bluuebunny/crossref_metadata_2025_split huggingface dataset:
The LDL-Receptor and its Molecular Properties: From Theory to Novel Biochemical and Pharmacological Approaches in Reducing LDL-cholesterol
Authors: Petroglou Dimitrios , Kanellos Ilias , Savopoulos Christos , Kaiafa Georgia , Chrysochoou Anastasios , Skantzis Panagiotis , Daios Stylianos , Hatzitolios Apostolos I. , Giannoglou Georgios 
Published: June 2018

Background:The Low-Density Lipoprotein (LDL) Receptor (LDL-R) is a transmembrane protein playing a crucial role in effective lipid homeostasis. Various therapeutic agents have been used in the management of dyslipidemias, however, the outcome of therapeutic target is debated.Objective:The aim of this review is to summarize and fully understand the current concept regarding LDL-R and its molecular properties, metabolic pathway, factors affecting LDL-R activity and all available pharmacological interventions. Additionally, non-lipid related properties of LDL-R are also referred.Methods:Literature from the PubMed database was extracted to identify papers between 1984 to 2017 regarding LDL-R and therapeutic agents on dyslipidemia management.Results:We analyzed basic data regarding agents associated with LDL-R (Sterol Regulating Element-Binding Proteins - SREBPs, Protein ARH, IDOL, Thyroid Hormones, Haematologic Disorders, Protein convertase subtilisin kexintype 9 - PCSK-9, ApoC-III) as well as non-lipid related properties of LDL-R, while all relevant (common and novel) pharmacological interventions (statins, fibrates, cholesterol absorption inhibitors, bile acid sequestrants and PCSK- 9) are also referred.Conclusion:LDL-R and its molecular properties are involved in lipid homeostasis, so potentially sets the therapeutic goals in cardiovascular patients, which is usually debated. Further research is needed in order to fully understand its properties, as well as to find the potential pharmacological interventions that could be beneficial in cholesterol homeostasis and various morbidities in order to reach the most appropriate therapeutic goal.
The Effect of Single and Double Acetylation of Lysine Residues on Structural and Dynamical Features of Human Splicing Factor TDP-43 - A Statistical Ensemble Analysis
Authors: Makhouri Farahnaz Rezaei , Ghasemi Jahan B. 
Published: June 2018

Background:
The acetylated inclusions containing TDP-43 are found in the spinal cord of
amyotrophic lateral sclerosis (ALS) patients, suggesting that aberrant TDP-43 acetylation and
resulting disruption of RNA binding are linked to onset and progression of TDP-43 proteinopathy.

Methods:
Here, the consequences of TDP-43 acetylation at Lys145 within the RRM1 domain and
Lys192 within the RRM2 domain were studied using experimentally verifiable molecular models, in
which lysine residues (K) were substituted with glutamine (Q) as an acetylation mimic (K→Q) and
with arginine (R) as a non-mimic (K→R) mutant. We used a series of computer simulations to
characterize the impact of lysine acetylation on TDP-43 function and TDP-43 association with target
RNA.

Results:
Using snapshots collected from the MD simulation trajectories, the cross-correlation and
principal component analyses (PCA) were applied to shed light on the dynamic discrepancy among
the ten studied systems and to discern TDP-43 subdomains that exhibit conformational plasticity in
response to acetylation mimic and non-mimic mutations. Moreover, we also investigated the global
network parameter, betweenness, to model communication pathways and identify a network of
critical mediating nodes involved in long-range signaling. These nodes describe the functionally
significant TDP-43 residues involved in TDP-43 regulation.

Conclusion:
The identification of the critical nodes and optimal path mediating the dynamical
network communication could offer new strategies to manipulate TDP-43 function. Disrupting a
specific network communication could represent a rational approach to the design of drugs with
improved potency and selectivity.
Prediction and Targeting of Interaction Interfaces in G-protein Coupled Receptor Oligomers
Authors: Schiedel Anke C. , Kose Meryem , Barreto Carlos , Bueschbell Beatriz , Morra Giulia , Sensoy Ozge , Moreira Irina S. 
Published: June 2018

Background:
Communication within a protein complex is mediated by physical interactions
made among the protomers. Evidence for both the allosteric regulation present among the protomers of
the protein oligomer and of the direct effect of membrane composition on this regulation has made it
essential to investigate the underlying molecular mechanism that drives oligomerization, the type of interactions
present within the complex, and to determine the identity of the interaction interface. This
knowledge allows a holistic understanding of dynamics and also modulation of the function of the resulting
oligomers/signalling complexes. G-Protein-Coupled Receptors (GPCRs), which are targeted by
40% of currently prescribed drugs in the market, are widely involved in the formation of such physiological
oligomers/signalling complexes.

Scope:
This review highlights the importance of studying Protein-Protein Interactions (PPI) by using a
combination of data obtained from cutting-edge experimental and computational methods that were developed
for this purpose. In particular, we focused on interaction interfaces found at GPCR oligomers as
well as signalling complexes, since any problem associated with these interactions causes the onset of
various crucial diseases.

Conclusion:
In order to have a holistic mechanistic understanding of allosteric PPIs that drive the
formation of GPCR oligomers and also to determine the composition of interaction interfaces with respect
to different membrane compositions, it is essential to combine both relevant experimental and
computational data. In this way, efficient and specific targeting of these interaction interfaces in oligomers/
complexes can be achieved. Thus, effective therapeutic molecules with fewer side effects can be
designed to modulate the function of these physiologically important receptor family.
Visible Vessels of Vocal Folds: Can they have a Diagnostic Role?
Authors: Turkmen Hafiza Irem , Karsligil Mine Elif , Kocak Ismail 
Published: June 2018

Background:
Challenges in visual identification of laryngeal disorders lead researchers
to investigate new opportunities to help clinical examination. This paper presents an efficient and
simple method which extracts and assesses blood vessels on vocal fold tissue in order to serve
medical diagnosis.

Methods:
The proposed vessel segmentation approach has been designed in order to overcome difficulties
raised by design specifications of videolaryngostroboscopy and anatomic structure of vocal
fold vasculature. The limited number of medical studies on vocal fold vasculature point out that
the direction of blood vessels and amount of vasculature are discriminative features for vocal fold
disorders. Therefore, we extracted the features of vessels on the basis of these studies. We represent
vessels as vascular vectors and suggest a vector field based measurement that quantifies the
orientation pattern of blood vessels towards vocal fold pathologies.

Results:
In order to demonstrate the relationship between vessel structure and vocal fold disorders,
we performed classification of vocal fold disorders by using only vessel features. A binary tree of
Support Vector Machine (SVM) has been exploited for classification. Average recall of proposed
vessel extraction method was calculated as 0.82 while healthy, sulcus vocalis, laryngitis classification
accuracy of 0.75 was achieved.

Conclusion:
Obtained success rates showed the efficiency of vocal fold vessels in serving as an
indicator of laryngeal diseases.
Computed Tomographic Angiography for Risk Stratification in Patients with Acute Chest Pain - The Triple Rule-out Concept in the Emergency Department
Authors: Monica Marton-Popovici , Merkely Béla , Szilveszter Bálint , Drobni Zsófia Dora , Maurovich-Horvat Pál 
Published: June 2018

Background:
Acute chest pain is one of the most common reasons for Emergency Department
(ED) visits and hospital admissions. As this could represent the first symptom of a lifethreatening
condition, urgent identification of the etiology of chest pain is of utmost importance in
emergency settings. Such high-risk conditions that can present with acute chest pain in the ED include
Acute Coronary Syndromes (ACS), Pulmonary Embolisms (PE) and Acute Aortic Syndromes
(AAS).

Discussion:
The concept of Triple Rule-out Computed Tomographic Angiography (TRO-CTA) for
patients presenting with acute chest pain in the ED is based on the use of coronary computed tomographic
angiography as a single imaging technique, able to diagnose or exclude three lifethreatening
conditions in one single step: ACS, AAS and PE. TRO-CTA protocols have been
proved to be efficient in the ED for diagnosis or exclusion of life-threatening conditions and for
differentiation between various etiologies of chest pain, and application of the TRO-CTA protocol
in the ED for acute chest pain of uncertain etiology has been shown to improve the further clinical
evaluation and outcomes of these patients.

Conclusion:
This review aims to summarize the main indications and techniques used in TRO protocols
in EDs, and the role of TRO-CTA protocols in risk stratification of patients with acute chest
pain.
Halilectin-3, a Lectin from the Marine Sponge Haliclona caerulea, Induces Apoptosis and Autophagy in Human Breast Cancer MCF7 Cells Through Caspase-9 Pathway and LC3-II Protein Expression
Authors: do Nascimento-Neto Luiz G. , Cabral Maria G. , Carneiro Romulo F. , Silva Zelia , Arruda Francisco V.S. , Nagano Celso S. , Fernandes Alexandra R. , Sampaio Alexandre H. , Teixeira Edson H. , Videira Paula A. 
Published: June 2018

Background:
An ideal strategy for cancer treatment is the specific induction of tumor cell death, sparing
normal cells. Marine sponges are rich biological reservoirs of biomolecules, especially lectins, which have attracted
considerable attention due to potential biological effect on human cells. Lectins are proteins that bind specific
carbohydrate signatures and some gained further interest for their capacity to bind tumor associated carbohydrates
antigens and induce tumor cell apoptosis.

Objective:
This study aimed to evaluate the antitumor potential of H3, a lectin, recently reported from marine sponge
Haliclona caerulea on the human breast cancer cell line MCF7.

Results:
H3 reduced MCF7 cell viability with an IC50 of 100 µg/ml, without a significant effect on normal cells. At
24 h, H3 induced a significant arrest in the G1 cell cycle phase. Consistently, almost 50% of the cells were in early
apoptosis and showed remarkable increased expression of caspase-9 (CASP 9). H3 impaired dramatically the
adhesiveness of MCF7 cells in culture. Assays conducted with Lysotracker Red probe showed increased organelle
acidity, suggesting autophagic cell death, which was further supported by increased expression of microtubuleassociated
protein light chain 3 (LC3) and observable conversion of LC3-I in LC3-II by western blot.

Conclusion:
The apoptotic effect of H3 may be related to a balance between apoptotic and autophagic cell death,
mediated by increased expression of CASP 9 and LC3-II. To the best of our knowledge this is the first report about a
sponge lectin triggering both apoptosis and autophagy in MCF7 cell.
An Overview of Natural Plant Products in the Treatment of Hepatocellular Carcinoma
Authors: Rawat Divya , Shrivastava Somi , Naik Rayees A. , Chhonker Saurabh K. , Mehrotra Aditi , Koiri Raj K. 
Published: June 2018

Background:
Liver cancer is the fifth most commonly diagnosed cancer and the second leading cause
of cancer-related deaths worldwide. Among the liver cancers, hepatocellular carcinoma has been reported to be
responsible for 85-90% of primary liver cancer and it is the second most common cause of cancer mortality with
700,000 deaths documented annually. The major risk factors of HCC include chronic infections with the hepatitis
B (HBV) or hepatitis C (HCV) virus, chronic liver diseases, alcoholism as well as dietary carcinogens, such
as aflatoxins. Highest incidence rates are estimated to occur in Asia and Africa.

Objective:
The effectiveness of current man-made agents in treating chronic liver disease is not satisfactory and
they have uninvited side effects. Herbal medicines are extensively used all over the world; however, there is still
a vast gap in their acceptance by the scientific community. Plants are rich in secondary metabolites and phytochemicals
obtained from both, dietary and non-dietary sources. Natural plant products are potent therapeutic as
well as chemopreventive agents for numerous chronic diseases like cardiovascular, metabolic, neurodegenerative
and neoplastic diseases.

Results:
Dietary phytochemicals such as curcumin, resveratrol, quercetin, silibinin, N-trans-feruloyl octopamine,
lycopene, emodin, caffeine, urolithin A and Phloretin have been found to be useful for the treatment of
HCC and other diseases. According to recent reports 60% of the anticancer medication in current use has been
obtained from natural sources.

Conclusion:
Thus, derivatives from plants have played an essential role in cancer prevention due to their pleiotropic
abilities to scavenge free radicals, inhibit cell growth and induce apoptosis.
Artepillin C Induces Selective Oxidative Stress and Inhibits Migration and Invasion in a Comprehensive Panel of Human Cervical Cancer Cell Lines
Authors: Souza Raquel P. , Bonfim-Mendonça Patrícia S. , Damke Gabrielle M.Z.F. , de-Assis Carvalho Analine R.B. , Ratti Bianca A. , Dembogurski Djaceli S. O. , da-Silva Vânia R.S. , Silva Sueli O. , Da-Silva Denise B. , Bruschi Marcos L. , Maria-Engler Silvya S. , Consolaro Marcia E.L. 
Published: June 2018

Background:
Artepillin C (3,5-diprenyl-4-hydroxycinnamic acid) is the main bioactive component of
Brazilian green propolis, and possesses, among other things, anticancer properties. However, to the best of our
knowledge, there are no studies of artepillin C in cervical cancer.

Method:
To explore a new therapeutic candidate for cervical cancer, we have evaluated the effects of artepillin
C on cellular viability in a comprehensive panel of human cervical cancer-derived cell lines including HeLa
(human papillomavirus/HPV 18-positive), SiHa (HPV 16-positive), CaSki (HPV 16- and 18-positive) and C33A
(HPV-negative) cells compared to a spontaneously immortalized human epithelial cell line (HaCaT).

Results:
Our results demonstrated that artepillin C had a selective effect on cellular viability and could induce
apoptosis possibly by intrinsic pathway, likely a result of oxidative stress, in all cancer-derived cell lines but not
in HaCaT. Additionally, artepillin C was able to inhibit the migration and invasion of cancer cells.

Conclusion:
Thus, artepillin C appears to be a promising new candidate as an anticancer drug for cervical cancer
induced by different HPV types.
Bursal Hexapeptide, A Potential Immunomodulator, Inhibits Tumor Cells Proliferation via p53 Signaling Pathway
Authors: Zhang Cong , Zhou Jiangfei , Li Shengnan , Cai Kairui , Guo Xiangling , Liao Chengshui , Wang Chen 
Published: June 2018

Background:
The Bursa of Fabricius (BF) is acknowledged as the central humoral immune organ
unique to birds. Bursal Hexapeptide (BHP, AGCCNG) is a recently reported bursal-derived bioactive peptide.
However, there are few reports of the molecular basis of the mechanism on immune induction and potential
antitumor activity of BHP.

Method:
In this paper, Gene microarray analyses demonstrated that BHP regulated expression of 1347 genes,
of which 832 were up-regulated and 515 were down-regulated. Differentially expressed genes involved in
various pathways were identified, of which 16 pathways were associated with immune responses and tumorigenic
processes.

Result:
Specifically, we found that BHP selectively inhibited tumor cell proliferation. Furthermore, BHP
enhanced antitumor factor p53 luciferase activity and stimulated expression of p53, p21, and p130 protein.
Moreover, we observed that the inhibitory effect of BHP on cell proliferation and premature senescence in a
p53-dependent manner.

Conclusion:
Taken together, we uncovered that BHP may be involved in antitumor suppressor via p53 signaling
pathway.
Cytotoxic and Apoptotic Effects of Novel Pyrrolo[2,3-d]Pyrimidine Derivatives Containing Urea Moieties on Cancer Cell Lines
Authors: Kilic-Kurt Zühal , Bakar-Ates Filiz , Karakas Bahriye , Kütük Özgür 
Published: June 2018

Background:
Pyrrolo[2,3-d]pyrimidines have been recently reported to have anticancer activities
through inhibition of different targets such as, Epidermal Growth Factor Receptor (EGFR) tyrosine kinase,
Janus Kinase (JAK), mitotic checkpoint protein kinase (Mps1), carbonic anhydrase, MDM-2. On the other hand,
aryl urea moieties which are found in some tyrosine kinase inhibitors such as Sorafenib and Linifanib have
aroused recent attention as responsible for anticancer activities. The aims of this paper are to synthesize pyrrolo[
2,3-d]pyrimidine derivatives containing urea moiety and evaluate their anti-cancer activity against human
lung cancer cell line (A549), prostate cancer cell line (PC3), human colon cancer cell line (SW480) and human
breast cancer cell line (MCF-7).

Methods:
A series of new pyrrolo[2,3-d]pyrimidines containing urea moieties have been synthesized as
Scheme 1. In vitro cytotoxicity of target compounds were evaluated against, SW480, PC3, A549 and MCF-7
human cancer cell lines using a MTT assay. In order to evaluate the mechanism of cytotoxic activity of
compounds 9e, 10a and 10b, having the best cytotoxic activity, Annexin V binding assay, cell cycle analysis
and western blot analysis were performed.

Results:
Among the target compounds, 10a (IC50 = 0.19 µM) was found to be the most potent derivative against
PC3 cells. Compound 10b and 9e showed the strong cytotoxic activity against MCF-7 and A549 cells with IC50
value of 1.66 µM and 4.55 µM, respectively. Flow cytometry data suggest that the cytotoxic activity of the
compounds on cancer cells might be mediated by apoptosis revealing a significant increase in the percentage of
late apoptotic cells and causing a cell cycle arrest at different stages. Western blot analysis of apoptosis marker
demonstrated that these compounds induce apoptosis through the intrinsic pathway.

Conclusion:
Compound 9e displayed the strongest cytotoxicity against A549 cancer cell line, and induced late
apoptosis in A549, as confirmed by cell cycle arrest in G0/G1 phase. In addition, compound 9e reduced expression
of the anti-apoptotic protein Bcl-2 and enhanced expression of the pro-apoptotic protein Bax, besides increased
caspase-9 and caspase-3, as well as cleavage of PARP levels. These results suggest that compound 9e
showed a cytotoxic effect in A549 cells through activation of the mitochondrial apoptotic pathway. Further
studies will be undertaken in our laboratory to improve cytotoxic activity of compound 9e and to identify the
biological targets of 9e which are responsible for anticancer activity.
Hydrogen Sulfide in Physiological and Pathological Mechanisms in Brain
Authors: Kumar Mohit , Sandhir Rajat 
Published: June 2018

Background & Objective: Hydrogen sulfide [H2S] has been widely known as a toxic gas
for more than 300 years in the scientific community. However, the understanding about this small
molecule has changed after the discovery of involvement of H2S in physiological and pathological
mechanisms in brain. H2S is a third gasotransmitter and neuromodulator after carbon monoxide [CO]
and nitric oxide [NO]. H2S plays an important role in memory and cognition by regulating long-term
potentiation [LTP] and calcium homeostasis in neuronal cells. The disturbances in endogenous H2S
levels and trans-sulfuration pathway have been implicated in neurodegenerative disorders like Alzheimer’s
disease, Parkinson disease, stroke and traumatic brain injury. According to the results obtained
from various studies, H2S not only behaves as neuromodulator but also is a potent antioxidant,
anti-inflammatory and anti-apoptotic molecule suggesting its neuroprotective potential.

Conclusion:
Recently, there is an increased interest in developing H2S releasing pharmaceuticals to
target various neurological disorders. This review covers the information about the involvement of
H2S in neurodegenerative diseases, its molecular targets and its role as potential therapeutic molecule.
Fibrinolytic, Anti-Inflammatory and Cytotoxic Potentialities of Extracts and Chemical Constituents of Manglicolous Lichen, Graphis ajarekarii Patw. & C. R. Kulk
Authors: Tatipamula Vinay Bharadwaj , Vedula Girija Sastry 
Published: June 2018

Background:
Lichens which are betide to mangroves are termed as Manglicolous Lichens
(ML). As these ML are habituated under stress conditions, they are screened for unique metabolites
and biological activities.

Objective:
The study aimed to establish the chemical and biological profile of ML, Graphis
ajarekarii.

Methods:
The Ethyl Acetate Extract of G. ajarekarii (EAE) was subjected to chromatographic techniques
and the obtained isolates were characterized by spectroscopic analysis. The hydroalcoholic extract
of G. ajarekarii (AE), EAE, isolates and Hydroalcoholic Extract of host (HE) were evaluated for
fibrinolytic (fibrin clot method), in vitro (protein denaturation method) and in vivo (formalin-induced
rat paw oedema assay), anti-inflammatory and cytotoxicity (MTT assay) activities.

Results:
Chemical investigation of the EAE led to the isolation of two known compounds namely
atranorin (1) and ribenone (2), which were confirmed by spectral data. The AE and EAE gradually
lysed the fibrin clot with 94.54 and 65.07%, respectively, at 24 h. The AE inhibited protein denaturation
of about 88.06%, while the standard (Indomethacin) with 93.62%. Similarly, the in vivo antiinflammatory
analysis of AE (200 mg/mL) showed potent reduction of rat paw oedema than the
standard, whereas EAE and 1 depicted moderate depletion. In addition, the AE revealed prominence
inhibition on MCF-7, DU145 and K-562 with IC50 values of 69.5, 42.5 and 38 µg/mL, respectively,
whereas the HE exhibited mild inhibitory profile against fibrin clot, inflammation and cancer.

Conclusion:
From the results, it can be concluded that the G. ajarekarii has an aptitude to act
against coagulation, inflammation and cancer cells.
Microsponge Based Gel of Tea Tree Oil for Dermatological Microbial Infections
Authors: Yadav Erosh , Rao Rekha , Kumar Sunil , Mahant Sheefali , Vohra Prakriti 
Published: June 2018

Objective:Tea Tree Oil (TTO), derived from Melaleuca alternifolia possesses broad spectrum antimicrobial potential. However, its therapeutic utility is impaired due to its high volatility, poor aqueous solubility and low stability in the presence of light, oxygen and temperature. The present study was attempted to investigate Ethyl Cellulose (EC) microsponges (MSs) as topical carriers for TTO to circumvent above mentioned limitations.Methods:TTO MSs were prepared using quasi emulsion solvent diffusion technique. The effect of formulation variables on the production yield, entrapment efficiency, particle size and drug release of MSs was investigated. The optimized MSs were dispersed into Carbopol 934 gel and evaluated for drug release, skin irritation, antibacterial activity and photostability.Results:Scanning electron microscopy revealed spherical and porous nature of TTO microsponges. The optimized MSs possessed particle size of 36.98 μm, percent entrapment efficiency of 93.12% and percent cumulative drug release of 79.18%, respectively. MS-loaded gels were found nonirritant. In addition, TTO loaded MS gels exhibited good stability. Antimicrobial effect of TTO MS gel showed broader zones of inhibition in comparison to TTO gel.Conclusion:The findings of our study suggest that MS loaded gel could prove alternative to conventional antibacterial formulations for dermatological microbial infections.