bluuebunny/crossref_metadata_2025 huggingface dataset:
Association of High-sensitivity C-reactive Protein with Patient Prognosis Following Mechanical Thrombectomy for Acute Ischemic Stroke
Authors: Kim Seonggon , Yi Ho J. , Lee Dong H. , Sung Jae H.
Published: May 2020

Objective:

The aim of this investigation was to examine the association of hsCRP (highsensitivity
C-reactive protein) with outcomes and prognosis of patients who underwent mechanical
thrombectomy (MT) for large vessel occlusion (LVO) after acute ischemic stroke (AIS).

Methods:

A total of 404 patients were enrolled, and outcomes included unfavorable clinical outcome
at three months (modified Rankin Scale, mRS scores 3-6), the occurrence of symptomatic
intracerebral hemorrhage (sICH) and hemorrhagic transformation (HT) of the infarct. Receiver
operating characteristic (ROC) curve analysis was performed to identify the cutoff value of hsCRP
to discriminate between favorable and unfavorable outcomes. The association of hsCRP with outcomes
was evaluated using a logistic regression model.

Results:

The best cutoff value of hsCRP to distinguish between favorable and unfavorable outcomes
at three months was identified as 3.0 mg/L (area under the curve, [AUC] 0.641, 95% confidence
interval, [CI] 0.535-0.748; P = 0.014). In, multivariate analysis, patients with hsCRP ≥3
mg/L had more unfavorable outcome (odds ratio [OR] 1.72, 95% CI 1.42-2.02; P = 0.010), sICH
(OR 2.64, 95% CI 1.62-3.66; P = 0.004), and HT of infarct (OR 1.72, 95% CI 1.42-2.02; P =
0.008) compared to those with hsCRP <1 mg/L.

Conclusion:

Our study demonstrates that patients with higher CRP levels had more unfavorable
outcome, and exhibited higher sICH, and HT of infarct than those with lower CRP levels. Elevated
hsCRP level, especially when higher than 3 mg/L, is an independent predictor for poor clinical
prognosis in patients with MT for LVO.
Platelet-to-neutrophil Ratio after Intravenous Thrombolysis Predicts Unfavorable Outcomes in Acute Ischemic Stroke
Authors: Wang Mei-Qi , Sun Ying-Ying , Wang Yan , Yan Xiu-Li , Jin Hang , Sun Xin , Zhang Peng , Zhu Hong-Jing , Guo Zhen-Ni , Yang Yi
Published: May 2020

Background and Purpose:

Platelet-to-neutrophil ratio (PNR) was suggested to be an independent
protective predictor for 90-days outcomes in acute ischemic stroke (AIS) patients in previous
studies. This study aims to investigate the association between PNR and outcomes of AIS in
intravenous thrombolysis (IVT) group.

Methods:

Data on acute ischemic stroke patients who received intravenous thrombolysis from April
2015 to March 2019 were collected. We defined the PNR value at admission as pre-IVT PNR and
after IVT within 24 h was defined as post-IVT PNR. Clinical outcome indicators included early neurological
deterioration (END), hemorrhagic transformation (HT), delayed neurological deterioration
(DND), and poor 3-month outcome (3m-mRS >2).

Results:

A total of 581 patients were enrolled in the final analysis. The age was 61(53-69) years, and
423(72.8%) were males. Post-IVT PNR was independently associated with hemorrhagic transformation
(OR = 0.974; 95%CI = 0.956-0.992; P=0.006), early neurological deterioration (OR = 0.939;
95%CI = 0.913-0.966; P = 0.01), delayed neurological deterioration (OR = 0.949; 95%CI = 0.912-
0.988; P = 0.011), and poor outcome (OR = 0.962; 95%CI = 0.948-0.976; P<0.001). PNR level was
identified as high (at the cut-off value or above) or low (below the cut-off value) according to receiver
operating curve (ROC) analyses on each endpoint. Comparison of early neurological deterioration,
hemorrhagic transformation, delayed neurological deterioration, and poor 3-month outcome
(3m-mRS >2) between patients at high and low levels for platelet-to-neutrophil ratio (PNR) showed
statistical differences (p<0.001).

Conclusions:

Post-IVT PNR was independently associated with early neurological deterioration,
hemorrhagic transformation, delayed neurological deterioration, and poor 3-month outcome. Lower
PNR can predict a worse outcome.
Small Molecule CDK Inhibitors for the Therapeutic Management of Cancer
Authors: Goel Bharat , Tripathi Nancy , Bhardwaj Nivedita , Jain Shreyans K.
Published: May 2020

:

Cyclin-dependent kinases (CDKs) are a group of multifunctional enzymes consisting of catalytic and regulatory subunits. The regulatory subunit, cyclin, remains dissociated under normal circumstances, and complexation of cyclin with the catalytic subunit of CDK leads to its activation for phosphorylation of protein substrates. The primary role of CDKs is in the regulation of the cell cycle. Retinoblastoma protein (Rb) is one of the widely investigated tumor suppressor protein substrates of CDK, which prevents cells from entering into cell-cycle under normal conditions. Phosphorylation of Rb by CDKs causes its inactivation and ultimately allows cells to enter a new cell cycle. Many cancers are associated with hyperactivation of CDKs as a result of mutation of the CDK genes or CDK inhibitor genes. Therefore, CDK modulators are of great interest to explore as novel therapeutic agents against cancer and led to the discovery of several CDK inhibitors to clinics. This review focuses on the current progress and development of anti-cancer CDK inhibitors from preclinical to clinical and synthetic to natural small molecules.
Glycogen Synthase Kinase 3 (GSK3): Its Role and Inhibitors
Authors: Wadhwa Pankaj , Jain Priti , Jadhav Hemant R.
Published: May 2020

:

Glycogen Synthase Kinase 3 (GSK3) is one of the Serine/Threonine protein kinases, which
has gained a lot of attention for its role in a variety of pathways. It has two isoforms, GSK3α and
GSK3β. However, GSK3β is highly expressed in different areas of the brain and has been implicated
in Alzheimer’s disease as it is involved in tau phosphorylation. Due to its high specificity concerning
substrate recognition, GSK3 has been considered as an important target. In the last decade, several
GSK3 inhibitors have been reported and two molecules are in clinical trials. This review collates the
information published in the last decade about the role of GSK3 in Alzheimer’s disease and progress in
the development of its inhibitors. Using this collated information, medicinal chemists can strategize
and design novel GSK3 inhibitors that could be useful in the treatment of Alzheimer’s disease.
Computer-Aided Structure Prediction of Bluetongue Virus Coat Protein VP2 Assisted by Optimized Potential for Liquid Simulations (OPLS)
Authors: Prajapati Leena , Khandelwal Ravina , Yogalakshmi Kadapakkam Nandabalan , Munshi Anjana , Nayarisseri Anuraj
Published: May 2020

Background:

The capsid coated protein of Bluetongue virus (BTV) VP2 is responsible for
BTV transmission by the Culicoides vector to vertebrate hosts. Besides, VP2 is responsible for BTV
entry into permissive cells and hence plays a major role in disease progression. However, its mechanism
of action is still unknown.

Objective:

The present investigation aimed to predict the 3D structure of Viral Protein 2 of the bluetongue
virus assisted by Optimized Potential for Liquid Simulations (OPLS), structure validation, and an
active site prediction.

Methods:

The 3D structure of the VP2 protein was built using a Python-based Computational algorithm.
The templates were identified using Smith waterman’s Local alignment. The VP2 protein structure validated
using PROCHECK. Molecular Dynamics Simulation (MDS) studies were performed using an
academic software Desmond, Schrodinger dynamics, for determining the stability of a model protein.
The Ligand-Binding site was predicted by structure comparison using homology search and proteinprotein
network analysis to reveal their stability and inhibition mechanism, followed by the active site
identification.

Results:

The secondary structure of the VP2 reveals that the protein contains 220 alpha helix atoms,
40 310 helix, 151 beta sheets, 134 coils and 424 turns, whereas the 3D structure of Viral Protein 2 of
BTV has been found to have 15774 total atoms in the structure. However, 961 amino acids were found
in the final model. The dynamical cross-correlation matrix (DCCM) analysis tool identifies putative protein
domains and also confirms the stability of the predicted model and their dynamical behavior difference
with the correlative fluctuations in motion.

Conclusion:

The biological interpretation of the Viral Protein 2 was carried out. DCCM maps were calculated,
using a different coordinate reference frame, through which, protein domain boundaries and
protein domain residue constituents were identified. The obtained model shows good reliability. Moreover,
we anticipated that this research should play a promising role in the identification of novel candidates
with the target protein to inhibit their functional significance.
Novel Drugs Targeting the SARS-CoV-2/COVID-19 Machinery
Authors: Sternberg Ariane , McKee Dwight L. , Naujokat Cord
Published: May 2020

Like other human pathogenic viruses, coronavirus SARS-CoV-2 employs sophisticated macromolecular
machines for viral host cell entry, genome replication and protein processing. Such machinery
encompasses SARS-CoV-2 envelope spike (S) glycoprotein required for host cell entry by binding
to the ACE2 receptor, viral RNA-dependent RNA polymerase (RdRp) and 3-chymotrypsin-like main
protease (3Clpro/Mpro). Under the pressure of the accelerating COVID-19 pandemic caused by the outbreak
of SARS-CoV-2 in Wuhan, China in December 2019, novel and repurposed drugs were recently
designed and identified for targeting the SARS-CoV-2 reproduction machinery, with the aim to limit the
spread of SARS-CoV-2 and morbidity and mortality due to the COVID-19 pandemic.
Microwave-Assisted Synthesis of Thiazole/Benzothiazole Fused Pyranopyrimidine Derivatives and Evaluation of their Biological Activity
Authors: Nagaraju Pallava , Reddy Pedavenkatagari Narayana , Padmaja Pannala , Ugale Vinod G.
Published: May 2020

A new class of phenylbenzo[4,5]thiazolo[3,2-a]pyrano[2,3-d]pyrimidin-5-one and pyrano[
2,3-d]thiazolo[3,2-a]pyrimidine-5-one derivatives have been synthesized via one-pot threecomponent
reaction of 2-hydroxy-4H-benzo[4,5]thiazolo[3,2-a]pyrimidin-4-one and 7-hydroxy-5Hthiazolo[
3,2-a]pyrimidin-5-one with various aromatic aldehydes and (E)-N-methyl-1-(methylthio)-2-
nitroethenamine under microwave irradiation. This transformation involves the formation of thiazole or
benzothiazole fused pyranopyrimidinone ring by the formation of two C-C bonds and one C-O bond in
a single synthetic operation. This rapid one-pot reaction does not require a catalyst, it is solvent-free,
avoids chromatographic purification, and provides good yields. The synthesized compounds were
evaluated for their antiproliferative activity against four cancer cell lines, namely DU 145 (prostate
cancer), MDA-MB-231 (breast cancer), Hela (Human cervical cancer), HT-29 (Human colon cancer)
and HEK293 (human embryonic kidney cells). The results demonstrated that synthesized compounds
were selective in its cytotoxicity to cancer cells compared to normal HEK293 cells. Compound 12h
exhibited the most potent antiproliferative activity against the tested cell lines, while other test compounds
showed weak or moderate antiproliferative activity, among them 12d, 12e and 14d displayed
showed IC50 values in the low micromolar range. Molecular docking studies revealed that these active
heterocyclic molecules bind selectively in the colchicine binding site of tubulin polymer.
Condition Optimization for Synthesis of 5-methyl-2(pyrimidin-2-yl) Benzoic Acid
Authors: Liu Fei , Zhao Shengyong , Yu Linpo , Liu Haibiao
Published: May 2020

Orexin has been emerged as a hot and frontier research theme in the close relationship with
sleep-wake regulation. In this paper, we report a synthetic method for the preparation of 5-methyl-2-
(pyrimidin-2-yl)benzoic acid, which is an important molecular fragment of orexin Filorexant (MK-
6096). Compared to the previously reported methods, the current route has the advantages of a short
synthetic pathway, simple post-treatment, and high yield that provide an effective new methodology
for the synthesis of the target compound. Using 2-bromo-5-methyl benzoic acid and 2-
chloropyrimidine as raw materials, PdCl2(PPh3)2 is used as a metal catalyst to mediate one-pot generation
of 5-methyl-2-(pyrimidin-2-yl)benzoic acid using the Negishi cross-coupling method. The optimum
condition involves 2-bromo-5-methylbenzoic acid (10.00 g) and anhydrous zinc chloride powder
(6.32 g) together with the catalyst: 2-bromo-5-methylbenzoic acid molar ratio of 0.02 and 2-
chloropyrimidine: 2-bromo-5-methylbenzoic acid molar ratio of 1.1:1 at a reaction temperature of 55°C
for 14 h. Under these optimum reaction conditions, the maximum yield of 78.4% is attained for 5-
methyl-2-(pyrimidin-2-yl) benzoic acid.
Pro-Phe Derivatives as Organocatalysts in Asymmetric Aldol Reaction
Authors: Karaoglu Merve , Aydogan Feray , Yolacan Cigdem
Published: May 2020

The aldol reaction which is the most important one among the C-C bond forming reactions,
is widely used by synthetic organic chemists to obtain β-hydroxycarbonyl compounds which are important
starting components for biologically active compounds in optically pure form. In this research,
five Pro-Phe derivatives were synthesized by simple amidation reactions and characterized by their
spectral data. Their catalytic activities in asymmetric aldol reaction were investigated. The catalytic
activity studies were performed with aliphatic ketones and various aromatic aldehydes. Especially, (S)-
methyl 3-mercapto-2-((S)-3-phenyl-2-((S)-pyrrolidine-2-carboxamido)propanamido)propanoate showed
good catalytic activities in water at 0oC in the presence of p-nitrobenzoic acid cocatalyst. The enantioselectivities
were up to 90.4%, the diastereomeric ratios were up to 97/3 and yields were 99%. The
results showed that these organocatalysts were promising organocatalysts for aldol reaction. Besides,
this catalyst showed its best catalytic activities in water which is also an important contribution to
green chemistry requirements.
Relationship between Invasive and Non-Invasive Hemodynamic Measures in Experimental Pulmonary Hypertension
Authors: Benavides-Córdoba Vicente , Gómez Mauricio Palacios
Published: May 2020

Introduction:

Animal models have been used to understand the pathophysiology of
pulmonary hypertension, to describe the mechanisms of action and to evaluate promising active
ingredients. The monocrotaline-induced pulmonary hypertension model is the most used animal
model. In this model, invasive and non-invasive hemodynamic variables that resemble human
measurements have been used. Aim: To define if non-invasive variables can predict hemodynamic
measures in the monocrotaline-induced pulmonary hypertension model.

Materials and Methods:

Twenty 6-week old male Wistar rats weighing between 250-300g from the
bioterium of the Universidad del Valle (Cali - Colombia) were used in order to establish that the
relationships between invasive and non-invasive variables are sustained in different conditions
(healthy, hypertrophy and treated). The animals were organized into three groups, a control group
who was given 0.9% saline solution subcutaneously (sc), a group with pulmonary hypertension
induced with a single subcutaneous dose of Monocrotaline 30 mg/kg, and a group with pulmonary
hypertension with 30 mg/kg of monocrotaline treated with Sildenafil. Right ventricle ejection
fraction, heart rate, right ventricle systolic pressure and the extent of hypertrophy were measured.
The functional relation between any two variables was evaluated by the Pearson correlation
coefficient.

Results:

It was found that all correlations were statistically significant (p <0.01). The strongest
correlation was the inverse one between the RVEF and the Fulton index (r = -0.82). The Fulton index
also had a strong correlation with the RVSP (r = 0.79). The Pearson correlation coefficient between
the RVEF and the RVSP was -0.81, meaning that the higher the systolic pressure in the right
ventricle, the lower the ejection fraction value. Heart rate was significantly correlated to the other
three variables studied, although with relatively low correlation.

Conclusion:

The correlations obtained in this study indicate that the parameters evaluated in the
research related to experimental pulmonary hypertension correlate adequately and that the
measurements that are currently made are adequate and consistent with each other, that is, they have
good predictive capacity.
The Possible Role of Saponin in Type-II Diabetes- A Review
Authors: Choudhary Neeraj , Khatik Gopal Lal , Suttee Ashish
Published: May 2020

Background:

The possible role of secondary metabolites in the management of diabetes is a
great concern and constant discussion. This characteristic seems relevant and should be the subject of
thorough discussion with respect to saponin.

Objective:

The current data mainly focus on the impact of saponin in the treatment of type-II diabetes.
The majority of studies emphasize on other secondary metabolites such as alkaloids and flavonoids, but
very few papers are there representing the possible role of saponin as these papers express the narrow
perspective of saponin phytoconstituents but lacking in providing the complete information on various
saponin plants. The aim of the study was to summarize all available data concerning the saponin containing
plant in the management of type-II diabetes.

Methods:

All relevant papers on saponin were selected. This review summarizes the saponin isolation
method, mechanism of action, clinical significance, medicinal plants and phytoconstituents responsible
for producing a therapeutic effect in the management of diabetes.

Results:

The saponin is of high potential with structural diversity and inhibits diabetic complications
along with reducing the hyperglycemia through different mechanisms thereby providing scope for improving
the existing therapy and developing the novel medicinal agents for curing diabetes.

Conclusion:

Saponins having potential therapeutic benefits and are theorized as an alternative medication
in decreasing serum blood glucose levels in the patient suffering from diabetes.
High Prevalence of Vitamin D Deficiency and Correlation with Cystatin-C and Other Cardiovascular and Renal Risk Biomarkers in Patients with Type 2 Diabetes Mellitus Complicated with Hypertension
Authors: Alkhatatbeh Mohammad J. , Smadi Sajedah A. , Abdul-Razzak Khalid K. , Saadeh Nesreen A.
Published: May 2020

Background:

Vitamin D is increasingly investigated as having a role in Type 2 Diabetes
Mellitus (T2DM) and its cardiovascular and renal complications.

Objective:

This study aimed to investigate the association between 25-hydroxyvitamin D (25-OHD) and
biomarkers of cardiovascular and renal complications, including cystatin-C.

Methods:

This cross-sectional study involved 117 participants with T2DM that was not complicated
with cardiovascular or renal diseases except hypertension. 25-OHD was measured by electrochemiluminescence
immunoassay, while cystatin-C was measured by enzyme-linked-immunosorbent-assay. Other
biomarkers, including lipids, creatinine, urea and glycemic measures, were determined by the routine
biochemistry assays.

Results:

The prevalence of vitamin D deficiency was 74.36%. There was no significant difference in
cardiovascular and renal biomarkers, including glucose, HbA1c, lipids, urea, creatinine and cystatin-C
between participants with adequate and deficient vitamin D (p-values>0.05). Participants with adequate
vitamin D were older in age, more obese and having lower eGFR (p-values<0.05). 25-OHD was weakly
correlated with age, duration of DM, urea, creatinine and inversely correlated with eGFR (rvalues<
0.32, p-values<0.05). Although creatinine and cystatin-C were directly correlated (r=0.42, pvalue<
0.001), cystatin-C and 25-OHD were not correlated (p-value>0.05). Hypertensive participants
were more obese, having a longer duration of DM and higher urea and cystatin-C compared to nonhypertensive
participants (p-values<0.05). Binary logistic regression analysis revealed that hypertension
could be predicted from increased BMI.

Conclusion:

25-OHD was not found to be correlated with cardiovascular risk biomarkers, but it was
correlated with renal biomarkers, including urea, creatinine and eGFR. Cystatin-C and 25-OHD were
not observed to be correlated to each other, but both were correlated to renal function. Obesity was a
significant predictor of hypertension.
Multiparametric MRI Evaluation of Developmental Venous Anomalies in the Brain: Association with Signal Changes on FLAIR in Patients with Multiple Sclerosis
Authors: Sagtas Ergin , Guneyli Serkan , Akyilmaz Dincer Aydin , Yavas Huseyin Gokhan , Cakmak Pinar , Ufuk Furkan
Published: May 2020

Background:

Developmental venous anomalies (DVAs) can be determined on magnetic
resonance imaging (MRI), and they may be associated with multiple sclerosis (MS) lesions.

Purpose:

The objective was to evaluate the MRI findings of DVAs in the brain, to compare the prevalence
of them between MS patients and control subjects, and to investigate the correlation of
DVA-associated fluid-attenuated inversion recovery (FLAIR) hyperintensities and MRI-derived parameters
between MS patients and control subjects having DVA.

Methods:

Total 160 patients with a mean age of 45 ± 16 years who underwent multiparametric
MRI including susceptibility-weighted imaging (SWI), diffusion-weighted imaging, 3D FLAIR,
and contrast-enhanced imaging were included in this retrospective study. First, the presence of
DVA was compared between the MS and control groups using the Chi-square test. Then, among
the subjects having DVA, age, gender, and MRI-derived parameters such as the signal increase of
DVA on FLAIR, location, and drainage of DVA were compared between the MS and control
groups using Chi-square test.

Results:

The presence of DVA did not differ between the MS and control groups (P = 0.828). Signal
increase around DVA on FLAIR (P = 0.03) and the age of less than 45 years demonstrated a
significant correlation with MS group (P = 0.022).

Conclusion:

In our study, DVAs were effectively detected using SWI and 3D contrast-enhanced
T1-weighted imaging on MRI. The signal increase of DVA was better revealed on 3D FLAIR on
MRI, and it was the only significant MRI-derived parameter in patients with MS.
Synthesis of Thiazolyl-N-phenylmorpholine Derivatives and their Biological Activities
Authors: Al-Soliemy Amerah M. , Farghaly Thoraya A. , Abbas Eman M.H. , Shaaban Mohamed R. , Zayed Mohie E.M. , El-Naggar Tarek B.A.
Published: May 2020

Background:

Morpholine and thiazole rings are two heterocycles which are wellknown
with a wide spectrum of different biological activities, especially antitumor activity.

Objective:

The aim of the work is to design and synthesize hybrid heterocyclic compounds of
morpholine and thiazole moieties via the reaction of morpholino-thiosemicarbazone derivatives
with various α-halocarbonyl compounds and screening their antitumor activity against three tumor
cell lines namely, TK-10, MCF-7 and UACC-62.

Methods:

An efficient synthesis of a series of N-phenylmorpholine derivatives linked with thiazole
moiety was accomplished. The reaction of N-subistituted-2-(N-phenylmorpholine)ethylidene) hydrazine-
1-carbothioamide (thiosemicarbazone derivative) with acetyl and ester-hydrazonoyl chlorides,
α-chloroketones, or α-bromoesters afforded the corresponding thiazole derivatives pendent
to N-phenylmorpholine moiety in good to excellent yields.

Result:

Mass, 1H NMR, 13C NMR, and elemental analysis were used to confirm the structure of
all the new derivatives. The antitumor activities of synthesized N-phenylmorpholine-thiazole derivatives
were investigated against three tumor cells namely, TK-10, MCF-7 and UACC-62. The
results of such investigation indicated that some derivatives showed good potential to inhibit the
growth of the two cells of the tested tumor cells. One of the tested compounds, N-ethyl thiosemicarbazone
derivative 7 revealed potent growth inhibition of all the three tumor cells.

Conclusion:

We have succeeded to synthesize a series of N-phenylmorpholine derivatives pendant
to thiazole moiety as antitumor agents.
A Validated LC-MS/MS Method for the Determination of Mezlocillin in Plasma: An Adapted Method for Therapeutic Drug Monitoring in Children
Authors: Tang Bo-Hao , Kan Min , Yang Xin-Mei , Wang Rong-Hua , Shi Hai-Yan , Zheng Yi , Hao Guo-Xiang , Song Lin-Lin , Zhao Wei
Published: May 2020

Background:

Mezlocillin is off-label used for the treatment of respiratory infections in children.
Therapeutic Drug Monitoring (TDM) data are also limited in children. A sensitive Liquid chromatography-
tandem mass spectrometry (LC–MS/MS) method adapted to children was developed and
validated for the determination of mezlocillin plasma concentration in the present study.

Methods:

Mezlocillin, extracted from a volume of 50 μL plasma using acetonitrile, was analyzed on an
online LC-MS/MS system with an Agilent 1290 Infinity UHPLC (Agilent Technologies, CA, USA)
coupled to an AB SCIEX QTRAP 6500PLUS MS/MS (AB Sciex, Framingham, MA, USA) with ceftiofur
as an internal standard. HPLC separation was performed on a C18 column with ultra-pure water
and acetonitrile as gradient elution at a flow rate of 0.4 mL/min at 30°C. Analyst TM Version 1.5.2
(Applied Biosystems) was used for data acquisition. The total chromatographic run time was 1.6 min.

Results:

LC/MS/MS method used for TDM of mezlocillin in children was developed and validated.
This assay has a lower limit of quantification of 0.025 μg/mL for mezlocillin with 50 μL plasma. Good
linearity was achieved for mezlocillin over the range from 0.025 to 20 μg /mL. The acceptance criteria
were met in all cases. Among 36 patients aged between 0.16-1.63 years old, only one patient had detectable
trough concentration higher than 1 μg/mL.

Conclusion:

LC-MS/MS method with 50 μL plasma developed in this study was successfully applied
to TDM of mezlocillin in children. The high variability of trough concentration highlighted that TDM
is important to optimize mezlocillin therapy in children.
Linezolid Induced Skin Reactions in a Multi Drug Resistant Infective Endocarditis Patient: A Rare Case
Authors: Rajan Asha K. , Kashyap Ananth , Chhabra Manik , Rashid Muhammed
Published: May 2020

Rationale:

Linezolid (LNZ) induced Cutaneous Adverse Drug Reactions (CADRs) have
rare atypical presentation. Till date, there are very few published case reports on LNZ induced CADRs
among the multidrug-resistant patients suffering from Infective Endocarditis (MDR IE). Here,
we present a rare case report of LNZ induced CARs in a MDR IE patient.

Case report:

A 24-year-old female patient was admitted to the hospital with chief complaints of
fever (101°C) associated with rigors, chills, and shortness of breath (grade IV) for the past 4 days.
She was diagnosed with MDR IE, having a prior history of rheumatic heart disease. She was prescribed
LNZ 600mg IV BD for MDR IE, against Staphylococcus coagulase-negative. The patient
experienced flares of cutaneous reactions with multiple hyper-pigmented maculopapular lesions all
over the body after one week of LNZ therapy. Upon causality assessment, she was found to be suffering
from LNZ induced CADRs. LNZ dose was tapered gradually and discontinued. The patient
was prescribed corticosteroids along with other supportive care. Her reactions completely subsided
and infection got controlled following 1 month of therapy.

Conclusion:

Healthcare professionals should be vigilant for rare CADRs, while monitoring the patients
on LNZ therapy especially in MDR patients as they are exposed to multiple drugs. Moreover,
strengthened spontaneous reporting is required for better quantification.
Benzophenone Sulfonamide Derivatives as Interacting Partners and Inhibitors of Human P-glycoprotein
Authors: Farman Saira , Javed Aneela , Arshia  , Khan Khalid M. , Nasir Abdul , Khan Asif Ullah , Lodhi Muhammad A. , Gul Humaira , Khan Faisal , Asad Muhammad , Parveen Zahida
Published: May 2020

Background:

Human P-glycoprotein (P-gp) is a transmembrane protein that belongs to the ATPBinding
Cassette (ABC) transporters family. Physiologically, it exports toxins out of the cell, however, its overexpression
leads to the phenomena of Multidrug-Resistance (MDR) by exporting a diverse range of compounds,
which are structurally and chemically different from each other, thus creating a hurdle in the treatment of various
diseases including cancer. The current study was designed to screen benzophenone sulfonamide derivatives
as a class of inhibitors and potential anticancer agents for P-gp.

Methods:

A total number of 15 compounds were evaluated. These compounds were screened in daunorubicin
efflux inhibition assays using CCRF-CEM Vcr1000 cell line that overexpressed human P-gp. Cytotoxicity assay
was also performed for active compounds 11, 14, and 13. These scaffolds were then docked in the homology
model of human P-gp using mouse P-gp as a template (PDB ID: 4MIM) and the recently published Cryo Electron
Microscopy (CEM) structure of human mouse chimeric P-gp to find their interactions with specified residues
in the binding pocket. Analysis was performed using Labview VI and Graph pad prism version 5.0.

Results:

Results revealed the potency of all these compounds in low nanomolar range whereas, compound 14
was found to be most active with IC50 value of 18.35nM±4.90 followed by 11 and 13 having IC50 values of
30.66nM±5.49 and 46.12nM±3.06, respectively. Moreover, IC50 values calculated for 14, 11 and 13 in cytotoxicity
assay were found to be 22.97μM±0.026, 583.1μM±0.027 and 117.8μM±0.062, respectively. Docking
results showed the interaction of these scaffolds in transmembrane helices (TM) where Tyr307, Tyr310, Tyr953,
Met986 and Gln946 were found to be the major interaction partners, thus they might play a significant role in
the transport of these scaffolds.

Conclusion:

Benzophenone sulfonamide derivatives showed IC50 values in low nanomolar range comparable to
the standard inhibitor Verapamil, therefore they can be good inhibitors of P-gp and can serve as anticancer
agents. Also, they have shown interactions in the transmembrane region sharing the same binding region of
verapamil and zosuquidar.
MicroRNA-372-3p Predicts Response of TACE Patients Treated with Doxorubicin and Enhances Chemosensitivity in Hepatocellular Carcinoma
Authors: Soliman Marwa H. , Ragheb Mohamed A. , Elzayat Emad M. , Mohamed Mervat S. , El-Ekiaby Nada , Abdelaziz Ahmed I. , Abdel-Wahab Abdel-Hady A.
Published: May 2020

Background:

Identification of factors to detect and improve chemotherapy-response in cancer is the
main concern. microRNA-372-3p (miR-372-3p) has been demonstrated to play a crucial role in cellular proliferation,
apoptosis and metastasis of various cancers including Hepatocellular Carcinoma (HCC). However, its
contribution towards Doxorubicin (Dox) chemosensitivity in HCC has never been studied.

Objective:

This study aims to investigate the potential role of miR-372-3p in enhancing Dox effects on HCC cell line (HepG2). Their
correlation has been additionally analyzed for HCC patients who received Transarterial Chemoembolization (TACE) with Dox treatment.

Methods:

Different cell processes were elucidated by cell viability, colony formation, apoptosis and wound healing assays after miR372-3p transfection in HepG2 cells Furthermore, miR-372-3p level has been estimated in blood of primary HCC patients treated with
TACE/Dox by quantitative real-time PCR assay. Receiver Operating Curve (ROC) analysis for serum miR-372-3p was constructed
for its prognostic significance. Finally, protein level of Mcl-1, the anti-apoptotic player, has been evaluated using western blot.

Results:

We found a significant higher level of miR-372-3p in blood of responder group of HCC patients received TACE with Dox
than of non-responders. Ectopic expression of miR-372-3p reduced cell proliferation, migration and significantly induced apoptosis in
HepG2 cells which was coupled with decreased of anti-apoptotic protein Mcl-1.

Conclusion:

Our study demonstrated that miR-372-3p acts as tumor suppressor in HCC and can act as a predictor biomarker for drug
response. Furthermore, the data referred for the first time its potential role in drug sensitivity that might be a therapeutic target for
HCC.
Recent Progress in the Development of Quinoline Derivatives for the Exploitation of Anti-Cancer Agents
Authors: Man Ruo-Jun , Jeelani Nasreen , Zhou Chongchen , Yang Yu-Shun
Published: May 2020

Background:

Along with the progress in medicine and therapies, the exploitation of anti-cancer agents focused more on the vital signaling pathways and key biological macromolecules. With rational design and advanced synthesis, quinoline derivatives have been utilized frequently in medicinal chemistry, especially in developing anti-cancer drugs or candidates.

Methods:

Using DOI searching, articles published before 2020 all over the world have been reviewed as comprehensively as possible.

Results:

In this review, we selected the representative quinoline derivate drugs in market or clinical trials, classified them into five major categories with detailed targets according to their main mechanisms, discussed the relationship within the same mechanism, and generated a summative discussion with prospective expectations. For each mechanism, the introduction of the target was presented, with the typical examples of quinoline derivate drugs.

Conclusion:

This review has highlighted the quinoline drugs or candidates, suited them into corresponding targets in their pathways, summarized and discussed. We hope that this review may help the researchers who are interested in discovering quinoline derivate anti-cancer agents obtain considerable understanding of this specific topic. Through the flourishing period and the vigorous strategies in clinical trials, quinoline drugs would be potential but facing new challenges in the future.
The Potential of Flavonoids and Tannins from Medicinal Plants as Anticancer Agents
Authors: Teodor Eugenia D. , Ungureanu Oana , Gatea Florentina , Radu Gabriel L.
Published: May 2020

The tendency of using herbs extracts or natural compounds extracted from herbs for preventing or
treating different illnesses, including cancer, continues to be an alternative to drug use. Many studies of plant
compounds aimed at finding substances with selective cytotoxicity on abnormal cells. Phenolic compounds, as
important secondary metabolites from plants, are one of them. In this review, the recent literature data from the
past five years about anticancer/antitumor effect of flavonoids and tannins extracted from medicinal plants are
surveyed. The cytostatic/antitumor effects of the individual compounds extracted from plants and/or of the
plants' polyphenolic extracts are considered, in order to point out the most significant constituents or plants with
anticancer potential. The most important results concerning these compounds and their derivatives in cancer
prevention and treatment, the importance of their chemical structure, their mechanism of action in vitro and in
vivo, and some bioavailability aspects are discussed.
Anticancer Properties of Amino Acid and Peptide Derivatives of Mycophenolic Acid
Authors: Siebert Agnieszka , Deptuła Milena , Cichorek Mirosława , Ronowska Anna , Cholewiński Grzegorz , Rachon Janusz
Published: May 2020

Background:

Although Mycophenolic Acid (MPA) is applied as prodrugs in clinic as an immunosuppressant,
it also possesses anticancer activity. MPA acts as Inosine-5’-Monophosphate Dehydrogenase
(IMPDH) inhibitor, where the carboxylic group at the end of the side chain interacts with Ser 276 of the enzyme
via hydrogen bonds. Therefore, MPA derivatives with other polar groups indicated high inhibition too. On the
other hand, potent anticancer agents like dacarbazine and cisplatin give numerous side-effects.

Objective:

Based on the literature data, MPA derivatives should be explored towards anticancer properties.
Conversion of the carboxylic group of MPA to amide could maintain antiproliferative activity. Therefore, we
decided to investigate several amino acid and peptide derivatives of MPA against chosen cancer cell lines in vitro.

Methods:

Amides of MPA hold threonine and arginine amino acid unit. These amino acid derivatives were
tested as L and D enantiomers and both in free acid and methyl esters forms. Additionally, MPA was modified
with tuftsin or retro-tuftsin as biologically active peptides, which could act as a drug carrier.

Results:

Amino acid and peptide derivatives of MPA were investigated in vitro as potential anticancer agents on
cell lines: Ab melanoma, A375 melanoma and SHSY5Y neuroblastoma. The activity of the tested compounds
was compared to parent MPA and known chemotherapeutics: dacarbazine and cisplatin.

Conclusion:

Amino acid moiety and the sequence of amino acids in the peptide part influenced observed activity.
The most active amino acid MPA analogues occurred to be D and L-threonine derivatives as methyl esters,
probably due to better cell membrane penetration.
Evaluation of Glutathione Bioactivity on Toxoplasma Gondii in BALB/c Mice Post Impact of Selenium and Calcium Supplementation
Authors: Namazi Mohammad Javad , Nikpour Saeideh , Rahimi-Moghaddam Parvaneh , Hosseini Seyed Abdollah , Siyadatpanah Abolghasem , Mostafavi Neda Sadat Shokouhi , Golmohammadi Rahim , Tabatabaie Fatemeh
Published: May 2020

Background:

Studies have shown that selenium is an essential component of glutathione
as an important antioxidant to reduce oxidative stress and inhibit intracellular parasites’
growth. In contrast, calcium in the cytosol of such parasites plays a key role in the entry of the parasite
into the host cell and its primary motility.

Aim and Objective:

The present study was designed to evaluate and compare glutathione peroxidase
bioactivity effects post administration of selenium and calcium in BALB/c mice infected by
Toxoplasma gondii.

Methods:

Sixty BALB/c mice susceptible to T. gondii were randomly divided into twelve groups
of case and control groups. There were six control groups including two positive controls infected
only with the parasites either 104 or 5×104, non-infected and untreated groups. Treated controls received
only calcium, selenium, or both respectively. Case groups were infected with 104 or 5×104
parasites. While each set of three case groups separately received minerals alone or together. Mice
were orally fed with 200 μg selenium, 50 μg calcium or their combination for 7 days. Mice were infected
by parasite’s tachyzoites. Sera of mice were kept and the peritoneal macrophages were isolated
for counting tachyzoites during infection.

Results:

The results showed that selenium unlike calcium was significantly effective in reducing
Toxoplasma tachyzoites compared to control groups. Moreover, glutathione peroxidase [GPX] activity
was elevated in mice treated with selenium and vice versa decreased in mice treated with calcium.

Conclusion:

Administration of selenium unlike calcium reduced Toxoplasma tachyzoites proliferation
by elevating bioactivity of selenium-dependent detoxification enzyme, GPX.
Nocardia Infections: Ten Years Experience from a Tertiary Health Care Center in North India (2007-2016)
Authors: Bansal Yashik , Singla Nidhi , Butta Hena , Aggarwal Deepak , Gulati Neelam , Chander Jagdish
Published: May 2020

Background:

Nocardia species are important cause of infections in humans but are underreported due to
missed diagnosis as well as misdiagnosis. Majority of the literature on these infections consists of case
reports or series with few articles describing high number of cases.

Objective:

To study the epidemiology of Nocardia infections in a tertiary care center.

Materials and Methods:

This retrospective observational study was done in a tertiary care centre of North
India over a period of 10 years (2007-2016). The detection of Nocardia spp. from clinical specimens was
done by conventional methods viz. direct microscopy (Gram’s stain, modified Ziehl-Neelsen stain [1%],
KOH examination) and culture.

Results:

A total of 25 cases of nocardiosis were diagnosed during the study period. The mean age
of the patients was 50.9 years (range 30-72 years) with a male:female ratio of 3:2. The site of disease
in these patients included pulmonary (n=18), cutaneous (n=4), perinephric abscess (n=1), ocular
(n=1) and bone (n=1). Risk factors associated were underlying lung disease (n=11), smoking
(n=7), diabetes (n=5) and steroid therapy (n=4) in pulmonary nocardiosis, iatrogenic (n=1) and leprosy
(n=1) in cutaneous nocardiosis, diabetes in perinephric abscess and cataract surgery in ocular
nocardiosis. Culture was positive in 12/25 (48%) patients for Nocardia spp. Direct microscopy
was positive in 22 patients. We wish to highlight that meticulous observation of KOH wet mount
examination helped in clinching the diagnosis of Nocardiosis in 3 cases which were earlier missed
by other methods.

Conclusions:

Good communication with the clinician alongside a meticulous effort in the laboratory is
essential for appropriate diagnosis and management of these cases.
Targeting the PI3K/AKT/mTOR Signaling Pathway in Primary Central Nervous System Lymphoma: Current Status and Future Prospects
Authors: Zhang Xiaowei , Liu Yuanbo
Published: May 2020

Primary Central Nervous System Lymphoma (PCNSL) is a rare invasive extranodal non-
Hodgkin lymphoma, a vast majority of which is Diffuse Large B-Cell Lymphoma (DLBCL). Although
high-dose methotrexate-based immunochemotherapy achieves a high remission rate, the risk of
relapse and related death remains a crucial obstruction to long-term survival. Novel agents for the
treatment of lymphatic malignancies have significantly broadened the horizons of therapeutic options
for PCNSL. The PI3K/AKT/mTOR signaling pathway is one of the most important pathways for Bcell
malignancy growth and survival. Novel therapies that target key components of this pathway have
shown antitumor effects in many B-cell malignancies, including DLBCL. This review will discuss the
aberrant status of the PI3K/AKT/mTOR signaling pathways in PCNSL and the application prospects
of inhibitors in hopes of providing alternative clinical therapeutic strategies and improving prognosis.
Combination of Naringenin and Lisinopril Ameliorates Nephropathy in Type-1 Diabetic Rats
Authors: Kulkarni Yogesh A. , Suryavanshi Sachin V.
Published: May 2020

Background:

Diabetes is a metabolic disorder affecting a large percentage of the population
worldwide. The chronic hyperglycemic condition leads to the generation of advanced glycation end
products, reactive oxygen species and inflammatory cytokines, which worsen the functioning of the
kidney. Clinical management of diabetic nephropathy is difficult as it requires a multi-focused approach.
Hence, a combination of lisinopril a drug used in clinical practice for nephropathy, and
naringenin, a flavonoid reported to have a significant effect in nephropathy, may show additive or synergistic
effect with less side effects.

Objective:

The objective of the present study was to evaluate the effect of a combination of lisinopril
with naringenin in diabetic nephropathy.

Methods:

Diabetes was induced in male Sprague Dawley rats by streptozotocin (55 mg/kg, i.p.). After
four weeks of diabetes induction animals were treated with naringenin alone and a combination of
Lisinopril and naringenin for the next four weeks. At the end of the study, various urine and biochemical
parameters were evaluated. Oxidative stress parameters like malondialdehyde, reduced glutathione;
catalase and superoxide dismutase for kidney tissues were estimated and histopathology studies of
kidneys were carried out.

Results:

The combination of lisinopril (10 mg/kg) and naringenin (25 and 50 mg/kg) treatment showed
significant improvement in the biochemical and urine parameters. Combination treatment also attenuated
renal oxidative stress and renal damage as observed in histopathological studies.

Conclusion:

Treatment with a combination of lisinopril and naringenin showed a promising effect on
diabetic nephropathy in rats.
Effect of Mirabegron on the Body's Exercise Capacity: A Review
Authors: Leis Kamil , Mazur Ewelina , Racinowski Mariusz , Świerczyński Wojciech , Baska Aleksandra , Gałązka Przemysław
Published: May 2020

Mirabegron is a β3-agonist drug approved by the FDA for use in 2012 and administered in
overactive bladder. Activating of adrenergic receptors leads to the relaxation of the detrusor muscle.
According to the latest research and reports, it also has lipolytic activity, affecting the reduction of
mainly brown adipose tissue (BAT) but also of white adipose tissue (WAT). This results in a decrease
in body weight and triglyceride concentration and an increase in lipoprotein lipase activity, as well as
in the level of free fatty acids or adipokines in the plasma. The drug indirectly participates in the regulation
of carbohydrate metabolism, influencing the increase in insulin sensitivity, supporting cellular
uptake of glucose. However, due to the elevation of blood pressure and pulse, as a supplement, the
drug should be taken with care to avoid cardiovascular complications. In our review, below, we present
a description and discussion of available studies in terms of mirabegron action on the exercise capacity
of the body in the context of its potential use as a doping agent.
Recent Advances in the Reliability Evaluation and Optimization of Linear Multistate Consecutively-connected Systems
Authors: Qu Li , Han Chenjing , Li Yingchun , Gao Kaiye , Peng Rui
Published: May 2020

With the progression of technology, models of linear multistate consecutively-connected
systems (LMCCSs) have been applied more widely, such as in telecommunication systems and the
Internet of Things, among other applications. LMCCSs contain a series of linearly arranged nodes,
and any disconnection between nodes will lead to the failure of the entire system. Thus, the reliability
of a linear multistate system is affected by many factors, such as the positioning of elements.
To be able to incorporate different types of complicated practical factors, researchers have proposed
various extensions for the LMCCS model. Moreover, models have been proposed to study
the optimal system configurations of such systems while considering reliability and some other objectives
or constraints. Due to the amount of existing research on LMCCSs, this paper aims to review
the related literature, classify these works, and elicit some future research directions.