bluuebunny/crossref_metadata_2025_split huggingface dataset:
GLP-1 Targeted Novel 3-phenyl-7-hydroxy Substituted Coumarins
Mitigate STZ-induced Pancreatic Damage and Improve Glucose
Homeostasis in OGTT Method
Authors: Gupta Mandeep Kumar , Srivastava Rajnish , Kumar Sushil , Varshney Krishna Kumar , Singh Hariram 
Published: August 2022

Background:
Worldwide, type 2 diabetes mellitus accounts for a considerable burden of
disease, with an estimated global cost of >800 billion USD annually. For this reason, the search for
more effective and efficient therapeutic anti-diabetic agents is continuing. Recent studies support the
search for coumarins or related compounds with potential blood glucose-lowering properties.

Aim:
The study aims to design, synthesize and evaluate the hypoglycemic activity of a new class of
7-hydroxy coumarin derivatives.

Objective:
To explore and establish the in-silico-driven pharmacological role of a new class of 7-
hydroxy coumarin derivatives as the therapeutic strategies against type 2 diabetes mellitus.

Methods:
A new class of 7-hydroxy coumarin derivatives was designed by assessment of their
physicochemical properties and molecular docking against the Glucagon-like peptide-1 (GLP-1)
receptor. Two novel series of 30 compounds were synthesized. The chemical structures of all the
synthesized analogues have been elucidated by spectral studies of IR, 1H-NMR, and mass
spectroscopy. After considering the molecular docking score and their physicochemical properties,
the compounds were screened out for the evaluation of their hypoglycemic potential. The compounds
were investigated for their hypoglycemic activity using a streptozotocin (STZ) induced diabetic
model and an oral glucose tolerance test (OGTT) method at different dose levels.

Result:
The molecular docking studies of synthesized derivatives reveal significant molecular
interaction with the various amino acid residues of the GLP-1 receptor. IR spectral analysis revealed a
strong band of -NH stretching in the range of 3406.7-3201.61 cm-1 and one strong band for the
lactone carbonyl group of the coumarin ring in the range of 1722.0-1703.5 cm-1, confirming the
chemical structure of all produced compounds. The synthesized coumarin analogues with the best
docking score exhibited remarkable hypoglycemic potential as assessed by the STZ model and the
OGTT method.

Conclusion:
Coumarin derivatives explored a good structure-activity relationship (SAR) and
produced significant hypoglycemic potential.
Cannabinoids Receptors in COVID-19: Perpetrators and Victims
Authors: Al-Kuraishy Hayder M. , Al-Gareeb Ali I. , Alexiou Athanasios , Batiha Gaber El-Saber 
Published: August 2022

Abstract:COVID-19 is caused by SARS-CoV-2 and leads to acute lung injury (ALI), acute respiratory distress syndrome (ARDS), and extrapulmonary manifestations in severely affected cases. However, most of the affected cases are mild or asymptomatic. Cannabinoids (CBs) such as tetrahydrocannabinol (THC) and cannabidiol (CBD), which act on G-protein-coupled receptors called CB1 and CB2, have anti-inflammatory effects. Many published studies show that CBs are effective in various inflammatory disorders, viral infections, and attenuation of ALI and ARDS. Therefore, the present narrative review aimed to summarize the possible immunological role of CBs in COVID-19. The effects of CBs are controversial, although they have beneficial effects via CB2 receptors and adverse effects via CB1 receptors against ALI, ARDS, and hyperinflammation, which are hallmarks of COVID-19. The present narrative review has shown that CBs effectively manage ALI and ARDS by suppressing pro-inflammatory cytokines, which are common in COVID-19. Therefore, CBs may be used to manage COVID-19 because of their potent anti-inflammatory effects, suppressing pro-inflammatory cytokines and inhibiting inflammatory signaling pathways.
The Role of MicroRNA-126 in Atherosclerotic Cardiovascular
Diseases
Authors: Theofilis Panagiotis , Oikonomou Evangelos , Vogiatzi Georgia , Sagris Marios , Antonopoulos Alexios S. , Siasos Gerasimos , Iliopoulos Dimitrios C. , Perrea Despoina , Vavouranakis Manolis , Tsioufis Konstantinos , Tousoulis Dimitris 
Published: August 2022

Abstract:
Atherosclerotic cardiovascular diseases remain the leading cause of morbidity
and mortality worldwide despite all efforts made towards their management. Other than
targeting the traditional risk factors for their development, scientific interest has been
shifted towards epigenetic regulation, with microRNAs (miRs) being at the forefront.
MiR-126, in particular, has been extensively studied in the context of cardiovascular diseases.
Downregulated expression of this miR has been associated with highly prevalent
cardiovascular risk factors such as arterial hypertension and diabetes mellitus. At the
same time, its diagnostic and prognostic capability concerning coronary artery disease is
still under investigation, with up-to-date data pointing towards a dysregulated expression
in a stable disease state and acute myocardial infarction. Moreover, a lower expression of
miR-126 may indicate a higher disease complexity, as well as an increased risk for future
major adverse cardiac and cerebrovascular events. Ultimately, overexpression of
miR-126 may emerge as a novel therapeutic target in atherosclerotic cardiovascular diseases
due to its potential in promoting therapeutic angiogenesis and anti-inflammatory effects.
However, the existing challenges in miR therapeutics need to be resolved before
translation to clinical practice.
An Insight to Heat Shock Protein 90: A Remedy for Multiple Problems
Authors: Yadav Megha , Singh Ankit Kumar , Kumar Adarsh , Thareja Suresh , Kumar Pradeep 
Published: August 2022

Abstract:
Heat shock protein 90 (Hsp90) is a chaperone protein that prevents many other proteins from aggregating by folding them in a certain way. Hsp90 consists of three structural domains: N-terminal, middle and C-terminal domains. Hsp90 has many activities in numerous proteins and signaling pathways like chimeric fusion proteins, steroid hormone receptors, tumor suppressor genes, and cell cycle regulatory proteins. The role of Hsp90 is not only in cancer but also in other diseases like COVID-19, leishmaniasis, diabetes, flavi virus, systemic sclerosis, grass carp reovirus, psoriasis, malaria, cardiac fibrosis, and alcohol-related liver diseases. This review is a compilation of the pharmacological profile of Hsp90 inhibitors, problems associated with them, and suggested remedies for the same.
Small-molecule High-throughput Screening Identifies an MEK Inhibitor
PD198306 that Enhances Sorafenib Efficacy via MCL-1 and BIM in
Hepatocellular Carcinoma Cells
Authors: Hong Junjie , Zheng Wei , Cai Xiujun 
Published: August 2022

Background:
Sorafenib is the most widely used systematic therapy drug for treating unresectable
Hepatocellular Carcinoma (HCC) but showed dissatisfactory efficacy in clinical applications.

Objective:
We conducted a combinational quantitative small-molecule high-throughput screening
(qHTS) to identify potential candidates to enhance the treatment effectiveness of sorafenib.

Methods:
First, using a Hep3B human HCC cell line, 7051 approved drugs and bioactive compounds
were screened, then the primary hits were tested with/without 0.5 μM sorafenib respectively,
the compound has the half maximal Inhibitory Concentration (IC50) shift value greater than 1.5 was
thought to have the synergistic effect with sorafenib. Furthermore, the MEK inhibitor PD198306
was selected for the further mechanistic study.

Results:
12 effective compounds were identified, including kinase inhibitors targeting MEK,
AURKB, CAMK, ROCK2, BRAF, PI3K, AKT and EGFR, and a μ-opioid receptor agonist and a Ltype
calcium channel blocker. The mechanistic research of the combination of sorafenib plus
PD198306 showed that the two compounds synergistically inhibited MEK-ERK and mTORC1-
4EBP1 and induced apoptosis in HCC cells, which can be attributed to the transcriptional and posttranslational
regulation of MCL-1 and BIM.

Conclusion:
Small-molecule qHTS identifies MEK inhibitor PD1938306 as a potent sorafenib enhancer,
together with several novel combination strategies that are valuable for further studies.
Ketogenic Diet: An Effective Treatment Approach for Neurodegenerative
Diseases
Authors: Zhang Haiyan , Tao Ye , Leng Sean X. 
Published: August 2022

Abstract:
This review discusses the effects and mechanisms of a ketogenic diet on neurodegenerative
diseases on the basis of available evidence. A ketogenic diet refers to a high-fat, mediumprotein,
and low-carbohydrate diet that leads to a metabolic shift to ketosis. This review systematically
summarizes the scientific literature supporting this effective treatment approach for neurodegenerative
diseases, including effects on mitochondrial function, oxidative stress, neuronal apoptosis,
neuroinflammation, and the microbiota–gut-brain axis. It also highlights the clinical evidence
for the effects of the ketogenic diet in the treatment of Alzheimer's disease, Parkinson's disease, and
motor neuron disease. Finally, it discusses the common adverse effects of ketogenic therapy.
Although the complete mechanism of the ketogenic diet in the treatment of neurodegenerative
diseases remains to be elucidated, its clinical efficacy has attracted many new followers. The ketogenic
diet is a good candidate for adjuvant therapy, but its specific applicability depends on the type
and the degree of the disease.
Tadalafil Improves Haemodynamics and Arterial Stiffness but Not Flow-
Mediated Dilation in Grade 1 Obesity. A Single-dose, Placebo-controlled
Clinical Trial
Authors: Larios-Cárdenas Mariana , González-Radillo Oscar I. , Trujillo-Quirós Jhonatan , Cardona-Müller David , Barocio-Pantoja Marycruz , Cardona-Muñoz Ernesto G. , Grover-Páez Fernando 
Published: August 2022

Objective:
Obesity, a major health issue worldwide, is associated with increased cardiovascular
risk, endothelial dysfunction, and arterial stiffness. Tadalafil has been demonstrated to improve
vascular parameters.

Aim:
To evaluate the effect of a single 20 mg dose of tadalafil on flow-mediated dilation and hemodynamic
and arterial stiffness markers.

Methods:
A randomized, double-blind, placebo-controlled study was conducted on 80 participants (41
assigned to placebo and 39 to tadalafil) with grade 1 obesity, to evaluate the acute effect of a single dose
of 20 mg of tadalafil on flow-mediated dilation and hemodynamic and arterial stiffness markers.

Results:
Tadalafil did not modify flow-mediated dilation. However, it significantly lowered systolic
blood pressure (SBP) (130.6±17.1 vs. 125.0±12.7 mmHg, p=0.011), diastolic blood pressure (82.7±18.2
vs. 76.5±11.8 mmHg, p≤0.001), central systolic blood pressure (116.33±19.16 vs. 109.90±15.05 mmHg,
p=0.001), the augmentation index (69.1±17.1 vs. 65.7±14.4, p=0.012), and brachial-ankle pulse wave
velocity (1229.7±218.4 vs. 1164.0±181.7, p=0.001).

Conclusion:
A single dose of tadalafil did not modify flow-mediated dilation in patients with grade
1 obesity but improved blood pressure and brachial-ankle pulse wave velocity.

Clinical Trial Registration Number:
The clinical trial registration number is (NCT03905018).
Ru Nanoparticle Intercalated Montmorillonite Clay Catalytic System for
the Reduction of Aliphatic/Aromatic Nitro Compounds
Authors: Prakash Om , Jangir Bhawana , Srivastava Vivek 
Published: August 2022

Abstract:
The Ru exchanged MMT clay was synthesized with different Ru metal stacking using the
wet impregnation method. All the developed materials were analyzed with advanced analytical techniques. All the data were found in good agreement with each other. Furthermore, all the catalysts were
tested for the reduction of aromatic and aliphatic nitro compounds to the corresponding amines in
conventional and ionic liquid reaction mediums. The amines were easily isolated with simple ether
washing in ionic liquid medium, and the catalyst was recycled up to 8 times. Various amines were also
synthesized using the proposed methodology, having direct importance as building blocks of several
biologically active compounds.
The Synthetic Approaches for Preparation of Indigo and Applications in
Denim Industry
Authors: Seferoğlu Zeynel , Kaplan Gökhan 
Published: August 2022

Abstract:
This paper describes indigo chemistry and its brief scientific history beginning with the
first characterization and chemical synthesis of indigo via various precursors such as isatin, cinnamic
acid, 2-nitrobenzaldehyde, anthranilic acid, N-phenylglycine, aniline, and indole. Furthermore, alternative
methods such as eco-friendly microbial synthesis of indigo using a variety of enzymes are
reported: Cytochrome P450 monooxygenases, flavin-containing monooxygenases, and unspecific
peroxygenases. Subsequently, the application of indigo in the denim industry, reduction methods
(chemical, electrochemical, enzymatic and catalytic) and dyeing methods (all parameters in dyeing,
ring dye) are discussed. In addition, the main reason for the use of indigo in the denim industry is
briefly explained.
Medicinal Plants in the Regulation of PD-L1/PD-1 Immune Checkpoint of
Various Human Cancer Cells: A Narrative Review
Authors: Marzuki Nur Fatin Najihah , Zakaria Yusmazura 
Published: August 2022

Background:
Immunotherapy has garnered attention in cancer treatment following the
success of recent trials in solid tumors adopting PD-L1/PD-1 checkpoint inhibition. PD-1 is a T-cell
checkpoint molecule that limits autoimmune and auto-inflammatory reactivity in the normal host by
suppressing adaptive immune responses. Although PD-L1 expression in the tumor is generally considered
a poor prognostic marker, it has been used to screen patients for cancer therapy since it is
associated with a positive response to PD-L1/PD-1 blocking antibodies.

Outline:
This review focuses on the complex interconnections between cancer-reactive and selfreactive
immune cells, as well as the potential contribution of a wide range of leading immunomodulatory
chemical products from plant-based origins as cancer therapeutics or to foreseeably ameliorate
autoimmune diseases. The natural compounds derived from plants should be used as a PD-L1/PD-1
checkpoint modulator to combat cancer cells and other chronic diseases.

Conclusion:
The significance of herbal plant extracts in the regulation of the PD-L1/PD-1 checkpoint
is presented in this review together with the expression of PD-L1 and PD-1 in cancer cells and
diseases in human bodies.
Current Concepts of Corticosteroids Use for the Prevention of Bronchopulmonary
Dysplasia
Authors: Perrone Serafina , Orlando Serena , Petrolini Chiara , Marinelli Francesca , Moretti Sabrina , Corradi Mara , Giordano Maurizio , De Bernardo Giuseppe 
Published: August 2022

Abstract:
Despite using antenatal steroids, surfactants and protective ventilation, bronchopulmo-nary dysplasia (BPD) affects 10-89% of preterm infants. Since lung inflammation is central to the BPD pathogenesis, postnatal systemic corticosteroids could reduce the risk of BPD onset in preterm infants, but short and long-term adverse consequences have been underlined in literature after their use (i.e., hyperglycaemia, hypertension, hypertrophic cardiomyopathy, growth failure, gastrointesti-nal bleeding, cerebral palsy). Alternative therapeutic strategies such as postponing corticosteroid administration, lowering the cumulative dose, giving pulse rather than continuous doses, or individ-ualizing the dose according to the respiratory condition of the infant have been proposed to avoid their adverse effects. Dexamethasone remains the first-line drug for newborns with severe pulmo-nary disease beyond the second to the third week of life. Hydrocortisone administration in very pre-term infants does not appear to be associated with neurotoxic effects, even if its efficacy in prevent-ing and treating BPD has yet been clearly demonstrated. Alternative methods of corticosteroid ad-ministration seem promising. A positive effect on BPD prevention occurs when budesonide is nebu-lized and intratracheally instilled with a surfactant, but more data are required to establish safety and efficacy in preterm newborns. Additional studies are still needed before the chronic lung dis-ease issue, and its related challenges can be solved.
Treatment Approaches for Swallowing Disorders in Children
Authors: Toro-Monjaraz Erick M. , Cano-Larios Miriam J. , Gallardo-Luna Miguel S. , Zarate-Mondragón Flora E. , Cadena-León Jose F. , Ignorosa-Arellano Karen R. , Montijo-Barrios Ericka , Cervantes-Bustamante Roberto , Ramirez-Mayans Jaime 
Published: August 2022

Abstract:
A swallowing disorder or dysphagia is defined as a disorder in the sequence of swallow-ing, during the oral or pharyngeal phase, which compromises the safety and/or efficiency of transit of the food bolus to the esophagus.
The evaluation of neurodevelopment, nutrition, and preventive medicine actions are as important as the clinical evaluation of dysphagia, so they must be included and systematized in all pediatric evaluations; This evaluation can be divided into different parts: bedside swallowing evaluation, in-strumental swallowing evaluation, and additional studies.
The management of swallowing disorders requires a multidisciplinary team approach, depending on the child's age, cognitive and physical abilities, and the specific swallowing and feeding disorder, ensuring adequate and safe nutrition and improving the patient's quality of life.
Common Childhood Sleep Problems and Disorders
Authors: Leung Theresa Ngan Ho , Wong Kin Lok , Chan Anthony Kam Chuen , Li Albert Martin 
Published: August 2022

Background:
Sleep insufficiency and disturbances affect the physical, cognitive, and emotional well-being of children.

Objective:
To perform a narrative review on common sleep problems and disorders encountered in primary care for children and adolescents.

Methods:
A search of English literature in the Pubmed and Google Scholar databases published from 1 January 2000 till 31 October 2021 was conducted with the keywords “sleep problem” or “sleep disorder” and “child” or “adolescent”. Findings in the relevant articles and cross-references were compiled.

Results:
Sleep duration and habits of children vary widely across countries with different cultural backgrounds. There is robust evidence to support the promotion of positive bedtime routines and sleep hygiene as prevention and management of sleep problems. 15-70% of parents reported their children having sleep problems or disturbances. Common sleep complaints include difficulty in ini-tiation or maintenance of sleep, abnormal behaviors or movements, snoring or abnormal breathing, and excessive daytime sleepiness. Comprehensive sleep history and a sleep diary are the first steps for evaluation. Home video and actigraphy may be used as preliminary tools to confirm the history. Referrals to a sleep specialist for polysomnography and other tests are needed, if suspecting specific sleep disorders, such as obstructive sleep apnea and narcolepsy, needs timely intervention. Common sleep disorders in different age groups encountered in primary care are reviewed with clinical fea-tures, indications for evaluation, and treatment options summarized.

Conclusion:
Screening for sleep problems shall be an integral part of each child's health care visit. It is important to evaluate the impact of common sleep problems and identify specific sleep disor-ders for early intervention to prevent long-term adverse outcomes.
Comparison of Umbilical Cord Arterial Blood Gas and Neonatal
Outcomes in Women with and without Meconium-Stained Amniotic Fluid
During Labor
Authors: Mousavi Sanaz , Akhgari Aisan , Dehghan Mahshid , Hoseinzadeh Maryam , Mirghafourvand Mojgan , Tafreshi Rosa , Nikniaz Leila 
Published: August 2022

Introduction:
Meconium-stained amniotic fluid (MSAF) may increase maternal and neonatal
complications. The favorable mode of delivery is controversial in women with MSAF. This
study aimed to compare umbilical cord arterial blood gas (ABG) and neonatal outcomes in deliveries
complicated by meconium and clear amniotic fluid during the active phase of labor.

Materials and Methods:
This observational study was performed on 144 term pregnant women (72
with MSAF and 72 with clear amniotic fluid) during the active phase of labor with ruptured membranes
admitted to Al-Zahra and Taleghani hospitals in Tabriz, Iran, from June 2019 to June 2020.
A checklist was used to record the ABG and neonatal outcomes.

Results:
The frequency of cesarean delivery in the MSAF group (25%) was significantly higher
than in the women with clear amniotic fluid (20%) (P = 0.006). There was no statistically significant
difference between the groups regarding pH, base excess, PCO2, 1- and 5- minute Apgar scores, and
neonatal intensive care unit (NICU) admission of the newborn due to MSAF (P> 0.05). There was
no incidence of hypoxic-ischemic encephalopathy, sepsis, and seizure.

Conclusion:
Given the non-significant difference between two groups of women with and without
MSAF during labor in terms of neonatal outcomes and umbilical cord ABG, it seems that MSAF
alone is not an indication for cesarean delivery. Thus, vaginal delivery is recommended in pregnant
women with MSAF.
Diffusion MRI in Intracranial Hypertension: Quantitative Assessment
Authors: Aktaş Fatma , Özmen Zafer 
Published: August 2022

Purpose:
Intracranial hypertension (IH) is a neurological disease characterized by increased
intracranial pressure. Idiopathic intracranial hypertension (IIH) is characterized by increased intracranial
pressure without an underlying neuroradiological cause (1-3). The IH associated with a reason such as
a mass, hydrocephalus, or drug use, is referred to as secondary intracranial hypertension (SIH). We
aimed to detect and determine whether the increased intracranial pressure causes a change in the
diffusion values of the brain in the diffusion MRI images.

Methods:
The study includes 24 consecutive patients diagnosed with IIH and 18 consecutive patients
diagnosed with secondary intracranial hypertension (SIH). The control group included 24 patients.
Measurement of apparent diffusion coefficient (ADC) was performed using DWI sections obtained
from subcortical white matter and the cortex of the frontal lobe in the basal ganglia plane, caudate
nucleus head, thalamus, the posterior leg of the internal capsule, corpus callosum splenium; in the
centrum semiovale plane, from the central white matter region. with 1.5T MRI using b=500s/mm2 and
b=1000s/mm2 values both in patients and control groups. Mean ADC values were compared between
IIH, SIH patients and control groups

Results:
The ADC values from the head of the caudate nucleus and the cortex were significantly
higher in the IIH group compared to the control group. When the ADC values of the SIH and control
groups were compared, it was found that some of the ADC measurements (subcortical white matter,
cortex and semioval center) were significantly different. The comparison of the IIH and the SIH groups
revealed that the ADC measurements of central white matter in the centrum semiovale, the subcortical
white matter and the posterior leg of the internal capsule were significantly different.

Conclusions:
We have found increased diffusion of IIH and SIH patients, which supports the
development of brain edema. Even though the mechanism of the brain edema in IIH is not entirely
clear, it is thought that the mechanism is different from the brain edema caused by a mass or a sinus
thrombosis.