bluuebunny/crossref_metadata_2025_split huggingface dataset:
Pharmacological Modulation of Apoptosis and Autophagy in Pancreatic Cancer Treatment
Authors: Stanslas Johnson , Islam Mohammad Kaisarul , Selvarajoo Nityaa , Sagineedu Sreenivasa Rao , Lian Ho Kok , Lim Jonathan Chee Woei 
Published: March 2022

Background:
Pancreatic cancer is a fatal malignant neoplasm with infrequent signs and symptoms until a progressive stage. In 2020, GLOBOCAN reported that pancreatic cancer accounts for 4.7% of all cancer deaths. Despite the availability of standard chemotherapy regimens for treatment, the survival benefits are not guaranteed because tumor cells become chemoresistant even due to the development of chemoresistance in tumor cells even with a short treatment course, where apoptosis and autophagy play critical roles.

Objective:
This review compiled essential information on the regulatory mechanisms and roles of apoptosis and autophagy in pancreatic cancer, as well as drug-like molecules that target different pathways in pancreatic cancer eradication, with an aim to provide ideas to the scientific communities in discovering novel and specific drugs to treat pancreatic cancer, specifically PDAC.

Method:
Electronic databases that were searched for research articles for this review were Scopus, Science Direct, PubMed, Springer Link, and Google Scholar. The published studies were identified and retrieved using selected keywords.

Discussion/ Conclusion:
Many small-molecule anticancer agents have been developed to regulate autophagy and apoptosis associated with pancreatic cancer treatment, where most of them target apoptosis directly through EGFR/Ras/Raf/MAPK and PI3K/Akt/mTOR pathways. The cancer drugs that regulate autophagy in treating cancer can be categorized into three groups: i) direct autophagy inducers (e.g., rapamycin), ii) indirect autophagy inducers (e.g., resveratrol), and iii) autophagy inhibitors. Resveratrol persuades both apoptosis and autophagy with a cytoprotective effect, while autophagy inhibitors (e.g., 3-methyladenine, chloroquine) can turn off the protective autophagic effect for therapeutic benefits. Several studies showed that autophagy inhibition resulted in a synergistic effect with chemotherapy (e.g., a combination of metformin with gemcitabine/ 5FU). Such drugs possess a unique clinical value in treating pancreatic cancer as well as other autophagy-dependent carcinomas.
Oxidative Damage by 3-nitrotyrosine in Young Adults with Obesity: Its Implication in Chronic and Contagious Diseases
Authors: Calderón-Torres Claudia Marissa , Ortiz-Reyes Ana E. , Murguía-Romero Miguel 
Published: March 2022

Introduction:
Cellular damage by oxidation occurs in numerous chronic diseases, such as
obesity, type II diabetes, cardiovascular disease, nonalcoholic fatty liver, etc. The oxidized compound
3-nitrotyrosine is a marker of oxidative stress and protein oxidation damage.

Objective:
The article aims to assess whether 3-nitrotyrosine levels are higher in young people with
obesity than in the same population without obesity.

Method:
Anthropometry and blood chemistry analyses were performed on 24 young Mexican
participants (18-30 years old), categorized into two groups based on their waist circumference: Withobesity
(≥ 80 cm women; ≥ 90 cm men) and without-obesity (<80 cm women; <90 cm men).
Additionally, 3-nitrotyrosine blood values were quantified by ELISA.

Results:
Except for HDL-cholesterol, the mean values of lipids increased in women and men with
obesity (p<0.05), and 3-nitrotyrosine concentration (nM/μg total protein) was higher by 60% in the
group with-obesity compared to the group without-obesity, both for women (66.21 ± 23.85 vs. 40.69 ±
16.25, p<0.05) and men (51.72 ± 20.56 vs. 30.52 ± 5.21, p<0.05).

Conclusions:
Oxidative damage measured by compound 3-nitrotyrosine was higher in the group with
obesity than in the group without obesity, which, if not controlled, could lead to a chronic oxidative
condition and thereby to a degree of cellular aging with adverse health effects.
Nanostructured Lipid Carriers for the Delivery of Natural Bioactive
Compounds
Authors: Zulfakar Mohd. Hanif , Shamsuddin Nur Amira Mohd. 
Published: March 2022

Abstract:
Natural products contain bioactive compounds that are produced naturally via synthetic or
semisynthetic processes. These bioactive compounds play significant biological roles, especially for
growth as well as in defense mechanisms against pathogens. Bioactive compounds in natural products
have been extensively studied in recent decades for their pharmacological activities, such as anticancer,
wound healing, anti-microbial, anti-inflammatory, and anti-oxidative properties. However, their
pharmaceutical significance has always been hindered by their low bioavailability and instability with
variations in pH, temperature, and exposure to light. Nanotechnology paves the way for the development
of drug delivery systems by enhancing therapeutic efficacy. Nanostructured lipid carriers, a lipidbased
drug delivery system, are recently being studied to improve the biocompatibility, biodegradability,
bioavailability, solubility, permeability, and shelf life of bioactive compounds in the pharmaceutical
industry. The ideal component and preparation method for bioactive compounds in nanostructured lipid
carrier development is necessary for their physicochemical properties and therapeutic efficiency. Therefore,
this review seeks to highlight recent developments, preparation, and application of nanostructured
lipid carriers as carriers for natural bioactive compounds in improving their therapeutic potential in
drug delivery systems.
Synthesis, Molecular Docking, and 2D-QSAR Modeling of Quinoxaline
Derivatives as Potent Anticancer Agents against Triple-negative Breast
Cancer
Authors: Kaushal Tanu , Khan Sana , Fatima Kaneez , Luqman Suaib , Khan Feroz , Negi Arvind Singh 
Published: March 2022

Background:
Breast carcinomas aka triple-negative breast cancers (TNBC) are one of the most complex and aggressive forms of cancers in females. Recently, studies have shown that these carcinomas are resistant to hormone-targeted therapies, which makes it a priority to search for effective and potential anticancer drugs. The present study was aimed to synthesize and develop the 2D-quantitative structural activity relationship model (QSAR) of quinoxaline derivatives as a potential anticancer agent.

Methods:
Quinoxaline derivatives were designed and synthesized (8a-8i and 9a-9d) and the 2D-QSAR model against TNBC was developed using VLife MDS v4.4. The anticancer activity was investigated against the TNBC MDA-MB-231 cell line using an MTT cytotoxicity assay. Molecular docking studies along with the estimation of ADMET parameters were done, using Discovery Studio. The most potent compound was docked against the β-tubulin protein target (PDB: 4O2B), using the Autodock Vina v0.8 program.

Results:
Eleven derivatives of quinoxaline were designed and synthesized (8a-8i and 9a-9d) and a 2D-QSAR model was developed against the TNBC MDA-MB231 cell line. The regression coefficient values for the training set were (r2) 0.78 and (q2) 0.71. Further, external test set regression (pred_r2) was 0.68. Five molecular descriptors viz., energy dispersive (Epsilon3), protein-coding gene (T_T_C_6), molecular force field (MMFF_6), most hydrophobic hydrophilic distance (XA), and Zcomp Dipole were identified. After ADMET, the best analog 8a showed the best activity against the TNBC cell line. The best-predicted hit '8a' was found to bind within the active site of the β-tubulin protein target.

Conclusion:
The newly synthesized quinoxaline compounds could serve as potent leads for the development of novel anti-cancer agents against TNBC.
Recent Advances in Copper-Catalyzed Carbon Chalcogenides Cross- Coupling Reactions
Authors: Kundu Debasish , Roy Totan , Mahata Atanu 
Published: March 2022

Abstract:Cu-catalyzed carbon-heteroatom bond formation is a powerful tool for in the field of Organic synthesis. In past two decades numerous Cu-based catalytic systems are developed in both homogeneous and heterogenous form. Important developments were reported on Cu-based catalytic systems in the field of C-Chalcogenide cross coupling in last few decades. Where homogeneous Cu/L based catalytic systems are found to perform reactions with high selectivity, heterogeneous supported-Cu and Cu-based nanoparticles are found to perform the reactions under sustainable conditions and high recyclability of catalytic systems. This present overview mainly focuses on the recent advances and applications in this fast-growing research field with an emphasis on copper catalyzed cross-coupling generations of carbon–chalcogenide (S/Se/Te) bonds
Obesity Paradox in Atrial Fibrillation and its Relation with the New Oral
Anticoagulants
Authors: Lima Filho André Inocêncio Novaes , do Rego Barros Mariana Costa , de Barros Guimarães Alice Almeida , Celestino Sobral Filho Dário 
Published: March 2022

Abstract:
Obesity, a chronic disease established as a global epidemic by the World Health Organization,
is considered a risk factor for atrial fibrillation (AF), the most common sustained cardiac
arrhythmia, which has high morbidity and mortality. Although both obesity and AF are diseases
associated with negative outcomes, studies have shown the presence of an obesity paradox, in
which patients with a high body mass index (BMI) and AF have a better prognosis than patients
with a normal BMI. Despite the fact that the mechanisms that lead to this paradox are still uncertain,
adequate anticoagulation in obese patients seems to play an important role in reducing adverse
events in this group. In this perspective article, the authors discuss the relationship between new
oral anticoagulants (NOACs), namely, apixaban, edoxaban and rivaroxaban (factor Xa inhibitors)
and dabigatran (direct inhibitor of thrombin), and the obesity paradox, seeking to deepen the understanding
of the mechanism that leads to this paradox.
Dry Grinding Synthesis and Docking Study of Cyclopentanone-Sulfur
Containing Compounds with Anti-Proliferative Activity for HepG-2 and
A-549 Cancer Cell Lines
Authors: Muhammad Zeinab A. , Farghaly Thoraya A. , Al-Hussain Sami A. , Edrees Mastoura M. , Zaki Magdi E. A. , Shabaan Sara N. 
Published: March 2022

Background:
The dry grinding method is a green technique for efficient organic synthesis
with numerous advantages, such as mild reaction conditions, environmental acceptability, simple
segregation, and refinement, as well as elevated selectivity and efficiency.

Objective:
The aim of the present work is to design and synthesize cyclopentylidene-hydrazino)-
thiazole derivatives using dry grinding conditions to investigate their antitumor activity against two
cell lines, namely, HepG-2 and A-549.

Methods:
In this context, we synthesized a series of thiazole incorporated cyclopentane through hydrazone-
group and 2-cyclopentylidenehydrazine-1-carbimidic-2-ethoxy-N-aryl-2-oxoacetohydrazonic
thioanhydride under dry grinding within minutes and excellent to good yield.

Results:
All spectral data confirmed the proposed structures. In addition to antitumor activity investigations
against the two kinds of cancer cells, molecular docking studies were conducted using Macrophage
Migration Inhibitory Factor (Pdb: 4k9g) and Lysozyme C (Pdb: 2f4a), the overexpressed
proteins in the human liver cancer cell (HepG-2) and lung cancer cell lines (A-549), respectively.

Conclusion:
Two derivatives, 9b, and 9d, showed the highest antitumor activity against the two cell
lines HepG-2 and A-549. Also, docking results revealed a high energy score ranging from -7.1590 to
-5.9364 Kcal/mol with Macrophage Migration Inhibitory Factor (Pdb: 4k9g), more than that the energy
score = -4.118 Kcal/mol of co-crystallized ligand. Moreover, the tested derivatives showed energy
score varies from -6.0802 to -4.5503 Kcal/mol against Lysozyme C (Pdb: 2f4a).
Contribution to Pharmacological Valorisation of Algerian Arctium minus
(Hill) Bernh. Subsp. Atlanticum (Pomel) Maire; Antioxidant an d
Acetylcholinesterase Inhibitory Activities
Authors: Guettaf Sofiane , Benmerzoug Abdelmoumen , Chawki Bensouici , Çakmak Yavuz Selim , Dahamna Saliha , Baghiani Abderrahmane , Harzallah Daoud 
Published: March 2022

Background:
The traditional pharmacopoeia is full of potential resources for molecules with
therapeutic effects involving the inhibition of enzymes linked to some diseases.

Objective:
This work aimed to test in vitro neuroprotective activity against Alzheimer's disease (AD)
combined with the antioxidant effect of root extracts obtained by water, water/methanol, and ethyl acetate
of the endemic Arctium minus. subsp. Atlanticum, a native of Algeria.

Methods:
The different extracts of the root of the studied plant were obtained by decoction or maceration.
The inhibitory effect of acetyl/butyrylcholinesterase (AChE/BChE) was achieved by a colorimetric
method. Similarly, the antioxidant activity was measured based on several mechanisms: 1, 1-
diphenyl-2-picryl-hydrazyl (DPPH) and galvinoxyl (GOR) radicals free scavenging assays, β-carotene
bleaching inhibition activity, and cupric ion reducing antioxidant capacity (CUPRAC).

Results:
In the various tests carried out, the ethyl acetate extract (EAE) possessed the most powerful
antioxidant and anticholinesterase activities compared to the other samples. The IC50 and A0.5 values of
DPPH, GOR, β-carotene, CUPRAC, anti-AChE, and anti-BChE assays were 69.45±5.49, 28.87±0.18,
121.58±16.76, 37.41±1.59, 265±21, and 240±6.3 μg / mL, respectively. Likewise, a correlation could
be deduced between the type of extract and the potent antioxidant/anticholinesterase potential.

Conclusion:
This work examines for the first time the anticholinesterase potential combined with the
antioxidant effect of Algerian Arctium minus. subsp. atlanticum. This association between the two effects
could be effective in the fight against AD, and therefore, the use of this natural resource may be
possible in combating this aspect of neurodegeneration.
Alpha-glucosidase and Alpha-amylase Inhibition Activity of Avocado Fruit
of Nepalese Origin
Authors: Adhikari Achyut , Dhakal Kamal , Shrestha Dipesh , Pokhrel Tamlal , Bhandari Devi Prasad 
Published: March 2022

Background:
Diabetes has become a major health problem due to its high prevalence, morbidity,
and mortality rate. Reducing postprandial hyperglycemia has become the main target in the
treatment of diabetes mellitus. So, developing new drugs with fewer side effects has been a major priority.

Objective:
The main objective of this study is to investigate total phenolic and flavonoid content, antioxidant
activity, α-glucosidase, and α-amylase inhibition activity of Persea Americana Mill (avocado)
pulp and seed.

Methods:
The α-glucosidase and α-amylase inhibition activity were performed using substrates PNPG
and CNPG3, respectively. DPPH free radical scavenging assay was used to perform the antioxidant activity.
The total phenolic content was estimated using folin-ciocalu’s reagent. Likewise, the aluminium
trichloride method was applied to find out the total flavonoid content.

Results:
The crude methanolic extract of avocado seed revealed potent α-glucosidase inhibition activity
with an IC50 1.959±0.93μg/mL followed by the avocado pulp 308±2.36μg/mL. Similarly, the IC50 for
the α-amylase inhibition activity of avocado seed was found to be 120.3±1.382μg/mL. In addition, the
avocado pulp and seed revealed a significant antioxidant activity with IC50 values of 75.01±0.72μg/mL
and 6.445±0.62μg/mL, respectively, compared to the standard quercetin 1.525±0.5μg/mL. The total
phenolic content of avocado pulp and the seed was reported as 7.031±2.87 mg of GAE/g, and
142.96±1.589 mg of GAE/g, respectively. Similarly, the total flavonoid content of avocado pulp and
the seed was found to be 6.313±1.301 mg of QE/g and 48.696±0.110 mg of GAE/g, respectively.

Conclusions:
The avocado seed of Nepali origin was found to inhibit the digestive enzyme significantly.
These findings indicate that avocado fruit of Nepali origin has the potential to develop as an alternative
food therapy for diabetic patients. Further research is required to find out the inhibitor compounds.
A Comprehensive Assessment of Knowledge, Attitudes, and Practicalities Related to Doping Agents use among Jordanians
Authors: Odeh Mohanad , Tailakh Haneen M. , Al Bawab Abdel Qader F. , Elsahoryi Nour A. , Alzoubi Karem H. 
Published: March 2022

Background:
People perform sports for better health and wellbeing. However, the use of doping agents is emerging among young adults. This study investigated aspects related to doping agents.

Methods:
A reliable self-administered questionnaire (Cronbach’s alpha =0.72, Pearson's r = 0.89) was used to assess knowledge, attitudes, and practicalities related to the use of doping agents. Results for pharmacists as health care providers (HCP, n=550) were compared with non-healthcare providers (Non-HCP, n=319).

Results:
Among pharmacists, 82.9% knew the definition of doping agents vs. 72.4% of non-HCP (P<0.001). However, 36.7% of pharmacists vs. 39.6% of non-HCP incorrectly classified doping agents (P=0.02). The majority of responders (89.8%) supported having an anti-doping authority, yet, only 15% were aware of the anti-doping organizations. The majority of responders (83%) did not receive an official education related to doping agents. Enhancing physical performance was perceived as a leading driver (82.1%) to use doping agents. More than 90% of responders supported awareness in the community. The perceived best tool for awareness was social media and TV sites, as suggested by pharmacists (95.0%) and non-HCP (92.1%, P=0.312). A total of 6.1% had ever used doping agents (3.6% pharmacist vs. 9.8% non-HCP, P<0.001). Almost half of the users utilized a diet or medication to counteract the side effects of doping agents. Within pharmacists, males received more requests to provide doping agents (41.9%) compared with females (23.8%, P<0.001).

Conclusion:
It is crucial to enhance professional and legal knowledge and public awareness about doping agents, not only for non-HCP but also for HCPs. Applying more restrictions on doping agents is strongly recommended.
Technology in the Era of COVID-19: A Systematic Review of Current
Evidence
Authors: Mehraeen Esmaeil , Mehrtak Mohammad , SeyedAlinaghi SeyedAhmad , Nazeri Zahra , Afsahi Amir Masoud , Behnezhad Farzane , Vahedi Farzin , Barzegary Alireza , Karimi Amirali , Mehrabi Nahid , Dadras Omid , Jahanfar Shayesteh 
Published: March 2022

Background:
During the COVID-19 pandemic, the use of technology-based services has
been incremental by the care providers for patients scheduling, regulatory considerations, resource
allocation, thus enabling virus exposure prevention while maintaining effective patient care. This study
aims to review the currently available evidence to identify available technology solutions in the era of
COVID-19.

Methods:
A systematic review in July 2020 using the PubMed, Scopus, Embase, Science Direct, and
Web of Science databases has been carried out. After evaluating the title and abstract to select the most
relevant studies based on inclusion and exclusion criteria, the selected articles underwent quality assessment.
The full text of selected articles was then thoroughly evaluated to extract the essential findings.

Results:
In this study, 20 technology-based approaches have been identified for provision of healthcare
services to patients with COVID-19. These methods included telemedicine, virtual visits, e-consult,
tele-consulting, video conference, virtual healthcare, mobile-based self-care, social media, tele ICU,
3D printing technology, telemonitoring, teleradiology, telesurgical, and cloud-based service.

Conclusion:
Due to the rapid spread of the coronavirus, the use of technology-based methods for the
provision of remote healthcare services can help control the disease. The effectiveness of each of these
approaches can be investigated in future research.
The Protective Effect of Vitexin Compound B-1 on Rat Cerebral I/R
Injury through a Mechanism Involving Modulation of miR-92b/NOX4
Pathway
Authors: Luo Xiu-Ju , Peng Jun , Hu Zhong-Yang , Yang Zhong-Bao , Zhang Ruxu 
Published: March 2022

Background:
Recent studies have uncovered that vitexin compound B-1 (VB-1) can protect
neurons against hypoxia/reoxygenation (H/R)-induced oxidative injury through suppressing NOX4
expression.

Objective:
The aims of this study are to investigate whether VB-1 can protect the rat brain against ischemia/
reperfusion (I/R) injury and whether its effect on NOX4 expression is related to modulation of
certain miRNAs expression.

Methods:
Rats were subjected to 2 h of cerebral ischemia followed by 24 h of reperfusion to establish
an I/R injury model, which showed an increase in neurological deficit score and infarct volume concomitant
with an upregulation of NOX4 expression, increase in NOX activity, and downregulation of
miR-92b.

Results:
Administration of VB-1 reduced I/R cerebral injury accompanied by a reverse in NOX4 and
miR-92b expression. Similar results were achieved in a neuron H/R injury model. Next, we evaluated
the association of miR-92b with NOX4 by its mimics in the H/R model. H/R treatment increased neurons
apoptosis concomitant with an upregulation of NOX4 and NOX activity while downregulation of
miR-92b. All these effects were reversed in the presence of miR-92b mimics, confirming the function
of miR-92b in suppressing NOX4 expression.

Conclusion:
We conclude the protective effect of VB-1 against rat cerebral I/R injury through a
mechanism involving modulation of miR-92b/NOX4 pathway.
Searching for a Link between Bone Decay and Diabetes Type 2
Authors: Isacco Ciro G. , Nguyen Kieu C.D. , Pham Van H. , Di Palma Gianna , Aityan Sergey K. , Tomassone Diego , Distratis Pietro , Lazzaro Rita , Balzanelli Mario G. , Inchingolo Francesco 
Published: March 2022

Abstract:The current commentary describes the possible existing link between metabolic diseases such as diabetes type 2 and the degenerative patterns of bones via the molecular mechanism that inhibits the mesenchymal stem cells’ differentiation into osteoblasts and osteocytes.
Swiftly Evolving CRISPR Genome Editing: A Revolution in Genetic Engineering
for Developing Stress-Resilient Crops
Authors: Nejat Naghmeh , Han Yong , Zhang Xiao-Qi , He Tianhua , Wang Penghao , Li Chengdao 
Published: March 2022

Abstract:
Environmental stresses adversely impact crop production, crop quality, and product safety.
Climate change is predicted to exacerbate the impacts of stresses on current cropping systems
with multilateral impacts on crop productivity and yield, biodiversity, soil fertility, microbial activity,
and carbon sequestration. Transforming crop production systems and developing stress and climate-
resilient crops are paramount to alleviate pervasive food and nutrition security and food safety
issues and achieve a world free from hunger and malnutrition. Modern breeding techniques have
been the key to transforming crop production systems and developing stress- and climate-resilient
crops. As a rapidly evolving technology, the Nobel Prize-winning CRISPR method is a leading
choice for genome editing and a possible major contributor to solving environmental and food insecurity
issues. Here, a background on the stressors with far-reaching impacts on food security has
been provided, and the principles and advances in classical genome editing (CRISPR/Cas9) that
generate DNA double-strand breaks (DSB) have been reviewed. Base editing and prime editing
platforms, which are DSB- and template-free, enabling targeted base substitutions, have been discussed.
The application of such tools for trait improvement has been evaluated to develop stressresilient
crops and high-throughput mutant libraries. Recent developments in the regulatory landscape
for genome-edited crops in various countries have been examined. Finally, the challenges and
future perspectives toward crop improvement have been highlighted.