bluuebunny/crossref_metadata_2025_split huggingface dataset:
Molecular Determination of Tumor Necrosis Factor-alpha, Interleukin-8,
Interleukin-10, and C-X-C Chemokine Receptor-2 Genetic Variations and
their Association with Disease Susceptibility and Mortality in COVID-19
Patients
Authors: Alsayed Badr A. , Mir Rashid , Mir Mohammad M. , Alnour Tarig M.S. , Fawzy Shereen , Ahmed Mesaik M. , Amle Dnyanesh 
Published: January 2024

Background:
Altered cytokine levels have been associated with poor outcomes among
COVID-19 patients. TNF-α, IL-8 and IL-10 are key cytokines in COVID-19 pathogenesis, and
CXCR-2 is a major chemokine receptor involved in inflammatory response. Polymorphisms in the
genes of these proteins are proposed to influence disease outcomes. In this study, we aimed to find
out the association of genetic polymorphisms in TNF-α, IL-8, IL-10 and CXCR-2 genes with susceptibility
to and mortality of COVID-19.

Methods:
The present case-control study was conducted on 230 subjects, among whom 115 were
clinically diagnosed and RT-PCR-confirmed COVID-19 patients and 115 healthy control subjects.
The polymorphisms in TNFα -308 G>A (rs1800629), IL-8 -251T>A (rs4073), CXCR2 +785 C>T
(rs2230054) genes were detected by ARMS -PCR assay whereas for IL-10 (-1082 G>A),
rs1800896 G>A allele-specific PCR assay was used and their association with COVID-19 susceptibility
and mortality was estimated by multivariate analysis. The results were analyzed for risk
of infection and mortality through different inheritance models.

Results:
Frequencies of TNF-α rs1800629 GA, AA, IL-8 rs4073 TA, AA, IL-10 (-1082 G>A),
rs1800896 GA and GG, and CXCR2 rs2230054 CT genotypes were significantly higher in
COVID-19 patients compared to the control group (p < 0.05). Furthermore, COVID-19 patients
had a higher frequency of the polymorphic A allele of TNF-α, the A allele of IL-8, the G allele of
IL-10, and the T allele of CXCR2. The risk of susceptibility to COVID-19 was significantly associated
with TNF-α rs1800629 GA, GA+AA genotypes and the A allele, IL-8 rs4073 TA, AA genotypes
and A allele, IL-10 rs1800872 GA and CC genotypes and C allele, and CXCR2 rs2230054
CT and CT+CC genotypes. TNF-α-GA and AA genotypes and A allele, IL-8 TA and AA genotypes
and A allele and CXCR-2 CC and CT genotypes have significant associations with mortality
risk in COVID-19 patients, while GA and GG genotypes of the IL-10 are shown to confer significant
protection against mortality from COVID-19.

Conclusion:
The findings of this study provide important insights into the COVID-19 disease and
susceptibility risk. The polymorphisms in TNFα -308 G>A (rs1800629), IL-8 -251T>A (rs4073),
IL-10 (-1082 G>A), rs1800896 and CXCR2 +785 C>T (rs2230054) are associated with the risk of
susceptibility to COVID-19 and with mortality in COVID-19 patients. Further studies with larger
sample sizes are necessary to confirm our findings.
Neurokinin B Administration Induces Dose Dependent Proliferation of
Seminal Vesicles in Adult Rats
Authors: Ramzan Muhammad Haris , Shah Mohsin , Ramzan Faiqah 
Published: January 2024

Background:
Neurokinin B; an endogenous decapeptide, mediates its reproductive physiological
actions through gonadotropin releasing hormone. Despite the potential role of Neurokinin
B on seminal vesicles, its effects on seminal vesicles in adult male mammals remain elusive.
We aimed to investigate the potentials of variable doses of Neurokinin B, its agonist and antagonist
on histomorphology and expression of NK3R on seminal vesicles, and secretory activity of
seminal vesicles in adult male rats.

Methods:
Adult male Sprague Dawley rats (n=10 in each group) were administered intraperitoneally
with Neurokinin B in three variable doses: 1 μg, 1 ηg and 10 ρg while, Senktide (Neurokinin
B agonist) and SB222200 (Neurokinin B antagonist) in 1 μg doses consecutively for 12
days. After 12 days of peptide treatment, half of the animals (n=05) in each group were sacrificed
while remaining half (n=05) were kept for another 12 days without any treatment to investigate
treatment reversal. Seminal vesicles were dissected and excised tissue was processed for light microscopy,
immunohistochemistry and estimation of seminal fructose levels.

Results::
Treatment with Neurokinin B and Senktide significantly increased while SB222200
slightly decrease the seminal vesicles weight, epithelial height and seminal fructose levels as compared
to control. Light microscopy revealed increased epithelial height and epithelial folding as
compared to control in all Neurokinin B and Senktide treated groups while decreased in
SB222200. Effects of various doses of Neurokinin B, Senktide and SB222200 on seminal vesicles
weight, epithelial height, seminal fructose levels and histomorphology were reversed when rats
were maintained without treatments. Immuno-expression of Neurokinin B shows no change in
treatment and reversal groups

Conclusion::
Continuous administration of Neurokinin B and Senktide effect positively while
SB222200 have detrimental effects on cellular morphology, epithelial height and seminal fructose
levels in seminal vesicles. Effects of peptide treatments depicted a reversal towards control group
when rats were kept without any treatment.
Artificial Intelligence in Drug Discovery: A Bibliometric Analysis and
Literature Review
Authors: He Baoyu , Guo Jingjing , Tong Henry H.Y. , To Wai Ming 
Published: January 2024

Abstract:
Drug discovery is a complex and iterative process, making it ideal for using artificial
intelligence (AI). This paper uses a bibliometric approach to reveal AI's trend and underlying structure
in drug discovery (AIDD). A total of 4310 journal articles and reviews indexed in Scopus were
analyzed, revealing that AIDD has been rapidly growing over the past two decades, with a significant
increase after 2017. The United States, China, and the United Kingdom were the leading countries
in research output, with academic institutions, particularly the Chinese Academy of Sciences
and the University of Cambridge, being the most productive. In addition, industrial companies, including
both pharmaceutical and high-tech ones, also made significant contributions. Additionally,
this paper thoroughly discussed the evolution and research frontiers of AIDD, which were uncovered
through co-occurrence analyses of keywords using VOSviewer. Our findings highlight that
AIDD is an interdisciplinary and promising research field that has the potential to revolutionize drug
discovery. The comprehensive overview provided here will be of significant interest to researchers,
practitioners, and policy-makers in related fields. The results emphasize the need for continued investment
and collaboration in AIDD to accelerate drug discovery, reduce costs, and improve patient
outcomes.
Dextran-based Drug Delivery Approaches for Lung Diseases: A Review
Authors: Kumari Manisha , Sharma Sanyam , Kanwar Navjot , Naman Subh , Baldi Ashish 
Published: January 2024

:
Respiratory disorders, such as tuberculosis, cystic fibrosis, chronic obstructive pulmonary
disease, asthma, lung cancer, and pulmonary inflammation, are among the most prevalent ailments in
today’s world. Dextran, an exopolysaccharide formed by Leuconostoc mesenteroides (slimeproducing
bacteria), and its derivatives are investigated for several therapeutic utilities. Dextranbased
drug delivery system can become an innovative strategy in the treatment of several respiratory
ailments as it offers numerous advantages, such as mucolytic action, airway hydration, antiinflammatory
properties, and radioprotective effect as compared to other polysaccharides. Being biocompatible,
flexible hydrophilic nature, biodegradable, tasteless, odourless, non-mutagenic, watersoluble
and non-toxic edible polymer, dextran-based drug delivery systems have been explored for a
wide range of therapeutic applications, especially in lungs and respiratory diseases. The present article
comprehensively discusses various derivatives of dextran with their attributes to be considered for
drug delivery and extensive therapeutic benefits, with a special emphasis on the armamentarium of
dextran-based formulations for the treatment of respiratory disorders and associated pathological
conditions. The information provided will act as a platform for formulation scientists as important
considerations in designing therapeutic approaches for lung and respiratory diseases.

:
With an emphasis on lung illnesses, this article will offer an in-depth understanding of dextran-based
delivery systems in respiratory illnesses.
Tectorigenin Inhibits Glycolysis-induced Cell Growth and Proliferation by
Modulating LncRNA CCAT2/miR-145 Pathway in Colorectal Cancer
Authors: Xing Ying , Lin Bofan , Liu Baoxinzi , Shao Jie , Jin Zhichao 
Published: January 2024

Background:
Colorectal cancer (CRC) places a heavy burden on global health. Tectorigenin
(Tec) is a type of flavonoid-based compound obtained from the Chinese medical herb Leopard
Lily Rhizome. It was found to exhibit remarkable anti-tumor properties in previous studies.
However, the effect and molecular mechanisms of Tec in colorectal cancer have not been reported.

Objective:
The objective of this study was to explore the action of Tec in proliferation and glycolysis
in CRC and the potential mechanism with regard to the long non-coding RNA (lncRNA)
CCAT2/micro RNA-145(miR-145) pathway in vitro and in vivo.

Methods:
The anti-tumor effect of Tec in CRC was examined in cell and animal studies, applying
Cell Counting Kit-8 (CCK-8) assay as well as xenograft model experiments. Assay kits were utilized
to detect glucose consumption and lactate production in the supernatant of cells and animal
serum. The expression of the glycolysis-related proteins was assessed by Western Blotting, and
levels of lncRNA CCAT2 and miR-145 in CRC tissue specimens and cells were assessed by realtime
quantitative PCR (RT-qPCR).

Results:
Tec significantly suppressed cell glycolysis and proliferative rate in CRC cells. It could
decrease lncRNA CCAT2 in CRC cells but increase the expression of miR-145. LncRNA CCAT2
overexpression or inhibition of miR-145 could abolish the inhibitive effects of Tec on the proliferation
and glycolysis of CRC cells. The miR-145 mimic rescued the increased cell viability and glycolysis
levels caused by lncRNA CCAT2 overexpression. Tec significantly inhibited the growth
and glycolysis of CRC xenograft tumor. The expression of lncRNA CCAT2 decreased while the
expression of miR-145 increased after Tec treatment in vivo.

Conclusion:
Tec can inhibit the proliferation and glycolysis of CRC cells through the lncRNA
CCAT2/miR-145 axis. Altogether, the potential targets discovered in this research are of great significance
for CRC treatment and new drug development.
Stimuli-induced NOergic Molecules and Neuropeptides Mediated Axon
Reflexes Contribute to Tracers along Meridian Pathways
Authors: Ma Shengxing 
Published: January 2024

Abstract:
An abundance of studies from different international groups have demonstrated tracers
along linear pathways resembling meridians over the body surface of humans. All experiments of
the studies have been conducted by injection of a radiotracer solution or tracer dyes in a volume of
solution into acupuncture points (acupoints). The solution injected into acupoints produces much
stronger mechanical stimuli than acupuncture, which causes axon reflex. Anatomical studies have
demonstrated that acupoints/meridians exist higher number of small nerve fibers and blood vessels
with rich nitric oxide (NO) and neuropeptides in the cutaneous tissues as structures for the biomolecules
mediated axon reflexes. Recent advances have determined that NO and calcitonin generelated
peptides play crucial roles in the comprehension of the axon reflex. The stimuli-evoked axon
reflex and NOergic biomolecules/neuropeptides increase local blood flow with higher levels in
acupoints/meridians, which move radioactive substances or tracer dyes in the skin and subcutaneous
tissue under a linear path resembling acupoints and meridians, the important phenomena of
meridians induced by the stimuli. The evidence and understanding of the biomolecular processes
of the tracers along linear pathways resembling meridians have been summarized with an emphasis
on recent developments of NO and neuropeptides mediating stimuli-evoked axon reflexes to increase
local blood flow with higher levels in acupoints/meridians, which move radioactive substances
or tracer dyes in the skin and subcutaneous tissue contributing to tracers along linear pathways
resembling meridians in this mini-review.
Recent Advances in Metallic Nanostructures-assisted Biosensors for
Medical Diagnosis and Therapy
Authors: Tiryaki Ecem , Zorlu Tolga 
Published: January 2024

Abstract:
The field of nanotechnology has witnessed remarkable progress in recent years, particularly
in its application to medical diagnosis and therapy. Metallic nanostructures-assisted biosensors
have emerged as a powerful and versatile platform, offering unprecedented opportunities for
sensitive, specific, and minimally invasive diagnostic techniques, as well as innovative therapeutic
interventions. These biosensors exploit the molecular interactions occurring between biomolecules,
such as antibodies, enzymes, aptamers, or nucleic acids, and metallic surfaces to induce
observable alterations in multiple physical attributes, encompassing electrical, optical, colorimetric,
and electrochemical signals. These interactions yield measurable data concerning the existence
and concentration of particular biomolecules. The inherent characteristics of metal nanostructures,
such as conductivity, plasmon resonance, and catalytic activity, serve to amplify both
sensitivity and specificity in these biosensors. This review provides an in-depth exploration of the
latest advancements in metallic nanostructures-assisted biosensors, highlighting their transformative
impact on medical science and envisioning their potential in shaping the future of personalized
healthcare.
In-silico, in-vitro and in-vivo Biological Activities of Flavonoids for the
Management of Type 2 Diabetes
Authors: Dash Jyoshna Rani , Kar Biswakanth , Pattnaik Gurudutta 
Published: January 2024

Abstract:
In spite of the fact that many medicinal plants have been truly utilized for the management
of diabetes all through the world, very few of them have been reported scientifically. Recently, a
diverse variety of animal models have been established to better understand the pathophysiology of
diabetes mellitus, and new medications to treat the condition have been introduced in the market.
Flavonoids are naturally occurring substances that can be found in plants and various foods and may
have health benefits in the treatment of neuropathic pain. Flavonoids have also been shown to have
an anti-inflammatory impact that is significant to neuropathic pain, as indicated by a decrease in
several pro-inflammatory mediators such TNF-, NF-B IL-6, and IL-1. Flavonoids appear to be a viable
novel therapy option for macrovasular complications in preclinical models; however, human
clinical data is still inadequate. Recently, several in silico, in-vitro and in-vivo aproaches were made
to evaluate mechanisms associated with the pathogenesis of diabetes in a better way. Screening of
natural antidiabetic agents from plant sources can be analysed by utilizing advanced in-vitro techniques
and animal models. Natural compounds, mostly derived from plants, have been studied in
diabetes models generated by chemical agents in the majority of research. The aim of this work was
to review the available in silico, in-vitro and animal models of diabetes for screening of natural antidiabetic
agents. This review contributes to the scientist's design of new methodologies for the development
of novel therapeutic agents having potential antihyperglycemic activity.
Development of Morphea Following Treatment with an ADA Biosimilar:
A Case Report
Authors: Venetsanopoulou Aliki I. , Mavridou Konstantina , Pelechas Eleftherios , Voulgari Paraskevi V. , Drosos Alexandros A. 
Published: January 2024

Background:
Tumor necrosis factor alpha (TNFα) is a pivotal cytokine involved in the
pathogenesis of certain inflammatory diseases, such as rheumatoid arthritis (RA), spondyloarthropathies,
and inflammatory bowel diseases. In the last two decades, TNFα inhibitors (TNFi) have
revolutionized the treatment and outcome of the above disorders. However, the use of TNFi has
been associated with the development of many autoimmune phenomena and paradoxical skin manifestations
that may present as the same type of clinical indications for which the TNFi effectively
used. Thus, they may display as arthritis, uveitis, colitis, psoriasis, and several other cutaneous
clinical manifestations, among them the development of morphea, a localized scleroderma skin lesion.

Case Presentation:
We describe a 58-year-old woman with seronegative RA, refractory to
methotrexate, who was treated with ABP-501 (Hefiya), an adalimumab (ADA) biosimilar and developed
an oval-shaped, deep skin lesion of approximately 3.5cm in size, affecting the left part of
her back compatible with morphea 3 months after the initiation of therapy. ADA biosimilar was
discontinued and two months later, she had substantial skin improvement.

Conclusion:
This is the first report of morphea manifestation during TNFi biosimilar since the patient
had no other trigger factors for morphea development like trauma and infections. Physicians
dealing with patients treated with TNFi biosimilars should be aware of paradoxical skin reactions,
among them morphea; thus, close monitoring, a minute and careful clinical examination, and a follow-
up check are required.
Predictors of Clinical Benefit with Intra-articular Hyaluronic Acid in
Patients with Knee Osteoarthritis - A Narrative Review
Authors: Chevalier Xavier , Sheehan Brendan 
Published: January 2024

Background:
There is conflicting evidence regarding the efficacy of viscosupplementation
with intra-articular hyaluronic acid injections in knee osteoarthritis. One possible explanation
for the inconsistent findings on its efficacy is that only certain subpopulations of patients benefit
from this therapy.

Objective:
The purpose of this narrative review is to succinctly summarize the existing data on the
predictive factors of clinical response to intra-articular hyaluronic acid to identify the patient profile
most likely to benefit from this therapy.

Methods:
For this narrative review, a PubMed search was conducted in January 2023, with no
date limits, to identify publications reporting predictive factors of response to viscosupplementation
using the following terms: hyaluronic acid OR viscosupplem* AND osteoarthritis AND knee
AND predict*. Searches were limited to randomized controlled trials, systematic reviews and meta-
analyses, or observational studies written in English. Other relevant references were identified
by searching the references of retrieved articles.

Results:
The disease severity was found to reliably predict response to intra-articular hyaluronic
acid injections; patients with less severe disease consistently had a more robust therapeutic response
than those with more severe disease. Other clinical variables such as level of baseline pain
did not reliably predict response. Body mass index, and possibly age, may also be independent predictors
of the response.

Conclusion:
A review of the existing literature suggests that patients with less severe clinical
symptoms and radiological findings, who are younger, and with a lower or normal body mass index
are the best candidates for intra-articular hyaluronic acid therapy.
Association and Mechanisms of Proton Pump Inhibitors Use with Type-2
Diabetes Mellitus Incidence in Adults: A Systemic Review and
Meta-Analysis
Authors: Chenchula Santenna , Sharma Phulen , Ghanta Mohan Krishna , Amerneni Krishna Chaitanya , Rajakarunakaran Padmavathi , Saggurthi Pavani , Chandra Madhu Bhargavi , Gupta Rupesh , Chavan Madhavrao 
Published: January 2024

Background:
Proton pump inhibitors (PPIs) are an extensively prescribed class of
anti-ulcer drugs. This systematic review aimed to investigate the association between PPI use and
the risk of new-onset diabetes mellitus or type 2 diabetes (T2DM) incidence.

Methods:
A comprehensive literature search was conducted in PubMed, Scopus, Cochrane Library, and ClinicalTrials.gov using the search terms “proton pump inhibitor,” “proton pump inhibitors,” “PPIs,” “diabetes mellitus,” and “type 2 diabetes” from inception to February 2023.
Statistical analyses were performed using the “Review Manager 5.4” version, and a statistically
highly significant P value <0.05 was set.

Results:
This systematic review identified 12 studies (8 cohort, 1 RCT, and 3 case-control) with a
total of 12, 64, 816 population, and the median age ranged from ≥18 yrs to ≤ 75 yrs. The pooled
relative risk (RR) observations of a random-effects meta-analysis model showed that chronic
exposure to PPI use has a significant association with T2DM risk incidence (RR, 2.44; 95% confidence interval, 1.31–4.54; I
2 = 99%, P < 0.00001). The systematic review findings of the three
case-control studies also supported an association of dose-dependent and chronic use of PPIs with
an incidence of T2DM among chronic users.

Conclusion:
The systematic review concludes that chronic PPI exposure increases the risk of
T2DM incidence. The authors recommend the shortest possible duration of PPI use and not prescribing PPIs to high-risk prediabetics and those without a compelling indication for PPI use.
Regular education to patients regarding adverse reactions with prolonged use may decrease the
risk of adverse effects associated with PPIs. The authors suggest that gut dysbiosis, hypergastrinemia, hypomagnesemia, decreased pancreatic secretions and IGF-1 levels, and PXR activation
associated with chronic acid suppression among chronic PPI users and the potency of PPIs might
explain the association between abnormal glucose metabolism and T2DM incidence. Finally, the
authors recommend further randomized controlled trials to investigate the association between
PPIs and the risk of new-onset T2DM incidence.
Physiological Evidence and Therapeutic Outcomes of Vitamin D on
Cardiovascular Diseases
Authors: Zendehdel Abolfazl , Shakarami Amir , Moghadam Ehsan Sekhavati 
Published: January 2024

Abstract:
Vitamin D hormone is an important regulator of various physiological functions, and
its deficiency is characterized by an imbalance in parathyroid hormone and calcium homeostasis.
The role of vitamin D in cardiovascular physiology is well demonstrated in animal and humanbased studies. In this context, hyperlipidemia, increased atherogenic plaques, cardiac inflammation, hypertension, myocarditis, myocardial infarction, and heart failure are some of the commonest known conditions connected with vitamin D deficiency. Supplementation of vitamin D is recommended to achieve normal serum vitamin D concentrations, nonetheless, in clinical trials often
seen discrepancies concerning the supplementation effects and effectiveness. This review summarizes the data on the role of vitamin D in cardiovascular health along with some recent clinical
findings regarding the effects of vitamin D supplementation.