bluuebunny/crossref_metadata_2025_split huggingface dataset:
Comprehensive Overview of Innovative Strategies in Preventing Renal
Ischemia-reperfusion Injury: Insights from Bibliometric and In silico Analyses
Authors: Rysmakhanov Myltykbay S. , Zare Afshin , Smagulov Aibolat S. , Abenova Nurgul A. , Mussin Nadiar M. , Sultangereyev Yerlan B. , Zhakiyev Bazylbek S. , Kuttymuratov Gani K. , Haberal Mehmet , Jafari Nazanin , Baneshi Hanieh , Bakhshalizadeh Shabnam , Mahdipour Mahdi , Rahmanifar Farhad , Tamadon Amin 
Published: April 2024

Background:
Ischemia-Reperfusion Injury (IRI) is a complex pathophysiological process with severe
consequences, including irreversible loss of renal function. Various intraoperative prevention methods
have been proposed to mitigate the harmful effects of warm ischemia and kidney reperfusion.

Aim:
This comprehensive analysis provides an overview of pharmacological agents and intraoperative methods
for preventing and treating renal IRI.

Methods:
Our analysis revealed that eplerenone exhibited the highest binding affinity to crucial targets, including
Aldehyde Dehydrogenase (AD), Estrogen Receptor (ER), Klotho protein, Mineralocorticoid Receptor
(MR), and Toll-like Receptor 4 (TLR4). This finding indicates eplerenone's potential as a potent preventive
agent against IRI, surpassing other available therapeutics like Benzodioxole, Hydrocortisone, Indoles, Nicotinamide
adenine dinucleotide, and Niacinamide. In preventing kidney IRI, our comprehensive analysis emphasizes
the significance of eplerenone due to its strong binding affinity to key targets involved in the pathogenesis
of IRI.

Results:
This finding positions eplerenone as a promising candidate for further clinical investigation and consideration
for future clinical practice.

Conclusion:
The insights provided in this analysis will assist clinicians and researchers in selecting effective
preventive approaches for renal IRI in surgical settings, potentially improving patient outcomes.
Exploring the Causal Effects of Gut Microbiota on Diabetic Nephropathy:
A Two-Sample Mendelian Randomization Study
Authors: Chen Kai , Wang Xu , Shang Zhihao , Li Qingyue , Yao Wenqiang , Guo Shaobo , Guan Yingting 
Published: April 2024

Background:
In recent years, an increasing number of studies have indicated a bidirectional relationship between gut microbiota and the kidneys (the gut-kidney axis). Currently,
the potential causal relationship between gut microbiota and diabetic nephropathy remains unclear. This study explores the causal effects of gut microbiota on diabetic nephropathy through
Mendelian randomization.

Methods:
We carried out a comprehensive Mendelian Randomization (MR) analysis, drawing
on the Genome-wide Association Study (GWAS) data for 196 varieties of gut microbiota and
diabetic nephropathy. The primary analytical approach employed was the inverse-variance
weighted, supplemented by the MR-Egger, weighted median, simple mode, and weighted mode.
We rigorously assessed heterogeneity with Cochran's Q test and examined pleiotropy via MREgger intercept and MR-PRESSO tests. To ensure the reliability of our findings, we conducted
funnel plots and leave-one-out analysis.

Results:
Our study indicates a causal relationship between the increased risk of diabetic
nephropathy and specific gut microbiota, including the Bacteroidia (P=0.01892; OR=1.593;
95%CI, 1.080-2.350), Bacteroidales (P=0.01892; OR=1.593; 95%CI, 1.080-2.350), and LachnospiraceaeUCG008 (P=0.01350; OR=1.452; 95%CI, 1.080-1.953). Conversely, potential protective factors include the Proteobacteria (P=0.00397; OR=0.528; 95%CI, 0.342-0.815), Gammaproteobacteria (P=0.00965; OR=0.474; 95%CI, 0.270-0.834), Lentisphaeria (P=0.04417;
OR=0.756; 95%CI, 0.576-0.993), Victivallales (P=0.04417; OR=0.756; 95%CI, 0.576-0.993),
and Dialister (P=0.00118; OR=0.513; 95%CI, 0.343-0.768).

Conclusion:
This study confirms the causal effects of gut microbiota on diabetic nephropathy.
Identifying the risk and protective factors within the gut microbiota for diabetic nephropathy offers fresh insights and novel approaches for preventing and treating this condition.
Integrated Analysis of Clinical Outcome of Mesenchymal Stem
Cell-related Genes in Pan-cancer
Authors: Jiang Mingzhe , Zhu Dantong , Zhao Dong , Liu Yongye , Li Jia , Zheng Zhendong 
Published: April 2024

Background:
Although the application of mesenchymal stem cells (MSCs) in engineered
medicine, such as tissue regeneration, is well known, new evidence is emerging that shows
that MSCs can also promote cancer progression, metastasis, and drug resistance. However, no
large-scale cohort analysis of MSCs has been conducted to reveal their impact on the prognosis of
cancer patients.

Objective:
We propose the MSC score as a novel surrogate for poor prognosis in pan-cancer.

Methods:
We used single sample gene set enrichment analysis to quantify MSC-related genes into
a signature score and identify the signature score as a potential independent prognostic marker for
cancer using multivariate Cox regression analysis. TIDE algorithm and neural network were utilized
to assess the predictive accuracy of MSC-related genes for immunotherapy.

Results:
MSC-related gene expression significantly differed between normal and tumor samples
across the 33 cancer types. Cox regression analysis suggested the MSC score as an independent
prognostic marker for kidney renal papillary cell carcinoma, mesothelioma, glioma, and stomach
adenocarcinoma. The abundance of fibroblasts was also more representative of the MSC score
than the stromal score. Our findings supported the combined use of the TIDE algorithm and neural
network to predict the accuracy of MSC-related genes for immunotherapy.

Conclusion:
We comprehensively characterized the transcriptome, genome, and epigenetics of
MSCs in pan-cancer and revealed the crosstalk of MSCs in the tumor microenvironment, especially
with cancer-related fibroblasts. It is suggested that this may be one of the key sources of resistance
to cancer immunotherapy.
Nanoparticle-based Gene Therapy for Neurodegenerative Disorders
Authors: Ereej Nelofer , Hameed Huma , Khan Mahtab Ahmad , Faheem Saleha , Hameed Anam 
Published: April 2024

Abstract::
Neurological disorders present a formidable challenge in modern medicine due to the
intricate obstacles set for the brain and the multipart nature of genetic interventions. This review
article delves into the promising realm of nanoparticle-based gene therapy as an innovative approach
to addressing the intricacies of neurological disorders. Nanoparticles (NPs) provide a multipurpose
podium for the conveyance of therapeutic genes, offering unique properties such as precise
targeting, enhanced stability, and the potential to bypass blood-brain barrier (BBB) restrictions. This
comprehensive exploration reviews the current state of nanoparticle-mediated gene therapy in neurological
disorders, highlighting recent advancements and breakthroughs. The discussion encompasses
the synthesis of nanoparticles from various materials and their conjugation to therapeutic
genes, emphasizing the flexibility in design that contributes to specific tissue targeting. The abstract
also addresses the low immunogenicity of these nanoparticles and their stability in circulation, critical
factors for successful gene delivery. While the potential of NP-based gene therapy for neurological
disorders is vast, challenges and gaps in knowledge persist. The lack of extensive clinical trials
leaves questions about safety and potential side effects unanswered. Therefore, this abstract emphasizes
the need for further research to validate the therapeutic applications of NP-mediated gene therapy
and to address nanosafety concerns. In conclusion, nanoparticle-based gene therapy emerges as
a promising avenue in the pursuit of effective treatments for neurological disorders. This abstract
advocates for continued research efforts to bridge existing knowledge gaps, unlocking the full potential
of this innovative approach and paving the way for transformative solutions in the realm of
neurological health.
Structure-property Relationships Reported for the New Drugs Approved in 2023
Authors: Choi Kihang 
Published: April 2024

:
Drug-like properties play pivotal roles in drug adsorption, distribution, metabolism, excretion,
and toxicity. Therefore, efficiently optimizing these properties is essential for the successful
development of novel therapeutics. Understanding the structure–property relationships of clinically
approved drugs can provide valuable insights for drug design and optimization strategies.
Among the new drugs approved in 2023, which include 31 small-molecule drugs in the US, the
structure-property relationships of nine drugs were compiled from the medicinal chemistry literature,
in which detailed information on pharmacokinetic and/or physicochemical properties was reported
not only for the final drug but also for its key analogs generated during drug development.
The structure-property relationships of nine newly approved drugs are summarized, including three
kinase inhibitors and three G-protein-coupled receptor antagonists. Several optimization strategies,
such as bioisosteric replacement and steric handle installation, have successfully produced clinical
candidates with enhanced physicochemical and pharmacokinetic properties.
The summarized structure–property relationships demonstrate how appropriate structural modifications
can effectively improve overall drug-like properties. The ongoing exploration of structure–
property relationships of clinically approved drugs is expected to offer valuable guidance for developing
future drugs.
Development of Cell and Gene Therapies for Clinical Use in the US and EU: Summary of Regulatory Guidelines
Authors: Rotte Anand 
Published: April 2024

:
Recent decades have seen advancements in the management and treatment of difficultto-
treat diseases such as cancer. A special class of therapeutics called cell and gene therapy has
been introduced in the past 10 years. Cell and gene therapy products have strengthened the treatment
options for life-threatening diseases with unmet clinical needs and also provided the possibility
of a potential cure for the disease in some of the patients. Cell and gene therapy products are
gaining recognition, and the interest in clinical development of cell and gene therapy products is
increasing. Moreover, as the class of cell and gene therapy products is relatively new, there is a
limited regulatory experience in the development, and the developers of the cell and gene therapy
products can often be puzzled with an array of questions on regulations. The current review intends
to provide a basic understanding of regulatory guidelines from the FDA and EMA that are
applicable to cell and gene therapy products. Essentials such as which office is responsible for the
evaluation of applications, which regulatory class/pathway is appropriate for development, and
what are the quality, nonclinical and clinical studies that are needed to support the application are
discussed in the article. In addition, a summary of regulatory designations and the post-approval
requirements, such as Risk Evaluation and Mitigation Strategies (REMS) and long-term follow-
up, is included in the article. Developers (referred to as ‘sponsors’ in this article) of cell and
gene therapies can use the respective guidance documents and other specific review articles cited
in this review for detailed information on the topics.
Low Expression MCEMP1 Promotes Lung Adenocarcinoma Progression and its Clinical Value
Authors: Ling Liqun , Hu Tianqi , Zhou Chenkang , Chen Shuhui , Chou Lunan , Chen Yuxin , Hu Zhaoting , Huang Kate , Chen Jie , Wang Yumin , Wang Junjun 
Published: April 2024

Background:
Lung cancer is a highly prevalent tumor with a lack of biological markers
that reflect its progression. Mast cell surface membrane protein 1 (MCEMP1, also known as
C19ORF59) has not been reported in lung adenocarcinoma (LUAD).

Objective:
We aimed to investigate the role of MCEMP1 in LUAD.

Methods:
MCEMP1 expression in LUAD was analyzed using The Cancer Genome Atlas (TCGA)
data, and conducted univariate and multivariate Cox regression analyses to evaluate the prognostic
significance of MCEMP1 expression in TCGA. Tumor Immune Estimation Resource (TIMER)
was used for examining the correlation between MCEMP1 expression and immune cell infiltration
in LUAD. Furthermore, proliferation, migration, invasion, and colony-forming ability were investigated
using LUAD cell lines.

Results:
MCEMP1 expression in LUAD patient tissues and was correlated with lymph node metastasis,
differentiation level, and tumor status. The Area under Curve (AUC) value of MCEMP1
for the Receiver Operating Characteristic (ROC) curve analysis was 0.984. The immune infiltration
analysis revealed a correlation between MCEMP1 expression and the extent of macrophages
and neutrophil infiltration in LUAD. Additionally, MCEMP1 has low expression in clinical samples,
MCEMP1 overexpressed in LUAD cells substantially reduced cell growth, migration, and invasion
of malignant cells.

Conclusion:
Low expression MCEMP1 promotes LUAD progression, which provides new insights
and a potential biological target for future LUAD therapies.
A New Approach to Melanoma Treatment: microRNAs
Authors: Ilhan Suleyman , Oguz Ferdi , Atmaca Harika 
Published: April 2024

Abstract::
Although immunotherapy and targeted therapy have radically changed melanoma treatment,
the development of resistance and reduction of patient responses are still significant
problems. Small molecule inhibitors are needed to overcome this situation, and biomarkers that
can estimate whether patients will reply to existing treatments need to be developed. miRNAs are
involved in diverse processes such as tumor development, tumor progression, metastasis, and invasion.
While some miRNAs act as tumor suppressors, others may be oncogenic. miRNAs also contribute
to the processes involved in drug resistance. There is increasing evidence demonstrating
the possible effect of miRNAs on the diagnosis and treatment markers of melanoma. The
manuscript focuses on the current challenges in melanoma treatment, highlighting issues such as
the development of resistance and reduced patient responses despite the revolutionary advancements
in targeted therapy and immunotherapy. It underscores the need for small molecule inhibitors
and the creation of biomarkers for predicting patient responses to current treatments. The role
of miRNAs in processes such as tumor development, metastasis, and invasion has been highlighted.
While certain miRNAs function as tumor suppressors, others may exhibit oncogenic properties.
Furthermore, increasing evidence is presented demonstrating the potential significance of
miRNAs as markers for the symptom and identification of melanoma. These findings indicate a
promising avenue for future research and clinical applications. In summary, the article effectively
communicates key insights, making it a valuable resource for those interested in melanoma research
and treatment.
Neuroprotective Role of Phytoconstituents-based Nanoemulsion for the
Treatment of Alzheimer’s Disease
Authors: Vishwas Sukriti , Bashir Bushra , Birla Devendra , Khandale Nikhil , Chaitanya Motamarri Venkata Naga Lalitha , Chellappan Dinesh Kumar , Gupta Gaurav , Negi Poonam , Dua Kamal , Singh Sachin Kumar 
Published: April 2024

:
Alzheimer's disease (AD) is the most prevalent form of neurodegenerative disorder
(ND), affecting more than 44 million individuals globally as of 2023. It is characterized by cognitive
dysfunction and an inability to perform daily activities. The progression of AD is associated
with the accumulation of amyloid beta (Aβ), the formation of neurofibrillary tangles (NFT), increased
oxidative stress, neuroinflammation, mitochondrial dysfunction, and endoplasmic reticulum
stress. Presently, various phytomedicines and their bioactive compounds have been identified
for their neuroprotective effects in reducing oxidative stress, alleviating neuroinflammation, and
mitigating the accumulation of Aβ and acetylcholinesterase enzymes in the hippocampus and cerebral
cortex regions of the brain. However, despite demonstrating promising anti-Alzheimer's effects,
the clinical utilization of phytoconstituents remains limited in scope. The key factor contributing
to this limitation is the challenges inherent in traditional drug delivery systems, which impede
their effectiveness and efficiency. These difficulties encompass insufficient drug targeting, restricted
drug solubility and stability, brief duration of action, and a lack of control over drug release.
Consequently, these constraints result in diminished bioavailability and insufficient permeability
across the blood-brain barrier (BBB). In response to these challenges, novel drug delivery
systems (NDDS) founded on nanoformulations have emerged as a hopeful strategy to augment the
bioavailability and BBB permeability of bioactive compounds with poor solubility. Among these
systems, nanoemulsion (NE) have been extensively investigated for their potential in targeting
AD. NE offers several advantages, such as ease of preparation, high drug loading, and high stability.
Due to their nanosize droplets, NE also improves gut and BBB permeability leading to enhanced
permeability of the drug in systemic circulation and the brain. Various studies have reported
the testing of NE-based phytoconstituents and their bioactives in different animal species, including
transgenic, Wistar, and Sprague-Dawley (SD) rats, as well as mice. However, transgenic
mice are commonly employed in AD research to analyze the effects of Aβ. In this review, various
aspects such as the neuroprotective role of various phytoconstituents, the challenges associated
with conventional drug delivery, and the need for NDDS, particularly NE, are discussed. Various
studies involving phytoconstituent-based NE for the treatment of AD are also discussed.
In Silico approach: Design an Optimized shRNA against RUNX1 Gene to
Target HIV
Authors: Kakavand-Ghalehnoei Rezvan , Patrad Elham , Ravanshad Mehrdad 
Published: April 2024

Introduction:
Human Immunodeficiency Virus (HIV) is a retrovirus with single-stranded RNA that leads to the challenging disease of acquired immunodeficiency syndrome (AIDS).
Combination antiretroviral therapy (cART) can prevent the progression of the disease, but it is not
capable of long-term HIV elimination. One of the significant obstacles to treating HIV-1-infected
individuals is the creation of latent cell reservoirs early in the infection. Gene-based therapies that
utilize RNA interference (RNAi) to silence host or viral gene expression are considered promising
therapeutic approaches. It has been demonstrated that RUNX1, a T-cell-specific transcription factor, may significantly affect HIV replication and infection. According to accumulating evidence
on the role of interfering RNA techniques in inhibiting gene expression and considering the role
of RUNX1 in the replication of HIV-1. In this study, we aim to design shRNAs against RUNX1
that can target the replication of HIV-1.

Methods:
Several computational methods, including target alignment, similarity search, and secondary structure prediction, have been employed in the design of shRNA against RUNX1.

Results:
Seven shRNA molecules with the highest efficiency were designed and validated using
computational methods to silence the RUNX1 gene.

Conclusions:
In the present study, we designed shRNA against RUNX1, which can target latent
cells infected with HIV. Suppression of RUNX1 by shRNA reactivates HIV in the latent cells and
subsequently potentiates the immune response toward identifying accurate virus-infected cells.
This process may lead to an effective and efficient reduction of the volume of cell reservoirs infected with HIV.
Preclinical Data Extrapolation to Clinical Reality: A Translational
Approach
Authors: Varshney Prakhar , Chandra Phool 
Published: April 2024

Abstract:
In vivo investigations are much more complex than trials conducted in a test tube; the
results sometimes aren't as illuminating and could raise more questions than answers. Preclinical
data projection into clinical truth is a transcriptional science that remains a compelling trial in
drug development. Preclinical in vivo and in vitro education is important in novel drug's non-violent or active growth. Pharmacokinetic and metabolic research is necessary to better understand
the chemical and biological effects of medicines and their metabolites. Information produced by
such a policy can be used to progress Phase I studies, primarily for anticancer medication. Both
living and deceased in vitro models are theoretically excellent preclinical tools for calculating the
pharmacological action of counterparts from the same family, such as vinca alkaloids. The animal
species most closely linked to humans are chosen based on metabolic patterns. The estimation of
the duration of drug action, particularly for medicines with varied metabolic clearances (e.g., benzodiazepines); The empathetic or estimate of medicine relations, i.e., those defined for cyclosporin A and macrolide antibiotics; and Sclarification of the metabolic roots of individual inconsistencies in pharmaceutical action.
Non-Pharmaceutical Interventions in Cancer Therapy
Authors: Tyagi Vanshika , Tanwar Neha , Kumar Nihal , Phogat Nishu , Kumar Pawan , Kumar Virender 
Published: April 2024

Abstract:
Cancer was the most significant reason for mortality worldwide. It accounted for over 10
million deaths worldwide by 2020. Patients experiencing excruciating pain from this malignant disease
are worn out of using the conventional allopathic method for recovery; as a result, they opt for
the non-medical, otherwise stated non-pharmaceutical approaches as the escape route. This study encloses
the development of these non-pharmaceutical interventions in cancer treatment, which include
meditation, yoga, music therapy, acupuncture, hypnosis, massage, physical activity/exercise, and
stress management to manage psych and physical symptoms. Besides, various natural products procured
from the rich aqua life comprising marine fauna and flora are used. We also use multiple terrestrial
plants and herbs as the source for many nutraceutical preparations. Due to the lift of these nonconventional
methods, the world is using these extracts to treat cancer, whether symptomatic or the
root cause of the disease itself.
Mixed Connective Tissue Disease (MCTD) in a Girl with Lower Extremities Edema: A Brief Report
Authors: Shashaani Niloofar , Yeganeh Mehrnoush Hasas , Sinaei Reza , Salehi Shima , Shiari Reza 
Published: April 2024

Background:
Mixed Connective Tissue Disease (MCTD) is a rare condition in children,
characterized by a high titer of anti-ribonucleoprotein-U1 (anti-U1 RNP) antibodies, often
presenting with overlapping features of two or more rheumatologic disorders, including juvenile
idiopathic arthritis (JIA), systemic lupus erythematous (SLE), systemic sclerosis (SSc), and juvenile
dermatomyositis/polymyositis (JDM/PM).

Case Presentation:
We report the case of an 8-year-old girl with a history of fever, hair loss, lower
extremities edema, weakness, oral aphthous ulcers, and a high titer of anti-U1 RNP antibodies,
which is consistent with the diagnosis of MCTD. The patient received immunomodulator drugs,
and her disease went into remission.

Conclusion:
Diagnosing MCTD in pediatric patients can be challenging. It should be considered
especially in cases with recurrent muscular weakness or pain, lupus-like manifestations, and edema.
Moreover, serum anti-U1 RNP testing can be a helpful diagnostic tool.