bluuebunny/crossref_metadata_2025_split huggingface dataset:
FN1 Promotes Thyroid Carcinoma Cell Proliferation and Metastasis by
Activating the NF-Κb Pathway
Authors: Shen Zhijun , Chen Chen 
Published: October 2022

Background:
Thyroid cancer (THCA) is a common endocrine tumor. This study aims to
identify the THCA-related key gene Fibronectin 1 (FN1) by bioinformatics methods and explore its
function and regulatory mechanism.

Methods:
Gene Expression Omnibus database (GSE3678, GSE33630, and GSE53157 datasets) was
searched for the analysis of differentially expressed genes (DEGs) in THCA tissues v.s. (normal
tissues). The enrichment of DEGs was investigated by Gene Ontology and Kyoto Encyclopedia of
Genes and Genomes pathways using the DAVID database. Screening the hub gene was performed with
the STRING database and Cytoscape software. The expression and survival analyses of these hub
genes in THCA were studied with the Gene Expression Profiling Interactive Analysis database.
LinkedOmics database was searched for the related signaling pathways regulated by FN1 in THCA.
Real-time quantitative reverse transcriptase polymerase chain reaction was adopted to detect the
mRNA expression of Fibromodulin, microfibril-associated protein 4, Osteoglycin, and FN1. The cell
viability, growth, migration and aggressiveness were examined by Cell counting kit-8, 5-Ethynyl-2 ′-
deoxyuridine assay, scratch assay, and Transwell assay. The expression levels of NF-κB signaling
pathway-related proteins (p-IκB-α, p-IKK-β, NF-κB p65) were detected by Western blot.

Results:
FN1 mRNA was up-regulated in THCA tissues and cell lines (MDA-T85 and MDA-T41).
The high expression of FN1 is relevant to larger tumor diameters and lymph node metastasis in
sufferers with THCA. Functional experiments showed that overexpression of FN1 in the MDA-T85
cell line promoted growth, migration and aggressiveness; knockdown of FN1 in MDA-T41 cells
inhibited these malignant behaviors. In mechanism, FN1 promoted the expression levels of proteins
related with NF-κB signaling pathway and activated NF-κB signaling pathway.

Conclusions:
FN1 is up-regulated in THCA and facilitates cell growth, migration and invasion by
activating the NF-κB signaling pathway. FN1 will be a promising biomarker of THCA and may
become a molecular target for THCA treatment.
Local Drug Delivery and Tissue Engineering Regulate Vascular Injury
Authors: Edelman Blazer R. , Nugent Helen M. 
Published: October 2022

Abstract:
It has become apparent that mechanical interventions designed to alleviate atherosclerotic vascular disease are beset by accelerated vascular diseases of their own. A multitude of agents have been directed against one or more of the cellular events thought to be involved in this process known as restenosis. Most of these agents suppress smooth muscle cell growth in tissue culture and in animal models, and yet no drug to date
has shown any demonstrable benefit against human disease. This may be due to the suboptimal manner in which these drugs were administered. It has been demonstrated that far more beneficial effects are observed if one matches the delivery of a drug to the natural release of endogenous growth regulators. Controlled release of heparin from polymeric matrices inhibited smooth muscle cell proliferation following injury to vascular endothelium in a manner more efficient than in systemic administration. Moreover, the biologic control achieved by the endothelium is not due to one or several compounds, but rather to the concomitant presence and complimentary activity of all the cell-based products. Perivascular implantation of tissue engineered endothelial cell implants around injured arteries reduced intimal hyperplasia far better than isolated administration of heparin. Thus the coupling of polymer based drug delivery technology and tissue engineering with the science of molecular and cell biology provides a means to understanding the paradox of restenosis and even potential therapies.
Characterization, Antifungal Evaluation against Candida spp. Strains and
Application of Nystatin: β-cyclodextrin Inclusion Complexes
Authors: Urban Amanda Migliorini , Morikava Francine Sumie , Schoeffel Amanda Cristina , Novatski Andressa , Moraes Gustavo Simão , Cachoeira Victoria Schlumberger , Matioli Graciette , Sanches Ito Carmen Antonia , Ferrari Priscileila Colerato , Neppelenbroek Karin Hermana , Urban Vanessa Migliorini , Farago Paulo Vitor 
Published: October 2022

Background:
Nystatin (Nys) is a fungicidal drug commonly prescribed for candidiasis disease in several administration routes. However, Nys is a class IV drug according to the Biopharmaceutical Classification System, that possesses limited bioavailability, and is used for local activity.

Objective:
This study developed and characterized nystatin:β-cyclodextrin (Nys:βCD) inclusion complexes and evaluated their activity against Candida spp.

Methods:
Complexes were characterized by physicochemical techniques and drug dissolution profiles. The susceptibility of C. albicans, C. krusei, C. parapsilosis, C. glabrata, C. guilliermondii, C. tropicalis, and C. auris was assessed using the broth microdilution method. The applicability of Nys:βCD inclusion complex was evaluated by incorporating it into a temporary soft material for denture stomatitis treatment

Results:
Nys was better complexed in a 1:1 molar ratio by freeze-drying and spray-drying methods. The inclusion complexes show bi-exponential release, an initial burst release followed by a sustained manner, presenting higher dissolution efficiency than raw Nys. The 1:1 freeze-drying Nys:βCD complex presents antifungal activity against all evaluated Candida strains, showing the maintenance of the drug effectiveness. The inclusion complex incorporated into a tissue conditioner material for denture stomatitis treatment effectively inhibited more than 90% of C. albicans biofilm growth during 7 and 14 days, in a half dose compared to raw Nys.

Conclusion:
This work represents a significant contribution to treating a wide variety of diseases caused by the Candida species, optimizing the drug bioavailability and compliance to the treatment due to improved drug solubility, dissolution, and sustained delivery.
Early Memory Impairment is Accompanied by Changes in GluA1/
p-GluA1 in APP/PS1 Mice
Authors: Zhao Ya-Bo , Hou Xue-Fei , Li Xin , Zhu Li-Su , zhu Jing , Ma Guo-Rui , Liu Yu-Xuan , Miao Yu-Can , Zhou Qian-Yu , Xu Lin , Zhou Qi-Xin 
Published: October 2022

Aims:
Exploring the neurobiological mechanisms of early AD damage.

Background:
The early diagnosis of Alzheimer's disease (AD) has a very important impact on the
prognosis of AD. However, the early symptoms of AD are not obvious and difficult to diagnose. Existing
studies have rarely explored the mechanism of early AD. AMPARs are early important learning
memory-related receptors. However, it is not clear how the expression levels of AMPARs change in
early AD.

Objective:
We explored learning memory abilities and AMPAR expression changes in APP/PS1 mice
at 4 months, 8 months, and 12 months.

Method:
We used the classic Morris water maze to explore the learning and memory impairment of
APP/PS1 mice and used western blotting to explore the changes in AMPARs in APP/PS1 mice.

Result:
We found that memory impairment occurred in APP/PS1 mice as early as 4 months of age,
and the impairment of learning and memory gradually became serious with age. The changes in GluA1
and p-GluA1 were most pronounced in the early stages of AD in APP/PS1 mice.

Conclusion:
Our study found that memory impairment in APP/PS1 mice could be detected as early as
4 months of age, and this early injury may be related to GluA1.
Hesperidin: A Potential Therapeutic Agent against COVID-19
Authors: Dhingra Ashwani K. , Chopra Bhawna , Rathi Vaibhav , Sapra Sameer 
Published: October 2022

Abstract:
COVID-19, aka Coronavirus Disease 2019, triggered by new severe acute respiratory syndrome
coronavirus-2 or SARS-CoV-2, is now a public health emergency due to its rapid spread, high
transmission efficiency, and severe viral pandemic that is significantly increasing the number of
patients and associated deaths. Currently, no specific treatment is available for this highly contagious
virus. The unavailability of effective and specific treatments and the severity of this epidemic situation
potentiate medicinal chemists’ in supporting new prophylactic or therapeutic interventions against
COVID-19. This study discusses the therapeutic potential of hesperidin, a traditionally used herbal
medicine with an exceptional safety profile. Recent studies on hesperidin advocate its promising potential
in the prevention and management of COVID 19. This paper also discusses the recent clinical
studies based on the previously documented antiviral activity of hesperidin. Herein, we propose the
detailed preclinical and clinical manifestations of hesperidin based on its multifaceted bioactivities to
develop a novel anti-COVID-19 lead.
Review on the Discovery of New Benzimidazole Derivatives as Anticancer
Agents: Synthesis and Structure-activity Relationship (2010-2022)
Authors: Shabana Km , Salahuddin  , Mazumder Avijit , Kumar Rajnish , Datt Vimal , Tyagi Sonakshi , Yar Mohammad Shahar , Ahsan Mohamed Jawed , Sarafroz Mohammad 
Published: October 2022

Background:
Benzimidazole (Benz-fused bicyclic ring system) is the most versatile class of
heterocyclic compounds due to its numerous applications in industrial and synthetic organic chemistry
because of its many biological actions. Benzimidazole analogs have been used to discover various medical
problems, such as cancer, bacterial infections, fungi infections, etc. Researchers are studying nitrogencontaining
hybrid heterocyclic compounds because they provide a broad range of therapeutic potential
and have minimal side effects.

Objective:
The current literature review emphasizes recent developments in the design of new benzimidazole
derivatives as possible anticancer agents with their relationship between structure and activity,
which will give insight into the future design of more active benzimidazole molecules.

Results:
The present review consists of synthetic protocols for the synthesis of benzimidazole derivatives
along with their pharmacological potentials and structure-activity relationship in correlation with synthetic
molecules to provide a depth view of the work done on benzimidazole.

Conclusion:
It would be significant for further research in developing better drug molecules representing
a potent derivative of medicinal agents.
Natural Products as a Major Source of Candidates for Potential Senolytic
Compounds obtained by in silico Screening
Authors: Barrera-Vázquez Oscar S. , Magos-Guerrero Gil A. , Escobar-Ramírez Juan L. , Gomez-Verjan Juan C. 
Published: October 2022

Background:
Preclinical studies suggest that senolytic compounds such as quercetin (a
natural product) and dasatinib (a synthetic product) decrease senescent cells, reduce inflammation,
and alleviate human frailty. This evidence has opened a new field of research for studying the effect
of these compounds on age-related dysfunction and diseases.

Objective:
The present study performed in silico and we identified new potential senolytic candidates
from an extensive database that contains natural products (NPs) and semi-synthetic products (SMSs).

Methods:
Computer programs Chemminer and rcdk packages, which compared the fingerprints of
numerous molecules (40,383) with reference senolytics, and the creation of a pharmacological network
built with signaling pathways and targets involved in senescence processes were used to identify
compounds with a potential activity.

Results:
Six drug-like candidates (3,4'-dihydroxypropiophenone, baicalein, α, β-dehydrocurvularin,
lovastatin, luteolin, and phloretin) were identified.

Conclusion:
To our knowledge, this is the first time that these six natural molecules have been proposed
to have senolytic activity. To validate the methodology employed in the identification of new
drug-like senolytics, experimental evidence is needed with models that evaluate senolytic activity.
Assessment of Knowledge and Awareness Among the Stakeholders of Clinical Research at the Site: A Collaborative, Electronic-Survey Approach to Identify the Indicators of Quality
Authors: Pal Chandana , Rengan Aravind Kumar , Moodahadu Latha , Swaminathan Jayanthi , Nagalla Balakrishna 
Published: October 2022

Background:There has been a concern in the quality of clinical trials conducted in terms of data integrity, accuracy or ethical conduct. This study aimed to assess the tangible gap existing in knowledge and application of rules and guidelines among Researcher, Research staff (RS) and Eth-ics Committee (EC) members - the three research stakeholders at the study sites.Method:A validated e-questionnaire with details for demography, role, years of experience, affilia-tion and questions on knowledge and understanding about their clinical research functions based on the New Drugs and Clinical Trials (NDCT) Rules 2019, including: ‘Role and responsibility, Regula-tions, Reporting timelines, Documentation, Conflict of interest and Miscellaneous’ was circulated among the seven research sites of one organization with their fourteen Institutional ECs as part of the planned annual survey. Responses with >60% correct answers were arbitrarily considered to rep-resent adequate knowledgeResults:Of 201participants, there were 27.4% Researchers, 50.2% were from the EC and 22.4% RS. A greater proportion of Researchers had >5 years (43.6%) of experience. The mean ±SD of correct an-swers obtained was 66.9±14.77 and was statistically significant (p<0.05) among the groups, highest for EC members (71.4±11.51), those with 2-5 years of experience (68.4±14.40), and least for the RS (56.8±11.93). Researchers (> 90%) were aware of their role in the clinical trial agreement and importance of the trial registration in Clinical Trials Registry-India. There were gaps in the Informed Consent (IC) process and post-trial access. Awareness regarding the IC process was adequate among the RS (84%). Awareness that the re-sponsibility of all delegation at site finally lies with the Researchers was adequate (60%) but 20% wrongly believed that the sponsor can have access to subject identification details. Deficiencies were noted regarding documentation, NDCT rules -2019 and serious adverse event (SAE) reporting process. Five percent answered that Data Clarification Forms were generated after reviewing the case report forms. The awareness that NDCT rules-2019 was not for medical devices, student pro-jects or Investigator Initiated Studies was inadequate (56%). The EC members’ awareness in roles and responsibilities was adequate (≥ 90%). Knowledge gaps were noted in EC monitoring of the ongoing trials (32%), and SAE reporting on SUGAM portal (8.8%), where stakeholders can access the regulator's web services using a single window interface for clinical trial related activities.Conclusion:There are gaps in the knowledge of the 3 stakeholders at site. Identifying and rectifying the gray areas will have the site better placed in performance. There is a need for regular training and assess-ments.
LncRNA TCTN2 Promotes the Malignant Development of Hepatocellular
Carcinoma via Regulating mIR-1285-3p/ARF6 Axis
Authors: Liu Qian , Zhu Chunfu , Dong Yanfen 
Published: October 2022

Background:
Hepatocellular carcinoma (HCC) is one of the most life-threatening malignant
diseases. TCTN2 protein participates in tumorigenesis and development. However, whether
lncRNA TCTN2 is associated with HCC pathogenesis remains unclear.

Methods:
The expression of lncRNA, TCTN2, miR-1285-3p, and ARF6 in HCC tissues and cells was detected by a quantitative Real-Time PCR (qRT-PCR) assay. lncRNA TCTN2 specific shRNA was transfected into HCC cells and a functional investigation was performed. The direct interactions between lncRNA TCTN2 and miR-1285-3p and ARF6 were verified by dual-luciferase reporter gene assay. A rescue experiment was performed to confirm the role of miR-1285-3p/ARF6 in association with lncRNA TCTN2.

Results:
LncRNA TCTN2 exhibited a high expression in HCC tumor tissues and cell lines. Knockdown of lncRNA TCTN2 suppressed cell proliferation, and induced cell cycle arrest, and apoptosis through regulating Cyclin D1/p21 and Bax/Bcl-2 signals. Meanwhile, the Knockdown of lncRNA TCTN2 inhibited HCC cell migration and invasion through upregulating MMP2/MMP9. Mechanistic investigation revealed that lncRNA TCTN2 upregulated the expression of ARF6 via sponging miR-1285-3p. Rescue experiments indicated that miR-1285-3p inhibitor reversed the antitumor effects of lncRNA TCTN2 and ARF6 knockdown inhibited the progression of HCC.

Conclusion:
Our results suggested that the knockdown of lncRNA TCTN2 inhibited HCC development by regulating the miR-1285-3p/ARF6 axis, implying that the lncRNA TCTN2 is upregulated in HCC and may serve as a useful patent of diagnosis biomarker in HCC and may demonstrate an important value for the clinical treatment of patients with HCC.
New Era: Mavacamten for Obstructive Hypertrophic Cardiomyopathy
Authors: Al-Horani Rami A. , Woodland Ma’Lik 
Published: October 2022

Abstract:
Obstructive hypertrophic cardiomyopathy results from asymmetric septal hypertrophy,
which eventually obstructs the outflow of the left ventricle. Obstructive hypertrophic cardiomyopathy
is linked to mutations in genes that encode for sarcomere proteins, including actin, β-myosin
heavy chain, titin, and troponin. The mutations lead to structural abnormalities in myocytes and
myofibrils, causing conduction irregularities and abnormal force generation. Obstructive hypertrophic
cardiomyopathy is a chronic disease that worsens over time, and patients become at higher
risk of developing atrial fibrillation, heart failure, and stroke. Up until recently, there were no disease-
specific medications for obstructive hypertrophic cardiomyopathy. Nevertheless, the US Food
and Drug Administration approved mavacamten on April 28, 2022, for the treatment of symptomatic
obstructive hypertrophic cardiomyopathy (New York Heart Association class II to III) in
adults to improve functional capacity and symptoms. Its approval was based on data from EXPLORER-
HCM and EXPLORER-LTE (NCT03723655). Mavacamten is a novel, first-in-class,
orally active, allosteric inhibitor of cardiac myosin ATPase, which decreases the formation of actin-
myosin cross-bridges, and thus, it reduces myocardial contractility, and it improves myocardial
energetics. It represents a paradigm-shifting pharmacological treatment of obstructive hypertrophic
cardiomyopathy. In this review, we describe its chemical and mechanistic aspects as well as its
pharmacokinetics, adverse effects and warnings, potential drug-drug interactions, and contraindications.
Healthy Diet, Grape Phytochemicals, and Vitamin D: Preventing Chronic
Inflammation and Keeping Good Microbiota
Authors: Santa Kazuki 
Published: October 2022

Background:
Since the discovery of penicillin, natural antibiotics have protected humans
from malicious microbes. A breakthrough, however, is needed to tackle problems like antimicrobial
resistance (AMR). This review introduces one of the new approaches for the prevention of several
diseases through a healthy diet, grape phytochemicals, and vitamin D, which nurture the growth of
beneficial bacteria, including gut microbiota, suppressing chronic inflammation and up-regulating
immunity. Antibiotics provide protection against infectious diseases by preventing the growth of
pathogenic microbes. However, inappropriate use of antibiotics increases antimicrobial resistance to
bacteria and limits the benefits of antibiotics. In addition, it is well known that antibiotics kill not
only pathogenic microbes but also beneficial ones that reside in healthy individuals. As a result, the
excess use of antibiotics increases the threat of diseases caused by antibiotic-resistant bacteria. We
can reduce the risk of several diseases, including infectious diseases, in the future by nurturing the
good microbes that live in the human body, thereby preventing chronic inflammation induced by the
proinflammatory cytokine TNF-α, improving predisposition, and up-regulating immunity. Along
with human evolution, residing bacteria in the skin, digestive system, and other areas have changed.
They defend their hosts from malicious microbes in the surrounding environment. With the progress
of medicine, science, and technology, the quality of life and environmental public health have improved
over the years. Under these circumstances, it is necessary to reduce the risk of illness and
keep ourselves healthy by nurturing the good resident microbiota in our bodies and preventing
chronic inflammation through the diet and the intake of phytochemicals and vitamin D. This new
approach is important, along with the traditional method for preventing emerging infectious diseases
in the future.
Interleukin-6 Blockers Improve Inflammation-Induced Lipid Metabolism
Impairments but Induce Liver Fibrosis in Collagen-Induced Arthritis
Authors: Denga Tshimangadzo M. , Gunter Sulè , Fourie Serena , Roux Regina le , Manilall Ashmeetha , Millen Aletta M.E. , Mokotedi Lebogang 
Published: October 2022

Background:
Interleukin-6 (IL-6) receptor blockers improve systemic inflammation,
however, their inconsistent effects on lipid metabolism and drug-induced liver injuries warrant
further investigation. This study aimed to determine the effects of IL-6 receptor blocker therapy
on lipid metabolism and liver morphology in collagen-induced arthritis.

Methods:
Sixty-three Sprague-Dawley rats were divided into control (n = 24), inflammation (n =
24), and IL-6 blocker (n = 15) groups. Inflammation was induced in the inflammation and IL-6-
blocker groups using Bovine type-II collagen and incomplete Freund’s adjuvant. At first signs of
arthritis, the IL-6 blocker group received an IL-6 blocker, tocilizumab for six weeks. Serum
concentrations of low-density lipoprotein cholesterol (LDL-C), high-density lipoprotein
cholesterol (HDL-C) and ATP-binding cassette transporter-A1 (ABCA1) were measured. Liver
fibrosis was determined by histological stains and liver enzymes were measured using the
colorimetric-chemistry analyzer.

Results:
In the inflammation group, HDL-C and ABCA1 were reduced compared to control (p <
0.0001 and p = 0.04, respectively) and IL-6 blocker (p = 0.0003 and p < 0.0001, respectively)
groups. LDL-C was increased in the inflammation compared to control (p = 0.02). Markers of
liver fibrosis were increased in the IL-6 blocker group compared to control and inflammation
groups (picrosirius red collagen area fraction: p < 0.0001 and p = 0.0008, respectively; Masson’s
trichrome collagen area fraction: p = 0.0002 and p = 0.01, respectively). Alkaline phosphatase
concentrations were increased in the IL-6 blocker group compared to the control (p < 0.0001) and
inflammation (p = 0.002) groups.

Conclusion:
IL-6 blockers ameliorated inflammation-induced lipid metabolism impairments,
however they induced liver fibrosis. Although IL-6 blockers may reduce inflammation-induced
metabolic impairments in chronic inflammatory disorders, routine monitoring of liver function is
warranted while on treatment.