bluuebunny/crossref_metadata_2025 huggingface dataset:
Exosomal microRNA-150-5p from bone marrow mesenchymal stromal cells mitigates cerebral ischemia/reperfusion injury via targeting B-cell translocation gene 2
Authors: Yang shuo , Li Xue , Bi Ting
Published: August 2021

Objective

MicroRNA(miR)-150-5p has been investigated in many studies, while the role of exosomal miR-150-5p from bone marrow mesenchymal stromal cells (BMSCs) on cerebral ischemia/reperfusion (I/R) injury remains extensive exploration. This research aims to probe the protective effects of exosomal miR-150-5p from BMSCs on cerebral I/R injury via regulating B-cell translocation gene 2 (BTG2).
Methods

BMSCs were cultured and transfected with miR-150-5p mimic, then exosomes from BMSCs were extracted. Middle cerebral artery occlusion (MCAO) rat model was established, and miR-150-5p and BTG2 levels in rat brain tissues were detected. Then gain and loss-function assays were conducted to probe the impact of exosomes, miR-150-5p and BTG2 on neurological function, pathological changes, apoptosis and inflammatory factors of MCAO rats. The binding relationship between miR-150-5p and BTG2 was validated.
Results

MiR-150-5p was decreased and BTG2 was augmented in MCAO rats. The exosomes from BMSCs could improve neurological function, pathological changes, apoptosis and reduce inflammatory factors in MCAO rats. Enriched miR-150-5p or decreased BTG2 could enhance the protective effects of exosomes from BMSCs on cerebral I/R injury. The elevated BTG2 reversed the impacts of enriched exosomal miR-150-5p. BTG2 was targeted by miR-150-5p.
Conclusion

Exosomal miR-150-5p from BMSCs exerts protective effects on cerebral I/R injury via repressing BTG2. This study provided novel therapeutic strategies for treatment of cerebral I/R injury.
3-hydroxykynurenine as a Potential Ligand for Hsp70 Proteins and its Effects on Drosophila Memory After Heat Shock
Authors: Zhuravlev Aleksandr V. , Shchegolev Boris F. , Zakharov Gennadii A. , Ivanova Polina N. , Nikitina Ekaterina A. , Savvateeva-Popova Elena V.
Published: August 2021

Kynurenine products of tryptophan metabolism are modifiers of the nervous activity and oxidative processes in mammals and invertebrates. 3-hydroxykynurenine (3HOK) in moderate concentrations is a lipid peroxidation inhibitor. However, its accumulation and oxidative auto dimerization lead to oxidative stress development manifested in age-related neurodegenerative diseases (NDDs) and neurologic disorders provoked by acute stress. Different forms of stress, the mostly studied being heat shock response, rely on functioning of heat shock proteins of Hsp70 superfamily. Since kynurenines are called “kids of stress”, we performed computational estimation of affinity of 3HOK and other kynurenines binding to predicted ATP site of Drosophila Hsp70 cognate 71 protein (Dhsp71) using Autodock Vina. The binding energy of 3HOK dimer is -9.4 kcal/mol, its orientation within the active site is close to that of ATP. This might be a new mechanism of producing a competitive inhibitor of Hsp70 chaperones that decreases organism ability to adapt to heat shock. We also showed that the Drosophila melanogaster cardinal (cd1) mutant with 3HOK excess, serving as a model for Huntington's disease (HD), manifests severe defects of short-term memory after heat shock applied either in adults, or at the prepupal stage.
α-Pinene inhibits the growth and induces the apoptosis of cervical cancer cells through regulating miR-34a/Bcl-2 signaling axis
Authors: Xiao-Su Huang , Pei Yan , Chang Zhou , Qiuxiang Xu , Ming Li , Lianbao Ye , Wenqing Ding , Wei-Qiang Chen
Published: August 2021

Purpose α-pinene was a chemical compound which was extracted from pine needles oil, and it exerted effects on various diseases. However, the effect of α-pinene on cervical cancer had not been reported. The goal of this study was to explore the anti-tumor role of α-pinene. Methods Methyl thiazolyl tetrazolium (MTT) method was used to detect cytotoxicity of α-pinene. Flow cytometry was used to quantify the cell cycle and apoptosis. TUNEL staining was also performed for the revalidation of apoptosis. QRT-PCR and western blot was implemented to detect the expression levels of apoptosis genes and miR-34a-5p. Tumor-bearing nude mouse models was adopted to assess the anti-tumor action of α-pinene in vivo. Results The results displayed α-pinene restrained proliferation of Hela cells in G1 phase and induced Hela cell apoptosis, which was related to up-regulating expressions of Bax, Bid, Caspase-9, Caspase-3, miR-34a-5p and down-regulating the expression of Bcl-2. Afterwards, α-Pinene could regulate miR-34a-5p/Bcl-2 pathway. Furthermore, α-pinene treatment also induced apoptosis in xenografts tumor models. The fluorescence intensity of Bax, Bid, Caspase-9, Caspase-3 increased and fluorescence intensity of Bcl-2 decreased. Conclusions Our research demonstrated α-pinene could restrain the development of cervical cancer growth, and it might be an effective chemical compound for therapy of cervical cancer.
Progression of COVID-19 under the highly restrictive measures imposed in Argentina
Authors: Sagripanti Jose-Luis , Aquilano Daniel R.
Published: August 2021

The variety and extent of non-pharmaceutical measures implemented by the government to control COVID-19 in Argentina were exceptional, making this country the best example to analyze the evolution of COVID-19 under the most stringent and longer-lasting restrictive policies- which up to May 31st 2021 included 119 days of strict nation-wide lock-down, 304 days of less restrictive lock-downs, and 35 days of curfews. Two of the three peaks of infection correlated with the germicidal solar flux received in Argentina, suggesting a seasonal component and a role for the virus persisting in the environment. A massive public gathering crowding the presidential square in Buenos Aires, during which nearly half of those present were without face masks, did not alter the infection curve in that city. Comparative epidemiological data (standardized per million inhabitants) shows that COVID-19 in Uruguay, a neighboring country whose capital is at a similar latitude than Buenos Aires and who did not mandate lock-downs or curfews, progressed much slower (until vaccination started) than in Argentina. The number of yearly deaths caused by respiratory diseases and influenza in Argentina before the pandemic was similar to the total number of deaths attributed to COVID-19 cumulated on April 25, 2021, more than a year after the pandemic started. The failure to detect any benefit on ameliorating COVID-19 by the long and strict nation-wide lock-downs in Argentina should raise world-wide concerns about mandating costly and ineffective restrictive measures during ongoing or future pandemics
Livelihood vulnerability assessments and adaptation strategies to climate change: a case study in Tanguar haor, Sylhet
Authors: Raihan Farzana , Melon Hossain Mohammad
Published: August 2021

Bangladesh is very prone to climate-driven hazards due to its unique geographical location, high population density, and low climate resilience. Therefore, this study addresses the livelihood vulnerabilities and adaptation strategies in response to the climate change issues based on empirical evidence from wetland communities using the livelihood vulnerability index (LVI) in Tanguar haor, located in Sylhet, Bangladesh. The finding shows that people of the study area are switching their formal livelihood activities into alternative sources. Crop diversification, homestead gardening, erosion proofing, and cage aquaculture are commonly used by the studied communities to adapt to climate change impacts. The main driver of vulnerabilities was found to be lack of education, underdeveloped infrastructures, lack of advanced health facilities, and lack of alternative livelihoods during extreme events. Therefore, people living in and around the haor region need special consideration. Overall, the study suggests that policy or institutional arrangements are required to promote the better governance system for local communities to improve their living standard so that they can achieve resilience to the impacts of climate variability and change in this area.
Evaluating the potential impact of climate change on the hydrology ofRibbcatchment, Lake Tana Basin, Ethiopia
Authors: Ayalew Dessalegn Worku , Asefa Tirusew , Moges Mamaru Ayalew , Leyew Sileshie Mesfin
Published: August 2021

Scientific findings indicated there is climate change that affects given hydrology and, hence, water availability worldwide. To quantify its impact on a specific catchment scale, since spatial and temporal variability of climate change impact, this study was carried out at Ribb catchment, Lake Tana basin, Ethiopia. The catchment hydrology was represented by the Soil and Water Analysis Tool (SWAT) through using historical observed data. Regional Climate Model (RCM) projection data set for Nile Basin studies at Representative Concentration Pathway (RCPs) (RCP4.5 and RCP8.5) were used for future streamflow generation on three-time horizons; 2020s (2011–2040), 2050s (2041–2070), and 2080s (2071–2098). A baseline period (1976–2005) was used as a reference. SWAT was calibrated (R2 = 0.83 and NSE = 0.74) and validated (R2 = 0.72 and NSE = 0.71). The analysis was done based on the changes from the baseline period to the 2080s. Temperature showed an increasing trend but rainfall is decreasing. The mean annual streamflow could potentially reduce from 42.78 m3/s to 40.24 m3/s and from 42.78 m3/s to 37.58 m3/s based on RCP4.5 and RCP8.5 scenarios, respectively. On a monthly time scale, decreases in streamflow were found from March to August whereas there was a slight increase from September to February. Concerning individual months, June flows were found to have maximum impact in both scenarios (63.3% at RCP8.5 and 55.45% at RCP4.5 scenarios). The least impacted month was August based on the RCP8.5 scenario which is decreased by 6.64% and April based on the RCP4.5 scenario which is reduced by 1.21%. Looking at total volume, July showed a maximum decrease in both scenarios which is reduced by 21.08 m3/s at the RCP4.5 scenario and 51.22 m3/s at the RCP8.5 scenario. The maximum increase was found in October with 10.31 m3/s and 11.26 m3/s at RCP4.5 and RCP8.5 scenarios respectively. The future streamflow of Ribb River has decreased annually and monthly due to increasing temperature and reduction of rainfall.
Krebs Cycle Rewired: Driver of Atherosclerosis Progression?
Authors: Liang Yamin , Chen Yanmei , Li Lu , Zhang Shulei , Xiao Jinyan , Wei Dangheng
Published: August 2021

:

The tricarboxylic acid (TCA) cycle is the center of energy metabolism in eukaryotic cells and is dynamically adjusted according to the energy needs of cells. Macrophages are activated by inflammatory stimuli, and then two breakpoints in TCA cycle lead to the accumulation of intermediates. Atherosclerosis is a chronic inflammatory process. Here, the "non-metabolic" signaling functions of TCA cycle intermediates in the macrophage under inflammatory stimulation and the role of intermediates in the progression of atherosclerosis are discussed.
Computational Prediction of Binding Affinity for CDK2-ligand Complexes.
A Protein Target for Cancer Drug Discovery
Authors: Veit-Acosta Martina , de Azevedo Junior Walter Filgueira
Published: August 2021

Background:

CDK2 participates in the control of eukaryotic cell-cycle progression. Due to
the great interest in CDK2 for drug development and the relative easiness in crystallizing this enzyme,
we have over 400 structural studies focused on this protein target. This structural data is the basis for
the development of computational models to estimate CDK2-ligand binding affinity.

Objective:

This work focuses on the recent developments in the application of supervised machine
learning modeling to develop scoring functions to predict the binding affinity of CDK2.

Method:

We employed the structures available at the protein data bank and the ligand information accessed
from the BindingDB, Binding MOAD, and PDBbind to evaluate the predictive performance of
machine learning techniques combined with physical modeling used to calculate binding affinity. We
compared this hybrid methodology with classical scoring functions available in docking programs.

Results:

Our comparative analysis of previously published models indicated that a model created using
a combination of a mass-spring system and cross-validated Elastic Net to predict the binding affinity of
CDK2-inhibitor complexes outperformed classical scoring functions available in AutoDock4 and AutoDock
Vina.

Conclusion:

All studies reviewed here suggest that targeted machine learning models are superior to
classical scoring functions to calculate binding affinities. Specifically for CDK2, we see that the combination
of physical modeling with supervised machine learning techniques exhibits improved predictive
performance to calculate the protein-ligand binding affinity. These results find theoretical support
in the application of the concept of scoring function space.
A Comparative Insight on the Newly Emerging Rifamycins: Rifametane, Rifalazil, TNP-2092 and TNP-2198
Authors: Nazli Adila , He David L. , Xu Huacheng , Wang Zhi-Peng , He Yun
Published: August 2021

Rifamycins are considered a milestone for tuberculosis (TB) treatment because of their proficient sterilizing ability. Currently, available TB treatments are complicated and need a long duration, which ultimately leads to failure of patient compliance. Some new rifamycin derivatives, i.e., rifametane, TNP-2092 (rifamycin-quinolizinonehybrid), and TNP-2198 (rifamycin-nitromidazole hybrid) are under clinical trials, which are attempting to overcome the problems associated with TB treatment. The undertaken review is intended to compare the pharmacokinetics, pharmacodynamics and safety profiles of these rifamycins, including rifalazil, another derivative terminated in phase II trials, and already approved rifamycins. The emerging resistance of microbes is an imperative consideration associated with antibiotics. Resistance development potential of microbial strains against rifamycins and an overview of chemistry, as well as structure-activity relationship (SAR) of rifamycins, are briefly described. Moreover, issues associated with rifamycins are discussed as well. We expect that newly emerging rifamycins shall appear as potential tools for TB treatment in the near future.
Structure and Functions of T-cell Immunoglobulin-domain and Mucin- domain Protein 3 in Cancer
Authors: Lu Xinjie
Published: August 2021

Background:

T-cell immunoglobulin (Ig)-domain and mucin-domain (TIM) proteins represent a family of receptors expressed on T-cells that play essential cellular immunity roles. The TIM proteins span across the membrane belonging to type I transmembrane proteins. The N terminus contains an Ig-like V-type domain and a Ser/Thr-rich mucin stalk as a co-inhibitory receptor. The C-terminal tail oriented toward the cytosol predominantly mediates intracellular signaling.

Methods:

This review discusses the structural features and functions of TIM-3, specifically on its role in mediating immune responses in different cell types and the rationale for TIM-3-targeted cancer immunotherapy.

Results:

TIM-3 has gained significant importance to be a potential biomarker in cancer immunotherapy. It has been shown that blockade with checkpoint inhibitors promotes anti-tumor immunity and inhibits tumor growth in several preclinical tumor models.

Conclusion:

TIM-3 is an immune regulating molecule expressed on several cell types, including IFNγ-producing T-cells, FoxP3+ Treg cells, and innate immune cells. The roles of TIM-3 in immunosuppression support its merit as a target for cancer immunotherapy.
Pentacyclic Triterpenoids as Antibiofilm Agents against Methicillinresistant
and Biofilm-forming Staphylococcus aureus (MRSA)
Authors: Chung Pooi Yin Katrina , Gan Ming Yi , Chin Beek Yoke
Published: August 2021

Background:

Methicillin-resistant Staphylococcus aureus (MRSA) has been constantly evolv-ing and developing resistance against conventional antibiotics. One of the key features of MRSA that enables it to develop resistance to antibiotics and host immune system is its ability to form biofilm in indwelling medical devices. In previous studies, the antimicrobial activity and mechanisms of action of three known pentacyclic triterpenoids α-amyrin, betulinic acid and betulinaldehyde against planktonic cells of MRSA were determined and elucidated.

Objective:

This study was carried out to evaluate the ability of the three compounds to significantly reduce the biomass of pre-formed biofilms of MRSA and metabolic activity of the bacterial cells in the biofilm.

Methods:

The anti-biofilm activity of α-amyrin, betulinic acid and betulinaldehyde, individually and in combination with oxacillin or vancomycin, against reference strain of MRSA in pre-formed biofilm were evaluated using the crystal violet and resazurin assays.

Results:

α-amyrin and betulinic acid significantly reduced the biomass of pre-formed biofilms of MRSA as individual compounds and in combination with oxacillin or vancomycin. Although betulinaldehyde individually increased the biomass, selected combinations with oxacillin and vancomycin were able to reduce the biomass. All three compounds did not show cytotoxic properties on normal mammalian cells.

Conclusion:

The three pentacyclic triterpenoids could significantly reduce pre-formed biofilm of MRSA with no cytotoxic effects on normal mammalian cells. These findings demonstrated that pentacyclic triterpenoids have the potential to be developed further as antibiofilm agents against MRSA cells in bio-films, to combat infections caused by multidrug-resistant and biofilm-forming S. aureus.
The Role of Bacterial Proteases in Microbe and Host-microbe Interactions
Authors: Hammers Daniel , Carothers Katelyn , Lee Shaun
Published: August 2021

Background:

Secreted proteases are an important class of factors used by bacterial to
modulate their extracellular environment through the cleavage of peptides and proteins. These proteases
can range from broad, general proteolytic activity to high degrees of substrate specificity.
They are often involved in interactions between bacteria and other species, even across kingdoms,
allowing bacteria to survive and compete within their niche. As a result, many bacterial proteases
are of clinical importance. The immune system is a common target for these enzymes, and bacteria
have evolved ways to use these proteases to alter immune responses for their benefit. In addition to
the wide variety of human proteins that can be targeted by bacterial proteases, bacteria also use these
secreted factors to disrupt competing microbes, ranging from outright antimicrobial activity to
disrupting processes like biofilm formation.

Objective:

In this review, we address how bacterial proteases modulate host mechanisms of protection
from infection and injury, including immune factors and cell barriers. We also discuss the contributions
of bacterial proteases to microbe-microbe interactions, including antimicrobial and anti-
biofilm dynamics.

Conclusion:

Bacterial secreted proteases represent an incredibly diverse group of factors that bacteria
use to shape and thrive in their microenvironment. Due to the range of activities and targets of
these proteases, some have been noted for having potential as therapeutics. The vast array of bacterial
proteases and their targets remains an expanding field of research, and this field has many important
implications for human health.
The Role of Stem Cells in the Therapy of Stroke
Authors: Brzecka Anna , Ejma Maria , Madetko Natalia , Alster Piotr , Budrewicz Sławomir , Koszewicz Magdalena , Misiuk-Hojło Marta , Tomilova Irina K. , Somasundaram Siva G. , Kirkland Cecil E.
Published: August 2021

Background:

Stroke is a major challenge in neurology due to its multifactorial genesis and
irreversible consequences. Processes of endogenous post-stroke neurogenesis, although
insufficient, may indicate possible direction of future therapy. Multiple research considers
stem-cell-based approaches in order to maximize neuroregeneration and minimize post-stroke
deficits.

Objective:

Aim of this study is to review current literature considering post-stroke stem-cell-
based therapy and possibilities of inducing neuroregeneration after brain vascular damage.

Methods:

Papers included in this article were obtained from PubMed and MEDLINE
databases. The following medical subject headings (MeSH) were used: “stem cell therapy”,
“post-stroke neurogenesis”, “stem-cells stroke”, “stroke neurogenesis”, “stroke stem cells”,
“stroke”, “cell therapy”, “neuroregeneration”, “neurogenesis”, “stem-cell human”, “cell therapy
in human”. Ultimate inclusion was made after manual review of the obtained reference list.

Results:

Attempts of stimulating neuroregeneration after stroke found in current literature
include supporting endogenous neurogenesis, different routes of exogenous stem cells
supplying and extracellular vesicles used as a method of particle transport.

Conclusion:

Although further research in this field is required, post stroke brain recovery
supported by exogenous stem cells seems to be promising future therapy revolutionizing
modern neurology.
Phytochemicals Targeting Oxidative Stress, Interconnected Neuroinflammatory,
and Neuroapoptotic Pathways Following Radiation
Authors: Fakhri Sajad , Piri Sana , Moradi Seyed Zachariah , Khan Haroon
Published: August 2021

:

The radiation for therapeutic purposes has shown positive effects in different contexts;
however, it can increase the risk of many age-related and neurodegenerative diseases such as Alzheimer’s
disease (AD), amyotrophic lateral sclerosis (ALS), Huntington’s disease (HD), and Parkinson’s
disease (PD). These different outcomes highlight a dose-response phenomenon called
hormesis. Prevailing studies indicate that high doses of radiation could play several destructive roles
in triggering oxidative stress, neuroapoptosis, and neuroinflammation in neurodegeneration. However,
there is a lack of effective treatments in combating radiation-induced neurodegeneration, and
the present drugs suffer from some drawbacks, including side effects and drug resistance. Among
natural entities, polyphenols are suggested as multi-target agents affecting the dysregulated pathogenic
mechanisms in neurodegenerative disease. This review discusses the destructive effects of radiation
on the induction of neurodegenerative diseases by dysregulating oxidative stress, apoptosis,
and inflammation. We also describe the promising effects of polyphenols and other candidate phytochemicals
in preventing and treating radiation-induced neurodegenerative disorders, aiming to
find novel/potential therapeutic compounds against such disorders.
Stress-Reducing Psychological Interventions as Adjuvant Therapies for
Diabetic Chronic Wounds
Authors: Carvalho Eugénia , Pombeiro Isadora , Moura João , Pereira M. Graça
Published: August 2021

Background:

Diabetic foot ulcers (DFUs) are a major complication of diabetes mellitus
and a leading cause of lower limb amputation. Interventions to reduce psychological stress may
have the potential to improve self-care and greatly reduce the morbidity and mortality associated
with DFU. This review is focused on the consequences of psychological stress in wound healing
and reflects on the effects of currently used psychological stress-reducing interventions in patients
with DFU, proposing new applications for currently used stress-reduction interventions.

Results:

Stress is a natural and fundamental survival mechanism that becomes harmful when chronic.
DFU is associated with high levels of anxiety and chronic psychological stress. Chronic stressinduced
cortisol and adrenaline release impair wound healing, independently of the stressor. Psychological
stress-reducing interventions, such as relaxation with guided imagery, biofeedback-assisted
relaxation, mindfulness-based strategies, and hypnosis, can lead to a reduction in perceived
stress and improve wound healing by reducing wound inflammation and pain while improving
glycemic control. All stress reduction interventions also lead to pain relief and improved patient’s
quality of life.

Conclusion:

Psychological stress-reducing interventions are promising adjuvant therapies for
DFU. Their clinical application can improve self-care by tackling patient’s expectations, anxieties,
and fears. They can also help patients manage stress and pain while reducing wound inflammation
and improving wound healing.
Synthesis of 4-styrylpyrazoles and Evaluation of their Inhibitory Effects on
Cyclin-dependent Kinases
Authors: Kryštof Vladimír , Cankař Petr , Toman Daniel , Jorda Radek , Ajani Haresh
Published: August 2021

Background:

Cycle-regulating and transcriptional cyclin-dependent kinases (CDKs) are
attractive targets in cancer drug development. Several CDK inhibitors have already been obtained or
are close to regulatory approval for clinical applications.

Objective:

Phenylazopyrazole CAN508 has been described as the first selective CDK9 inhibitor with
an IC50 of 350 nM. Since the azo-moiety is not a suitable functionality for drugs due to pharmacological
reasons, the preparation of carbo-analogues of CAN508 with similar biological activities is desirable.
The present work is focused on the synthesis of carbo-analogues similar to CAN508 and their
CDK inhibition activity.

Methods:

Herein, the synthesis of 21 novel carbo analogues of CAN508 and their intermediates is
reported. Subsequently, target compounds 8a - 8u were evaluated for protein kinase inhibition
(CDK2/cyclin E, CDK4/cyclin D, CDK9/cyclin T) and antiproliferative activities in cell lines (K562,
MCF-7, MV4-11). Moreover, the binding mode of derivative 8s in the active site of CDK9
was modelled.

Results:

Compounds 8a - 8u were obtained from key intermediate 7, which was prepared by linear
synthesis involving Vilsmeier-Haack, Knoevenagel, Hunsdiecker, and Suzuki-Miyaura reactions.
Styrylpyrazoles 8t and 8u were the most potent CDK9 inhibitors with IC50 values of approximately 1
μM. Molecular modelling suggested binding in the active site of CDK9. The flow cytometric analysis
of MV4-11 cells treated with the most active styrylpyrazoles showed a significant G1-arrest.

Conclusion:

The prepared styrylpyrazoles showed inhibition activity towards CDKs and can provide
a novel chemotype of kinase inhibitors.
Novel Pathways and Mechanisms of Nicotine-Induced Oral Carcinogenesis
Authors: Radhakrishnan Raghu A. , Sharma Mohit , Shetty Smitha S.
Published: August 2021

Background:

Smokeless Tobacco (SLT) contains 9 times more nicotine than Smoked
Tobacco (SMT). The carcinogenic effect of nicotine is intensified by converting nicotine-to-nicotine-
derived Nitrosamines (NDNs).

Methods:

A review of the literature was conducted with a tailored search strategy to unravel the
novel pathways and mechanisms of nicotine-induced oral carcinogenesis.

Results:

Nicotine and NDNs act on nicotinic Acetylcholine Receptors (nAChRs) as agonists. Nicotine
facilitates cravings through α4β2nAChR and α7nAChR, via enhanced brain dopamine release.
Nicotine binding to nAChR promotes proliferation, migration, invasion, chemoresistance, radioresistance,
and metastasis of oral cancer cells. Nicotine binding to α7nAChR on keratinocytes triggers
Ras/Raf-1/MEK1/ERK cascade, promoting anti-apoptosis and pro-proliferative effects. Furthermore,
the nicotine-enhanced metastasis is subdued on nAChR blockade through reduced nuclear
localization of p-EGFR.

Conclusion:

Protracted exposure to nicotine/NDN augments cancer-stimulatory α7nAChR and desensitizes
cancer inhibitory α4β2nAChR. Since nAChRs dictate both addictive and carcinogenic effects
of nicotine, it seems counterintuitive to designate nicotine just as an addictive agent devoid of
any carcinogenicity.
Direct Modulation of the Gut Microbiota as a Therapeutic Approach for
Alzheimer’s Disease
Authors: Wang Yi , Dykes Gary A.
Published: August 2021

:

Alzheimer’s disease is a neurodegenerative disease characterized by a progressive decline
in memory and cognitive functions. It is a multifactorial disease involving a wide range of
pathological factors that are not fully understood. As supported by a growing amount of evidence
in recent years, gut microbiota plays an important role in the pathogenesis of Alzheimer’s disease
through the brain-gut-microbiota axis. This suggests that direct modulation of the gut microbiota
can be a potential therapeutic target for Alzheimer’s disease. This review summarizes recent research
findings on the modulation of the gut microbiota by probiotic therapies and faecal microbiota
transplantation for controlling the pathologies of Alzheimer’s disease. Current limitations and future
research directions of this field are also discussed.
Medicinal Herbs and Nutritional Supplements for Dementia Therapy:
Potential Targets and Clinical Evidence
Authors: Dorman Guido , Flores Ignacio , Gutiérrez Carlos , Castaño Ramiro Fernández , Aldecoa Mayra , Kim Leandro
Published: August 2021

:

Spices and herbs have been used for medicinal purposes for centuries. Also, in the last
decades, the use of different nutritional supplements has been implemented to treat all kinds of diseases,
including those that present an alteration in cognitive functioning. Dementia is a clinical syndrome
in which a person's mental and cognitive capacities gradually decline. As the disease progresses,
the person’s autonomy diminishes. As there is not an effective treatment to prevent progressive
deterioration in many of these pathologies, nutritional interventions have been, and still
are, one of the most widely explored therapeutic possibilities. In this review, we have discussed a
great number of potentially interesting plants, nutritional derivatives, and probiotics for the treatment
of dementia around the world. Their action mechanisms generally involve neuroprotective effects
via anti-inflammatory, antioxidant, anti-apoptotic, b-amyloid, and tau anti-aggregate actions;
brain blood flow improvement, and effects on synaptic cholinergic and dopaminergic neurotransmission,
which may optimize cognitive performance in patients with cognitive impairment. As for
their efficacy in patients with cognitive impairment and/or dementias, evidence is still scarce
andthe outcomes are controversial. We consider that many of these substances have promising therapeutic
properties. Therefore, the scientific community has to continue with a complete research focused
on both identifying possible action mechanisms and carrying out clinical trials, preferably
randomized, double-blind ones, with a greater number of patients, a long-term follow-up, dose standardization,
and the use of current diagnostic criteria.
Antihyperlipidemic and Hepatoprotective Properties of Vitamin B6 Supplementation in Rats with High-Fat Diet-Induced Hyperlipidemia
Authors: Zhang Qian , Zhang Da-long , Zhou Xiao-li , Li Qian , He Ning , Zhang Jing , Gu Qing , Qian Zhi-Yong
Published: August 2021

Background:

The incidence and mortality of hyperlipidemia are increasing year by
year, showing a younger trend. At present, the treatment of hyperlipidemia is mainly dependent on
western medicine, but its side effects on liver and kidney function are common in clinics. Therefore,
it is necessary to study the treatment of hyperlipidemia by augmenting effective dietary nutrition
supplements. Vitamin B6 (VitB6), as an essential cofactor for enzymes, participates in lipid
metabolism. The effects of VitB6 on hyperlipidemia, however, have not been reported until now.

Aim:

The present study was to investigate the influence of VitB6 on hepatic lipid metabolism in hyperlipidaemia
rats induced by a High-Fat Diet (HFD).

Methods:

Male Sprague-Dawley rats were kept on HFD for two weeks to establish the hyperlipidemia
model. The rats in low-dosage and high-dosage groups were received 2.00 and 3.00 mg/kg/-
day of VitB6 for eight weeks, respectively.

Results:

The results showed that both doses of VitB6 reduced HFD-induced hepatic Low-Density
Lipoprotein Cholesterol (LDL-C); decreased blood cholesterol (TC), triglycerides, LDL-C, atherogenic
index (AI), Atherogenic Index of Plasma (AIP), apolipoprotein B (ApoB) and ApoB/apolipoprotein
A-1(ApoA1) ratio; increased liver High-Density Lipoprotein Cholesterol (HDL-C) and
serum ApoA1; reduced hepatic steatosis and triglyceride accumulation, lowered fat storage, and recovered
heart/body and brain/body ratio to a normal level. In addition, VitB6 supplementation
markedly decreased HMGR level, increased the mRNA abundance of LDLR and CYP7A1, and
protein expression of SIRT1, following the downregulation of SREBP-1 and PPARγ protein expression
in the liver of hyperlipidemia rats.

Conclusion:

In summary, oral VitB6 supplementation can ameliorate HFD-induced hepatic lipid
accumulation and dyslipidemia in SD rats by inhibiting fatty acid and cholesterol synthesis, promoting
fatty acid decomposition and cholesterol transport.
Therapeutic Options for the Management of Aromatase Inhibitor-
Associated Bone Loss
Authors: Gaudio Agostino , Xourafa Anastasia , Rapisarda Rosario , Castellino Pietro
Published: August 2021

Background:

Breast cancer is the most commonly occurring cancer in women worldwide.
Early breast cancer is a kind of invasive neoplasm that has not proliferated beyond the breast
or the axillary lymph nodes. Current therapeutic strategies for breast cancer mainly include local
therapies such as surgery or radiotherapy and systemic therapies like chemotherapy, endocrine, and
targeted therapy. Nowadays, the adjuvant treatment for hormone receptor-positive early breast cancer
in postmenopausal women remains the main effective systemic therapy which can improve disease-
free survival and overall survival; it involves several endocrine treatment regimens, including
Selective Estrogen Receptor Modulators (SERMs), Aromatase Inhibitors (AIs), or a combination
of them. AIs have been shown to be more effective in preventing recurrence in postmenopausal women
with early breast cancer when compared with tamoxifen, thus representing the standard of
care for adjuvant endocrine therapy. Although AIs are usually well-tolerated, they can have some
side effects. Apart from the appearance of arthralgias or myalgias and cardiovascular events, AI
therapies, reducing already low endogenous postmenopausal estradiol levels, cause increased bone
loss and increase fracture risk in postmenopausal women.

Objectives:

The objective of this review is to evaluate the therapeutic options in the management
of Aromatase Inhibitor-Associated Bone Loss (AIBL).

Methods:

We reviewed the current literature dealing with different therapeutic options in the treatment
of AIBL.

Results:

Clinical practice guidelines recommend a careful evaluation of skeletal health in all women
with breast cancer before AI therapy initiation. Adequate calcium and vitamin D intake have also
been suggested. Pharmacological attempts to minimize AI-related bone loss have focused on the
use of antiresorptive agents, such as bisphosphonates and denosumab to protect bone integrity and
reduce the risk of fractures. Furthermore, clinical trials have shown that by making the bone microenvironment
less susceptible to breast cancer metastasis, these drugs are able to increase disease-
free survival.

Conclusions:

AI, that are the pillar of the systemic treatment for patients with hormone receptor--
positive breast cancer, are associated with different side effects, and in particular, osteoporosis and
fractures. Both bisphosphonates and denosumab are able to prevent this negative effect.
Anti-Diabetic Drugs GLP-1 Agonists and DPP-4 Inhibitors may Represent
Potential Therapeutic Approaches for COVID-19
Authors: Alshanwani Aliah , Kashour Tarek , Badr Amira
Published: August 2021

:

The fast spread of coronavirus 2019 (COVID-19) calls for immediate action to counter
the associated significant loss of human life and deep economic impact. Certain patient populations
like those with obesity and diabetes are at higher risk for acquiring severe COVID-19 disease and
have a higher risk of COVID-19 associated mortality. In the absence of an effective and safe
vaccine, the only immediate promising approach is to repurpose an existing approved drug. Several
drugs have been proposed and tested as adjunctive therapy for COVID-19. Among these drugs are
the glucagon-like peptide-1 (GLP-1) 2 agonists and the dipeptidylpeptidase-4 (DPP-4) inhibitors.
Beyond their glucose-lowering effects, these drugs have several pleiotropic protective properties,
which include cardioprotective effects, anti-inflammatory and immunomodulatory activities, antifibrotic
effects, antithrombotic effects, and vascular endothelial protective properties. This narrative
review discusses these protective properties and addresses their scientific plausibility for their potential
use as adjunctive therapy for COVID-19 disease.
Determinants of Use of the Care Information Exchange Portal: Cross-sectional Study
Authors: Neves Ana Luisa , Smalley Katelyn R , Freise Lisa , Harrison Paul , Darzi Ara , Mayer Erik K
Published: August 2021

Background

Sharing electronic health records with patients has been shown to improve patient safety and quality of care. Patient portals represent a convenient tool to enhance patient access to their own health care data. However, the success of portals will only be possible through sustained adoption by its end users: the patients. A better understanding of the characteristics of users and nonusers is critical for understanding which groups remain excluded from using such tools.

Objective

This study aims to identify the determinants of the use of the Care Information Exchange, a shared patient portal program in the United Kingdom.

Methods

A cross-sectional study was conducted using a web-based questionnaire. Information collected included age, gender, ethnicity, educational level, health status, postcode, and digital literacy. Registered individuals were defined as having had an account created in the portal, independent of their actual use of the platform; users were defined as having ever used the portal. Multivariate logistic regression was used to model the probability of being a user. Statistical analysis was performed in R and Tableau was used to create maps of the proportion of Care Information Exchange users by postcode area.

Results

A total of 1083 participants replied to the survey (186% of the estimated minimum target sample). The proportion of users was 61.58% (667/1083). Among these, most (385/667, 57.7%) used the portal at least once a month. To characterize the system’s users and nonusers, we performed a subanalysis of the sample, including only participants who had provided at least information regarding gender and age. The subanalysis included 650 individuals (389/650, 59.8% women; 551/650, 84.8% >40 years). Most participants were White (498/650, 76.6%) and resided in London (420/650, 64.6%). Individuals with a higher educational degree (undergraduate and professional, or postgraduate and higher) had higher odds of being a portal user (adjusted odds ratio [OR] 1.58, 95% CI 1.04-2.39 and OR 2.38, 95% CI 1.42-4.02, respectively) compared with those with a secondary degree or below. Higher digital literacy scores (≥30) were associated with higher odds of being a user (adjusted OR 2.96, 95% CI 2.02-4.35). Those with a good overall health status had lower odds of being a user (adjusted OR 0.58, 95% CI 0.37-0.91).

Conclusions

This work adds to the growing body of evidence highlighting the importance of educational aspects (educational level and digital literacy) in the adoption of patient portals. Further research should not only describe but also systematically address these inequalities through patient-centered interventions aimed at reducing the digital divide. Health care providers and policy makers must partner in investing and delivering strategic programs that improve access to technology and digital literacy in an effort to improve digital inclusion and reduce inequities in the delivery of care.
Clinical Utility of Wearable Sensors and Patient-Reported Surveys in Patients With Schizophrenia: Noninterventional, Observational Study
Authors: Lahti Adrienne C , Wang Dai , Pei Huiling , Baker Susan , Narayan Vaibhav A
Published: August 2021

Background

Relapse in schizophrenia may be preceded by early warning signs of biological, sensory, and clinical status. Early detection of warning signs may facilitate intervention and prevent relapses.

Objective

This study aims to investigate the feasibility of using wearable devices and self-reported technologies to identify symptom exacerbation correlates and relapse in patients with schizophrenia.

Methods

In this observational study, patients with schizophrenia were provided with remote sensing devices to continuously monitor activity (Garmin vivofit) and sleep (Philips Actiwatch), and smartphones were used to record patient-reported outcomes. Clinical assessments of symptoms (Positive and Negative Syndrome Scale and Brief Psychiatric Rating Scale) were performed biweekly, and other clinical scales on symptoms (Clinical Global Impression-Schizophrenia, Calgary Depression Scale), psychosocial functioning, physical activity (Yale Physical Activity Survey), and sleep (Pittsburgh Sleep Quality Index) were assessed every 4 weeks. Patients were observed for 4 months, and correlations between clinical assessments and aggregated device metrics data were assessed using a mixed-effect model. An elastic net model was used to predict the clinical symptoms based on the device features.

Results

Of the 40 patients enrolled, 1 patient relapsed after being stable with evaluable postbaseline data. Weekly patient-reported outcomes were moderately correlated with psychiatric symptoms (Brief Psychiatric Rating Scale total score, r=0.29; Calgary Depression Scale total score, r=0.37; and Positive and Negative Syndrome Scale total score, r=0.3). In the elastic net model, sleep and activity features derived from Philips Actigraph and Garmin vivofit were predictive of the sitting index of the Yale Physical Activity Survey and sleep duration component of the Pittsburgh Sleep Quality Index. On the basis of the combined patient data, a high percentage of data coverage and compliance (>80%) was observed for each device.

Conclusions

This study demonstrated that wearable devices and smartphones could be effectively deployed and potentially used to monitor patients with schizophrenia. Furthermore, metrics-based prediction models can assist in detecting earlier signs of symptom changes. The operational learnings from this study may provide insights to conduct future studies.

Trial Registration

ClinicalTrials.gov NCT02224430; https://www.clinicaltrials.gov/ct2/show/NCT02224430
Experiences of Using a Self-management Mobile App Among Individuals With Heart Failure: Qualitative Study (Preprint)
Authors: Schmaderer Myra , Miller Jennifer N , Mollard Elizabeth
Published: August 2021

BACKGROUND

Interventions that focus on the self-management of heart failure are vital to promoting health in patients with heart failure. Mobile health (mHealth) apps are becoming more integrated into practice to promote self-management strategies for chronic diseases, optimize care delivery, and reduce health disparities.

OBJECTIVE

The purpose of this study was to explore the experience of using a self-management mHealth intervention in individuals with heart failure to inform a future mHealth intervention study.

METHODS

This study used a qualitative descriptive design. Participants were enrolled in the intervention groups of a larger parent study using a mobile app related to self-management of heart failure. The purposive, convenient, criterion-based sample for this qualitative analysis comprised 10 patients who responded to phone calls and were willing to be interviewed. Inclusion criteria for the parent study were adults who were hospitalized at Nebraska Medical Center with a primary diagnosis and an episode of acute decompensated heart failure; discharged to home without services such as home health care; had access to a mobile phone; and were able to speak, hear, and understand English.

RESULTS

Study participants were middle-aged (mean age 55.8, SD 12 years; range 36-73 years). They had completed a mean of 13.5 (SD 2.2) years (range 11-17 years) of education. Of the 10 participants, 6 (60%) were male. Half of them (5/10, 50%) were New York Heart Association Classification Class III patients and the other half were Class IV patients. The intervention revealed four self-management themes, including (1) I didn’t realize, and now I know; (2) It feels good to focus on my health; (3) I am the leader of my health care team; and (4) My health is improving.

CONCLUSIONS

Participants who used a self-management mHealth app intervention for heart failure reported an overall positive experience. Their statements were organized into four major themes. The education provided during the study increased self-awareness and promoted self-management of their heart failure. The mHealth app supported patient empowerment, resulting in better heart failure management and improved quality of life. Participants advocated for themselves by becoming the leader of their health, especially when communicating with their health care team. Finally, the mHealth app was used by the participants as a self-management tool to assist in symptom management and improve their overall health. Future research should study symptom evaluation, medication tracking, and possibly serve as a health provider communication platform to empower individuals to be leaders in their chronic disease management.
A Fine-Tuned Bidirectional Encoder Representations From Transformers Model for Food Named-Entity Recognition: Algorithm Development and Validation (Preprint)
Authors: Stojanov Riste , Popovski Gorjan , Cenikj Gjorgjina , Koroušić Seljak Barbara , Eftimov Tome
Published: August 2021

BACKGROUND

Recently, food science has been garnering a lot of attention. There are many open research questions on food interactions, as one of the main environmental factors, with other health-related entities such as diseases, treatments, and drugs. In the last 2 decades, a large amount of work has been done in natural language processing and machine learning to enable biomedical information extraction. However, machine learning in food science domains remains inadequately resourced, which brings to attention the problem of developing methods for food information extraction. There are only few food semantic resources and few rule-based methods for food information extraction, which often depend on some external resources. However, an annotated corpus with food entities along with their normalization was published in 2019 by using several food semantic resources.

OBJECTIVE

In this study, we investigated how the recently published bidirectional encoder representations from transformers (BERT) model, which provides state-of-the-art results in information extraction, can be fine-tuned for food information extraction.

METHODS

We introduce FoodNER, which is a collection of corpus-based food named-entity recognition methods. It consists of 15 different models obtained by fine-tuning 3 pretrained BERT models on 5 groups of semantic resources: food versus nonfood entity, 2 subsets of Hansard food semantic tags, FoodOn semantic tags, and Systematized Nomenclature of Medicine Clinical Terms food semantic tags.

RESULTS

All BERT models provided very promising results with 93.30% to 94.31% macro F1 scores in the task of distinguishing food versus nonfood entity, which represents the new state-of-the-art technology in food information extraction. Considering the tasks where semantic tags are predicted, all BERT models obtained very promising results once again, with their macro F1 scores ranging from 73.39% to 78.96%.

CONCLUSIONS

FoodNER can be used to extract and annotate food entities in 5 different tasks: food versus nonfood entities and distinguishing food entities on the level of food groups by using the closest Hansard semantic tags, the parent Hansard semantic tags, the FoodOn semantic tags, or the Systematized Nomenclature of Medicine Clinical Terms semantic tags.