bluuebunny/crossref_metadata_2025_split huggingface dataset:
Targeting TRIM29 As a Negative Regulator of CAR-NK Cell
Effector Function to Improve Antitumor Efficacy of these Cells:
A Perspective
Authors: Saleh Zahra , Noroozi Maryam , Eshkevar Vakili Mahsa , Kabelitz Dieter , Nasrollahi Hamid , Kalantar Kurosh 
Published: May 2023

Abstract:
Natural killer (NK) cells are among the most important cells in innate immune
defense. In contrast to T cells, the effector function of NK cells does not require prior
stimulation and is not MHC restricted. Therefore, chimeric antigen receptor (CAR)-NK
cells are superior to CAR-T cells. The complexity of the tumor microenvironment (TME)
makes it necessary to explore various pathways involved in NK cell negative regulation.
CAR-NK cell effector function can be improved by inhibiting the negative regulatory
mechanisms. In this respect, the E3 ubiquitin ligase tripartite motif containing 29
(TRIM29) is known to be involved in reducing NK cell cytotoxicity and cytokine
production. Also, targeting TRIM29 may enhance the antitumor efficacy of CAR-NK
cells. The present study discusses the negative effects of TRIM29 on NK cell activity
and proposes genomic deletion or suppression of the expression of TRIM29 as a novel
approach to optimize CAR-NK cell-based immunotherapy.
A Computational Study of Famciclovir Derivatives Against Thymidine
Kinase as a Molecular Target for the Development of Novel Anticancer
Drugs via Suicide Gene Therapy Concepts
Authors: Thangavelu Saravanan , Thangavelu Prabha , Kumar M.R. Pradeep , Singaravel Sengotuvelu , Vivekanandan Lalitha , Murugesan Jagadeeswaran , Thangavel Sivakumar 
Published: May 2023

Background:
The viral thymidine kinase (TK) phosphorylates the antiviral medication
famciclovir (FCV), which treats herpes simplex virus (HSV-TK). The phosphorylated FCV destroys
the infected cells by preventing cellular DNA synthesis.

Objective:
We hypothesize that FCV impurity, which is a related substance to FCV, should be efficient
in killing cells independent of HSV-TK and is currently the most widely used suicide agent for
gene therapy of cancer.

Methods:
This study proposes the binding affinity of these derivatives for the active site of TK
through molecular docking to a protein (PDB ID: 1W4R). The derivatives' reliability was ensured
through the in-silico preliminary drug designing model by screening their Lipinski rule of five violations,
if any, ADMET prediction for their profile using online tools. Using MOE 2009.10 computational
software, we performed molecular docking of approximately 22 famciclovir derivatives alongside
the famciclovir drug.

Results:
Our results suggest that these derivatives are indicative of possible chemical stability irrespective
of all the parameters used to evaluate the selected derivatives as a possible drug candidates
for their cytotoxicity. FC20 (i.e., 2-(2-(2-((1-(9-(4-Acetoxy-3-(acetoxymethyl)butyl)-2-amino-9Hpurin-
8-yl)ethyl)amino)-9H-purin-9-yl)ethyl)propane-1,3-diyl diacetate) and FC21 (i.e., 2-Amino-1,9-
dihydro-9-(4-hydroxybutyl)-6H-purin-6-one), showed maximum and minimum scores of -26.95 and -
7.21 kcal/mol, respectively when compared to famciclovir (-15.4122 kcal/mol).

Conclusion:
Considering that there might be a cytotoxicity effect due to competition between protein
TK and the suicidal gene of famciclovir derivatives. The outcome of the study proved that the FCV
impurity could successfully modify an HSV-TK-dependent antiviral drug into an anti-tumor drug.
Further, it can be used for the design and development of novel compounds of FCV impurity that
could be cytotoxic agents if properly delivered to cancer cells.
Concise Review on Scientific Approaches to Burns and Scars
Authors: Malhotra Hitesh , Sharma Prerna , Kamal Mohammad Amjad , Kaushik Peeyush , Rani Nidhi 
Published: May 2023

Abstract:
Burns are large open surgical lesions bathed in virulent pus that result in rupturing of the
cutaneous membrane, which has serious consequences such as an extensive loss of proteins, and
body fluids, increased chances of infections, and sometimes death. These can be classified based
on their penetration levels, i.e., first-degree burns penetrating the epidermis, second-degree burns
including both epidermis and dermis, third-degree burns to both layers including the hair follicular
cells, sweat glands and various core tissues, fourth-degree burns to adipose tissue, fifth stage burns
to muscles, and sixth stage burns to bones. Wound healing/wound repair is a very perplexing process
in which the tissues of the affected/burnt area repairs themselves to attain their original form
and functionality but develop a scar at the wound site. This article mainly focuses on the algorithms
to differentiate various degrees of burns, general first aid approaches to burns and scars, the
rationale of treatment of burns, basic mechanisms highlighting the healing processes in humans in
terms of free from scar formation as well as with scar formation at their elementary levels including
cellular as well as biochemical levels, utility, and progression of pre-clinical data to humans
and finally approaches for the improvement of scar formation in man.
Total Saponins of Panax Notoginseng Modulate the Astrocyte Inflammatory
Signaling Pathway and Attenuate Inflammatory Injury Induced by Oxygen-
Glucose Deprivation/Reperfusion Injury in Rat Brain Microvascular
Endothelial Cells
Authors: Wei Xiaobing , Wen Yiqi , Hu Yongzhen , Guo Xuli 
Published: May 2023

Objective:
Reperfusion after cerebral ischemia causes brain injury. Total saponins of Panax
notoginseng (PNS) have potential roles in protecting against cerebral ischemia-reperfusion injury. However,
whether PNS regulates astrocytes on oxygen-glucose deprivation/reperfusion (OGD/R) injury in rat
brain microvascular endothelial cells (BMECs) and its mechanism still need further clarification.

Methods:
Rat C6 glial cells were treated with PNS at different doses. Cell models were established by
exposing C6 glial cells and BMECs to OGD/R. Cell viability was assessed, and levels of nitrite concentration,
inflammatory factors (iNOS, IL-1β, IL-6, IL-8, TNF-α), and oxidative stress-related factors
(MDA, SOD, GSH-Px, T-AOC) were subsequently measured through CCK8, Grice analysis, Western
blot, and ELISA, respectively. The co-cultured C6 and endothelial cells were treated with PNS for 24
hours before model establishment. Then transendothelial electrical resistance (TEER), lactate dehydrogenase
(LDH) activity, brain-derived neurotrophic factor (BDNF) content, and mRNA and protein levels
and positive rates of tight junction proteins [Claudin-5, Occludin, ZO-1] were measured by a cell resistance
meter, corresponding kits, ELISA, RT-qPCR, Western blot, and immunohistochemistry, respectively.

Results:
PNS had no cytotoxicity. PNS reduced iNOS, IL-1β, IL-6, IL-8, and TNF-α levels in astrocytes,
promoted T-AOC level and SOD and GSH-Px activities, and inhibited MDA levels, thus inhibiting oxidative
stress in astrocytes. In addition, PNS alleviated OGD/R injury, reduced Na-Flu permeability, and
enhanced TEER, LDH activity, BDNF content, and levels of tight junction proteins Claudin-5, Occludin,
ZO-1 in the culture system of astrocytes and rat BMECs after OGD/R.

Conclusion:
PNS repressed astrocyte inflammation and attenuated OGD/R injury in rat BMECs.
Preclinical Evidence for the Effectiveness of Mesenchymal Stromal Cells
for Diabetic Cardiomyopathy: A Systematic Review and Meta-analysis
Authors: Liu Boxin , Zhang Jinyu , Zhou Zijing , Feng Baofeng , He Jingjing , Yan Wei , Zhou Xinghong , Amponsah Asiamah Ernest , Guo Ruiyun , Du Xiaofeng , Liu Xin , Cui Huixian , O'Brien Timothy , Ma Jun 
Published: May 2023

Background:
Diabetic cardiomyopathy (DCM) is a complication of diabetes mellitus that
endangers human health. DCM results in cardiac dysfunction, which eventually progresses to heart failure.
Mesenchymal stromal cells (MSCs), a type of multipotent stem cell, have shown promising therapeutic
effects in various cardiovascular diseases and diabetic complications in preclinical studies due to their
immunomodulatory and regenerative abilities. However, there is still a lack of evidence to summarize the
effectiveness of MSCs in the treatment of DCM. Therefore, a meta-analysis and systematic review are
warranted to evaluate the therapeutic potential of MSCs for DCM in preclinical studies.

Methods:
A comprehensive literature search in English or Chinese was conducted in PubMed, EMBASE,
web of Science, Cochrane Library, and China National Knowledge Internet from inception to June 30,
2022. The summarized outcomes included echocardiography, morphology, and pathology. Data were
independently extracted and analyzed by two authors. The software we adopted was Review Manager5.4.1.
This systematic review was written in compliance with PRISMA 2020 and the review protocol
was registered on PROSPERO, registration no. CRD42022350032.

Results:
We included 20 studies in our meta-analysis to examine the efficacy of MSCs in the treatment of
DCM. The MSC-treated group showed a statistically significant effect on left ventricular ejection fraction
(WMD=12.61, 95% CI 4.32 to 20.90, P=0.003) and short axis fractional shortening (WMD=6.84, 95% CI
4.09 to 9.59, P < 0.00001). The overall effects on the ratio of early to late diastolic mitral annular velocity,
left ventricular end-diastolic pressure, maximum positive pressure development, maximum negative
pressure development, left ventricular relaxation time constant, heart weight to body weight ratio, fibrosis
area, and arteriole density were analyzed, suggesting that MSCs represent an effective therapy for the
treatment of DCM.

Conclusion:
Our results suggest a therapeutic role for MSCs in the treatment of DCM, and these results
provide support for the use of MSCs in clinical trials of patients with DCM.
Carbon Nanotubes in Breast Cancer Treatment: An Insight into Properties, Functionalization,
and Toxicity
Authors: Srivastava Neha , Mishra Yachana , Mishra Vijay , Ranjan Abhigyan , Tambuwala Murtaza M. 
Published: May 2023

Abstract:
Breast cancer is the most common cancer among women worldwide. It is the main reason why women die
from cancer. Early diagnosis due to increased public awareness and better screening helps to tackle the disease through
surgical resection and curative therapies. Chemotherapies are frequently used for cancer treatment, but these have
severe adverse effects due to a lack of target specificity. Formulation development scientists and clinicians are now
particularly concerned with developing safe and efficient drug delivery systems for breast cancer treatment. Potentially
relevant literature to get the latest developments and updated information related to properties, functionalization, toxicity
and application of carbon nanotubes in breast cancer treatment has been obtained from Web of Science, Scopus,
and PubMed portals. Nanomedicine has emerged as a novel tool for target-specific delivery systems and other biomedical
applications. Carbon nanotubes (CNTs) are gaining popularity due to their unique mechanical and physiochemical
properties for the diagnosis and treatment of cancer. It is a promising carrier that can deliver micro and macromolecules
to the cancer cell. CNTs can be functionalized at the surface with different functional groups, which helps in
targeting the drugs to target cancer cells. The present review has elaborated on different functionalization approaches
and toxicity aspects of CNTs.
The Effects and Mechanism of Scutellaria baicalensis Georgi Stems
and Leaves Flavonoids on Myelin Sheath Degeneration Induced by
Composite Aβ in Rats
Authors: Congcong Xu , Yuanyuan Ye , Caixia Li , Yazhen Shang 
Published: May 2023

Background:
Alzheimer's disease is a degenerative disease of the central nervous system,
and its characteristic pathological changes are closely associated with Aβ deposition and neurofibrillary
tangles. Many studies have found that malignant changes in the myelin sheath and oligodendrocyte
(OL) are accompanied by the occurrence and development of AD. Therefore, any method that can resist
myelin sheath and OL disorders may be a potential strategy for AD.

Objective:
To investigate the effects and mechanism of Scutellaria baicalensis Georgi stem and leaf
flavonoids (SSFs) on the myelin sheath degeneration induced by Aβ25-35 combined with AlC13 and
RHTGF-β1 (composite Aβ) in rats.

Methods:
A rat AD model was established by intracerebroventricular injection of composite Aβ. The
Morris water maze was used to screen the memory impairment rat model. The successful model rats
were divided into the model group and the 35, 70, and 140 mg/kg SSFS groups. The myelin sheath
changes in the cerebral cortex were observed with an electron microscope. The expression of the oligodendrocyte-
specific protein claudin 11 was detected with immunohistochemistry. The protein expression
levels of myelin oligodendrocyte glycoprotein (MOG), myelin-associated glycoprotein
(MAG) and myelin basic protein (MBP), sphingomyelin synthase-1 (SMS1), and sphingomyelinase-2
(SMPD2) were assayed by Western blotting.

Results:
The intracerebroventricular injection of composite Aβ caused degeneration of the myelin
sheath structure and was accompanied by the decreased claudin 11, MOG, MAG, MBP, and SMS1,
and increased SMPD2 protein expression in the cerebral cortex. However, 35, 70, and 140 mg/kg
SSFs can differentially ameliorate the above abnormal changes induced by composite Aβ.

Conclusion:
SSFs can alleviate myelin sheath degeneration and increase the protein expression of
claudin 11, MOG, MAG, and MBP, and the effective mechanism may be related to the positive regulation
of SMS1 and SMPD2 activities.
Xanthones from Securidaca inappendiculata and Securidaca longepedunculata:
Chemistry and Biological Activity
Authors: Bojase Gomotsang , Ombito Japheth O. 
Published: May 2023

Abstract:
The genus Securidaca (Polygalaceae) comprises 49 taxonomically accepted species distributed in Asia and Africa. The roots, barks, and leaves of Securidaca species are famous for medicinal purposes, especially in Africa and Asia. In this paper, we review the xanthones isolated from S. inappendiculata and S. longepedunculata, the two main species that have been investigated and the bioactivities of these compounds to evaluate the traditional use of these plant species and future development. The references regarding Securidaca species were retrieved from Scopus, Web of Science, PubMed, ScienceDirect, Google Scholar, and SciFinder between 1990 and 2022. Chemical structures of more than 70 xanthones isolated mainly from the stems and roots of S. inappendiculata and S. longepedunculata are presented. These xanthones might be responsible for the ethnomedicinal uses reported in the literature based on the exhibited biological properties such as cytotoxic, antidiabetic, antiviral, and erectile dysfunction of these compounds. Reviewing the research progress made on the isolated xanthones from the genus Securidaca lays a foundation for the future utilization and development of this genus.
Hexokinase and Glycolysis: Between Brain Cells Life and Death
Authors: da Mata Larissa Rodrigues Souza , dos Santos Lais Damásio , de Cerqueira Cesar Marcelo 
Published: May 2023

Abstract:
Hexokinase catalyses the first regulatory step of the glycolytic pathway. We can say without
any exaggeration that both hexokinase and glycolysis are involved in the control of brain cells' life
and death. To perform these pivotal roles, hexokinase occurs in four different isoforms in mammalian
cells. Type I isozyme is best suited for energy generation, introducing glucose in glycolysis. In contrast,
Type II and Type III isoforms product is directed to generation of NADPH through the pentose
phosphate pathway, utilized in biosynthetic processes. Nevertheless, hexokinase has another unique
property to accomplish its multiple functions: the capacity for mitochondrial binding. Linked to its
role in apoptosis control, the binding of hexokinase inhibits the action of apoptosis inducers, such as
Bax, from initiating the release of intramitochondrial proteins. Akt mediates HKII binding to mitochondria.
Overexpression of the phosphatase SHIP2 reduces Akt activity and enhances apoptosis, emphasizing
the role of hexokinase in cell death. Furthermore, hexokinase also participates in cellular
signaling and functional regulation. Adding complexity to this multidimensional enzyme´s attributes,
glycolysis occurs in aerobic or anaerobic situations. “Aerobic glycolysis” participates in the control of
cell excitability, in synapse formation and neurite growth. Here we provide an overview of the multiple
roles of hexokinase and glycolysis in neuronal metabolic association with astrocytes, oligodendrocytes,
and microglia. We also provide an update on the role of hexokinase and glycolysis in microglia
activation and in brain aging and neurodegenerative diseases.
Evaluating the Feasibility of Emotion Expressions in Avatars Created From Real Person Photos: Pilot Web-Based Survey of Virtual Reality Software
Authors: Dechsling Anders , Cogo-Moreira Hugo , Gangestad Jonathan Spydevold , Johannessen Sandra Nettum , Nordahl-Hansen Anders 
Published: May 2023

Background
The availability and potential of virtual reality (VR) has led to an increase of its application. VR is suggested to be helpful in training elements of social competence but with an emphasis on interventions being tailored. Recognizing facial expressions is an important social skill and thus a target for training. Using VR in training these skills could have advantages over desktop alternatives. Children with autism, for instance, appear to prefer avatars over real images when assessing facial expressions. Available software provides the opportunity to transform profile pictures into avatars, thereby giving the possibility of tailoring according to an individual’s own environment. However, the emotions provided by such software should be validated before application.

Objective
Our aim was to investigate whether available software is a quick, easy, and viable way of providing emotion expressions in avatars transformed from real images.

Methods
A total of 401 participants from a general population completed a survey on the web containing 27 different images of avatars transformed, using a software, from real images. We calculated the reliability of each image and their level of difficulty using a structural equation modeling approach. We used Bayesian confirmatory factor analysis testing under a multidimensional first-order correlated factor structure where faces showing the same emotions represented a latent variable.

Results
Few emotions were correctly perceived and rated as higher than other emotions. The factor loadings indicating the discrimination of the image were around 0.7, which means 49% shared variance with the latent factor that the face is linked with. The standardized thresholds indicating the difficulty level of the images are mostly around average, and the highest correlation is between faces showing happiness and anger.

Conclusions
Only using a software to transform profile pictures to avatars is not sufficient to provide valid emotion expressions. Adjustments are needed to increase faces’ discrimination (eg, increasing reliabilities). The faces showed average levels of difficulty, meaning that they are neither very difficult nor very easy to perceive, which fits a general population. Adjustments should be made for specific populations and when applying this technology in clinical practice.
A Smart System for Remote Monitoring of Patients in Palliative Care (HumanITcare Platform): Mixed Methods Study
Authors: Castillo Padrós Manuel Ramón , Pastor Nuria , Altarriba Paracolls Júlia , Mosquera Peña Marcelino , Pergolizzi Denise , Salvador Vergès Àngels 
Published: May 2023

Background
Due to the complexities of advanced illnesses and their treatments, it can be difficult for patients in palliative care to maintain their quality of life. Telemedicine interventions in chronic disease management engage patients in their care, provide continuous follow-up by their health care providers, identify symptoms earlier, and allow a quick response to illness-related decline.

Objective
We aimed to detail and reflect on the design of an app and evaluate its feasibility to monitor the clinical situation of patients with advanced illnesses.

Methods
This study used a mixed methods design using qualitative methods to inform app development and design and quantitative methods for data collection and analysis of patient evaluations. Palliative care units in 2 Spanish university hospitals (Nuestra Señora de la Candelaria in Santa Cruz de Tenerife and University Hospital Complex of Ferrol in A Coruña) carried out a literature review, designed the study protocol, and obtained approval from the Ethics Committee from June to December 2020. In addition, focus group meetings were held, and the design and technical development of the app were elaborated on and subsequently presented in the participating palliative care units. From January to March 2021, the app was made public on the App Store and Play Store, and a pilot study with patients was carried out in April to September 2021.

Results
Six focus group meetings were held that included doctors, nurses, app developers, technology consultants, and sponsors. In addition, the technology consultants presented their results 3 times in the participating palliative care units to obtain feedback. After the app’s final design, it was possible to publish it on the usual servers and begin its evaluation in patients (n=60, median age 72 years). Sixty percent (n=36) of the participants were women and 40% (n=24) were men. The most prevalent advanced pathology was cancer (n=46, 76%), followed by other diseases (n=7, 12%) and amyotrophic lateral sclerosis (n=5, 8%). Seventy percent (n=42) of the patients were already in follow-up prior to the start of the study, while 30% (n=18) were included at the start of their follow-up. The information in the app was collected and entered by relatives or caregivers in 60% (n=36) of the cases. The median follow-up was 52 (IQR 14-104) days. In all, 69% (n=41) had a follow-up >30 days (10 were deceased and 9 were missing data). The use of the different sections of the app ranged from 37% (n=22) for the glycemic record to 90% (n=54) for the constipation scale). Patients and caregivers were delighted with its ease of use and usefulness.

Conclusions
Incorporating an intelligent remote patient monitoring system in clinical practice for patients in palliative care can improve access to health services and provide more information to professionals.