bluuebunny/crossref_metadata_2025_split huggingface dataset:
Dephosphorylation Targeting Chimaera (DEPTAC): Targeting Tau Proteins
in Tauopathies
Authors: Soumbasis Andrea , Eldeeb Mohamed A. , Ragheb Mohamed A. , Zorca Cornelia E. 
Published: May 2022

Abstract:
One salient hallmark of neurodegeneration is the accumulation of toxic protein aggregates in
neuronal cells. This proteotoxicity culminates in the deterioration of neuronal function. In AD and related
tauopathies, the microtubule-associated protein tau becomes hyperphosphorylated. Hyperphosphorylated
tau forms neurofibrillary tangles (NFTs) within neurons, which constitute a unique feature
of tauopathies, including AD. A recent study has exploited a novel molecular strategy to counteract
hyperphosphorylated tau and enhance its degradation. Analogous to the PROTAC methodology, a
novel dephosphorylation targeting chimera (DEPTAC) was designed to promote the molecular interaction
between tau and phosphatase, which, in turn, augments its degradation. Herein, we briefly discuss
this novel finding and its potential therapeutic implications.
Pyridoxal Kinase of Disease-causing Human Parasites: Structural and
Functional Insights to Understand its Role in Drug Discovery
Authors: Qureshi Insaf Ahmed , Saini Mayank , Are Sayanna 
Published: May 2022

Abstract:
Human parasites cause several diseased conditions with high morbidity and mortality in a
large section of the population residing in various geographical areas. Nearly three billion people suffer
from either one or many parasitic infections globally, with almost one million deaths annually. In spite
of extensive research and advancement in the medical field, no effective vaccine is available against
prominent human parasitic diseases that necessitate identification of novel targets for designing specific
inhibitors. Vitamin B6 is an important ubiquitous co-enzyme that participates in several biological processes
and plays an important role in scavenging ROS (reactive oxygen species) along with providing
resistance to oxidative stress. Moreover, the absence of the de novo vitamin B6 biosynthetic pathway in
human parasites makes this pathway indispensable for the survival of these pathogens. Pyridoxal kinase
(PdxK) is a crucial enzyme for vitamin B6 salvage pathway and participates in the process of vitamers
B6 phosphorylation. Since the parasites are dependent on pyridoxal kinase for their survival and infectivity
to the respective hosts, it is considered a promising candidate for drug discovery. The detailed
structural analysis of PdxK from disease-causing parasites has provided insights into the catalytic
mechanism of this enzyme as well as significant differences from their human counterpart. Simultaneously,
structure-based studies have identified small lead molecules that can be exploited for drug discovery
against protozoan parasites. The present review provides structural and functional highlights of
pyridoxal kinase for its implication in developing novel and potent therapeutics to combat fatal parasitic
diseases.
Biological Functions and Applications of Antimicrobial Peptides
Authors: Jin Libo , Dong Hao , Sun Da , Wang Lei , Qu Linkai , Lin Sue , Yang Qinsi , Zhang Xingxing 
Published: May 2022

Abstract:
Despite antimicrobial resistance, which is attributed to the misuse of broad-spectrum antibiotics,
antibiotics can indiscriminately kill pathogenic and beneficial microorganisms. These events
disrupt the delicate microbial balance in both humans and animals, leading to secondary infections
and other negative effects. Antimicrobial peptides (AMPs) are functional natural biopolymers in
plants and animals. Due to their excellent antimicrobial activities and absence of microbial resistance,
AMPs have attracted enormous research attention. We reviewed the antibacterial, antifungal, antiviral,
antiparasitic, as well as antitumor properties of AMPs and research progress on AMPs. In addition,
we highlighted various recommendations and potential research areas for their progress and
challenges in practical applications.
Sulfonium Lipids: Synthesis and Evaluation as DNA Delivery Vectors
Authors: Li Jing , Zhang Lei , Lu Yanjie , Lin Yue , Yang Kun , Zhou Xiaodong , Shen Guinan 
Published: May 2022

Background:
Cationic lipids can be used as nonviral vectors in gene delivery therapy. Most
cationic lipids contain quaternary ammonium that can bind to negative phosphates of the plasmid. In
this study, sulfonium—a trialkylated sulfur cation was adopted in the synthesis of a series of cationic
lipids which were evaluated for their ability to function as gene delivery vectors.

Methods:
The sulfonium lipids were synthesized by condensing cyclic thioether and aliphatic carbon
chains with ethoxy linkage and the structure was characterized by NMR and mass. The DNA condensing
abilities of sulfonium lipids were evaluated using a gel retardation experiment. Sulfonium lipids/
DNA condensates were measured for particle size and Zeta potential. The cytotoxicity of sulfoniums
was evaluated with the MTT assay. The intracellular uptake of sulfonium lipid/DNA complexes
was observed with a fluorescence microscope.

Results:
The results showed that the sulfonium head can effectively bind to the phosphate of DNA.
When the S/P ratio is larger than 10/1, sulfonium lipids with longer carbon chains can completely condense
DNA to form a nanoparticle with particle size ranging from 135 nm to 155 nm and zeta potential
ranging from 28 mV to 42 mV. The IC50 of sulfonium lipids on HepG2 cells ranged from 2.37 μg/mL to
3.67 μg/mL. Cellular uptake experiments showed that sulfonium lipids/DNA condensate can be taken
into cells.

Conclusion:
Sulfonium lipids can effectively condense DNA and transfer DNA into cells. The sulfonium
compound is worth further development to reduce the cytotoxicity and increase the transfection
rate as gene vectors.
Effects on Sleep Bruxism Activity of Three Different Oral Appliances: One
Year Longitudinal Cohort Study
Authors: Bargellini Andrea , Castroflorio Tommaso , Graziano Vanessa , Cugliari Giovanni , Deregibus Andrea 
Published: May 2022

Background:
Different oral appliances (OAs) have been proposed to control sleep bruxism
(SB) detrimental effects on the stomatognathic system.

Objective:
The aim of the study was to evaluate the effect of different OAs on SB activity and masticatory
muscle activity (sMMA) measured by EMG.

Methods:
This longitudinal cohort study was conducted on 51 patients (21 M, 30 F, mean age 26,5 ±
3,5) suffering from SB diagnosed with a validated portable EMG-ECG holter and wearing different
OAs: occlusal splints, functional appliance with metallic bites and clear aligners followed after 1 week,
1 month, 3 months, 6 months and 12 months from delivery. A control group of 16 non-treated SB patients
(6 M, 10 F mean age 27,1 ± 1,4) was used as a reference. A multiple regression analysis was performed
to estimate the differences between groups. The level of significance was set as P value <0,05.

Results:
Occlusal splint reduced sleep bruxism index after 1 week, 3, 6 and 12 months from delivery
while functional appliance only after 12 months. Occlusal splints reduced general phasic contractions
only in the first week and sleep bruxism-related phasic contractions at 1 week, 3 and 6 months after
delivery with no significant reductions after 12 months. Patients wearing clear aligners showed a reduction
in general tonic contractions after 6 and 12 months.

Conclusion:
Resin and metal bites can reduce sleep bruxism index, while resin bites can reduce sleep
bruxism-related phasic contractions. Clear aligners do not influence sleep bruxism index but can reduce
tonic contractions.
Exploring the Role of Self-Nanoemulsifying Systems in Drug Delivery:
Challenges, Issues, Applications and Recent Advances
Authors: Verma Ravinder , Mittal Vineet , Pandey Parijat , Bhatia Saurabh , Bhatia Meenakshi , Karavasili Christina , Behl Tapan , Al-Harrasi Ahmed , Tagde Priti , Kumar Manish , Kaushik Deepak 
Published: May 2022

Abstract:
Nanotechnology has attracted researchers around the globe owing to the small size and targeting
properties of the drug delivery vectors. The interest in self-nanoemulsifying drug delivery systems
(SNEDDS) has shown an exponential increase from the formulator's point of view. SNEDDS have
shown wide applicability in terms of controlled and targeted delivery of various types of drugs. They
chemically consist of oil, surfactants and co-surfactants that decrease the emulsion particle size to the
range of <100 nm. However, stability issues such as drug precipitation during storage, incompatibility
of ingredients in shell, decrease their application for the long run and these issues have been highlighted
in this paper. The current review throws limelight on the biological aspects and process parameters. In
addition, the process of absorption from GI is also discussed in detail. SNEDDS have been utilized as a
treatment option for various diseases like cancer, diabetes, and ocular and pulmonary diseases. Along
with this, the authors highlight the advances involving in vivo and in vitro lipolysis studies on
SNEDDS, also highlighting recent innovations in this field, such as novel combinations of drug-free
solid SNEDDS + solid dispersions, lipid-modified chitosan containing mucoadhesive SNEDDS, pHsensitive
SNEDDS and several others.
A Convergent Approach for Protected (+)-Paecilomycin F
Authors: Pabbaraja Srihari , Gurram Ravi 
Published: May 2022

Background:
A stereoselective synthetic strategy toward (+)-paecilomycin F is reported.
The approach utilizes readily available commercial 2,4,6-trihydroxy benzoic acid and easily accessible
chiral R(+)-propylene oxide as starting materials.

Methods:
The synthesis involves regioselective Grignard reaction, Wittig reaction, Sharpless asymmetric
dihydroxylation, Barbier-type allylation, Stille-coupling and ring-closing metathesis as key reactions.

Results:
The target molecule is produced in a 7-step linear sequence with an overall yield of 20% starting
from 2,4,6-trihydroxy benzoic acid or a 12-step sequence with an overall yield of 12.95% starting
from R(+)-propylene oxide.

Conclusion:
The aromatic fragment synthesis was achieved using earlier known protocols starting
from 2,4,6-trihydroxy benzoic acid (vide infra).
Synthesis of Novel Substituted Thiazolo Azapurines and Pyrimido Thiazolo
Azapurines and Evaluation of their Biological Activities
Authors: Annareddygari Srikanth , Kasireddy Venkateshwerreddy , Reddy Jayachandra , Shagum Shashidharreddy , Vantikommu Jyothi 
Published: May 2022

Background:
Nitrogen-rich heterocycles have occupied a special place in medicinal chemistry
due to their exceptional biological activities. In that, thiazolo azapurines and pyrimido thiazolo azapurines
are compounds of interest with their medicinal properties.

Objective:
The objective is to synthesize novel substituted thiazolo azapurines and pyrimido thiazolo
azapurines and evaluate their biological activities.

Methods:
Herein, we have demonstrated the efficient synthesis of thiazole fused triazolo[4,5-d]pyrimidin-
7-ones starting from the easily accessible feedstock chemical cyano acetamide. The reaction proceeds
under mild reaction conditions with diversified substrate scope.

Results:
Notably, the obtained compounds are further derivatized under various sets of conditions to give
the corresponding nitrogen-rich tetracyclic core. All synthesized compounds were tested against four
pathogenic microorganisms and some of the compounds were found potent with good inhibition.

Conclusion:
We have synthesized a diversely substituted nitrogen-rich thiazolo azapurines and pyrimido
thiazolo azapurines and evaluated them for their anti-bacterial activity. All synthesized compounds were
tested against four pathogenic microorganisms, and some of the compounds were found to be potent with
good inhibition.
Propranolol as a Model Drug to Treat Smoking Cessation and its Formulation
as a Transdermal Patch for Effective Management
Authors: Mohapatra Prasanta Kumar , Srivastava Rajnish , Varshney Krishna Kumar , Bhavani Sarvasudhi Durga 
Published: May 2022

Background:
Smoking causes cancer, heart attacks, and stroke and leads to asthma and breathing
problems. Nicotine replacement therapy (NRT) is considered one of the most widely accepted methods
to quit smoking. However, it can lead to relapsed physical and psychological dependence.

Aim:
The present study aimed to explore propranolol, as a model drug to treat relapsed physical and psychological
dependence due to NRT in smoking cessation. Furthermore, for its effective management, the
transdermal drug delivery system has opted for the effective and long-term release of propranolol.

Objective:
The objective of the present study was to investigate and establish the molecular associations
between propranolol with different targets associated with smoking cessation.

Material and Methods:
The molecular association of propranolol with eight different potential targets,
namely, Acetylcholine Binding Protein (AChBP), Cannabinoid Receptor, CB1 and CB2, Monoamine
oxidase (MAO), human dopamine D3 receptor, kainite, Leu- biogenic amine transporters (BAT) and α-
type peroxisome proliferator-activated receptor, was studied via molecular simulation models. Polymeric
films containing propranolol HCI were prepared and evaluated to select a suitable formulation for
developing transdermal drug delivery systems (TDDS). Films containing different ratios of HPMC K4M,
HPMC 15M, and Sodium CMC were prepared by the solvent evaporation technique using PEG 4000
incorporated as a plasticizer, and SLS was used to act as a penetration enhancer. Manufactured transdermal
films were physically evaluated for thickness, weight uniformity %, moisture content %, moisture
uptake %, drug content % and folding endurance.

Results:
Results indicated that propranolol can interact with all eight receptors at the active binding site.
It was found to show considerable interaction with Acetylcholine Binding Protein (AChBP), MAO, human
dopamine D3 receptor, kainite, and Leu- biogenic amine transporters (BAT) with the binding energy
of -6.27, -6.74, -7.07, -6.84, and -6.63 kcal/mol, respectively. The release rate of propranolol HCI
decreased linearly with increasing polymer concentration in the film and depended on the film thickness.
In contrast, the quantity of drug release was proportional to the square root of time. Kinetic data based on
the release exponent, ‘n’ in the Peppas model showed that n values were between 0.95 and 1.08,
indicating that drug release from polymer matrix was predominantly by diffusion with swelling.

Conclusion:
Transdermal drug delivery of propranolol could act as a potential regulator of all studied
targets associated with physical and psychological dependence associated with NRT and smoking cessation.
Furthermore, propranolol-loaded transdermal patches with optimized release could be utilized to
deliver the drug with optimum bioavailability for a considerable time.
Herbal Medicine-derived Compounds for the Prevention and Treatment of Hepatocellular Carcinoma
Authors: Farzaneh Maryam , Farzaneh Zahra 
Published: May 2022

Abstract:Hepatocellular carcinoma (HCC) is the second malignancy worldwide. Dysregulation of various signaling pathways has been detected in HCC. Recent investigations have suggested a new approach for the prevention and treatment of HCC with herbal drugs. The anticancer effects of herbal drugs can be evaluated in animal models or HCC cell lines. Various molecular mechanisms and signaling pathways such as TGF-β, Wnt/β-catenin, SHH, Notch, Hippo, PI3K, and VEGF have been found to induce and promote carcinogenesis of HCC. Herbal drugs can target the signaling pathways in HCC and trigger apoptosis, suppress proliferation, and tumor growth. Molecularly targeted therapies using herbal drugs can be novel therapeutic strategies against HCC. This study provides the latest findings on using herbal medicine-derived compounds in the control of HCC.
Absence of Association Between Serum Mutant p53 with HbA1c and
Insulin in Brain Tumor Patients with Type 2 Diabetes Mellitus
Authors: Sauriasari Rani , Syarif Hardiyanti , Takhwifa Famila , Aninditha Tiara 
Published: May 2022

Aim:
This study aims to determine the prevalence of Type 2 Diabetes Mellitus (T2DM)
in primary Brain Tumor (BT) subjects and assess the relationship between serum mutant p53 serum
and HbA1c and insulin.

Background:
T2DM is known to increase the risk of various types of cancer, which are thought to
be caused by hyperglycemia, hyperinsulinemia, and inflammation. A cohort study that looked at
more than 500,000 subjects with DM over 11 years showed an increased risk of different types of
cancer, including brain tumors. However, several recent studies have shown the opposite. One of
the important pathways in the pathogenesis of brain tumors is the p53 pathway, in which mutations
in the TP53 gene can cause brain cell growth abnormalities.

Objective:
The first stage involved taking subject data for the period January 2017-November 2020
from the medical records of the RSUPN Dr. Cipto Mangunkusumo Hospital Indonesia to assess the
prevalence of T2DM in BT subjects. The second stage was an observational study with a crosssectional
design that collected primary data on subjects (n=86) to assess the relationship between
serum mutant p53 serum and HbA1c and insulin.

Methods:
The analysis of serum mutant p53 serum and insulin was made using the ELISA method,
while measurement of HbA1c was made using the boronate affinity method.

Results:
The results show the prevalence of T2DM in BT subjects at Dr. Cipto Mangunkusumo
Hospital Indonesia was relatively low (9%). Serum mutant p53 levels in T2DM (1.53 ng/mL ± 0.60)
were significantly higher than in BT+T2DM and BT (P < 0.001). The HbA1c value was significantly
lower in BT (5.15% ± 0.44) compared to BT+T2DM and T2DM (P < 0.001), while T2DM insulin
levels (39.54 IU/mL ± 19.1) were significantly higher than BT+T2DM and BT (P < 0.001). There
was no correlation between serum mutant p53 levels and HbA1c and insulin in the three groups.

Conclusion:
The study concludes that the prevalence of BT with T2DM is relatively low (9%) and
that serum levels of mutant p53 in T2DM subjects are higher than in subjects with BT, but there is
no correlation between serum mutant p53 levels and HbA1c and insulin values. Further research
needs to be conducted by analyzing p53 mutants from other specimens, such as brain tumor tissue.
In silico Approach and Molecular Docking Studies of Potent Bioactive Compounds
of Carica papaya as Anti-breast Cancer Agents
Authors: Mirunalini Sankaran , Maruthanila V.L. , Elancheran Ramakrishnan 
Published: May 2022

Background:
Breast cancer is one of the greatest global dilemmas, and the current treatment
option is to target hormone receptors with partial agonists/antagonists. Estrogen and aromatase enzymes
play important roles in breast cancer. Excessive estrogen activity or inadequate estrogen production leads
to various hormonal issues, including breast cancer. Potent breast cancer drugs are Tamoxifen, Paclitaxel,
Cyclophosphamide, Trastuzumab, etc., and aromatase inhibitors, include Anastrozole, Letrozole, and Exemestane,
etc. In general, breast cancer drugs cause numerous adverse effects in humans.

Objectives:
This study has attempted to identify alternative drug candidates from Carica papaya for treating
breast cancer with fewer side effects.

Methods:
To achieve this, we have utilized computational methods to predict the characteristics of bioactive
compounds from Carica papaya and determine the target binding affinities using the Schrödinger suite
(Maestro 9.5). The target protein and ligands were obtained from the well-known database. Carica papaya
has 35 identified bioactive compounds that were drawn using ChemDraw software and performed Ligand
preparation wizard. Absorption, Distribution, Metabolism, and Excretion (ADME) analysis is performed
with QikProp.

Results:
From the docking studies, the phytocompounds such as Chlorogenic acid, Myricetin, Quercetin,
Isorhamnetin, and Catechin showed the highest Glide scores (G Score). Among the five bioactive phytocompounds,
Chlorogenic acid has a higher G Score with good binding energy than Tamoxifen, Anastrozole,
and Letrozole standards. The pharmacokinetic properties and drug-likeness of phytocompounds were
determined using ADME profiling.

Conclusion:
Carica papaya phytocompounds serve as an antiestrogen or aromatase inhibitor that regulates
estrogen levels to reduce the risk of breast cancer in postmenopausal women. As a result, we recommend
that these top five bioactive phytocompounds be investigated further in in vitro and in vivo studies.
Decoding Seven Basic Odors by Investigating Pharmacophores and Molecular
Features of Odorants
Authors: Sharma Anju , Kumar Rajnish , Varadwaj Pritish Kumar 
Published: May 2022

Background:
The odors we perceive are primarily the result of a mixture of odorants. There
can be one or multiple odors associated with an odorant. Several studies have attempted to link odorant
physicochemical properties to specific olfactory perception; however, no universal rule that can determine
how and to what extent molecular properties affect odor perception exists.

Objective:
This study aims to identify important and common features of odorants with seven basic
odors (floral, fruity, minty, nutty, pungent, sweet, woody) to comprehend the complex topic of odors
better.

Methods:
We adopted an in-silico approach to study key and common odorants features with seven
fundamental odors (floral, fruity, minty, nutty, pungent, sweet, and woody). A dataset of 1136 odorants
having one of the odors was built and studied.

Results:
A set of nineteen structural features has been proposed to identify seven fundamental odors
rapidly. The findings also indicated associations between odors, and specific molecular features
associated with each group of odorants and shared spatial distribution of odor features.

Conclusion:
This study revealed olfactory associations, unique chemical properties linked with each set
of odorants, and a common spatial distribution of odor features for considered odors.
The Cytochrome P450 2C19 Polymorphism Associated with Major Adverse
Cardiovascular Events Risk in Kazak Patients Undergoing Percutaneous
Coronary Intervention and Receiving Clopidogrel
Authors: Li Hongjian , Yu Luhai , Wang Tingting , Feng Jie , Zhou Liying , Zhao Ting , Zhang Huilan , Shen Hao , Xu Li , Sun Li , Wu Jianhua 
Published: May 2022

Background:
Clopidogrel activity is influenced by cytochrome P450 (CYP450). CYP2C19 polymorphisms vary by ethnicity and region.

Objectives:
To assess the effect of genetic polymorphisms in CYP2C19*2 and *3 and with clinical and demographic factors on major adverse cardiovascular events (MACE) in Kazak patients following percutaneous coronary intervention (PCI).

Methods:
We enrolled 397 patients with PCI treated with clopidogrel and aspirin for at least 12 months and recorded outcomes within 1 year. Approximately 2 mL of peripheral venous blood samples were used for genotype detection. Multivariable logistic regression analyses were performed to identify factors associated with MACE.

Results:
There were 95 patients (23.9%) who suffered MACE during the period. Logistic regression analysis revealed that CYP2C19*2 carriers (odds ratio [OR]: 2.431, 95% [confidence interval] CI: 1.136–5.275, P = 0.027) and poor metabolizers (OR: 2.128, 95% CI: 0.899–4.82, P = 0.043) were significantly associated with MACE.

Conclusion:
The CYP2C19*2 allele variants and poor metabolizers are associated with MACE in a clopidogrel-treated Kazak population with acute coronary syndrome following PCI.