bluuebunny/crossref_metadata_2025_split huggingface dataset:
Combinatorial Chemosensitive Nanomedicine Approach for the
Treatment of Breast Cancer
Authors: Gupta Priya , Neupane Yub Raj , Parvez Suhel , Kohli Kanchan , Sultana Yasmin 
Published: August 2022

Abstract:
Breast cancer is the most commonly diagnosed type of cancer and ranks
second among cancer that leads to death. From becoming the foremost reason for
global concern, this multifactorial disease is being treated by conventional
chemotherapies that are associated with severe side effects, with chemoresistance
being the ruling reason. Exemestane, an aromatase inhibitor that has been approved by
the US FDA for the treatment of breast cancer in post-menopausal women, acts by
inhibiting the aromatase enzyme, in turn, inhibiting the production of estrogen. However,
the clinical application of exemestane remains limited due to its poor aqueous solubility
and low oral bioavailability. Furthermore, the treatment regimen of exemestane often
leads to thinning of bone mineral density. Thymoquinone, a natural compound derived
from the oil of the seeds of Nigella sativa Linn, possesses the dual property of being a
chemosensitizer and chemotherapeutic agent. In addition, it has been found to exhibit
potent bone protection properties, as evidenced by several studies. To mitigate the
limitations associated with exemestane and to deliver to the cancerous cells overcoming
chemoresistance, the present hypothesis has been put forth, wherein a natural
chemosensitizer and chemotherapeutic agent thymoquinone will be incorporated into a
lipid nanocarrier along with exemestane for combinatorial delivery to cancer cells.
Additionally, thymoquinone being bone protecting will help in ousting the untoward effect
of exemestane at the same time delivering it to the required malignant cells,
safeguarding the healthy cells, reducing the offsite toxicity, and providing potent
synergistic action.
Desonide Nanoemulsion Gel for Transdermal Absorption Drug Delivery:
Pharmacodynamic and Safety Evaluation
Authors: Zhang Jiaqi , Yao Yu , Liu Hanbing , Ma Qiuyan , Huang Lanyi , Chen Yuan , Lin Huaqing 
Published: August 2022

Backgrounds:
When administered transdermally, desonide has an unsatisfactory effectiveness due to its poor solubility. As a new transdermal delivery system, nanoemulsion gel has demonstrated significant advantages for drug delivery over conventional formulations. We have established desonide nanoemulsion gel (DES NE gel) for better transdermal absorption, but its efficacy and safety still need to be evaluated. This study aims to provide additional evidence that demonstrating the improved pharmacodynamics and safety of transdermal delivery of Desonide via nanoemulsion gel.

Methods:
Pharmacodynamics and safety of Desonide nanoemulsion gel were evaluated using Desonate® as the reference formulation. To assess the difference in curative effect between DES NE gel and Desonate® and to ensure the safety, the atopic dermatitis (AD) models in KM mice were developed using 2,4-dinitrofluorobenzene (DNFB). The degree of ear swelling, ear mass difference, thymus, spleen index, and HE conventional pathology of mice were used as pharmacodynamic evaluation indexes, and the irritation was predicted by the New Zealand rabbit epidermal stimulation assay.

Results:
Nanoemulsion gels may facilitate transdermal penetration of drugs by influencing the skin condition. Medium and high doses of DES NE gel significantly ameliorated the inflammation and swelling of ear caused by dermatitis/eczema in mice. In addition, compared with DES gel, skin irritation extent did not increase.

Conclusion:
Nanoemulsion gel can be applied to improve the efficacy of drugs with low potency or poor solubility. DES NE gel provides the higher transdermal potential than other delivery systems. In this study, it was found that nano-emulsion gel is a promising percutaneous carrier of DES. DES NE-GEL has significant curative effect on dermatitis/eczema in mouse model, and is expected to provide a new, efficient and low toxic preparation for clinical treatment of dermatitis/eczema through percutaneous system.
Research Progress of Plant Active Ingredients in Pharmaceutical Cocrystal
Authors: Wang Zimeng , Shang Hongzhou , Gao Linghuan , Qiao Ning 
Published: August 2022

Abstract:
The disadvantages of active ingredients extracted from medicinal plants due to poor solubility in the body and low bioavailability limits their clinical application. Pharmaceutical cocrystal as a new type of drug in solid form has attracted the attention of researchers. This article reviews the effects of cocrystal in various poorly soluble herbal active ingredients of medicinal plants on their physicochemical properties and biological properties, and provides references for the application of pharmaceutical cocrystal in poorly soluble active compounds of medicinal plants.
Pharmacological Activities of the Genus Passiflora (Passifloraceae):
A Patent Review
Authors: Pereira Leal Ana Ediléia Barbosa , de Lavor Érica Martins , de Menezes Barbosa Jackson , de Moura Fontes Araújo Maria Taís , dos Santos Cerqueira Alves Cristiane , de Oliveira Júnior Raimundo Gonçalves , de Lima Ádley Antonini Neves , da Silva Almeida Jackson Roberto Guedes 
Published: August 2022

Background:
Passiflora L. is a genus belonging to the Passifloraceae family, with many species widely used in folk medicine and several pharmacological activities described in the scien-tific literature, being a major target for the development of new therapeutic products. Studies have identified several bioactive compounds in their composition as responsible for these activities, mainly C-glycoside flavonoids.

Objective:
The aim of this study was to carry out a review of patents related to the genus and its ap-plication in several pharmacological activities, important for the development of new drugs and formulations.

Method:
The search was carried out in 5 specialized databases, INPI, EPO, WIPO, Latipat and Derwent, using the term ‘Passiflora’ combined with ‘A61K and A61P', subclasses of section A of the International Patent Classification (IPC), which are destined to medical, dental or hygienic pur-poses, and therapeutic activity of chemical compounds or medicinal preparation, respectively.

Results:
1,198 patents citing the genus in the title or abstract have been found, 508 being duplicates. After exclusion and inclusion criteria, 23 patents written in English, Portuguese and Spanish were selected, which demonstrated biological assays in vivo with species of Passiflora as the only active constituent or incorporated in formulations with other compounds.

Conclusion:
The findings of this search showed growing interest in research and industrial areas in the pharmaceutical development with species of Passiflora, suggesting that the different bioactive compounds present in the genus can be considered as an important tool for the development of new effective and safe products with pharmacological potential.
Herbal Medicines for Idiopathic Male Infertility: A Systematic Review
Authors: Bahrami-Taghanaki Hamid Reza , Ahmadian Mohammad , Salari Roshanak , Noras Mohammad Reza 
Published: August 2022

Background:
Various medications, surgeries, and assisted reproductive techniques are used to treat male infertility, but the high cost and low effectiveness have made these methods unpopular. the use of herbal medicines such as Withania somnifera, Ceratonia siliqua, Nigella sativa and Alpinia officinarum for the treatment of male infertility has become highly popular in recent years.

Objective:
We conducted this systematic review to evaluate the recent scientific evidence regarding herbal medicines used to treat idiopathic male infertility [IMI].

Method:
Online literature resources were checked using different search engines, including ISI, Web of Knowledge, Medline, PubMed, Scopus, and Google Scholar. Date restrictions were applied to 2020, and the publication language was restricted to English and Persian. The risk of bias was evaluated using the Cochrane method.

Result:
Out of 851 articles, 14 trials with 1218 participants were included. Of the 15 plants and medicinal products introduced in the selected studies, 12 cases were effective in treating male infertility. Each of these plants or products affects specific components of male fertility for which various mechanisms were mentioned, but most of them had antioxidant effects. No serious side effects were reported.

Conclusion:
Whitania somnifera roots, Alpinia officinarum, Nigella sativa seeds, Tomato, and Ceratonia siliqua and the formulation of Xperm, PHF, Churna Ratnam, Svaguptadi Churna, Y virilin capsule, manix capsule, and Tradafertil tablet revealed successful outcomes in treatment of idiopathic male infertility.
Lycopene-Loaded Solid Lipid Nanoparticles: Preparation, Characterization,
ROS-Scavenging, and In vitro Anti-Melanogenesis Evaluations
Authors: Shahraki Omolbanin , Daneshmand Sara 
Published: August 2022

Background:
Lycopene, a natural antioxidant from carotenoids, is produced by plants and
microorganisms. It has been investigated in many studies in relation with potential health effects.

Objective:
Due to the high lipid-solubility of lycopene, its skin penetration is challenged. Therefore, in the
present study, lycopene was loaded into lipid nanoparticles to improve penetration and pharmacological
properties.

Methods:
Solid lipid nanoparticles (SLNs) containing lycopene were prepared and anti-tyrosinase properties
were studied in the present study. The formulation was investigated in terms of drug release and antityrosinase
properties. Determination of encapsulation efficiency was performed directly. Electron microscopy
was used to examine the shape of the nanoparticles. Subsequently, the rate of drug release was investigated
by the cell diffusion method. The present study applied cytotoxicity tests, cellular tyrosinase
inhibition, melanin content, and free radical level to evaluate the effect of formulations on melanogenesis
inhibition, and western blot assay was used to determine tyrosinase and MITF levels.

Results:
The results from particle size investigation for LYC-SLNs were 151.1 ± 2.3, and exploring the
data of electron microscopy showed that the shapes of nanoparticles were spherical, and the encapsulation
efficiency was 85.76 ± 2.75%. In determining the anti-tyrosinase effects of LYC-SLNs, a significant reduction
in cellular tyrosinase activity and melanin and ROS levels were observed; It is also worth noting
that LYC-SLNs reduced melanin production with minimal toxicity against melanoma cells.

Conclusion:
In general, the results confirm that SLNs can be an efficient delivery platform for the topical
delivery of lycopene as a natural anti-oxidant and anti-melanogenic agent.
Predicting Binding Affinity Between MHC-I Receptor and Peptides Based on Molecular Docking and Protein-peptide Interaction Interface Characteristics
Authors: Huang Songtao , Ding Yanrui 
Published: August 2022

Background:Predicting protein-peptide binding affinity is one of the leading research subjects in peptide drug design and repositioning. In previous studies, models constructed by researchers just used features of peptide structures. These features had limited information and could not describe the proteinpeptide interaction mode. This made models and predicted results lack interpretability in pharmacy and biology, which led to the protein-peptide interaction mode not being reflected. Therefore, it was of little significance for the design of peptide drugs.Objective:Considering the protein-peptide interaction mode, we extracted protein-peptide interaction interface characteristics and built machine learning models to improve the performance and enhance the interpretability of models.Methods:Taking MHC-I protein and its binding peptides as the research object, protein-peptide complexes were obtained by molecular docking, and 94 protein-peptide interaction interface characteristics were calculated. Then ten important features were selected using recursive feature elimination to construct SVR, RF, and MLP models to predict protein-peptide binding affinity.Results:The MAE of the SVR, RF and MLP models constructed using protein-peptide interaction interface characteristics are 0.2279, 0.2939 and 0.2041, their MSE are 0.1289, 0.1308 and 0.0780, and their R2 reached 0.8711, 0.8692 and 0.9220, respectively.Conclusion:The model constructed using protein-peptide interaction interface characteristics showed better prediction results. The key features for predicting protein-peptide binding affinity are the bSASA of negatively charged species, hydrogen bond acceptor, hydrophobic group, planarity, and aromatic ring.
Evaluation of Cytotoxic, COX Inhibitory, and Antimicrobial Activities of
Novel Isoxazole-carboxamide Derivatives
Authors: Hawash Mohammed , Jaradat Nidal , Abualhasan Murad , Qneibi Mohammad , Rifai Hama , Saqfelhait Tala , Shqirat Yaqeen , Nazal Alaa , Omarya Salam , Ibrahim Tymaa , Sobuh Shorooq , Zarour Abdulraziq , Mousa Ahmed 
Published: August 2022

Abstract:
Isoxazole derivatives are one of the heterocyclic structures that have various biological activities.

Objective:
This study aimed to design and synthesize novel isoxazole derivatives and evaluate their cytotoxic,
cyclooxygenase (COX) inhibitory, and antimicrobial activities.

Methods:
Coupling reactions of aniline derivatives and isoxazole carboxylic acid have been established to
synthesize chloro-fluorophenyl-isoxazole carboxamide derivatives. The synthesized compounds were
characterized using 1H, 13C-NMR, IR, and HRMS spectrum analysis and evaluated by MTS, COX kit,
and antimicrobial microdilution assays.

Results:
The synthesized compounds showed moderate to potent cytotoxic activity against all the
screened cancer cell lines (except 2b against HepG2) with an IC50 range of 0.107-77.83 μg/ml. The results
showed that the most potent compound against cervical cancer cell line (HeLa) was the 2b compound,
with an IC50 value of 0.11±0.10 μg/ml, which is less than the IC50 for the potent anticancer drug
Doxorubicin. While the 2a and 2b compounds have potential antiproliferative activities against Hep3B
with IC50 doses of 2.774±0.53 and 3.621±1.56 μg/ml, respectively. Furthermore, 2c compound was the
most active against MCF7, with an IC50 value of 1.59±1.60 μg/ml. In addition, the most potent isoxazole
derivative against the COX1 enzyme was the 2b compound, with an IC50 value of 0.391 μg/ml, and compound
2a had a good selectivity ratio of 1.44 compared to the Ketoprofen positive control. However,
compound 2c showed antifungal activity against Candida albicans with an MIC value of 2.0 mg/ml in
comparison to the antifungal drug Fluconazole (MIC = 1.65 mg/ml).

Conclusion:
The synthesized compounds could be candidates for anticancer drugs in the future, and other
analogues and cytotoxicity evaluations should be conducted.
Palladium (Pd)-based Photocatalysts for Suzuki Coupling Reactions: An
Overview
Authors: Boruah Jeena Jyoti , Das Siva Prasad 
Published: August 2022

Abstract:
Extensive research has been documented in the last few decades on the utilization of near
IR, visible and UV light in organic chemical transformations. In this brief review, we provide an
overview of the most noteworthy achievements in the area of photocatalytic Suzuki coupling reactions
by palladium (Pd)-based catalytic systems. The works on different types of Pd-based photocatalysts
for Suzuki coupling reaction and their characteristic as well as catalytic activity in terms of substrate
scope, recyclability, TON or TOF are discussed herein.
Multiple Cancer Combating by Natural Bioactives: A Review
Authors: Mishra Rakhi , Singh Ayushi , Mazumder Avijit , Mazumder Rupa , Tiwari Prashant 
Published: August 2022

Background:
Significant progress in the field of anticancer research has led to a rise in the study of bioactive chemicals with potential anticancer effects. Still, many bioactive natural chemicals must be investigated in order to generate more effective anti-cancer therapeutics.

Outline:
There have been many attempts to treat cancer, and this review summarizes many bioactive substances obtained from nature that have the ability to fight against different types of malignancies with minimal harm, based on diverse research. Polyphenolic flavonoids, carotenoid (fucoxanthin), tannin, and other notable natural bioactive with anticancer potential were examined and reviewed systematically with an eye toward their significance in many types of cancer treatment.

Conclusion:
Throughout the text, it was concluded that the natural bioactive play a very prominent role in combating different types of cancer, and the information related to the bioactive role in cancer treatment over the last 10 years was gathered from several research and review articles. The material kept in this paper can act as a template for future research in expressing the more beneficial role of other bioactive in acting as an adjuvant in chemotherapy practice for prevention and treatment of various cancer additionally with no or minimal adverse effects which are prominent with the conventional drugs used for the treatment of cancer.
Association between Sleep Duration and Early Pubertal Timing in Children
and Adolescents: A Systematic Review and Meta-analysis
Authors: Hashemipour Mahin , Maracy Mohammad Reza , Mozafarian Nafiseh , Yazdi Maryam , Hovsepian Silva 
Published: August 2022

Background:
Early puberty increases the risk of diverse health outcomes during adolescence and beyond. Several studies have explored the links between short sleep duration and early puberty worldwide.

Objective:
The current systematic review and meta-analysis aimed to evaluate the association between sleep duration and early pubertal timing based on published evidence systematically.

Methods:
We searched important electronic databases for articles that reported the association between childhood sleep duration and puberty timing up to October 2020. A total of 848 papers were identified from the databases and manual search. Finally, 10 studies including 23752 participants were included in the meta-analysis. We used the STROBE checklist to assess the quality of the included studies. We calculated the pooled effect sizes using a random or fixed effects model as appropriate.

Results:
Ten studies were eligible for this meta-analysis. There was an inverse significant association between sleep duration and the risk of early puberty, longer duration of sleep was associated with 0.34% decreased odds of early puberty (OR = 0.66, 95% CI = 0.58–0.77, I2 = 96.6%). In a subgroup analysis, when pubertal status was assessed by physical examination compared with Pubertal Development Scale (PDS) or Sexual Maturation Scale (SMS), the associations between sleep duration and age of puberty were attenuated. The pooled OR (95% CI) of studies measuring pubertal timing by PDS/SMS and Tanner stage were 0.50(0.37-0.69) and 0.91(0.77-1.09) respectively. In the subgroup analysis by BMI levels, the pooled OR (95% CI) was slightly attenuated 0.95(0.89-1.01).

Conclusions:
Longer sleep duration is associated with a lower risk of early puberty in children. The association between sleep duration and risk of early puberty may be modified by other factors such as BMI. To clarify the effect of sleep duration on the risk of early puberty in children, further prospective studies are needed.
Association of Asthma with COVID-19 Disease Severity in Pediatric
Patients
Authors: Torabizadeh Mehdi , Heidari Solmaz , Shokouhifar Shokoufeh , Mirkarimi Mohammadreza , Alisamir Mohsen , Mohammadi Shooka 
Published: August 2022

Background:
The impact of COVID-19 on asthmatic patients is still uncertain.

Objective:
This study intended to examine the associations between the severity of coronavirus dis-ease 2019 (COVID-19), asthma, and some inflammatory markers among pediatric patients.

Methods:
A retrospective study enrolled pediatric COVID-19 patients who were admitted to Abuzar Hospital (Ahvaz, Iran) during eight months. The diagnosis of COVID-19 was according to the real-time reverse transcription-polymerase chain reaction (RT‐PCR) method. Asthma diagnosis was confirmed by specialists through functional and clinical evaluations (positive bronchodilator reversibility test or positive methacholine challenge test). Demographic and clinical characteristics of the patients were documented. Asthmatic patients with COVID-19 were considered as Group 1 (n= 52) and non-asthmatic COVID-19 patients were assigned as Group 2 (n= 54).

Results:
The mean age of 106 patients was 71.28 ± 50.09 months (range: 1-16 years). Children with severe and moderate COVID-19 had significantly lower levels of neutrophils and lymphocytes, higher inflammatory markers, and longer hospital length of stay (LOS) than patients with a mild course of COVID-19 (p < 0.001). Patients in Group 1 had significantly longer LOS, higher dry cough, chest radiographic findings, fever, levels of D-dimer, fibrinogen, and C-reactive protein (CRP), as well as lower neutrophil and lymphocyte counts, compared with those in Group 2 (p < 0.001).

Conclusion:
The presence of asthma in COVID-19 patients was associated with severe COVID-19 in comparison with their non-asthmatic counterparts. Additional studies with large sample sizes are deemed necessary to determine the impact of asthma on the management and incidence of COVID-19 disease.
CADD Studies in the Discovery of Potential ARI (Aldose Reductase Inhibitors)
Agents for the Treatment of Diabetic Complications
Authors: Gupta Saurabh Kumar , Tripathi Pushpendra Kumar 
Published: August 2022

Abstract::
The lack of currently available drugs for treating diabetes complications has stimulated
our interest in finding new Aldose Reductase inhibitors (ARIs) with more beneficial biological
properties. One metabolic method uses aldose reductase inhibitors in the first step of the polyol
pathway to control excess glucose flux in diabetic tissues. Computer-aided drug discovery
(CADD) is key in finding and optimizing potential lead substances. AR inhibitors (ARI) have been
widely discussed in the literature. For example, Epalrestat is currently the only ARI used to treat
patients with diabetic neuropathy in Japan, India, and China. Inhibiting R in patients with severe to
moderate diabetic autonomic neuropathy benefits heart rate variability. AT-001, an AR inhibitor, is
now being tested in COVID-19 to see how safe and effective it reduces inflammation and cardiac
damage. In summary, these results from animal and human studies strongly indicate that AR can
cause cardiovascular complications in diabetes. The current multi-center, large-scale randomized
human study of the newly developed powerful ARI may prove its role in diabetic cardiovascular
disease to establish therapeutic potential. During the recent coronavirus disease (COVID-19) outbreak
in 2019, diabetes and cardiovascular disease were risk factors for severely negative clinical
outcomes in patients with COVID19. New data shows that diabetes and obesity are among the
strongest predictors of COVID-19 hospitalization. Patients and risk factors for severe morbidity
and mortality of COVID- 19.