bluuebunny/crossref_metadata_2025_split huggingface dataset:
Phytochemistry, Pharmacological Targets, Biological Mechanisms and Patented Formulations of Salacia reticulata Wight (Celastaceae): An Appraisal of its Potential
Authors: Wal Pranay , Dwivedi Jyotsana , Kaushal Shubhi , Aparna Tatapudi Naga , Bhaskararao Pulagurtha , Sahu Devendra Kumar , Bedi Onkar , Sharma Mukesh Chandra 
Published: February 2025

Abstract:
Herbal medications provide universal benefits such as effectiveness, safety, cost, and acceptance.
With increased interest in plant extract research, there is also increased concern about the activity of bioactive
lumberjack climber plants indigenous to Sri Lanka and Indian submontane forests. It was recently determined
that plants containing kotalanol, salacinol (derived from roots, especially stems), and mangiferin (xanthone
from roots) are anti-diabetic agents. Salacia reticulata (S. reticulata) contains 1,3-diketone, dulcitol, leucopelargonidin,
epicatechin, furovatannin, glycoside tannin, triterpene, 30-hydroxy-20(30)-dihydroisoigesterol, hydroxyferruginol,
acidic Lambert, and 16-acetate. Chemical components such as collagen in 26-hydroxy-1,3-
friederandione and maitenfolate have also been discovered in S. reticulata roots. Root decoction treats skin
conditions, rheumatic conditions, gonorrhoea, hemorrhoids, asthma, edema, irritation, dry mouth, menstrual
cramps, and dysmenorrhea. The gastrointestinal suppression of enzymes that take over glucose through the
blood reduces postprandial hyperglycemia and improves blood sugar control. Additionally, mangiferin can impede
the action of aldose reductase, which delays the development or worsening of diabetes. Consequently,
efforts are underway to discover new therapeutic targets, signifying a novel approach to medication development.
In this regard, S. reticulata has been widely consumed owing to its discoveries and is currently the focus
of substantial studies on diabetes treatment.
Circulating SFRP2 in Iranian Polycystic Ovarian Syndrome Patients with Infertility and Recurrent Pregnancy Loss and its Correlation with Insulin Resistance and Inflammation
Authors: Jawad Ali Abdul Kareem , Nabatchian Fariba , Moradi Nariman , Choobineh Hamid , Fadaei Reza , Afrisham Reza 
Published: February 2025

Introduction:
Secreted Frizzled-Related Protein 2 (SFRP2) is considered to be the
most potent modulator of the Wnt signaling. This pathway is involved in the pathogenesis of Polycystic
Ovary Syndrome (PCOS). This research aimed to compare the levels of SFRP2 in PCOS
[infertile and Recurrent Pregnancy Loss (RPL) patients] with the control group and determine the
correlation of SFRP2 with inflammation and insulin resistance.

Methods:
This case-control study was conducted on 108 POCS patients (53 infertile patients and
55 women with RPL) and 54 healthy controls. The levels of biochemical factors along with SFRP2,
adiponectin, Luteinizing Hormone (LH), Follicle-Stimulating Hormone (FSH), free testosterone,
and insulin, high-sensitivity C-Reactive Protein (hs-CRP) were measured following the
manufacturer's instructions.

Results:
Both infertile and RPL groups presented notably higher levels of SFRP2 (49.32 ± 17.72
ng/ml and 55.89 ± 17.36 ng/ml, respectively) compared to the control group (30.21 ± 10.12 ng/ml,
P<0.001 for both groups). In PCOS patients, a positive correlation was observed between SFRP2
and body mass index (BMI) (r = 0.42, P < 0.001), insulin (r = 0.19, P = 0.04), fasting blood glucose
(FBG) (r = 0.24, P = 0.01), Homeostatic Model Assessment for Insulin Resistance (HOMA-
IR) (r = 0.21, P = 0.03), triglyceride (r = 0.25, P = 0.009), and hs-CRP (r = 0.21, P = 0.02).
Furthermore, SFRP2 increased the risk of RPL (OR [95% CI] = 1.15 [1.10 -1.20], P < 0.001) and
infertility (OR [95% CI] = 1.12 [1.07 -1.17], P < 0.001) in comparison with the controls.

Conclusion:
Our findings suggested that SFRP2 may have a potential involvement in the development
of PCOS and might be a promising target for diagnosis, but additional research is required to
confirm this.
Combating Drug Resistance in Lung Cancer: Exploring the Synergistic
Potential of Metformin and Cisplatin in a Novel Combination Therapy; A
Systematic Review
Authors: Jafarzadeh Emad , Sarajar Behnam Omidi , Lalani Armineh Rezaghol , Rastegar-Pouyani Nima , Aliebrahimi Shima , Montazeri Vahideh , Ghahremani Mohammad H , Ostad Seyed Nasser 
Published: February 2025

Introduction:
The persistent drug resistance observed in lung cancer necessitates innovative
strategies to improve therapeutic outcomes. This review investigates the potential of combining
metformin (Met) and cisplatin (Cis) to overcome drug resistance and enhance treatment
efficacy. Cis's limitations, including drug resistance and adverse effects, coupled with Met’s established
safety profile, form the backdrop for this exploration.

Methods:
Systematic literature searches across major databases identified relevant studies exploring
the synergistic effects of Met and Cis in the context of drug-resistant lung cancer. Data extraction
encompassed diverse facets, including treatment protocols, cellular responses, and mechanistic
insights. The synthesis of these findings sheds light on the potential of this combination therapy to
combat drug resistance.

Results:
Numerous in vitro and in vivo studies have demonstrated the ability of the Met + Cis
combination to sensitize drug-resistant lung cancer cells. The co-treatment consistently showed
enhanced inhibition of cell proliferation, elevated apoptosis rates, and attenuated migration and
invasion capabilities compared to monotherapies. Mechanistically, Met’s modulatory effect on key
pathways, such as AMPK-mTOR and ROS-mediated signaling, appears to underlie its ability to
counter drug resistance.

Conclusion:
The Met + Cis combination holds promise as an innovative strategy to counter drug
resistance in lung cancer. By harnessing the synergistic effects of these agents, combination therapy
offers a novel approach to enhance treatment efficacy and mitigate the challenges posed by
drug-resistant lung cancer. Although further clinical validation is required, the Met + Cis synergy
represents a promising avenue in the pursuit of improved lung cancer therapy outcomes.
Prevalence of Metabolic Syndrome in Iranian Adults Receiving Antiretroviral Treatment for HIV
Authors: Khazdooz Hamid , Abbasian Ladan , Shirzad Nooshin , Khashayar Pouria , SeyedAlinaghi SeyedAhmad , Malekahmadi Mahsa , Hemmatabadi Mahboobeh 
Published: February 2025

Background:
The increased risk of metabolic syndrome (MetS) and its subcomponents among people living with HIV/AIDS, especially in developing countries, is well documented with the global pooled prevalence of the related risk factors in this population.

Objective:
This study aimed to explore the prevalence of MetS among Iranian People living with HIV according to the ATP III and Iranian criteria.

Methods:
The cross-sectional study was conducted on consecutive patients who visited THE re-ferral centre for AIDS/HIV between May to December 2023. A total of 130 participants (n=83; 63.8% male) were investigated based on the inclusion criteria, which included having a minimum age of 25 and a maximum of 65 years and following a stable ART treatment regimen for at least six months. A Chi-square test was used to determine the relationship between the categorical variables. Uni/Multi-variable linear regression analysis was used to quantify the associations be-tween MetS and HIV by the independent variables.

Results:
The incidence of MetS according to ATP III and Iranian criteria were 42 (32.3%) and 45 (34.6%), which was higher in older patients (p=0.001) and those with more duration since HIV diagnosis (p=0.02). Around 33.1% and 16.1% were overweight and obese, respectively. Among the components of MetS, the highest prevalence (50.8%) was related to low HDL, and the lowest was related to fasting blood sugar (21.5%). The average body fat mass, protein mass, Soft lean mass, and percentage body fat were 18.54±9.46 kg, 10.91±2.17 kg, 51.31±9.61 kg, and 24.86±10.25% that were higher in MetS group (p<0.05).

Conclusion:
Our study points out the high prevalence of MetS in an Iranian population living with HIV, especially those suffering from the underlying disease for a longer time. Conducting multi-centric studies with larger sample sizes is needed to confirm our results and determine the most effective measures.

conclusion:
Our study offers valuable insights into the study of the prevalence of MetS in a population living with HIV/AIDS. Conducting multi-centric studies with higher sample sizes according to Iranian and ATP III Criteria would effectively parallel this study.
In silico based Diabetic Wound Healer from Nature: An Update
Authors: Lather Amit , Rathee Pratibha , Gautam Manish Kumar , Sharma Kalicharan , Hooda Tanuj 
Published: February 2025

Abstract:
Diabetes is a chronic metabolic disease of high levels of glucose in the blood and affecting
536.6 million people in the world between the age group of 20-79 with management spent of
11% of the total worldwide. Wound healing in diabetics is impaired due to many factors like high
blood sugar, poor blood circulation, damaged blood vessels, diabetic neuropathy, decreased immune
responses etc. The presently used synthetic drugs have high costs, a toxic nature, and are full of
adverse effects drawing attention to the need to identify new and successful treatment approaches
for diabetic wounds. In silico drug screening methods of drug development made it easy to screen
thousands of active constituents against a target specifically responsible for diabetes and wound
healing. Thus the current review compiled the naturally available active compounds screened by in
silico docking from natural resources and has the potential to treat diabetic wound healing with their
specificity and target-based mechanism. This information will be helpful for further screening of
non-reported natural compounds having antidiabetic as well as wound healing potential
CDH1-involved Ubiquitination of SIRT5 Promotes the Entry of Colorectal Cancer Cells into Quiescence and Enhances Cell Stemness
Authors: Li Wei , Chen Jian , Yang Jinbao , Zhang Bo , Wen Dihao , Jiang Zhibin 
Published: February 2025

Background:
This study explored whether the cell cycle regulator cadherin 1 (CDH1) impacts colorectal
cancer cell cycle and stemness via mediating ubiquitination of sirtuin 5 (SIRT5).

Methods:
We first constructed CDH1 overexpression plasmid and small interfering RNA against SIRT5
(siSIRT5) and transfected them into HCT116/HT29 cells, followed by transfection efficiency verification. The
effect of CDH1 on Cyclin F/SIRT5/CDH1 protein levels in HCT116/HT29 cells was verified by Western blot.
After up-regulation of CDH1, changes in SIRT5 ubiquitination (immunoprecipitation), cell cycle (cell cycle kit),
proliferation (5-Bromodeoxyuridine assay), and stemness marker expressions (qRT-PCR) in HCT116/HT29 cells
were detected. Rescue assays were performed to examine cell proliferation and stemness marker expressions.

Results:
Overexpression of CDH1 decreased Cyclin F expression and increased SIRT5 and CDH1 expressions in
HCT116/HT29 cells. Up-regulation of CDH1 suppressed SIRT5 ubiquitination, promoted G0/G1 phase blockage
in HCT116/HT29 cells, boosted cell proliferation into quiescence and enhanced cell stemness. siSIRT5 counteracted
the regulatory effect of CDH1 overexpression on colorectal cancer cells.

Conclusion:
CDH1 promotes the entry of colorectal cancer cells into quiescence and enhances stemness by
dampening SIRT5 ubiquitination.
Investigation of the Status of Epidemiology, Pathophysiology, Virology, Clinical Symptoms, Diagnosis, Prevention, Treatment and Classification of Ebola Virus Disease (EVD): A Systematic Review
Authors: Raesi Rasoul , Tabatabae Seyed Saeed , Saadat Seyed Hassan , Bokaie Saied , Daneshi Salman , Hushmandi Kiavash 
Published: February 2025

Background and Objectives:
Ebola Virus Disease (EVD) is one of the deadliest viral diseases in history, rapidly spreading to other parts of the world. Due to frequent travel, the popularity of tourism, public international contacts, and imported goods, Ebola is consid-ered a threat to people around the world. The present study was conducted with the aim of determining the status of epidemiology, pathophysiology, virology, clinical symptoms, diag-nosis, prevention, treatment, and classification of EVD.

Methods:
This systematic review was conducted in the spring of 2024 by searching English articles using desired keywords in PubMed, Google Scholar, ISC, Scopus, and Web of Sci-ence databases without time limits. The search strategy was based on the PRISMA 2020 statement.

Results:
Frequent outbreaks of EVD have caused numerous deaths and complications. Since the virus may lead to a pandemic, its prevention is of great importance due to its high potential to cause a significant physical and economic burden.

Conclusion:
Hence, there is an urgent need to conduct clinical trials on EVD to develop possible treatments and strategies to prevent any further outbreaks of the disease.
Pelvic Hematoma Revealing Chronic Myeloid Leukemia: Case Report of Two Patients
Authors: Kachhwaha Arjun , Baveja Avriti , Dev Rahul , Huda Farhanul , Nath Uttam Kumar 
Published: February 2025

Background:
Chronic myeloid leukemia [CML] is a common hematological malignancy
where patients present with varied clinical symptoms and are usually diagnosed with incidentally
detected elevated total leucocyte counts in hemogram. The presence of pelvic hematoma at the
presentation of CML is an uncommon finding.

Case Presentation:
Two male young adults presented with massive splenomegaly and pelvic hematoma.
On evaluation for anemia and leukocytosis with massive splenomegaly, diagnosis of
CML chronic phase [CML-CP] was made on peripheral smear, bone marrow examination including
cytogenetic study and molecular methods [peripheral blood quantitative BCR: ABL1 by real--
time PCR]. The first patient underwent aspiration of hematoma, and the second patient presented
late where the hematoma organized into a solid mass and no intervention could be possible. A basic
available coagulation study revealed no abnormalities and was managed with tyrosine kinase
inhibitors.

Conclusion:
Initial manifestation of CML with pelvic hematoma is uncommon and should undergo
aspiration or drainage to avoid organization of hematoma and compressive symptoms locally.
Abnormal Elevation of the Expression of Costimulatory Molecule CD226 in Graves' Disease: Two Cross-Sectional Studies
Authors: Huang Zhaowei , Liu Xuerong , Cai Tiantian , Jiang Yanfei , Wu Yuqing , Zhang Xinwei , Song Rong-hua , Zhang Jin an 
Published: February 2025

Objective:
This study aimed to explore the differential expression of the co-stimulatory
molecule CD226 in lymphocytes from patients with New-Onset Graves' Disease (NOGD) and its
correlation with clinical indicators.

Methods:
Sixty-eight participants were recruited for the discovery experiment (NOGD: healthy
control (HC) = 39:29). Peripheral Blood Mononuclear Cells (PBMCs) were isolated. Flow cytometry
was performed to detect CD226 expression on multiple lymphocyte subtypes. CD226 mRNA
expression in PBMCs was detected by qPCR. Fifty-eight participants were recruited for the validation
experiment (NOGD: HC=35:23). CD4+ T cells were isolated, and the level of CD226 mRNA
in CD4+ T cells was detected. Five cases of each of Graves' disease (GD) thyroid and control thyroid
were collected for CD226 immunohistochemical staining.

Results:
CD226 expression was the highest in monocytes (NOGD: 94.1% vs. HC: 94.8%) and the
lowest in CD8+ T cells (NOGD: 65.3% vs. HC: 64.9%). Compared with HC, CD226 expression
on the CD4+ T cells increased in the peripheral blood of NOGD patients and correlated with
TPO-Ab. Meanwhile, CD226 mRNA levels were elevated in CD4+ T cells and positively correlated
with TR-Ab. CD226 expression was significantly increased in the thyroid tissues of GD patients.

Conclusion:
This study demonstrates for the first time the elevated expression of CD226 in CD4+
T cells and thyroid tissue of NOGD. The abnormal elevation of CD226 is correlated with clinical
indicators. It suggests that the co-stimulatory molecule CD226 is involved in the pathogenesis of
GD.
Screening Co-Diagnostic Genes for Lung Adenocarcinoma and Myocardial Infarction and Analysis of the Molecular Functions and Drug Value of the Genes
Authors: Du Nannan , Liang Mengting , Liu Zongjun 
Published: February 2025

Background:
Lung adenocarcinoma (LUAD) is the most common subtype of non-small
cell lung cancer, and myocardial infarction (MI) is an acute cardiovascular disease resulting
from the disruption of coronary blood supply. Recent studies have suggested that these two diseases
may share common molecular mechanisms.

Aim:
The aim of this study was to discover common diagnostic genes for LUAD and MI and analyze
their molecular functions and potential drug values by applying bioinformatics analysis.

Objective:
The objective was to provide a theoretical basis for further research on the pathological
mechanisms of LUAD and MI, contributing to the development of novel diagnostic and therapeutic
strategies for the two diseases.

Methods:
In this study, the datasets of LUAD and MI were obtained from TCGA and GEO
databases, and differential expression analysis was performed to screen significantly differentially
expressed genes (DEGs). Subsequently, disease-related genes were identified using WGCNA analysis,
and the biological functions of these genes were explored by functional enrichment analysis.
After screening key genes using the protein-protein interaction (PPI) network and the cytoHubba
algorithm, biomarkers were determined by LASSO and SVM-RFE machine-learning methods. Finally,
immune infiltration analysis and drug prediction were performed, and biomarker expression
was verified by single-cell sequencing analysis.

Results:
A total of 158 differentially upregulated genes were identified between LUAD and MI.
WGCNA analysis screened 86 genes that were significantly associated with both diseases and
were enriched in an inflammatory response and immune regulation-related pathways, such as the
IL-17 signaling pathway. Ten significant genes were identified by the PPI network and cytoHubba
and then reduced to 4 using LASSO and SVM-RFE. Noticeably, MMP9 was significantly overexpressed
in both diseases. Immune infiltration analysis showed that MMP9 was significantly related
to multiple immune cell infiltration. Drug prediction and molecular docking analysis predicted
Ilomastat and Osthole as the potential target drugs. Single-cell sequencing analysis revealed that
MMP9 was high-expressed in the macrophages in LUAD tissues.

Conclusion:
This study identified MMP9 as a common diagnostic gene and potential therapeutic
target for both LUAD and MI and revealed its role in inflammation and immune regulation
through comprehensive bioinformatics analysis. These findings provided a theoretical basis for further
research on the pathological mechanisms of LUAD and MI, contributing to the development
of novel diagnostic and therapeutic strategies.
Bone Marrow Mesenchymal Stem Cells Overexpressing MicroRNA-126 to Treat Critical Limb Ischemia
Authors: Nammian Pegah , Asadi-Yousefabad Seyedeh-Leili , Daneshi Seyyed Sajad , Fallahi Jafar , Khajeh Sahar , Tabei Seyed Mohammad Bagher , Razban Vahid 
Published: February 2025

Background:
Critical limb ischemia (CLI) is considered the most severe form of peripheral artery disease (PAD). Nowadays, using stem cells such as mesenchymal stem cells (MSCs) to induce angiogenesis seems like a promising method for CLI therapy. Among the many factors that affect the angiogenesis process, microRNA-126 has an important role. Objective: The goal of this study was to increase the angiogenic potential of bone marrow mesenchymal stem cells (BMSCs) via using microRNA-126.

Methods:
BMSCs were isolated from male C57BL/6 inbred mice. CLI model was created by femoral artery ligation on C57BL/6 mice. Animals were allocated to control, BMSCs, miR-126, and BMSCsmiR-126 groups, and a defined number of the cells and virus were injected 24 h after surgery. Then, wound-healing assay, functional tests, real-time PCR, histopathological evaluation, and donor cell survival were performed.

Results:
Results showed that BMSCs and miR-126 groups had a positive effect on angiogenesis. BMSCs miR-126 group had a significant effect on functional improvements, endothelial cell migration, neovascularization, and muscle restructures. In vivo evaluation showed that miR-126 could increase BMSCs survival and paracrine secretion of angiogenic factors such as VEGF and led to remarkable functional improvements and neovascularization in ischemic tissues.

Conclusion:
It can be concluded that the combination uses of BMSCs and miR-126 lead to more effective recovery from ischemic damage compared with using them alone. MiR-126 can be used as a strong modifier to reinforce the angiogenic potential, paracrine secretion, and survival of the BMSCs.
Development and In-Vitro Evaluation of Azithromycin-Enriched Niosomal Gel for the Management of Eczema
Authors: Kapoor Anupriya , Trivedi Manisha , Shukla Neha , Patel Aman Singh 
Published: February 2025

Background:
The goal of the current study was to create Azithromycin-loaded niosomes
and conduct in vitro evaluation for topical eczema management. Eczema is a common dry
skin disorder that causes inflammation and may affect people of any age, mainly in early infancy
ages. Another term for dermatitis is “Derma” which refers to skin, and “dermatitis” “Tis” refers to
inflammation. Both phrases are interchangeably employed. The most prevalent kind of eczema is
atopic eczema, which is also often the most chronic type. Azithromycin is a macrolide antibiotic
that is employed to treat infection of both the lower and upper respiratory tracts. It also has antimicrobial
properties that help in the treatment of skin infections. The topical appeal of AZM-loaded
niosomal gel can probably reduce side effects associated with drug molecules.

Objectives:
The objective of the present study was to formulate and evaluate topical gel with loaded
niosomes for sustained effect that could be beneficial for the treatment of eczema. Creating topical
formulations increases drug absorption, diminishes side effects, and improves patient compliance.

Methods:
AZM-loaded niosomes were prepared by Ether injection method by using Span60 and
Brij30 as a surfactant in a ratio of 2:1:1 along with the combination of Cholesterol.

Results:
After several optimization tests, formulation F3 was found to be the best fit for gel formulation.
According to SEM analysis, the shape of the particles was almost spherical. A Zetasizer
measured the mean diameter of the improved formulation and found it to be 576 nm. The entrapment
efficiency of the formulations was found to be 60-89%. Next, employing Carbopol 940,
which acts as the gelling agent, the improved formulation was added to a gel. An evaluation of the
antibacterial activity of Azithromycin's well-known antimicrobial properties, which are crucial for
managing skin infections associated with eczema, was carried out. The optimized formulation exhibited
a zone of inhibition that was 3 mm smaller than that of the pure drug. In-vitro release experiments
revealed 59% release for eight hours.

Conclusion:
In conclusion, this research successfully developed a topical Azithromycin-loaded
niosomal gel, demonstrating promising results in terms of particle morphology, size, drug release
profile, and antibacterial activity. The optimized formulation, characterized by its controlled release
and potential for reduced side effects, represents a significant advancement in the topical
treatment of eczema. Future studies should focus on further clinical evaluations and potential modifications
to enhance the efficacy and patient acceptability of the formulation.