bluuebunny/crossref_metadata_2025 huggingface dataset:
N,N'-disubstituted Ureas as Novel Antiplatelet Agents: Synthesis, Pharmacological Evaluation and In Silico Studies
Authors: de Souza Furtado Priscila , Viana Gil Mendes , de Oliveira Alana Agnes Silva Camargo , Rabelo Vitor Won-Held , Cerqueira Ingryd Wenderroschy , Paschoal Caroline Reis Santiago , da Silva Honorio Thiago , Simon Alice , Rodrigues Carlos Rangel , Abreu Paula Alvarez , Cabral Lucio Mendes , Sathler Plínio Cunha
Published: February 2024

Introduction:

Thrombotic disorders are among the leading causes of morbidity and
mortality worldwide. Drugs used in the prevention and treatment of atherothrombosis have pharmacokinetic
limitations and adverse effects such as hemorrhagic conditions, highlighting the importance
of developing more effective antiplatelet agents.

Methods:

In this work, we synthesized N,N'-disubstituted ureas 3a-3j and evaluated their antiplatelet
profiles through in vitro, ex vivo, and in silico studies.

Results:

The synthesized derivatives exhibited a selective inhibitory profile against platelet aggregation
induced by arachidonic acid (AA) in vitro, without significantly affecting other aspects of
primary hemostasis and blood coagulation. The compounds that showed inhibition greater than
85% were submitted to the analysis of their potency by calculating the concentration required to inhibit
50% of platelet aggregation induced by AA (IC50). Urea derivative 3a was the most potent
with IC50 of 1.45 μM. Interestingly, this derivative inhibited more than 90% of platelet aggregation
induced by AA ex vivo, with a similar effect to acetylsalicylic acid. In the hemolysis assay,
most of the urea derivatives presented values below 10% suggesting good hemocompatibility. Additionally,
the compounds tested at 100 μM also showed no cytotoxic effects in HepG2 and Vero
cells. The in silico results suggested that compound 3a may bind to the key residue of COX-1 similar
to AA and known COX-1 inhibitors, and the results are also in agreement with our SAR,
which suggests that the inhibition of this enzyme is the most likely mechanism of antiplatelet activity.

Conclusion:

Therefore, these results demonstrated that N,N'-disubstituted ureas are promising candidates
for the development of novel antiplatelet agents.
Human Umbilical Cord Mesenchymal Stem Cell Exosome-derived
miR-335-5p Alleviated Lipopolysaccharide-induced Acute Lung
Injury by Regulating the m6A Level of ITGβ4 Gene
Authors: Li Linrui , Zhang Xi , Chen Yanping
Published: February 2024

Background:

Acute lung injury (ALI) is a serious complication that may accompany
severe pneumonia in children. Derived from exosomes of human umbilical
cord mesenchymal stem cell exosome (HucMSC-Exo) can contribute to the regeneration
of damaged lung tissue. This study aims to investigate the impact of HucMSC-Exo on
ALI and its potential mechanisms.

Methods:

Firstly, RT-qPCR was performed to assess the expression of miR-335-5p. Subsequently,
Pearson correlation analysis was performed to examine the correlation between
METTL14 and miR-335-5p, as well as the correlation between METTL14 and ITGB4.,
while RNA immunoprecipitation (RIP) was used to determine the m6A modification
level of ITGβ4. Additionally, molecular biology techniques were employed to evaluate
the expression of glycolysis-related factors. Definitively, an LPS-induced ALI model
was established to investigate the effect of miR-335-5p on mice lung tissue.

Results:

miR-335-5p was found to be highly expressed in HucMSC-Exo. Transfection
with miR-335-5p mimics resulted in increased glucose uptake. Pearson correlation analysis
revealed a negative correlation between METTL14 and miR-335-5p, as well as between
METTL14 and ITGβ4. The m6A level of ITGβ4 was elevated in ALI. Overexpression
of METTL14 was found to reduce the expression and glucose uptake of ITGβ4,
while overexpression of ITGβ4 reversed the effects of METTL14 overexpression. in
vivo, results demonstrated that miR-335-5p can improve the extent of lung tissue lesions
and reduce glycolytic levels.

method:

HucMSC-Exos were successfully cultured and identified. The LPS-induced ALI model was established using A549 cells and BALB/c mice. Pearson correlation coefficient analyzed the association between METTL14 and miR-335-5p or ITGβ4 in clinical specimens. The modification level of m6A was detected using RNA m6A colorimetry and RNA immunoprecipitation. The cell damage, apoptosis, expression of inflammatory factors, and glycolytic-related factors were determined molecularly and immunohistochemically in various groups.

Conclusion:

This study reveals the mechanism by which miR-335-5p derived from
HucMSC-Exo could alleviate LPS-induced ALI by regulating the m6A modification of
ITGβ4, providing a new direction for the treatment of ALI.
Rhodotorulic Acid and its Derivatives: Synthesis, Properties, and Applications
Authors: Stefaniak Joanna , Nowak Michał Grzegorz , Skwarecki Andrzej Stanisław
Published: February 2024

:

Siderophores are low molecular weight compounds produced by microorganisms
to scavenge iron in iron-deficient environments. Rhodotorulic acid, a natural hydroxamate
siderophore, plays a vital role in iron acquisition for fungi and bacteria. As
the simplest natural hydroxamate siderophore, it exhibits a high affinity for ferric ions,
enabling it to form stable complexes that facilitate iron uptake and transport within microorganisms.
This article provides a comprehensive analysis of this hydroxamate
siderophore, rhodotorulic acid, its synthesis, physicochemical properties, and biological
significance. It also explores its applications in antifungal and plant protection strategies.
Insights into RA derivatives reveal distinct biological effects and applications with
potential in various fields, from antioxidants to antifungals. Rhodotorulic acid and its
derivatives show promise for novel therapies, plant protection strategies, and iron supplementation
in agriculture. Understanding their properties could advance science and
medicine with sustainable practices.
Role of Ferroptosis in the Progression of COVID-19 and the Development
of Long COVID
Authors: Zhao Wen , Wang Siyuan , Han Yuxin , Zhang Hongkun , Cao Jiacen , Dong Shasha , Li Dongdong , Lei Miao , Liu Chuanmiao , Gao Yu
Published: February 2024

Objective::

This study aimed to examine the role of ferroptosis on the pathogenesis
and progression of COVID-19.

background:

-

Materials and Methods:

A total of 127 patients who were hospitalized for COVID-19
were categorized into two groups according to the intensity of oxygen therapy (highflow
or low-flow). Clinical characteristics, laboratory parameters, plasma markers, and
peripheral blood mononuclear cell (PBMC) markers were measured at baseline and one
or two weeks after treatment. Telephone follow-up was performed 3 months after
discharge to assess long COVID.

Results::

Patients receiving high-flow oxygen therapy had greater levels of neutrophils,
D-dimer, C reactive protein, procalcitonin, plasma protein levels of tumor necrosis factor-
alpha (TNF-α), interleukin 6 (IL-6), IL-17, acyl-CoA synthetase long-chain family
member 4 (ACSL4), and PBMC mRNA level of TNF-α but had lower levels of lymphocytes
and plasma glutathione peroxidase 4 (GPX4). There were negative correlations of
plasma GPX4 and cystine/glutamate transporter-11 (SLC7A11) with TNF-α, IL-6, and
IL-17 and positive correlations of ACSL4 with inflammatory markers in plasma and
PBMCs. The plasma levels of TNF-α, IL-6, IL-17, and ACSL4 were significantly lower
after treatment than at baseline, but there were higher post-treatment levels of lymphocytes,
GPX4, and SLC7A11. Patients with long COVID had a lower baseline level of
plasma SLC7A11.

Conclusion::

Ferroptosis is activated during the progression of COVID-19, and a low
baseline level of a ferroptosis marker (SLC7A11) may indicate an increased risk for
long COVID-19. Ferroptosis has potential as a clinical indicator of long COVID and as
a therapeutic target.
Polyphenols as Potential Antioxidants for the Treatment of Intervertebral Disc Degeneration
Authors: Li Xiao-Long , Yu Xiao-Yu , Tao Yu-Ao , Xu Yu-Zhu , Li Xi , Wang Jia-Dong , Zhang Le-Le , Wang Yun-Tao , Fan Pan
Published: February 2024

Intervertebral disc degeneration (IDD) is a common musculoskeletal system
disease, which is one of the most important causes of low back pain. Despite the high
prevalence of IDD, current treatments are limited to relieving symptoms, and there are
no effective therapeutic agents that can block or reverse the progression of IDD. Oxidative
stress, the result of an imbalance between the production of reactive oxygen species
(ROS) and clearance by the antioxidant defense system, plays an important role in the
progression of IDD. Polyphenols are antioxidant compounds that can inhibit ROS production,
which can scavenge free radicals, reduce hydrogen peroxide production, and inhibit
lipid oxidation in nucleus pulposus (NP) cells and IDD animal models. In this review,
we discussed the antioxidant effects of polyphenols and their regulatory role in different
molecular pathways associated with the pathogenesis of IDD, as well as the limitations
and future prospects of polyphenols as a potential treatment of IDD.
Targeting NLRP3 Inflammasome: Structure, Function, and Inhibitors
Authors: Lou Shengying , Wu Miaolian , Cui Sunliang
Published: February 2024

Inflammasomes are multimeric protein complexes that can detect various physiological
stimuli and danger signals. As a result, they perform a crucial function in the innate
immune response. The NLRP3 inflammasome, as a vital constituent of the inflammasome
family, is significant in defending against pathogen invasion and preserving cellhomeostasis.
NLRP3 inflammasome dysregulation is connected to various pathological
conditions, including inflammatory diseases, cancer, and cardiovascular and neurodegenerative
diseases. This profile makes NLRP3 an applicable target for treating related diseases,
and therefore, there are rising NLRP3 inhibitors disclosed for therapy. Herein, we
summarized the updated advances in the structure, function, and inhibitors of NLRP3 inflammasome.
Moreover, we aimed to provide an overview of the existing products and future
directions for drug research and development.
Network Pharmacology and In vitro Experimental Verification to Explore the
Mechanism of Chaiqin Qingning Capsule in the Treatment of Pain
Authors: Gao Hongjin , Chen Zhengwei , Halihaman Buliduhong , Huang Lianzhan , Wang Zhen , Ding Xuansheng
Published: February 2024

Background:

Chaiqin Qingning capsule (CQQNC) has been used to relieve pain in practice.
However, the active components, pain targets, and molecular mechanisms for pain control are unclear.

Objective:

To explore the active components and potential mechanisms of the analgesic effect of CQQNC
through network pharmacology and in vitro experiments.

Methods:

The main active components and the corresponding targets of CQQNC were screened from the
TCMSP and the SwissTargetPrediction databases. Pain-related targets were selected in the OMIM, Gene-
Cards, and DrugBank databases. These targets were intersected to obtain potential analgesic targets. The analgesic
targets were imported into the STRING and DAVID databases for protein-protein interaction (PPI),
gene ontology (GO) function enrichment and Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway
enrichment analyses. Cytoscape software (V3.7.1) was used to construct an active component-intersection
network. Finally, the key components were docked with the core targets. The analgesic mechanism of
CQQNC was verified by RAW264.7 cell experiment.

Results:

30 active CQQNC components, 617 corresponding targets, and 3,214 pain-related target genes were
found. The main active components were quercetin, kaempferol, and chenodeoxycholic acid etc. The key targets
were ALB, AKT1, TNF, IL6, TP53, IL1B, and SRC. CQQNC can exert an analgesic effect through
PI3K-Akt, MAPK signaling pathways, etc. Molecular docking showed that these active components had good
binding activities with key targets. The results of in vitro experiments showed that CQQNC could exert antiinflammatory
and analgesic effects through MAPK/AKT/NF-kB signaling pathways.

Conclusion:

CQQNC exerts pain control through inhibiting MAPK/AKT/NF-kB signaling pathways.
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

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.
Direct Bilirubin, but not Indirect Bilirubin, is Associated with Short-term
Adverse Events in HFpEF
Authors: Wang Sunying , Chen Yan , Ma Hanghao , Wang Yuwei , Luo Manqing , Xie Xianwei , Yang Qingyong , Lin Kaijin , Lin Meihua , Lin Lin , Chen Ping , Zheng Qiaowen , Sun Fuqing
Published: February 2024

Objective:

Abnormal live function tests have been identified as independent risk factors
for ominous prognosis in patients with heart failure. However, most of the previous studies have
failed to determine the contribution of direct bilirubin (DBIL) and indirect bilirubin (IBIL) separately.
Hence, we aimed to explore whether DBIL or IBIL is correlated with the prognosis of heart failure
with preserved ejection fraction (HFpEF).

Methods:

A total of 19837 patients were hospitalized for HFpEF between January 2012 and January
2022 in Fuqing City Hospital affiliated with Fujian Medical University. The primary endpoint
was in-hospital all-cause mortality. Secondary endpoints included in-hospital cardiovascular mortality
and 30-day re-admission for heart failure.

Results:

Univariable analysis indicated that patients with elevated DBIL or IBIL were exposed to a
higher risk of mortality and re-admission. However, in multivariable models, both ln-transformed
DBIL and TBIL, but not IBIL, were independent risk factors for in-hospital all-cause mortality
[hazard ratio (HR)=1.796, 95% confidential interval (CI)=1.477-2.183, P＜0.001; HR=1.854, 95%
CI=1.461-2.352, P＜0.001; HR=1.161, 95% CI=0.959-1.407, P=0.126] and in-hospital cardiovascular
mortality (HR=1.831, 95% CI=1.345-2.492, P＜0.001; HR=1.899, 95% CI=1.300-2.773,
P=0.001; HR=1.145, 95% CI=0.841-1.561, P=0.389). Only DBIL remained independently associated
with 30-day readmission for heart failure (HR=1.361, 95% CI=1.036-1.787, P=0.027). Adding
ln-transformed DBIL to model 1 increased its discriminatory capacity (C-statistic: 0.851 to 0.869,
respectively), whereas adding ln-transformed IBIL yielded little increment (C-statistic: 0.851 to
0.852, respectively).

Conclusion:

DBIL, but not IBIL, was associated with short-term ominous prognosis in patients
with HFpEF. Hence, DBIL may be the superior predictor for prognosis in HFpEF.
CRISPR-Based Therapies: Revolutionizing Drug Development and
Precision Medicine
Authors: Chanchal Dilip Kumar , Chaudhary Jitendra Singh , Kumar Pushpendra , Agnihotri Neha , Porwal Prateek
Published: February 2024

With the discovery of CRISPR-Cas9, drug development and precision medicine have
undergone a major change. This review article looks at the new ways that CRISPR-based therapies
are being used and how they are changing the way medicine is done. CRISPR technology's
ability to precisely and flexibly edit genes has opened up new ways to find, validate, and develop
drug targets. Also, it has made way for personalized gene therapies, precise gene editing, and advanced
screening techniques, all of which hold great promise for treating a wide range of diseases.
In this article, we look at the latest research and clinical trials that show how CRISPR could be
used to treat genetic diseases, cancer, infectious diseases, and other hard-to-treat conditions. However,
ethical issues and problems with regulations are also discussed in relation to CRISPR-based
therapies, which shows how important it is to use them safely and responsibly. As CRISPR continues
to change how drugs are made and used, this review shines a light on the amazing things that
have been done and what the future might hold in this rapidly changing field.
Potential Therapeutic Approach using Aromatic l-amino Acid
Decarboxylase and Glial-derived Neurotrophic Factor Therapy Targeting
Putamen in Parkinson's Disease
Authors: Tripathi Raman Kumar , Goyal Lav , Singh Shamsher
Published: February 2024

Parkinson's disease (PD) is a neurodegenerative illness characterized by specific loss of
dopaminergic neurons, resulting in impaired motor movement. Its prevalence is twice as compared
to the previous 25 years and affects more than 10 million individuals. Lack of treatment still
uses levodopa and other options as disease management measures. Treatment shifts to gene therapy
(GT), which utilizes direct delivery of specific genes at the targeted area. Therefore, the use of
aromatic L-amino acid decarboxylase (AADC) and glial-derived neurotrophic factor (GDNF) therapy
achieves an effective control to treat PD. Patients diagnosed with PD may experience improved
therapeutic outcomes by reducing the frequency of drug administration while utilizing provasin
and AADC as dopaminergic protective therapy. Enhancing the enzymatic activity of tyrosine
hydroxylase (TH), glucocorticoid hormone (GCH), and AADC in the striatum would be useful
for external L-DOPA to restore the dopamine (DA) level. Increased expression of glutamic
acid decarboxylase (GAD) in the subthalamic nucleus (STN) may also be beneficial in PD. Targeting
GDNF therapy specifically to the putaminal region is clinically sound and beneficial in protecting
the dopaminergic neurons. Furthermore, preclinical and clinical studies supported the role of
GDNF in exhibiting its neuroprotective effect in neurological disorders. Another Ret receptor,
which belongs to the tyrosine kinase family, is expressed in dopaminergic neurons and sounds to
play a vital role in inhibiting the advancement of PD. GDNF binding on those receptors results in
the formation of a receptor-ligand complex. On the other hand, venous delivery of recombinant
GDNF by liposome-based and encapsulated cellular approaches enables the secure and effective
distribution of neurotrophic factors into the putamen and parenchyma. The current review emphasized
the rate of GT target GDNF and AADC therapy, along with the corresponding empirical evidence.
Role of MicroRNA in Hypoxic Tumours and their Potential as
Biomarkers for Early Detection of Cancer
Authors: Jayashree Pawar , Kalpita Mulye , Judith Talker , Singh Ahirwar Sonu , Ashwin Kotnis
Published: February 2024

Hypoxia is a pathophysiological condition characterized by oxygen
deficiency in tissues, which negatively affects normal biological functions. It is a typical
microenvironment character of almost all solid tumours. Noncoding RNA are small
functional RNA molecules that regulate gene expression at chromatin and posttranscriptional
levels. Micro-RNAs (miRNAs) are a type of noncoding RNA and are
~12-22 nucleotides long that are crucial in regulating gene expression by partnering
with the mRNAs of protein-coding genes. It is widely reported that miRs play an
important role in various key processes and pathways during tumour formation, as well
as advancement in hypoxic tumors by influencing the HIF pathway. The role of
miRNAs in hypoxic tumours, namely in pancreatic, kidney, breast, lung and colorectal,
are described. These miRNAs have immense potential as diagnostic and prognostic
biomarkers for early cancer detection.
Pharmacological Activation of AMPK Prevents Drp1-mediated Mitochondrial Fission and Alleviates Hepatic Steatosis In vitro
Authors: Du Jingxia , Wang Tingting , Xiao Chengyao , Dong Yibo , Zhou Shiyao , Zhu Yujiao
Published: February 2024

Background:

The incidence of non-alcoholic fatty liver disease (NAFLD) is
increasing worldwide. Adenosine monophosphate-activated protein kinase (AMPK)
activation is beneficial for NAFLD treatment. Recent studies show the excessive
fission of mitochondria during NAFLD progression, so targeting mitochondria dynamics
may be a possible target for NAFLD. Still, little is known about whether AMPK
regulates mitochondrial dynamics in hepar.

Objective:

This study investigated whether AMPK activation alleviates hepatic
steatosis by regulating mitochondrial dynamics mediated by GTPase dynamin-related
protein 1 (Drp1).

Methods:

Human hepatocyte line L-02 cells were cultured and subjected to palmitic
acid (PA) treatment for 24 h to establish a hepatic steatosis model in vitro, which was
pre-treated with different tool drugs. Hepatocyte function, hepatocyte lipid content,
mitochondrial reactive oxygen species (ROS) production, and mitochondrial
membrane potential (MMP) were examined. The expression levels of genes and
proteins associated with mitochondrial dynamics were assessed using reverse
transcription-quantitative PCR and western blotting.

Results:

The results indicated that 5-Aminoimidazole-4-carboxamide 1-β-D-ribofuranoside
(AICAR), an AMPK activator, improved hepatocyte function, as demonstrated
by decreased alanine aminotransferase (ALT) and aspartate aminotransferase (AST)
activity (P＜0.05 or P＜0.01). In addition, AICAR decreased total cholesterol (TC) and
triglyceride (TG) content and lipid deposition in hepatocytes (P＜0.01); decreased
ROS production; improved MMP (P＜0.01); reduced fission-1 (Fis1) and mitochondrial
fission factor (Mff) mRNA expression; and downregulated p-Drp1 (Ser 616) protein
expression. In contrast, AICAR increased mitochondrial fusion factor mitofusin-1
(Mfn1) and mitofusin-2 (Mfn2) mRNA expression and upregulated p-Drp1 (Ser 637)
protein expression. Mdivi-1, a Drp-1 inhibitor, was used to confirm whether
mitochondrial dynamics regulated by Drp1-mediated the role of AICAR. Similar to
AICAR, Mdivi-1 improved hepatocyte function and MMP significantly, decreased ROS
production and lipid deposition, downregulated Fis1 and Mff mRNA expression,
downregulated p-Drp1 (Ser 616) protein expression, and enhanced Mfn1 and Mfn2
mRNA and p-Drp1 (Ser 637) protein expression. However, Compound C, an AMPKspecific
inhibitor, had less impact on the protective effect of Mdivi-1.

Conclusion:

The results demonstrated that AMPK activation has a protective effect on
hepatic steatosis in vitro, largely dependent on the inhibition of Drp1-mediated
mitochondrial fission.
LKB1 Mutations Enhance Radiosensitivity in Non-Small Cell Lung Cancer Cells by Inducing G2/M Cell Cycle Phase Arrest
Authors: Yao Yuanhu , Qiu Xiangnan , Chen Meng , Qin Zhaohui , Zhang Xinjun , Zhang Wei
Published: February 2024

Background:

Radiosensitivity remains an important factor affecting the
clinical outcome of radiotherapy for non-small cell lung cancer (NSCLC). Liver kinase
B1 (LKB1) as a tumor suppressor, is one of the most commonly mutated genes in
NSCLC. However, the role of LKB1 on radiosensitivity and the possible mechanism
have not been elucidated in the NSCLC. In this study, we investigated the regulatory
function of LKB1 in the radiosensitivity of NSCLC cells and its possible signaling
pathways.

Methods:

After regulating the expression of LKB1, cell proliferation was determined by
Cell Counting Kit-8 (CCK-8) assay. The flow cytometry assay was used to analyse cell
cycle distribution. Survival fraction and sensitization enhancement ratio (SER) were
generated by clonogenic survival assay. Western blot analysis was used to assess
expression levels of LKB1, p53, p21, γ-H2AX and p-Chk2.

Results:

Our study found that when the NSCLC cells were exposed to ionizing
radiation, LKB1 could inhibit NSCLC cell proliferation by promoting DNA double strand
break and inducing DNA repair. In addition, LKB1 could induce NSCLC cells G1 and
G2/M phase arrest through up-regulating expression of p53 and p21 proteins.

Conclusion:

This current study demonstrates that LKB1 enhances the radiosensitivity
of NSCLC cells via inhibiting NSCLC cell proliferation and inducing G2/M phase arrest,
and the mechanism of cell cycle arrest associated with signaling pathways of p53 and
p21 probably.