bluuebunny/crossref_metadata_2025_split huggingface dataset:
The Role of RNA m6A Modification in Cancer Glycolytic Reprogramming
Authors: Zhou You , Huang Tao , Jiang Jingting , Li Yuanqi , Huang Hao , Wu Shaoxian 
Published: August 2022

Abstract:
As one of the main characteristics of neoplasia, metabolic reprogramming provides nutrition
and energy to enhance cell proliferation and maintain environment homeostasis. Glycolysis is one
of the most important components of cancer metabolism and the Warburg effect contributes to the
competitive advantages of cancer cells in the threatened microenvironment. Studies show strong links
between N6-methyladenosine (m6A) modification and metabolic recombination of cancer cells. As the
most abundant modification in eukaryotic RNA, m6A methylation plays important roles in regulating
RNA processing, including splicing, stability, transportation, translation and degradation. The aberration
of m6A modification can be observed in a variety of diseases such as diabetes, neurological diseases
and cancers. This review describes the mechanisms of m6A on cancer glycolysis and their applications
in cancer therapy and prognosis evaluation, aiming to emphasize the importance of targeting
m6A in modulating cancer metabolism.
Caffeic Acid Phenethyl Ester Inhibits Ubiquitination and Degradation
of p53 and Blocks Cervical Cancer Cell Growth
Authors: Li Wei , Yang Cong , Shi Zhongxiu , Long Qingqing , Cheng Zhiying , He Shan , Dong Jiahui , Liu Tao , Wang Chengcheng 
Published: August 2022

Background:
In high-risk human papillomavirus (HR-HPV)-positive cervical
cancer, E6-associated protein (E6AP), an E3 ubiquitin ligase, mediates the ubiquitination
and proteasomal degradation of the tumor suppressor p53. Here, we addressed the
question of whether caffeic acid phenethyl ester (CAPE), a natural product mainly derived
from propolis, can disrupt the interaction between E6AP and p53, inhibit ubiquitination
degradation of p53 and exhibit anti-cervical cancer activity.

Methods:
The ability of CAPE to inhibit growth and to induce apoptosis was shown in
HR-HPV-positive cervical cancer cell lines by performing CCK-8, colony formation and
TUNEL assays. Apoptosis-related proteins were tested by western blotting. Coimmunoprecipitation,
ubiquitination assay and protein stability assay were carried out to determine
whether CAPE can disrupt the E6AP-p53 interaction and inhibit ubiquitination degradation
of p53.

Results:
Our results showed that CAPE inhibits the growth of HR-HPV-positive cervical
cancer cells and induces the activation of apoptosis-related pathways. Importantly, CAPE
inhibits E6AP expression and disrupts the interaction between E6AP and p53. It inhibits
the ubiquitination of p53 and promotes its stabilization.

Conclusion:
In summary, CAPE has a therapeutic effect on HPV-positive malignant
cells, so further studies are needed to assess its clinical application.
Preparation of β-CD-Vitexin Microspheres and their Effects on SW480
Cell Proliferation
Authors: Ding Chengshi , Deng Yanmei , Zhang Kai , Li Shumeng , Wang Deya , Tian Zhongjing , Kang Meiling , Zhang Yingxia , Ma Jing 
Published: August 2022

Objective:
In order to overcome the insolution and low bioavailability of the vitexin in vivo, β-cyclodextrin-vitexin (β-CD–vitexin) microspheres were prepared, and their effects on the proliferation of SW480 cells were observed.

Methods:
Scanning electron microscopy, ultraviolet spectrum, Fourier transform infrared spectroscopy, and release rate analysis were used to identify the formation of β-CD–vitexin microspheres. MTT assay was used to detect the effect of β-CD–vitexin microspheres on tumor cell proliferation at 6, 12, 24, and 48 h. Fluorescence microscopy and flow cytometry were used to observe the effect of β-CD–vitexin microspheres on the apoptosis of SW480 cells. The mRNA expression of p53 gene was measured by qPCR.

Results:
β-CD–vitexin microspheres were successfully prepared. SW480 cell proliferation was inhibited by 0.1, 0.2, and 0.4 mg/mL of β-CD–vitexin microspheres in a dose- and time-dependent manner, and the mechanism of proliferation inhibition was related to cell apoptosis caused by the upregulated expression of p53 gene.

Conclusion:
The preparation of β-CD–vitexin sustained release microspheres is feasible, and β-CD–vitexin microspheres have potential anti-colorectal cancer value.
Phosphoserine Aminotransferase 1: A Metabolic Enzyme Target of
Cancers
Authors: Chen Yuping , Yang Xue , Li Chaojie 
Published: August 2022

Abstract:
Phosphoserine aminotransferase 1 (PSAT1) catalyzes 3-phosphohydroxylpyruvate and glutamate
into 3-phosphoserine and α-ketoglutamate. It integrates metabolic pathways critical for cell proliferation,
survival, migration and epigenetics, such as glycolysis, de novo serine synthesis, citric acid
cycle and one-carbon metabolism. The level of this enzyme has been disclosed to be closely related to
the occurrence, progression and prognosis of cancers like non-small cell lung cancer, colorectal cancer,
esophageal squamous cell carcinoma, breast cancer, etc. Via metabolic catalyzation, PSAT1 offers anabolic
and energic supports for these tumor cells, affecting their proliferation, survival, autophagy, migration
and invasion. Such functions also influence the epigenetics of other noncancerous cells and
drive them to serve tumor cells. Moreover, PSAT1 exerts a non-enzymatic regulation of the IGF1
pathway and nuclear PKM2 to promote EMT and cancer metastasis. Genetically manipulating PSAT1
alters tumor progression in vitro and in vivo. This paper reviews the role and action mechanism of
PSAT1 in tumor biology and chemotherapy as well as the regulation of PSAT1 expression, exhibiting
the perspective for PSAT1 as a new molecular marker and target for cancer diagnosis and treatment.
Virtual Screening-Based Drug Development for the Treatment of Nervous
System Diseases
Authors: Li Qian , Ma Zhaobin , Qin Shuhua , Zhao Wei-Jiang 
Published: August 2022

Abstract:
The incidence rate of nervous system diseases has increased in recent years. Nerve injury or
neurodegenerative diseases usually cause neuronal loss and neuronal circuit damage, which seriously
affect motor nerve and autonomic nervous function. Therefore, safe and effective treatment is needed.
As traditional drug research becomes slower and more expensive, it is vital to enlist the help of cutting-
edge technology. Virtual screening (VS) is an attractive option for the identification and development
of promising new compounds with high efficiency and low cost. With the assistance of computer-
aided drug design (CADD), VS is becoming more and more popular in new drug development
and research. In recent years, it has become a reality to transform non-neuronal cells into functional
neurons through small molecular compounds, which provides a broader application prospect than transcription
factor-mediated neuronal reprogramming. This review mainly summarizes related theory and
technology of VS and the drug research and development using VS technology in nervous system diseases
in recent years, and focuses more on the potential application of VS technology in neuronal reprogramming,
thus facilitating new drug design for both prevention and treatment of nervous system
diseases.
Secondary White Matter Injury Mediated by Neuroinflammation after
Intracerebral Hemorrhage and Promising Therapeutic Strategies of
Targeting the NLRP3 Inflammasome
Authors: Xiao Linglong , Wang Mengqi , Shi Yifeng , Xu Yangyang , Gao Yuan , Zhang Wei , Wu Yang , Deng Hao , Pan Wei , Wang Wei , Sun Haitao 
Published: August 2022

Abstract:
Intracerebral hemorrhage (ICH) is a neurological disease with high mortality and disability. Recent studies showed that white matter injury (WMI) plays an important role in motor dysfunction after ICH. WMI includes WMI proximal to the lesion and WMI distal to the lesion, such as corticospinal tract injury located at the cervical enlargement of the spinal cord after ICH. Previous studies have tended to focus only on gray matter (GM) injury after ICH, and fewer studies have paid attention to WMI, which may be one of the reasons for the poor outcome of previous drug treatments. Microglia and astrocyte-mediated neuroinflammation are significant mechanisms responsible for secondary WMI following ICH. The NOD-like receptor family, pyrin domain-containing 3 (NLRP3) inflammasome activation, has been shown to exacerbate neuroinflammation and brain injury after ICH. Moreover, NLRP3 inflammasome is activated in microglia and astrocytes and exerts a vital role in microglia and astrocytes-mediated neuroinflammation. We speculate that NLRP3 inflammasome activation is closely related to the polarization of microglia and astrocytes and that NLRP3 inflammasome activation may exacerbate WMI by polarizing microglia and astrocytes to the pro-inflammatory phenotype after ICH, while NLRP3 inflammasome inhibition may attenuate WMI by polarizing microglia and astrocytes to the anti-inflammatory phenotype following ICH. Therefore, NLRP3 inflammasome may act as leveraged regulatory fulcrums for microglia and astrocytes polarization to modulate WMI and WM repair after ICH. This review summarized the possible mechanisms by which neuroinflammation mediated by NLRP3 inflammasome exacerbates secondary WMI after ICH and discussed the potential therapeutic targets.
A Case of Spontaneous Mediastinal and Subcutaneous Emphysema in a
Patient with HIV-Infected Pneumonia
Authors: Nie Gang , Dai Hai-Feng , Li Jun-Chen 
Published: August 2022

Background:
Acquired immunodeficiency syndrome is a chronic infectious disease with
high mortality and is caused by the human immunodeficiency virus (HIV). Pneumonia caused by
HIV is common, but it rarely causes spontaneous mediastinal and subcutaneous emphysema.

Case Presentation:
A 21-year-old man with severe pneumonia was hospitalized owing to dyspnea
that had been persisting for 1 day; blood test results confirmed HIV infection. Initial chest computed
tomography (CT) did not reveal mediastinal or subcutaneous emphysema. However, after 21 days
of treatment, the patient experienced discomfort in the neck region and experienced the feeling of
snowflakes on applying pressure. Chest CT showed mediastinal and subcutaneous emphysema, located
in the bilateral cervical roots, anterior upper chest wall, left axillary chest wall, mediastinum,
and other parts. Metagenomic next generation sequencing (mNGS) of the sputum and blood samples
suggested multiple pathogenic infections. Antiinfection treatment was initiated, and changes in
the patient’s condition were monitored. The patient’s subcutaneous emphysema improved during
the follow-up.

Conclusion:
In HIV-infected patients with sudden mediastinal and subcutaneous emphysema,
mNGS can be used to determine the etiological agent during symptomatic treatment. Targeted antipathogen
therapy is helpful in improving the condition of patients with subcutaneous emphysema.
In Silico, In Vitro and In Vivo Assessment of Acetylcholinesterase Inhibitory
Activity of Theobromine Derivatives Containing an Arylpiperazine Fragment
Authors: Andonova Lily , Georgieva Maya , Atanasova Mariyana , Valkova Iva , Doytchinova Irini , Simeonova Rumyana , Zheleva-Dimitrova Dimitrina , Zlatkov Alexander 
Published: August 2022

Background:
In the current Alzheimer’s disease therapy as the preferred treatment are applied acetylcholinesterase inhibitors. Aiming to identify the active pharmacophores necessary for increased acetylcholinesterase inhibitory activity, some docking studies have been applied.

Methods:
In silico docking evaluation of the binding modes, identification of acetylcholinesterase inhibitory activity in vitro through Ellman’s test and ITC protocol, and the in vivo effect. PAMPA evaluation of the GIT and BBB permeability.

Results:
In the present study, two series previously synthesized in our laboratory, arylpiperazine derivatives of theobromine were docked into the rhAChE active sites. Ellman’s test outlined molecules LA1 and LA7 as the most active, with IC50 of 0.708 and 0.299 μM, respectively. In the acute toxicity test, LA7 given intraperitoneally in mice showed moderate toxicity with LD50 of 87.5 mg/kg. The new compound, administered i.p. for 12 days at doses 2 mg/kg/day and 4 mg/kg/day, respectively, showed a pronounced acetylcholinesterase inhibitory activity in vivo.

Conclusion:
The corresponding binding modes were identified, where the docking pose for the studied molecules depends on the protonated state of the nitrogen atom of the piperazine moiety. In the best scored pose for LA7, the xanthine moiety is bound into the catalytic active site (CAS) of acetylcholinesterase, while the arylpiperazine fragment is placed into the peripheral binding site (PAS). For the evaluated selected structures, good permeability through the GIT and BBB assessed by PAMPA was also determined.
Some New 1,2,4-triazole Derivatives Bearing the Pyrimidine Moiety as
Potential Antimycobacterial Agents: Synthesis and Docking Analysis
Authors: Reddy Ganji Sreekanth , Rao Anna Venkateswara , Prasad Mukkanti Siva Naga Anjaneya , Viswanath Ivaturi Venkata Kasi , Laxminarayana Eppakayala 
Published: August 2022

Background:
Pyrimidine and 1,2,4-triazole heterocycles have been linked to a variety of biological
and pharmacological properties such as effective bactericides, fungicides, vermicides, insecticides,
anticancer and antiviral agents. Accordingly, the synthetic derivatives and analogs of these molecules
have attracted attention as potential pharmacological agents.

Objective:
A novel set of heterocyclic derivatives comprising 1,2,4-triazole, pyrimidine moieties was
developed, synthesized, and assessed for their antimicrobial activity.

Methods:
In this study, we performed ligand-based pharmacophore modeling as a promising design strategy
for the design of substituted triazolyl-pyrimidine derivatives as antitubercular agents. The designed
compounds were synthesized and characterized by proton, carbon nuclear magnetic resonance spectroscopy,
infrared, and mass spectroscopy. Synthesized compounds were screened for anti-TB activity using
the agar micro dilution method against M. tuberculosis H37Rv strain.

Results:
Our results revealed that the target 1,2,4-triazoles 7d, 7e, 7c have potent potency against Gram-
(+ve) bacteria S. epidermidis (MICs: 1.7, 3.7, 16.4 μg/mL), whereas final pyrimidines 7c, 7e, 7f, have the
strongest antibacterial activity against Gram-(-ve) strain P. aeruginosa (MICs: 3.5, 6.4, 8.4 μg/mL).
Among all tested compounds, 7a, 7e, and 7h revealed an outstanding antitubercular activity against M.
tuberculosis H37RV strain with MICs of 3.24, 8.93, and 4.70 μg/mL, respectively. The most active ligand
7b reveals highest hydrophobic binding modes with ThrA:127 [2.194 A°], LysA:103 [3.103, 2.164 A°],
GlyA:102 [1.713 A°], ArgA:238 [1.713 A°], ValA:101 [2.113 A°] (hydrogen bondings), AspA:129,
GluA:201 [Pi-anion], AlaA:246, LeuA:180 [Pi-alkyl] and HisA:179 [3.104 A°] [Pi-Pi], respectively.

Conclusion:
In this communication, our aim has been verified by the synthesis of 3-methoxy-10,12-
dimethyl-8-phenyl-6,7,8,12-tetrahydrobenzo[2,3]oxepino[4,5-d][1,2,4]triazolo[4,3-a] pyrimidine derivatives
7 in which 1,2,4-triazole and pyrimidine moieties with benzoxepine in a single molecular framework
were found. After all the above findings, it can be concluded that these molecules become lead molecules
for further synthetic and biological evaluation.
Comprehensive Review on Metal Nanoparticles Catalyzed Synthesis of
Aza- and Oxa-Heterocycles Reported in 2021
Authors: Dhameliya Tejas M. , Patel Rutvi J. , Amin Rajvi H. , Sureja Dipen K. , Bodiwala Kunjan B. 
Published: August 2022

Abstract:
Among the several heterocyclic compounds containing aza- and oxa-heterocycles are predominant
due to their abundant biological importance. The nanoparticles have demonstrated excellent
catalytic activity under optimum conditions with higher reusability or recyclability and higher yields
of synthetic heterocyclic targets. Previously we reviewed the synthesis of aza- and oxa-heterocycles
catalyzed by metal nanoparticles (MNPs) during 2009-2019 and published an update of such reports
of 2020 on the same subject. With anticipations to the next, the present comprehensive work highlights
the synthesis of aza- and oxa-heterocycles catalyzed by MNPs reported during the year 2021 to
update the reader of the present work with the most recent trends in selection of MNPs in the synthesis
of desired heterocyclic scaffolds.
Interventions for Enuresis in Children and Adolescents: An Overview of
Systematic Reviews
Authors: Correia Moretti Eduarda , da Silva Ivson Bezerra , Boaviagem Alessandra , de Lima Anna Myrna Jaguaribe , Lemos Andrea 
Published: August 2022

Background:
enuresis is an involuntary and intermittent loss of urine during sleep and its treatment can be done by pharmacological and non-pharmacological strategies.

Objective:
to conduct an overview to carry out a survey of the systematic reviews about treatment options for children/adolescents with enuresis.

Methods:
Databases used were Cochrane Library, PROSPERO, MEDLINE/PubMed, EMBASE, LILACS/BVS, PEDro, SciELO and Google Scholar. Any type of intervention for the treatment of enuresis in children/adolescents were selected by two independent researchers. Data extraction was done by two independent researchers. The risk of bias was assessed using Risk of Bias in Systematic Reviews (ROBIS) and A MeaSurement Tool to Assess Systematic Reviews (AMSTAR-2).

Results:
seven systematic reviews were included. According to ROBIS, three reviews had a low risk of bias, while the others had a high risk of bias. Based on AMSTAR-2, four systematic reviews were of moderate quality, two were low quality and one was critically low quality.

Conclusion:
there is moderate confidence that the use of desmopressin plus an anticholinergic agent increases the chance of complete response compared to desmopressin alone. Neurostimulation may increase the risk of responses ≥50% and ≥90% compared to the control group. Likewise, it appears that electrical stimulation is superior to placebo about the chance of response ≥50%. In addition, there is the clinical relevance in reducing enuresis episodes per week when neurostimulation is used compared to control groups.
Structural Scaffolds as Anti- Alzheimer Agents
Authors: Alka Tyagi , Sati Bhawana , Chaudhary Anurag 
Published: August 2022

Background:
Understanding the cognitive and behavioral aspects of Alzheimer's disease-
related dementia is surely a sturdy task to deal with. In recent years, a broad search for novel
anti-Alzheimer agents has been continuously conducted. The malfunctioning of various neurotransmitter
systems and the accumulation of abnormal proteins in the brain are the two key characteristics
of this disorder. This is supported by a growing amount of evidence. Some Pharmacophoric
groups/combinations exhibit potential neuroprotective activity.

Methods:
This study aims to compile the most recent and interesting target/target combinations/
pharmacophoric combinations to cure Alzheimer's disease. We concentrated our efforts to find the
ability of certain pharmacophoric elements to interfere with various enzymatic and/or receptor systems
or to work as neuroprotective agents. These pharmacophoric elements may be proved to be
promising leads for future multi-target anti-Alzheimer drug discovery programs.

Result:
Anticholinesterase drugs were mentioned as the best treatment thus far. Additionally, impairments
in the serotonergic, GABAergic, noradrenergic, dopaminergic, and glutaminergic and a
few other pathways have all been linked to memory, speech, behavioral and other alterations in
Alzheimer's disease.

Conclusion:
This includes the study of workable pharmacophoric groups/combinations, receptors/
enzymatic systems and related hypotheses to find the promising therapeutic lead compounds
which could work as future anti-Alzheimer drugs. We discuss future work that would improve our
understanding of this Disease.
An Insight into COVID-19 and Traditional Herbs: Bangladesh Perspective
Authors: Rahman Md. Mominur , Shohag Sheikh , Islam Md. Rezaul , Akhter Shomaya , Mim Sadia Afsana , Sharma Rohit , Rauf Abdur 
Published: August 2022

Abstract:
SARS-CoV-2 was first discovered in Wuhan in late 2019 and has since spread over the
world, resulting in the present epidemic. Because targeted therapeutics are unavailable, scientists have
the opportunity to discover new drugs or vaccines to counter COVID-19, and therefore a number of
synthetic bioactive compounds are now being tested in clinical studies. Due to its broad therapeutic
spectrum and low adverse effects, medicinal herbs have been used as traditional healing medication in
those countries for ages. Due to a lack of synthetic bioactive antiviral medications, pharmaceutical and
alternative therapies have been developed using a variety of herbal compositions. Due to the widespread
availability of herbal and dietary products worldwide, people frequently use them. Notably, the
majority of Bangladeshi people continue to use a variety of natural plants and herbs to treat various
types of diseases. This review discusses how previous research has shown that some herbs in Bangladesh
have immunomodulatory and antiviral effects and how their active ingredients have been gathered.
Even though FDA-approved medications and vaccines are available for the treatment of Covid-
19, the purpose is to encourage the use of herbal medicine as immunomodulators and vaccine adjuvants
for the treatment of COVID-19 prevention.
MDO: A Computational Protocol for Prediction of Flexible Enzyme-ligand
Binding Mode
Authors: Lin Zijing , Al-Ansi Amar Y. 
Published: August 2022

Aim:
Developing a method for use in computer aided drug design

Background:
Predicting the structure of enzyme-ligand binding mode is essential for understanding the properties, functions, and mechanisms of the bio-complex, but is rather difficult due to the enormous sampling space involved.

Objective:
Accurate prediction of enzyme-ligand binding mode conformation.

Method:
A new computational protocol, MDO, is proposed for finding the structure of ligand binding pose. MDO consists of sampling enzyme sidechain conformations via molecular dynamics simulation of enzyme-ligand system and clustering of the enzyme configurations, sampling ligand binding poses via molecular docking and clustering of the ligand conformations, and the optimal ligand binding pose prediction via geometry optimization and ranking by the ONIOM method. MDO is tested on 15 enzyme-ligand complexes with known accurate structures.

Results:
The success rate of MDO predictions, with RMSD < 2 Å, is 67%, substantially higher than the 40% success rate of conventional methods. The MDO success rate can be increased to 83% if the ONIOM calculations are applied only for the starting poses with ligands inside the binding cavities.

Conclusion:
The MDO protocol provides high quality enzyme-ligand binding mode prediction with reasonable computational cost. The MDO protocol is recommended for use in the structure-based drug design.