bluuebunny/crossref_metadata_2025_split huggingface dataset:
Theaflavins Induce Autophagy in Ehrlich’s Ascites Carcinoma Cells both
In vivo and In vitro
Authors: Ghosh Arijit Kumar , Verma Aanchal , Majumder Debabrata , Maiti Debasish , Choudhuri Tathagata , Banerjee Antara , Saha Samiran 
Published: January 2024

Aims:
To investigate the efficacy of Theaflavins to induce autophagy and its tumoricidal activity towards Ehrlich’s Ascites Carcinoma cells.

Background:
The apoptosis-inducing role of Theaflavins against cancer is reported. Autophagy,
a cellular mechanism under stress, occurs either as a survival process or Type-II programmed-cell
death in the presence/absence of apoptosis. The report of Theaflavins inducing autophagy against
cancer is poor.

Objective:
Here, for the first time, the investigation for the anti-tumor efficacy of Theaflavins via
autophagy in EAC was attempted.

Methods:
EAC-bearing mice were treated orally with Theaflavins (10 mg/kg b.w.) every alternate
day with a total of 27 doses. Body weight, tumor volume and survivability were recorded. Tumoricidal
and cellular dehydrogenase activity, in vivo and in vitro, were studied using Trypan-blue
exclusion and MTT assay respectively. Theaflavins-treated EAC cells were subjected to Monodansylcadaverine-
staining. LC3II turnover and LC3I conversion were detected by western blotting.
Apoptosis up to 12 h TF-treatment was estimated by AnnexinV binding.

Results:
This is the first report of Theaflavins inducing autophagy in EAC cells in vivo and in
vitro. Oral Theaflavins treatment restricted excessive body-weight increase due to tumors, reduced
tumor volume, and increased survivability of tumor-bearing mice. Theaflavins caused EAC
cell death (~8% in vitro, ~30% in vivo), significantly reduced metabolic activity, and created conspicuous
vacuolization in surviving cells. Resultant vacuoles (in vitro, 6 h) were marked as autophagosomes
by Monodansylcadaverine-staining. Autophagy was confirmed by LC3II augmentation.
No significant apoptosis was observed up to 12 h TF-treatment in vitro.

Conclusion:
Theaflavins were efficient inducing autophagy and Type-II PCD in EAC cells. Notably,
Theaflavins induced autophagy prior to apoptosis in vitro.
Metabolite Profiling and in silico Studies to Elucidate the
Anti-inflammatory Properties of Pterocarpus milbreadii
Authors: Aba Patrick Emeka , Odugbo Ismaila Onuche 
Published: January 2024

Background::
Pterocarpus milbreadii (PM), called Rosewood in English, is a leafy vegetable
used in preparing soup and has also proven medicinal.

Objective::
This study aimed to evaluate the most abundant compound in the ethylacetate fraction of
PM using Gas Chromatography-mass Spectrometry (GC-MS) and docking it against cyclooxygenase
isoenzymes.

Methods::
The PM leaves were extracted with ethyl acetate using the cold maceration method. The
extract was subjected to GC-MS assay. The spectra obtained were matched with NIST 17. AutoDock
Vina was used to perform the molecular docking of the most abundant compound of PM and cyclooxygenase.
Celecoxib was used as the standard ligand.

Results::
The results of the study revealed that the ethyl acetate leaf extract of PM contained different
phytochemicals, with hexadecenoic acid being the most abundant, with an intensity count of 9.5 x108
CPS. Docking of hexadecenoic acid and Celecoxib with COX-2 yielded binding energies of -6.7 and
-7.7 kcal/mol, respectively, while with COX-1, the binding energies of -6.3 and -9.8 kcal/mol were
respectively recorded. Hexadecenoic acid interacted with both COX-1 and COX-2 largely via Van
der waals and pi-Alkyl bonds. Celecoxib made conventional hydrogen, carbon-hydrogen, halogen,
pi-sigma, pi-alkyl interactions with the cyclooxygenase isoenzymes.

Conclusion::
It was concluded that hexadecenoic acid was the predominant phytochemical in the
ethylacetate leaf extract of PM. The hexadecanoic acid ligand produced a better inhibitory effect on
COX-2 compared to COX-1.
Molecular Mechanism Analysis of the Effect of Hederagenin Combined with L-OHP on Chemosensitivity of AGS/L-OHP Based on Network
Pharmacology
Authors: Tang Hongyue , Wang Chao , Xing Chenhao , liang Guoxin , Guo Chang , Liu Xin , Li YanJie , Zhang Mingming 
Published: January 2024

Aims and Objectives:
This study aimed to evaluate the pharmacological mechanism
of Hederagenin (HD) combined with oxaliplatin (L-OHP) in treating gastric cancer (GC)
through network pharmacology combined with experimental verification.

background:
Gastric cancer (GC) is the world’s most common gastrointestinal cancer[1]. This malignancy is of challenge to be eradicated by surgical operation since most diagnosed patients have developed into the advanced stage. Chemotherapy is a crucial part of the comprehensive treatment for GC, despite that the potential drug resistance may reduce the therapeutic efficacy[2,3]. Oxaliplatin (L-OHP) is the third-generation platinum-based antineoplastic drug, which has been widely used for GC treatment because of its excellent performance compared with many other chemotherapeutic drugs such as cisplatin[4]. However, previous studies have reported that GC cells still show some resistance to L-OHP .

Material and Methods:
Network pharmacology methods were used to screen potential targets
for HD, L-OHP, and GC-related targets from public databases, and the intersection of the three
gene sets was taken. Cross genes were analyzed through protein-protein interaction (PPI) networks
to predict core targets, and related pathways were predicted through GO and KEGG enrichment
analysis. The experimental results were verified by the in vitro experiments. HD was
applied on AGS/L-OHP cells, and then cellular chemosensitivity and the expressions of P-gp,
Survivin, Bcl-2, p-Akt, and p-PI3K genes were detected. Wound assay and Transwell Chamber
assay were employed to detect the effect of HD on AGS/L-OHP cells. Nude mice xenograft
models transfected using AGS/L-OHP cells were also treated with HD in order to verify the
results. The size and weight of the tumor, as well as the expressions of P-gp, Survivin, Bcl-2, p-
Akt and p-PI3K genes, were also measured.

Results:
KEGG analysis showed that the anti-gastric cancer effect of HD was mediated mainly
by PI3K-Akt signaling pathways. The PI3K-Akt signaling pathway containing more enriched
genes may play a greater role in anti-gastric cancer. It was observed that for AGS/L-OHP cells
jointly treated with HD and L-OHP, their activity, migration and invasion were significantly
lower than those treated only using HD or L-OHP group. Moreover, expressions of p-Akt, p-
PI3K, Bcl-2, P-gp, and Survivin for the HD+L-OHP group decreased significantly. Results of
the in vivo experiments showed that the sizes and weights of tumors in the HD+L-OHP group
were the lowest compared to the HD group and L-OHP group.

Conclusion:
Our findings suggest that HD may reduce the resistance of AGS/L-OHP cells to LOHP
by regulating the PI3K/Akt signaling pathway.
Targeting Epigenetic Modifiers: Promising Strategies for Cancer Therapy and Beyond
Authors: Chanchal Dilip Kumar , Porwal Prateek , Mittal Nidhi 
Published: January 2024

:
Epigenetic changes are important for controlling how genes are expressed and how cells
work, and their misregulation has been linked to many diseases, including cancer. Targeting epigenetic
modifiers has become a promising way to treat cancer, and it may also be useful outside of
oncology. This review article goes into detail about the rapidly changing field of epigenetic-based
therapies, with a focus on how they are used to treat cancer. We discuss in-depth the main epigenetic
changes seen in cancer, such as DNA methylation, changes to histones, and dysregulation of noncoding
RNA, as well as their roles in tumour growth, metastasis, and drug resistance. Epigenetic
drugs and small molecule inhibitors that target epigenetic enzymes and reader proteins have shown a
lot of promise in both preclinical and clinical studies on different types of cancer. We show the most
recent evidence that these epigenetic therapies work and look into how they might be used in combination
with other treatments. We talk about new research into the therapeutic potential of epigenetic
modifiers in diseases other than cancer, such as neurological disorders, autoimmune diseases, and
heart conditions. Even though there is a lot of potential for therapy, there are still problems, such as
side effects and differences between patients. We talk about the work that is still being done to get
around these problems and explain new ways to deliver epigenetic-based interventions that are more
precise and effective. For epigenetic-based therapies to be used in clinical settings, it is important to
understand how they work and how they interact with other types of treatment. As the field moves
forward, we try to figure out where it is going and what it means to target epigenetic modifiers in
cancer therapy and other areas of disease. This review looks at the role of epigenetic modulation in
shaping the landscape of precision medicine and its possible effects on human health from a broad
and forward-looking point of view.
Enhancing Spermatogenesis in Non-obstructive Azoospermia Through Mesenchymal Stem Cell Therapy22
Authors: Margiana Ria 
Published: January 2024

:
Stem cells hold great promise as novel and encouraging therapeutic tools in the treatment
of degenerative disorders due to their differentiation potential while maintaining the capability
to self-renewal and their unlimited ability to divide and regenerate tissue. A variety of different
types of stem cells can be used in cell therapy. Among these, mesenchymal stem cell (MSC) therapy
has gradually established itself as a novel method for treating damaged tissues that need restoration
and renewal. Male infertility is an important health challenge affecting approximately
8-12% of people around the world. This abnormality can be caused by primary, congenital, acquired,
or idiopathic reasons. Men with no sperm in their semen have a condition called azoospermia,
caused by non-obstructive (NOA) causes and post-testicular obstructive causes. Accumulating
evidence has shown that various types of MSCs can differentiate into germ cells and improve
spermatogenesis in the seminiferous tubules of animal models. In addition, recent studies in animal
models have exhibited that extracellular vesicles derived from MSCs can stimulate the progression
of spermatogenesis and germ cell regeneration in the recipient testes. In spite of the fact
that various improvements have been made in the treatment of azoospermia disorder in animal
models by MSC or their extracellular vesicles, no clinical trials have been carried out to test their
therapeutic effect on the NOA. In this review, we summarize the potential of MSC transplantation
for treating infertility caused by NOA.
Preparation, Characterization, and Anticancer Activity Assessment of Chitosan/TPP Nanoparticles Loaded with Echis carinatus Venom
Authors: Kancha Maral Mahboubi , Mehrabi Mohsen , Bitaraf Fatemeh Sadat , Vahedi Hamid , Alizadeh Morteza , Bernkop-Schnürch Andreas 
Published: January 2024

Aims and Background:Echis carinatus venom is a toxic substance naturally produced by special glands in this snake species. Alongside various toxic properties, this venom has been used for its therapeutic effects, which are applicable in treating various cancers (liver, breast, etc.).Objective:Nanotechnology-based drug delivery systems are suitable for protecting Echis carinatus venom against destruction and unwanted absorption. They can manage its controlled transfer and absorption, significantly reducing side effectsMethods:In the present study, chitosan nanoparticles were prepared using the ionotropic gelation method with emulsion cross-linking. The venom's encapsulation efficiency, loading capacity, and release rate were calculated at certain time points. Moreover, the nanoparticles' optimal formulation and cytotoxic effects were determined using the MTT assay.Results:The optimized nanoparticle formulation increases cell death induction in various cancerous cell lines. Moreover, chitosan nanoparticles loaded with Echis carinatus venom had a significant rate of cytotoxicity against cancer cells.Conclusion:It is proposed that this formulation may act as a suitable candidate for more extensive assessments of cancer treatment using nanotechnology-based drug delivery systems.
Ameliorating Gonorrhea: Recent Therapeutic Adaptations and Scope to
Improve its Prevailing Condition
Authors: Bishi Munyaradzi Amon , Kaur Palwinder , Vyas Manish , Sharma Sandeep 
Published: January 2024

Background::
Gonorrhea is a sexually transmitted infection (STI) caused by the bacteria
Neisseria gonorrhoeae. According to recent research, the prevalence of gonorrhea has been increasing
in many parts of the world, with some areas reporting high rates of antibiotic resistance. In the
United States, the Centers for Disease Control and Prevention (CDC) reported that the number of
reported gonorrhea cases increased by 56% between 2015 and 2019. Globally, the World Health Organization
(WHO) estimated that there were 87 million new cases of gonorrhea in 2016, with the
highest burden of infection in low- and middle-income countries. Research has also shown that gonorrhea
is becoming increasingly resistant to conventional antibiotics, increasing the prevalence of
gonorrhea. This raises concerns and challenges in disease management.

Objectives::
The present review gives updated insight on the current state of the disease, challenges,
and shortcomings of existing approaches along with the modern and alternative direction like vaccine
development, its challenges, and scope to confront the existing state of drug resistance and increased
rate of incidence. Alternative strategies like immunotherapy and phage therapy along with recent
antibiotics researched for the treatment of gonorrhea.

Conclusion::
The review provides a thorough insight into the current state of the disease and various
available methods used currently and recommended by WHO. To overcome disease prevalence, various
alternate therapies are coming into the limelight. However, scientists and researchers show a lack
of interest in the drug development and research of gonorrhea, due to less commercial scope, lack of
funding, and limited scope in the scientific scenario. These hurdles need to be overcome to meet the
WHO vision of reducing gonorrhea by 90% by 2030. So, there is a need to optimize the drug therapy
(optimizing dosing schedule, and precision monitoring) to reduce the chance of drug resistance. Also,
there is a wide scope for drug and therapeutic system development.
Uniparental Disomy as a Mechanism for Combined Oxidative Phosphorylation
Deficiency Associated with MRPS34 Gene
Authors: Soares Marta P. , Travessa André M. , Custódio Sónia , Pereira Carla , Pinto Patrícia , Sousa Ana Berta 
Published: January 2024

Introduction:
Mitochondrial oxidative phosphorylation (OXPHOS) is a cellular process
that generates most of the cellular energy required by the body. Disorders affecting
OXPHOS are multisystem diseases caused by pathogenic variants in more than 50 genes. In
2017, biallelic variants in the MRPS34 gene were shown to cause combined oxidative phosphorylation
deficiency type 32 (COPD32) (OMIM#617664); however, only 7 patients have
been reported in the literature up to this moment. COPD32 is characterized mainly by a severe
Leigh-like syndrome.

Methods:
Whole-exome sequencing identified a homozygous pathogenic variant in the
MRPS34 gene, c.322-10G>A. Only the mother was heterozygous for this variant. SNP-array
analysis was performed, which revealed a region of absence of heterozygosity in variant 16q
with 9.8Mb, compatible with maternal uniparental disomy.

Results/Case Report:
We report the case of an 18-year-old female with unremarkable family
history. The pregnancy was complicated by oligohydramnios, and the neonatal period was unremarkable.
She evolved with low weight, mild-moderate developmental delay/intellectual disability,
and hypogonadotropic hypogonadism. On examination, she had slender habitus, joint
laxity, and kyphoscoliosis. The cardiac evaluation was normal, and the head MRI showed bilateral
olivary nucleus degeneration that was not confirmed subsequently. Extensive metabolic
studies documented only mild lactate and pyruvate elevation, and the chromosomal microarray
was normal.

Conclusion:
We have reported the case of the first patient with COPD32 due to partial maternal
uniparental disomy of chromosome 16, being first in Portugal and seventh in the literature. Contrarily
to previous patients, who died in the first months of life or survived with severe DD/ID,
and had a Leigh-like syndrome, this case is significantly milder, contributing to a better characterization
of the phenotypic spectrum. Recurrence risk is unexpectedly low in this instance. This
case illustrates the importance of segregation analysis in patients with homozygous recessive
mutations.
Analysis and Design of CUK-SEPIC-based Converter for Hybrid Power Generation Systems
Authors: P.K. Vineeth Kumar , J.J. Jijesh 
Published: January 2024

Background:
The increasing demand for electricity, coupled with an imbalanced supply
and demand, population growth, and climate change, has prompted the shift from conventional to
non-conventional energy systems. However, the unreliability and intermittency of the latter pose a
challenge to their feasibility. To address this challenge, a proposal has been made to explore the
combination of two renewable energy sources (RES) using a unique DC-DC converter topology,
with the aim of meeting the load demand in a sustainable and efficient manner.

Objective:
The focus of this research was to explore solutions for the challenges associated with operating
RES independently, including issues with intermittency, weather dependence, and meeting load
demands. The proposed hybrid system features exclusively RES, offering a promising approach to reducing
carbon footprint. Ultimately, we aimed to develop a CUK-SEPIC-based converter that can effectively
integrate two independent RES to satisfy the load demand of a standalone application.

Method:
Effective hybrid power generation through RES is a complex challenge, but it has been found
that combining solar and biomass energy sources is one of the best options for achieving this goal. To
tap into these sources, it is essential to have a suitable power electronic converter, and the CUK-SEPIC
converter has been chosen for its many benefits. The features of this converter have been described in
detail. The integration of solar and biomass energy sources is achieved using this converter, which has
been designed and mathematically modeled in the MATLAB/Simulink environment to ensure optimal
performance. To validate the effectiveness of the proposed converter, a comparison with existing power
electronic converters has been done using the MATLAB/Simulink platform.

Results:
The hybrid power generation system model has been comprehensively developed in this work
using the sophisticated MATLAB/Simulink environment. The input and output parameters have been
diligently estimated through an extensive simulation process. The research has yielded valuable insights,
indicating that the CUK-SEPIC converter exhibits an impressive power conversion efficiency of
96.57%, along with an overall step-up ratio of 5.25 and significantly reduced ripple content.

Conclusion:
Upon conducting a comprehensive analysis of the CUK-SEPIC DC-DC converter, it
has been observed that the proposed system exhibits significant promise in rectifying the reliability
issues commonly associated with renewable energy power generation. Therefore, it is recommended
that this system be considered for implementation in rural electrification initiatives. Furthermore, it is
worth noting that this system represents one of the most recent developments in the field of renewable
energy power generation technology.
Factors Affecting the Micropropagation of Sapindus trifoliatus from Nodal Explants of Mature Tree
Authors: Asthana Pooja , Rai Manoj K. , Jaiswal Uma 
Published: January 2024

Background::
Explant recalcitrance is one of the major challenges during the tissue culture of a tree species, especially when explants are derived from mature plants. It is mainly as-sociated with the genotypes/species, source and physiological status of explants, seasonal variations, and competency/incompetency of explants towards PGRs for in vitro manipulations. There-fore, to optimize the appropriate conditions and minimize explant recalcitrance, it is necessary to elucidate the different factors influencing the tissue culture of a tree species.

Objective::
Several factors influencing in vitro shoot induction from nodal explants derived from mature plants of Sapindus trifoliatus were investigated.

Methods::
Nodal segment obtained from mature plants was used as an explant for shoot regeneration. The factors assessed in this study included the types and concentrations of plant growth regulators, nutrient composition of MS (Murashige and Skoog) medium, sucrose concentrations, the position of nodes on their respective branches, seasonal variations, and successive transfers of mother explant.

Results::
The performance of nodal explants was better on modified MS medium, i.e., M4 medium (half-strength of MS major salts and full-strengths of MS minor salts, Fe-EDTA and MS organic nutrients each) than the full-strength MS medium. The addition of BAP in the medium resulted in a higher shoot induction rate than other cytokinins i.e., Kin, Zeatin, TDZ. M4 medium supplemented with 3.0 mg l-1 BAP and 2% sucrose was optimum for shoot proliferation. However, elongation of shoots was observed only when induced shoots, along with the mother explant, were subcultured on a medium containing 1.0 mg l-1 BAP. The shoot multiplication was positively affected by the repeated transfer of the mother explant for different passages on the multiplica-tion medium. Mother explant transferred to multiplication medium (0.8% agar-solidified M4 medium + 2% sucrose + 1.0 mg l-1 BAP) proliferated maximum shoots after fourth passages. Regenerated shoots were rooted in vitro and further successfully acclimatized in field conditions.

Conclusion::
The in vitro regeneration system developed from an explant obtained from mature trees can be successfully exploited for mass multiplication of Sapindus trifoliatus, a medicinally and commercially important tree.