bluuebunny/crossref_metadata_2025_split huggingface dataset:
Ethnobotanical Significance, Phytopharmacology, and Toxicological Profile of Limonia acidissima L. (Rutaceae): A Review
Authors: Mohanty Satyajit , Pattnaik Ashok 
Published: April 2024

Abstract:
Medicinal plants play a crucial role in traditional medicine, where they are extensively
employed by traditional physicians for treating a wide array of ailments. Limonia acidissima
(Linn), commonly known as the Wood apple and belonging to the Rutaceae family, is widely
cultivated in countries, such as Pakistan, India, and Sri Lanka. The various parts of Limonia
acidissima, including its roots, leaves, fruits, stem, and even the whole plant, have been traditionally
used in the treatment of numerous conditions, such as constipation, diarrhea, dysentery,
skin diseases, asthma, astringent, diabetes, jaundice, and dyspepsia and act as diuretic agents,
cardiotonic, cardiac stimulant, and hepato-protectant. Extensive research has revealed that Limonia
acidissima possesses a rich chemical composition, including quinones, lignans, flavonoids,
sterols, coumarins, alkaloids, triterpenoids, phenolic acids, and volatile oils, present in its
stem, leaves, fruits, stem bark, and roots. These chemical constituents contribute to its diverse
therapeutic properties. In recent years, numerous studies have explored the ethanopharmacological
properties of Limonia acidissima extracts, highlighting their anticancer, antidiabetic,
anti-diarrheal, antimicrobial, antiulcer, wound healing, antioxidant, hepatoprotective, antibacterial,
antifungal, larvicidal, neuroprotective, antispermatogenic, antihistaminic, diuretic,
and adsorbent activities. This comprehensive review focuses on the traditional uses, biological
activities, and phytoconstituents isolated from different parts of Limonia acidissima Linn. The
gathered information provides valuable insights into the therapeutic potential of this plant, serving
as a foundation for further research and the development of novel pharmaceuticals. The integration
of traditional knowledge with scientific evidence enhances the understanding of the medicinal
properties of Limonia acidissima, fostering its utilization in modern medicine and
healthcare systems.
To Explore Potential Inhibitors Against Various Enzymatic Targets of Human African Trypanosomiasis
Authors: Brahma Sayandeep , Moitra Susmita , Bagchi Soumya Ranjan , Samadder Asmita , Nandi Sisir 
Published: April 2024

Abstract:
Synthetic drugs currently prescribed for the treatment of Human African Trypanosomiasis
(HAT) are non-specific, toxic, demand extended therapeutic regimes and are of varying
efficacy. Along with the challenging demographic and socio-economic hurdles, the everincreasing
risk of drug resistance is another major problem to be addressed. Cysteine protease,
Heat shock proteins (HSP-90), Trypanothione reductase (TR), Farnesyl diphosphate synthase,
Glucose-6-phosphate dehydrogenase, UP-4-galactose epimerase, and Cytidine triphosphate synthetase
are potential enzymatic targets for the development of novel inhibitors against HAT
which are the main focus of this review. The potential enzymatic targets of Trypanosoma brucei,
especially small molecules like cysteine proteases and heat shock proteins are identified as major
candidates for the sustenance of the parasite, their proliferation, infection, and spread of the disease.
The development of new compounds to combat the disease by thorough ligand modification
has been explored in the current review. Extracting these compounds and studying their efficacy,
toxicity, and target mechanism extensively, this review has proposed a list of different
compounds, including some synthetic and natural compounds along with multi-target inhibitors
such as acoziborole, fexinidazole, etc. Potential inhibitors against these enzymatic targets of the
T. brucei are important candidates for designing novel therapeutics against HAT. Multi-target
inhibitors have also been identified as crucial molecules because of their potential advantage
against the development of drug resistance.

method:
The potential enzymatic targets of Trypanosoma brucei, especially small molecules like cysteine proteases and heat shock proteins are identified as major candidates for the sustenance of the parasite, their proliferation, infection and spread of the disease. Development of new compounds to combat the disease by thorough ligand modification have been explored in the current review.

result:
Extracting these compounds and studying their efficacy, toxicity, and target mechanism extensively, this review have proposed a list of different compounds, including some synthetic and natural compounds along with multi-target inhibitors such as acoziborole, fexinidazole etc.
Mogroside V Promotes Osteogenic Differentiation of Bone Marrow Mesenchymal Stem Cells from Diabetic Mice by Altering MicroRNA Profiles
Authors: Luo Yicai , Ye Zhimao , Li Cuiping , Hong Le , Li Hao 
Published: April 2024

Background:
Mogroside V (MV), a triterpene glycoside, exhibits diverse biological
functions. However, its ability to promote the osteogenic differentiation of bone marrow mesenchymal
stem cells (BMSCs) under diabetic conditions is yet to be elucidated.

Objective:
To study the regulation of osteogenic differentiation of BMSCs in diabetic mice by
MV and determine the potential mechanism.

Methods:
BMSCs were isolated from both normal (referred to as N-BMSCs) and diabetic (referred
to as DM-BMSCs) C57BL/6 mice. DM-BMSCs were treated with different concentrations
of MV for varying durations, and cell viability was detected using the cell counting kit-8
assay. Following 2 weeks of osteogenic induction, osteogenic differentiation capability was
evaluated using alizarin red S staining, alkaline phosphatase (ALP) activity analysis, and quantitative
real-time reverse transcription polymerase chain reaction. Furthermore, the microRNA
(miRNA) expression profiles of N-BMSCs, DM-BMSCs, and DM-BMSCs treated with MV
were tested using high-throughput sequencing.

Results:
Treatment with MV enhanced the viability of DM-BMSCs and mitigated the reduction
of calcium nodule deposition, ALP activity, and mRNA expression of ALP, osteocalcin, and
runt-related transcription factor 2. Of the analyzed miRNAs, miR-10b-5p was the only one that
exhibited differential expression in N-BMSCs, DM-BMSCs, and DM-BMSCs treated with MV.
An analysis of the top four protein clusters based on KEGG suggested that the target genes of
differentially expressed miRNAs were closely linked to the PI3K/AKT pathway.

Conclusion:
MV significantly enhances the viability and osteogenic differentiation of BMSCs
under diabetic conditions. The alteration of miRNA profiles provides a foundation for further
research into the regulatory role of miRNAs and MV in this process.
The NeuroProtect Formula: A Preventive Approach to AD Targeting the
HIF-1/PI3K-AKT Signaling Pathway Evaluated through In Vivo, In Vitro,
and Network Pharmacology Approaches
Authors: Li Haiyan , Hua Qian , Cheng Shuo , Liu Xiaoge , Cai Qingyuan , Zhang Jiani , Peng Tiantian , Li Jiao , Wang Chunxiang , Liang Chengbang , shi Yu , Wang Xu , Tan Yan 
Published: April 2024

Objective:
Alzheimer’s Disease (AD) is a progressive neurodegenerative disorder
with limited options for reversing its middle-to-late stages. Early intervention is crucial to slow
down disease progression. This study aimed to investigate the potential of the NeuroProtect
(NP) formula, a combination of geniposide and Panax notoginseng saponins, in preventing AD.
We evaluated the effects of the NP formula on amyloid plaque accumulation, neuronal degeneration, and molecular signaling pathways using in vivo and in vitro models.

Methods:
To predict functional pathways and potential downstream targets of NP intervention,
we employed network pharmacology. The preventative impact of the NP formula was assessed
using APP/PS1 mice. We conducted HE staining, ELISA assay, Golgi staining, and immunohistochemistry to detect the protective effect of NP. Additionally, cell experiments were performed to assess cell activity and target protein expression.

Results:
Network pharmacology analysis revealed 145 drug-disease interactions and identified 5
core active targets associated with AD. Molecular docking results demonstrated strong binding
affinity between the components of the NP formula (GP, GN-Rb1, GN-Rg1, NS-R1) and target
proteins (STAT3, HIF1A, TLR4, mTOR, VEGFA). Notably, the binding energy between NS-R1
and mTOR was -11.4kcal/mol. Among the top 10 enriched KEGG pathways, the HIF-1 and
PI3K-AKT signaling pathways were highlighted. In vivo experiments demonstrated that the NP
formula significantly ameliorated pathological changes, decreased the Aβ42/Aβ40 ratio in the
hippocampus and cortex, and increased dendritic spine density in the CA1 region during the early stage of AD. In vitro experiments further illustrated the NP formula’s ability to reverse the inhibitory effects of Aβ25-35 on cell viability and regulate the expression of Tlr4, Mtor, Hif1a,
Stat3, and Vegfa.

Conclusion:
Our findings suggest that NP exhibits neuroprotective effects during the early stages of AD, positioning it as a potential candidate for AD prevention. The NP formula may exert
its preventive effects through the HIF-1/PI3K-AKT signaling pathway, with mTOR identified as
a key target.
Phloridzin's Diabetic Wound Healing Potential through DPP-4 Enzyme
Inhibition: A Review Article
Authors: Sharma Khushi , Ramachandran Vadivelan , Sharma Ashutosh , Mohanasundaram Tharani , Mageshkumar Harshini 
Published: April 2024

Abstract:
Diabetic wound healing is a dynamic medical process that takes place in an environment
within the body that is complex and contains elevated sugar levels, oxygen deprivation,
and cellular oxidative stress. Phloridzin (Phlorizin) is one of the most well-known polyphenols
found in apples because of its anti-inflammatory, antioxidant, antibacterial, antidiabetic, and antiseptic
properties; it can also play a significant part in the healing of diabetic wounds.
The study aimed to investigate the role of phloridzin as an efficient DPP-4 inhibitor with additional
therapeutic effects in diabetic wound healing, as Dipeptidyl Peptidase-4 (DPP-4) expression
increases in response to increases in glucose, Reactive Oxygen Species (ROS), and inflammation.
Phloridzin inhibiting DPP-4 preserves Stromal cell-derived Factor-1α (SDF-1α),
Insulin-like Growth Factor (IGF), and Glucagon-like Peptide-1 (GLP-1), which are possible
DPP-4 substrates involved in wound healing.
The accessible material from systemic searches in PubMed, Scopus, and published articles was
reviewed with no period of limitation.
The in silico study showed strong binding of phloridzin with DPP-4 protein (2P8S); also, in
vitro DPP-4 inhibition assay has shown better inhibition by phloridzin. This study offers new
research directions for examining phloridzin’s capacity to withstand oxidative stress, as well as
for redefining its tactical function as a powerful DPP-4 inhibitor to regulate the process involved
in the healing of diabetic wounds.
Substituted 4H-3,1-benzoxazine-4-one Derivatives as Inhibitors of Cathepsin G
Authors: Aliter Kholoud F. , Al-Horani Rami A. 
Published: April 2024

Background:
Cathepsin G (CatG) is a cationic serine protease with a wide substrate
specificity. CatG has been reported to play a role in several pathologies, including rheumatoid arthritis,
ischemic reperfusion injury, acute respiratory distress syndrome, and cystic fibrosis, among
others.

Objective:
We aim to develop a new class of CatG inhibitors and evaluate their potency and selectivity
against a series of serine proteases.

Methods:
In this communication, we report on a new class of CatG inhibitors of 4H-3,1-benzoxazin-
4-one derivatives. We constructed a small library of seven substituted 4H-3,1-benzoxazin-4-one
derivatives and identified their inhibition potential against CatG. Five molecules were identified as
CatG inhibitors with values of 0.84-5.5 μM. Inhibitor 2 was the most potent, with an IC50 of 0.84 ±
0.11 μM and significant selectivity over representative serine proteases of thrombin, factor XIa,
factor XIIa, and kallikrein.

Results:
In this communication, we report on a new class of CatG inhibitors of 4H-3,1-benzoxazin-
4-one derivatives. We constructed a small library of seven substituted 4H-3,1-benzoxazin-4-one
derivatives and identified their inhibition potential against CatG. Five molecules were identified as
CatG inhibitors with values of 0.84-5.5 μM. Inhibitor 2 was the most potent, with an IC50 of 0.84 ±
0.11 μM and significant selectivity over representative serine proteases of thrombin, factor XIa,
factor XIIa, and kallikrein.

Conclusion:
Thus, we propose this inhibitor as a lead molecule to guide subsequent efforts to develop
clinically relevant potent and selective CatG inhibitors for use as anti-inflammatory agents.
Designing a Novel di-epitope Diphtheria Vaccine: A Rational Structural
Immunoinformatics Approach
Authors: Shadmani Mahsa , Ghasemnejad Atefeh , Bazmara Samira , Bagheri Kamran Pooshang 
Published: April 2024

Background:
The design of an epitope-based vaccine against diphtheria toxin (DT)
originated from the idea that many strong binder epitopes may be structurally located in the
depth of DT. Subsequently, many ineffective antibodies may be produced by the presentation of
those epitopes to T and B lymphocytes. The other critical issue is the population coverage of a
vaccine that has been neglected in traditional vaccines.

Objective:
Given the issues above, our study aimed to design a peptide-based diphtheria vaccine, considering the issues of unwanted epitopes and population coverage.

Methods:
The frequencies of pre-determined HLA alleles were listed. A country in which almost all HLA alleles had been determined in almost all geographical distribution was selected.
The epitopes within the sequence of diphtheria toxin were predicted by the NetMHCIIPan server based on the selected HLA alleles. Strong binder epitopes on the surface of diphtheria toxin
were selected by structural epitope mapping. The epitopes, which cover almost all the human
population for each of the HLA alleles in the candidate country, were then selected as epitopebased vaccines.

Results:
At first, 793 strong binder epitopes were predicted, of which 82 were surface epitopes.
Nine surface epitopes whose amino acids had extruding side chains were selected. Finally, 2
epitopes had the most population coverage and were suggested as a di-epitope diphtheria vaccine. The population coverage of the di-epitope vaccine in France and the world was 100 and
99.24 %, respectively. HLA-DP had the most roles in epitope presentation.
Rapid Development and Validation of Atoltivimab, Maftivimab and
Odesivimab in Pharmaceutical Dosage form by using the RP-HPLC
Method
Authors: Rao Pallepogu Venkateswara , Rao Naidu Srinivasa , Sahoo Biswa Mohan , Babu Nayaka Raghavendra 
Published: April 2024

Background:
The reverse-phase high-performance liquid chromatography (RP-HPLC)
method was developed for the quantitative measurement of monoclonal antibodies (Maftivimab, Atoltivimab,
and Odesivimab) in the pharmaceutical dosage form. The Food and Drug Administration (FDA)
has approved these monoclonal antibodies for the treatment of Zaire ebolavirus infection in adults

Methods:
Maftivimab, Atoltivimab, and Odesivimab were separated chromatographically on the Waters
Alliance-e2695 platform using the Luna Phenyl Hexyl (250 x 4.6 mm, 5 μm) column and a mobile
phase made up of Acetonitrile (ACN) and ortho-phosphoric acid (OPA) buffer in a ratio of 70:30 (v/v).

Results:
The flow rate was 1.0 ml/min, and a photodiode array (PDA) detector operating at room temperature
was used to measure absorption at 282 nm. For Maftivimab, Atoltivimab, and Odesivimab, the
theoretical plates were not less than 2000, and the tailing factor shouldn't be greater than 2, accordingly.
All measurements have a constant relative standard deviation of peak areas that is less than 2.0.

Conclusion:
The suggested procedure was approved following the International Conference on Harmonisation
(ICH) recommendations. When used for the quantitative analysis of Maftivimab, Atoltivimab,
and Odesivimab, the approach was found to be straightforward, affordable, appropriate, exact,
accurate, and robust.
From Evidence to Practice: A Comprehensive Analysis of Side Effects in Synthetic Anti-Depressant Therapy
Authors: Pannu Arzoo , Goyal Ramesh K. 
Published: April 2024

Abstract:
Depression, a pervasive mental health disorder, affects millions worldwide, necessitating
the widespread use of synthetic anti-depressant medications. While these pharmaceutical
interventions have demonstrated efficacy in alleviating depressive symptoms, they are not without
their associated side effects. This review provides a comprehensive overview of the side effects
of synthetic anti-depressants, aiming to enhance the understanding of their clinical implications.
Common side effects explored include gastrointestinal disturbances, sexual dysfunction,
insomnia, weight gain, and cognitive impairments. Additionally, this review delves into less
frequent but potentially severe adverse events, such as serotonin syndrome, hyponatremia, and
cardiac complications associated with specific classes of synthetic anti-depressants.
Moreover, the review examines the interplay between side effects and treatment adherence,
emphasizing the importance of monitoring and managing these effects in clinical practice. It
also discusses strategies to mitigate side effects, including dose adjustments, combination
therapy, and alternative treatment approaches. In conclusion, this comprehensive review sheds
light on the multifaceted landscape of side effects associated with synthetic anti-depressants. By
providing clinicians with a nuanced understanding of these effects, it aims to facilitate informed
decision-making, personalized treatment plans, and improved patient outcomes in managing
depression.
Effects of Metformin Therapy on Thyroid Volume and Functions in Patients with Newly Diagnosed Type 2 Diabetes Mellitus: A Single-center Prospective Study
Authors: Olgun Mehtap Evran , Pire Gizem , Güney İsa Burak 
Published: April 2024

Objective:
Patients with impaired glucose metabolism have increased thyroid volume
and a higher prevalence of nodules. Yet, some studies show that there is an improvement in
these thyroid parameters after diabetes treatment. Our observational study aimed to reveal the
effect of treatment on thyroid function, thyroid volume, and the presence of nodules in newly
diagnosed type 2 diabetes mellitus (T2DM) patients who were started on metformin treatment.

Methods:
Euthyroid and subclinically hypothyroid patients with a serum TSH level of <10 mU/L,
who were newly diagnosed with T2DM and started on metformin as an antidiabetic treatment and
not used any thyroid medication previously, were included in our study. Patients' characteristics
were recorded. Baseline and 6th-month serum thyroid function tests were scheduled. Baseline and
6th-month thyroid gland characteristics were examined by thyroid ultrasonography.

Results:
A total of 101 (37 males, 64 females) newly diagnosed T2DM patients with euthyroid
(n=95) or subclinical hypothyroidism (n=6) were included in the study. The mean age of the patients
was 53.02 ± 11.9 years, and the mean BMI was 29.60 ± 3.9 kg/m2. Fifty-two (52%) patients
were classified as obese. Body weight, BMI, serum TSH, ALT, Anti-TPO levels, and thyroid volume
decreased significantly in the 6th-month compared to baseline values (p = 0.000; p = 0.000; p
= 0.011; p = 0.022; p = 0.000, respectively). Serum anti-Tg, fT4, fT3 levels, and thyroid nodule
count did not change significantly. A high agreement was found between the baseline and 6thmonth
nodule counts (gamma= 0.886; p < 0.001) and the presence of multi-nodularity in the thyroid
(gamma= 0.941; p < 0.001), but no significant change was observed. Anti-TPO levels showed
a significant decrease in both with and without obesity groups at the end of 6 months (p = 0.003, p
= 0.009, respectively). Serum TSH level decreased significantly only in non-obese subjects (p =
0.004), and thyroid volume decreased significantly only in obese subjects (p = 0.000).

Conclusion:
Our results suggest that metformin treatment significantly reduces body weight,
BMI, thyroid volume, and serum TSH, ALT, and Anti-TPO levels in patients with newly diagnosed
T2DM. Moreover, serum TSH levels showed a significant decrease in non-obese subjects,
while thyroid volume showed a significant decrease in obese subjects.
Radioprotective effect of Cerebrolysin in the Rat’s Brain Tissues
Authors: Ghavipanjeh Gholamreza , Taeb Shahram , Farzin Mohammad Amin , Farhood Bagher , Najafi Masoud , Ardjmand Abolfazl 
Published: April 2024

Aim:
The aim of this study is to evaluate radioprotective effects of Cerebrolysin (CBL)
in rats' brain tissues after local irradiation.

background:
CBL has demonstrated antioxidant, anti-inflammatory, and tissue repair properties. In this study, the radioprotective effects of CBL (50 mg/ kg) were evaluated in the brain tissues of rats after RT.

Background:
CBL has demonstrated antioxidant, anti-inflammatory, and tissue repair properties.
In this study, the radioprotective effects of CBL in the brain tissues of rats after Irradiation (IR)
(50 mg/ kg) were evaluated.

objective:
The levels of different oxidative stress markers, including malondialdehyde (MDA), nitric oxide (NO), glutathione peroxidase (GPx), catalase (CAT), and superoxide dismutase (SOD) were examined after treatment with radiation and CBL.

Objective:
The levels of different oxidative stress markers, including malondialdehyde (MDA), nitric
oxide (NO), glutathione peroxidase (GPx), catalase (CAT), and superoxide dismutase (SOD)
were examined after treatment with radiation and CBL.

Methods:
First, 20 male adult Wistar rats weighing 180-200 g were used. The animals were exposed
to a single fraction of 15Gy using a linear accelerator unit at a dose rate of 200 cGy/mine.
In this study, to check the amount of oxidative stress following the IR, the level of four markers
MDA, NO, GPx, CAT, and SOD were examined and measured using the spectrophotometric
method and purchased kits.

Results:
The results showed that compared to the IR group, the administration of CBL increases
the levels of GPX and SOD significantly (p < 0.05).

Conclusion:
Our finding suggests that CBL has radioprotective effects on the brain by enhancing
antioxidant defense mechanisms.
Role of Artificial Intelligence in VLSI Design: A Review
Authors: Thakur Garima , Jain Shruti 
Published: April 2024

:
Artificial intelligence (AI) related technologies are being employed more and more
in a range of industries to increase automation and improve productivity. The increasing volumes
of data and advancements in high-performance computing have led to a sharp increase in
the application of these methods in recent years. AI technology has been widely applied in the
field of hardware design, notably in the design of digital and analogue integrated circuits (ICs),
to address challenges such as rising networked devices, aggressive time-to-market, and everincreasing
design complexity. However, very little attention has been paid to the issues and
problems related to the design of integrated circuits. The authors of this article review the stateof-
the-art in AI for circuit design and optimization. AI offers knowledge-based technologies
that give challenges a foundation and structure. A technology known as AI makes it possible
for machines to mimic human behavior. Data in all formats, including unstructured, semistructured,
and structured, can be processed by AI. It is crucial to incorporate all of the features
and levels of the many CAD programmes into a single, cohesive environment for creation, as
was mentioned in the section that came before this one. Consequently, the application of AI
automation helps to enhance the effectiveness and efficiency of CAD's performance.