bluuebunny/crossref_metadata_2025_split huggingface dataset:
Signal Peptides - Promising Ingredients in Cosmetics
Authors: Skibska Agnieszka , Perlikowska Renata 
Published: August 2021

:
Naturally occurring peptides found in the human skin can serve particular biological activities
and play roles as signaling molecules of various physiological processes such as homeostasis,
growth, defense or immunity. Their great biological activity resulted in a growing interest in the
pharmaceutical industry. Researchers consider peptides either promising compounds with potential
application for human diagnosis, therapy or cosmetics. Peptides are becoming interesting cosmetic
ingredients with the functions to reduce premature skin aging, improve the barrier function of skin,
moisturize the skin, protect it from UV damage, and anti-inflammatory properties that alleviate acne
and irritation. Till now, peptides of different origins were investigated in formulation developed to
enhance collagen or elastin production, increase fibroblast proliferation, improve wound healing or
skin condition. Most of them are obtained by chemical synthesis or by partial digestion of animal
proteins. Short and easily synthesized peptides with alternative amino acid sequence, and combinations
have created a new field of molecules inspired by nature and implemented in the cosmetic
industry. Nowadays, peptides are cheaper and easier to produce in large quantities. The efficient
process development methods allow obtaining nearly unlimited sequences, which makes them functionally
preferred. Generally, cosmetic peptides are categorized as carrier peptides, neurotransmitter-
affecting peptides, enzyme inhibitor peptides and signal peptides. The use of signal peptides in
cosmetics increased over a few years. These molecules trigger a signaling cascade and stimulate
fibroblast collagen production, the proliferation of elastin, fibronectin, laminin, etc. Thus, a literature
search on a topical application of the most common signal peptides; and their current status in
the cosmetic industry was carried out.
Targeting the HIF-1α/Cav-1 Pathway with a Chicory Extract/Daidzein Combination Plays a Potential Role in Retarding Hepatocellular Carcinoma
Authors: Zakaria Sherin , Nawaya Reem , Abdel-Hamid Nabil M. , Eldomany Ramadan A. , El-Shishtawy Mamdouh M. 
Published: August 2021

Background:Hepatocellular carcinoma (HCC) is one of the most rapidly growing solid cancers, that is characterized by hypoxia. Hypoxia-inducible factor-1α (HIF-1α) is a transcription factor that regulates tumor proliferation and metastasis. It induces caveolin-1 (Cav-1) expression, a glycoprotein found on the membrane surface, then Cav-1 triggers angiogenesis and metastasis in HCC.Objectives:We hypothesize that targeting HIF-1α and consequently, Cav-1 using the antioxidant natural compound such as chicoric acid and a Cav-1 inhibitor daidzein (DAZ) could be a useful approach in the management of HCC. This study was conducted to investigate the possible therapeutic efficacy of standardized chicory leaf extract (SCLE) and DAZ via modulation of HIF-1α and Cav-1 in HCC rats.Methods:Diethyl nitrosamine (DENA) was used for HCC induction. After the induction period, four groups (10 rats for each) were treated with SCLE, DAZ, a combination of both, as well as sorafenib, all compared to the non-treated control. We assessed hepatic HIF-1α protein expression, Cav-1 gene expression, serum level of AFP, hepatic tissue content of VEGF, MMP-9, oxidative stress markers MDA and SOD.Results:DAZ, SCLE, and their combination, significantly down-regulated the expression of HIF-1α, Cav-1, and consequently dampened MMP-9, VEGF, hepatic content. It has been observed that the combination treatment showed a synergistic effect compared to either treatment alone. Importantly, the combination treatment exhibited a significantly more potent effect than sorafenib.Conclusion:This study showed the potential role of the HIF-1α/Cav-1 pathway in HCC progression, moreover, SCLE and DAZ showed a potent efficacy in retarding HCC via modulation of this pathway.
Effectiveness of Relationship Enrichment Program (REP) on Sexual Dysfunction
and Satisfaction of Females with Multiple Sclerosis-An Educational
Study
Authors: Vakilian Katayon , Sayari Negin , Khalajinia Zohre , Hejazi Seyyed Amir , Vahedian Mostafa 
Published: August 2021

Aims:
Improving sexual function in women with disability such as multiple sclerosis
was aimed.

Background:
Sexual dysfunction and the consequent low satisfaction is very common in females
with Multiple Sclerosis (MS).

Objectives:
This study aimed to investigate the effectiveness of Relationship Enhancement Therapy
(REP) on sexual function and satisfaction of females with MS.

Methods:
The present study was an educational design with two groups, in which 44 females with
MS participated and their spouses (N= 88) participated and randomly divided in two groups of intervention
(N= 22 couples) and control (N= 22 couples). They signed written consent forms and
were included in the project. The intervention group received the REP in six 90-minute sessions.
The groups completed standard questionnaires of sexual dysfunction and sexual satisfaction in
three stages of pretest-posttest and 3 months later. The Descriptive and inferential statistics (Twoway
repeated measures ANOVA, chi-square, t-test and Mann-Whitney U test) were used to analyze
data.

Results:
The results of analysis showed that there was a clinically significant difference between
the scores of sexual dysfunction in different phases of the assessment between two groups (p
<0.05). Also sexual satisfaction was higher in the intervention group vs. in the control (p <0.05).

Conclusion:
According to the findings, marital enrichment program was effective in improvement
of sexual function and sexual satisfaction of females with multiple sclerosis. It is recommended to
healthcare providers to use enrichment alongside medical services to improve patients' sexual life.
Possible Role of PTEN Expression in Discriminating Benign Endometrial
Hyperplasia from Atypical Hyperplasia/Endometrial Intraepithelial Neoplasia
in a Series of Egyptian Patients
Authors: Khalifa Sara E. , Ramzy Nevine I. , Ibrahiam Wael S. , Ali Hanan H.M. , Akle Mona M.A. 
Published: August 2021

Background:
Endometrial hyperplasia represents a heterogeneous group of lesions in response to the unopposed growth-promoting action of estrogen. WHO classified endometrial hyperplastic lesions into Benign Hyperplasia (BH) and atypical hyperplasia/ endometrial intraepithelial neoplasia AH/EIN. Phosphatase and tensin homolog (PTEN) is one of the earliest and most common genetic abnormalities detected in endometrioid adenocarcinoma (type I) and even in its precursors. This study aimed at histological evaluation of hyperplastic endometrial lesions according to WHO 2014 and investigating the role of PTEN expression in highlighting the precancerous group (AH/EIN).

Patient and Method:
This study included a series of 70 Egyptian patients suffered from hyperplastic endometrial lesions. They were previously diagnosed according to WHO1994 schema simple endometrial hyperplasia without atypia (n=18), simple endometrial hyperplasia with atypia (n=2), complex hyperplasia without atypia (n=25), complex hyperplasia with atypia (n=5) and hyperplastic endometrial polyps (n=20).

Results:
Cases were histologically re-evaluated according to WHO 2014 classification; BH (62 cases) and eight cases of AH/EIN. A significant difference in PTEN expression (regarding percentage and intensity of staining) in relation to histopathological diagnosis was detected (P-value 0.02 and <0.05, respectively). The sensitivity and specificity of the absence of diffuse PTEN protein expression (>50%) to detect AH/EIN were 100% and 77.4%, respectively. Conclusion: Diffuse, dim or loss of immunohistochemical expression of PTEN protein is significantly correlated with the new WHO classification segregation of AH/EIN as precancerous lesions. However, further studies are recommended to confirm this association.
Patterns of Cell Death Induced by Thiohydantoins in Human MCF-7 Breast Cancer
Cells
Authors: Fagundes Tatiane Renata , Bortoleti Bruna , Camargo Priscila , Concato Vírgínia , Tomiotto-Pellissier Fernanda , Carloto Amanda , Panis Carolina , Bispo Marcelle , Junior Fernando Macedo , Conchon-Costa Ivete , Pavanelli Wander Rogério 
Published: August 2021

Background:
Conventional therapies for breast cancer are still a challenge due to cytotoxic drugs not being
highly effective with significant adverse effects. Thiohydantoins are biologically active heterocyclic compounds reported
for several biological activities, including anticarcinogenic properties, etc. This work aims to assess the use of
thiohydantoin as a potential antitumor agent against MCF-7 breast cancer cells.

Methods:
MTT and neutral red assays were used to assess the possible cytotoxic activity of compounds against MCF-7
cells. Cell volume measurement and analysis were performed by flow cytometry. Fluorescence analysis was carried out
to determine patterns of cell death induced by thiohydantoins.

Results:
The treatment with micromolar doses of thiohydantoins promoted a decrease in the viability of MCF-7 breast
tumor cells. An increase in the ROS and NO production, reduction in cell volume, loss of membrane integrity, mitochondrial
depolarization, and increased fluorescence for annexin-V and caspase-3 were also observed. These findings
indicate cell death by apoptosis and increased autophagic vacuoles, stopping the cell cycle in the G1/ G0 phase.

Conclusions:
Our results indicate that thiohydantoins are cytotoxic to breast tumor cells, and this effect is linked to the
increase in ROS production. This phenomenon changes tumorigenic pathways, which halt the cell cycle in G1/G0. This
is an essential checkpoint for DNA errors, which may have altered how cells produce energy, causing a decrease in
mitochondrial viability and thus leading to the apoptotic process. Furthermore, the results indicate increased autophagy,
a vital process linked to a decrease in lysosomal viability and thus considered a cell death and tumor suppression
mechanism.
Alkylating Agents, the Road Less Traversed, Changing Anticancer Therapy
Authors: Kumar Dileep , Karati Dipanjan , Mahadik Kakasaheb Ramoo , Trivedi Piyush 
Published: August 2021

:Cancer is considered one of the gruelling challenges and poses a grave health hazard across the globe. According to the International Agency for Research on Cancer (IARC), new cancer cases increased to 18.1 million in 2018, with 9.6 million deaths, bringing the global cancer rate to 23.6 million by 2030. In 1942, the discovery of nitrogen mustard as an alkylating agent was a tremendous breakthrough in cancer chemotherapy. It acts by binding to the DNA, and creating cross linkages between the two strands, leading to halt of DNA replication and eventual cell death. Nitrogen lone pairs of ‘nitrogen mustard’ produce an intermediate 'aziridinium ion' at the molecular level, which is very reactive towards DNA of tumour cells, resulting in multiple side effects with therapeutic consequences. Owing to its high reactivity and peripheral cytotoxicity, several improvements have been made with structural modifications for the past 75 years to enhance its efficacy and improve the direct transport of drugs to the tumour cells. Alkylating agents were among the first non-hormonal substances proven to be active against malignant cells and also the most valuable cytotoxic therapies available for the treatment of leukaemia and lymphoma patients. This review focus on the versatile use of alkylating agents and the Structure Activity Relationship (SAR) of each class of these compounds. This could provide an understanding for design and synthesis of new alkylating agents having enhanced target specificity and adequate bioavailability.
Pulmonary Delivery of Docetaxel and Celecoxib by PLGA Porous Microparticles for
Their Synergistic Effects Against Lung Cancer
Authors: Emami Jaber , Ziaei Elham , Rezazadeh Mahboubeh , Kazemi Moloud 
Published: August 2021

Background:
using a combination of chemotherapeutic agents with novel drug delivery platforms to enhance
the anticancer efficacy of the drug and minimizing the side effects, is imperative to lung cancer treatments.

Objective:
The aim of the present study was to develop, characterize, and optimize porous poly (D, L-lactic-co-glycolic
acid) (PLGA) microparticles for simultaneous delivery of docetaxel (DTX) and celecoxib (CXB) through the pulmonary
route for lung cancer.

Methods:
Drug-loaded porous microparticles were prepared by an emulsion solvent evaporation method. The impact
of various processing and formulation variables including PLGA amount, dichloromethane volume, homogenization
speed, polyvinyl alcohol volume, and concentration, was assessed based on entrapment efficiency, mean release time,
particle size, mass median aerodynamic diameter, fine particle fraction, and geometric standard deviation using a twolevel
factorial design. An optimized formulation was prepared and evaluated in terms of size and morphology using a
scanning electron microscope.

Results:
FTIR, DSC, and XRD analyses confirmed drug entrapment and revealed no drug-polymer chemical interaction.
Cytotoxicity of DTX along with CXB against A549 cells was significantly enhanced compared to DTX and CXB
alone and the combination of DTX and CXB showed the greatest synergistic effect at a 1/500 ratio.

Conclusion:
In conclusion, the results of the present study suggest that encapsulation of DTX and CXB in porous
PLGA microspheres with desirable features is feasible and their pulmonary co-administration would be a promising
strategy for the effective and less toxic treatment of various lung cancers.
Strategic Approaches to Target the Enzymes using Natural Compounds
for the Management of Alzheimer’s Disease: A Review
Authors: Ahmad Syed Sayeed , Younis Kaiser , Philippe Jeandet , Aschner Michael , Khan Haroon 
Published: August 2021

:
Alzheimer's Disease (AD) is a chronic neurodegenerative disease. It is clinically characterized
by memory loss and intellectual decrease, among other neurological deficits. The etiology
of AD is not completely understood but includes amyloid plaques and intracellular helical filaments
as well as neurofibrillary tangles with hyperphosphorylated tau protein. AD is also associated
with alterations in amyloid processing genes, such as PSEN1 or PSEN2 and APP. The modulation
of the immune system, cholesterol metabolism, and synaptic vesicle endocytosis have all been
shown to remediate AD. In this review, enzymes such as AChE, BuChE, β-secretase, γ-secretase,
MAO, and RAGE are discussed as potential targets for AD treatment. The aim of this review was
to address the molecular mechanisms as well as various genetic factors in AD etiology. The use of
natural compounds against these targets might be beneficial for the management of AD.
Efficacy and Outcomes of a Novel Telephone-based Gout Disease Management Program
Authors: Al Harash Abdalhamid , Laginya Gina , Ayoub William T. 
Published: August 2021

Objective:
Gout is the most common inflammatory arthritis in the United States. Despite published guidelines, management remains suboptimal, leading to unnecessary morbidity and increased cost of care. We have designed the gout disease management program (GDMP) to improve outcomes, increase patient satisfaction, and decrease healthcare utilization.

Methods:
Gout patients were seen at their usual rheumatology clinical visit and offered participation in the GDMP. Data were collected between April 2017 and November 2019. Serum uric acid (SUA) levels were measured at the initial outpatient encounter, at the entrance to GDMP, and every 4 weeks until SUA was at the goal of ≤6 mg/dl. Through telephonic encounters, gout-related recent hospitalizations, and ER or urgent care visits since the last encounter were ascertained. Self-reported gout medication usage and adherence were also determined. Patient satisfaction with GDMP was surveyed using a 5-point Likert scale.

Results:
A total of 158 patients were enrolled, of which 112 had ≥ 1 telephone encounter and were included in our analyses. During the telephone phase, 79 patients (70%) achieved the SUA goal of ≤6.0 mg/dl. Only 3 patients (2.6%) required hospitalization or visits to an ER or urgent care center due to gout flare, and 98% rated their encounter as a 5 on the 5-point Likert scale.

Conclusion:
Our telephone-based management program for gout led to improved clinical outcomes as defined by the ACR guidelines, decreased healthcare visits, and had high patient satisfaction.

Significance and Innovations:
• First telephone-based, rheumatology providers-led study to manage gout
• Additional evidence to confirm the feasibility and benefit of telemedicine in common diseases
• First study to show excellent patient satisfaction
The Role of Attitude, Behavior, and Road Conditions in Traffic Violation among Workers and Students in Bandung City, Indonesia
Authors: Prasetyanto Dwi , Rizki Muhamad , Maulana Andrean 
Published: August 2021

Introduction:
This study aims to explore the attitudes towards riding safety, behavior regarding safety gear, documents, and vehicle and riding preparedness, and perceived road conditions among worker and student motorcyclists, and the influence of these on their violation behavior.

Methods:
To further explore the violation behavior, the effects of the infrastructure quality, personal and travel characteristics, and the experience of accidents were also included in the variables. This study collected data on motorcycle users’ behavior in Bandung City and used Structural Equation Modeling (SEM).

Results and Discussion:
This research underlines that behavior regarding safety gear, documents, and vehicle and riding preparedness is an important factor that decreases the violation behavior. Interestingly, a positive attitude towards safe riding does not straightforwardly lead to better behavior in preparing the vehicle, safety gear, and documents.

Conclusion:
Good quality infrastructure also promotes a reduction of traffic violations. Improving road infrastructure safety and both promoting and monitoring users’ safe riding behavior are suggested to lower the number of traffic violations.
Chimeric Antigen Receptor T-cells (CARs) in Cancer Treatment
Authors: Zam Wissam , Assaad Amany 
Published: August 2021

Background:
Cancer is one of the leading causes of death worldwide. Chemotherapy, radiation
therapy, and stem cell transplantation were the main cancer treatment approaches for several
years but due to their limited effectiveness, there was a constant search for new therapeutic approaches.
Cancer immunotherapy that utilizes and enhances the normal capacity of the patient's immune
system was used to fight against cancer. Genetically engineered T-cells that express Chimeric
Antigen Receptors (CARs) showed remarkable anti-tumor activity against hematologic malignancies
and are now being investigated in a variety of solid tumors. The use of this therapy in the last
few years has been successful, achieving great success in improving the quality of life and prolonging
the survival time of patients with a reduction in remission rates. However, many challenges
still need to be resolved in order for this technology to gain widespread adoption.

Objective:
This review summarizes various experimental approaches towards the use of CAR T--
cells in hematologic malignancies and solid tumors.

Conclusion:
Finally, we address the challenges posed by CAR T-cells and discuss strategies for improving
the performance of these T-cells in fighting cancers.
Development and Validation of a Simple Micromethod for the Determination of Metformin in Plasma by HPLC-UV for Application in Pharmacokinetic Studies
Authors: Morales-Barragán Miriam N. , del Carmen Romero-Méndez María , del Carmen Milán-Segovia Rosa , Rodríguez-Rivera Jaime G. , Aguilar-Torres María A. , Romano-Moreno Silvia 
Published: August 2021

Background:
Metformin is the first-line drug to enhance glycemic control of type 2 DIABETES
Mellitus (DM2) patients. Some reported methods to determine plasma metformin by
HPLC-UV are not sensitive enough. Other methods require long extraction processes.

Objective:
The objective of this study was to develop and validate a simple and rapid analytical
method to determine plasma metformin by HPLC-UV for application in a population pharmacokinetic
study.

Methods:
Analyte was extracted from plasma by a simple protein precipitation technique using
trichloroacetic acid (15%, w/v) as the precipitating agent. Plasma samples were analyzed using a
C18 column (3.0 x 150 mm, 3.5 μm) under isocratic elution with 30 mM sodium hexansulfonate
(pH 5) and acetonitrile (95: 5, v,v).

Results:
The limit of quantification (LOQ) was 0.1 μg mL-1 and the calibration curve was linear up
to 4 μg mL-1 with a correlation coefficient >0.99. The mean recovery for metformin using this extraction
procedure was 84.4 - 86.6%. The intra- and inter-day coefficients of variation and percent
error values of the assayed method were <20% and <15% for LOQ and QCs, respectively. Metformin
was stable in plasma samples by subjecting it to three freeze-thaw cycles and storing it up to
60 days at -80°C. This method was applied to determine plasma metformin concentrations in patients
with type 2 diabetes mellitus treated with this drug.

Conclusion:
The HPLC-UV method developed is selective, accurate and precise for the quantification
of metformin in plasma samples, since sample processing is fast and simple, in addition to being
applicable in pharmacokinetic studies.
Pendidikan Agama Islam Non Formal dalam Setting Inklusif bagi Anak dengan Hambatan Pendengaran
Authors: Pamungkas Bayu , Alimin Zaenal 
Published: August 2021

Penelitian ini bertujuan untuk menggambarkan pelaksanaan pendidikan agama Islam bagi anak dengan hambatan pendengaran di Masjid Khoiru Ummah Semarang. Jenis penelitian ini adalah penelitian kualitatif deskriptif menggunakan desain studi kasus. Teknik observasi partisipatif dan wawancara semi terstruktur terhadap subjek penelitian yakni tiga pembimbing anak dengan hambatan pendengaran dan tiga anak dengan hambatan pendengaran digunakan untuk pengumpulan data. Dari penelitian ini diperoleh data hasil penelitian sebagai berikut: (1) dalam proses pendidikan terdapat lima kegiatan pendidikan agama. Seluruh pelaksanaan kegiatan melibatkan masyarakat umum, BISINDO digunakan sebagai sistem komunikasi utamanya selain penggunaan Komunikasi total, Contextual Teaching and Learning diterapkan sebagai metode pembelajaran, serta materi pendidikan agama yang diajarkan disesuaikam; (2) dalam setting kegiatan terdapat tiga setting yang disesuaikan dengan kompleksitas materi yang diajarkan; (3) profil anak dengan hambatan pendengaran yang mengikuti pendidikan agama adalah anak dengan hambatan pendengaran usia remaja. Mereka juga mengajak anak dengan hambatan pendengaran lain untuk ikut bergabung; (4) terkait profil pembimbing anak dengan hambatan pendengaran, mereka adalah masyarakat yang sukarela membimbing anak dengan hambatan pendengaran yang kemudian mengikuti pelatihan intensif; (5) hasil pendidikan agama menunjukkan bahwa anak dengan hambatan pendengaran memiliki kefahaman beragama, ketaatan dalam beribadah dan hubungan bermasyarakat yang baik.