bluuebunny/crossref_metadata_2025_split huggingface dataset:
Potential Inhibitors of Protein Tyrosine Phosphatase (PTP1B) Enzyme: Promising Target for Type-II Diabetes Mellitus
Authors: Nandi Sisir , Saxena Mridula 
Published: September 2020

Background:
There has been growing interest in the development of highly potent and
selective protein tyrosine phosphatase (PTP1B) inhibitors for the past 2-3 decades. Though most
PTPs share a common active site motif, the interest in selective inhibitors, particularly against PTP1B
is increasing to discover new chemical entities as antidiabetic agents. In the current paradigm to find
potent and selective PTP1B inhibitors, which is currently considered as one of the best validated
biological targets for non-insulin-dependent diabetic and obese individuals, resistance to insulin due
to decreased sensitivity of the insulin receptor is a pathological factor and is also genetically linked,
causing type II diabetes.

Objectives:
Insulin receptor sensitization is performed by a signal transduction mechanism via a
selective protein tyrosine phosphatase (PTP1B). After the interaction of insulin with its receptor,
autophosphorylation of the intracellular part of the receptor takes place, turning it into an active
kinase (sensitization). PTP1B is involved in the desensitization of the receptor by dephosphorylation.
PTP1b inhibitors delay the receptor desensitization, prolonging insulin effect and making PTP1B as a
drug target for the treatment of diabetes II. Therefore, it has become a major target for the discovery
of potent drugs for the treatment of type II diabetes and obesity. An attempt has been made in the
present study to discuss the latest design and discovery of protein tyrosine phosphatase (PTP1B) inhibitors.

Methods:
Many PTP1B inhibitors such as diaminopyrroloquinazoline, triazines, pyrimido triazine derivatives,
2-(benzylamino)-1-phenylethanol, urea, acetamides and piperazinylpropanols,
phenylsulphonamides and phenylcarboxamide, benzamido, arylcarboxylic acid derivatives, arylsupfonyl
derivatives, thiazoles, isothiozolidiones and thiazolodinones have been discussed, citing the disease
mechanisms.

Results:
The reader will gain an overview of the structure and biological activity of recently developed
PTPs inhibitors.

Conclusion:
The co-crystallized ligands and the screened inhibitors could be used as a template for
the further design of potent congeners.
In Silico Analysis of Relative Rareness, Codon Usage, and Enzymesubstrate Docking of Lampyroidea Maculata luciferase
Authors: Mortazavi Mojtaba , Hosseinkhani Saman , Torkzadeh-Mahani Masoud , Lotfi Safa , Emamzadeh Rahman , Ghasemi Younes 
Published: September 2020

Aim:
The purpose of this study was to conduct in silico analysis of the Lampyroidea
maculata luciferase enzyme.

Background:
Bioluminescence is the production and emission of light by the luciferase enzymes
in a living organism. The luciferase enzyme has been widely used in biotechnology due to its excellent
properties.

Objective:
Recently, the new gene of the luciferase from the Lampyroidea maculata, has been
cloned and characterized.

Methods:
In the following, in silico analysis of this enzyme were conducted by structural modeling
in the I-TASSER web server. Finally, the binding site properties were studied using the AutoDock
Vina. In the following, the codon usage bias parameters as the CAI, CBI, ENC, and the base composition
of this sequence were studied. After analysis of the base composition, it was found that the
coding DNA sequence is rich in AT. Moreover, the indices GC1, GC2, and GC3 were computed to
establish the relationship among three codon positions. On the other hand, the GC2 has a much lower
frequency.

Results:
By molecular modeling, some rare codons were identified that may have a critical role in
the structure and function of this luciferase. The GC3% of the CDs was 17/304 and GC3 Skewness
was 0.115. The GC content at the first codon position (GC1) and second codon position (GC2) was
compared with that of the third codon position (GC3). AutoDock Vina was used in the molecular
docking that recognizes some residues that yield closely related to the ADSL binding site. This
bioinformatics analyzes play an important role in the design of new drugs.

Conclusion:
Previous studies show that mutation pressure and natural selection reasons for codon
usage variation among different genes. If the mutational pressure was the only effective reason for
the codon usage bias, then the frequency of nucleotides C and G should be equal to A and T at the
synonymous third codon position. By these analyses, a new understanding of the sequence and
structure of this enzyme was created, and our findings can be used in some fields of clinical and industrial
biotechnology.
Structural Investigations of Aroylindole Derivatives through 3D-QSAR and Multiple Pharmacophore Modeling for the Search of Novel Colchicines Inhibitor
Authors: Patel Vijay Kumar , Rajak Harish 
Published: September 2020

Background :
The ligand and structure based integrated strategies are being repeatedly
and effectively employed for the precise search and design of novel ligands against various disease
targets. Aroylindole derivative has a similar structural analogy as Combretastatin A-4, and exhibited
potent anticancer activity on several cancer cell lines.

Objective:
To identify structural features of aroylindole derivatives through 3D-QSAR and multiple
pharmacophore modelling for the search of novel colchicines inhibitor via virtual screening.

Method:
The present study utilizes ligand and structure based methodology for the establishment
of structure activity correlation among trimethoxyaroylindole derivatives and the search of novel
colchicines inhibitor via virtual screening. The 3D-QSAR studies were performed using Phase module
and provided details of relationship between structure and biological activity. A single ligand
based pharmacophore model was generated from Phase on compound 3 and compound 29 and three
energetically optimized structure based pharmacophore models were generated from epharmacophore
for co-crystallized ligand, compound 3 and compound 29 with protein PBD ID
1SA0, 5EYP and 5LYJ. These pharmacophoric features containing hit-like compounds were collected
from commercially available ZINC database and screened using virtual screening workflow.

Results and Discussion:
The 3D-QSAR model studies with good PLSs statistics for factor four was
characterized by the best prediction coefficient Q2 (0.8122), regression R2 (0.9405), SD (0.2581), F
(102.7), P (1.56e-015), RMSE (0.402), Stability (0.5411) and Pearson-r (0.9397). The generated epharmacophores
have GH scores over 0.5 and AUAC ≥ 0.7 indicated that all the pharmacophores
were suitable for pharmacophore-based virtual screening. The virtual screened compounds
ZINC12323179, ZINC01642724, and ZINC14238006 have showed similar structural alignment as
co-crystallized ligand and showed the hydrogen bonding of ligand with ASN101, SER178,
THR179, VAL238, CYS241 amino acid of protein.

Conclusion:
The study illustrates that the ligand and structure based pharmacophoric approach is
beneficial for identification of structurally diverse hits, having better binding affinity on colchicines
binding site as novel anticancer agents.
Effects of Menopausal Symptoms on Work Life and Organizational Environment
Authors: Besen Meltem Aydın , Eker Aslı , Yurdakul Mine 
Published: September 2020

Background:
Every working woman has the right to continue to live as a healthy individual.
The working environment has important effects on the general health status and reproductive
health of women. If menopause period of women is not taken into consideration and if appropriate
arrangements are not made at workplaces, their work performance and productivity decrease.
It is important to have detailed knowledge about factors creating risk for health in order to develop
effective policies and programs directed towards preventing them.

Objective:
This study was performed to determine the perceived effects of menopause on work life
and attitudes of an institution towards menopausal women.

Methods:
The study population included 419 women aged 45-55 years and working at a university.
Out of 419 women, 291 could be contacted. Data were collected with a questionnaire composed of
questions about descriptive characteristics, effects of menopause on work life, and support from and
attitudes of the institution about menopause. Data collected to reveal menopausal women’s experiences
at work were analyzed with statistical methods frequency, percentages, and mean.

Results:
The mean age at which menopause started was 47 years and 89.7% of the women experienced
menopausal complaints.

Conclusions:
Physical conditions at work and stressors were found to increase menopausal complaints
and had a negative effect on work performance.
Strategies of Comfort Management During Childbirth: A Qualitative Systematic Review
Authors: Chaisitsanguan Kunnikar , Kongvattananon Puangpaka , Somprasert Chomchuen 
Published: September 2020

Background:
Childbirth is often conducted in a traditional biomedical paradigm. Nature’s
simple plan for birth has been replaced by a maternity care system that increases unnecessary
risks for mother and child. Strategies of comfort management can guide nurse professionals to face
serious challenges and help a woman get benefits from normal birth.

Objective:
The purpose of this article is to determine strategies of comfort management in pregnant
women during childbirth.

Methods:
Published articles from the electric databases, including CINAHL, PsyINFO, Pubmed,
Cochrane, ThaiJO and other sources, were included from January 1, 2009, to March 1, 2019. The
PICo mnemonics were used to guide the research question. The PICo tool was applied for search
strategies. Two authors evaluated title, abstract and quality. The JBI Critical Appraisal Checklist for
Qualitative Research has been used as a methodology for appraising the quality of all studies. Data
were extracted by using a standard data extract tool from the JBI-Qualitative Appraisal tool by two
independent researchers. Ten published articles have been selected to study by the PRISMA process.

Results:
Six themes of the strategy of comfort management emerged: 1) encourage a strong sense
of self-control 2) support and continuous attendance 3) education and information 4) multidisciplinary
approach 5) environment preparation and 6) attending a woman’s need.

Conclusion:
This study adds new knowledge about the strategies of comfort management that may
guide the midwife with expanded options for women during childbirth, give the midwife understanding
of their role and can provide comfort in effective childbirth.
The Effect of Sex Education and Counseling on the Sexual Function of Iranian Reproductive Age Women: A Systematic Review and Meta-Analysis
Authors: Ranjbaran Mehdi , Omani-Samani Reza , Alimoradi Zainab , Mansori Kamyar , Chizari Mina , Ghandian Ali , Mahdavi Nader , Hafezi Maryam 
Published: September 2020

Background:
The prevalence of female sexual dysfunction is high and various interventions
are used for the treatment of this disorder.

Objective:
This systematic review and meta-analysis study aimed to determine the effect of sex
education and counseling on the sexual function of Iranian married reproductive age women.

Methods:
We searched the international databases, including ISI Web of Sciences, Pub-
Med/Medline, Scopus and local databases for published randomized clinical trials without time
limitation until March 2020. Mean Difference (MD) with 95% Confidence Interval (95% CI) was
considered as a summary effect. In order to identify factors related to heterogeneity between studies,
we conducted subgroups and Meta-regression analysis.

Results:
The results showed significant differences in the pooled mean score of female sexual function
between intervention and control groups (MD=5.03, CI 95 %; 3.42 to 6.65). The education and
counseling were more effective in pregnant women (MD= 6.34, CI 95 %; 4.31 to 8.38), than other
married women (MD= 3.87, CI 95 %; 1.25 to 6.49). Counseling interventions (MD= 5.58, CI 95 %; 3.22
to 7.93) were more effective than other sexual education methods (MD= 4.31, CI 95 %; 2.06 to 6.67).

Conclusion:
Educational and counseling interventions could improve the sexual performance of
women, and interventions were more effective in pregnant women. The effectiveness of counseling
interventions was better than education.
Evaluation of Ligustrazine-Based Synthetic Compounds for their Antiproliferative Effects
Authors: Bukhari Syed N.A. , Alotaibi Nasser H. , Ahmad Waqas , Alharbi Khalid S. , Abdelgawad Mohamed A. , Al-Sanea Mohammad M. , Ahmad Muhammad M. , Amjad Muhammad W. , Raja Maria A.G. , Hussain Muhammad A. 
Published: September 2020

Background:
Ligustrazine and chalcones have been reported previously for various
biological activities including anticancer effects.

Objectives:
Based on the multitargeted biological activities approach of ligustrazine-based chalcones,
in the current study 18 synthetic ligustrazine-containing α, β-unsaturated carbonyl-based 1, 3-
Diphenyl-2-propen-1-one derivatives were evaluated for their inhibitory effects on the growth of five
different types of cancer cells.

Methods:
All the compounds were evaluated for anticancer effects on various cancer cell lines by
propidium iodide fluorescence assay and various other assays were performed for mechanistic studies.

Results:
A majority of compounds exhibited strong inhibition of cancer cells, especially synthetic
compounds 4a and 4b, bearing 1-Pyridin-3-yl-ethanone as a ketone moiety in the main structural
backbone were found to be most powerful inhibitors of cancer cell growth. Nine most active compounds
among the whole series were selected for further studies related to different cancer targets, including
EGFR TK kinases, tubulin polymerization, KAF and BRAFV600E.

Conclusion:
Synthetic derivatives, including 4a-b and 5a-b showed a multitarget approach and
strong inhibitory effects on EGFR, FAK and BRAF while three compounds, including 3e bearing
methoxy substitution, 4a and 4b with 1-pyridin-3-yl-ethanone moiety showed the inhibition of tubulin
polymerization.
Development and Validation of an HPLC Method for the Quantification of Morin Flavonoid Encapsulated within PLGA Nanoparticles
Authors: Alonso Mario , Barcia Emilia , Córdoba-Díaz Manuel , Negro Sofia , Córdoba-Díaz Damián , Fernández-Carballido Ana 
Published: September 2020

Background:
Morin flavonoid exerts neuroprotective effects with potential interest in neurodegenerative
disorders. For this, the use of surface-modified polymeric nanoparticles loaded with morin is an interesting approach.

Objective:
To develop and validate an HPLC method for the quantification of morin released from a new delivery
system consisting of poly lactic-co-glycolic (PLGA) nanoparticles functionalized with the dipeptide phe-phe
(phenylalanine-phenylalanine) used to facilitate their access to the CNS.

Method:
The HPLC procedure was developed and validated with morin hydrate dissolved either in methanol (method A)
or in methanol: 0.1N HCl (50:50, v/v, method B). Two new nanoparticle formulations were developed and characterized:
morin-loaded PLGA nanoparticles (formulation F1), and morin-loaded PLGA phe-phe nanoparticles (formulation F2).

Results:
Method A was linear within the concentration range of 5-30 μg.mL-1 and, 1-30 μg mL-1
for method B. LOD and LOQ with method A were 1.23 μg.mL-1 and 3.90 μg.mL-1, respectively,
and 0.481 μg.mL-1 and 1.458 μg.mL-1, respectively for method B. The average amount of phe-phe
bound to formulation F2 (50 mg of NPs) was 431.33 μg. The encapsulation efficiency of morin
within PLGA nanoparticles was around 80%. After functionalization, this value decreased significantly.

Conclusion:
Method B showed better sensitivity, accuracy and precision for the quantification of morin. The procedure
used to functionalize the nanoparticles was adequate for linking the dipeptide to their surfaces, but this procedure is not
adequate when encapsulating water-soluble compounds.
Impact of COVID-19 on Indian Pharmaceutical Industry and Way Forward
Authors: Jadhav Nikita Vijay , Singh Nisha , Targhotra Monika , Chauhan Meenakshi K. 
Published: September 2020

Background:
As countries and industries continue to cope with the unparalleled challenges
presented by the novel coronavirus (COVID-19), a specific area of concern has been the uncertainty
surrounding the impact of the COVID-19 pandemic on the global and Indian supply
chains of the pharmaceutical industry. The COVID-19 crisis has demonstrated the importance of
establishing a risk management system that focuses on assessing future risks resulting from the
loss of a supply chain among countries.

Objective:
This review focuses on the role of the Indian pharmaceutical industry towards the pandemic.
This review investigates the economic effect of COVID-19 across segments and what it implies
for the Indian economy.

Method:
The COVID 19 flare-up has additionally commenced the Indian pharmaceutical organizations an opportunity to
transform into a supported trade place point for gathering drugs and intermediates.

Result:
An enormous pharmaceutical industry in India has consistently been a foundation of reasonable
human services, and this pattern would now be able to be required to heighten further.

Conclusion:
The activities from COVID-19 are with a need to change the overall impression of Indian
pharmaceutical associations and even more altogether, reduce the dependence of the private
pharma associations on alone suppliers like China.
Involvement of the AcrAB Efflux Pump in Ciprofloxacin Resistance in Clinical Klebsiella Pneumoniae Isolates
Authors: Khoshnood Saeed , Heidary Mohsen , Hashemi Ali , Shahi Fatemeh , Saki Morteza , Kouhsari Ebrahim , Eslami Gita , Goudarzi Hossein 
Published: September 2020

Background:
Increasing prevalence of multiple antibiotic resistance in Klebsiella pneumoniae
strains confines the therapeutic options used to treat bacterial infections.

Objective:
We aimed in this study to investigate the role of AcrAB, qepA efflux pump, and AAC(6′)-Ib-cr enzyme in ciprofloxacin resistance and to detect the RAPD-PCR fingerprint of K. pneumoniae isolates.

Methods:
A total of , 117 K. pneumoniae isolates were collected from hospitalized patients in three
hospitals in Tehran, Iran, from August 2013 to March 2014. Antimicrobial susceptibility tests were
performed by the disk diffusion method. Molecular identification and expression level of encoding
quinolone resistance genes, acrA, acrB, qepA, and aac(6')-Ib-cr, were performed by PCR and real--
time PCR assays, respectively. All the K. pneumoniae isolates containing the mentioned genes
were used simultaneously for RAPD-PCR typing.

Results:
Colistin and carbapenems were the most efficient antibiotics against the clinical isolates
of K. pneumoniae. PCR assay demonstrated that among the 117 isolates, 110 (94%) and 102 (87%)
were positive for acrA and acrB gene and 5 (4%) and 100 (85%) isolates showed to have qepA and
aac(6′)-Ib-cr genes, respectively. Determination for AcrAB pump expression in 21% of strains demonstrated
an increased expression, and the mean increase expression for acrB genes was 0.5-81.
The results of RAPD-PCR reflected that in 95% CI, all isolates belonged to a clone.

Conclusion:
A high prevalence of genes encoding quinolone resistance in K. pneumoniae was detected
in clinical samples. Therefore, the control of infection and prevention of drug-resistant bacteria
spread need careful management of medication and identification of resistant isolates.
Design and Microwave-Assisted Synthesis of Aza-Resveratrol Analogs with Potent Cholinesterase Inhibition
Authors: Biscussi Brunella , Richmond Victoria , Baier Carlos Javier , Mañez Pau Arroyo , Murray Ana Paula 
Published: September 2020

Background:
Currently approved Alzheimer’s disease medications mainly comprise acetylcholinesterase
inhibitors. Many of these inhibitors are either natural compounds or synthetic molecules
inspired in natural compounds. Hybrid molecules that can interact with different target sites of the enzyme
could lead to the discovery of effective multitarget drugs.

Objective:
To design, synthesize, and evaluate a series of new aza-resveratrol analogs as in vitro acetyl-
and butyrylcholinesterase inhibitors.

Methods:
The synthesis is achieved by a simple and efficient microwave-assisted method, from commercially
available starting materials. Compounds are designed as hybrids of an aza-stilbene nucleus
(Schiff base) connected to a tertiary amine by a hydrocarbon chain of variable length, designed to interact
both with the peripheric anionic site and the catalytic site of the enzyme.

Results:
All the derivatives inhibit both enzymes in a concentration-dependent manner, acting as moderate
to potent cholinesterase inhibitors. The most potent inhibitors are compounds 12b (IC50 = 0.43
μM) and 12a (IC50 = 0.31 μM) for acetyl- and butyrylcholinesterase, respectively. Compounds 12a
and 12b also exhibit significant acetylcholinesterase inhibition in SH-SY5Y human neuroblastoma
cells without cytotoxic properties. Enzyme kinetic studies and molecular modeling reveal that inhibitor
12b targets both the catalytic active site and the peripheral anionic site of acetylcholinesterase what
makes it able to modulate the self-induced β-amyloid aggregation. Furthermore, the molecular modeling
analysis helps to assess the impact of the linker length in the inhibitory activity of this family of
new cholinesterase inhibitors.

Conclusion:
These compounds have the potential to serve as a dual binding site inhibitor and might
provide a useful template for the development of new anti-Alzheimer’s disease agents.