bluuebunny/crossref_metadata_2025_split huggingface dataset:
A Strategy based on Bioinformatics and Machine Learning Algorithms Reveals
Potential Mechanisms of Shelian Capsule against Hepatocellular Carcinoma
Authors: Zhou Xianqiang , Tan Fang , Zhang Suxian , Wang An'an , Zhang Tiansong 
Published: February 2024

Background:
Hepatocellular carcinoma (HCC) is a prevalent and life-threatening form of cancer,
with Shelian Capsule (SLC), a traditional Chinese medicine (TCM) formulation, being recommended for clinical
treatment. However, the mechanisms underlying its efficacy remain elusive. This study sought to uncover
the potential mechanisms of SLC in HCC treatment using bioinformatics methods.

Methods:
Bioactive components of SLC were obtained from the Traditional Chinese Medicine Systems
Pharmacology Database and Analysis Platform (TCMSP), and HCC-related microarray chip data were
sourced from the Gene Expression Omnibus (GEO) database. The selection criteria for components included
OB ≧ 30% and DL ≧ 0.18. By integrating the results of differential expression analysis and weighted gene
co-expression network analysis (WGCNA), disease-related genes were identified. Therapeutic targets were
determined as shared items between candidate targets and disease genes. Protein-protein interaction (PPI)
network analysis was conducted for concatenated genes, with core protein clusters identified using the
MCODE plugin. Machine learning algorithms were applied to identify signature genes within therapeutic targets.
Subsequently, immune cell infiltration analysis, single-cell RNA sequencing (sc-RNA seq) analysis, molecular
docking, and ADME analysis were performed for the screened genes.

Result:
A total of 153 SLC ingredients and 170 candidate targets were identified, along with 494 HCCrelated
disease genes. Overlapping items between disease genes and drug candidates represented therapeutic
genes, and PPI network analysis was conducted using concatenated genes. MCODE1 and MCODE2 cluster
genes underwent Disease Ontology (DO), Gene Ontology (GO), and Kyoto Encyclopedia of Genes and Genomes
(KEGG) enrichment analyses. Four signature genes (TOP2A, CYP1A2, CYP2B6, and IGFBP3) were
identified from 28 therapeutic genes using 3 machine learning algorithms, with ROC curves plotted. Molecular
docking validated the interaction modes and binding abilities between signature genes and corresponding
compounds, with free binding energy all <-7 kcal/mol. Finally, ADME analysis revealed similarities between
certain SLC components and the clinical drugs Sorafenib and Lenvatinib.

Conclusion:
In summary, our study revealed that the mechanism underlying the anti-HCC effects of SLC involves
interactions at three levels: components (quercetin, beta-sitosterol, kaempferol, baicalein, stigmasterol,
and luteolin), pathways (PI3K-Akt signaling pathway, TNF signaling pathway, and IL-17 signaling pathway),
and targets (TOP2A, CYP1A2, CYP2B6, and IGFBP3). This study provides preliminary insights into the potential
pharmacological mechanisms of SLC in HCC treatment, aiming to support its clinical application and
serve as a reference for future laboratory investigations.
An Update to Novel Therapeutic Options for Combating Tuberculosis:
Challenges and Future Prospectives
Authors: Suresh Swathi , Fatma Begum Rukaiah , S. Ankul Singh , Vellapandian Chitra 
Published: February 2024

:
Drug repurposing is an ongoing and clever strategy that is being developed to eradicate
tuberculosis amid challenges, of which one of the major challenges is the resistance developed
towards antibiotics used in standard directly observed treatment, short-course regimen.
Surpassing the challenges in developing anti-tuberculous drugs, some novel host-directed therapies,
repurposed drugs, and drugs with novel targets are being studied, and few are being approved
too. After almost 4 decades since the approval of rifampicin as a potent drug for drugsusceptible
tuberculosis, the first drug to be approved for drug-resistant tuberculosis is bedaquiline.
Ever since the urge to drug discovery has been at a brisk as this milestone in tuberculosis
treatment has provoked the hunt for novel targets in tuberculosis. Host-directed therapy and repurposed
drugs are in trend as their pharmacological and toxicological properties have already
been researched for some other diseases making the trial facile. This review discusses the remonstrance
faced by researchers in developing a drug candidate with a novel target, the furtherance
in tuberculosis research, novel anti-tuberculosis agents approved so far, and candidates on
trial including the host-directed therapy, repurposed drug and drug combinations that may prove
to be potential in treating tuberculosis soon, aiming to augment the awareness in this context to
the imminent researchers.
Role of Nutraceuticals in Treating Erectile Dysfunction via Inhibition of
Phosphodiesterase-5 Enzyme: A Mini Review
Authors: Kulshrestha Rashi , Singla Neelam , Afzal Obaid , Goyal Ahsas , Saini Mahendra , Altamimi Abdulmalik Saleh Alfawaz , Almalki Waleed Hassan , Kazmi Imran , Al-Abbasi Fahad , Alzarea Sami I. , Gupta Gaurav 
Published: February 2024

:
Erectile Dysfunction (ED) is a prevalent sexual health condition affecting a significant
portion of the male population worldwide. The conventional therapeutic approaches for ED often
involve the use of pharmaceutical agents targeting the phosphodiesterase-5 (PDE5) enzyme.
Currently, treatment with PDE-5 inhibitors is the standard approach for ED, and four PDE-5
inhibitors, namely sildenafil, vardenafil, tadalafil, and avanafil, are in use. However, these pharmaceutical
interventions may be associated with adverse effects and limitations. As a result,
there has been a growing interest in exploring alternative and complementary treatment options
for ED, such as nutraceuticals, which are bioactive compounds derived from natural sources.
Nutraceuticals, which include vitamins, minerals, herbs, and other dietary supplements, have
gained popularity for their potential health benefits. Certain nutraceuticals have demonstrated the
ability to modulate various physiological pathways, including those involved in erectile function.
A notable mechanism of action is the inhibition of the PDE5 enzyme, which plays a pivotal role
in the regulation of cGMP levels. By inhibiting PDE5, nutraceuticals can promote the accumulation
of cGMP, leading to enhanced penile blood flow and improved erectile function. A comprehensive
analysis of the literature showcases various nutraceutical agents, including plant-derived
compounds like flavonoids, polyphenols, and amino acids which have exhibited PDE5 inhibitory
effects. Mechanistic insights into their action involve modulation of NO release, cGMP elevation,
and relaxation of penile smooth muscles, all critical factors for achieving and sustaining
erections. This review focuses on elucidating the role of nutraceuticals in treating erectile dysfunction
through the inhibition of the PDE5 enzyme.
Single Nucleotide Polymorphisms (SNPs) in the Shadows: Uncovering
their Function in Non-Coding Region of Esophageal Cancer
Authors: Saikia Surovi , Postwala Humzah , Athilingam Vishnu Prabhu , Anandan Aparna , Padma V. Vijaya , Kalita Partha P. , Chorawala Mehul , Prajapati Bhupendra 
Published: February 2024

:
Esophageal cancer is a complex disease influenced by genetic and environmental
factors. Single nucleotide polymorphisms [SNPs] in non-coding regions of the genome have
emerged as crucial contributors to esophageal cancer susceptibility. This review provides a
comprehensive overview of the role of SNPs in non-coding regions and their association with
esophageal cancer. The accumulation of SNPs in the genome has been implicated in esophageal
cancer risk. Various studies have identified specific locations in the genome where SNPs are
more likely to occur, suggesting a location-specific response. Chromatin conformational studies
have shed light on the localization of SNPs and their impact on gene transcription, posttranscriptional
modifications, gene expression regulation, and histone modification. Furthermore,
miRNA-related SNPs have been found to play a significant role in esophageal squamous
cell carcinoma [ESCC]. These SNPs can affect miRNA binding sites, thereby altering target
gene regulation and contributing to ESCC development. Additionally, the risk of ESCC has
been linked to base excision repair, suggesting that SNPs in this pathway may influence disease
susceptibility. Somatic DNA segment alterations and modified expression quantitative trait loci
[eQTL] have also been associated with ESCC. These alterations can lead to disrupted gene expression
and cellular processes, ultimately contributing to cancer development and progression.
Moreover, SNPs have been found to be associated with the long non-coding RNA HOTAIR,
which plays a crucial role in ESCC pathogenesis. This review concludes with a discussion of the
current and future perspectives in the field of SNPs in non-coding regions and their relevance to
esophageal cancer. Understanding the functional implications of these SNPs may lead to the
identification of novel therapeutic targets and the development of personalized approaches for
esophageal cancer prevention and treatment.
Harnessing Chimeric Antigen Receptor-engineered Invariant Natural
Killer T Cells: Therapeutic Strategies for Cancer and the Tumor
Microenvironment
Authors: Wang Yiqing , Li Yan-Ruide 
Published: February 2024

:
Chimeric antigen receptor (CAR)-engineered T (CAR-T) cell therapy has emerged as
a revolutionary approach for cancer treatment, especially for hematologic cancers. However,
CAR-T therapy has some limitations, including cytokine release syndrome (CRS), immune cellassociated
neurologic syndrome (ICANS), and difficulty in targeting solid tumors and delivering
allogeneic cell therapy due to graft-versus-host disease (GvHD). Therefore, it is important to
explore other cell sources for CAR engineering. Invariant natural killer T (iNKT) cells are a
potential target, as they possess powerful antitumor ability and do not recognize mismatched
major histocompatibility complexes (MHCs) and protein antigens, thus avoiding the risk of
GvHD. CAR-engineered iNKT (CAR-iNKT) cell therapy offers a promising new approach to
cancer immunotherapy by overcoming the drawbacks of CAR-T cell therapy while retaining
potent antitumor capabilities. This review summarizes the current CAR-iNKT cell products,
their functions and phenotypes, and their potential for off-the-shelf cancer immunotherapy.
Iron(III) Monoglycerolate as a New Biocompatible Precursor in the
Synthesis of Bioactive Nanocomposite Glycerohydrogels
Authors: Khonina Tat’yana Grigor’evna , Tishin Denis Sergeevich , Larionov Leonid Petrovich , Osipenko Artur Vasil’evich , Dobrinskaya Maria Nikolaevna , Bogdanova Ekaterina Anatol’evna , Karabanalov Maxim Sergeevich , Bulatova Maria Alekseevna , Shadrina Elena Vladimirovna , Chupakhin Oleg Nikolaevich 
Published: February 2024

Background:
Nanocomposite glycerohydrogels based on biocompatible elementcontaining
glycerolates are of practicular interest for biomedical applications.

Objective:
Using two biocompatible precursors, silicon and iron glycerolates, a new bioactive
nanocomposite silicon‒iron glycerolates hydrogel was obtained by sol-gel method.

Methods:
The composition and structural features of the hydrogel were studied using a complex
of modern analytical techniques, including TEM, XRD, and AES. On the example of experimental
animals hemostatic activity of the hydrogel was studied, as well as primary toxicological
studies were carried out.

Results:
The composition of dispersed phase and dispersion medium of silicon‒iron glycerolates
hydrogel was determined. The structural features of hydrogel were revealed and its structure
model was proposed. It was shown that silcon-iron glycerolates hydrogel is nontoxic, and exhibits
pronounced hemostatic activity.

Conclusion:
Silicon-iron glycerolates hydrogel is a potential hemostatic agent for topical application
in medical and veterinary practice.
Deciphering Immune-related Gene Signatures in Diabetic Retinopathy:
Insights from In silico Analysis and In vitro Experiment
Authors: Xia Nan , Zhao Qingsong , Xu Jinmei , Cheng Zhifeng 
Published: February 2024

Background:
Diabetes retinopathy (DR) is one of the most common microvascular
consequences of diabetes, and the economic burden is increasing. Our aim is to decipher the
relevant mechanisms of immune-related gene features in DR and explore biomarkers targeting
DR. Provide a basis for the treatment and prevention of DR.

Methods:
The immune infiltration enrichment score of DR patients was evaluated from the single-
cell RNA sequencing dataset, and the samples were divided into low immune subgroups and
high immune subgroups based on this result. Through weighted gene correlation network analysis,
differentially expressed genes (DEGs) between two subgroups were identified and crossed
with genes with the strongest immune association, resulting in significant key genes. Then divide
the DR individuals into two immune related differentially expressed gene (IDEG) clusters, A and
B. Submit cross DEGs between two clusters through Gene Set Enrichment Analysis (GSEA) to
further explore their functions. A protein-protein interaction (PPI) network of IDEG was established
to further identify central genes associated with DR. Use the discovered central genes to
predict the regulatory network involved in the pathogenesis of DR. Then, the role of the identified
hub gene in the pathogenesis of DR was further studied through in vitro experiments.

Results:
We found that the immune scores of DR and control groups were different, and 27
IDEGs were found in the DR subgroup. Compared with cluster A, the proportion of cytotoxic
lymphocytes, B lineage, monocyte lineage, and fibroblasts in DR patients in cluster B is significantly
enriched. GSEA indicates that these genes are associated with T cell activation, regulation
of immune response processes, lymphocyte-mediated immunity, TNF signaling pathway, and
other signaling pathways. The PPI network subsequently identified 10 hub genes in DR, including
SIGLEC10, RGS10, PENK, FGD2, LILRA6, CIITA, EGR2, SIGLEC7, LILRB1, and
CD300LB. The upstream regulatory network and lncRNA miRNA mRNA ceRNA network of
these hub genes were ultimately constructed. The discovery and identification of these genes will
provide biomarkers for targeted prediction and treatment of DR.

Conclusion:
By integrating bioinformatics analysis and in vitro experiments, we have identified
a set of central genes, indicating that these genes can serve as potential biomarkers for DR,
which may be promising targets for future DR immunotherapy interventions.
Effects and Mechanisms of Fisetin against Ischemia-reperfusion Injuries:
A Systematic Review
Authors: Adeli Omid-Ali , Heidari-Soureshjani Saeid , Rostamian Sahar , Azadegan-Dehkordi Zahra , Khaghani Armin 
Published: February 2024

Background:
Ischemia-reperfusion injury (IRI) is a well-known ailment that can disturb
organ function.

Objectives:
This systematic review study investigated fisetin's effects and possible mechanisms
in attenuating myocardial, cerebral, renal, and hepatic IRIs.

Methods:
This systematic review included studies earlier than Sep 2023 by following the
PRISMA statement 2020. After determining inclusion and exclusion criteria and related keywords,
bibliographic databases, such as Cochrane Library, PubMed, Web of Science, Embase,
and Scopus databases, were used to search the relevant studies. Studies were imported in End-
Note X8, and the primary information was recorded in Excel.

Results:
Fisetin reduced reactive oxygen species (ROS) generation and upregulated antioxidant
enzymes, such as superoxide dismutase (SOD), glutathione (GSH), catalase (CAT), and glutathione
peroxidase (GPx), in ischemic tissues. Moreover, fisetin can attenuate oxidative stress by
activating phosphoinositide-3-kinase–protein kinase B/Akt (PI3K/Akt) and nuclear factor
erythroid 2-related factor 2 (Nrf2) signaling pathways. Fisetin has been indicated to prevent the
activation of several pro-inflammatory signaling pathways, including NF-κB (Nuclear factor
kappa-light-chain-enhancer of activated B cells) and MAPKs (Mitogen-activated protein kinases).
It also inhibits the production of pro-inflammatory cytokines and enzymes like tumor necrosis
factor-a (TNF-α), inducible-NO synthase (iNOS), cyclooxygenase-2 (COX-2), prostaglandin
E2 (PGE2), interleukin-1β (IL-1β), IL-1, and IL-6. Fisetin attenuates IRI by improving mitochondrial
function, anti-apoptotic effects, promoting autophagy, and preserving tissues from
histological changes induced by IRIs.

Conclusion:
Fisetin, by antioxidant, anti-inflammatory, mitochondrial protection, promoting
autophagy, and anti-apoptotic properties, can reduce cell injury due to myocardial, cerebral renal,
and hepatic IRIs without any significant side effects.
Recent Insight into Herbal Bioactives-based Novel Approaches for
Chronic Intestinal Inflammatory Disorders Therapy
Authors: Harwansh Ranjit K. , Chauhan Sonia , Deshmukh Rohitas , Mazumder Rupa 
Published: February 2024

:
Inflammatory bowel disease (IBD) is a life-threatening complex disease. It causes
chronic intestinal inflammation in GIT. IBD significantly affects people’s lifestyles and carries a
high risk of colon cancer. IBD involves the rectum, ileum, and colon, with clinical manifestations
of bloody stools, weight loss, diarrhea, and abdominal pain. The prevalence of inflammatory
disease is increasing dramatically worldwide. Over 16 million people are affected annually in
India, with an economic burden of $6.8- $8.8 billion for treatment. Modern medicine can manage
IBD as immunosuppressive agents, corticosteroids, tumor necrosis factor antagonists, integrin
blockers, and amino-salicylates. However, these approaches are allied with limitations such
as limited efficacy, drug resistance, undesired side effects, and overall cost, which cannot be
ignored. Hence, the herbal bioactives derived from various plant resources can be employed in
managing IBD. Science Direct, PubMed, Google, and Scopus databases have been searched for
conclusively relevant herbal plant-based anti-inflammatory agent compositions. Studies were
screened through analysis of previously published review articles. Eminent herbal bioactives,
namely curcumin, resveratrol, ellagic acid, silybin, catechin, kaempferol, icariin, glycyrrhizin
acid, berberine, quercetin, rutin, and thymol are reported to be effective against IBD. Herbal
leads are promising treatment options for IBD; they have been shown to display antiinflammatory
and antioxidant properties by targeting enzymes and regulating the expressions of
various inflammatory mediators. Natural products have been reported to have anti-inflammatory
properties in various clinical and preclinical studies, and some are available as herbal preparations.
Herbal medicine would be promising in association with the implication of a novel drug
delivery system for managing IBD.
Essential Oils of Some Potential Medicinal Plants and their Wound
Healing Activities
Authors: Bahadur Shiv , Fatima Sana 
Published: February 2024

:
The wound has been recognised as a deep cut or tearing of the epidermis, which is
also referred to as trauma and harm to the body tissues. Healing of wounds requires a coordinated
series of cellular processes, including cell attraction, proliferation, differentiation, and angiogenesis.
These processes involve interactions between various cells, such as macrophages, endothelial
cells, keratinocytes, fibroblasts, growth hormones, and proteases. The outcome of wounds
can be fatal if not treated properly, resulting in chronic wounds, chronic pain, and even death.
Wound healing is replacing missing tissue with tissue repairs and regeneration. Some local variables
are the presence of tissue maceration, foreign objects, biofilm, hypoxia, ischemia, and
wound infection. Sustained growth factor delivery, siRNA delivery, micro-RNA targeting, and
stem cell therapy are all emerging possible therapeutic approaches for wound healing. Traditional
approaches, such as Ayurveda, Siddha, and Unani medicines, are also being used for
treatment. The therapeutic application of nanoformulations in wound infections has shown various
beneficial effects. Several herbal medicines, especially essential oils have shown potential
wound healing activities, such as lavender, tea tree, sesame, olive, etc. Various nanoparticles
and their nanoformulations have been explored in wound healing therapy. The present review
article highlights several aspects of essential oils for wound healing activity through a novel
drug delivery system. Further, some patents on wound healing through herbal medicine have
been listed.
Segmentation of Thoracic Organs through Distributed Extraction of Visual
Feature Patterns Utilizing Resio-Inception U-Net and Deep Cluster
Recognition Techniques
Authors: Saminathan Karthikeyan , Banerjee Tathagat , Rangasamy Devi Priya , Vimal Cruz Meenalosini 
Published: February 2024

Background:
Segmentation of medical images plays a key role in the correct identification
and management of different diseases. In this study, we present a new segmentation method
that meets the difficulties posed by sophisticated organ shapes in computed tomography (CT) images,
particularly targeting lung, breast, and gastric cancers

Method:
Our suggested methods, Resio-Inception U-Net and Deep Cluster Recognition
(RIUDCR), use a Residual Inception Architecture, which combines the power of residual connections
and inception blocks to achieve cutting-edge segmentation performance while reducing the
risk of overfitting.

Result:
We present mathematical equations and functions that describe the design, including the
encoding and decoding steps within the UC-Net system. Furthermore, we provide strong testing results
that show the effectiveness of our method. Through thorough testing on varied datasets, our
method regularly beats current techniques, achieving amazing precision and stability in organ task
segmentation. These results show the promise of our residual inception architecture in better medical
picture analysis.

Conclusion:
In summary, our research not only shows a state-of-the-art segment methodology but
also reinforces its usefulness through thorough testing. The inclusion of residual inception architecture
in medical picture segmentation offers good possibilities for improving the identification and
management of disease planning.
Therapeutic Potential of CRISPR/Cas in Hashimoto's Thyroiditis:
A
Comprehensive Review
Authors: Upreti Apoorva , Mukherjee Sayali 
Published: February 2024

Abstract:
Hashimoto’s thyroiditis (HT) is a commonly occurring illness of autoimmune endocrine
origin. It is usually present in the pediatric age group along with other well-known diseases,
such as type 1 insulin-dependent diabetes. The defining feature of this disease is the immune--
mediated attack on the thyroid gland resulting in the destruction of thyroid tissues and cells. Given
that HT frequently affects family members, it is well-recognized that individuals are genetically
predisposed to this disease. Patients with HT also display a significantly increased risk for several
different cancers, justifying the eminent need for the development of therapies for managing and
treating HT. Gene editing has made several advancements in the field of molecular biology and
has turned out to become a promising approach to correct several autoimmune diseases. Currently,
CRISPR/Cas, a nuclease-based editing technique, is publicized as a promising tool for curing several
genetic diseases and cancers. However, very limited research has been conducted as of now
on autoimmune disease management and cure via CRISPR/Cas technique. This review provides
an account of the potential candidate genes associated with Hashimoto’s thyroiditis, and only a
few animal and human models have been generated via the CRISPR/Cas gene editing technique.
Mouse models of autoimmune thyroiditis generated through the CRISPR/Cas gene editing technique
by targeting the candidate genes will provide us with a deeper insight into the pathophysiology
of HT and further pave the way for the immunomodulation of HT via gene editing.