bluuebunny/crossref_metadata_2025_split huggingface dataset:
ڕۆلی سەربازی یارمحەمەدخانی کرماشانی لە پێشهاتە ناوخۆییەکانی ئێران لەماوەی ساڵانی (1908 - 1912)
Authors: Sadiq Delzar Salih 
Published: October 2024

پوختە

وڵاتی ئێران لەسەرەتای سەدەی بیستەم کۆمەڵێک پێشهاتی ناوخۆیی گرنگ و هەستیاری بەخۆوەبینی، بەجۆرێک کاریگەری لەسەر سەرجەم کایەکانی ژیانی سیاسی و ئابووری و کۆمەڵایەتی ئەو وڵاتە هەبوو، کە بەقۆناغێکی هەستیاری پڕ لەکێشمەکێشی سیاسی تێپەڕی، لەدیارترین ئەو پێشهاتانەش کە لەئەنجامی خەبات و تێکۆشانی شۆڕشگێڕان و ئازادیخوازان لە ئێران کە لەپێناو هێنانەدی ئازادی سیاسی و ژیانێکی دەستووری هەوڵەکانی خۆیان خستبووەگەڕ هاتە بەرهەم، زۆری نەبرد لەساڵی 1908 بەهۆی ململانێی ناوخۆیی لەنێوان شا و ئازادیخوازەکان سەری کێشا بۆ شەڕی ناوخۆیی و تا ساڵی 1912 درێژەی کێشا. گومانی تێدانییە لەم نێوەندەدا کوردەکانیش لە ڕۆژهەڵاتی کوردستان لەپێناو هاتنەکایەی ئازادی سیاسی و ڕادەربڕین و نەهێشتنی جیاوازی نەتەوەیی و چینایەتی و دابینکردنی یەکسانی و دادپەروەری کۆمەڵایەتی لەپاڵ ئازادیخوازانی ئێرانی خەباتیان کردو ژیانی خۆیان کردە قوربانی، لەدیارترین ئەو کەسایەتیانەش یارمحەمەخانی کرماشانی بوو، کە یەكێک لەدیارترین سەرکردە کوردە ئازادیخوازەکانی وڵاتی ئێران بەگشتی و ڕۆژەهەڵاتی کوردستان بەتایبەتی بوو، ناوبراو لەڕیزی سەرکردە هەرە گەورەو ناودارەکانی مێژووی ئێران دێت، کە لەپێناو ئازادی سیاسی و ڕادەربڕین لەوڵاتی ئێران بەگشتی گیانی خۆی بەخشی.
Medicamentos de uso off-label para terapia subcutânea: uma revisão sistemática
Authors: Santos Fernanda Maria Ramos dos , De Paula Danielle Galdino , Antunes Alice Andrade , Barbosa Maria Fernanda 
Published: October 2024

Trata-se de artigo de revisão sistemática que aborda tema relevante para a área da saúde relacionado ao uso da via subcutânea para administração de medicamentos a pacientes de cuidados paliativos. Com a progressão da doença, para tais pacientes, muitas vezes o uso da via endovenosa e até mesmo da via oral, acabam contraindicados. Contudo o uso da via subcutânea constitui-se, na maioria das vezes, uma prática off-label. Consequentemente, com vistas a garantir a eficácia terapêutica e a segurança do paciente, o levantamento de evidências atualizadas para a implementação desta estratégia assistencial no ambiente hospitalar, é fundamental. Desta forma este artigo representa o primeiro passo necessário para a futura elaboração de um guia validado de medicamentos para administração off-label pela via subcutânea, fruto de Mestrado Profissional em curso. Objetivo: O estudo teve como objetivo identificar e analisar evidências sobre medicamentos administrados por via subcutânea para hidratação e controle de dor, náuseas, vômitos e dispneia. Método: Realizou-se uma revisão sistemática da literatura entre 2013 e 2023, utilizando bases de dados como Pubmed, LiLACS, SCIELO e Google. Resultados: Foram analisados qualitativamente 22 artigos científicos e 2 guias de instituições renomadas em Cuidados Paliativos. A administração off-label subcutânea foi considerada segura e eficaz em 77,3% dos estudos, apesar da baixa robustez das evidências. Conclusões: O estudo permitiu a identificação dos medicamentos mais utilizados em cuidados paliativos que são passíveis de administração off-label por via subcutânea. No entanto, destaca-se a necessidade de estabelecimentos de critérios rigorosos para sua utilização devido à precaução indicada pelo nível de evidência, enfatizando a importância de estudos mais consistentes nessa área.
Astaxanthin Is a Novel Candidate for Glioblastoma Treatment? A Review
Authors: Rezaee Arian , Radmanesh Mehrsa , Asghari Atena , Nazari Ahmad , Shahidi Amir Abbas , Chahardehi Amir Modarresi , Arefnezhad Reza , Farkhondeh Tahreh , Saminin Mohammad , Samarghandian Saeed 
Published: October 2024

Abstract:
Glioblastoma (GBM) is a malignant primary brain tumor with a poor prognosis
and high recurrence rates. At present, the current treatments available for GBM patients
can only prolong their overall survival and cannot provide a complete cure. Discovering
an effective therapy against the disease is a challenge due to its recurrence and
resistance to common available treatments for GBM. Several natural products have been
documented to possess the potential to function as anticancer agents through diverse
mechanisms. Astaxanthin (AXT) is an orange-red pigment that is a natural lipophilic
and xanthophyll carotenoid derived mostly from microalgae. Numerous studies have examined
that AXT impacts GBM cells in laboratory settings and animal models. This review
aims to provide the latest information about the potential of astaxanthin as a novel
therapeutic option for GBM. AXT has been targeted more on reactive oxygen species
(ROS), and suppressed tumor growth in vitro and in vivo conditions. The available data
suggests that AXT might serve as a key component in the development of innovative
cancer therapies, especially for glioblastoma.
Role of Ferroptosis in ALD: Focusing on Hepcidin and Besides Hepcidin
Authors: Chen Leijie , Zhou Hejun , Cheng Zongyong , Liu Deliang , Tan Yuyong 
Published: October 2024

Abstract:
Ascending incidence and poor outcomes make Alcoholic Liver Disease
(ALD) a considerable public health concern. This review concluded the iron metabolism
under physiology conditions and alcohol disturbance (leading to ferroptosis in ALD)
and summarized the novel treatment, diagnosis, and prognosis of ferroptosis for ALD.
ALD is characterized by alcohol-induced chronic metabolism disorder, peroxidation damage,
and dysfunction of the anti-oxidant system. Current animal experiments and clinical
studies identified ferroptosis as a new form of regulated cell death involved in ALD.
One strong evidence is that the key iron regulatory hormone, hepcidin, is downgraded in
ALD through NF-κB/IL-6/STAT3, BMP/SMAD, and Jak/STAT3 pathways, which
would impair iron hemostasis and induce ferroptosis in ALD. Also, imbalance
metabolism and other pathological responses in ALD induce and regulate ferroptosis,
which proves ferroptosis participates in the pathophysiology of ALD via oxidative
stress, steatosis, and fibrosis. Inhibition of ferroptosis via regulating hepcidin expression
and metabolism impairment may provide new therapies for ALD.
Astaxanthin Alleviates Chronic Prostatitis via the ERK1/2 Signaling Pathway: Evidence from Network Pharmacology and Experimental Validation
Authors: Liu Yifu , Huang Liang , Zhang Zhicheng , Zhu Qiqi , Xi Ping , Sun Ting , Gong Binbin 
Published: October 2024

Background:
Astaxanthin (AST) has been widely recognized for its therapeutic potential
in chronic inflammatory ailments. This study investigates the therapeutic efficacy and underlying
mechanisms of AST in the management of chronic prostatitis (CP).

Methods:
Male Sprague-Dawley (SD) rats were randomly divided into control, complete
Freund's adjuvant (CFA), and CFA + AST groups. CFA was used to induce the CP model, and
saline was used for the control group. Inflammation of the prostate was detected 28 days after
oral administration of AST. qRT-PCR and ELISA were used to detect pro-inflammatory factors
in RWPE-1 and WPMY-1 cells. Potential targets of AST for CP were explored by network
pharmacology, and related proteins were detected by Western blotting.

objective:
This study investigates the therapeutic efficacy and underlying mechanisms of AST in the management of chronic prostatitis (CP).

Results:
Oral administration of AST alleviated the increase in prostate stroma and reduced inflammatory
cell infiltration in CP rats. The IC50 of AST-treated RWPE-1 and WPMY-1 cells for
48 h were 171 and 212.1 μM, respectively. AST pretreatment reduced IL-6 and IL-8 expression
in these cells. PPI network, GO, and KEGG enrichment analyses suggested that the antiinflammatory
effect of AST was associated with the ERK1/2 pathway. Western blotting showed
that AST inhibited ERK1/2 phosphorylation. In addition, AST and ERK1/2 pathway inhibitors
(U0126) synergistically inhibited LPS-induced inflammation in prostate cells.

Conclusion:
Our study identified the potential of AST in the treatment of CP. However, subsequent
randomized controlled trials are needed to validate its clinical efficacy.
Anthelmintic Activity of Carica papaya Leaf Extracts: Insights from In Vitro and In Silico Investigations
Authors: Alhaiqi Nawal S. , Afifi Sherine M. , Mahyoub Jazem A. , Abdel-Gaber Rewaida A. , Delic Denis , Dkhil Mohamed A. 
Published: October 2024

Introduction:
Helminthiasis remains a major global health concern. Exploring natural
alternatives due to drug resistance and synthetic drug side effects has become increasingly urgent.

Method:
This study investigates the anthelmintic potential of Carica papaya leaf extracts
(CPLE) against Allolobophora caliginosa, along with elucidating the underlying structural alterations
and molecular interactions. Carica papaya underwent methanolic extraction. Gas chromatography-
mass spectrometry analysis revealed 11 active phytochemical compounds within
CPLE. The anthelmintic activity was evaluated against A. caliginosa, with CPLE demonstrating
efficacy comparable to albendazole. Light microscopy and scanning electron microscopy depicted
structural modifications in worms exposed to CPLE, characterized by reduced size, uniform
shrinkage, and increased cuticle thickness.

Result:
Molecular docking studies with proteins Ascaris lumbricoides β-tubulin and Trichuris
trichiura β-tubulin revealed potential binding interactions of CPLE compounds, notably Hexadecanoic
acid, 2-hydroxy-1-(hydroxymethyl) ethyl ester, and Albendazole oxide.

Conclusión:
These findings suggest the anthelmintic efficacy of CPLE and provide insights into
its mode of action at the molecular level.
Potentiation of Tumor Hallmarks by the Loss of GULO, a Vitamin C Biosynthesis Gene in Humans
Authors: Sekar Gopinath , Bahot Anjali , Bansode Mahima , Phadnis Anushka , Sarode Sachin C , Sharma Nilesh Kumar 
Published: October 2024

Abstract:
Vitamin C plays a significant role in various physiological functions. Humans
depend on external sources of vitamin C due to the loss of the L-gulono-γ-lactone
oxidase (GULO) gene that contributes to the synthesis of vitamin C. During the
evolutionary loss of the GULO gene, physical, chemical, and biological factors were
different from the present environmental settings. Besides the evolutionary genetic
loss of the GULO gene, there is a gap in the insightful discussion on the potential
implications of the non-functional GULO gene towards the predisposition of humans to
cancer that faces hostile and carcinogenic environments. Various methods by which
vitamin C modulates cellular processes related to cancer, including DNA repair,
epigenetic changes, and redox balance, are discussed. Furthermore, we present
experimental and clinical evidence indicating that vitamin C deficiency promotes tumor
growth, metastasis, and therapy resistance, emphasizing its potential as a cancer
phenotypic modulator. Therapeutic implications of restoring vitamin C levels in cancer
treatment range from improving the efficacy of conventional medicines to exploiting
metabolic vulnerabilities in tumors. The relevance of assessing vitamin C status in
cancer patients and the basis for additional research into vitamin C supplementation
as an adjuvant therapy is emphasized. This paper presents a comprehensive overview
of the implications associated with the functional deficiency of the GULO gene in
human subjects exhibiting diverse tumor hallmarks, encompassing ECM remodeling,
hypoxia, epigenetic reprogramming, oxidative stress, and drug responsiveness.
Alleviation of Tumor Invasion by the Development of Natural Polymerbased Low-risk Chemotherapeutic Systems – review on the Malignant
Carcinoma Treatments
Authors: Natarajan Vignesh 
Published: October 2024

Introduction/Objective:
The spread of tumors (48% in men and 51% in women), as well
as the protection of malignant tumors by stromal cells and complex blood vessels, pose significant
challenges to drug delivery to tumors. Modern chemotherapy, on the other hand, addresses tumor
growth suppression by at least 60% through versatile formulation systems and numerous modifications
to drug delivery systems. The renewable and naturally occurring polymers present invariably in
all living cells form the fundamental foundation for most anticancer drug development. The review
aims to discuss in detail the preparations of polysaccharide, lipid, and protein-based drug-loading
vehicles for the targeted delivery of prominent anticancer drugs. It also provides an explanation of
drug distribution in blood (cumulative releases of nearly 80% drug) and drug accumulation at tumor
sites (1–5 mg/kg) due to enhanced permeability and retention (EPR).

Methods:
Specific delivery examples for treating colorectal and breast carcinomas have been presented
to distinguish the varied drug administration, bioavailability, and tumor internalization mechanisms
between sugar, fatty acid, and amino acid polymers. Current therapy possibilities based on
cutting-edge literature are provided, along with drug delivery systems tailored to tumor location and
invasive properties.

Results:
The unique combinations of the three natural polymers provide unparalleled solutions to
minimize the toxicity (<20% drug release) of the chemotherapeutic drugs on normal tissues. Moreover,
the development of a consolidated drug delivery system has contributed to a substantial reduction
(dose reduction from 10.43 μM to 1.9 μM) in the undesirable consequences of higher dosages of
chemotherapeutic drugs.

Conclusion:
The review extensively covers safe chemotherapeutic systems with significant advantages
(tumor volume shrinkage of 4T1 cells from 1000 mm3 to 200 mm3) in clinical applications
of carcinoma treatments using natural polymers.
Identification of PANoptosis Subtypes to Assess the Prognosis and Immune Microenvironment of Lung Adenocarcinoma Patients: A Bioinformatics Combined Machine Learning Study
Authors: Zhou Xiaofeng , Wang Bolin , Wu Di , Gao Lu , Wan Zhihua , Wu Ruifeng 
Published: October 2024

Background:
PANoptosis, a novelty mechanism of cell death involving crosstalk between apoptosis, pyroptosis, and necroptosis, is strongly associated with tumor cell death and immunotherapy efficacy. However, its relevance in lung adenocarcinoma (LUAD) remains to be elucidated.

Methods:
In this study, we acquired 18 PANoptosis-related differentially expressed gene (PRDEG) of LUAD. Based on these genes, LUAD samples were identified with different sub-types by unsupervised clustering. Next, we compared the differences between the subtypes, including clinical features, immune microenvironment, and potentially sensitive drugs. Further-more, we used machine learning to identify hub prognostic PRDEGs, construct a risk score, and validate it on other external datasets. We incorporated the patient's clinical information and risk score into the proportional hazards model and lasso-cox models to find key prognostic features and constructed five prognostic models. The best model was identified via the area under the curve and validated on an external dataset.

Results:
LUAD patients were divided into two clusters named C1 and C2, respectively. The C2 cluster exhibited shorter survival time, more advanced tumor stage, higher suppressive immune cell scores, such as dendritic cells, and higher expression of inhibitory immune checkpoints, such as LAG3 and CD86. TIMP1, CAV1, and CD69 were recognized as key prognostic factors, and risk scores predicted survival with significant differences in the external validation set. Risk score and N-stage were identified as critical prognostic features. The Coxph model outper-formed other machine learning clinical models. The 1-, 3-, and 5-year time-ROCs in the exter-nal validation set were 0.55, 0.59, and 0.60, respectively.

Conclusion:
We demonstrated the potential of PANoptosis-based molecular clustering and prognostic features in predicting the survival of patients with LUAD as well as the tumor mi-croenvironment.
Determination of FGFR1 Functions in Cytarabine Treatment of Acute Myeloid Leukemia Through Bioinformatics Analysis
Authors: Misir Sema , Yaman Serap Ozer , Aykac Okan , Akidan Osman , Merde Irem Bozbey , Hepokur Ceylan 
Published: October 2024

Aim:
Among the most prevalent subtypes of acute leukemia is acute myeloid leukemia
(LAML). Consequently, it is essential to understand the molecular causes of LAML and find its
predictive and diagnostic biomarkers. The aim of this study is to determine the molecular functions
of fibroblast growth factor receptor 1(FGFR1) involved in LAML pathogenesis and its potential
therapeutic effect for AML treatment.

Methods:
The molecular docking interaction of the Cytarabine with its target FGFR1 was examined.
The Gene Expression Profiling Interactive Analysis, version 2 (GEPIA2), and UALCAN
tools database were used to obtain the LAML gene expression datasets. Gene functional annotation
was performed to investigate the DEGs' possible role. Using the Interactive Gene database retrieval
tool (STRING) and a few chosen hub modules from the GeneMANIA database, the protein-
protein interaction (PPI) network were constructed. A survival analysis was performed on the
effects of hub genes on the overall survival of LAML patients.

Results:
As a result of docking, a strong interaction was observed between cytarabine and
FGFR1. It has been discovered that cytarabine can reverse FGFR1 expression. The survival study
results showed an association between the prognosis of AML patients and one of the central
genes, FGFR1.

Conclusion:
The expression profile and functions of FGFR1 were determined in LAML patients.
It has been shown that FGFR1 can be a viable therapeutic target for LAML and a possible biomarker
for diagnosis.
Cucurbitacin-E; Curvularia lunata Secondary Metabolite as a BRCA 1 and 2 Regulator in Mice Associated Breast Cancer
Authors: Abd El-Mongy Mahmoud , Hussein Mohammed Abdalla , EL-Sayed Nooran T. , Salah Ahmed , Roshdy Tamer 
Published: October 2024

Background:
Cucurbitacin-induced apoptosis and inhibition of cell growth can render
several cancers ineffective. The microbial transformation of cucurbitacin-E-glucoside to cucurbitacin-
E was carried out by Curvularia lunata (NRRL 2178). Moreover, in vitro anticancer activity
against the MCF-7 cell line as well as in vivo anticancer activity against dimethylbenz (a)
anthracene (DMBA)-induced breast cancer in mice using cucurbitacin-E was evaluated.

Methods:
The cucurbitacin-E-glucoside was biotransformed by Curvularia lunata to cucurbitacin-
E, and the isolated compound was tested in vitro against the MCF-7 cell line, and its IC50 was
calculated. LD50 of cucurbitacin-E was estimated in mice, and its protective activity against
DMBA-induced cancer in mice was studied. Breast cancer induction was done by a single-dose
subcutaneous administration of DMBA (50 mg). Plasma ALT, AST, ALP, and LDH, as well as
GSH, SOD, GPx, MDA, TNF-α, IL-6, and tumor suppressor P53 assays, were used to assess cucurbitacin-
E's capacity to protect the liver and breast against DMBA-induced toxicity. Moreover,
by assessing the gene expression of tumor suppressor genes (BRCA 1 and 2) and conducting histopathological
analysis, the suppressive effect of cucurbitacin-E was examined.

Results:
The IC50 value of cucurbitacin-E against MCF-7 cell lines equals 72.15 ± 0.64 μg/ml.
LD50 of cucurbitacin-E given orally in adult mice is equal to 1200 mg/kg b.w. The levels of
plasma ALT, AST, ALP, and LDH were decreased significantly in DMBA-treated mice when
administered with cucurbitacin-E at 1/50 LD50 (24 mg/kg/b.w.) and 1/20 LD50 (60 mg/kg/b.w.).
In breast tissue, the levels of GSH, SOD, GPx, and P53 were significantly increased, as were decreased
levels of TNF-α, IL-6, P53, and MDA. Conversely, there was a downregulation in the
mRNA expression levels of BRCA1 and BRCA2. The histopathological analysis revealed that
cucurbitacin-E management improved the tissue architecture of breast tumors.

Conclusions:
These findings demonstrate the ability of cucurbitacin-E to inhibit cancer cells in
the rat breast by controlling oxidative stress and inflammatory biomarkers, as well as downregulating
the mRNA expression levels of BRCA1 and BRCA2.
Design, Synthesis, and Study of Novel Memantine Schiff Base Derivatives Against Targeted Enzymes in Alzheimer’s Disease
Authors: K Girija , E Logesh , P Sowmiya , Krishnamurthy Sairam , T.A Gajendra 
Published: October 2024

Introduction:
According to WHO, Alzheimer’s disease was estimated at 74.4 million
cases in 2023, which will increase by 152.8 million cases in 2050. The therapeutic options available
in the market for the treatment of AD are only capable of reducing the symptoms of dementia
but not preventing progressive degeneration. Memantine is a non-competitive NMDAR antagonist
used for the treatment of patients with moderate-to-severe AD, but it has a high toxicity profile.
To counter this, the Memantine Schiff base derivatives were designed as simple and lowtoxicity
compounds.

Materials and Methods:
Molecular docking was performed against the targeted enzymes Acetylcholinesterase
and Butyrylcholinesterase using AUTODOCK 1.5.7 software. A series of novel
Memantine derivatives of Schiff base were synthesized by condensing Memantine with various
aryl aldehydes and screened for their invitro-cholinesterase inhibitory activity towards Acetylcholinesterase
(AChE) and Butyrylcholinesterase (BChE) by Ellman’s method.

Results and Discussion:
Among the designed compounds, compounds LMV and LMC showed
maximum binding scores of -10.35 kcal/mol and -10.12 kcal/mol, respectively, than the standard
Donepezil (-8.78 kcal/mol) against Acetylcholinesterase. The compounds LMONB and LMDMB
produced significant binding scores of -9.31 kcal/mol and -9.11 kcal/mol, respectively, compared
to the standard Donepezil (-7.57 kcal/mol) against Butyrylcholinesterase. Also, compounds LMV
(30.9 ± 2.13 μM) and LMDMB (13.51 ± 1.12 μM) showed potent inhibitory activity against the
AChE and BChE. These compounds possess drug-like characteristics and are also capable of
crossing the Blood Brain Barrier (BBB).

Conclusion:
The studied compounds LMV and LMDMB, being non-toxic, obey Lipinski’s rule
of 5 and are potential inhibitors against targeted enzymes, which may be promising clinical candidates
for treating Alzheimer’s disease.
A Method to Determine Metoclopramide Hydrochloride in Oral Dosage Forms by Micellar Liquid Chromatography
Authors: García Ferrer Daniel , Peris-Vicente Juan , Durgbanshi Abhilasha , Bose Devashish , Carda-Broch Samuel 
Published: October 2024

Background:
Metoclopramide is a widely prescribed antiemetic drug. Its analysis in
pharmaceutical formulations often involves procedures using high amounts of toxic chemicals.

Objective:
A method based on micellar liquid chromatography to determine metoclopramide hydrochloride
in several oral dosage forms has been developed.

Methods:
The drug was resolved from matrix compounds within 6 min using a C18 column with
isocratic elution at 1 mL/min utilizing a solution of 0.10 mol/L sodium dodecyl sulfate – 6 % 1-
pentanol phosphate buffered at pH 7 as mobile phase, and detection by absorbance at 210 nm. Samples
were dissolved or diluted in the mobile phase and directly injected; thus, only one solution had
to be prepared for the entire procedure. Besides, it contained mainly harmless chemicals and a minimal
amount of organic solvent. Results The procedure was validated by the International Council of
Harmonization guidelines and the results were: specificity, calibration range (0.5 – 5.0 mg/L), linearity
(r2 > 0.9990), trueness (98.1 – 100.3 %), precision (< 0.7%), robustness, carry-over effect, and
system suitability. It was used to analyze commercial samples. Otherwise, it was found the influence
of the surfactant on elution strength was nearly three times stronger than that of 1-pentanol.

Conclusion:
The procedure was reliable, easy-to-conduct, safe, eco-friendly, short-time, widely
available and highly sample-throughput, and then useful for routine analysis of metoclopramidebased
dosage forms in pharmaceutical quality control.