bluuebunny/crossref_metadata_2025 huggingface dataset:
Identification of SPINT3 as a metastatic suppressor in gastric cancer through induction of TGF-β1 secretion
Authors: Wang Haifeng , Wang Haohao , Li-song Teng
Published: May 2022

Background
Cancer metastasis is responsible for most cancer-related deaths. SPINT3 (serine peptidase inhibitor, Kunitz type, 3) is a newly identified gene, and its relationship with gastric cancer has not been well studied.
Methods
We first designed an sgRNA sub-library to screen for metastatic suppressors, and chose SPINT3. We then used QPCR and western blotting to detect the expression level of SPINT3 in gastric cancer tumor tissues. In addition, we used annexin V/propidium iodide (PI) to detect changes in apoptosis. PI staining and wound healing assays were used to detect the cell cycle and changes in cell migration, respectively. Finally, CyTOF and T cell proliferation experiments were performed to detect changes in immune cells in the tumor microenvironment.
Results
sgRNA which target the SPINT3 gene was present in every metastatic tumor. The expression of SPINT3 was low in gastric cancer tissues, and this increased the metastatic ability of gastric cancer cells. In addition, high expression of SPINT3 induced cell apoptosis, downregulated cell proliferation, and impaired cell migration. Furthermore, low expression of SPINT3 induced the secretion of TGF-β1 and an immunosuppressive signal, which could be blocked by Apatinib and SB431542.
Conclusion
We confirmed that SPINT3 is a metastasis suppressor in gastric cancer.
Eu speciation in apatite at 1 bar: An experimental study of valence-state partitioning by XANES, lattice strain, and Eu/Eu* in basaltic systems
Authors: Tailby Nicholas D. , Trail Dustin , Watson Bruce , Lanzirotti Antonio , Newville Matthew , Wang Yanling
Published: May 2022

Partition coefficients for rare earth elements (REEs) between apatite and basaltic melt were determined as a function of oxygen fugacity (fO2; iron-wüstite to hematite-magnetite buffers) at 1 bar and between 1110 and 1175 °C. Apatite-melt partitioning data for REE3+ (La, Sm, Gd, Lu) show near constant values at all experimental conditions, while bulk Eu becomes more incompatible (with an increasing negative anomaly) with decreasing fO2. Experiments define three apatite calibrations that can theoretically be used as redox sensors. The first, a XANES calibration that directly measures Eu valence in apatite, requires saturation at similar temperature-composition conditions to experiments and is defined by:

( E u 3 + ∑ E u ) Apatite  = 1 1 + 10 - 0.10 ± 0.01 × l o g ⁡ ( f o 2 ) - 1.63 ± 0.16 .

The second technique involves analysis of Sm, Eu, and Gd in both apatite and coexisting basaltic melt (glass), and is defined by:

( Eu E u * ) D Sm × Gd = 1 1 + 10 - 0.15 ± 0.03 × l o g ⁡ ( f o 2 ) - 2.46 ± 0.41 .

The third technique is based on the lattice strain model and also requires analysis of REE in both apatite and basalt. This calibration is defined by

( Eu E u * ) D lattice strain = 1 1 + 10 - 0.20 ± 0.03 × l o g ⁡ ( f o 2 ) - 3.03 ± 0.42 .

The Eu valence-state partitioning techniques based on (Sm×Gd) and lattice strain are virtually indistinguishable, such that either methodology is valid. Application of any of these calibrations is best carried out in systems where both apatite and coexisting glass are present and in direct contact with one another. In holocrystalline rocks, whole rock analyses can be used as a guide to melt composition, but considerations and corrections must be made to either the lattice strain or Sm×Gd techniques to ensure that the effect of plagioclase crystallization either prior to or during apatite growth can be removed. Similarly, if the melt source has an inherited either a positive or negative Eu anomaly, appropriate corrections must also be made to lattice strain or Sm×Gd techniques that are based on whole rock analyses. This being the case, if apatite is primary and saturates from the parent melt early during the crystallization sequence, these corrections may be minimal.

The partition coefficients for the REE between apatite and melt range from a maximum DEu3+ = 1.67 ± 0.25 (as determined by lattice strain) to DLu3+ = 0.69 ± 0.10. The REE partition coefficient pattern, as observed in the Onuma diagram, is in a fortuitous situation where the most compatible REE (Eu3+) is also the polyvalent element used to monitor fO2. These experiments provide a quantitative means of assessing Eu anomalies in apatite and how they be used to constrain the oxygen fugacity of silicate melts.
Research on the safe utilization of agricultural water resources in the Yellow River Basin
Authors: Li Yanbin , Du Xuefang , Li Daoxi , Zhang Xiuyu
Published: May 2022

Considering the current problems related to the utilization of agricultural water resources in the Yellow River Basin, we propose the definition of the safe utilization of agricultural water resources based on the summary and analysis of recent studies on water resources security. Through the analysis of water resources development and utilization in the basin over the years, an evaluation index system for agricultural water resources security in the basin was constructed, and a weighted cooperative game method combination was used to evaluate the agricultural water resources security in the basin using the weighted TOPSIS model. The evaluation results show that the utilization of agricultural water resources in the areas under the jurisdiction of Sichuan and Shandong Provinces in the basin was in a secure or a relatively higher state, whereas Ningxia was in a relatively unsecure state, and the remaining provinces were in a basic secure state. Based on the evaluation results, we have provided the corresponding countermeasures for the safe utilization of agricultural water resources in terms of water-saving irrigation technology, water resources monitoring system, and water resources management system to support the effective implementation of efficient water-saving irrigation of agricultural water resources in the Yellow River Basin.
Azapeptides -A History of Synthetic Milestones and Key Examples
Authors: Fan Cheng Kai , VanPatten Sonya , He Mingzhu , Al-Abed Yousef
Published: May 2022

For over 50 years of azapeptide synthetic techniques, developments have renewed
the field of peptidomimetic therapeutics. Azapeptides are close surrogates of natural peptides:
they contain a substitution of the amino acid α-carbon by a nitrogen atom. Goserelin
(1989) and Atazanavir (2003) are two well-known, FDA-approved azapeptide-based drugs
for the treatment of cancers and HIV infection, providing evidence for the successful clinical
implementation of this class of therapeutic. This review highlights the azapeptides in recent
medicinal chemistry applications and synthetic milestones. We describe the current techniques
for azapeptide bond formation by introducing azapeptide coupling reagents and chain
elongation methods both in solution and solid-phase strategies.
Toll-Like Receptor Signaling in the Pathogenesis of Chronic Dacryocystitis:
Implication of c-FOS Transcription Factor and its Downstream Effector
Chemokine Genes CCL2, CCL4, CXCL3, CXCR4 with a Shift of the
M1/M2 Macrophage Phenotype
Authors: Aboulhoda Basma Emad , Edris Noha Ahmed , El-Din Shimaa Saad , Fouad Amina Mahmoud , Albadawi Emad , Rashed Laila Ahmed , Elessawy Kareem Bakr
Published: May 2022

Introduction:

TLRs are fundamental elements in the orchestration of the innate immune
system. These receptors seem to be responsible for the inflammation and fibrosis in chronic dacryocystitis.
The aim of the present study was to investigate the role of the toll-Like receptors (TLR2
and TLR4) signaling pathway and its downstream effector chemokine genes in the pathogenesis of
chronic dacryocystitis.

Method:

This study was conducted on 20 patients diagnosed with chronic dacryocystitis and
underwent external dacryocystorhinostomy. Estimation of gene expression of TLR2, TLR4, CCL2,
CCL4, CXCL3, CXCR4, and c-FOS genes in the lacrimal sac tissues was performed together with
the assessment of the inflammatory markers TNFα, IL-1β, IFN-γ, and IL-22. Histopathological examination
of the lacrimal sac walls using hematoxylin and eosin (H&E) stain, in addition to
immunohistochemical staining of the CD68 and CD163 macrophage markers, was also performed.

Results:

Our results showed that TLR2, TLR4, and c-FOS gene expressions were significantly increased
in the chronic dacryocystitis group with a subsequent increase in their downstream effector
chemokine genes CCL2, CCL4, and CXCL3. This up-regulation of genes was accompanied by
macrophage shift of polarization toward the M1 pro-inflammatory phenotype (increased CD68 and
decreased CD163 expression), leading to increased levels of the pro-inflammatory cytokines (TNF-
α, IL-1β and IFN-γ) and decreased anti-inflammatory marker IL-22 with chronic dacryocystitis.

Conclusion:

It is essential to fine-tune TLR activation through emerging therapeutic approaches.
Targeting TLR signaling at the level of receptors or downstream adaptor molecules represents a
new challenge for treating chronic dacryocystitis.
Identification of Genes as Potential Biomarkers for Sepsis-related ARDS
using Weighted Gene Co-expression Network Analysis
Authors: Fei Aihua , Wang Xiaowan
Published: May 2022

Background: Acute respiratory distress syndrome (ARDS) caused by sepsis presents a
high mortality rate; therefore, identification of susceptibility genes of sepsis to ARDS at an early
stage is particularly critical.

Methods: The GSE66890 dataset was downloaded and analyzed by WGCNA to obtain modules.
Then, GO and KEGG analyses of the module genes were performed. Then, the PPI network and
LASSO model were constructed to identify the key genes. Finally, expression levels of the
screened genes were validated in clinical subjects.

Results: We obtained 17 genes merged modules via WGCNA, and the dark module and tan module
were the most positively and negatively correlated with sepsis-induced ARDS, respectively.
Based on gene intersections of the module genes, 11 hub genes were identified in the dark module,
and 5 hub genes were identified in the tan module. Finally, the six key genes were identified by
constructing the LASSO model. We further detected the screened genes expression in clinical
samples, and as the bioinformatics analysis revealed, the expressions of NANOG, RAC1,
TWIST1, and SNW1 were significantly upregulated in the ARDS group compared to the sepsis
group, and IMP3 and TUBB4B were significantly downregulated.

Conclusion: We identified six genes as the potential biomarkers in sepsis-related ARDS. Our findings
may enhance the knowledge of the molecular mechanisms behind the development of sepsisinduced
ARDS.
Gasdermins: Pore-forming Proteins as a Potential Therapeutic Target
Authors: Jain Kripa , Barve Kalyani , Bhatt Lokesh Kumar
Published: May 2022

Gasdermins are novel pore forming proteins that comprise Gasdermin A, Gasdermin B,
Gasdermin C, Gasdermin D, Gasdermin E and Pejvakin (DFNB59). Recently, pyroptosis has been
redefined as "Gasdermin mediated necrosis", as gasdermins are key regulators of apoptosis, necrosis,
and pyroptosis. The discovery of the gasdermin family has broadened the field of pyroptosis studies.
Studies have correlated gasdermins with several diseases. This review summarizes the physiological
roles and signal transduction of gasdermins. It further highlights the role of gasdermins in pathological
conditions like autoimmune disease, kidney diseases, and central nervous system diseases.
A Smart Hydrogel from Salvia spinosa Seeds: pH Responsiveness, On-off
Switching, Sustained Drug Release, and Transit Detection
Authors: Hussain Muhammad Ajaz , Bukhari Syed Nasir Abbas , Ali Arshad , Haseeb Muhammad Tahir , Muhammad Gulzar , Sheikh Fatima Akbar , Farid-ul-Haq Muhammad , Ahmad Naveed
Published: May 2022

Background:

The use of synthetic and semi-synthetic materials in drug delivery systems has
associated drawbacks like costly synthesis, toxicity, and biocompatibility issues. Therefore, there is a
need to introduce novel materials to overcome such issues. Naturally occurring and water-swellable
polysaccharides are advantageous in overcoming the above-mentioned issues. Therefore, we are reporting
a novel hydrogel (SSH) isolated from the seeds of Salvia spinosa as a sustained release material.

Methods:

SSH was explored for its pH-dependent and salt-responsive swelling before and after compression
in a tablet form. Stimuli-responsive swelling and deswelling were also monitored at pH 7.4 and
pH 1.2 in deionized water (DW) and normal saline and DW and ethanol. The sustained-release potential
of SSH-based tablets was monitored at gastrointestinal tract (GIT) pH. The transit of SSH tablets was
ascertained through an X-ray study.

Results:

The swelling of SSH in powder and tablet form was found in the order of DW > pH 7.4 > pH
6.8 > pH 1.2. An inverse relation was found between the swelling of SSH and the concentration of the
salt solution. The SSH showed stimuli-responsive swelling and de-swelling before and after compression,
indicating the unaltered nature of SSH even in a closely packed form, i.e., tablets. Sustained release
of theophylline (< 80%) was witnessed at pH 6.8 and 7.4 during the 12 h study following zeroorder
kinetics, and radiographic images also showed 9 h retention in GIT.

Conclusion:

These investigations showed the potential of SSH as a pH-sensitive material for sustained
and targeted drug delivery.
Current Insights on the Role of Irisin in Endothelial Dysfunction
Authors: Luna-Ceron Eder , González-Gil Adrian M. , Elizondo-Montemayor Leticia
Published: May 2022

Endothelial dysfunction is a crucial physiopathological mechanism for cardiovascular diseases
that results from the harmful impact of metabolic disorders. Irisin, a recently discovered adipomyokine,
has been shown to exert beneficial metabolic effects by increasing energy consumption, improving
insulin sensitivity, and reducing the proinflammatory milieu. Multiple preclinical models have assessed
irisin's possible role in the development of endothelial dysfunction, displaying that treatment with exogenous
irisin can decrease the production of oxidative stress mediators by up-regulating Akt/mTOR/Nrf2
pathway, promote endothelial-dependent vasodilatation through the activation of AMPK-PI3K-AkteNOS
pathway, and increase the endothelial cell viability by activation of ERK proliferation pathway
and downregulation of Bad/Bax/Caspase 3 pro-apoptotic pathway. However, there is scarce evidence of
these mechanisms in clinical studies, and available results are controversial. Some have shown negative
correlations of irisin levels with the burden of coronary atherosclerosis and leukocyte adhesion molecules'
expression. Others have demonstrated associations between irisin levels and increased atherosclerosis
risk and higher carotid intima-media thickness. Since the role of irisin in endothelial damage remains
unclear, in this review, we compare, contrast, and integrate the current knowledge from preclinical
and clinical studies to elucidate the potential preventive role and the underlying mechanisms and
pathways of irisin in endothelial dysfunction. This review also comprises original figures to illustrate
these mechanisms.
Varicocele at High Altitude; Venous Outflow Restriction by Hypobaric
Hypoxia
Authors: Alcántara-Zapata Diana , Nazzal Carolina , Muñoz Sergio , De Gregorio Nicole , Marchetti Nella , Behn Claus
Published: May 2022

Background:

Testicular aches have been reported to occur on exposure to high altitude (HA).
As a painful expression of venous congestion at the pampiniform plexus, varicocele (VC) might be a
consequence of cardiovascular adjustments at HA. Chile’s National Social Security Regulatory Body
(SUSESO) emphasized evaluating this condition in the running follow-up study “Health effects of exposure
to chronic intermittent hypoxia in Chilean mining workers.”

Objectives:

This study aimed at investigating the prevalence of VC in a population usually shifting between
sea level and HA, thereby intermittently being exposed to hypobaric hypoxia.

Methodology:

Miners (n=492) agreed to be examined at their working place by a physician, in the context
of a general health survey, for the presence of palpable VC, either visible or not. Among them was a
group exposed to low altitude (LA) <2,400 m; n=123; another one exposed to moderate high altitude
(MHA) working 3,050 m; n=70, and a third one exposed to very high altitude (VHA) >3,900 m, n=165.
The Chi2 test and Kruskal-Wallis test were used for the descriptive analyses, and logistic regression was
applied to evaluate the association of VC with exposure to HA. The Ethics Committee for Research in
Human Beings, Faculty of Medicine, University of Chile, approved this project.

Results:

VC prevalence (grades 2 and 3) was found to be 10% at LA, 4.1% at MHA, and 16.7% at VHA
(p≤0.05). Hemoglobin oxygen saturation (SaO2) was lower, and hemoglobin concentrations were higher
in workers with high-grade VC at VHA compared to LA and MHA (Wilcoxon tests, p<0.001). Odds
ratios (OR) for the association of VC with HA were 3.7 (95%CI: 1.26 to 12.3) and 4.06 (95%CI: 1.73 to
11.2) for MHA and VHA, respectively

Conclusions:

Association of VC with HA, a clinically relevant finding, may be related to blood volume
centralization mediated by hypobaric hypoxia.
A Comparative Study of Binding Interactions of Natural Flavonoids and
Conventional Drug Donepezil for Multiple Alzheimer's Disease Targets
Using In silico Approach
Authors: Sonawane Devika , Pokharkar Varsha
Published: May 2022

Background:

Alzheimer's disease (AD) is one of the major causes of morbidity, affecting more
than 36 million population worldwide. Current anti-AD treatments result in limited therapeutic outcomes
owing to the complexity of the disease. Some natural promising herbal drugs and phytoconstituents
utilized as an alternative treatment for AD have been reported by several researchers for their
neuroprotective action.

Objective:

This study aimed at carrying out molecular docking studies of selected promising flavonoids
such as curcumin, quercetin, bilobalide, ferulic acid, reseveratrol for their molecular interactions with
multiple AD target proteins and further compare the data with the standard acetylcholine esterase
inhibitor drug donepezil.

Methods:

The molecular docking interactions were studied between the selected actives and the AD
target proteins acetylcholine esterase, butyrylcholine esterase, and tau protein using the AutoDock Vina
software. The Swiss ADME approach performed prediction of the ADME properties. Binding interactions
of the ligands at the target protein binding sites were examined using the Discovery Studio Visualizer
2021.

Results:

The binding energy for quercetin in the active site of the selected target enzymes acetylcholine
esterase, butyrylcholine esterase, and tau protein was -9.5 , -7.8 , and -8.2 kcal/mol, respectively which
was much greater than other flavonoids and comparable to the standard drug donepezil binding energy -
10.3, -7.5,-7.9 kcal/mol respectively.

Conclusion:

This work focuses on recognizing structural features and comparing selected flavonoids and
standard acetylcholine esterase (AChEs) inhibitors for molecular docking with three primary targets of
AD, namely AChEs, Butyrylcholine esterase, and tau protein. This in silico study concluded that quercetin
had significant docking interactions and good pharmacokinetic features, making it a potential therapeutic
candidate for the treatment of AD.
Impact of Metabolic Risk Factors on COVID-19 Clinical Outcomes: An
Extensive Review
Authors: Muxfeldt Elizabeth S. , Azevedo Rafael B. , Wandermurem Débora C.R. , Libório Flávia C.F. , Machado Maíra K. , Ushijima Natália M. , Narde Ramon S. , D. Pecly Inah Maria
Published: May 2022

Background:

Cardiovascular (CV) risk factors, particularly cardiometabolic, seem to be
associated with heightened severity and increased morbimortality in patients infected with the novel
Coronavirus disease-2019 (COVID-19).

Methods:

A thorough scoping review was conducted to elucidate and summarize the latest evidence
for the effects of adverse cardiac metabolic profiles on the severity, morbidity, and prognosis
of COVID-19 infection.

Results:

The pathophysiology of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2)
is complex, being characterized by viral-induced immune dysregulation and hypercytokinemia,
particularly in patients with critical disease, evolving with profound endothelial dysfunction, systemic
inflammation, and prothrombotic state. Moreover, cardiovascular comorbidities such as diabetes
are the most prevalent amongst individuals requiring hospitalization, raising concerns towards
the clinical evolution and prognosis of these patients. The chronic proinflammatory state observed
in patients with cardiovascular risk factors may contribute to the immune dysregulation mediated
by SARS-CoV-2, favoring more adverse clinical outcomes and increased severity. Cardiometabolism
is defined as a combination of interrelated risk factors and metabolic dysfunctions
such as dyslipidemia, insulin resistance, impaired glucose tolerance, and central adiposity, which
increase the likelihood of vascular events, being imperative to specifically analyze its clinical association
with COVID-19 outcomes.

Conclusion:

DM and obesity appears to be important risk factors for severe COVID-19. The
chronic proinflammatory state observed in patients with excess visceral adipose tissue (VAT) possibly
augments COVID-19 immune hyperactivity leading to more adverse clinical outcomes in these
patients.
Post COVID-19 Vaccination Acute Disseminated Encephalomyelitis: A
Case Report
Authors: Garg Amit , Batra Parveen Kumar , Gupta Pranav
Published: May 2022

Introduction:

A 67-year-old female with no significant past medical history presented to the
critical care department with symptoms of encephalopathy.

Case Presentation:

The patient’s Main Concerns and the Important Clinical Findings: The patient
had a history of COVID -19 vaccination (recombinant ChAdOX1 nCoV-19) 14 days prior to the symptoms.
She underwent an MRI of the brain and cervical spine and a lumbar puncture.

The Primary Diagnoses, Interventions, and Outcomes:

The patient was examined and sent for an
MRI of the brain and cervical spine, followed by extensive blood and CSF investigations to rule out
any infective, paraneoplastic, connective tissue disorder, or inflammatory disorder. The patient was
given steroids, and a good response was reported. The primary diagnosis was made as vaccine-induced
ADEM.

Conclusion:

The clinical exam, location, sparse contrast enhancement, and CSF findings were all consistent
with an acute demyelinating event, and the history of vaccination, together with the clinical
situation, was found to be favourable for the development of acute disseminated encephalomyelitis.
Diffusion-weighted Imaging and Arterial Spin Labeling for Prediction of
Cerebral Infarct Volume in Acute Atherothrombotic Stroke
Authors: Huang Hai-Tao , Li Xie , Wang Xinmin , Liang Bo , Li Huan , Liang Jianye
Published: May 2022

Objectives:

To investigate the usefulness of diffusion weighted imaging (DWI) and arterial spin labeling (ASL) for predicting final infarct volume in patients with acute atherothrombotic subtype cerebral infarction (AT-type stroke).

Methods:

The data of 77 patients with AT-type stroke were retrospectively analyzed. ASL and DWI values of minimum apparent diffusion coefficient (minADC), mean ADC (meanADC), minimum cerebral blood flow (minCBF), and mean CBF (meanCBF) of the infarction lesions were measured. Changes in cerebral infarction volume (ΔVolume) were determined by DWI reexamination on the 7th day after onset. Correlations of ADC and CBF with ΔVolume were analyzed. Receiver operating characteristic (ROC) curve analysis was used to determine the usefulness of ADC and CBF values for predicting final infarct volume.

Results:

There was significant difference in the distribution of the ΔVolume in AT-type stroke (P < 0.0001). The ADC and minCBF values were negatively correlated with the infarct ΔVolume (P < 0.05); meanCBF and ΔCBF were not correlated with ΔVolume. When minADC was ≤0.303 × 10−3 mm2/s, minCBF1.5 ≤2.415 mL/100 g/min, or minCBF2.5 ≤4.25 mL/100 g/min, ΔVolume was likely to be large. The ROC curve showed highest predictive value for minADC and minCBF.

Conclusions:

Distinctive patterns of quantitative ADC and CBF can be used as a simple and rapid method for predicting change of infarction volume in AT-type stroke.
In Vitro Evaluation of Cytotoxic Activity of Algerian propolis against Human
Breast Adenocarcinoma (MDA-MB-231) Cells and Investigation of its
Potential Mechanism of Action
Authors: Segueni Narimane , Nasirli Farid , Daikh Amina , Doğan Nazime Mercan , Arslan Sevki , Mutlu Doğukan
Published: May 2022

Background: Breast cancer is a major cause of death in women worldwide. Propolis
antitumor activity has become the subject of growing research related to breast cancer. Algerian
propolis is being studied for its antitumor activity on several cell lines. However, little is known
about its cytotoxic activity on the human breast adenocarcinoma cell line.

Objective: The present study aimed to investigate the cytotoxic effect of Algerian propolis on human
breast adenocarcinoma cells (MDA-MB-231) and explain its mechanism of action.

Methods: Cytotoxic activity was evaluated using an MTT assay, and mechanisms involved in the
cytotoxic activity were also investigated. In addition, the chemical profile was analyzed by the
determination of TP and TF contents.

Results: TP and TF of the tested propolis varied between 1.36±0.15 and 97.85±2.98 GAE μg/mg
for TP and 0.08±0.10 and 33.22±1,17QE μg/mg for TF. Propolis treatment of MD-MB-231 cells
for 24 hours was found to suppress the growth of the tested cell line in a dose-dependent manner.
The tested propolis probably induced an intrinsic pathway of apoptosis through caspase cascade
and activation of pro-apoptotic proteins, such as BAX, p53, and p21. In addition, cell proliferation
was found to be inhibited by the diminution of CYCLIN2 and CDK4 activities associated with the
increase in P21 acting as a protein inhibitor.

Conclusion: Our results demonstrated that Algerian propolis could be used as a complementary
treatment for breast cancer. Our propolis was found to suppress the growth of MDA-MB-231 cells
by inducing apoptosis and inhibiting cell proliferation.
Nanotechnology: A Promising Approach in Nerve Regeneration
Authors: Chaskar Atul , Azmi Namrah , Tiwari Abhishekh , Kaur Navjeet
Published: May 2022

This review focuses on nerve degeneration a major health problem of nowadays,
caused due to different nerve diseases or injuries. The low regenerative capacity of the nerve
leads to primary brain injury. Clinical therapies available were only able to stabilize lesion progression.
Reversal of the degeneration process and functional regeneration promotion were
brought about by the implementation of nanotechnology in biology, allowing cell tissue integration.
Nanomaterials implemented in the delivery of drugs and bioactive materials treat specifically
targeted cells. Nanomaterials made in contact with cells lead to stem cell therapy, promoting
stem cell differentiation and neurogenesis. Nanomaterials were also screened for their appropriateness
as potential scaffold materials, owing to their neuroprotectant activity in nerve regeneration.
hiPSC-Neural Stem/Progenitor Cell Transplantation Therapy for Spinal
Cord Injury
Authors: Du Xiaofeng , Amponsah Asiamah Ernest , Kong Desheng , He Jingjing , Ma Zhenhuan , Ma Jun , Cui Huixian
Published: May 2022

Spinal cord injury (SCI) is a catastrophic event that incurs substantial personal and social costs.
The complex pathophysiology associated with SCI often limits the regeneration of nerve tissue at the
injured site and leads to permanent nerve damage. With advances in stem cell biology, the field of regenerative
medicine offers the hope of solving this challenging problem. Neural stem/progenitor cells
(NSPCs) possess nerve regenerative and neuroprotective effects, and transplanting NSPCs in their optimized
form into an injured area holds promising therapeutic potential for SCI. In this review, we summarize
the advantages and disadvantages of NSPCs derived from different sources while highlighting the
utility of NSPCs derived from induced pluripotent stem cells, an NSPC source with superior advantages,
according to data from in vivo animal models and the latest clinical trials.
Long-term Effect of Hematopoietic Stem Cell Transplantation on the
Quality of Life of Patients with β-thalassemia Major in Guangxi, China - A
Cross-sectional Study
Authors: Zhai Lu , Liu Yuhua , Huo Rongrui , Pan Zhaofang , Zhang Yaqun , Li Zhi , Li Fang , Fan Jing , Wei Wei
Published: May 2022

Objective:

The purpose of our study was to compare the quality of life (QOL) of patients with
hematopoietic stem cell transplantation (HSCT) for more than 2 years for β-thalassemia major (β-TM)
with that of β-TM patients with conventional therapy (blood infusion and iron chelation) and that of the
general population.

Methods:

This was a cross-sectional comparative study on the QOL of 225 β-TM patients treated with
blood transfusion and iron chelation therapy, 133 β-TM patients who had undergone HSCT or 270 ageand
sex-matched healthy individuals from Guangxi, China. Child-self and parent-proxy reports of the
PedsQL 4.0 Generic Core Scales were used to prospectively evaluate QOL.

Results:

The incidence of acute GVHD was 14.3% (grade III-IV in 4.5% of patients), and that of chronic
GVHD was 3.8%. This was lower than that of previous studies since the inclusion of anti-thymocyte
globulin (ATG). Patients who underwent transplantation from a voluntary donor had higher QOL scores
and lower rates of acute GVHD, chronic GVHD and comorbidities than those receiving stem cell sources
from an HLA mismatched related donor (haploidentical donor). Transplants with PBSCs or UCBT,
PBSCT+BMT, BMT, or BMT+UCBT as stem cell sources did not have any impact on QOL. The QOL of
β-TM patients was very similar to that of the general population. More complications (P<0.001), shorter
post-transplantation time (P<0.001), and older age at HSCT (P=0.01) were associated with poorer child
QOL (P=0.020). Additional analyses investigating QOL of β-TM patients receiving conventional treatment
with β-TM revealed poorer outcomes than the cohort of transplanted patients.

Conclusion:

β-TM patients can be cured by HSCT and regain QOL as good as that of the general population.
β-TM patients are suggested to undergo HSCT as soon as possible to avoid complications related to
iron overload and blood infusion.
The SDF-1/CXCR4 Signaling Pathway Directs the Migration of Systemically
Transplanted Bone Marrow Mesenchymal Stem Cells Towards the
Lesion Site in a Rat Model of Spinal Cord Injury
Authors: Zhao Andong , Chung Manhon , Yang Yi , Pan Xiaohua , Pan Yu , Cai Sa
Published: May 2022

Background:

It has been observed that bone marrow-derived mesenchymal stem cells (MSCs)
migrate towards the injured spinal cord and promote functional recovery when systemically transplanted
into the traumatized spinal cord. However, the mechanisms underlying their migration to the spinal cord
remain poorly understood.

Methods:

In this study, we systemically transplanted GFP- and luciferase-expressing MSCs into rat models
of spinal cord injury and examined the role of the stromal cell-derived factor 1 (SDF-1)/CXCR4 axis
in regulating the migration of transplanted MSCs to the spinal cord. After intravenous injection, MSCs
migrated to the injured spinal cord where the expression of SDF-1 was increased. Spinal cord recruitment
of MSCs was blocked by pre-incubation with an inhibitor of CXCR4. Their presence correlated with
morphological and functional recovery. In vitro, SDF-1 or cerebrospinal fluid (CSF) collected from SCI
rats promoted a dose-dependent migration of MSCs in culture, which was blocked by an inhibitor of
CXCR4 or SDF-1 antibody.

Results and Conclusion:

The study suggests that SDF-1/CXCR4 interactions recruit exogenous MSCs to
injured spinal cord tissues and may enhance neural regeneration. Modulation of the homing capacity may
be instrumental in harnessing the therapeutic potential of MSCs.
pH-responsive Sulfated Hyaluronic Acid Nanoparticles Targeting Tumor Cells and CAFs for the Treatment of Breast Cancer
Authors: Wang Di , Wu Jingliang , Qi Cuiping , Dong Jinping , Ding Xueying , Yu Guohua , Liu Shuzhen , Zhang Bo , Gao Zhiqin , Wei Xiuhong , Liu Hongying
Published: May 2022

Background:

Tumor metastasis is a main cause of death in patients with breast cancer. The cross-talk between cancer-associated fibroblasts (CAFs) and tumor cells plays an important role in promoting tumor invasion and metastasis. It is important to develop a novel delivery system to inhibit tumor development by simultaneously targeting both CAFs and tumor cells.

Objective:

The main objective of this research was to prepare nanoparticles to inhibit tumor prolifer-ation and migration by blocking the cross-talk of tumor-CAFs. Additionally, a novel “MCF-7+NIH/3T3” mixed cell model was established to mimic the tumor microenvironment (TME).

Methods:

In this study, the pH-responsive nanoparticles (MIF/DOX-sul-HA NPs) based on sulfated hyaluronic acid (sul-HA) polymers were prepared for co-delivery of doxorubicin (DOX) and mife-pristone (MIF). The effects of anti-proliferation and anti-metastasis of MIF/DOX-sul-HA NPs were investigated both in vitro and in vivo.

Results:

The results showed that MIF/DOX-sul-HA NPs were nearly spherical in shape with narrow particle size distribution and pH-responsive drug release, and could be taken up by both MCF-7 and NIH/3T3 cells. Compared with MCF-7 cells alone, the anti-tumor effect of single DOX was weak in the “MCF-7+NIH/3T3” mixed cell model. MIF/DOX-sul-HA NPs exhibited strong effects of anti-proliferation and anti-metastasis than the free single drug.

Conclusion:

The sul-HA nanoparticles for co-delivery of DOX and MIF could be a promising com-bined therapy strategy for the treatment of breast cancer.
Chronological Order Based Wrapper Technique for Drug-Target Interaction
Prediction (CO-WT DTI)
Authors: Gananathan Kavipriya , Dhanabalachandran Manjula , Sugumaran Vijayan
Published: May 2022

Background:

Drug-Target Interactions (DTIs) are used to suggest new medications for diseases
or reuse existing drugs to treat other diseases since experimental procedures take years to complete,
and FDA (Food and Drug Administration) permission is necessary for drugs to be made available
in the market.

Objective:

Computational methods are favoured over wet-lab experiments in drug analysis, considering
that the process is tedious, time-consuming, and costly. The interactions between drug targets are computationally
identified, paving the way for unknown drug-target interactions for numerous diseases unknown
to researchers.

Methods:

This paper presents a Chronological Order-based Wrapper Technique for Drug-Target Interaction
prediction (CO-WT DTI) to discover novel DTI. In our proposed approach, drug features, as
well as protein features, are obtained by three feature extraction techniques while dimensionality reduction
is implemented to remove unfavourable features. The imbalance issue is taken care of by balancing
methods while the performance of the proposed approach is validated on benchmark datasets.

Results:

The proposed approach has been validated using four broadly used benchmark datasets, namely,
GPCR (G protein-coupled receptors), enzymes, nuclear receptors, and ion channels. Our experimental
results outperform other state-of-the-art methods based on the AUC (area under the Receiver
Operating Characteristic (ROC) curve) metric, and Leave-One-Out Cross-Validation (LOOCV) is used
to evaluate the prediction performance of the proposed approach.

Conclusion:

The performance of feature extraction, balancing methods, dimensionality reduction, and
classifier suggests ways to contribute data to the development of new drugs. It is anticipated that our
model will help refine ensuing explorations, especially in the drug-target interaction domain.
The Underlying Mechanisms of Wujiayizhi Granule in Treating Alzheimer's Disease
Authors: Xiang Liu , Lin Yue , Li Xianhai , Tang Qiang , Meng Fanbo , Chen Wei
Published: May 2022

Background:

Wujiayizhi granule (WJYZG) is a kind of traditional Chinese medicine, which is used for treating Alzheimer's disease (AD). Although the clinical effect of WJYZG for AD is obvious, its underlying mechanism is still obscure.

Objective:

Explore the mechanism of WJYZG in the treatment of AD by using bioinformatics methods.

Methods:

Traditional Chinese Medicine Systems Pharmacology Database and Analysis Platform (TCMSP), Traditional Chinese Medicine Integrated Database (TCMID) and Encyclopedia Database of Chinese Medicine (ETCM) were used to search the ingredients and targets of WJYZG. DisGeNET, Drugbank, Online Mendelian Inheritance in Man (OMIM), and Terapeutic Target Database (TTD) were used to retrieve the targets of AD. The Cytoscape3.6.1 software was used to construct the interaction network of herbs-ingredients-targets. The Gene Ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) enrichment analyses were performed to explore the treatment mechanism of WJYZG on AD. Molecular docking was used to validate the interactions between the ingredients and targets.

Results:

One hundred and thirty-three ingredients were identified from WJYZG. According to the herbingredient- targets network, quercetin, kaempferol, luteolin, anhydroicaritin, and 8-prenyl-flavone were screened out as the key ingredients, which can interact with the core targets encompassing INS, IL6, TNF, IL1B, CASP3, PTGS2, VEGFA, and PPARG. The enrichment analysis indicates that the treatment of AD by WJYZG was through inhibiting inflammation and neurocyte apoptosis, regulating the calcium ion signaling pathway and adjusting INS levels.

Conclusion:

The underlying mechanisms of WJYZG in the treatment of AD were theoretically illustrated. We hope these results will enlighten the researches on AD.
Pan-Cancer Analysis of CENPA as a Potential Prognostic and Immunological
Biomarker in Human Cancer
Authors: Hu Zhongjiao , Zhang Shutao , Yan Xueling , Zheng Lulu , Ding Ke , Liu Shanshan , Shi Zheng
Published: May 2022

Background:

CENPA is a rare histone variant that regulates various active centromeres and neocentromeres via diverse signal pathways. However, the expression of CENPA correlated with the prognosis of patients in human pan-cancer is still largely under explored.

Objective:

To find the role of CENPA in the prognosis and immunotherapy of cancer patients.

Methods:

In this study, multiple bioinformatic methods, including ONCOMINE database, TCGA database, GEPIA database, DAVID database, and TIMER database were integrated to comprehensively investigate the prognosis and immunity of CENPA in pan-cancer.

Results:

The results showed that CENPA was widely expressed in numerous cancer types, including liver cancer, lung cancer, bladder cancer, gastric cancer. Meanwhile, the increased CENPA expression was significantly related to poor prognosis in breast cancer, lung cancer, and sarcoma. Additionally, CENPA expression had a positive coefficient for immune cell infiltration, including B cells, CD4+T cells, CD8+T cells, neutrophils, dendritic cells, and macrophages. Furthermore, we screened out TGCT, THCA, and LUSC as the most vital cancers correlated with CENPA expression in the immune microenvironment, according to immune score and stromal score. Notably, 47 common immune checkpoint genes were explored in 33 cancer types based on the coefficients of CENPA expression. In addition, CENPA expression was strongly associated with TMB and MSI in various cancers, like BLCA, BRCA, CESC, and CHOL. Moreover, there was a high correlation between CENPA expression and DNA methylation was obtained by calculating relatedness coefficients. Enrichment analysis showed that CENPA might be involved in the progression of cancer through cell cycle-related pathways, p53 signaling pathways, and mismatch repair enrichment pathway.

Conclusions:

Taken together, our results suggested that CEPNA could be considered as a promising predictive biomarker affecting prognosis and immune infiltration in human pan-cancer.
A Systematic Review of Updated Mechanistic Insights Towards
Alzheimer’s Disease
Authors: Mittal Arun , Sharma Rupali , Sardana Satish , Goyal Parveen Kumar , Piplani Mona , Pandey Anima
Published: May 2022

Background:

Alzheimer's disease (AD) is a degenerative neurological disorder that impairs
memory, cognitive abilities, and the ability to do everyday activities. This neurodegenerative disease is
growing increasingly common as the world's population ages. Here, we reviewed some of the key findings
showing the function of Aβ peptide, oxidative stress, free radical damage Triggering Receptors Expressed
cn Myeloid Cells 2 (TREM2), Nitric Oxide (NO) and gut microbiota in the aetiology of AD.

Methods:

The potentially relevant online medical databases, namely PubMed, Scopus, Google Scholar,
Cochrane Library, and JSTOR, were exhaustively researched. In addition, the data reported in the
present study were primarily intervened on the basis of the timeline selected from 1 January 2000 to 31
October 2021. The whole framework was designed substantially based on key terms and studies selected
by virtue of their relevance to our investigations.

Results:

Findings suggested that channels of free radicals, such as transition metal accumulation and
genetic factors, are mainly accountable for the redox imbalance that assist to understand better the
pathogenesis of AD and incorporating new therapeutic approaches. Moreover, TREM2 might elicit a
protective function for microglia in AD. NO causes an increase in oxidative stress and mitochondrial
damage, compromising cellular integrity and viability. The study also explored that the gut and CNS
communicate with one another and that regulating gut commensal flora might be a viable therapeutic
for neurodegenerative illnesses like AD.

Conclusion:

There are presently no viable therapies for Alzheimer's disease, but recent breakthroughs in
our knowledge of the disease's pathophysiology may aid in the discovery of prospective therapeutic targets.
Berberis aristata DC Extract Counteracts the High Fat Diet-Induced Reproductive
Toxicity in Female Wistar Rats via Modulating Oxidative Stress and
Resistance to Leptin and Insulin
Authors: Mushtaq Faiza , Akhtar Muhammad Furqan , Saleem Ammara , Sharif Ali , Akhtar Bushra , Askary Ahmad El , Abdel-Daim Mohamed M. , Javaid Zeeshan , Sohail Kashif , Anwar Fareeha
Published: May 2022

Background:

The plant Berberis aristata is traditionally used and scientifically validated
for treating obesity and hyperlipidemia. It is also traditionally used to treat gynecological
abnormalities. Therefore, the present study was designed to evaluate the therapeutic potential of
Berberis aristata for obesity-related reproductive changes and chemically characterize it.

Methods:

High-fat diet was given to 36 female rats for six weeks to induce obesity and infertility.
These obese rats were treated with 10 mg/kg orlistat or the plant extract at 125-500 mg/kg for 45
days.

Results:

The GC-MS analysis of the plant extract included fructose, thymic acid and other hydrocarbons.
The plant extract revealed a remarkable free radical scavenging activity. The treated
animals exhibited a decrease in total cholesterol and triglycerides (p<0.001), insulin and leptin
levels (p<0.05), visceral fat, and body weight while increasing the estradiol level at 500 mg/kg
dose of the plant extract as compared with untreated animals as demonstrated from the histology
of the ovary. Oxidative stress biomarkers such as superoxide dismutase, nitric oxide, malondialdehyde
and reduced glutathione were significantly (p<0.01-0.001) ameliorated in treated rats.

Conclutions:

B. aristata exhibited substantial potential against obesity-inducedreproductive damage
in female rats by reducing oxidative stress and resistance to leptin and insulin.
Proteome Exploration of Human Coronaviruses for Identifying
Novel Vaccine Candidate: A Hierarchical Subtractive Genomics
and Reverse Vaccinology Approach
Authors: Dorosti Hesam , Zarei Mahboubeh , Nezafat Navid
Published: May 2022

Background:

The SARS-CoV-2 has been responsible for infecting more than
613,615,658 people in 222 countries by September 11, 2022, of which 6,516,076 have
died. COVID-19 was introduced by World Health Organization as a global concern and a
pandemic disease due to its prevalence.

Objectives:

Developing preventive or therapeutic medications against 2019-nCoV is an urgent
need, and has been deemed as a high priority among scientific societies; in this regard,
the production of effective vaccines is one of the most significant and high-priority requirements.
Because of costly and time-consuming process of vaccine design, different
immunoinformatics methods have been developed.

Methods:

At the beginning of vaccine design, the proteome study is essential. In this investigation,
the whole human coronavirus proteome was evaluated using the proteome subtraction
strategy. Out of 5945 human coronavirus proteins, five new antigenic proteins
were selected by analyzing the hierarchical proteome subtraction, and then their various
physicochemical and immunological properties were investigated bioinformatically.

Results:

All five protein sequences are antigenic and non-allergenic proteins; moreover,
the spike protein group, including spike glycoprotein (E2) (Peplomer protein), spike fragment
and spike glycoprotein fragment, showed acceptable stability, which can be used to
design new vaccines against human coronaviruses.

Conclusion:

The selected peptides and the other proteins introduced in this study (HE,
orf7a, SARS_X4 domain-containing protein and protein 8) can be employed as a suitable
candidate for developing a novel prophylactic or therapeutic vaccine against human coronaviruses.
Characterization of AlInN/GaN based HEMT for Radio Frequency
Applications
Authors: Prasad Santashraya , Islam Aminul
Published: May 2022

Background:

The Si- and GaAs-based devices are not suitable for very high-speed and
high-power applications. Therefore, GaN-based devices have emerged as a potential contender. Further
improvement in the device characteristics using appropriate mole fractions of Al and InN in the barrier
layer of AlInN has become inevitable.

Objective:

To design AlInN/GaN HEMT and present its salient features.

Methods:

The design method for the proposed AlInN/GaN HEMT includes a selection of materials,
optimization of mole fraction in AlInN barrier layer, optimization of gate oxide thickness, optimization
of device dimensions, and doping concentration. The fabrication steps necessary for the AlInN/GaN
HEMT are also explained in the paper. Analysis of the structure has been carried out using the Silvaco
TCAD tool.

Results:

All the obtained results have revealed that the proposed device can operate up to the cut-off
frequency of 102 GHz and a maximum oscillation frequency of 230 GHz, which are suitable for radiofrequency
applications. The minimum noise figure and maximum transducer power gain (~18 dB)
achieved by the proposed device is quite acceptable.

Conclusion:

The use of the AlN spacer layer has improved the AlInN film quality and mitigates strain
at the heterointerface. Moreover, it reduces the Coulomb attraction between ions in the supply layer
and electrons in the channel layer thereby improving carrier mobility. Usage of a SiO2 layer between
the gate and AlInN barrier layer has decreased the gate leakage current. This has reduced the subthreshold
slope and increased ON/OFF current ratio (~1010). The proposed Si3N4 passivated HEMT
offers a breakdown voltage of ~1395 V.