bluuebunny/crossref_metadata_2025 huggingface dataset:
Purification of Glutathione Reductase from Human Erythrocytes: Inhibition Profile of Some Anti-Epileptic Drugs
Authors: DEMİR Yeliz
Published: November 2019

Glutathione reductase (GR) is found in the NADPH-dependent oxidoreductase family. GR has various important functions in the cell, such as protein and DNA biosynthesis, the detoxification of reactive oxygen species and free radicals. The purpose of this research was to perform the in vitro inhibition effects of anti-epileptic drugs (phenytoin, gabapentin, and primidone) on GR enzyme. In the current study, the GR enzyme was purified from human erythrocytes with a specific activity of 20.08 EU/mg protein and 2135.97-purification fold. To determine the inhibition effects of anti-epileptic drugs on GR enzyme, Lineweaver-Burk graphs were drawn for each inhibitor. Ki values and inhibition types were determined from these plotted graphs. The Ki values of drugs were found in ranging from 0.15± 0.03-5.74±1.14 mM. Phenytoin was shown the most effective inhibitor feature with a competitive inhibition type.
A Generalization on Right Ideals of Prime Rings with α-Derivations
Authors: ALBAYRAK Barış
Published: November 2019

In this paper, we generalize previous studies on right ideals of prime ring 𝑅 with generalized 𝛼− derivation 𝐷 and show that 𝑅 is commutative under different conditions. Also, we investigate commutative property of prime ring 𝑅 for two generalized 𝛼− derivations 𝐷 and 𝐻.
Drought Analysis in Ceyhan Basin Using Standardized Precipitation Index
Authors: ÇUHADAR Muhammed , ATIŞ Ela
Published: November 2019

Drought is defined as a disaster that affects vital activities negatively due to the decrease in the water supply caused by falling rainfall below normal levels observed over the years. Agricultural drought means that the moisture content in the soil is consistently falling below the climatically appropriate amount, so this directly affects vegetative production and indirectly affects animal production. This study aims to determine dry periods and areas in the Ceyhan Basin by using the Standardized Precipitation Index (SPI). Thus, policies that will reduce the effects of drought will be developed in the regions affected by drought. The SPI has several features that are more advanced than previous indexes, including simplicity and temporal flexibility, and allow for use in all timelines for water resources. The results have shown that the past five years have been dry and the drought has increased over the years, and it is also wiser to grow drought-resistant crops and use pressurized irrigation methods in Afşin and Elbistan, the driest districts of the basin, to improve water efficiency.
Türkiye’nin Nohut Üretiminin ARIMA Modeli ile Tahmini
Authors: BERK Ali , UÇUM İlkay
Published: November 2019

Türkiye’de nohut üretimi yaklaşık 630.000 ton düzeyinde olup, yıllara göre ekim alanında azalmaya karşın üretim miktarı da dalgalanma göstermektedir. Üretimdeki dalgalanmaya paralel olarak artan ithalat ve kişi başına tüketim, üretimde devamlılık sorunu olduğunu ortaya koymaktadır. Bu çalışmada, nohutun beslenme ve tüketim alışkanlıklarımızdaki önemi nedeniyle, Türkiye’de nohut üretim ve dış ticaretinin mevcut durumu ortaya konulmuş ve gelecek beş yıla ait (2019-2023) üretim öngörüsünde bulunulmuştur. Çalışmada, nohutun gelecek 5 yıla ilişkin üretim miktarı Box-Jenkins metodu olan ARIMA modeli ile tahmin edilmiştir. Analizde kullanılan veriler 1985-2018 dönemini kapsamaktadır. Yapılana analizler sonucunda ARIMA (1,3,1) modeli nohut üretiminin tahminine ilişkin en uygun model olarak tespit edilmiştir. Yapılan tahmine göre 2019-2023 yılları arasında nohut üretiminde artış olacağı öngörülmüştür.
HT-29 Kolon Kanser Hücre Hattında Senkronizasyon Başlatıcıların Sirkadiyen Ritimdeki Rolü
Authors: ÖZTÜRK Dilek , GÖNCÜ Beyza
Published: November 2019

Memelilerde merkezi sirkadiyen saat, hipotalamusta konumlanmıştır. Periferal saatleri nöronal ve endokrin sinyaller ile koordine etmektedir. Sirkadiyen saat gen ve proteinlerinin, merkezi saatten bağımsız olarak da periferal hücre ve dokularda ritmik ekspresyona devam ettiği yapılan çalışmalar ile gösterilmiştir. İmmortalize hücre hatlarında da ritim devam etmekte ancak hücreler arası koordinasyon bozulmaktadır. Hücre hatları kanser ile ilgili yolaklar ve sirkadiyen ritim ilişkisini çalışmak için en elverişli aracılardır. Ancak öncelikle ritmik gen ekspresyonunun devam ettiğinin gösterilmesi gerekmektedir. Hücreler arası senkronizasyonun sağlanması için bazı aracılar kullanılmaktadır. Bu çalışmadaki amacımız; güçlü senkronizasyon başlatıcılar olan fetal bovin serum ve deksametazonun HT-29 kolon kanseri hücre hattında PER2 saat geninin ekspresyonu üzerindeki rolünü incelemektir. Bu amaçla; fetal bovin serum veya deksametazon uygulamasını takiben HT-29 hücreleri altı farklı zamanda toplanarak RNA izole edilmiş ve PER2 ve ACTB gen ekspresyonları gerçek zamanlı PZR deneyi ile kantifiye edilmiştir. Sonuçlar Lineer Cosinor analizleri ile değerlendirilmiştir. PER2 genine ait mRNA ekspresyonlarındaki değişim ACTB referans geni ile kıyaslanarak değerlendirildiğinde, her iki başlatıcı ile de ritmik ekspresyonun sağlandığı gösterilmiştir. Her iki başlatıcı ile de Cosinor analizine göre 18 ve 24 saatlik periyot sürelerinde anlamlı ritmik değişim gösterilmiştir. Ek olarak deksametazon ile başlatılan senkronizasyonda, 24 saatlik periyot süresinde zaman dilimindeki güven aralığının anlamlı olduğu gözlenmiştir. HT-29 hücre hattında iki farklı başlatıcı ile yapılan bu çalışmada sirkadiyen periyot sürelerinin hesaplanmasında başlatıcıların değişkenlik gösterebildiği tespit edilmiştir.
Satureja cuneifolia Ten. (Lamiaceae) Türünün Farklı Kurutma Yöntemleri Uygulanarak Uçucu Yağ Oranlarının ve Uçucu Yağ Bileşenlerinin Tespit Edilmesi
Authors: PAŞA Cenk , KILIÇ Turgut , SELVİ Selami , ÖZER SAĞIR Züleyha
Published: November 2019

Bu araştırmada, Satureja cuneifolia Ten. türü üzerinde farklı kurutma yöntemleri uygulanarak farklı diurnal dönemlerde uçucu yağ oranı ve uçucu yağ bileşenlerinin belirlenmesi amaçlanmıştır. Bu amaçla araştırmada S. cuneifolia türünün uçucu yağ oranları ve uçucu yağ bileşenleri tespit edilmiştir. S. cuneifolia’nın yaprakları, üç farklı kurutma yöntemi kullanılarak (güneşte 10 saat, gölgede 16 saat ve etüvde 40 °C'de 10 saat) kurutulmuştur. Uçucu yağ hidrodistilasyon yöntemi ile elde edildikten sonra uçucu yağ bileşenleri GC-MS cihazı ile analiz edilmiştir. Farklı kurutma yöntemlerinin uçucu yağ oranı üzerine etkisi istatistiki olarak önemli bulunmuştur. Elde edilen verilere göre en yüksek uçucu yağ oranı gölgede kurutmada (% 1.88), en düşük uçucu yağ oranı ise etüvde kurutmada (% 1.78) tespit edilmiştir. Uçucu yağ bileşenlerinden carvacrol ve p-cymene gölgede kurutma yönteminde en yüksek değerlere ulaşmıştır.
CuO-grafen Nanokompozitlerinde Etanol Elektrooksidasyonu
Authors: DOĞAN Hülya
Published: November 2019

Bu çalışmada Au elektrot yüzeyinde CuO-grafen (CuO/G) nanokompozitlerinin tek aşamalı elektrokimyasal sentezi gerçekleştirilmiştir. CuO/G yapılarının analitik karakterizasyonu için XRD ve EDS teknikleri kullanılmıştır. Morfolojik karakterizasyonu ise SEM kullanılarak yapılmıştır. CuO/G kompozitlerinin etanol elektro-oksidasyon reaksiyonunda elektrokatalizör olarak kullanımı incelenmiş ve dönüşümlü voltametri tekniği kullanılarak katalitik özellikleri araştırılmıştır. Etanol oksidasyonu için en yüksek akım yoğunluğu CuO/G kompozitinde elde edilmiştir. Sentezlenen nanokompozit filmin yakıt hücrelerinde elektrot malzemesi olarak kullanılabileceği belirlenmiştir.
Detección del gen fusión PML-RARα en pacientes colombianos con leucemia mieloide aguda
Authors: Pérez Aura Cristina , Prada-Arismendy Jeanette , Castillo-Peñuela Erwing , Castellanos William
Published: November 2019

Introducción: la leucemia promielocítica aguda es un subtipo de leucemia mieloide aguda caracterizada por la presencia de una translocación entre los cromosomas 15 y 17 que provoca la formación de un gen fusión denominado PML/RARα. Determinar la presencia de este gen fusión es crítico para estos pacientes ya que su presencia hace el diagnóstico de la enfermedad, aún sin tener resultados de patología. Con esta investigación se busca ajustar e implementar una prueba altamente sensible y específica para la detección del reordenamiento PML/RARα.

Métodos: a partir de sangre periférica se extrajo RNA de pacientes diagnosticados con leucemia mieloide aguda en dos instituciones de Antioquia (Colombia). Se realizó RT-PCR anidada para la detección de PML/RARα, ajustando un protocolo previamente publicado.

Resultados: se ajustó y estandarizó un método para detectar mediante RT-PCR el gen fusión PML/RARα. Mediante esta técnica se logró identificar la traslocación en cuatro pacientes (22 %) de la cohorte estudiada.

Conclusiones: los resultados están de acuerdo con estudios previos. La detección de esta y otras alteraciones citogenéticas mediante pruebas moleculares permitirá tener información valiosa a nivel de diagnóstico y pronóstico de los pacientes con leucemia mieloide aguda en Antioquia.
What happens to patients who leave without being seen in an emergency department?
Authors: Cardozo-Ocampo Alejandro , Grajales Yeimi Natalia
Published: November 2019

Patients who leave without being seen from the emergencys services represent a risk, because some of them may have diseases that can eventually lead to major adverse events.
Relación de calidad de vida y salud oral en la población adolescente
Authors: Cerón Bastidas Ximena Andrea
Published: November 2019

La calidad de vida, comprendida desde la percepción del individuo sobre suposición en la vida está relacionada directamente con la salud oral, la cual se considera parte de la salud humana integral. En este sentido, los adolescentes se han considerado un grupo de riesgo por múltiples factores que pueden afectar su calidad de vida, tales como la pobreza, acceso a la salud, estrato socioeconómico, adicionalmente a los cambios biológicos y fisiológicos de esta etapa. Esta transición de la niñez a la edad adulta puede impactar negativamente la salud oral. La aparición de enfermedades como caries dental, gingivitis y/o periodontitis, entre otras, puede generar problemas psicosociales asociados con la estética y la autoestima. Estarevisión temática tomó en cuenta información a partir del 2001 e incluyó estudios realizados en poblaciones adolescentes donde se estableció la relación entre calidad de vida y la salud oral.
Osteonecrose dos maxilares relacionada ao uso de medicações: Diagnóstico, tratamento e prevenção
Authors: Vilela-Carvalho Lidia Nunes , Tuany-Duarte Nathália , Andrade-Figueiredo Marília , López-Ortega Karem
Published: November 2019

A osteonecrose dos maxilares é uma alteração óssea que pode ser induzidapelo uso de drogas indicadas para o tratamento de pacientes comosteoporose e tumores malignos. Inicialmente acreditava-se estar associadaapenas ao uso de bisfosfonatos, atualmente sabe-se que tambémestá vinculada ao uso de outro antirresorptivo (denosumabe) e de antiangiogênico(bevacizumabe). Não se sabe ao certo qual é o mecanismo dedesenvolvimento e ainda não existe um protocolo único de tratamento definido,mas existem diversos trabalhos sendo publicados sobre o tema.Com a crescente quantidade de casos relatados é de suma importânciaque o profissional de saúde saiba diagnosticar, identificar os riscos e trataressa condição.
Effects of surface loading on groundwater flow and skeletal deformation
Authors: Yu Qingyang , Wang Chengbin , Dai Zhenxue , Ran Xinglong , Amooie Mohammad Amin , Soltanian Mohamad Reza , Soltanian Mojtaba
Published: November 2019

This paper proposes a relationship for the physics and mechanics constants of porous media related to water storage rate and ground settlement under a surface load variation condition. This provides the basis for accurate calculation of ground subsidence. Traditional equations for vertical deformation, groundwater flow and land subsidence due to surface loading were developed using Jacob's assumptions. This paper derives a skeletal elastic specific storage rate. The new deformation and flow equations are similar to the traditional ones based on Jacob's assumptions except that the pore-water head in the traditional equations corresponds with the margin between the pore-water head and the water-column height given in the proposed equations representing the surface load. The analysis show that increasing the surface loading leads to land subsidence, rise in pore-water head and decrease in elastic water storage capacity. The maximum subsidence is equivalent to the subsidence triggered by lowering the water head to the equivalent water column height. The maximum rise of the water head is also equal to the equivalent water column height. The maximum water released to a specific volume of porous medium is close to that resulting from reduction in the water head by the equivalent column height.
Effects of IGF-1 on the Cardiovascular System
Authors: Obradovic Milan , Zafirovic Sonja , Soskic Sanja , Stanimirovic Julijana , Trpkovic Andreja , Jevremovic Danimir , Isenovic Esma R.
Published: November 2019

:

Cardiovascular (CV) diseases are the most common health problems worldwide, with a permanent increase in incidence. Growing evidence underlines that insulin-like growth factor 1 (IGF-1) is a very important hormone responsible for normal CV system physiology. IGF-1 is an anabolic growth hormone, responsible for cell growth, differentiation, proliferation, and survival. Despite systemic effects, IGF-1 exerts a wide array of influences in the CV system affecting metabolic homeostasis, vasorelaxation, cardiac contractility and hypertrophy, autophagy, apoptosis, and antioxidative processes. The vasodilatory effect of IGF-1, is achieved through the regulation of the activity of endothelial nitric oxide synthase (eNOS) and, at least partly, through enhancing inducible NOS (iNOS) activity. Also, IGF-1 stimulates vascular relaxation through regulation of sodium/potassiumadenosine- triphosphatase. Numerous animal studies provided evidence of diverse influences of IGF-1 in the CV system such as vasorelaxation, anti-apoptotic and prosurvival effects. Human studies indicate that low serum levels of free or total IGF-1 contribute to an increased risk of CV and cerebrovascular disease. Large human trials aiming at finding clinical efficacy and outcome of IGF-1-related therapy are of great interest.

:

We look forward to the development of new IGF 1 therapies with minor side effects. In this review, we discuss the latest literature data regarding the function of IGF-1 in the CV system in the physiological and pathophysiological conditions.
An Update on the Management of Severe Cutaneous Drug Hypersensitivity Reactions
Authors: Gelincik Aslı , Cavkaytar Ozlem , Kuyucu Semanur
Published: November 2019

Severe cutaneous drug hypersensitivity reactions involve of different mechanisms , some of which are
life-threatening, such as Stevens-Johnson syndrome/toxic epidermal necrolysis, drug reaction with eosinophilia
and systemic symptoms, acute generalized exanthematous pustulosis, generalized bullous fixed drug eruptions,
serum sickness and serum sickness-like reaction and drug-induced vasculitis. These reactions may have substantial
morbidity and mortality. In the past years, successive studies have provided new evidence regarding the
pathogenesis of some of these severe reactions and revealed that underlying mechanisms are highly variable.
Since these reactions have unique presentations and distinct pathomechanisms, the treatment methods and response
rates might be different among various entities. Although supportive and local therapies are sufficient in
some of these reactions, targeted immunosuppressive treatments and even mechanistic therapies such as plasmapheresis
may be required in severe ones. However, there is still insufficient evidence to support the best treatment
options for these patients since number of patients and large-scale studies are limited. In this review, conventional
and new treatment options for severe cutaneous drug hypersensitivity reactions are presented in detail in
order to provide the contemporary approaches to lessen the morbidity and mortality relevant to these severe iatrogenic
diseases.
Cisplatin Toxicology: The Role of Pro-inflammatory Cytokines and GABA Transporters in Cochlear Spiral Ganglion
Authors: Gao Dongmei , Yu Hong , Li Bo , Chen Li , Li Xiaoyu , Gu Wenqing
Published: November 2019

Background:

The current study was conducted to examine the specific activation of pro-inflammatory
cytokines (PICs), namely IL-1β, IL-6 and TNF-α in the cochlear spiral ganglion of rats after ototoxicity induced
by cisplatin. Since γ-aminobutyric acid (GABA) and its receptors are involved in pathophysiological processes of
ototoxicity, we further examined the role played by PICs in regulating expression of GABA transporter type 1
and 3 (GAT-1 and GAT-3), as two essential subtypes of GATs responsible for the regulation of extracellular
GABA levels in the neuronal tissues.

Methods:

ELISA and western blot analysis were employed to examine the levels of PICs and GATs; and auditory
brainstem response was used to assess ototoxicity induced by cisplatin.

Results:

IL-1β, IL-6 and TNF-α as well as their receptors were significantly increased in the spiral ganglion of
ototoxic rats as compared with sham control animals (P<0.05, ototoxic rats vs. control rats). Cisplatin-ototoxicity
also induced upregulation of the protein levels of GAT-1 and GAT-3 in the spiral ganglion (P<0.05 vs. controls).
In addition, administration of inhibitors to IL-1β, IL-6 and TNF-α attenuated amplification of GAT-1 and GAT-3
and improved hearing impairment induced by cisplatin.

Conclusion:

Our data indicate that PIC signals are activated in the spiral ganglion during cisplatin-ototoxicity
which thereby leads to upregulation of GABA transporters. As a result, it is likely that de-inhibition of GABA
system is enhanced in the cochlear spiral ganglion. This supports a role for PICs in engagement of the signal
mechanisms associated with cisplatin-ototoxicity, and has pharmacological implications to target specific PICs
for GABAergic dysfunction and vulnerability related to cisplatin-ototoxicity.
Toxicity Mechanism of Gadolinium Oxide Nanoparticles and Gadolinium Ions in Human Breast Cancer Cells
Authors: Akhtar Mohd Javed , Ahamed Maqusood , Alhadlaq Hisham , Alrokayan Salman
Published: November 2019

Background:

Due to the potential advantages of Gadolinium Nanoparticles (NPs) over gadolinium elements, gadolinium based NPs are currently being explored in the field of MRI. Either in elemental form or nanoparticulate form, gadolinium toxicity is believed to occur due to the deposition of gadolinium ion (designated as Gd3+ ion or simply G ion).

Objective:

There is a serious lack of literature on the mechanisms of toxicity caused by either gadolinium-based NPs or ions. Breast cancer tumors are often subjected to MRIs, therefore, human breast cancer (MCF-7) cells could serve as an appropriate in vitro model for the study of Gadolinium Oxide (GO) NP and G ion.

Methods:

Cytotoxicity and oxidative damage was determined by quantifying cell viability, cell membrane damage, and Reactive Oxygen Species (ROS). Intracellular Glutathione (GSH) was measured along with cellular Total Antioxidant Capacity (TAC). Autophagy was determined by using Monodansylcadaverine (MDC) and Lysotracker Red (LTR) dyes in tandem. Mitochondrial Membrane Potential (MMP) was measured by JC-1 fluorescence. Physicochemical properties of GO NPs were characterized by field emission transmission electron microscopy, X-ray diffraction, and energy dispersive spectrum.

Results:

A time- and concentration-dependent toxicity and oxidative damage was observed due to GO NPs and G ions. Bax/Bcl2 ratios, FITC-7AAD double staining, and cell membrane blebbing in phase-contrast images all suggested different modes of cell death induced by NPs and ions.

Conclusion:

In summary, cell death induced by GO NPs with high aspect ratio favored apoptosis-independent cell death, whereas G ions favored apoptosis-dependent cell death.
Common Pathological Mechanisms and Risk Factors for Alzheimer’s Disease and Type-2 Diabetes: Focus on Inflammation
Authors: Moyse Emmanuel , Haddad Mohamed , Benlabiod Camelia , Ramassamy Charles , Krantic Slavica
Published: November 2019

Background :

Diabetes is considered as a risk factor for Alzheimer’s Disease, but it is yet unclear whether this pathological link is reciprocal. Although Alzheimer’s disease and diabetes appear as entirely different pathological entities affecting the Central Nervous System and a peripheral organ (pancreas), respectively, they share a common pathological core. Recent evidence suggests that in the pancreas in the case of diabetes, as in the brain for Alzheimer’s Disease, the initial pathological event may be the accumulation of toxic proteins yielding amyloidosis. Moreover, in both pathologies, amyloidosis is likely responsible for local inflammation, which acts as a driving force for cell death and tissue degeneration. These pathological events are all inter-connected and establish a vicious cycle resulting in the progressive character of both pathologies.

Objective:

To address the literature supporting the hypothesis of a common pathological core for both diseases.

Discussion:

We will focus on the analogies and differences between the disease-related inflammatory changes in a peripheral organ, such as the pancreas, versus those observed in the brain. Recent evidence suggesting an impact of peripheral inflammation on neuroinflammation in Alzheimer’s disease will be presented.

Conclusion:

We propose that it is now necessary to consider whether neuroinflammation in Alzheimer’s disease affects inflammation in the pancreas related to diabetes.
Synthesis, Biological Evaluation and Molecular Docking Studies of Novel Di-hydropyridine Analogs as Potent Antioxidants
Authors: Sudhana Saddala Madhu , Adi Pradeepkiran Jangampalli
Published: November 2019

Aims:

The aim of this study is to synthesize, characterize and biological evaluation of 3-ethyl 5-
methyl2-(2-aminoethoxy)-4-(2-chlorophenyl)-1,4-dihydropyridine-3,5-dicarboxylate derivatives.

Background:

An efficient synthesis of two series of novel carbamate and sulfonamide derivatives of amlodipine,
3-ethyl 5-methyl 2-(2-aminoethoxy)-4-(2-chlorophenyl)-1,4-dihydropyridine-3,5-dicarboxylate (amlodipine)
1 were chemical synthesized process.

Materials & Methods:

In this process, various chloroformates 2(a-e) and sulfonyl chlorides 4(a-e) on reaction
with 1 in the presence of N,N–dimethylpiperazine as a base in THF at 50-550 oC, the corresponding title compounds
3(a-e) and 5(a-e) in high yields. Furthermore, the compounds 3(a-e) and 5(a-e) were evaluated for antioxidant
activity (DPPH method), metal chelating activity, hemolytic activity, antioxidant assay (ABTS
method), cytotoxicity, molecular docking and in silico ADMET properties.

Result:

Results revealed that 5a, 5e, 3d, 3a and 5c exhibited high antioxidant, metal chelating activities, but
5a, 5e and 3d exhibited low activity. The molecular docking studies and ADMET of suggested ligands showed
the best binding energies and non-toxic properties.

Conclusion:

The present in silico and in vitro evaluations suggested that these dihydropyridine derivatives act
as potent antioxidants and chelating agents which may be useful in treating metals induced oxidative stress
associated diseases.
In-silico Subtractive Proteomic Analysis Approach for Therapeutic Targets in MDR Salmonella enterica subsp. enterica serovar Typhi str. CT18
Authors: Rahman Noor , Muhammad Ijaz , Nayab Gul E. , Khan Haroon , Filosa Rosanna , Xiao Jianbo , Hassan Sherif T.S.
Published: November 2019

Objective:

In the present study, an attempt has been made for subtractive proteomic analysis
approach for novel drug targets in Salmonella enterica subsp. enterica serover Typhi str.CT18 using
computational tools.

Method:

Paralogous, redundant and less than 100 amino acid protein sequences were removed by using
CD-HIT. Further detection of bacterial proteins which are non-homologous to host and are essential for
the survival of pathogens by using BLASTp against host proteome and DEG`s, respectively. Comparative
Metabolic pathways analysis was performed to find unique and common metabolic pathways. The
non-redundant, non-homologous and essential proteins were BLAST against approved drug targets for
drug targets while Psortb and CELLO were used to predict subcellular localization.

Result:

There were 4473 protein sequences present in NCBI Database for Salmonella enterica subsp.
enterica serover Typhi str. CT18 out of these 327 were essential proteins which were non-homologous
to human. Among these essential proteins, 124 proteins were involved in 19 unique metabolic pathways.
These proteins were further BLAST against approved drug targets in which 7 cytoplasmic proteins
showed druggability and can be used as a therapeutic target.

Conclusion:

Drug targets identification is the prime step towards drug discovery. We identified 7 cytoplasmic
druggable proteins which are essential for the pathogen survival and non-homologous to human
proteome. Further in vitro and in vivo validation is needed for the evaluation of these targets to combat
against salmonellosis.
Cytotoxicity of Anchusa arvensis Against HepG-2 Cell Lines: Mechanistic and Computational Approaches
Authors: Hussain Sajid , Ullah Farhat , Sadiq Abdul , Ayaz Muhammad , Shah Azhar-ul-Haq Ali , Ali Shah Syed Adnan , Shah Syed Majid , Nadhman Akhtar , Ullah Farman , Wadood Abdul , El-Shazly Mohamed
Published: November 2019

Background:

Liver cancer is a devastating cancer with increasing incidence and mortality
rates worldwide. Plants possess numerous therapeutic properties, therefore the search for novel, naturally
occurring cytotoxic compounds is urgently needed.

Methods:

The anticancer activity of plant extracts and isolated compounds from Anchusa arvensis (A.
arvensis) were studied against the cell culture of HepG-2 (human hepatocellular carcinoma cell lines)
using 3-(4,5-Dimethylthiazol-yl)-diphenyl tetrazoliumbromide (MTT) assay. Apoptosis was investigated
by performing Acridine orange –ethidium bromide staining, styox green assay and DNA interaction
study. We also used tools for computational chemistry studies of isolated compounds with the tyrosine
kinase.

Results:

In MTT assay, the crude extract caused a significant cytotoxic effect with IC50 of 34.14 ± 0.9
μg/ml against HepG-2 cell lines. Upon fractionation, chloroform fraction (Aa.Chm) exhibited the highest
antiproliferative activity with IC50 6.55 ± 1.2 μg/ml followed by ethyl acetate (Aa.Et) fraction (IC50,
24.59 ± 0.85 μg/ml) and n-hexane (Aa.Hex) fraction (IC50 29.53 ± 1.5μg/ml). However, the aqueous
(Aa.Aq) fraction did not show any anti-proliferative activity. Bioactivity-guided isolation led to the isolation
of two compounds which were characterized as para–methoxycatechol (1) and decane (2) through
various spectroscopic techniques. Against HepG-2 cells, compound 1 showed marked potency with IC50
6.03 ± 0.75 μg/ml followed by 2 with IC50 18.52 ± 1.9 μg/ml. DMSO was used as a negative control and
doxorubicin as a reference standard (IC50 1.3 ± 0.21 μg/ml). It was observed that compounds 1-2 caused
apoptotic cell death evaluated by Acridine orange –ethidium bromide staining, styox green assay and
DNA interaction study, therefore both compounds were tested for molecular docking studies against tyrosine
kinase to support cytotoxic activity.

Conclusion:

This study revealed that the plant extracts and isolated compounds possess promising antiproliferative
activity against HepG-2 cell lines via apoptotic cell death.
Identification of Potential Dual Negative Allosteric Modulators of Group I mGluR Family: A Shape Based Screening, ADME Prediction, Induced Fit Docking and Molecular Dynamics Approach Against Neurodegenerative Diseases
Authors: Prabhu Sitrarasu Vijaya , Singh Sanjeev Kumar
Published: November 2019

Background:

Glutamate is the principal neurotransmitter in the human brain that exerts its
effects through ionotropic glutamate receptors (iGluRs) and metabotropic glutamate receptors
(mGluRs). The mGluRs are a class of C GPCRs that play a vital role in various neurobiological functions,
mGluR1 and mGluR5 are the two receptors distributed throughout the brain involved in cognition,
learning, memory, and other important neurological processes. Dysfunction of these receptors can cause
neurodegenerative diseases such as Alzheimer's disease, Parkinson's disease, X-fragile syndrome, anxiety,
depression, etc., hence these receptors are high profile targets for pharmaceutical industries.

Objective:

The objective of our study is to find the novel dual negative allosteric modulators to regulate
both mGluR1 and mGluR5.

Methods:

In this study, shape screening protocol was used to find the dual negative allosteric modulators
for both mGluR1 and mGluR5 followed by ADME prediction, induced-fit docking (IFD) and molecular
dynamics simulations. Further, DFT analysis and MESP studies were carried out for the selected
compounds.

Results:

Around 247 compounds were obtained from the eMolecules database and clustered through the
CANVAS module and filtered with ADME properties. Furthermore, IFD revealed that the top four
compounds (16059796, 25004252, 4667236 and 11670690) having good protein-ligand interactions and
binding free energies. The molecular electrostatic potential of the top compounds shows interactions in
the amine group and the oxygen atom in the negative potential regions. Finally, molecular dynamics
simulations were performed with all the selected as well as the reported compound 29 indicates that the
screened hits have better stability of protein ligand complex.

Conclusion:

Hence, from the results, it is evident that top hits 16059796, 25004252, 4667236 and
11670690 could be a novel and potent dual negative allosteric modulators for mGluR1 and mGluR5.
Unexpected Reactions of Terminal Alkynes in Targeted “Click Chemistry’’ Coppercatalyzed Azide-alkyne Cycloadditions
Authors: Ali Tammar H. , Heidelberg Thorsten , Hussen Rusnah S.D. , Tajuddin Hairul A.
Published: November 2019

Background:

High efficiency in terms of reaction yield and purity has led to the extensive
utilization of copper-catalyzed azide-alkyne cycloaddition (CuAAC) in various fields of chemistry. Its
compatibility with low molecular weight alcohols promotes the application in surfactant synthesis to tackle the
miscibility constraints of the reactants.

Objective:

For the tuning of surfactant properties, double click coupling of the antipode precursors was
attempted. Failure of the CuAAC to provide the targeted product in combination with unexpected reaction
outputs led to an investigation of the side reaction.

Methods:

The CuAAC-based coupling of sugar azide with propargyl building block in the presence of copper-
(I) catalyst exclusively led to the mono-coupling product in a respectable yield of almost 80%. Besides the
unexpected incomplete conversion, the loss of the remaining propargyl group, as indicated by both NMR and
MS. On the other hand, application of substantial amounts of CuSO4 under reducing conditions in refluxing
toluene/water furnished the alkyne dimer in a moderate yield of 43%, while no change of azide compound was
noticed.

Results:

The Cu(I)-catalyst applied for azide-alkyne cycloadditions enables the homo-coupling of certain
terminal alkynes at a higher temperature. Moreover, aromatic propargyl ethers may be cleaved to furnish the
corresponding phenol. The copper-catalyzed coupling appeared highly sensitive towards the alkyne compound.
Only selected derivatives of propargyl alcohol were successfully dimerized.

Conclusions:

The observed failure of the Huisgen reaction for the synthesis of sugar-based surfactants may
indicate non-recognized constrains of the reaction, which could affect its wide application in bioconjugation.
The temperature requirement for the alternative dimerization of terminal alkynes renders this side reaction nonrelevant
for typical click couplings, while narrow substrate diversity and moderate yield limit its synthetic
application.
Development of Novel Glitazones as Antidiabetic Agents: Molecular Design, Synthesis, Evaluation of Glucose Uptake Activity and SAR Studies
Authors: Srinivas Mahendra Gowdru , Prabhakaran Prabitha , Mandal Subhankar Probhat , Sivamani Yuvaraj , Guddur Pranesh , Kumar Bommenahally Ravanappa Prashantha
Published: November 2019

Background:

Thiazolidinediones and its bioisostere, namely, rhodanines have become
ubiquitous class of heterocyclic compounds in drug design and discovery. In the present study, as
part of molecular design, a series of novel glitazones that are feasible to synthesize in our laboratory
were subjected to docking studies against PPAR-γ receptor for their selection.

Methods and Results:

As part of the synthesis of selected twelve glitazones, the core moiety, pyridine
incorporated rhodanine was synthesized via dithiocarbamate. Later, a series of glitazones were
prepared via Knovenageal condensation. In silico docking studies were performed against PPARγ
protein (2PRG). The titled compounds were investigated for their cytotoxic activity against 3T3-L1
cells to identify the cytotoxicity window of the glitazones. Further, within the cytotoxicity window,
glitazones were screened for glucose uptake activity against L6 cells to assess their possible antidiabetic
activity.

Conclusion:

Based on the glucose uptake results, structure activity relationships are drawn for the
title compounds.
An Increasing Role of Polyphenols as Novel Therapeutics for Alzheimer’s: A Review
Authors: Karim Nasiara , Khan Haroon , Khan Imran , Guo Ouyang , Sobarzo-Sánchez Eduardo , Rastrelli Luca , Kamal Mohammad A.
Published: November 2019

Alzheimer’s disease (AD) is the most prevalent neurodegenerative disorder, with approximately
29 million older people suffering from this disease worldwide. This number is expected
to become triple by 2050. AD is a complex and multifactorial neurodegenerative condition,
characterized by complex pathology including oxidative stress, formation of aggregates of amyloid
and tau, enhanced immune responses, metal deposition and disturbances in cholinesterase enzymes.
There is no effective pharmacological treatment for combating the disease to date. The ineffectiveness
of current pharmacological interventions in AD has led scientists to search for more
safe and effective alternative therapeutic agents. Thus, natural products have become an important
avenue for drug discovery in AD research. In this regard, polyphenols are natural products that
have been shown to be effective in the modulation of the type of neurodegenerative changes seen
in AD, suggesting a possible therapeutic role. The present review focuses on the chemistry of
polyphenols, clinical studies for evaluating polyphenols as effective alternatives in AD treatment,
cellular and molecular aspects of polyphenols in improving cognitive deficits and the current challenges
and futuristic approaches to use polyphenols as safe and effective therapeutic agents in AD
treatment.
Bioactive Compounds and Distinctive Pharmacological Activity Guided Review of Aegle marmelos: A Miraculous Plant of Indigenous Medicine System
Authors: Ghosh Sourav , Kumar Arvind , Sachan Neetu , Chandra Phool
Published: November 2019

Background:

It is always thought that traditional herbal drugs are safe, effective and economical
and are used worldwide for healing purposes. Aegle marmelos, belonging to family Rutaceae, is
an important medicinal plant of the indigenous medicine system in India. Despite the study on ethnobotanical
uses and the presence of bioactive compounds, there was only a handful of research on A. marmelos.
The therapeutic use of bioactive compounds is not explored properly.

Objective:

The objective of this study is to provide comprehensive data on the botanical description,
ethnobotany, isolated bioactive compounds and their therapeutic effects according to the pharmacology
of A. marmelos and its future prospects for further scientific investigation for the development of effective
bioactive compounds.

Methods:

Literature searches were performed in various databases, such as PubMed, SciFinder and
Google Scholar, for peer-reviewed research literature pertaining to the bioactive compounds present and
distinctive pharmacological activities of A. marmelos.

Results:

The literature review indicates that different parts of A. marmelos possess various ethnobotanical
uses. A large number of bioactive compounds isolated from different parts of the plant were reviewed
which mainly belong to alkaloids, terpenoids, steroids, coumarins, flavonoids and carbohydrate
in nature. The plant also possesses a wide range of pharmacological activities, such as antidiarrheal,
antimicrobial, anticancer, hepatoprotective, antifertility, anti-inflammatory, wound healing, radioprotective,
hypoglycemic and cardioprotective activity.

Conclusion:

It is clearly proven that different parts of A. marmelos possess numerous therapeutic effects
for treating various ailments of human beings. As the scientists anticipated to develop new drugs
from natural sources, investigation of modern drugs from A. marmelos should be emphasized. Still,
extensive research studies are required on A. marmelos as it is the most important plant of the indigenous
medicine system in India. Therefore, this review could be used as a good source of information for
researchers who wish to proceed their exploration of A. marmelos.
Effect of Pregnenolone Derivatives on the Selective Inhibition of 5α-Reductase 2 Activity
Authors: Cabeza Marisa , Bautista Lucero , Bratoeff Eugene , Soriano Juan , Heuze Yvonne
Published: November 2019

Background:

Benign prostatic hyperplasia and prostate cancer are androgen-dependent diseases, and dihydrotestosterone (DHT), a 5α-reduced metabolite of testosterone (T), has been implicated as a causative factor in the progression of these diseases. The 5α-reductase enzyme (5α-R) converts T to DHT, which is responsible for increasing cell proliferation, and hence inhibition of this enzyme could lead to potential treatments for these afflictions.

Objective:

This study focused on evaluating the biological activity of three series of pregnenolone derivatives as inhibitors of 5α-R and as antiandrogens on androgen-dependent glands.

Method:

To determine the biological activity of these compounds, we evaluated the effect of each one on suppressing the activity of both types of isozymes of 5α-R (1 and 2) by 50% (IC50). Using animal studies, we assessed the effect of these derivatives on the weight of the prostate, seminal vesicles, and diameter of the flank organs of castrated hamsters previously dosed with 1 mg/Kg T.

Results:

In vitro experiments showed that derivatives 1f, 2b, and 3d were very effective inhibitors of the activity of 5α-R2, showing IC50 values of 21.8, 20, and 15 nM, respectively. Derivatives 2b and 3b showed a lower inhibition effect on 5α-R1.

:

The data also indicated that derivatives 2b, 1f, 3b, and 3d were very active in reducing prostate weight in the hamster model of benign prostatic hyperplasia.

Discussion:

Pharmacological experiments showed that pregnenolone derivatives possess an antiandrogenic effect because of the inhibition of DHT production in androgen-dependent glands.

Conclusion:

The pregnenolone derivatives studied suppressed type 2 5α-reductase activity and because of this, the weight and dimension of androgen-dependent organs were decreased.
Somatostatin Type 2 Receptor Antibody Enhances Mechanical Hyperalgesia in the Dorsal Root Ganglion Neurons after Sciatic Nerve-pinch Injury: Evidence of Behavioral Studies and Bax Protein Expression
Authors: Xiang Qiong , Li Jing-Jing , Li Chun-Yan , Tian Rong-Bo , Li Xian-Hui
Published: November 2019

Background:

Our previous study has indicated that somatostatin potently inhibits neuropathic pain through the activation of its type 2 receptor (SSTR2) in mouse dorsal root ganglion and spinal cord. However, the underlying mechanism of this activation has not been elucidated clearly

Objective:

The aim of this study is to perform the pharmacological studies on the basis of sciatic nerve-pinch mice model and explore the underlying mechanism involving SSTR2.

Methods:

On the basis of a sciatic nerve-pinch injury model, we aimed at comparing the painful behavior and dorsal root ganglion neurons neurochemical changes after the SSTR2 antibody (anti- SSTR2;5μl,1μg/ml) administration in the mouse.

Results:

After pinch nerve injury, we found that the mechanical hyperalgesia and severely painful behavior (autotomy) were detected after the application of SSTR2 antibody (anti-SSTR2; 5μl, 1μg/ml) on the pinch-injured nerve. The up-regulated phosphorylated ERK (p-ERK) expression and the apoptotic marker (i.e., Bax) were significantly decreased in DRGs after anti-SSTR2 treatment.

Conclusion:

The current data suggested that inhibitory changes in proteins from the apoptotic pathway in anti-SSTR2-treated groups might be taking place to overcome the protein deficits caused by SSTR2 antibody and supported the new therapeutic intervention with SSTR2 antagonist for neuronal degeneration following nerve injury.
Preventive Effects of Mallotus japonicus Cortex Extracts on Dextran Sulfate Sodium-Induced Ulcerative Colitis in C57 BL/6J Mice
Authors: Kimura Yoshiyuki
Published: November 2019

Background:

The cortex of Mallotus japonicus (Euphorbiaceae) has traditionally been
used to treat gastric ulcers, duodenal ulcers, and gastric hyperacidity in Japan. A large number of
studies have recently focused on its effects on Inflammatory Bowel Disease (IBD).

Objective:

The aim of the present study was to examine the effects of M. japonicus (MJ) extracts on
large intestinal diarrhea and inflammation using Inflammatory Bowel Disease (IBD) mouse models.

Methods:

The present study used 3% Dextran Sulfate Sodium (DSS)-treated colitis models. Red
blood cell, platelet, and leukocyte counts in addition to hematocrit (Ht), hemoglobin (Hb), and colonic
cytokine and chemokine levels were measured in DSS-treated C57BL/6J mice during the experimental
period.

Results:

The Disease Activity Index (DAI) was lower in 3% DSS-treated mice orally administered
MJ (200 and 500 mg/kg) than in mice administered 3% DSS only. Furthermore, MJ inhibited decreases
in red blood cell and platelet counts as well as Hb and Ht levels in DSS-treated mice. Colon
histology using direct fast scarlet staining revealed that MJ prevented mucosal membrane ulceration
and eosinophil infiltration of the mucosal membrane induced by the DSS treatment. Increases in
colonic Monocyte Chemoattractant Protein 1 (MCP)-1, interleukin (IL)-1β, and Tumor Necrosis
Factor (TNF)-α levels in DSS-treated mice were reduced by orally administered MJ extracts.

Conclusion:

The present results suggest that M. japonicus cortex extracts are an effective treatment
for IBD through the inhibition of increases in colonic IL-1β, TNF-α, and MCP-1 levels and eosinophil
infiltration of the colon in DSS-treated mice.
Caracterización estructural de una comunidad arbórea de un sistema silvopastoril en una zona de transición florística de Nuevo León
Authors: Canizales-Velázquez Pamela Anabel , Aguirre-Calderón Óscar Alberto , Alanís-Rodríguez Eduardo , Rubio-Camacho Ernesto , Mora-Olivo Arturo
Published: November 2019

Las comunidades arbóreas con sistemas silvopastoriles desempeñan un papel importante en los ecosistemas áridos y semiáridos del país, al conservar la biodiversidad y el desarrollo de las actividades ganaderas, que son de vital importancia en el norte de México. Con el objetivo de caracterizar una comunidad arbórea de un sistema silvopastoril en una zona de transición de matorral espinoso tamaulipeco y mezquital en Nuevo León, se establecieron cinco sitios de muestreo de 2500 m2, en los cuales se realizó un inventario de todas las especies arbóreas con diámetro a la altura de 1.30 m (DAP) igual o mayor que 7.5 cm. Se evaluaron composición y estructuras vertical y horizontal a través de parámetros estructurales de la vegetación (abundancia relativa, frecuencia relativa, dominancia relativa), índice de valor de importancia, índice de valor forestal y modelos para las variables diámetro normal - área de copa. Las especies principales desde el punto de vista ecológico fueron Prosopis laevigata (Hump. & Bonlp. ex. Willd.) M. C. Johnst. y Ebenopsis ebano (Berland.) Barneby & J. W. Grimes, la comunidad presentó alta densidad de individuos, alta cobertura de copa y una estructura vertical con alta proporción de individuos con altura mayor o igual a 6 m. El modelo lineal mostró los mejores ajustes al presentar un R2 = 0.621. El manejo silvo-pastoril ha conservado y promovido los atributos estructurales de la comunidad vegetal nativa.
Modelos para estimar biomasa de Euphorbia antisyphilitica Zucc. en seis municipios de Coahuila
Authors: Hernández-Ramos Adrián , Cano-Pineda Antonio , Flores-López Celestino , Hernández-Ramos Jonathan , García-Cuevas Xavier , Martínez-Salvador Martin , Martínez Angel Luis
Published: November 2019

El escaso conocimiento sobre el crecimiento y desarrollo de las especies de zonas áridas y semiáridas en México ha generado un sobreaprovechamiento. Entre las especies más importantes económicamente en Coahuila está la candelilla, cuya información técnica disponible para la toma de decisiones en el manejo es limitada. Por lo anterior, los objetivos del presente trabajo fueron a) agrupar seis municipios con base en la producción individual de biomasa evaluada en 10 poblaciones naturales de Euphorbia antisyphilitica Zucc. y b) ajustar modelos alométricos para estimar la biomasa de E. antisyphilitica en diferentes condiciones de crecimiento, en el centro y sur de Coahuila. Con un análisis de varianza y la diferencia mínima significativa, se agruparon los municipios; para cada grupo se ajustaron modelos, mediante el método de mínimos cuadrados ordinarios. Se obtuvieron tres grupos de producción de biomasa por individuo (GI, GII y GIII). Los modelos para estimar la biomasa total verde (kilogramo por individuo) para cada grupo, resultaron con R2Ajus superiores a 0.86, en los primeros dos grupos, y de 0.64 para GIII. La RCME (raíz del cuadrado medio del error) fue inferior a 0.425 y los parámetros de los modelos fueron significativos (p < 0.05), en los cuatro casos. Además, los cuatro modelos seleccionados presentaron normalidad, homogeneidad de varianzas y la inexistencia de colinealidad entre variables. Los modelos seleccionados son estadísticamente confiables para estimar la biomasa por individuo de cada grupo considerado en este estudio, por lo que podrán ser una herramienta útil en la elaboración de planes de manejo para el aprovechamiento de candelilla.