bluuebunny/crossref_metadata_2025_split huggingface dataset:
Advances in Genetic Reprogramming: Prospects from Developmental
Biology to Regenerative Medicine
Authors: Dhanjal Daljeet Singh , Singh Reena , Sharma Varun , Nepovimova Eugenie , Adam Vojtech , Kuca Kamil , Chopra Chirag 
Published: May 2023

Abstract:
The foundations of cell reprogramming were laid by Yamanaka and co-workers, who
showed that somatic cells can be reprogrammed into pluripotent cells (induced pluripotency).
Since this discovery, the field of regenerative medicine has seen advancements. For example, because
they can differentiate into multiple cell types, pluripotent stem cells are considered vital components
in regenerative medicine aimed at the functional restoration of damaged tissue. Despite
years of research, both replacement and restoration of failed organs/ tissues have remained
elusive scientific feats. However, with the inception of cell engineering and nuclear reprogramming,
useful solutions have been identified to counter the need for compatible and sustainable organs.
By combining the science underlying genetic engineering and nuclear reprogramming with regenerative
medicine, scientists have engineered cells to make gene and stem cell therapies applicable
and effective. These approaches have enabled the targeting of various pathways to reprogramme
cells, i.e., make them behave in beneficial ways in a patient-specific manner. Technological
advancements have clearly supported the concept and realization of regenerative medicine. Genetic
engineering is used for tissue engineering and nuclear reprogramming and has led to advances
in regenerative medicine. Targeted therapies and replacement of traumatized , damaged,
or aged organs can be realized through genetic engineering. Furthermore, the success of these
therapies has been validated through thousands of clinical trials. Scientists are currently evaluating
induced tissue-specific stem cells (iTSCs), which may lead to tumour-free applications of pluripotency
induction. In this review, we present state-of-the-art genetic engineering that has been used
in regenerative medicine. We also focus on ways that genetic engineering and nuclear reprogramming
have transformed regenerative medicine and have become unique therapeutic niches.
Comprehensive Analysis of Alternative Polyadenylation Events Associated
with the Tumor Immune Microenvironment in Colon Adenocarcinoma
Authors: Pang Fangning , Yang Peng , Wang Tongfei , Li Xuzhao , Wu Xiaoyong , Yue Rong , Bai Bin , Zhao Qingchuan 
Published: May 2023

Objective:
Colon adenocarcinoma (COAD) is one of the leading causes of cancer death
worldwide. Alternative polyadenylation (APA) is relevant to the variability of the 3'-UTR of mRNA.
However, the posttranscriptional dysregulation of APA in COAD is poorly understood.

Methods:
We collected APA data from The Cancer Genome Atlas (TCGA) COAD (n =7692). APA
events were evaluated using PDUI values, and the prognostically significant APA events were
screened by LASSO Cox regression to construct a prognostic model. Then, prognostic model functions
and possible regulatory genes of characteristic APA events were analyzed. Finally, the immune
regulatory network based on APA regulatory genes was analyzed and established.

Results:
A total of 95 APA events were found to influence the COAD outcomes. Among them, 39
genes were screened as characteristic prognostic APA events by LASSO Cox regression to construct a
COAD prognostic signature. The analysis results suggested that a high signature score was associated
with poor prognosis and was significantly correlated with a variety of immune cells, including NK and
Th1, 2 and 17 cells. Further analysis showed that APA regulators mainly served roles in the prognosis
of COAD. Based on the above results, we constructed an immunoregulatory network for APA regulatory
genes-APA genes-immune cells.

Conclusion:
Our study revealed that APA events in COAD may regulate tumor progression by influencing
immune cells, which provides a new direction for exploring the influencing mechanism of the
tumor immune microenvironment and is expected to provide a potential new target for COAD immunotherapy.
Toosendanin Restrains Idiopathic Pulmonary Fibrosis by Inhibiting
ZEB1/CTBP1 Interaction
Authors: Li Xingbin , Bai Zina , Li Zhensheng , Wang Jun , Yan Xixin 
Published: May 2023

Background:
Extensive deposition of extracellular matrix (ECM) in idiopathic
pulmonary fibrosis (IPF) is due to hyperactivation and proliferation of pulmonary
fibroblasts. However, the exact mechanism is not clear. Objective: This study focused
on the role of CTBP1 in lung fibroblast function, elaborated its regulation mechanism,
and analyzed the relationship between CTBP1 and ZEB1. Meanwhile, the antipulmonary
fibrosis effect and its molecular mechanism of Toosendanin were studied.

Methods:
Human IPF fibroblast cell lines (LL-97A and LL-29) and normal fibroblast
cell lines (LL-24) were cultured in vitro. The cells were stimulated with FCS, PDGF-BB,
IGF-1, and TGF-β1, respectively. BrdU detected cell proliferation. The mRNA expression
of CTBP1 and ZEB1 was detected by QRT-PCR. Western blotting was used to
detect the expression of COL1A1, COL3A1, LN, FN, and α-SMA proteins. An animal
model of pulmonary fibrosis was established to analyze the effects of CTBP1 silencing
on pulmonary fibrosis and lung function in mice.

Results:
CTBP1 was up-regulated in IPF lung fibroblasts. Silencing CTBP1 inhibits
growth factor-driven proliferation and activation of lung fibroblasts. Overexpression of
CTBP1 promotes growth factor-driven proliferation and activation of lung fibroblasts.
Silencing CTBP1 reduced the degree of pulmonary fibrosis in mice with pulmonary
fibrosis. Western blot, CO-IP, and BrdU assays confirmed that CTBP1 interacts with
ZEB1 and promotes the activation of lung fibroblasts. Toosendanin can inhibit the
ZEB1/CTBP1protein interaction and further inhibit the progression of pulmonary fibrosis.

Conclusion:
CTBP1 can promote the activation and proliferation of lung fibroblasts
through ZEB1. CTBP1 promotes lung fibroblast activation through ZEB1, thereby increasing
excessive deposition of ECM and aggravating IPF. Toosendanin may be a
potential treatment for pulmonary fibrosis. The results of this study provide a new basis
for clarifying the molecular mechanism of pulmonary fibrosis and developing new therapeutic
targets.
Effects of Cilostazol on the Myocardium in an Obese Wistar Rat Model of
Ischemia-Reperfusion Injury
Authors: Demir Tolga , Sahin Mazlum , Ilal Mert Fatma Tugba , Sarac Fatma 
Published: May 2023

Objectives:
This study aims to determine the protective effect of cilostazol on myocardium in
obese Wistar rats with induced ischemia-reperfusion injury (IRI).

Methods:
Four groups with 10 Wistar rats were included: 1] Sham Group: IRI was not established in
normal weight-Wistar rats. 2] Control Group: IRI but no cilostazol in normal weight-Wistar rats. 3]
Cilostazol in normal weight-Wistar rats: IRI and cilostazol was administered. 4] Cilostazol in obese-
Wistar rats: IRI and cilostazol was administered.

Results:
Tissue adenosine triphosphate (ATP) levels were significantly higher and superoxide dismutase
(SOD) levels significantly lower in the control group than in the sham group and normal weight cilostazol
group (p=0.024 and p=0.003). Fibrinogen levels were 198 mg/dL in the sham group, 204 mg/dL in
the control group, and 187 mg/dL in the normal-weight cilostazol group (p=0.046). Additionally, plasminogen
activator inhibitor-1 (PAI-1) levels were significantly higher in the control group (p=0.047).
The level of ATP was significantly lower in the normal-weight cilostazol group than in the obese group
(104 vs 131.2 nmol/g protein, p=0.043). PAI-1 level was 2.4 ng/mL in the normal weight cilostazol
group and 3.7 ng/mL in the obese cilostazol group (p=0.029). Normal-weight Wistar rats with cilostazol
had significantly better histologic outcomes than the control group and obese Wistar rats (p=0.001 and
p=0.001).

Conclusion:
Cilostazol has a protective effect on myocardial cells in IRI models by decreasing inflammation.
The protective role of cilostazol was reduced in obese Wistar rats compared with normal-weight
Wistar rats.
Molecular Mechanism and Structure-activity Relationship of the Inhibition
Effect between Monoamine Oxidase and Selegiline Analogues
Authors: Yang Chuanxi , Wang Xiaoning , Gao Chang , Liu Yunxiang , Ma Ziyi , Zang Jinqiu , Wang Haoce , Liu Lin , Liu Yonglin , Sun Haofen , Wang Weiliang 
Published: May 2023

Introduction:
To investigate the inhibition properties and structure-activity relationship
between monoamine oxidase (MAO) and selected monoamine oxidase inhibitors (MAOIs, including
selegiline, rasagiline and clorgiline).

Methods:
The inhibition effect and molecular mechanism between MAO and MAOIs were identified
via the half maximal inhibitory concentration (IC50) and molecular docking technology.

Results:
It was indicated that selegiline and rasagiline were MAO B inhibitors, but clorgiline was
MAO-A inhibitor based on the selectivity index (SI) of MAOIs (0.000264, 0.0197 and 14607.143
for selegiline, rasagiline and clorgiline, respectively). The high-frequency amino acid residues of
the MAOIs and MAO were Ser24, Arg51, Tyr69 and Tyr407 for MAO-A and Arg42 and Tyr435
for MAO B. The MAOIs and MAO A/B pharmacophores included the aromatic core, hydrogen
bond acceptor, hydrogen bond donor-acceptor and hydrophobic core.

Conclusion:
This study shows the inhibition effect and molecular mechanism between MAO and
MAOIs and provides valuable findings on the design and treatment of Alzheimer's and Parkinson's
diseases.
An Overview of Analytical Methods for the Identification and Quantification
of Baclofen
Authors: da Silva Milena Nogueira , da Silva João Victor Belo , da Fonsêca Naara Felipe , Oshiro Junior João Augusto , Dantas  Medeiros Ana Claudia 
Published: May 2023

Background:
Baclofen is a potent antispasmodic agent, acting as an analgesic and central
skeletal muscle relaxant. It is a GABA-B analog, and is widely used for the treatment of spasticity.
Due to its therapeutic importance, various analytical techniques are used in the pharmaceutical industry
and research to determine, identify, and characterize baclofen in bulk material, biological fluids,
and pharmaceutical forms.

Objective:
This review aimed to collect information on reported analytical techniques commonly
used to identify and quantify baclofen in pharmaceutical forms and biological samples.

Methods:
The authors explored various authenticated scientific journals using these descriptors: highperformance
liquid chromatography, liquid chromatography-tandem mass spectrometry, capillary
electrophoresis, differential scanning calorimetry, Fourier transform infrared spectroscopy, ultravioletvisible
spectroscopy, near-infrared spectroscopy, nuclear magnetic resonance, potentiometry, and Xray
diffraction.

Results:
Quantification of the drug by all the methods evaluated in the review was possible. There
were 73 articles reviewed, of which 26 used HPLC for baclofen quantification; the least used was near
infrared spectroscopy and potentiometry, both with one article identified.

Conclusion:
This review has shed light on a wide variety of analytical methods that can be used to
quantify and identify baclofen. The knowledge provided by the use of these analytical methods makes
this document an important tool for developing pharmaceutical formulations containing baclofen.
Side Effects Reported by Moroccan Medical Students Who Received
COVID-19 Vaccines
Authors: Moukafih Badreddine , Belaroussi Leila , Achour Sanae , Kartouti Abdeslam El 
Published: May 2023

Background:
Low confidence in the safety of COVID-19 vaccines was found to be a
key promoter of vaccine reluctance especially among youth. Furthermore, young adults are an important
demographic for building herd immunity through vaccination. As a result, their reactions to
getting COVID-19 vaccines are crucial in our fight against SARS-CoV-2.

Objective:
The overall goal of this study was to look into the shortterm side effects experienced by
Moroccan medical and pharmacy students after receiving COVID-19 vaccines.

Methods:
A cross-sectional survey-based study to assess the COVID-19 vaccines' short-term AEFIs
among Moroccan medical and pharmacy students. The validated questionnaire was delivered in a digital
form to explore the side effects (SE) they encountered after the first or the second dose of one of
three vaccines namely: AstraZeneca Vaxzevria, PfizerBioNTeck, and SinoPharm vaccines.

Results:
There were 510 students in total who took part. After the first and second doses, approximately
72 percent and 78 percent of subjects, respectively, reported no SE. The remainder had localized injection
site side effects (26%). Fatigue (21%), fever (19%), headache (17%), and myalgia (16%) were the
most common systemic adverse effects after the first dose. There were no serious SEs reported.

Conclusion:
The majority of the reported AEFIs in our data were mild to moderate in intensity and
lasted only one or two days. COVID-19 vaccinations are highly likely safe for young adults,
according to the findings of this study.
Hemofiltration as an Alternative for IL-6 Inhibitors in COVID-19
Cytokines Storm Associated with Underlaying Bacterial Infections: A
Review Article
Authors: Zaky Samy , Elbadry Mohamed , Makhlouf Hoda A. , Abd-Elsalam Sherief , Sarhan Tarik S. , Eltaweel Noha H. , Aly Heba , Abdelbary Akram , Said Ahmad , Farouk Mohammed Hamdy , Abdel Baki Amin , Fathelbab Hanaa , Hammad Reham , El-Raey Fathiya 
Published: May 2023

Abstract:
SARS-CoV-2 causes mostly mild cases. However, a considerable number of patients develop
fatal acute respiratory distress syndrome due to the cytokine storm and imbalanced immune response.
Several therapies depending on immunomodulation have been used, including glucocorticoids
and IL-6 blockers. However, their efficacy is not perfect with all patients and patients with concomitant
bacterial infections and sepsis. Accordingly, studies on different immunomodulators, including
extracorporeal techniques, are crucial to save this category of patients. In this review, we overviewed
the different immunomodulation techniques shortly, with a brief review of extracorporeal methods.
Autophagy Behavior in Post-myocardial Infarction Injury
Authors: Marzoog Basheer Abdullah 
Published: May 2023

Abstract:
Myocardial infarction and its sequalae remain the leading cause of death worldwide. Myocardial
infarction (MI) survivors continue to live a poor quality of life due to extinguished heart
failure. The post-MI period involves several changes at the cellular and subcellular levels, of which
autophagy dysfunction. Autophagy is involved in the regulation of post-MI changes. Physiologically,
autophagy preserves intracellular homeostasis by regulating energy expenditure and sources.
Furthermore, dysregulated autophagy is considered the hallmark of the post-MI pathophysiological
changes, which leads to the known short and long post-MI reperfusion injury sequalae. Autophagy
induction strengthens self-defense mechanisms of protection against energy deprivation through
economic energy sources and uses alternative sources of energy through the degradation of intracellular
components of the cardiomyocyte. The protective mechanism against post-MI injury includes
the enhancement of autophagy combined with hypothermia, which induces autophagy. However,
several factors regulate autophagy, including starvation, nicotinamide adenine dinucleotide (NAD+),
Sirtuins, other natural foods and pharmacological agents. Autophagy dysregulation involves genetics,
epigenetics, transcription factors, small noncoding RNAs, small molecules, and special microenvironment.
Autophagy therapeutic effects are signaling pathway-dependent and MI stage dependent.
The paper covers recent advances in the molecular physiopathology of autophagy in post-MI
injury and its potential target as a future therapeutic strategy.
Solid and Homogeneous Thermal Wall of Cored Lightweight Concrete
Blocks Solidarized in situ
Authors: Maia Lino 
Published: May 2023

Abstract:
The exterior walls of buildings play a major role in the road for a near-zero energy
building. Nowadays, in Portugal, the ETICS system is the most used technology to ensure the
thermal insulation of exterior walls of buildings. However, the ETICS system has low resistance to
impacts and requires a self-supporting sheet of wall, among other disadvantages. Here, the concept
of new technology for exterior walls of residential and commercial buildings is presented. It consists
of a hybrid technology for the easy and quick execution of a single sheet wall, which may
provide high thermal efficiency for buildings. This hybrid technology relates to parallelepipedshaped
cored lightweight concrete blocks comprising two parallel sides separated by one or more
solid connectors in which the connectors allow the filling of the block core with lightweight concrete.
No bed or head joints are used to connect the blocks because the wall made of cored blocks
gets solid and homogeneous when filled with lightweight concrete. When the block thickness is 30
cm and the thermal conductivity of the lightweight concrete is lower than 0.09 W/m.ºC, in Portugal,
this type of exterior wall does not require the application of extra thermal insulation materials.
Determination of the Re-188 Calibration Number for the Capintec CRC-
25PET Dose Calibrator
Authors: Ashley Klenner Mitchell , Poole Aron 
Published: May 2023

Background:
During the development of novel Re-188 radiopharmaceuticals, it was discovered
that no calibration settings were published to calibrate Re-188 on the Capintec CRC-25PET dose calibrator.

Methods:
Sodium [188Re]perrhenate was eluted from an OncoBeta 188W/188Re generator to measure activity
on a Capintec CRC-25R dose calibrator using established dose calibrator settings provided by the manufacturer.
The eluent was then used to tune the calibra on settings on a Capintec CRC-25PET dose calibrator,
accounting for geometry. Radionuclidic purity of the [188Re]perrhenate source was verified via
gamma spectroscopy.

Results:
The calibrator number for Re-188 was determined to be 469 x 10 for the Capintec CRC-25PET
dose calibrator, which differed from the manufacturer provided calibra on number of 496 x 10 for the
Capintec CRC-25R dose calibra on model. W-188 breakthrough was characterised as < 0.01%.

Conclusion:
This previously unreported calibration number can be used to determine the activity of Re-
188 labelled radiopharmaceuticals using the Capintec CRC-25PET dose calibrator model.
Liposomal Doxorubicin Kinetic Study in an In vitro 2D and 3D Tumor
Model for Osteosarcoma in a Perfusion Bioreactor
Authors: Abdollahzadeh H. , Amoabediny G. , Haghiralsadat F. , Rahimi F. , Adibfar A. 
Published: May 2023

Background:
In vivo drug screening in animal models is contrary to ethical values, costly
and time-consuming. Traditional static in vitro models do not reflect the basic characteristics of bone
tumor microenvironments; therefore, perfusion bioreactors, in particular, would be an applicable choice
due to their advantages to regenerate versatile bone tumor models for studying in vitro novel drug delivery
systems.

Methods:
In this study, an optimal drug formulation of liposomal doxorubicin was prepared, and the release
kinetics of the drug and its toxicity effect on MG-63 bone cancer cell line were investigated in
two-dimensional, static three-dimensional media on a PLGA/β-TCP scaffold and also in a dynamic media
in a perfusion bioreactor. In this assay, the efficacy of the IC50 of this formulation which had been
obtained in two-dimensional cell culture (= 0.1 μg/ml), was studied in static and dynamic threedimensional
media after 3 and 7 days. Liposomes with good morphology and encapsulation efficiency
of 95% had release kinetics of the Korsmeyer-Peppas model.

Results:
The results of cell growth before treatment and cell viability after treatment in all three environments
were compared. Cell growth in 2D was rapid, while it was slow in static 3D conditions. In the
dynamic 3D environment, it was significant compared to the static tumor models. Cell viability after 3
and 7 days from treatment was 54.73% and 13.39% in 2D conditions, 72.27% and 26.78% in the static
3D model, while 100% and 78.92% in the dynamic culture indicating the effect of drug toxicity over
time, but drug resistance of 3D models compared to 2D culture. In the bioreactor, the formulation used
in the mentioned concentration showed very small cytotoxicity demonstrating the dominance of mechanical
stimuli on cell growth over drug toxicity.

Conclusion:
Increasing drug resistance in 3D models compared to 2D models indicates the superiority
of liposomal Dox over free form to reduce IC50 concentration.
Spider Silk: Biosynthesis, Properties & Bioengineering
Authors: Singh Shivendra , Sharma Shivangi , Das Snigdha , Kumar Das Amlan 
Published: May 2023

Abstract:
Due to the remarkable and unique qualities of spider silk, it has much applicability in the
coming days. The complicated diversity and structure of spider silk ensure its use in both nature and
industry. Based on the uniqueness and distinctive qualities associated with spider silks, advancements
in cloning and expression of these silks are a growing area of research and industrial use. The environmentally
triggered spider silk assembly and further disassembly, the creation of fibers, films, and
novel chimeric composite materials from genetically modified spider silks are interesting areas of research
in nanotechnology. In this context, we have discussed the creation of hybrids made of spider
silk that combine with organic nanoparticles, both naturally occurring and bioengineered spider silk
proteins. The diversity of spider silk, its composition and architecture, the distinctions between spider
silk and silkworm silk, and the biosynthesis of natural silk are also discussed. This article describes the
current issues and expected outcomes using biochemical data and processes.