bluuebunny/crossref_metadata_2025_split huggingface dataset:
Dracaenone, a Novel Type of Homoisoflavone: Natural Source, Biological Activity
and Chemical Synthesis
Authors: Li Mei-Mei , Lu Jun , Deng Yun 
Published: May 2022

Abstract:
The discovery and synthesis of natural products, especially those possessing novel
scaffolds, are crucial to the development of new drugs. Dracaenones are part of homoisoflavone
natural products, owning a complex spiro-bridged polycyclic structure bearing benzylic
quaternary carbon centers, and some of them reveal considerable biological activity. There
have been continuous studies on these compounds due to the rare structure and important biological
properties. However, a systematic summary and analysis for dracaenone is lacking.
This review aims to generally summarize the natural source, synthetic strategies and biological
activities of dracaenones, moreover, the limitations, challenges, and future prospects were
discussed, wishing to provide references for the follow-up study of compounds with similar
skeleton.
FAM3 Family as Prognostic Factors for Head and Neck Squamous Cell
Carcinoma
Authors: Liu Jianguo , Guan Xiaoyan , Liao Chengcheng , Wang Qian , An Jiaxing , Wang Hui , Xiao Linlin , Long Qian , Zhao Hongbo 
Published: May 2022

Background:
Although head and neck squamous cell carcinoma (HNSCC) is a common
malignancy, the molecular biology landscape underlying its occurrence and development remains
poorly understood. The family with sequence similarity (FAM) 3 family of proteins includes four
family members, namely FAM3A, FAM3B, FAM3C and FAM3D. In particular, FAM3C has been
previously reported to be closely associated with various human malignancies.

Methods:
Combining analyses using The Cancer Genome Atlas, Gene Expression Profiling Interactive
Analysis, Tumor Immune Estimation Resource and MethSurv databases, coupled with the
Gene Ontology and Kyoto Encyclopedia of Genes and Genomes bioinformatics tools, the possible
biological function and key pathways regulated by the FAM3 family in HNSCC were probed.

Results:
High FAM3A expression was found to increase HNSCC mitochondrial biosynthesis and
energy metabolism, inhibit immune cell infiltration in the HNSCC tumor microenvironment, and
be associated with poor prognosis. By contrast, lower expression levels of FAM3B in HNSCC
were associated with a poorer prognosis in patients with HNSCC. This was most likely due to the
finding that FAM3B can inhibit the development of HNSCC by increasing immune cell infiltration,
inhibiting epithelial-mesenchymal transition (EMT) and the cytochrome P450 pathway.
FAM3C was overexpressed in oral squamous cell carcinoma (OSCC) and associated with increased
OSCC cell stemness, immune escape and EMT. In the present study, FAM3C expression
was associated with poor prognosis for patients with HNSCC by suppressing tumor immune cell
infiltration. FAM3C expression was also positively correlated with the expression of epithelial and
mesenchymal markers such as E-cadherin, N-cadherin, Vimentin and ZO-1, which may promote
the partial EMT status in HNSCC and greatly increase its malignancy. FAM3D is a maintenance
factor of the epithelial phenotype in HNSCC that can inhibit the progression of EMT, promote tumor
immune cell infiltration and inhibit HNSCC progression. In addition, methylation levels of the
FAM3 gene family were correlated with the overall survival rate of HNSCC.

Conclusion:
The FAM3 family may be applied as a biomarker and potential therapeutic target for
HNSCC.
Cannabinoids as Potential Molecules for Addiction Disorders
Authors: Martín Giménez Virna Margarita , Mazzei Luciana , Sanz Raúl , Manucha Walter 
Published: May 2022

Background:
Addictions are a group of chronic and recurrent diseases of the brain characterized
by a pathological search for reward or relief through the use of a substance or other action. This
situation implies an inability to control behavior, difficulty in permanent abstinence, a compelling desire
to consume, decreased recognition of significant problems caused by behavior and interpersonal
relationships, and a dysfunctional emotional response. The result is a decrease in the quality of life of
the affected person, generating problems in their work, academic activities, social relationships, or
family or partner relationships. Unfortunately, there are not enough pharmacotherapeutic solutions to
treat addictions due to the complexity of their physiopathology and signaling pathways. Therefore, it is
an imperative search for new pharmacological alternatives which may be used for this purpose.

Purpose of Review:
This review summarizes the main recent findings of the potential therapeutic effects
of different cannabinoids on treating several addictions, including alcohol, opioids, methamphetamine,
cocaine, and nicotine use disorders.

Highlights Standpoints:
It has been demonstrated that many phyto, synthetic, and endogenous cannabinoids
may act as therapeutic molecules in this psychiatric pathology through their action on multiple
cannabinoid receptors. To highlight, cannabinoid receptors, types 1 and 2 (CB1 and CB2) have a crucial
role in modulating the anti-addictive properties of these compounds.
Enhancing the Therapeutic Potential of Nanomedicines by Modifying Surface
Characteristics
Authors: Gulati Nisha , Dua Kamal , Dureja Harish 
Published: May 2022

Abstract:
Nanomedicines have been used over time because of their significant impact on human health
care for the prevention, early detection, diagnosis, treatment, and follow-up of a wide range of illnesses.
Nanomedicines must be adequately characterized in order to develop well-defined nanomedicines with
therapeutic value. The surface charge of nanomedicines plays an important role to determine how they
interact with biological components where the zeta potential is a useful tool for describing the chemical
composition of particle surfaces, such as functional groups, adsorption/desorption, and so on. The main
goal of this review is to present an overview of the impact of nanomedicines' surface charges on absorption,
distribution, metabolism, and in vivo drug release, for example negatively charged nanoparticles
diffuse well through mucus for mucosal drug delivery, whereas positively charged nanoparticles are
preferred for transvascular transport, tumor penetration, and cellular absorption. In this review, we also
highlight how to improve nanomedicines' therapeutic potential by altering their surface characteristics
with the help of various polymers. Future research should be focused on enhancing the therapeutic efficiency
of nanomedicines by changing their surface properties, as well as conducting in-depth mechanistic
studies by changing the surface properties of nanomedicines for the efficient treatment of diseases
with low or no nanomedicine toxicity.
Poloxamer-188 Exacerbates Brain Amyloidosis, Presynaptic Dystrophies,
and Pathogenic Microglial Activation in 5XFAD Mice
Authors: Di Meco Antonio , Kemal Shahrnaz , Popovic Jelena , Chandra Sidhanth , Sadleir Katherine , Vassar Robert 
Published: May 2022

Background:
Alzheimer’s disease (AD) is initiated by aberrant accumulation of amyloid
beta (Aβ) protein in the brain parenchyma. The microenvironment surrounding amyloid plaques is
characterized by the swelling of presynaptic terminals (dystrophic neurites) associated with lysosomal
dysfunction, microtubule disruption, and impaired axonal transport. Aβ-induced plasma membrane
damage and calcium influx could be potential mechanisms underlying dystrophic neurite formation.

Objective:
We tested whether promoting membrane integrity by brain administration of a safe FDA
approved surfactant molecule poloxamer-188 (P188) could attenuate AD pathology in vivo.

Methods:
Three-month-old 5XFAD male mice were administered several concentrations of P188 in the
brain for 42 days with mini-osmotic pumps. After 42 days, mice were euthanized and assessed for amyloid
pathology, dystrophic neurites, pathogenic microglia activation, tau phosphorylation, and lysosomal
/ vesicular trafficking markers in the brain.

Results:
P188 was lethal at the highest concentration of 10mM. Lower concentrations of P188 (1.2, 12,
and 120μM) were well tolerated. P188 increased brain Aβ burden, potentially through activation of the
γ-secretase pathway. Dystrophic neurite pathology was exacerbated in P188 treated mice as indicated
by increased LAMP1 accumulation around Aβ deposits. Pathogenic microglial activation was increased
by P188. Total tau levels were decreased by P188. Lysosomal enzyme cathepsin D and calciumdependent
vesicular trafficking regulator synaptotagmin-7 (SYT7) were dysregulated upon P188 administration.

Conclusion:
P188 brain delivery exacerbated amyloid pathology, dystrophic neurites, and pathogenic
microglial activation in 5XFAD mice. These effects correlated with lysosomal dysfunction and dysregulation
of plasma membrane vesicular trafficking. P188 is not a promising therapeutic strategy against
AD pathogenesis.
mGlu3 Metabotropic Glutamate Receptors as a Target for the Treatment
of Absence Epilepsy: Preclinical and Human Genetics Data
Authors: Russo Emilio , Celli Roberta , Striano Pasquale , Citraro Rita , Di Menna Luisa , Cannella Milena , Imbriglio Tiziana , Koko Mahmoud , Euro Epinomics-Cogie Consortium  , De Sarro Giovambattista , Monn James A. , Battaglia Giuseppe , Luijtelaar Gilles Van , Nicoletti Ferdinando , Leo Antonio 
Published: May 2022

Background:
Previous studies suggest that different metabotropic glutamate (mGlu) receptor subtypes are potential drug targets for the treatment of absence epilepsy. However, no information is available on mGlu3 receptors.

Objective:
To examine whether (i) abnormalities changes of mGlu3 receptor expression/signaling are found in the somatosensory cortex and thalamus of WAG/Rij rats developing spontaneous absence seizures; (ii) selective activation of mGlu3 receptors with LY2794193 affects the number and duration of spike-wave discharges (SWDs) in WAG/Rij rats; and (iii) a genetic variant of GRM3 (encoding the mGlu3 receptor) is associated with absence epilepsy.

Methods:
Animals: immunoblot analysis of mGlu3 receptors, GAT-1, GLAST, and GLT-1; real-time PCR analysis of mGlu3 mRNA levels; assessment of mGlu3 receptor signaling; EEG analysis of SWDs; assessment of depressive-like behavior.
Humans: search for GRM3 and GRM5 missense variants in 196 patients with absence epilepsy or other IGE/GGE Idiopathic Generalized Epilepsy (IGE)/ Genetic Generalized Epilepsy (GGE) and 125,748 controls.

Results:
mGlu3 protein levels and mGlu3-mediated inhibition of cAMP formation were reduced in the thalamus and somatosensory cortex of pre-symptomatic (25-27 days old) and symptomatic (6-7 months old) WAG/Rij rats compared to age-matched controls. Treatment with LY2794193 (1 or 10 mg/kg, i.p.) reduced absence seizures and depressive-like behavior in WAG/Rij rats. LY2794193 also enhanced GAT1, GLAST, and GLT-1 protein levels in the thalamus and somatosensory cortex. GRM3 and GRM5 gene variants did not differ between epileptic patients and controls.

Conclusions:
We suggest that mGlu3 receptors modulate the activity of the cortico-thalamo-cortical circuit underlying SWDs and that selective mGlu3 receptor agonists are promising candidate drugs for absence epilepsy treatment.
Structural Optimization for 4-hydroxyphenylpyruvate Dioxygenase Inhibitors
Based on 3D-QSAR, Molecular Docking, SBP Modeling and MOLCAD
Studies
Authors: He Jiaqin , Zhang Mei , Chen Keying , Wang Xiaomeng , Wang Juan , Lin Zhihua 
Published: May 2022

Background:
The research based on natural product herbicides has been increasingly attractive
in the field of agriculture. 4-hydroxyphenylpyruvate dioxygenase (HPPD) is one of the most promising
compounds in the field of herbicide innovation.

Objective:
This paper aims to study the relationship between the activity and structure of quinazoline-
2,4-dione derivatives, and to design novel HPPD inhibitors.

Methods:
A set of quinazoline-2,4-dione derivatives underwent 3D-QSAR studies as well as molecular
docking. MOLCAD analysis and 8-point pharmacophore model provided an important reference for us to
understand the interaction mode of HPPD and antagonists.

Results:
The CoMFA (n = 5; q2 = 0.778; r2 = 0.985) and CoMSIA (n = 6; q2 = 0.776; r2 = 0.95) models
had remarkable stability and predictability. MOLCAD studies and pharmacophore modeling proved the
validity of the 3D-QSAR model. On the basis of the gained information, nine novel derivatives as potential
candidates of HPPD inhibitors with better predicted activities were designed, mainly binding to HPPD
via lipophilic interaction and hydrogen bonding. The key hydrophobic residues of HPPD, Phe381,
His308, Asn282, Phe392 and Leu368, were found to be antagonist binding sites that are important factors
for the stability of the antagonist binding site.

Conclusion:
The structural basis and activity of HPPD inhibitors were revealed, which might provide
clear and solid insights to guide the rational design of novel HPPD inhibitors.
Insights into Evolutionary and Conservancy Analytics on Human Insulin
Receptor Proteins
Authors: Dwivedi Manish , Dharshini Kottaisamy Chidhambara Priya , Raj Divya S. 
Published: May 2022

Background:
The insulin receptor protein of humans is proposed to have substantial application
in the regulatory pathway of glucose levels in the blood. The cellular function of the insulin hormone
is initiated by its association with the insulin receptor (IR) protein, and this process is common to most
vertebrate species. Thus, phylogenetic analysis of IR protein among various associated species in vertebrates
can elucidate the importance of residues and structure, and the relationship with its function as the
conserved region of residues is associated with evolutionary conservation on insulin receptor proteins. In
the present study, we have used various in silico approaches and conducted the phylogenetic analysis.

Method:
The basic local alignment search tool (BLAST) was employed to screen the 250 vertebrates.
After evolutionary analysis, Pan troglodytes (Chimpanzees) have been observed as the closest relatives of
Homo sapiens concerning insulin receptor proteins.

Results:
Human insulin receptor protein was found to have hydrophobic nature by hydrophobicity profile
analysis, where most of the positions were above the mean hydrophobicity value from n-terminal to cterminal
residues, whereas carboxy-terminal residues were observed as hydrophilic. High entropy was
observed at the short stretch at N-terminal, C-terminal, and a linker region within the alignment, but the
overall positions which were aligned showed low entropic regions.

Conclusion:
The outcomes of this work have revealed some unexplored specific characteristics of the
conserved domains among different taxa of selected vertebrates and have also illustrated the hierarchical
assemblage-based inconsistent variation of the IR proteins, and further conservancy analysis discloses the
significance of each site for protein structure or function.
Trends of Receptor Tyrosine Kinase Researches Based on Bibliometric
Analysis
Authors: Rao Guo-Wu , Li Ying , Fang Hui , Wang Ju , Wan Yue-Hua 
Published: May 2022

Abstract:
Malignant tumor is one of the diseases threatening human life and health. Traditional antitumor therapy has some limitations in clinical application, so the development of targeted antitumor drugs has become one of the important research directions of cancer medicine. Since the first tyrosine kinase inhibitor was approved in 2001, this research field has attracted global attention. In this survey, the Web of Science database was adopted to make a bibliometric analysis of the global scientific production of receptor tyrosine kinases in recent 20 years. A total of 14378 documents related to the subject were retrieved and analyzed according to six main aspects: area, journal, country, institution, authors, and keywords. The results show that the United States is currently in a leading position in this field and has established the largest cooperation network with other countries. Harvard University has made the greatest contribution to the field of receptor tyrosine kinases, including the number of publications, the average number of citations per paper, and the h-index. Besides, PLOS One ranked first among the top 15 academic journals in the number of publications related to receptor tyrosine kinases during the survey period. Our research comprehensively evaluates the research status and cooperation network of receptor tyrosine kinases, hoping help researchers to guide their projects or find potential collaborators.
The Importance of Fracture Liaison Services to the Healthcare System: A Review
Authors: Patel Shaan , Daniels Natasha Faye , Lim Jiang An , Zhou Andrew Kailin , Thahir Azeem , Krkovic Matija 
Published: May 2022

Abstract:
Osteoporosis is an important public health concern, with secondary fragility fractures
carrying a poor prognosis. The role of a Fracture Liaison Service (FLS) is to identify fragility fracture
patients via investigation and risk assessment. This serves to address the osteoporosis treatment
care gap that exists where the majority of patients with a new fragility fracture over 50-years-old
fail to receive a bone mass density (BMD) scan and osteoporosis treatment, ultimately receiving inadequate
care. Osteoporosis medication is effective in reducing secondary fragility fractures. However,
treatment adherence poses a problem. The FLS serves to prevent more serious secondary fragility
fractures such as hip fractures. This minimises operative costs and the cost of postoperative
care and results in fewer secondary care and care home admissions, increasing healthcare savings.
Implementation of the FLS is effective in increasing investigation, treatment initiation, and adherence,
with a corresponding decrease in refracture rate and mortality. This paper aims to evaluate the
previous osteoporosis treatment care gap, the effectiveness of osteoporosis medications currently
available, and finally, the cost and clinical effectiveness of the FLS serving as a secondary prevention
tool.
The Spectrum of Airway Disease Associated with Rheumatoid Arthritis
Authors: Siddiqui Mohd Faizan , Sherbaevna Salieva Rana , Tashalievich Mamasaidov Abdumitalib , Momunovna Azhimamatova Rakhima , Alrefaee Salhah Hamed , Sovetbekovna Musaeva Begaiym , Mirzaevna Mamatova Sabirakhan 
Published: May 2022

Abstract:
Airway involvement results from long-standing rheumatoid arthritis leading to severe pulmonary complications, correlated with increased mortality and socioeconomic costs. Different types of pulmonary lesions, including pulmonary rheumatoid nodule, pulmonary arteritis, diffuse interstitial fibrosis, and rheumatoid pneumoconiosis or Caplan's syndrome, are believed to be relat-ed to rheumatoid arthritis (R.A.). The above changes may indicate the increased susceptibility to the infection, toxins from a disease, or chronic immunity activation. The symptoms vary from asymp-tomatic to severe life-treating conditions, and the prognosis varies depending on the genre and se-verity of involvement. Our study aims to assess the prevalence and characteristics of airways asso-ciation in rheumatoid arthritis as these data provide a brief insight into early diagnosis and treat-ment, which could be applied to minimize complications of airways diseases in rheumatoid arthritis.
Evaluation of Left Ventricular Function in Patients with Coronary Slow Flow by the Dobutamine Stress Echocardiography
Authors: Huang Rongchong , Yang Yanzong , Wu Jian , Meng Shuang , Wang Hui 
Published: May 2022

Background:
The study aims to assess the changes to left ventricular (LV) function of patients
with the coronary slow flow (CSF) in response to stress induced by low dose dobutamine.

Methods:
Based on coronary angiography (CAG) results, a total of 186 patients undergoing CAG for
chest pain and suspected coronary heart disease were assigned to the CSF group (n = 142) and control
group (n = 44). Patients in the CSF group underwent two-dimensional speckle-tracking echocardiography
(STE) during the dobutamine stress test to evaluate LV systolic and diastolic functions.

Results:
At rest, there were no statistically significant differences in LV peak systolic longitudinal
strain (LS), LV peak systolic longitudinal strain rate (LSRs), LV peak early diastolic longitudinal
strain rate (LSRed), LV circumferential strain (CS), or LV circumferential strain rate (CSRed) between
the CSF and control groups. In the CSF group, LS and LSRs first increased as the infusion rate was
increased to 10 μg/kg/min (all, p < 0.05), before decreasing at infusion rates of 15 and 20 μg/kg/min
(all, p < 0.05). CS and CSRed increased in the CSF group at infusion rates of 5, 10, and 15 μg/kg/min,
(all, p < 0.05), but decreased significantly at 20 μg/kg/min (all, p < 0.05).

Conclusions:
At rest, LV systolic and diastolic functions were comparable between the CSF and control
groups. However, when blood flow to the heart muscles was insufficient, LSRed decreased first, followed
by LS. In terms of sensitivity to myocardial ischemia, LS is a better strain parameter than CS.
Dynamic Volume Computed Tomography for Characterizing Pulsatile
Tinnitus Caused by Sigmoid Sinus Diverticulum with Bone Defects: Clinical
Implications
Authors: Pan Yu-Ning , Li Ai-Jing , Zhang Jie , Mao Quan-Liang , Shen Fang-Jie 
Published: May 2022

Objective:
The objective of this study is to investigate the diagnosis of dynamic volume
computed tomography (CT) for pulsatile tinnitus caused by sigmoid sinus diverticulum (SSD) and
bone defects.

Methods:
Data obtained by dynamic volume CT from 35 patients with SSD were retrospectively collected.
Then the ear morphological parameters, including bone defect, transverse sinus stenosis, position
of the jugular bulb, jugular bulb diverticulum, defect of the jugular bulb wall, gross venous sinus
thrombosis and SSD, and blood perfusion parameters, including cerebral blood flow (CBF), cerebral
blood volume (CBV), and mean transit time (MTT), were evaluated and compared between the tinnitus
side and the asymptomatic side of the ear.

Results:
The maximum diameters of the bone defects on the tinnitus side were greater than those on
the asymptomatic side (Horizontal 6.36±2.35mm vs. 1.12±0.78mm; Longitudinal 4.87±1.25 vs.
0.88±0.06mm). Dynamic volume CT visually displayed the SSD herniated into the adjacent mastoid
via the bone defect. Transverse sinus stenosis, high position of the jugular bulb, jugular bulb diverticulum,
defect of the jugular bulb wall, and gross venous sinus thrombosis were present more frequently
on the tinnitus side than on the asymptomatic side (P < 0.05). Moreover, CBF, CBV, and MTT were
significantly greater on the tinnitus side than on the asymptomatic side (P < 0.05).

Conclusion:
Dynamic volume CT examination is an effective method for the diagnosis of pulsatile
tinnitus caused by SSD with bone defects.