bluuebunny/crossref_metadata_2025_split huggingface dataset:
Identification of Key Diagnostic Markers and Immune Infiltration in
Osteoarthritis
Authors: Yan Mingyue , Zhao Haibo , Sun Zewen , Chen Jinli , Zhang Yi , Gao Jiake , Yu Tengbo 
Published: April 2022

Background:
Osteoarthritis (OA) is a worldwide chronic disease of the articulating
joints. An increasing body of data demonstrates the immune system's involvement in osteoarthritis.
The molecular mechanisms of OA are still unclear. This study aimed to search for OA immunerelated
hub genes and determine appropriate diagnostic markers to help the detection and treatment
of the disease.

Methods:
Gene expression data were downloaded from the GEO database. Firstly, we analyzed
and identified the differentially expressed genes（DEGs）using R packages. Meanwhile, ssGSEA
was used to determine the activation degree of immune-related genes (IRGs), and WGCNA analysis
was applied to search for co-expressed gene modules associated with immune cells. Then, critical
networks and hub genes were found in the PPI network. Gene Ontology (GO) annotation and
Kyoto Encyclopedia of Gene and Genomes (KEGG) pathway enrichment analyzed the biological
functions of genes. The ability of the hub genes to differentiate OA from controls was assessed by
the area under the ROC curve. A miRNA and transcription factor (TF) regulatory network was
constructed according to their relationship with hub genes. Finally, the validation of hub genes was
carried out by qPCR.

Results:
In total, 353 DEGs were identified in OA patients compared with controls, including 222
upregulated and 131 downregulated genes. WGCNA successfully identified 34 main functional
modules involved in the pathogenesis of OA. The most crucial functional module involved in OA
included 89 genes. 19 immune-related genes were obtained by overlapping DEGs with the
darkgrey module. The String database was constructed using the protein-protein interaction (PPI)
network of 19 target genes, and 7 hub genes were identified by MCODE. ROC curve showed that
7 hub genes were potential biomarkers of OA. The expression levels of hub genes were validated
by qPCR, and the results were consistent with those from bioinformatic analyses.

Conclusions:
Immune-related hub genes, including TYROBP, ITGAM, ITGB2, C1QC, MARCO,
C1QB, and TLR8, may play critical roles in OA development. ITGAM had the highest correction
on immune cells.
Inhaled Atorvastatin Nanoparticles for Lung Cancer
Authors: Tulbah Alaa S. 
Published: April 2022

Background:
Lung cancer is one of the main causes of mortality globally. This research paper
aims a the development of inhaled nanotechnology for lung cancer to deliver an atorvastatin calcium
compound, for lung cancer, capable of reaching the tumor site directly via inhalation.

Methods:
Atorvastatin calcium micellar nanoparticles (ATO-NPs) encapsulated with Pluronic F-127
and polyvinyl alcohol (PVA) were manufactured utilizing the solvent and anti-solvent precipitation
technique. The physicochemical features of the formulation were evaluated in terms of their physicochemical
characteristics using Fourier transform infrared spectroscopy, differential scanning calorimetry,
and dynamic light scattering. Additionally, the Andersen Cascade impactor was used at 15
L/minutes to assist in the aerosols performances of the formulation. The ATO-NPs formula's cell viability
was tested in vitro using the A549 non-small cell lung cancer cell type.

Results:
Transmission electron microscopy was utilized to determine the ATO-NPs particle morphology,
demonstrating a spherical shape with a smooth surface. The fine particle fraction of the aerosol produced
was 62.70 ± 1.18%. This finding suggests that atorvastatin micellar nanoparticles are suitable for
medication administration by inhalation with a wide particle size dispersion. Moreover, it was found in
vitro that concentrations of up to 21 μg/mL of the atorvastatin nanoparticles were safe and non-toxic in
the cell model.

Conclusion:
This study found that atorvastatin micellar nanoparticles for inhalation could potentially be
used for lung cancer treatment.
Open Questions on Gestational Diabetes Mellitus in Twin Pregnancies
Authors: Greco Elena , Savoia Fabiana , Muscettola Giulia , Iliodromiti Stamatina 
Published: April 2022

Abstract:
The concurrent increase in prevalence of Gestational Diabetes Mellitus (GDM) and twin pregnancy over recent decades, in combination with the shared risk factors, has led to speculation that multiples are a risk factor for GDM and that GDM may contribute to twin complications. A small number of heterogeneous studies investigating the impact of GDM in twin pregnancies have led to conflicting conclusions. In comparison to singleton pregnancies, multiple pregnancies have different physiology, requiring increased caloric intake, with a low risk for macrosomia and a high risk for fetal growth restriction. However, in twin pregnancies methods of GDM screening, thresholds for diagnosis and treatment, as well as glycaemic control targets, have been predominantly extrapolated from singletons. The present review provides a comprehensive, critical overview of current evidence on GDM in twin pregnancies with an emphasis on prevalence, methods of screening, thresholds for diagnosis, risk of maternal and feto-neonatal complications and the impact of treatment on perinatal outcomes.
Effects of a Combination of Phytoestrogens on Risk Factors for Cardiovascular
Diseases in Climacteric Women: A Randomized, Placebocontrolled
Trial
Authors: Koehnlein Eloá Angélica , de Barros Evayne , dos Santos Paola Cristine de Bortoli , Frigo Maiara , Weber Jucieli , Zanelatto Carla 
Published: April 2022

Background & Aims:
The incidence of cardiovascular disease in the climacteric has increased, becoming the main cause of death in mature women. The use of phytoestrogens, isoflavone,s and lignans, derived from soy and flaxseed can be natural alternative treatments for this phase of life. This study investigates the utility of isoflavones and lignans derived from soy and flaxseed as natural alternatives to pharmaceuticals to alleviate the symptoms of menopause.

Methods:
A clinical, prospective, randomized, blind, placebo-controlled trial was performed. Forty-eight women aged 40 to 65 years were divided into two groups, Phytoestrogen (PHY), which received a cereal bar containing isoflavones and lignans for 90 days, and Placebo (PLA), which received expanded rice flake bar. The sociodemographic, clinical, anthropometric data, blood pressure (BP) measurements, biochemical and hormonal tests were performed.

Results:
Forty-three women were studied (PHY=21 and PLA=22). There was a significant reduction of diastolic BP in the PHY group after the intervention (p <0.001). The frequency of BP fluctuations in the PHY group significantly decreased to 23.8% after the intervention period (p=0.027), with no significant differences for the other indicators studied.

Conclusion:
The combination of phytoestrogens showed a trend to reduce the blood pressure of climacteric women, however, no significant changes in cardiovascular risk factors were observed. The study was registered under essaclinicos.gov.br, Brazilian Clinical Trials, number 6z8qqy.
Transcriptomic Profiling of Ganoderic Acid Me-Mediated Prevention of
Sendai Virus Infection
Authors: Wan Guoqing , Fan Zheyu , Zhai Dan-Dan , Jiang Liying , Xia Shengli , Gu Xuefeng , Lu Changlian , Shi Ping , Zeng Xiaobin , Meng Jihong , Chen Nianhong 
Published: April 2022

Objectives:
Ganoderic acid Me [GA-Me], a major bioactive triterpene extracted from Ganoderma lucidum, is often used to treat immune system diseases caused by viral infections. Although triterpenes have been widely employed in traditional medicine, the comprehensive mechanisms by which GA-Me acts against viral infections have not been reported. Sendai virus [SeV]-infected host cells have been widely employed as an RNA viral model to elucidate the mechanisms of viral infection.

Methods:
In this study, SeV- and mock-infected [Control] cells were treated with or without 54.3 μM GA-Me. RNA-Seq was performed to identify differentially expressed mRNAs, followed by qRT-PCR validation for selected genes. GO and KEGG analyses were applied to investigate potential mechanisms and critical pathways associated with these genes.

Results:
GA-Me altered the levels of certain genes’ mRNA, these genes revealed are associated pathways related to immune processes, including antigen processing and presentation in SeV-infected cells. Multiple signaling pathways, such as the mTOR pathway, chemokine signaling pathway, and the p53 pathways, correlate significantly with GA-Me activity against the SeV infection process. qRT-PCR results were consistent with the trend of RNA-Seq findings. Moreover, PPI network analysis identified 20 crucial target proteins, including MTOR, CDKN2A, MDM2, RPL4, RPS6, CREBBP, UBC, UBB, and NEDD8. GA-Me significantly changed transcriptome-wide mRNA profiles of RNA polymerase II/III, protein posttranslational and immune signaling pathways.

Conclusion:
These results should be further assessed to determine the innate immune response against SeV infection, which might help in elucidating the functions of these genes affected by GA-Me treatment in virus-infected cells, including cells infected with SARS-CoV-2.
Abiraterone Acetate, in Combination with Apigenin, Attenuates the Survival of Human Castration-Sensitive Prostate Cancer Cells
Authors: Genc Fatih , Atabey Ugur Simal , Serttas Riza , Erdogan Suat 
Published: April 2022

Background:Abiraterone acetate (AA) is a selective inhibitor of CYP17 α-hydroxylase, which is crucial for androgen biosynthesis. Apigenin (Api) is a natural plant-derived flavonoid with potent antiproliferative and antimigration effects.Objectives:We aimed to investigate the possible role of Api in combination with the androgen receptor inhibitor AA in the treatment of androgen-sensitive human prostate cancer LNCaP cells.Methods:The cells were either exposed to 10 μM AA, 25 μM Api, or in combination for 48 hours, then the viability rate was determined by the MTT test, whilst apoptosis and cell cycle phases were assessed by image-based cytometry. The expression of selected mRNA and proteins were evaluated by RT-qPCR and Western blot, respectively.Results:The combination of AA and Api significantly inhibited LNCaP as well as androgen-insensitive PC3 cell survival in a manner more marked than observed with either single treatment. Co-administration of Api with AA triggered apoptosis. This effect was demonstrated by Hoechst staining, and up-regulation of Bax, cytochrome c, caspase -3, and - 8 and down-regulation of Bcl-2 expression confirmed the effect. AA and Api each individually arrested the cell cycle in the G1 phase, with dual applications, leading to no further increase in the effect produced. The expression of NF-κB p105/p50 and the phosphorylation of AKT markedly decreased after apigenin treatment, with combination treatment leading to a favourable effect in terms of further augmenting the reduction.Conclusion:The co-administration of Api with AA strongly enhanced the efficacy of AA therapy in the treatment of prostate cancer cells. These data suggested that the combination of AA and Api would be a potential chemotherapeutic strategy against prostate cancer.
Antitumor Effects of L-citrulline on Hela Cervical Cancer Cell Lines
Authors: Eren Ceren Yildiz , Gurer Hulusi Goktug , Gursoy Ozlem Ozgur , Sezer Canan Vejselova 
Published: April 2022

Introduction:
Cervical cancer is the deadliest gynecological malignancy. This study aims to examine the anticancer
effects of L-citrulline on HeLa cell culture.

Materials-Methods:
HeLa cells were cultured in complete Eagle's minimum essential medium. HeLa cells were
seeded in 96-well plates and incubated with L-citrulline. After incubation, MTT dye was added and incubated. Annexin-
V technique was used to test the apoptosis. The activated caspases of HeLa cells by L-citrulline exposure were
measured with the Caspase 3/7 technique. One-way variance analysis was conducted for statistical analysis by using
GraphPad Prism 6.0 for Windows.

Results:
L-citrulline showed its toxicity on HeLa cells in a dose-dependent manner in application times of 24 and 48
hours. The IC50 dose of L-citrulline was 0.19 and 0.16 mg/mL at 24 and 48 hours, respectively. When HeLa cells were
exposed to an IC50 dose of L-citrulline for 24 hours, the percentages of the dead, early apoptotic, and late apoptotic
cells were detected to be 0.75%, 23.05%, and 12.75%, respectively. The differences in the wideness of the scratch area
were observed at the initial stage and after 24 hours of applying L-citrulline.

Conclusion:
L-citrulline showed its toxicity on HeLa cells in a dose-dependent manner. Based on Annexin and Caspase
findings, it can be concluded that L-citrulline exerted a pro-apoptotic effect on HeLa cells in only a short exposure
time. L-citrulline also showed a migration inhibitory effect. The findings of this study indicate L-citrulline to be worthy
of investigation for its anticancer activities in vitro and in vivo, and as a candidate for cancer therapy.
Drug Targeting and Therapeutic Management of Chronic Myeloid Leukemia: Conventional
and Nanotherapeutic Drug Options
Authors: Akotiah Akrofi , Walker Dominique , Boddie Sarah , Campbell Robert B. 
Published: April 2022

:
Chronic myeloid leukemia (CML) is a blood cancer predominantly affecting older adult patients. According
to the American Cancer Society, an estimated 8,860 people will be diagnosed with CML in 2022. Treatments for CML
have evolved with a focus on CML phase severity or progression. Overall, there have been some breakthrough treatment
options for a high percentage of patients with CML. This is largely due to the discovery of tyrosine kinase inhibitors
(TKI); however, drug resistance continues to present a significant challenge in the management of CML disease.
The use of interferon (IFN), antimetabolites, and bone marrow transplants provides alternative treatment options,
but also presents limitations, including severe side effects, toxicity, and graft versus host disease. Nanomedicine
has demonstrated benefits in terms of efficacy, often reducing or eliminating unwanted toxicities associated with the
use of conventional drug agents. This review summarizes rational molecular targets of CML drugs and provides highlights
of current FDA-approved agents for the treatment of CML. Additionally, this communication includes an overview
of the limitations of conventional treatments and how nanomedicine has addressed challenges encountered during
CML treatment.
Behavioral Pharmacology of Five Uncommon Passiflora Species Indicates
Sedative and Anxiolytic-like Potential
Authors: Sakalem Marna Eliana , Tabach Ricardo , de Oliveira Miriane , Carlini Elisaldo Araújo 
Published: April 2022

Background:
There are over 500 species in the Passiflora genus, and while some of
them are very well known in folk medicine for their anxiolytic effects, very little is known for the
other genus representants, which could also present medicinal effects.

Objective:
In this study, we performed an interspecific pharmacological comparison of five investigated
Passiflora species, all native to Brazil, namely P. bahiensis, P. coccinea, P. quadrangularis,
P. sidaefolia, and P. vitifolia.

Method:
Extracts were administered to mice before behavioral testing, including a general pharmacological
screening and anxiolytic-like effect investigation.

Results:
Three of the species [P. coccinea, P. quadrangularis, and P. sidaefolia] induced a decrease
in locomotor activity of mice; P. coccinea also reduced the latency to sleep. Importantly,
none of the species interfered with motor coordination. Oral administration evoked no severe signs
of toxicity, even at higher doses. Regarding the anxiolytic-like profile, P. sidaefolia reduced the
anxious-like behavior in the Holeboard test in a similar way to the positive control, Passiflora
incarnata, while not affecting total motricity.

Conclusion:
These results indicated that P. coccinea, P. quadrangularis, and P. sidaefolia reduced
the general activity of mice and conferred a calmative/sedative potential to these three species,
which must be further elucidated by future investigations.
Common microRNAs in Epilepsy and Migraine: Their Possibility as Candidates
for Biomarkers and Therapeutic Targets during Comorbid Onset
of Both Conditions
Authors: Munshi Anjana , Ludhiadch Abhilash , Bhardwaj Nidhi , Gotra Palvi , Kumar Roshan 
Published: April 2022

Abstract:
Epilepsy and migraine are chronic neurological disorders with shared clinical as well as
pathophysiological mechanisms. Epileptic patients are at a higher risk of developing migraine compared
to normal individuals and vice versa. Several genetic and environmental risk factors have been
reported to be associated with the development of both diseases. Previous studies have already established
standard genetic markers involved in various pathways implicated in the pathogenesis of both
these comorbid conditions. In addition to genetic markers, epigenetic markers have also been found to
be involved in the pathogenesis of epilepsy and migraine. Among the epigenetic markers, miRNAs
have been explored at length and have emerged as significant players in regulating the expression of
their target genes. miRNAs like miR-22, miR-34a, miR-155, miR-211, and Let-7b play a significant
role in neuronal differentiation and seem to be associated with epilepsy and migraine as comorbid
conditions. However, the exact shared mechanisms underlying the role of these miRNAs in these
comorbid conditions are still unclear. The current review has been compiled with an aim to explore
common microRNAs targeting the genes involved in shared molecular pathways leading to epilepsy
and migraine as comorbid conditions. The new class of ncRNAs, i.e., tRNA transfer fragments, are also
discussed. In addition, their role as potential biomarkers and therapeutic targets has also been evaluated.
However, limitations exist, and based on the current literature available, only a few microRNAs
seem to be involved in the pathogenesis of both these disorders.
Nanostructured Lipid Carriers for Skin Depigmentation: A Modulated
Aspect in Cosmetics
Authors: Shende Pravin , Bevanahally Vineeth 
Published: April 2022

Background:
Hyperpigmentation is a common disorder characterized by brown patches, differential skin tone and sunburns on the area of exposure. Hydroquinone (HQ) is considered the most effective agent in treatment of pigmentation but exhibits skin irritation and local toxicity at higher concentrations. Hence, HQ encapsulated Nano Lipid Carriers (NLCs) were designed and assessed as an alternative for treatment of pigmentation to reduce skin irritation without exhibiting toxicity.

Objective:
The objective of this study was to formulate and evaluate hydroquinone-encapsulated NLCs in cream base as a treatment in hyperpigmentation.

Methods:
The present formulation aims to encapsulate adequate hydroquinone in NLCs for potential application of depigmentation. Hydroquinone was formulated utilizing melt- emulsification ultrasound dispersion technique where aqueous phase consisted of water and Tween 80 whereas; lipid phase was prepared with oleic acid and glyceryl monostearate. The characteristics of final formulation were analyzed by surface morphology, percentage entrapment efficiency, ex-vivo release, in-vitro release and cell line studies.

Results:
Hydroquinone-encapsulated lipid nanocarriers demonstrated promising results within the size range of 22 ± 1.22 nm to 164 ± 0.75 nm and encapsulation efficiency of 78 ± 5.05 % in partially crystallized lipid-based state. The system displayed enhancement in absorption and penetration with zeta potential of -10.2 ± 1.86 mV to -24.6 ± 0.45 mV and presented substantial decrease in water loss as a result of packet formation.

Conclusion:
The results indicated that hydroquinone encapsulated NLCs are safe and effective for treatment of pigmented skin and works by reducing the appearance of dark patches and improving skin texture.
Factors Associated With Protective Mask-Wearing Behavior to Avoid COVID-19 Infection in China: Internet-Based Cross-sectional Study
Authors: Xu Yue , Wu Qingqing , Xu Shuiyang , Zhao Yusui , Zhang Xuehai 
Published: April 2022

Background
The novel coronavirus disease COVID-19 is likely to spread from person to person in close-contact settings. The Chinese Center for Disease Control and Prevention released a handbook on COVID-19, which introduced health information to the public, specifically related to wearing masks correctly and adopting preventive measures to avoid COVID-19 infection.

Objective
The aim of this study was to assess the level of mask knowledge, behavior related to mask usage, and major information channels used for obtaining mask- and COVID-19–related information in China.

Methods
An internet-based survey was conducted primarily using DingXiang Doctor WeChat public accounts. The data about mask knowledge and behavior were collected and analyzed. In addition to descriptive statistics, logistic regression was used to analyze significant risk factors contributing to protective mask behavior.

Results
Data were collected from a total of 10,304 respondents to the survey. More than half of the respondents were under 30 years old and nearly three-quarters were women. Over 80% of participants had a bachelor’s degree or higher, and the largest proportion of respondents (n=4204, 40.80%) were employed as business/service workers. Over half of the study participants were married (n=5302, 51.46%). The findings revealed that 67.49% (6954/10,304) of the participants practiced protective mask behavior; 97.93% (10,091/10,304) believed that wearing masks is an effective protective measure against COVID-19; 96.85% (9979/10,304) chose a mask that has two or more layers of washable, breathable fabric; and 70.57% (7272/10,304) wore the masks correctly. Gender, age, occupation, and education level had significant effects on behavior, whereas marital status and the infection status of family members were not significantly related to mask-wearing behavior. In addition, WeChat public accounts (9227/10,304, 89.55%) were the most prominent source of obtaining health information for Chinese netizens after the outbreak of COVID-19.

Conclusions
This study elucidated that Chinese netizens’ protective mask behavior is far lower than their mask-related knowledge. Improved information channels and adequate information on wearing masks are necessary to improve the public’s protective mask behavior, particularly among men, the elderly, and people with less education.