bluuebunny/crossref_metadata_2025_split huggingface dataset:
Spray-dried Solid Lipid Nanoparticles for Enhancing Berberine Bioavailability
via Oral Administration
Authors: Nguyen Van Hong , Manh Le Khoa Nguyen , Nguyen Mai Chau Ngoc 
Published: November 2023

Background:
Berberine (BBR), an Eastern traditional medicine, has expressed novel therapeutic activities,
especially for chronic diseases like diabetes, hyperlipemia, hypertension, and Alzheimer's disease.
However, the low oral bioavailability of BBR has limited the applications of these treatments. Hence, BBRloaded
solid lipid nanoparticles (BBR-SLNs) were prepared to improve BBR absorption into systemic circulations
via this route.

Methods:
BBR-loaded solid lipid nanoparticles (BBR-SLNs) were prepared by ultrasonication and then transformed
into solid form via spray drying technique. The size morphology of BBR-SLNs was evaluated by dynamic
light scattering (DLS) and scanning electron microscope (SEM). Crystallinity of BBR and interaction
of BBR with other excipients were checked by spectroscopic methods. Entrapment efficiency of BBR-SLNs
as well as BBR release in gastrointestinal conditions were also taken into account. Lastly, SLN's cytotoxicity
for loading BBR was determined with human embryonic kidney cells (HEK293).

Results:
Stearic acid (SA), glyceryl monostearate (GMS), and poloxamer 407 (P407) were selected for BBRSLNs
fabrication. BBR-SLNs had homogenous particle sizes of less than 200 nm, high encapsulation efficiency
of nearly 90% and loading capacity of above 12%. BBR-SLN powder could be redispersed without significant
changes in physicochemical properties and was stable for 30 days. Spray-dried BBR-SLNs showed a better
sustained in vitro release profile than BBR-SLNs suspension and BBR during the initial period, followed
by complete dissolution of BBR over 24 hours. Notably, cell viability on HEK293 even increased up to 150%
compared to the control sample at 100 μg/mL BBR-unloaded SLNs.

Conclusion:
Hence, SLNs may reveal a promising drug delivery system to broaden BBR treatment for oral administration.
Exploring the Targets and Molecular Mechanisms of Thalidomide in the Treatment of Ulcerative Colitis: Network Pharmacology and Experimental
Validation
Authors: Li Jun , Tao Qin , Xie Yang , Wang Peng , Jin Ruiri , Huang Xia , Chen Youxiang , Zeng Chunyan 
Published: November 2023

Background:
Ulcerative colitis (UC) is a chronic, nonspecific, inflammatory disease of the intestine
with an unknown cause. Thalidomide (THA) has been shown to be an effective drug for the treatment of UC.
However, the molecular targets and mechanism of action of THA for the treatment of UC are not yet clear.

Objectives:
Combining network pharmacology with in vitro experiments, this study aimed to investigate the
potential targets and molecular mechanisms of THA for the treatment of UC.

Methods:
Firstly, relevant targets of THA against UC were obtained from public databases. Then, the top 10
hub targets and key molecular mechanisms of THA for UC were screened based on the network pharmacology
approach and bioinformatics method. Finally, an in vitro cellular inflammation model was constructed using
lipopolysaccharide (LPS) induced intestinal epithelial cells (NCM460) to validate the top 10 hub targets and
key signaling pathways.

Results:
A total of 121 relevant targets of THA against UC were obtained, of which the top 10 hub targets
were SRC, LCK, MAPK1, HSP90AA1, EGFR, HRAS, JAK2, RAC1, STAT1, and MAP2K1. The PI3K-Akt
pathway was significantly associated with THA treatment of UC. In vitro experiments revealed that THA treatment
reversed the expression of HSP90AA1, EGFR, STAT1, and JAK2 differential genes. THA was able to
up- regulate the mRNA expression of pro-inflammatory factor IL-10 and decrease the mRNA levels of anti-inflammatory
factors IL-6, IL-1β, and TNF-α. Furthermore, THA also exerted anti-inflammatory effects by inhibiting
the activation of the PI3K/Akt pathway.

Conclusion:
THA may play a therapeutic role in UC by inhibiting the PI3K-Akt pathway. HSP90AA1,
EGFR, STAT1, and JAK2 may be the most relevant potential therapeutic targets for THA in the treatment of
UC.
Integrated Network Pharmacology and Cellular Assay to Explore the
Mechanisms of Selenized Tripterine Phytosomes (Se@Tri-PTs) Alleviating
Podocyte Injury in Diabetic Nephropathy
Authors: Zhu Shiping , Liu Qiubo , Chang Yuling , Luo Chunhua , Zhang Xingwang , Sun Shengyun 
Published: November 2023

Aim:
This work aimed to elucidate the mechanisms of Se@Tri-PTs in alleviating podocyte injury
via network pharmacology and in vitro cellular assay.

Background:
Selenized tripterine phytosomes (Se@Tri-PTs) have been confirmed to undertake synergistic
and sensitized effects on inflammation, which may be curatively promising for diabetic nephropathy (DN).
However, the mechanisms of Se@Tri-PTs in alleviating podocyte injury, a major contributor to DN, still remain
unclear.

Objective:
The objective of the study was to find out the underlying mechanisms of Se@Tri-PTs in alleviating
podocyte injury in diabetic nephropathy.

Methods:
The key components and targets of Tripterygium wilfordii (TW) significant for DN as well as the signaling
pathways involved have been identified. A high glucose-induced podocyte injury model was established
and verified by western blot. The protective concentration of Se@Tri-PTs was screened by CCK-8 assay.
Podocytes cultured with high glucose were treated with Se@Tri-PTs under protective levels. The expression
of key protective proteins, nephrin and desmin, in podocytes, was assayed by western blot. Further, autophagy-
related proteins and factors, like NLRP3, Beclin-1, LC3II/LC3, P62, and SIRT1, were analyzed,
which was followed by apoptosis detection.

Results:
Network pharmacology revealed that several monomeric components of TW, especially Tri, act on
DN through multiple targets and pathways, including the NLRP3-mediated inflammatory pathway. Se@Tri-
PTs improved the viability of podocytes and alleviated their injury induced by high glucose at 5 μg/L or
above. High-glucose induction promoted the expression of NLRP3 in podocytes, while a low concentration of
Se@Tri-PTs suppressed the expression. A long-term exposure of high glucose significantly inhibited the autophagic
activity of podocytes, as manifested by decreased Beclin-1 level, lower ratio of LC3 II/LC3 I, and
up- regulation of P62. This abnormality was efficiently reversed by Se@Tri-PTs. Importantly, the expression
of SIRT1 was up-regulated and podocyte apoptosis was reduced.

Conclusion:
Se@Tri-PTs can alleviate podocyte injury associated with DN by modulating NLRP3 expression
through the pathway of SIRT1-mediated autophagy.
Molecular Dynamics of a N-Cyclohexyl-1,2,4-Oxadiazole Derivative as a Reversible Cruzain Inhibitor in Trypanosoma cruzi
Authors: Rocha Yasmim Mendes , de Moura Gabriel Acácio , Rodrigues João Pedro Viana , Pinheiro Cristian Vicson Gomes , de Oliveira Ronaldo Nascimento , Marinho Marcia Machado , Nicolete Roberto 
Published: November 2023

Background:
Chagas disease kills around 10,000 people yearly, primarily in Latin
America, where it is prevalent. Current treatment has limited chronic effectiveness, is unsafe,
and has substantial side effects. As a result, the use of oxadiazole derivatives and similar heterocyclic
compounds as bioisosteres are well known, and they are prospective candidates in the hunt
for novel anti-Trypanosoma cruzi chemicals. Recent research has revealed that the cysteine protease
cruzain from T. cruzi is a validated target for disease treatment.

Objective:
Thus, using a molecular dynamics simulation, the current study attempted to determine
if a significant interaction occurred between the enzyme cruzain and its ligand.

Results:
Interactions with the catalytic site and other critical locations were observed. Also, the
RMSD values suggested that the molecule under research had stable interactions with its target.

Conclusion:
Finally, the findings indicate that the investigated molecule 2b can interfere enzymatic
activity of cruzain, indicating that it might be a promising antichagasic drug.
In Silico Pharmacokinetics, Molecular Docking and Molecular Dynamics
Simulation Studies of Nucleoside Analogs for Drug Discovery- A Mini
Review
Authors: Kawsar Sarkar M.A. , Munia Nasrin S. , Saha Supriyo , Ozeki Yasuhiro 
Published: November 2023

Abstract:
Nucleoside analogs have been widely used as antiviral, antitumor, and antiparasitic
agents due to their ability to inhibit nucleic acid synthesis. Adenosine, cytidine, guanosine, thymidine
and uridine analogs such as didanosine, vidarabine, remdesivir, gemcitabine, lamivudine, acyclovir,
abacavir, zidovusine, stavudine, and idoxuridine showed remarkable anticancer and antiviral
activities. In our previously published articles, our main intention was to develop newer generation
nucleoside analogs with acylation-induced modification of the hydroxyl group and showcase their
biological potencies. In the process of developing nucleoside analogs, in silico studies play an important
role and provide a scientific background for biological data. Molecular interactions between
drugs and receptors followed by assessment of their stability in physiological environments, help to
optimize the drug development process and minimize the burden of unwanted synthesis. Computational
approaches, such as DFT, FMO, MEP, ADMET prediction, PASS prediction, POM analysis,
molecular docking, and molecular dynamics simulation, are the most popular tools to culminate all
preclinical study data and deliver a molecule with maximum bioactivity and minimum toxicity. Although
clinical drug trials are crucial for providing dosage recommendations, they can only indirectly
provide mechanistic information through researchers for pathological, physiological, and pharmacological
determinants. As a result, in silico approaches are increasingly used in drug discovery
and development to provide mechanistic information of clinical value. This article portrays the current
status of these methods and highlights some remarkable contributions to the development of
nucleoside analogs with optimized bioactivity.
Thyroid Disorders and Peripheral Arterial Disease
Authors: Studen Katica Bajuk , Gaberscek Simona , Zaletel Katja , Blinc Ales , Sabovic Miso , Schernthaner Gerit-Holger , Anagnostis Panagiotis , Antignani Pier Luigi , Jensterle Mojca , Mikhailidis Dimitri P , Poredos Pavel 
Published: November 2023

Abstract:
Hypothyroidism and hyperthyroidism, both overt and subclinical, are associated with increased
risk of cardiovascular morbidity and mortality. The association between thyroid-stimulating
hormone levels and cardiovascular risk has been demonstrated in large epidemiological studies and
meta-analyses and is now considered a U-shaped curve. Several pathophysiological mechanisms
linking thyroid and cardiovascular disease are known; however, specific clinical complications of
peripheral arterial disease as endpoints of clinical trials have not been adequately investigated.
The potential mechanisms linking hypothyroidism and peripheral arterial disease are endothelial
dysfunction, blood pressure changes, dyslipidemia, and low-grade systemic inflammation. The
potential mechanisms linking hyperthyroidism and peripheral arterial disease are hyperdynamic circulation,
elevated systolic blood pressure, hypercoagulability, and possibly increased arterial inflammation.
A New Scoring System to Differentiate Bladder Cancer from Intravesical
Prostatic Protrusion in the Bladder Neck: BCa-IPP Score
Authors: Yildiz Ali Kaan , Oktem Cagri , Keseroglu Bugra Bilge , Kacan Turgay , Ozgur Berat Cem , Doluoglu Omer Gokhan , Karakan Tolga 
Published: November 2023

Objective::
The aim of this study was to explore the criteria that can predict bladder cancer among the lesions that could not be differentiated from intravesical
prostate protrusion (IPP) and to create a scoring system using these criteria.

Methods::
A retrospective analysis was made of patients with an ultrasound report indicating lesions in the bladder neck, for which differentiation between
bladder cancer and IPP could not be determined. A total of 174 patients diagnosed with bladder cancer (n=102) or benign prostate lesion (n=72)
according to the biopsy results were enrolled in the study. Hemoglobin, prostate-specific antigen (PSA), prostate volume (PV), bladder wall
thickness (BWT), lesion height (LH), and the ratio of lesion width to base (LW/B) were compared between the two groups.

Results::
ROC analysis revealed an AUC value >0.7 for all factors, and the best cut-off value was identified for each factor. In the multivariate analysis, by
determining a score for each factor according to the ORs, the BCa-IPP scoring system was developed to provide a total score in the range of
minimum 0 and maximum 15. In the ROC analysis, the AUC value was 0.954 (95% CI: 0.923–0.986) for the BCa-IPP score. The best cut-off
value was found to be 10, with sensitivity of 0.93 and specificity of 0.85.

Conclusion::
Using simple laboratory and ultrasound findings, the BCa-IPP scoring system was created, which was seen to have high predictive value and can
be easily applied in the clinic. The BCa-IPP scoring system is a non-invasive test that can be successfully applied for the differentiation of bladder
cancer from benign lesions
An Insight into Emerging Phytocompounds for Glioblastoma Multiforme Therapy
Authors: Prakash Vijeta , Gabrani Reema 
Published: November 2023

:
Despite intense research in the field of glioblastoma multiforme (GBM) therapeutics,
the resistance against approved therapy remains an issue of concern. The resistance against the
therapy is widely reported due to factors like clonal selection, involvement of multiple developmental
pathways, and majorly defective mismatch repair (MMR) protein and functional O6-
methylguanine DNA methyltransferase (MGMT) repair enzyme. Phytotherapy is one of the most
effective alternatives to overcome resistance. It involves plant-based compounds, divided into
several classes: alkaloids; phenols; terpenes; organosulfur compounds. The phytocompounds
comprised in these classes are extracted or processed from certain plant sources. They can target
various proteins of molecular pathways associated with the progression and survival of GBM.
Phytocompounds have also shown promise as immunomodulatory agents and are being explored
for immune checkpoint inhibition. Therefore, research and innovations are required to understand
the mechanism of action of such phytocompounds against GBM to develop efficacious
treatments for the same. This review gives insight into the potential of phytochemical-based
therapeutic options for GBM treatment.
Effectiveness of Different Telerehabilitation Strategies on Pain and Physical Function in Patients With Knee Osteoarthritis: Systematic Review and Meta-Analysis
Authors: Xiang Wu , Wang Jun-Yu , Ji Bing-jin , Li Li-Jun , Xiang Han 
Published: November 2023

Background
Knee osteoarthritis (OA) is a chronic, degenerative bone and joint disease. It can lead to major pressure to the quality of life and mental health of patients, and also brings a serious economic burden to society. However, it is difficult for patients with knee OA to access rehabilitation when discharging from the hospital. Internet-based rehabilitation is one of the promising telemedicine strategies for the improvement of knee OA, but the effect of different telerehabilitation strategies on knee OA is not clear.

Objective
The aim of this systematic review and meta-analysis was to identify telerehabilitation strategies attributing to the improvement of pain and physical function outcomes in patients with knee OA.

Methods
We reviewed and analyzed telerehabilitation strategies from randomized controlled trials (RCTs) comparing telerehabilitation with conventional treatment or usual care. For each strategy, we examined whether RCTs that applied the telerehabilitation strategy resulted in a significant improvement in pain or physical function compared with conventional treatment or usual care.

Results
We included 6 RCTs (n=734) incorporating 8 different telerehabilitation strategies. The duration of the interventions ranged from 1 to 48 weeks, and sample sizes ranged from 20 to 350 patients. The results showed that RCTs that provided telerehabilitation were found to be more effective than conventional treatments for improving pain (P=.003; standardized mean difference [SMD] –0.21, 95% CI –0.35 to –0.07), but not physical function (P=.24; SMD –0.09, 95% CI –0.25 to 0.06). Furthermore, this systematic review and meta-analysis indicated that there is no significant correlation between different telerehabilitation strategies and the pain and physical function of patients with knee OA.

Conclusions
This systematic review and meta-analysis showed that telerehabilitation programs could relieve pain but not improve physical function for patients with knee OA. These results indicated that telerehabilitation is beneficial for the implementation of home rehabilitation exercises for patients with knee OA, thereby reducing the economic burden of health. However, there were limitations in terms of the number of search results and the number of studies that were eligible for this review and meta-analysis. Therefore, the results need to be interpreted with caution, and more high-quality studies with large samples are needed to focus on the long-term outcomes of telerehabilitation for patients with knee OA to address this limitation.
Use of Social Media for Health Advocacy for Digital Communities: Descriptive Study
Authors: Ezeilo Chidimma Ogechukwu , Leon Nicholas , Jajodia Anushka , Han Hae-Ra 
Published: November 2023

Background
There has been a growth surge in the use of social media among individuals today. The widespread adoption of these platforms, coupled with their engaging features, presents a unique opportunity for the dissemination of health advocacy information. Social media is known as a powerful tool used to share health policy and advocacy efforts and disseminate health information to digital community members and networks. Yet, there is still a gap in the full exploitation of this powerful instrument, among health care professionals, for health advocacy campaigns.

Objective
This paper aims to describe the process of mobilizing social media platforms such as Twitter (rebranded to X Corp in 2023) for health advocacy of the digital community. Additionally, it aims to share the lessons and insights gained during this digital health advocacy engagement process.

Methods
We performed a comprehensive review of Twitter analytical data to examine the impact of our social media posts. We then consolidated these analytic reports with our meeting logs to describe our systematic, iterative, and collaborative design process to implement social media efforts and generate key lessons learned.

Results
Our review of monthly Twitter analytical reports and regular team meeting logs revealed several themes for successful and less successful practices in relation to our social media–based health advocacy efforts. The successful practices noted by the team included using personable, picture-based tweets; using a series of posts on a particular topic rather than an isolated post; leveraging team members’ and partners’ collaborations in shared posts; incorporating hashtags in tweets; using a balanced mix of texts and graphics in posts; using inclusive (nondestigmatizing) languages in tweeted posts; and use of polls to share tweets. Among the many lessons learned, we also experienced limitations including a lack of comprehensive statistics on Twitter usage for health care–related purposes such as health advocacy and limits in collating the estimates of the actual impact made on the intended digital community members by our posts.

Conclusions
Twitter has been successfully used in promoting health advocacy content, and the social media team aims to explore other social media platforms that have a wider reach than Twitter. We will continue making necessary adjustments in strategies, techniques, and styles to engage the audience as we expand onto new platforms like Instagram and TikTok for health advocacy promotions.
Differential in Kidney Graft Years on the Basis of Solitary Kidney, Simultaneous Liver–Kidney, and Kidney-after-Liver Transplants
Authors: Schold Jesse D. , Mohan Sumit , Jackson Whitney E. , Stites Erik , Burton James R. , Bababekov Yanik J. , Saben Jessica L. , Pomposelli James J. , Pomfret Elizabeth A. , Kaplan Bruce 
Published: November 2023

Background
The number of simultaneous liver–kidney (SLK) transplants has significantly increased in the United States. There has also been an increase in kidney-after-liver transplants associated with 2017 policy revisions aimed to fairly allocate kidneys after livers. SLK and kidney-after-liver candidates are prioritized in allocation policy for kidney offers ahead of kidney-alone candidates.

Methods
We compared kidney graft outcomes of kidney-alone transplant recipients with SLK and kidney-after-liver transplants using paired kidney models to mitigate differences among donor risk factors. We evaluated recipient characteristics between transplant types and calculated differential graft years using restricted mean survival estimates.

Results
We evaluated 3053 paired donors to kidney-alone and SLK recipients and 516 paired donors to kidney-alone and kidney-after-liver recipients from August 2017 to August 2022. Kidney-alone recipients were younger, more likely on dialysis, and Black race. One-year and 3-year post-transplant kidney graft survival for kidney-alone recipients was 94% and 86% versus SLK recipients 89% and 80%, respectively, P < 0.001. One-year and 3-year kidney graft survival for kidney-alone recipients was 94% and 84% versus kidney-after-liver recipients 93% and 87%, respectively, P = 0.53. The additional kidney graft years for kidney-alone versus SLK transplants was 21 graft years/100 transplants (SEM=5.0) within 4 years post-transplantation, with no significant difference between kidney-after-liver and kidney-alone transplants.

Conclusions
Over a 5-year period in the United States, SLK transplantation was associated with significantly lower kidney graft survival compared with paired kidney-alone transplants. Most differences in graft survival between SLK and kidney-alone transplants occurred within the first year post-transplantation. By contrast, kidney-after-liver transplants had comparable graft survival with paired kidney-alone transplants.
Habilidades de pensamiento computacional en niños y niñas de las escuelas primarias utilizando tecnologías 4.0: un análisis bibliométrico
Authors: Cuesta-Quintero Byron , Duarte-Neira Wilder Andrés 
Published: November 2023

El desarrollo digital ha facilitado el desarrollo de la educación en tecnología. Este trabajo analiza literatura científica sobre el impacto del pensamiento computacional en los niños. Este pensamiento formado desde la infancia permite utilizar la tecnología y desarrollar sistemas que gestionen soluciones a problemas. Cada día son más los científicos e instituciones educativas que hablan de este tema observando que temáticas enfocadas en la construcción de distinciones lógicas están siendo incluidas en los curriculum académicos con la finalidad de fortalecer conocimientos en esta materia. El objetivo es presentar un análisis de diferentes publicaciones relacionados al pensamiento computacional en la educación primaria; para este propósito los datos fueron recopilados desde la base de datos Scopus y analizados con el software de VOSviewer, se encontraron 625 resultados filtrados con la siguiente búsqueda: [computational AND thinking] AND [children OR childhood], el análisis permite identificar autores más relevantes, países con mayor publicaciones, tasa de crecimiento anual, tipos de documentos, instituciones patrocinadoras, entre otros. Todos estos referentes científicos evidencian el incremento práctico y conceptual encontrado en el pensamiento computacional como una vía para la formación de las tecnologías de la información y comunicación en la educación infantil, logrando así una nueva alfabetización digital.