bluuebunny/crossref_metadata_2025_split huggingface dataset:
Advances in Heart Failure with Preserved Ejection Fraction Management - The Role of Sacubitril-Valsartan, Pirfenidone, Spironolactone and Empagliflozin: Is Success a Series of Small Victories?
Authors: Giannopoulos Georgios , Kousta Maria , Anagnostopoulos Ioannis , Karageorgiou Sofia , Myrovali Evangelia , Deftereos Gerasimos , Fragakis Nikolaos , Siasos Gerasimos , Vassilikos Vassilios P. 
Published: February 2023

Background:Heart failure with preserved ejection fraction (HFpEF) is a syndrome characterized by marked heterogeneity in comorbidities and etiopathology substrates, leading to a diverse range of clinical manifestations and courses. Treatment options have been extremely limited and up to this day, there are virtually no pharmaceutical agents proven to reduce mortality in these patients.Objective:The primary objective of this narrative review is to critically summarize existing evidence regarding the use of Angiotensin Receptor-Neprilysin Inhibitor (ARNI), spironolactone, pirfenidone and empagliflozin in HFpEF.Methods:Medline (via PubMed) and Scopus were searched - from inception up to May 2022- using adequately selected keywords. Additional hand-search was also performed using the references of the articles identified as relevant (snowball strategy).Results:Angiotensin Receptor-Neprilysin Inhibitor (ARNI) and spironolactone, despite being very successful in HFrEF, did not do well in clinical trials of HFpEF, although there appear to be certain subsets of patients who may derive benefit. Data regarding pirfenidone are limited and come from small trials; as a result, it would be premature to draw firm conclusions, although it seems improbable that this agent will ever become a mainstay in the general population of HFpEF patients, while there may be a niche for the drug in individuals with comorbidities associated with an intense fibrotic activity. Finally, empagliflozin, largely welcomed as the first agent to have a “positive” randomized clinical trial in HFpEF, does not seem to evade the general pattern of reduced hospitalizations for HF with no substantial effect on mortality, seen in ARNI and spironolactone HFpEF trials.Conclusion:Recent research in drug treatment for HFpEF has resulted in an overall mixed picture, with trials showing potential benefits from certain classes of drugs, such as sodium-glucose co-transporter 2 inhibitors, and no benefit from other drugs, which have shown to be effective in patients with reduced ejection fraction. However, small steps may be the way to go in HFpEF, and success is sometimes just a series of small victories.
Nucleic Acid Nanomaterials-based Therapy for Osteoarthritis: Progress and
Prospects
Authors: Yao Yangxue , Yang Maobin , Shi Sirong 
Published: February 2023

Abstract:
Osteoarthritis (OA) involves lesions of the entire joint and remains one of the health problems plaguing
the world. The pathological mechanism of OA is complex and involves multiple signaling pathways. Over 300 million
people worldwide are living with OA, which imposes a huge burden on society. Nucleic acid nanomaterials are
of interest to the biomedical field due to their small dimension, ideal biocompatibility, and structure editability. Various
nucleic acids have been used as therapeutic drugs to regulate the pathogenesis and development of OA. Among
them, some can enter the cell by themselves and others with the aid of vectors. Apart from high therapeutic efficiency,
nucleic acid nanomaterials also act as carriers for transporting drugs. This paper reviews recent advances in nucleic
acid nanomaterials in OA therapy, suggesting that nucleic acid nanomaterials-based therapy has good prospects
for development.
Dose-dependent Effects of PRC2 and HDAC Inhibitors on Cardiomyocyte
Hypertrophy Induced by Phenylephrine
Authors: Chen Weixin , Wang Zhihua , Zhao Zhenyi , Lv Jian , Guo Ningning , Guo Qiuxiao , Zeng Sai , Fang Yu 
Published: February 2023

aims:
To elucidate the roles of PRC2 and HDACs in cardiomyocyte hypertrophy.

background:
Postnatal cardiomyocytes respond to stress signals by hypertrophic growth and fetal gene reprogramming, which involves epigenetic remodeling mediated by histone methyltransferase polycomb repressive complex 2 (PRC2) and histone deacetylases (HDACs). However, it remains unclear to what extent these histone modifiers contribute to the development of cardiomyocyte hypertrophy.

objective:
To compare the dose-dependent effects of GSK126 and TSA, inhibitors of PRC2 and HDACs, respectively, on cardiomyocyte hypertrophy.

method:
Neonatal rat ventricular myocytes (NRVMs) were stimulated by phenylephrine (PE; 50μM) to induce hypertrophy in the presence or absence of the PRC2 inhibitor GSK126 or the HDACs inhibitor Trichostatin A (TSA). Histone methylation and acetylation were measured by Western blot. Cell size was determined by wheat germ agglutinin (WGA) staining. Cardiac hypertrophy markers were quantified by quantitative reverse transcription polymerase chain reaction (qRT-PCR).

result:
PE treatment induced the expression of cardiac hypertrophy markers, including natriuretic peptide A (Nppa), natriuretic peptide B (Nppb), and myosin heavy chain 7 (Myh7), in a time-dependent manner in NRVMs. Histone modifications, including H3K27me3, H3K9ac, and H3K27ac, were dynamically altered after PE treatment. Treatment with TSA and GSK126 dose-dependently repressed histone acetylation and methylation, respectively. Whereas TSA reversed the PE-induced cell size enlargement in a wide range of concentrations, cardiomyocyte hypertrophy was only inhibited by GSK126 at a higher dose (1μM). Consistently, TSA dose-dependently suppressed the induction of Nppa, Nppb, and Myh7/Myh6 ratio, while these indexes were only inhibited by GSK126 at 1μM. However, TSA, but not GSK126, caused pro-hypertrophic expression of pathological genes at the basal level.

conclusion:
Our data demonstrate diversified effects of TSA and GSK126 on PE-induced cardiomyocyte hypertrophy, and shed a light on the epigenetic reprogramming in the pathogenesis of cardiac hypertrophy.

other:
Our data systematically compared the effects of TSA and GSK126 on PE-induced cardiomyocyte hypertrophy, and demonstrate the concentration thresholds for their protective function.
Metal-Organic Framework in Pharmaceutical Drug Delivery
Authors: Selvaraj Jubie , Kundu Sudipto , Swaroop Akey Krishna 
Published: February 2023

Abstract:
Metal-organic frameworks (MOFs) are porous, crystalline materials made up of organic ligands and metal ions/metal clusters linked by coordinative bonds. This large family is becoming increasingly popular for drug delivery due to their tuneable porosity, chemical composition, size and shape, and ease of surface functionalization. There has been a growing interest over the last decades in the design of engineered MOFs with controlled sizes for a variety of biomedical applica-tions. Starting with the MOFs classification adapted for drug delivery systems (DDSs) based on the types of constituting metals and ligands. MOFs are appealing drug delivery vehicles because of their substantial drug absorption capacity and slow-release processes, which protect and convey sensitive drug molecules to target areas. Other guest materials have been incorporated into MOFs to create MOF-composite materials, which have added additional functionalities such as externally triggered drug release, improved pharmacokinetics, and diagnostic aids. Magnetic nanoparticles in MOFs for MRI image contrast and polymer coatings that increase blood circulation time are exam-ples of synthetically adaptable MOF-composites. By including photosensitizers, which exert lethal effects on cancer cells by converting tumour oxygen into reactive singlet oxygen (1O2), metal-organic frameworks have been employed for photodynamic treatment (PDT) of malignancies among a multitude of nanosized therapies. Importantly, a variety of representative MOF applica-tions are described from the perspectives of pharmaceutics, disease therapy, and advanced drug de-livery systems. However, because of their weak conductivity, selectivity, and lack of modification sites, MOF materials' uses in electrochemical biosensing are restricted. MOF-based composites provide excellent electrical conductivity and robust catalytic activity by adding functionalized na-noparticles into MOF structures, which process benefits over single component MOFs.
Effects of Perceived Social Support on Health-Related Quality of Life in
Asymptomatic and Symptomatic People Living with HIV in China: A
Cross-Sectional Study
Authors: Xie Meilian , Wang Aiping , Wang Kerong , Yu Yanping , Lin Zhaoxia 
Published: February 2023

Objective:
Improving health-related quality of life (HRQOL) in people living with HIV
(PLWH) is one of the critical goals of HIV prevention and control in the following decades, and
perceived social support (PSS) has always exhibited a positive influence on patients' HRQOL. This
study aims to describe the gap in social support in improving HRQOL between symptomatic and
asymptomatic PLWH.

Methods:
By analysing secondary data from an online survey, a multicenter, descriptive and crosssectional
study was conducted. The correlation trend and differences between PSS and HRQOL
among asymptomatic and symptomatic PLWH were determined.

Results:
Information from 493 PLWH with ART medication was finally analyzed: 34.89% asymptomatic
PLWH and 65.11% symptomatic PLWH. There were significant differences observed between
the two groups in terms of family income (χ2 = 9.782, P = 0.021), HIV-positive duration (χ2
= 19.541, P < 0.001), stage of disease (χ2 = 9.617, P = 0.008), and comorbidities (χ2 = 26.119, P <
0.001). The mean score of HRQOL of PLWH for the whole domain of the questionnaire was 86.56
(SD = 15.95). In six domains of QOL and PSS, the asymptomatic group had better conditions than
the symptomatic group. There was a linear association between PSS and HRQOL, not only in the
symptomatic group but also asymptomatic population, after adjusting for potential confounding factors.
When the level of PSS was between 60 and 80, the HRQOL of the symptomatic group was
similar to that of the asymptomatic group. While the score of PSS exceeded 80, the HRQOL of the
symptomatic group was less sensitive to the changes in PSS. The social and environmental status of
HRQOL in PLWH was most strongly correlated with their PSS.

Conclusion:
The value of PSS on the HRQOL in PLWH is confirmed, especially for asymptomatic
subjects. Healthcare providers need a complete understanding of the gap in social support between
the asymptomatic and symptomatic populations. The comprehensive strategies, including symptom
management, active treatment, and social support, should be more efficient for improving the overall
health of symptomatic PLWH.

Trial Registration:
Clinicaltrials.gov: ChiCTR2100046225. Registered 11 May 2021.
Reference Range of CT Value in NC-CBBCT Based on Female Breast
Structure
Authors: Wei Wei , Zhong Wuning , Kang Wei , Zhao Xin , Yi XianLin , Su DanKe 
Published: February 2023

Background:
As a new high-resolution three-dimensional CT imaging technology, the essential
reference range of CT values in Cone-beam breast computed tomography (CBBCT) has not
been established to date.

Purpose:
To determine the reference range of computed tomography (CT) values in CBBCT for clinical
breast examination.

Materials and Methods:
In total, 913 cases (1167 lateral) were subject to CBBCT. CT values of the
glandular tissue, fat and different quadrants and different distances of CBBCT images were analyzed.
The nipple and muscle were also evaluated.

Results:
A total of 672 lateral breasts were included in the normal group for investigation. The reference
range of the absolute CT value of the chest wall muscle is -136.68~43.36 HU. The reference
range of the absolute CT value of the nipple is 176.39~334.02 HU. The reference range of the absolute
CT value of fat is -190.4~-63.67HU, and of glandular tissue is -12.2~199.07HU.

Conclusion:
Our results firstly established the baseline CT values of Non-contrast CBBCT in female
breasts, which will benefit cancer screening and lesion locating. The closer the normal breast fat and
glandular tissue is to the nipple, the greater the CT value. The older the age, the lower the density. The
CT values of fat are unstable in a distance of less than 5 cm, and the CT values of glandular tissues are
relatively stable. The difference between the upper and lower quadrants is significant in the same lateral
breast and the same section.
Possible Mechanism and Pharmacological Activities of a Flavolignan
Silibinin
Authors: Bhardwaj Hemlata , Vasudeva Neeru , Sharma Sunil 
Published: February 2023

Abstract:
Silymarin, a flavonolignan derived from the seeds extract of Silybum marianum (milk
thistle), has been frequently used since ancient times. It is made up of flavonolignans such as silychristin,
isosilybin A and B, dehydrosilybin, and silybin as well as flavonoids like taxifolin, with
silibinin being the most active. Silibinin is a diastereoisomeric combination of two flavonolignans,
silybin A and silybin B, with a diastereoisomeric structure. It is found in a variety of phytopreparations
that are used to prevent and treat liver disorders. It is considered an important component
in a huge range of cosmetic, pharmacological, and medical formulations. Several investigations
have revealed that silibinin has anticancer and chemopreventive properties, as well as hypocholesterolaemic,
antimicrobial, antidiabetic, anticancer, antihypertension, antiparkinson, antiinflammatory,
antioxidant, cardioprotective, and neuroprotective benefits by the help of different
mechanisms such as inducing apoptosis, decreasing cell proliferation, inhibiting angiogenesis and
viral transition and its entry, and also regulating insulin secretion by decreasing or increasing the
expression of sterol regulatory element binding protein-1c (SREBP-1C) and insig-1 transcription
factor, etc. Silibinin data is gathered from many public databanks in order to emphasize its important
role in the treatment or prevention of various diseases.
Investigation of the Potential Antidiabetic Effect of Zygophyllum Sp. by
Studying the Interaction of its Chemical Compounds with Alpha-Amylase
and DPP-4 Enzymes using a Molecular Docking Approach
Authors: Arbi Bouziane , Bouchentouf Salim , EL-Shazly Mohamed 
Published: February 2023

Background:
Diabetes type II is one of the most serious metabolic diseases in the world attracting
the attention of many researchers who predict that diabetes will be one of the top major causes
of disability or death in the coming few decades. To tackle this disease several classes of synthetic
molecules were developed to target certain enzymes that are involved in sugar metabolism. Herbal extracts
targeting diabetes have witnessed renascence in the last few decades with the introduction of
highly effective herbal remedies that effectively regulate sugar levels in the blood.

Methods:
In this work, we studied the interaction of molecules from the Zygophyllum sp. with the
main enzymes involved in sugar metabolism (alpha-amylase and DPP-4) using Molecular Operating
Environment (MOE) as a molecular docking technique. The choice of Zygophyllum sp. was based on
an ethnopharmacological local survey.

Results:
The calculated scores of molecules from Zygophyllum sp. were better than those calculated
with the known inhibitors. The results demonstrated that many molecules showed good affinity
to two important enzymes involved in type II diabetes, suggesting that these molecules may possess
potential hypoglycemic and antidiabetic effects. These results added further scientific evidence supporting
the folk use of Zygophyllum sp. in targeting diabetes and suggested its potential as a valuable
source of antidiabetic drug leads.

Conclusion:
The calculated scores of molecules from Zygophyllum sp. were better than those calculated
with the known inhibitors. The results demonstrated that many molecules showed good affinity
to two important enzymes involved in type II diabetes, suggesting that these molecules may possess
potential hypoglycemic and antidiabetic effects. These results added further scientific evidence supporting
the folk use of Zygophyllum sp. in targeting diabetes and suggested its potential as a valuable
source of antidiabetic drug leads.
The Role of Various Factors in Neural Differentiation of Human Umbilical
Cord Mesenchymal Stem Cells with a Special Focus on the Physical Stimulants
Authors: Seyyedin Sajad , Ezzatabadipour Massood , Nematollahi-Mahani Seyed Noureddin 
Published: February 2023

Abstract:
Human umbilical cord matrix-derived mesenchymal stem cells (hUCMs) are considered as
ideal tools for cell therapy procedures and regenerative medicine. The capacity of these cells to differentiate
into neural lineage cells make them potentially important in the treatment of various neurodegenerative
diseases. An electronic search was performed in Web of Science, PubMed/MEDLINE, Scopus and
Google Scholar databases for articles published from January 1990 to March 2022. This review discusses
the current knowledge on the effect of various factors, including physical, chemical and biological stimuli
which play a key role in the differentiation of hUCMs into neural and glial cells. Moreover, the currently
understood molecular mechanisms involved in the neural differentiation of hUCMs under various environmental
stimuli are reviewed. Various stimuli, especially physical stimuli and specifically different
light sources, have revealed effects on neural differentiation of mesenchymal stem cells, including
hUCMs; however, due to the lack of information about the exact mechanisms, there is still a need to find
optimal conditions to promote the differentiation capacity of these cells which in turn can lead to significant
progress in the clinical application of hUCMs for the treatment of neurological disorders.
Coumarin and Piperazine Conjugates as Selective Inhibitors of the Tumor-associated
Carbonic Anhydrase IX and XII Isoforms
Authors: Sethi Aaftaab , Munagalasetty Sharon , Arifuddin Mohammed , Carradori Simone , Supuran Claudiu T. , Alvala Ravi , Alvala Mallika 
Published: February 2023

Background:
Carbonic Anhydrases (CAs) are a family of metalloenzymes that catalyze the reversible interconversion
of CO2 and water to bicarbonate and proton. CA isoforms I, II, IX, and XII are considered physiologically
and pharmacologically relevant.

Objective:
The objective of this study is to synthesize potent and selective tumor-associated CA IX and XII inhibitors.

Methods:
A library of 17 coumarin derivatives clubbed with piperazine and benzyl moiety was designed, synthesized
and evaluated for its inhibitory effects and selectivity profile towards physiologically and pharmacologically relevant
CA isoforms I, II, IX, and XII.

Results:
All the derivatives were found to be active against the tumor-associated isoforms IX and XII. The most active
compound against hCA (human Carbonic Anhydrase) IX was found to possess a Ki of 229 nM, while the one against
hCA XII had a Ki of 294.2 nM. Additionally, two of the compounds were found to have exquisite selectivity towards
the off-target hCA I and II isoforms. Moreover, they were found to be approximately 20-fold more selective towards
hCA IX than XII. The selectivity of the compounds was further investigated via molecular modeling techniques.

Conclusion:
Coumarin-piperazine hybrids were identified as potent and selective CA IX and XII inhibitors. Molecular
modeling techniques provided interesting cues pertaining to observed selectivity.
Development of an Automatic Tree Coating Machine Based on Cooperative
Functioning of Multiple Nozzles
Authors: Cao Yangfan , Wang Wenchao , Qi Wei , Jing Maoyan , Zhao Ying , Sun Qun 
Published: February 2023

Background:
At present, the tree whitewashing in China is mainly based on the
traditional manual whitewashing method, which has the shortcomings of high labor intensity, low
efficiency, excessive wastage of paint, danger to human health, and poor adaptability to the strong
seasonality of tree whitewashing.

Objective:
To reduce the sunburn and water evaporation of trees, prevent the invasion of diseases
and pests, and to enhance the disease resistance of trees, the tree trunk coating mainly uses a traditional
manual method. However, this mainstream manual whitewashing approach is labor- intensive
and inefficient. To resolve the issue, an automatic spraying device for tree coating based on multisprinkler
cooperative operation is designed. It can meet the requirements of tree whitening and replace
manual operation. To some extent, this machine can reduce labor intensity and promote the
healthy growth of trees.

Methods:
Through literature review and field research, the technical requirements and research status
of tree whitewashing have been explored. The three-dimensional Software Solidworks has been
used to model the rack assembly, device moving assembly, up and down moving assembly, nozzle
moving support assembly, and spraying assembly, and then the three-dimensional assembly of the
whole machine has been carried out. According to the simulation optimization results, the initial
three-dimensional model is modified, and then the engineering drawing is drawn through the threedimensional
model for prototype processing, manufacturing, and assembly. The schematic diagram
and PCB pattern of the circuit board of the electronic control system have been drawn, the program
of the controller k60dn512 single chip microcomputer has been written, simulation and debugging
have been conducted, and the control system has been designed. Laboratory and field tests on the
prototype have been conducted, and the device has been improved according to the test data.

Results:
Experiments show that the device can accurately spray trees with a trunk circumference of
50-125cm. When the trunk circumference is greater than 125 cm, repeated spraying can meet the
spraying requirements. The trunk circumference is in the range of 50-80 cm, and the opening and
closing angle is in the range of 80-100°. The spraying effect is good, and the average spraying coverage
can reach 97.73%. The trunk perimeter is in the range of 80-125 cm, and the opening and
closing angle is in the range of 100-120°. The spraying effect is the best, and the average spraying
coverage can reach 98.06%. During the experiment, the spraying efficiency of the device can reach
100 trees/hour, which is significantly higher than the efficiency of manual operation.

Conclusion:
The device improves the efficiency and quality of tree spraying, reduces the labor
intensity of operation, and realizes the high-efficiency spraying for tree coating.