was carried out, giving as a result an optimum concentration of 5% (w/w) for the 1-butyl-3-methylimidazolium tetrafluoroborate ionic liquid ([Bmim] [BF4]) solvent. The study indicates how with efficient operation conditions of solvent regeneration, [Bmim][Bf4] may be used for CO2 capture plans on the future.
El paradigma de la ética en la formación contable y el enfoque de sus intervinientes
Authors: Escalante Eslendy , Becerra Anllela , Rueda-Vera Gerson 
Published: April 2021

Actualmente el mundo vive una situación llamada corrupción en donde la cultura y la economía son la excusa de los medios públicos y el detonante de las fallas en algunos cargos desempeñados bajo la gran variedad de profesiones; llegando así a discutir el tema de la ética de un profesional quien trata de incursionar a fondo en la necesidad de formación como un proceso indispensable al cual debe acceder para fortalecer su capacidad de asumir el rol en la sociedad profesional. La ética es el valor por el cual se evalúa la conducta del ser humano en la sociedad, el poder de decisión del bien o el mal, comprendiendo los principios de la actuación íntegra, honesta y honrada en el ámbito laboral de un individuo dentro de su profesión, área, departamento, puesto de trabajo u obligación delegada bajo su responsabilidad. Según las anteriores pautas sobre la ética profesional, se pretende exponer con este artículo algunos paradigmas que se han generado a lo largo de los años en el ámbito contable, el por qué se han generado, el pensamiento de los que intervienen, las consecuencias y los beneficios que ha traído consigo el olvido de mantener, efectuar, incentivar y/o motivar este importante valor. Aclaremos que un contador público es una persona con responsabilidad decisiva en la sociedad, su actuación está sujeta a procesos fiscales de personas y organizaciones donde es el mismo quien da fe pública de la información contable y financiera.
The Rate of Sample Rejection and Pre-Analytical Errors at KCMC Clinical Laboratory in Moshi, Kilimanjaro
Authors: Mosha Victor V. , Kabanyana Claudia 
Published: April 2021

Background: Over the years, modern medicine has been able to provide a better quality services to patients. However, medical error is still prevalent and has a lot of negative consequences on patients’ outcome. These may include delayed treatment, longer hospital stays, or even worsening of the patient’s condition. The aim of this study was to determine the rate of sample rejection at KCMC Clinical Laboratory and the different pre-analytical errors that contribute to it.
Methods: Data extraction sheet was used to collect information from rejection forms from January to December 2016. Information on types of sample rejected, the wards/departments from which they were collected and the clinical laboratory section in which they were to be analysed were collected.
Results: Out of the 117181 samples received from January to December 2016, 234 were rejected, giving a 0.19% rate of rejection. The highest rates of rejection were from haematology section 78 (33.3%). The major type of rejected sample was blood (86.3%) and 20% of the rejected samples came from internal medicine department, mainly from its inpatient department (13.6%). The commonest reason for rejection was unpaid specimens 84 (35.9%).
Conclusion: The impact of pre-analytical errors on patient care is not negligible. A joint collaboration of all the stakeholders involved in patient care, specimen handling and analysis, and policymaking is necessary to arrive at quick and tangible solutions. Better communication between laboratory staff and other health care personnel is essential.