bluuebunny/crossref_metadata_2025_split huggingface dataset:
Single Injection AAV2-FGF18 Gene Therapy Reduces Cartilage Loss
and Subchondral Bone Damage in a Mechanically Induced Model of
Osteoarthritis
Authors: Hollander Judith M. , Goraltchouk Alex , Liu Jingshu , Xu Ellyn , Luppino Francesco , McAlindon Timothy E. , Zeng Li , Seregin Alexey 
Published: February 2024

Background::
Osteoarthritis (OA) is a highly debilitating, degenerative pathology of cartilaginous
joints affecting over 500 million people worldwide. The global economic burden of OA
is estimated at $260-519 billion and growing, driven by aging global population and increasing
rates of obesity. To date, only the multi-injection chondroanabolic treatment regimen of Fibroblast
Growth Factor 18 (FGF18) has demonstrated clinically meaningful disease-modifying efficacy in
placebo-controlled human trials. Our work focuses on the development of a novel single injection
disease-modifying gene therapy, based on FGF18’s chondroanabolic activity.

Methods::
OA was induced in Sprague-Dawley rats using destabilization of the medial meniscus
(DMM) (3 weeks), followed by intra-articular treatment with 3 dose levels of AAV2-FGF18, rh-
FGF18 protein, and PBS. Durability, redosability, and biodistribution were measured by quantifying
nLuc reporter bioluminescence. Transcriptomic analysis was performed by RNA-seq on cultured
human chondrocytes and rat knee joints. Morphological analysis was performed on knee
joints stained with Safranin O/Fast Green and anti-PRG antibody.

Results::
Dose-dependent reductions in cartilage defect size were observed in the AAV2-FGF18-
treated joints relative to the vehicle control. Total defect width was reduced by up to 76% and cartilage
thickness in the thinnest zone was increased by up to 106%. Morphologically, the vehicle-
treated joints exhibited pronounced degeneration, ranging from severe cartilage erosion and
bone void formation, to subchondral bone remodeling and near-complete subchondral bone collapse.
In contrast, AAV2-FGF18-treated joints appeared more anatomically normal, with only regional
glycosaminoglycan loss and marginal cartilage erosion. While effective at reducing cartilage
lesions, treatment with rhFGF18 injections resulted in significant joint swelling (19% increase
in diameter), as well as a decrease in PRG4 staining uniformity and intensity. In contrast to
early-timepoint in vitro RNA-seq analysis, which showed a high degree of concordance between
protein- and gene therapy-treated chondrocytes, in vivo transcriptomic analysis, revealed few gene
expression changes following protein treatment. On the other hand, the gene therapy treatment exhibited
a high degree of durability and localization over the study period, upregulating several
chondroanabolic genes while downregulating OA- and fibrocartilage-associated markers.

Conclusion::
FGF18 gene therapy treatment of OA joints can provide benefits to both cartilage
and subchondral bone, with a high degree of localization and durability.
Therapeutic Voyage of Graphene-based Biosensor
Authors: Sharma Rama 
Published: February 2024

:
The study of carbon-based materials and nanoparticles is currently an exciting field of
study in the domain of material science. One of the most prominent of these materials is graphene,
along with its related components graphene oxide and reduced graphene oxide. A single-layer, twodimensional
nanomaterial called graphene (GN) is employed in many different industries, such as
electronics and biology. Graphene is a remarkable two-dimensional substance that has earned the
title of "wonder material." Its remarkable electrical, optical, thermal, and mechanical qualities have
attracted significant attention. Graphene's intriguing characteristics have led to its integration into
numerous biosensing applications. Graphene possesses remarkable chemical, electrical, and physical
qualities. The distinctive properties of graphene, particularly its electrical conductivity, large surface
area, and significant electron mobility, are focusing more attention on applications in biomedicine
that facilitate easier health monitoring. Biosensors with high sensitivity and precision can enhance
patient care, and offer an opportunity for an early illness diagnosis and clinical pathogen identification.
Additionally, a wide range of biological molecules, including glucose, hydrogen peroxide, cholesterol,
dopamine, etc., can be detected using graphene-based biosensors. This study evaluates contemporary
developments regarding graphene-based biosensors and their prospects and difficulties in
this rapidly developing profession in the coming era. Graphene-based nanomaterials are appropriate
to be employed in various biological and sensory contexts, including medicine and gene transfer,
because of their unusual topologies and extraordinary properties. Graphene's outstanding characteristics
enable biosensing applications to obtain the appropriate sensitivity, selectivity, and repeatability
for a range of targets.
Randomised Clinical Trial Study: The Combination of Vitamin D and
Curcumin Piperine Attenuates Disease Activity and Pro-inflammatory
Cytokines Levels Insystemic Lupus Erythematosus Patients
Authors: Wahono Cesarius Singgih , Susianti Hani , Hakim Arif Luqman , Rosita Firdha , Pratama Mirza Zaka , Rahman Perdana Aditya , Anshory Muhammad 
Published: February 2024

Background::
Curcumin-piperine might synergise with vitamin D to induce clinical remission
in patients with systemic lupus erythematosus (SLE).

Objective::
To observe the improvement of patients with SLE clinically and the levels of inflammatory
cytokines after receiving supplements of curcumin-piperine and cholecalciferol (Vitamin
D3).

Methods::
Forty-five female SLE patients were included in a three-month double-blind, randomized
controlled trial. Participants were classified into: Group I (400 IU cholecalciferol + placebo
three times daily, n = 15), Group II (600 mg curcumin + 15,800 m piperine once daily and
three times daily placebo, n = 15), and Group III (cholecalciferol 400 IU three times and 600 mg
curcumin + 15,800 mg piperine once a day, n = 15). Mexican SLE disease activity score (Mex-
SLEDAI), fatigue severity scale (FSS), TGF-β, and IL-6 levels were measured from all patients before
and after the treatments.

Results::
Mex-SLEDAI, FSS, and IL-6 were reduced significantly, while TGF-β serum levels were
increased in all groups after the treatments (p <0.05). Changes in Mex-SLEDAI score (p = 0.003
and p = 0.008), FSS (p = 0.001 and p <0.001), and TGF-β (p = 0.003 and p = 0.004) serum levels
were significantly higher in group III compared to the group I or group II. On the other hand,
changes in Mex-SLEDAI, FSS, IL-6, and TGF-β serum levels were similar between groups I and
II.

Conclusion::
Although vitamin D or curcumin-piperine alone could improve the clinical outcome
and cytokines levels in SLE, curcumin-piperine combined with vitamin D had the best outcome in
improving the disease activity and cytokines levels among patients with SLE. (ClinicalTrials.gov
number, NCT05430087).
Assessment of Interleukin 17 in Egyptian Systemic Lupus Erythematosus
Patients as a Biomarker in Disease Activity
Authors: Behiry Mervat , Wadie Mary , Mohamed Nagwa Abdelghaffar , Farid Rania , Ramadan Hala 
Published: February 2024

Introduction:
Systemic lupus erythematosus (SLE) is a chronic idiopathic systemic autoimmune
disorder with dysregulation of adaptive and innate immune systems. Interleukin (IL)-17
is the prototypical pro-inflammatory cytokine of T helper 17 (Th17) cells. Therefore, it contributes
to the pathogenesis of human SLE.

Aim:
The aim of the research paper was the evaluation of IL-17 level as a biomarker in the SLE
cohort and its relation to disease activity and analysis of IL-17 concentration in patients with lupus
nephritis and non-lupus nephritis.

Methods:
The research enrolled 45 SLE patients according to Systemic Lupus International Collaborating
Clinics Classification Criteria (SLICC), and age and sex-matched. The patients underwent
full history, clinical examination, laboratory investigation, and Systemic Lupus Erythematosus
Disease Activity Index (SLEDAI) calculation.

Results:
The mean age ± SD of the participants equaled 32 ± 11 years, and serum IL-17 in SLE
cases was statistically significantly high (p < 0.001). No statistically significant correlations were
reported between disease activity according to SLEDAI and IL-17. In addition, a statistically significant
positive correlation was reported between IL-17 and ESR, and a high statistically significant
negative correlation was reported between IL-17 and C3 and C4 (P < 0.001). A statistically
significant positive correlation was reported between IL-17 and 24-hour urinary proteins with a Pvalue
of 0.01.

Conclusion:
SLE cases demonstrated higher levels of serum IL-17, contributing to SLE pathogenesis.
However, no statistically significant difference was reported between IL-17 and Lupus
nephritis. IL-17 and SLE activity (SLEDAI) did not correlate.

:
A statistically significant positive relation was reported between IL-17 and 24-hour urinary proteins.
Additionally, a high statistically significant negative correlation was reported between IL-17
and C3 and C4.
Examining the Efficacy, Safety, and Future Prospects of Tirofiban in Managing Myocardial Infarction among Diabetic Patients
Authors: Samsudeen Haajeera , Shrinivasan V.P. Dharani 
Published: February 2024

Background:
Myocardial infarction (MI) is a leading cause of death worldwide, particularly
in patients with diabetes mellitus (DM). Tirofiban, a platelet GP IIb/IIIa receptor inhibitor,
has shown promise as adjunctive therapy in the emergency management of MI in diabetic
patients. However, a comprehensive understanding of its use, efficacy, safety, and limitations in
this patient population is necessary to optimize treatment strategies and improve patient outcomes.

Methodology:
This review article utilized a systematic approach to gather relevant research articles,
clinical trials, and studies on the use of tirofiban in the therapy of MI in diabetic patients.
Databases, such as PubMed and Google Scholar, were extensively searched using specific keywords
related to tirofiban, MI, DM, STEMI, and antiplatelet therapy. The collected data were
carefully examined, summarized, and analyzed to provide an extensive overview of using tirofiban
in the management of MI in diabetic individuals.

Results:
The analysis of the gathered literature revealed that tirofiban has demonstrated efficacy
in improving clinical outcomes, reducing myocardial ischemia-reperfusion injury, and promoting
early recovery of heart function in diabetic patients with MI undergoing percutaneous coronary
intervention. The fast on- and off-rate and dose-dependent effect of the drug on platelet aggregation
contribute to its effectiveness. However, caution should be exercised due to the potential
risk of tirofiban-associated thrombocytopenia. Clinical trials and studies have provided evidence-
based dosing guidelines, enabling the safe and effective administration of tirofiban in this
patient population.

Conclusion:
Tirofiban, a platelet GP IIb/IIIa receptor inhibitor, shows promise as adjunctive
therapy in the emergency management of MI in diabetic patients. It has demonstrated efficacy in
improving clinical outcomes, reducing myocardial ischemia-reperfusion injury, and promoting
early recovery of heart function. However, healthcare providers should be cautious regarding the
potential risk of tirofiban-associated thrombocytopenia. Further research is needed to optimize
dosing guidelines, evaluate long-term safety, and fully understand the benefits and limitations of
tirofiban in this patient population. The comprehensive insights provided in this review aim to
enhance treatment strategies and improve patient outcomes in the emergency management of MI
in diabetic individuals.
Glp-1 Mimetics and Autophagy in Diabetic Milieu: State-of-the-Art
Authors: Yaribeygi Habib , Maleki Mina , Santos Raul D. , Jamialahmadi Tannaz , Sahebkar Amirhossein 
Published: February 2024

Abstract:
The diabetic milieu is associated with cascades of pathophysiological pathways that
culminate in diabetic complications and tissue injuries. Autophagy is an essential process mandatory
for cell survival and tissue homeostasis by degrading damaged organelles and removing injured
cells. However, it may turn into a pathological process in an aberrant mode in the diabetic
and/or malignant milieu. Moreover, autophagy could serve as a promising therapeutic target for
many complications related to tissue injury. Glp-1 mimetics are a class of newer antidiabetic
agents that reduce blood glucose through several pathways. However, some evidence suggests
that they can provide extra glycemic benefits by modulating autophagy, although there is no
complete understanding of this mechanism and its underlying molecular pathways. Hence, in the
current review, we aimed to provide new insights on the possible impact of Glp-1 mimetics on
autophagy and consequent benefits as well as mediating pathways.
Structure-Activity Relationship Studies on VEGFR2 Tyrosine Kinase
Inhibitors for Identification of Potential Natural Anticancer Compounds
Authors: Verma Meenakshi , Sarfraz Aqib , Hasan Inamul , Vasudev Prema Gauri , Khan Feroz 
Published: February 2024

Background:
Over-expression of Vascular Endothelial Growth Factor Receptors (VEGFRs)
leads to the hyperactivation of oncogenes. For inhibition of this hyperactivation, the USA
Food Drug Administration (FDA) has approved many drugs that show adverse effects, such as
hypertension, hypothyroidism, etc. There is a need to discover potent natural compounds that show
minimal side effects. In the present study, we have taken structurally diverse known VEGFR2 inhibitors
to develop a Quantitative Structure-Activity Relationship (QSAR) model and used this
model to predict the inhibitory activity of natural compounds for VEGFR2.

Methods:
The QSAR model was developed through the forward stepwise multiple linear regression
(MLR) method. A developed QSAR model was used to predict the inhibitory activity of natural
compounds. Absorption, distribution, metabolism, excretion, and toxicity (ADMET) assessment
and molecular docking studies were performed. The binding stability of the natural compounds
with VEGFR2 was elucidated through molecular dynamics (MD) simulation.

Results:
The developed QSAR model against VEGFR2 showed the regression coefficient of the
training dataset (r2) as 0.81 and the external regression coefficient of the test dataset (r2
test) 0.71.
Descriptors, viz., electro-topological state of potential hydrogen bonds (maxHBint2, nHBint6),
atom types (minssNH), maximum topological distance matrix (SpMAD_Dt), and 2D autocorrelation
(ATSC7v), have been identified. Using this model, 14 natural compounds have been selected
that have shown inhibitory activity for VEGFR2, of which six natural compounds have been found
to possess a strong binding affinity with VEGFR2. In MD simulation, four complexes have shown
binding stability up to 50ns.

Conclusion:
The developed QSAR model has identified 5 conserved activity-inducing physiochemical
properties, which have been found to be correlated with the anticancer activity of the nonidentical
ligand molecules bound with the VEGFR2 kinase. Lavendustin_A, 3’-O-acetylhamaudol,
and arctigenin have been obtained as possible lead natural compounds against the VEGFR2 kinase.
Quantification of Rutin, an Anti-glycating Drug, in Selected Euphorbia
Species by Florescence Spectroscopy and Partial Least Squares Regression
Analysis
Authors: Ali Maroof , Khan Ajmal , Gilani Syed Abdullah , Ali Liaqat , Maqsood Rabia , Hussain Amjad , Al Rabani Hamida , Rehman Najeeb Ur , Jabeen Farah , Mabood Fazal , Al-Harrasi Ahmed , Hussain Javid 
Published: February 2024

Background:
Rutin is a natural flavonol that showed excellent antiglycation activity with
an IC50 value of 294.5 ± 1.5 μM. In the current study, three selected plant species of Euphorbia, i.e.,
Euphorbia helioscopia, Euphorbia larica, and Euphorbia wallichii, were analyzed for the quantification
of rutin.

Methods:
The quantification was done through a newly developed method of Emission spectroscopy
coupled with Partial Least Square Regression (PLSR) and UV-visible spectroscopy as a parallel
cross-validation method.

Results:
The spectroscopic results indicated the highest rutin concentration in the roots of E. helioscopia
(11.25 mg/100 g) followed by roots of E. wallichii (9.93 mg/100 g), leaves of E. helioscopia
and the whole plant of E. larica (9.41 mg/100 g). The leaves of E. wallichii (8.66 mg/100 g) were
found to contain the lowest concentration of rutin among all the tested samples.

Conclusion:
The present method is one of the simple, robust, and non-destructive methods to carry
out the quantitative estimation of rutin in plants.
Effect of Syzygium cumini on Oxidative Stress Induced Cardiac Cellular Anomalies
Authors: Bhadana Renu , Rani Vibha 
Published: February 2024

Introduction:
Doxorubicin (Dox), an antineoplastic agent is used as a primary anticancerous
drug against various types of cancers. However, its associated toxicity to the cardiovascular
system is major. Literature has recorded the cases of mortality due to poor validation
and lack of prediagnosis of Dox-induced cardiotoxicity. Therapeutic interventions using natural
products having cardioprotective properties with low toxic outcomes hold therapeutic potential for
future cardio-oncological therapies. Syzygium cumini (Black berry), a traditional Indian herbal
plant, has been researched and found to exert cardioprotective, anti-inflammatory, and antioxidant
activities, which have been credited due to the presence of polyphenols, flavonoids, and tannins.

Methods:
In the current research, we investigated the cardioprotective potential of Syzygium
cumini against Doxorubicin-induced cardiotoxicity (DIC) in H9C2 cardiomyocytes. Methanolic
seed extract preparation of Syzygium cumini was performed using the Soxhlet apparatus. Cell
viability and cell death assays were performed to determine the cardiotoxic doses of Doxorubicin.
Furthermore, the cardioprotective potential of Syzygium cumini extract against DIC was
studied. Morphological and nuclear alterations in H9C2 cells were studied by microscopic assays
using Giemsa, Haematoxylin-Eosin stain, and PI. The intracellular stress level and ROS production
were studied using DCFH-DA followed by mitochondrial integrity analysis using fluorescent
microscopic methods.

Results:
In the results, we investigated that Dox exerted a dose and time-dependent cardiotoxicity
on H9C2 cardiomyocytes. Moreover, we observed that morphological and nuclear alterations
caused by doxorubicin in dose-dependent manner were prevented by supplementing with Syzygium
cumini polyphenols and it attenuated the oxidative stress in H9C2 cardiomyocytes effectively.

Conclusion:
Conclusively, Syzygium cumini possesses cardioprotective potential in H9C2 cardiomyocytes
in dox-induced cardiotoxicity.
Actinomyces-induced Osteomyelitis of the Mandible - A Rare Disease?
Authors: Nieves-Velez Caleb , Rivera-Gonzalez Gilberto , Antony Suresh 
Published: February 2024

Background:
Actinomyces species are commensal oral cavity flora that can cause jaw
osteomyelitis. Osteomyelitis of the jaw by Actinomyces is rare, and its presentation can be confused with many different pathologies.

Case presentation:
This is the case of a 61-year-old female with breast cancer and on chemotherapy as well as non-invasive carcinoma of the tongue who initially presented to the dentist with
white spots in the right mandible near the incisors associated with right mandible pain and swelling. Actinomyces-induced osteomyelitis of the mandible was diagnosed. The patient was treated
with penicillin V for 6 weeks along with a course of hyperbaric oxygen therapy, which resulted
in the complete resolution of the infection.

Conclusion:
In summary, jaw osteomyelitis caused by Actinomyces should always be part of the
differential diagnosis; as these organisms are commensal flora, the symptoms manifested are nonspecific, and such a diagnosis could be easily missed, resulting in delay of care and disease progression.
Construction of Camelus dromedaries Immune Single Domain Antibodies Library for Development of Schistosoma mansoni Specific Nanobodies Using Phage Display Strategy
Authors: El-Kalamawy Hadeer Adel , Awwad Mohammed H. , Diab Tarek M. , Okasha Hend , Abdel-Kareim Amal M. , Marawan Marawan A. , Shoulah Salma A. , El-Dabaa Ehab 
Published: February 2024

Background:
Schistosoma mansoni poses a considerable global public health challenge.
In Egypt, approximately 60% of the inhabitants in the Northern and Eastern areas of the
Nile Delta are affected by this parasite, whereas the Southern region experiences a significantly
lower infection rate of 6%.

Aim:
Construction of an immune phage display Nbs library based on the VHH framework for
selecting S. mansoni-specific Nbs for seeking cost-effective, sensitive, and specific diagnostic
tools for rapidly detecting Schistosoma mansoni.

Methods:
Camel was immunized using soluble adult worm antigens (SAWP) for the production
of Variable domains of heavy chains of camelid heavy-chain only antibodies (VHHs),
which are known as nanobodies (Nb). The PBMCs repertoires VHH sequences library have
been constructed with a high percentage of insertion and right orientation using pADL-23c
phagmid and M13 phage followed by three rounds of bio-panning against SAWP using phage
display technique. Evaluations using polyclonal phage ELISA and other techniques have been
carried out to reveal the successful enrichment of anti-SAWP Nbs (VHH) clones. Evaluation
of the diagnostic potentiality of these Nbs was carried out using ELISA on human serum samples
confirmed for S. mansoni infection. Receiver Operator of Characteristics (ROC) curve
analysis was used for discrimination between S. mansoni infection and both negative controls
and the Fasciola hepatica group.

Results:
Using monoclonal ELISA, Nbs of 22 clones out of 24 selected clones showed binding
affinity to SAWP. The cutoff values of the produced anti-S. mansoni Nbs was > 0.19, leading to
80% sensitivity, 95% specificity, and 90% accuracy. Sequence analysis of three of these Nbs with
high binding affinities showed diversity in their targets, considering their CDR3 aa sequences.

Conclusion:
This study successfully generated a diverse phage library enriched with anti-S.
mansoni VHHs. The nanobodies produced exhibit high diagnostic potential for detecting S.
mansoni infection in human patients, offering a promising avenue for the development of efficient
diagnostic tools. The innovative approach described herein may have potential applications
for patent considerations in the field of the field of diagnostic technology.