bluuebunny/crossref_metadata_2025_split huggingface dataset:
Ring Closure Reactions for the Synthesis of Cyclic Imines: An Analysis
from the 12 Principles of Green Chemistry and Circular Chemistry
Authors: Quiroga Diego , Borrego-Muñoz Paola , Coy-Barrera Ericsson 
Published: May 2022

Abstract:
Compounds containing a C=N moiety, namely imines, have been widely used for industrial purposes due to their various biological activities. Cyclic imines are an essential class of nitrogen-based heterocycles and valuable scaffolds for designing and obtaining new biologically active compounds. However, the proposal and implementation of synthetic methods for this heterocyclic system are mainly conditioned by different structural and stereoelectronic considerations. Therefore, it can be complex and sometimes limited to a selected group of heterocyclic compounds. The following review paper is structured to search and collect different synthesis methods of cyclic imines and identify the main progress currently achieved. It addresses this topic using structural considerations, physical properties, and reactivity. The synthesis methods described below have implemented strategies based on cyclo-condensation reactions, radical cyclizations, electrocyclic closures, and carbon-carbon coupling by metal-organic catalysis. These methods have significantly contributed significantly to organic chemistry knowledge. In addition, an analysis of such synthesis methods from applying the principles of green and circular chemistry is presented, evaluating the potential application of these methods, limitations, perspectives, and their impact on the environment.
Recent Updates on Folate Targeted Drug Delivery Systems in Cancer: A Mini Review
Authors: Bisht Gopal Singh , Sharma Deepika , Sharma Manu 
Published: May 2022

Abstract:Targeted drug delivery systems that selectively deliver anticancer drugs to tumour cells have always been a field of interest in reducing side effects associated with chemotherapy in cancer patients. Cancer cells require nutrients for their multiplication; folic acid is one such nutrient. The expression of folate receptors is negligible in normal cells, whereas they are overexpressed in a variety of cancer cells. A number of studies have shown that selective targeting of folate receptors in cancer is a beneficial approach, as folate targeted anticancer conjugates are selective towards cancer cells, thereby sparing non-cancerous cells. In this review, we have discussed folate receptor, folic acid as a cancer targeting moiety, different folate targeted anticancer drug conjugates, and different folate conjugated nanodelivery systems. This summarized information may turn out to be valuable for researchers to design novel folate targeted anticancer drug delivery systems that can potentially reduce the drawbacks associated with conventional cancer therapeutics.
Update on Etiology and Pathogenesis of Biliary Atresia
Authors: dos Santos Jorge Luiz , Quelhas Patrícia , Cerski Carlos 
Published: May 2022

Abstract:
Biliary atresia is a rare inflammatory sclerosing obstructive cholangiopathy that initiates
in infancy as complete choledochal blockage and progresses to the involvement of intrahepatic biliary
epithelium. Growing evidence shows that biliary atresia is not a single entity with a single etiology
but a phenotype resulting from multifactorial events whose common path is obliterative cholangiopathy.
The etiology of biliary atresia has been explained as resulting from genetic variants,
toxins, viral infection, chronic inflammation or bile duct lesions mediated by autoimmunity, abnormalities
in the development of the bile ducts, and defects in embryogenesis, abnormal fetal or prenatal
circulation and susceptibility factors. It is increasingly evident that the genetic and epigenetic
predisposition combined with the environmental factors to which the mother is exposed are potential
triggers for biliary atresia. There is also an indication that a progressive thickening of the arterial
middle layer occurs in this disease, suggestive of vascular remodeling and disappearance of the interlobular
bile ducts. It is suggested that the hypoxia/ischemia process can affect portal structures in
biliary atresia and is associated with both the extent of biliary proliferation and the thickening of the
medial layer.
Structure-Activity Relationships of Pyrimidine Derivatives and their
Biological Activity - A Review
Authors: Anthoni Samy Helina Navis , Natarajan Ramalakshmi , Sivaperuman Amuthalakshmi , Subramani Arunkumar 
Published: May 2022

Background:
Heterocycles play a major role in many fields of biochemical and physiological
such as amino acids, DNA bases, vitamins, endogenous neurotransmitters, etc. Nitrogencontaining
heterocyclic compounds play a vital role in medicinal chemistry and exhibit notable biological
and pharmacological activities. In the past two decades, scientists focused more on the diverse
biological activities of pyrimidine derivatives. Pyrimidine is a six-membered heterocyclic
compound, and it is present naturally in nucleic acid components (uracil, thymine, and cytosine) and
vitamin B1; it is a promising lead molecule for synthesising compounds with various substitutions to
treat various diseases.

Objective:
We focused on the structure-activity relationship of pyrimidine derivatives and its various
biological activities reported from 2010 to date.

Results:
From this review, we concluded that the position of substituents in the pyrimidine nucleus
greatly influences biological activities. Thus, the pyrimidine nucleus showed anti-microbial, anticancer,
anti-inflammatory, anti-tubercular, anti-convulsant, antihypertensive, anthelmintic, antidepressant,
analgesic, anti-hyperglycemic activities, etc.

Conclusion:
This study provides an overview of the pyrimidine nucleus and its derivatives from
2010 to date. There is a future scope for identifying a lead molecule for the target biological activity.
Synthesis and Potential Antidiabetic Properties of Curcumin-Based
Derivatives: An In Vitro and In Silico Study of α-Glucosidase and
α-Amylase Inhibition
Authors: Adibi Hadi , Khodarahmi Reza , Ezati Mohammad , Ghavamipour Fahimeh , Khosravi Narges , Sajedi Reza H. , Chalabi Maryam , Farokhi Alireza 
Published: May 2022

Background:
Over the past twenty years, the prevalence of diabetes as one of the most
common metabolic diseases has become a public health problem worldwide. Blood glucose control is
important in delaying the onset and progression of diabetes-related complications. α-Glycosidase (α-
Glu) and α-amylase (α-Amy) are important enzymes in glucose metabolism. Diabetic control through
the inhibition of carbohydrate hydrolyzing enzymes is established as an effective strategy.

Methods:
In this study, curcumin-based benzaldehyde derivatives with high stability, bioavailability,
and favorable efficiency were synthesized.

Results:
The results showed that L13, L8, and L11 derivatives have the highest inhibitory effect on
α-Glu with IC50 values of 18.65, 20.6, and 31.7 μM and, also L11, L13, and L8 derivatives have the
highest inhibitory effect on α-Amy with IC50 value of 14.8, 21.8, and 44.9 μM respectively. Furthermore,
enzyme inhibitory kinetic characterization was also performed to understand the mechanism of
enzyme inhibition.

Conclusion:
L13, compared to the other compounds, exhibited acceptable inhibitory activity against
both enzymes. The L13 derivative could be an appropriate candidate for further study through the
rational drug design to the exploration of a new class of powerful anti-diabetic drugs considering the
antioxidant properties of the synthesized compounds. The derivative helps reduce the glycemic index
and limits the activity of the major reactive oxygen species (ROS) producing pathways.
In vivo, in vitro and Molecular Modelling Analysis of Isoquercetin, Roseoside, Coreximine, Anonaine, and Arianacin Molecules
Authors: Azarkan Serap Yalcin , Ata Fatma Kübra , Ercan Fahriye 
Published: May 2022

Background:Annona muricata is a member of the Annonaceae family. This plant has a high concentration of acetogenin, which gives it excellent therapeutic property. Researchers have tested this miraculous herb in breast cancer cells treatment and observed that it could be a source of anti-cancer agents. The proposed study focused on screening the anticancer biological activity of Annona muricata plant by using the in vitro, in vivo, and in silico methods.Methods:In in vitro analysis, the IC50 was determined on two-dimensional and three-dimensional breast cancer cells. 2D cells were cultured on flat dishes typically made of plastic, while 3D cells were cultured using the hanging drop method. In in vivo analysis, Drosophila melanogaster was preferred, and the LC50 was determined. In in silico analysis, molecular docking studies have been carried out on the different classes of Annona muricata acetogenins against the target proteins. Nearly, five acetogenins were selected from the literature, and docking was performed against human Bcl-2, Bad and Akt-1 proteins.Results:In vitro and in vivo results revealed the IC50 value of 2D MDA-MB-231 cells as 330 μg.mℓ-1, of 2D MCF-7 cells as290 μg.mℓ-1, and of 3D MCF-7 and MDA-MB-231 cells about 0.005 g.mℓ-1; the LC50 value of Drosophila melanogaster was determined as 0.1 g.mℓ-1. In silico results revealed that the docked complex formed by Isoquercetin showed better binding affinity towards target proteins.Conclusion:As a result of the analysis, the Annona muricata plant has been observed to be effective against cancer and likely to be a potential drug.
Removal of Cd (II) Ions from Water Solutions Using Dispersive Solid-Phase
Extraction Method with 2-aminopyridine/graphene Oxide Nano-Plates
Authors: Abniki Milad , Moghimi Ali 
Published: May 2022

Background:
The effluent release containing heavy metals as Cd (II) ions has drastic risks to both the natural environment and human health. In this research, a novel nano sorbent from the pyridine derivative was prepared for dispersive solid-phase extraction of Cd (II) ions.

Methods:
Graphene oxide (GrO) was chemically modified by a 2-aminopyridine group (2Ap) through a multistep procedure. The affection of adsorbent amount, pH, temperature, equilibrium time on its sorption with Gr2Ap adsorbent was studied and Gr2Ap adsorbent displayed a high ability to adsorb Cd (II) at pH=6. Furthermore, to inquire about the adsorption isotherms of metal ions sorption mechanism, the model of Freundlich and Langmuir was fitted to empirical isotherm data. Besides, to inspect the basic process of the metal sorption mechanism pseudo-first and second-order kinetic, and Roginsky-Zeldovich types were compatible with adsorption kinetic results.

Results:
The concentration factor and limit of detection for Cd (II) were 12.5 and 1.84 µg/L, respectively. According to the value of the correlation coefficient factor, that the Gr2Ap adsorbent exhibits the highest ability to adsorb Cd (II) ions (22.54 mg/g) at pH=6. The pseudo-second-order pattern of Cd (II) adsorption fits best with the kinetic result.

Conclusion:
The Gr2Ap exhibited a high potential for removing the heavy metal ions from aqueous samples. Besides, the current research was shown an efficient, easy, inexpensive, and selectable method for evaluating the Cd (II) ions in several samples of water and wastewater.
Comparative Real Life Egyptian Experience of the Combination of Sofosbuvir
Plus Daclatasvir or Simeprevir for 12 Weeks in Naïve Cirrhotic Patients
Infected with HCV Genotype 4
Authors: A. Wahsh Engy , Ahmed Sayed , Hassan Essam , Gomaa Ahmed , Esamat Gamal , Ramadan Ahmed , Ahmed Manar , Elsayed Aya 
Published: May 2022

Background:
Chronic infection with HCV is progressive worldwide health problem and
the core reason for liver cirrhosis, portal hypertension, or hepatocellular carcinoma. HCV-G4 represents
the most common threat to transplantation of the liver in Egypt. New interferon-free regimens
have been started consuming direct-acting antiviral oral tablets for HCV cure.

Objectives:
In the current study, comparing the safety and efficacy of DAAs combination regimens
including sofosbuvir with daclatasvir or sofosbuvir with simeprevir plus ribavirin for naïve cirrhotic
Egyptian patients infected with HCV-G4 was our main goal.

Methods:
We recruited 150 naïve cirrhotic HCV patients from the Tropical patients’ clinic at Fayoum
General Hospital. They were classified randomly into two groups, group one (n=75 patients)
were administrated Sofosbuvir plus simeprevir (400 mg and 150 mg once daily respectively ) for
twelve weeks, and group two (n=75 patients) were administrated Sofosbuvir plus Daclatasvir (400
mg and 60 mg once daily respectively) with ribavirin (1-1.2 gm daily weight-based) for twelve
weeks. Clinical follow-up, laboratory investigations, and viral PCR were measured to detect treatment
efficacy, safety, and any adverse events.

Results:
Sustained virological response rates (SVR12) were 92%and 90.7% in the first and second
groups, respectively. The major unfavorable events were fatigue, arthralgia, and weight loss without
statistically meaningful differences between study groups. However, anemia and headache
were significantly widespread in the second group (P=0.0161 and 0.0495, respectively). We observed
four patients with photosensitivity in group I and not observed in the second group.

Conclusions:
The current study revealed that DAAs are safe and effective in the cure of naïve cirrhotic
patients chronically infected by HCV-G4 with better results in those treated with sofosbuvir
plus simeprevir regimen.
Berbamine Exerts an Anti-oncogenic Effect on Pancreatic Cancer by Regulating Wnt
and DNA Damage-related Pathways
Authors: Chen Gang , Hu Bingren , Yang Yingnan , Tu Jinfu , Cai Huajie , Yang Shouzhang , Chen Xinwei 
Published: May 2022

Objective:
This study aimed to determine the effects of berbamine on pancreatic cancer as well as the underlying
mechanisms.

Methods:
The pancreatic cancer cells were treated with different concentrations of berbamine and then subjected to
cell viability assay, colony formation assay, cell cycle analysis, and apoptosis detection. Western blotting and immunofluorescence
analyses were performed to investigate the mechanisms underlying the biological effects of berbamine on
the pancreatic cancer cells. Furthermore, the in vivo anti-pancreatic cancer effect of berbamine was examined using a
mouse xenograft model.

Results:
Berbamine significantly inhibited the proliferation and colony-forming ability of BxPC3 and PANC-1 pancreatic
cancer cells while inducing a cell cycle arrest and apoptosis. Moreover, berbamine decreased the expression of β-
catenin and phosphorylation of GSK3β but increased the expression of γ-H2AX and 53BP1. Meanwhile, in vivo studies
revealed that berbamine attenuated the growth of xenograft tumors derived from PANC-1 cells. Notably, berbamine
treatment led to an increase in the expression of Cleaved Caspase 3 and γ-H2AX, as well as a decrease in the expression
of Ki-67 and β-catenin in the tumor xenografts.

Conclusion:
Berbamine exerts an anti-pancreatic cancer effect, possibly by regulating Wnt and DNA damage-related
pathways, suggestive of its therapeutic potential for pancreatic cancer.
On the Regulation of NF-κB Pathway by HPV Oncoproteins: Are Pathway Inhibitors
a Good Alternative for the Treatment of Cervical Cancer?
Authors: Jave-Suárez Luis F. , Garcia-Becerra Natalia , Aguilar-Lemarroy Adriana 
Published: May 2022

Abstract:
Cervical Cancer (CC) is one of the most prevalent cancer-related pathologies in the female population. It is considered the second leading cause of cancer-related deaths in developing countries. The most important etiological factor for the development of CC is the persistent infection with high-risk human papillomavirus. HPV-oncoproteins have evolved to modulate cellular mechanisms to permit viral replication and the generation of new infectious viral particles. When the viral infection persists, there is an uncontrolled viral protein expression essential to commence and maintain the transformation of infected cells. Different cell pathways are affected during the transformation stage, including the NF-κB signaling pathway. NF-κB controls different cellular mechanisms, and its role is critical for various processes such as immunity, inflammation, cell differentiation, growth, and survival. NF-κB plays a double role in the development of CC. Evidence suggests that in the early stages of viral infection, the NF-κB activity impairs viral transcription and is beneficial to avoid cellular immortalization. However, in the advanced stages of cervical carcinogenesis, the activation of the NF-κB correlates with poor prognosis. Here we show and discuss some aspects of NF-κB activity during the development of CC and the use of NF-κB inhibitors to treat this pathology.
Effect of Pulicaria mauritanica on Glucose Metabolism and Glycogen
Content in Streptozotocin-Induced Diabetic Rats
Authors: Eddouks Mohamed , Azzane Amine , Amssayef Ayoub , El-Haidani Ahmed 
Published: May 2022

Aims:
The study aimed to assess the antihyperglycemic activity of Pulicaria mauritanica.

Background:
Pulicaria mauritanica is a medicinal and aromatic plant used for the treatment of many diseases such as inflammation, diabetes, and intestinal disorders.

Objective:
The main goals of this present paper were to confirm the antihyperglycemic capacity of aqueous extract from Pulicaria mauritanica in normoglycemic and diabetic rats over a period of time (7 days of treatment).

Methods:
The effect of the aqueous extract of Pulicaria mauritanica from aerial parts (AEPM) on glucose and lipid metabolism was tested using an acute test (single dose during 6 hours) and sub-chronic assay (repeated oral administration for seven days) at a dose of 60 mg/kg, the serum glucose levels were measured in normoglycemic and streptozotocin(STZ)-induced diabetic rats. In addition, the glycogen content in the liver, extensor digitorum longus (EDL), and soleus was evaluated. The antioxidant activity, phytochemical screening, and quantification of some secondary metabolites of this extract were also performed.

Results:
AEPM at a dose of 60 mg/kg reduced the plasma glucose concentrations significantly in STZ-induced diabetic rats after a single oral administration (p<0.05), this lowering effect became more significant during the repeated oral administration in hyperglycemic rats (p<0.0001). Also, the findings showed that this plant exhibited a significant increase in liver and skeletal soleus muscle glycogen content in diabetic rats. AEPM revealed a remarkable antioxidant activity in addition to the presence of polyphenol compounds such as flavonoids, tannins, saponins, sterols, glucides, terpenoids, quinones, anthraquinones, and mucilage.

Conclusion:
The study shows that AEPM exhibits antihyperglycemic activity in diabetic rats and it increases liver and muscle glycogen content.
The Role of Human Platelet-rich Plasma to Enhance the Differentiation of
Adipose-derived Mesenchymal Stem Cells into Cardiomyocyte: An Experimental
Study
Authors: Suryawan I.Gde Rurus , Andrianto  , Anggaraeni Arifta Devi , Agita Arisya , Nugraha Ricardo Adrian 
Published: May 2022

Background:
Several studies showed that Adipose derived mesenchymal stem cells (AMSCs) can differentiate into mesenchymal lineages, including cardiac cell types, but complete differentiation into cardiomyocytes is challenging. . Unfortunately, the optimal method to maximize AMSCs differentiation has not yet established. Platelet rich plasma (PRP) which contains rich growth factors, is believed could stimulate stem cell proliferation and differentiation in the context of cardiac tissue regeneration.

Objective:
To analyze the effect of PRP administration to enhance the differentiation of AMSCs into cardiomyocytes.

Methods:
This study used a randomized post-test-only controlled group design. AMSCs were isolated
from adipose tissues and cultured for 4 passages. The samples were divided into 3 groups, a
negative control group (α-MEM), a positive control group (differentiation medium), and a treatment
group (PRP). The assessment of GATA-4 expression was conducted using flow cytometry on
day-5. The assessment of troponin expression was conducted using immunocytochemistry on day-
10. Data analysis was conducted using T-test and One-Way ANOVA.

Results:
Results: Flowcytometry of GATA-4 expression revealed a significant improvement in PRP group compared to negative and positive control group (67.04 ± 4.49 vs 58.15 ± 1.23 p < 0.05; 67.04  4.49 vs 52.96 ± 2.02 p < 0.05). This was supported by the results of immunocytochemistry on troponin expression, which revealed significant improvement in the PRP group compared to negative and positive controls (38.13 ± 5.2 vs 10.73 ± 2.39 p < 0.05; 38.13  5.2 vs 26.00  0.4 p < 0.05).

Conclusion:
PRP administration in the AMSCs culture could significantly improve the differentiation of AMSCs into cardiomyocytes measured by GATA-4 and troponin expressions. This was concordant with our hypothesis, which stated that there was an effect of PRP administration on AMSCs differentiation into cardiomyocytes.
Genetic Markers as Predictors for Response to Treatment and Possible
Therapeutic Targets in Medulloblastoma
Authors: Torres-Espíndola Luz-María , Pérez-Pineda Perla-Lidia , Ortiz-Butrón Rocío , Pérez-De Marcos Juan-Carlos , Hernández-Regino Laura M. , Zapata-Tarrés Marta-Margarita 
Published: May 2022

Background:
Medulloblastomas (MB) are the most common malignant brain tumors in the
pediatric age. In 2021, WHO categorized medulloblastomas into two groups: molecularly defined and
histologically defined medulloblastomas. Molecularly defined medulloblastomas are divided into WNTactivated
medulloblastoma, SHH-activated and TP53-wildtype medulloblastoma, SHH-activated, and
TP53-mutant and non-WNT/non-SHH medulloblastoma, which include Group 3 (MYC) and Group 4
(CDK6 and MYCN). In this paper, we will focus on molecularly defined medulloblastomas.

Objective:
This paper aims to review the literature in order to describe the molecular structure of the
medulloblastoma groups and to emphasize the importance of genetic predictors in medulloblastoma
that can be used in clinical practice, either as a prognostic tool or as a therapeutic target in the future.

Results:
Each molecular subtype of medulloblastoma presents a different prognosis, and the molecular
subtype with the best prognosis is medulloblastoma-activated WNT. It has even been observed that a
reduction in the intensity of the combined treatment does not modify the prognosis of the patients, resulting
in even fewer adverse effects due to the treatment. On the other hand, it was observed that the
subtypes with the worst prognosis are medulloblastomas with activated MYC and medulloblastomas with
activated SHH and mutated TP53, due to their high capacity to metastasize or to their radio-resistance.
However, a new target therapy has emerged that could help improve the prognosis in these patients.

Conclusion:
The deeper knowledge of the molecular pathways involved in the appearance and progression
of medulloblastomas will allow us to offer a prognosis at the time of diagnosis and more specific
treatments through the development of the targeted therapy.