bluuebunny/crossref_metadata_2025 huggingface dataset:
The Computational Intervention of Macrolide Antibiotics in the Treatment of COVID-19
Authors: Anwar Firoz , Altayb Hisham N. , Al-Abbasi Fahad A. , Kumar Vikas , Kamal Mohammad A.
Published: January 2021

Background:

The spike (S) glycoprotein of SARS corona virus (SARS-CoV-2) and human Angiotensin-
converting enzyme 2 (ACE2), are both considered the key factors for the initiation of virus infection.
The present work is an effort for computational target to block the spike proteins (S) and ACE2 receptor proteins
with Macrolide antibiotics like Azithromycin, (AZM), Clarithromycin (CLAM) and Erythromycin (ERY)
along with RNA-dependent RNA polymerase (RdRp).

Methods:

Three-dimensional structure of the SARS-CoV-2RdRp was built by the SWISS-MODEL server, the
generated structure showed 96.35% identity to the available structure of SARS-Coronavirus NSP12 (6NUR),
for model validity, we utilized the SWISS-model server quality parameters and Ramachandran plots.

Results:

These compounds were able to block the residues (Arg553, Arg555, and Ala558) surrounding the deep
grove catalytic site (Val557) of RdRp and thus plays an important role in tight blocking of enzyme active site.
Reference drug Remdesivir was used to compare the docking score of antibiotics with RdRp. Docking value
exhibited good binding energy (-7.7 up to -8.2 kcal/mol) with RdRp, indicating their potential as a potent RdRp
inhibitor. Interaction of CLAM and ERY presented low binding energy (-6.8 and -6.6) with the ACE2 receptor.
At the same time, CLAM exhibited a good binding affinity of -6.4 kcal/mol, making it an excellent tool to
block the attachment of spike protein to ACE2 receptors. Macrolides not only affected the attachment to ACE2
but also blocked the spike proteins further, consequently inhibiting the internalization in the host cell. Three
Alkyl bonds between Arg555, Ala558, and Met542 by CLAM and two Alkyl bonds of Arg624 and Lys621 by
ERY plays an important role for RdRp inactivation, that can prevent the rise of newly budded progeny virus.
These macrolides interacted with the main protease protein in the pocket responsible for the dimerization and
catalytic function of this protein. The interaction occurred with residue Glu166, along with the catalytic residues
(Tyr343, and His235) of Endoribonuclease (NSP15) protein.

Conclusion:

The present study gives three-way options either by blocking S proteins or ACE2 receptor proteins
or inhibiting RdRp to counter any effect of COVID-19 by macrolide and could be useful in the treatment of
COVID-19 till some better option available.
Bioactive Peptides in Preventative Healthcare: An Overview of Bioactivities and Suggested Methods to Assess Potential Applications
Authors: Hayes Maria
Published: January 2021

Food derived bioactive peptides can be generated from various protein sources and usually consist of between 2-30
amino acids with bulky, side-chain aromatic amino acids preferred in the ultimate and penultimate positions at the C-terminal
end of the amino acid chain. They are reported to impart a myriad of preventative health beneficial effects to the consumer
once ingested and these include heart health benefits through inhibition of enzymes including renin (EC 3.4.23.15) and angiotensin-
I-converting enzyme (ACE-1; EC 3.4.15.1) within the renin angiotensin aldosterone system (RAAS) anti-inflammatory
(due to inhibition of ACE-I and other enzymes) and anti-cancer benefits, prevention of type-2 diabetes through inhibition of
dipeptidyl peptidase IV (DPP-IV), bone and dental strength, antimicrobial and immunomodulatory effects and several others.
Peptides have also reported health benefits in the treatment of asthma, neuropathic pain, HIV and wound healing. However, the
structure, amino acid composition and length of these peptides, along with the quantity of peptide that can pass through the gastrointestinal
tract and often the blood-brain barrier (BBB), intact and reach the target organ, are important for the realisation of
these health effects in an in vivo setting. This paper aims to collate recent important research concerning the generation and detection
of peptides in the laboratory. It discusses products currently available as preventative healthcare peptide options and relevant
legislation barriers to place a food peptide product on the market. The review also highlights useful in silico computer-
based methods and analysis that may be used to generate specific peptide sequences from proteins whose amino acid sequences
are known and also to determine if the peptides generated are unique and bioactive. The topic of food-derived bioactive
peptides for health is of great interest to scientific research and industry due to evolving drivers in food product innovation,
including health and wellness for the elderly, infant nutrition and optimum nutrition for sports athletes and the humanisation of
pets. This paper provides an overview of what is required to generate bioactive peptide containing hydrolysates, what methods
should be used in order to characterise the beneficial health effects of these hydrolysates and the active peptide sequences, potential
applications of bioactive peptides and legislative requirements in Europe and the United States. It also highlights success
stories and barriers to the development of peptide-containing food products that currently exist.
Vascular and Cardiac Oxidative Stress and Inflammation as Targets for Cardioprotection
Authors: Daiber Andreas , Steven Sebastian , Euler Gerhild , Schulz Rainer
Published: January 2021

Cardiac and vascular diseases are often associated with increased oxidative stress and inflammation,
and both may contribute to the disease progression. However, successful applications of antioxidants in the clinical
setting are very rare and specific anti-inflammatory therapeutics only emerged recently. Reasons for this rely
on the great diversity of oxidative stress and inflammatory cells that can either act as cardioprotective or
cause tissue damage in the heart. Recent large-scale clinical trials found that highly specific anti-inflammatory
therapies using monoclonal antibodies against cytokines resulted in lower cardiovascular mortality in patients
with pre-existing atherosclerotic disease. In addition, unspecific antiinflammatory medication and established
cardiovascular drugs with pleiotropic immunomodulatory properties such as angiotensin converting enzyme
(ACE) inhibitors or statins have proven beneficial cardiovascular effects. Normalization of oxidative stress
seems to be a common feature of these therapies, which can be explained by a close interaction/crosstalk of the
cellular redox state and inflammatory processes. In this review, we give an overview of cardiac reactive oxygen
species (ROS) sources and processes of cardiac inflammation as well as the connection of ROS and inflammation
in ischemic cardiomyopathy in order to shed light on possible cardioprotective interventions.
Emerging Therapeutic Approaches to COVID-19
Authors: Singh Indrakant K. , Kumari Pratibha , Mittal Pooja , Kumar Amit , Singal Bharti , Hasan Gulam M. , Aggarwal Rajiv , Kamal Md. Amjad , Singh Archana , Hassan Md. Imtaiyaz
Published: January 2021

Coronavirus disease (COVID-19) is caused by a novel severe acute respiratory syndrome coronavirus
(SARS-CoV-2), which is a positive single-stranded RNA virus having a large genome ~30 kb. SARSCoV-
2 is zoonotic and highly contagious, causing severe pneumonia-like symptoms. The efficacy of the different
potential drug and drug candidates against COVID-19 has been investigated, which are under various stages
of clinical trials. The drugs effective against SARS, and Middle east respiratory syndrome (MERS), have been
proposed to have a high potential for the treatment of COVID-19. Here, we selected plant-based materials implicated
in the prevention and therapy of COVID-19. The plant produces secondary metabolites in response to
viral infection. Different classes of secondary metabolites have different mechanisms to counter virus attacks.
Many nanomaterials produced by carbohydrates and lipids have been exploited for their in-vitro and in-vivo delivery
of antiviral therapeutics. The vaccine has shown impressive results in producing antibodies against
SARS-CoV2 and has been evaluated for safety, tolerance, and preliminary immunogenicity. Similarly,
DNA/RNA-based therapy has shown high clinical significance. Various forms of vitamins, minerals, herbs, and
phytonutrients help to enhance immunity and be implicated in the control of COVID-19. However, such
measures should not replace social distancing, quarantine and special care.
Exosomal hsa-miR-129-2 and hsa-miR-889 from a 6-microRNA Signature
Might be a Potential Biomarker for Predicting the Prognosis of Papillary
Thyroid Carcinoma
Authors: Yu Kun , Xin Ying , Meng Kexin , Guo Haiwei , Chen Bin , Zheng Chuanming , Shou Xin
Published: January 2021

Background:

Papillary thyroid carcinoma (PTC) is a subtype of thyroid cancer with increasing incidence over time.

Objective:

This study aimed to build a risk score (RS) system for PTC patients.

Methods:

PTC microRNA (miRNA) and messenger RNA (mRNA) expression data were extracted from The Cancer Genome Atlas (TCGA) database. The 491 PTC samples were randomly divided into training and validation sets. Using the limma software package, differentially expressed mRNAs (DEGs) and miRNAs (DEMs) between the tumor and control groups were screened. In order to construct an RS system, a survival package was used to select independent miRNAs related to prognosis. Enrichment analysis was performed, and a miRNA-mRNA co-expression network was constructed. High-throughput sequencing was also used to verify the prognostic miRNAs in exosomes.

Results:

We found 1363 DEGs and 171 DEMs between the tumor and control groups. After identifying 26 DEMs that were significantly related to prognosis, 6 independent prognosis-associated miRNAs were selected to build an RS system. The areas under the curves of the overall survival rates of the training, validation, and entire sets were 0.847, 0.772, and 0.819, respectively. By conducting pathway analysis using the miRNA-mRNA co-expression network, one overlapping factor and five overlapping pathways were obtained. In addition, high-throughput sequencing revealed that the hsa-miR-129-2, hsa-miR-548j, hsa-miR-6734, and hsa-miR-889 expression levels in TCGA tumor tissues and exosomes were consistent, and those of hsa-miR-129-2 and hsa-miR-889 between patients and controls were significantly different in exosomes.

Conclusion:

The six-miRNA RS system in exosomes may comprise independent signatures for predicting PTC patient prognosis.
P2X7 Receptor as a Potential Target for Major Depressive Disorder
Authors: Huang Zeyi , Tan Sijie
Published: January 2021

Major depressive disorder (MDD) is a common mental disorder. Although the genetic,
biochemical, and psychological factors have been related to the development of MDD, it is generally
believed that a series of pathological changes in the brain caused by chronic stress is the main
cause of MDD. However, the specific mechanisms underlying chronic stress-induced MDD are
largely undermined. Recent investigations have found that increased pro-inflammatory cytokines
and changes in the inflammatory pathway in the microglia cells in the brain are the potential pathophysiological
mechanism of MDD. P2X7 receptor (P2X7R) and its mediated signaling pathway
play a key role in microglia activation. The present review aimed to present and discuss the accumulating
data on the role of P2X7R in MDD. Firstly, we summarized the research progress in the
correlation between P2X7R and MDD. Subsequently, we presented the P2X7R mediated microglia
activation in MDD and the role of P2X7R in increased blood-brain barrier (BBB) permeability
caused by chronic stress. Lastly, we also discussed the potential mechanism underlying-P2X7R expression
changes after chronic stress. In conclusion, P2X7R is a key molecule regulating the activation
of microglia. Chronic stress activates microglia in the hippocampus by secreting interleukin-
1β (IL-1β) and other inflammatory cytokines, and increasing the BBB permeability, thus promoting
the occurrence and development of MDD, which indicated that P2X7R might be a promising
therapeutic target for MDD.
Implications of microRNAs in the Pathogenesis of Atherosclerosis and Prospects for Therapy
Authors: Gorabi Armita M. , Ghanbari Mohsen , Sathyapalan Thozhukat , Jamialahmadi Tannaz , Sahebkar Amirhossein
Published: January 2021

MicroRNAs (miRNAs) are non-coding RNAs containing around 22 nucleotides, which
are expressed in vertebrates and plants. They act as posttranscriptional gene expression regulators,
fine-tuning various biological processes in different cell types. There is emerging evidence on their
role in different stages of atherosclerosis. In addition to regulating the inflammatory cells involved
in atherosclerosis, miRNAs play fundamental roles in the pathophysiology of atherosclerosis, such
as endothelial cell (EC) dysfunction, the aberrant function of the vascular smooth muscle cell
(VSMC) and cholesterol metabolism. Moreover, miRNAs participate in several pathogenic pathways
of atherosclerotic plaque development, including their effects on immune cell signaling receptors
and lipid uptake. In this study, we review our current knowledge of the regulatory role of miRNAs
in various pathogenic pathways underlying atherosclerosis development and also outline potential
clinical applications of miRNAs in atherosclerosis.
Recent Advances in the Discovery of GSK-3 Inhibitors from Synthetic Origin in the Treatment of Neurological Disorders
Authors: Saha Supriyo , Pal Dilipkumar , Nimse Satish B.
Published: January 2021

Background:

Glycogen synthase kinase 3 (GSK-3) is a serine/threonine kinase enzyme
that controls neuronal functions such as neurite outgrowth, synapse formation, neurotransmission,
and neurogenesis. The enzyme has two subunits as GSK-3α and GSK-3β. 4ACC, 1Q3D, 3AFG,
1UV5, and 1Q5K are the important GSK-3 receptors isolated from Homo sapiens and Mus musculus.
This enzyme mainly phosphorylates Tau protein with the increased amount in neuronal fibres
together with beta-amyloid plaques that cause neuronal diseases like Alzheimer's, Parkinson’s and
many more.

Objective:

We investigated the developments of various synthetic GSK-3 inhibitors responsible for
the prevention and treatment of neurological disorders, like Alzheimer's disease, bipolar disorders,
acting as antidepressants, neuroprotective, etc.

Results and Conclusion:

It has been observed that structures of the GSK-3 inhibitors are comprised
of benzopyridine, benzothiazole, pyrazole, pyrazine, dioxolo-benzoxazine, oxadiazole, and
benzimidazole in the skeletal with cyclopropyl amide, phenyl carbamothioate, 3-[(propan-
2-yl)oxy]propan-1-amine in the side chain. The molecules were evaluated against the effectivity
of GSK-3, human adenosine kinase, cyclin-dependent kinase, and phosphodiesterase-4 along
with tail suspension test forced swim test, percent neuronal survival and other cognitive behaviours.
The observations confirmed the remarkable effects of the synthesized molecules to conquer
Alzheimer, Parkinson’s depression, psychosis and other forms of neurological disorders.
A Comprehensive Review on Therapeutic Applications of Ferulic Acid and its Novel Analogues: A Brief Literature
Authors: Babbar Ritchu , Dhiman Sonia , Grover Rupanshi , Kaur Arashmeet , Arora Sandeep
Published: January 2021

The compound 4-hydroxy-3-methoxycinnamic acid, named as ferulic acid (FA), is a ubiquitous phenolic
compound which is distributed extensively in the plant kingdom. Ferulic acid is a boon as it shows immense potential
therapeutic effects which are useful in the treatment of diabetes, cancer, pulmonary and CVS diseases majorly due to its
anti-oxidant and anti-inflammatory action. Ferulic acid exhibits other wide variety of biological activities such as,
anticarcinogenic, antiallergic, antimicrobial, antiviral, hepatoprotective, metal chelation, activation of transcriptional
factors, modulation of enzyme activity, gene expression as well as signal transduction. The structural characteristics of this
active ingredient make it an optimal substrate to form or synthesize various derivates and its formulations. The present
review addresses structure of ferulic acid, its pharmacodynamic parameters, applications and its various derivatives. In
addition, the review also aims to cover the main aspects related to use of ferulic acid in the food and health industry and
have listed various published patents on Ferulic acid.
Radioprotectors: Nature’s Boon
Authors: Lang Damanpreet Kaur , Singh Harwinder , Arora Arpita , Arora Rashmi , Saini Balraj , Arora Sandeep , Kaur Rajwinder
Published: January 2021

Objective:

To reduce the chances of toxicity, reduction in radiation dose or reducing the frequency of the therapy is done
which usually leads to a therapeutically poor outcome. The most feasible method is to protect the normal cells by
administration of radioprotective agents either before or after the exposure. These agents have been tested on animals and
human cellmodels for evaluating theirsafety window and toxicityprofile at the cellular level. The study aims to compile the
effective natural radioprotective agents available which can be further exploited by using certain QSAR studies to increase
their potency.

Method:

Structured literature search from EMBASE, PubMed, Bentham Science, Scopus, and ScienceDirect was done and
appropriate peer-reviewed review articles, as well as certain research articles, were included and compiled in this review
paper.

Conclusion:

As various studies have indicated the harmful effects of ionizing radiations on normal cells, to reduce these
effects radioprotective agents are used before or after exposure to radiations. Compounds derived from natural sources are
proved to have few side effects and they possess radioprotective property due to the presence of alkaloids, resins, volatile
oils, tannins in their molecular structure. Various plants having such radioprotective constitutes have been identified for
their radioprotective action and compiled in the present study.

Conclusion:

As various studies have indicated the harmful effects of ionizing radiations on normal cells, to reduce these
effects radioprotective agents are used before or after exposure to radiations. Compounds derived from natural sources are
proved to have few side effects and they possess radioprotective property due to the presence of alkaloids, resins, volatile
oils, tannins in their molecular structure. Various plants having such radioprotective constitutes have been identified for
their radioprotective action and compiled in the present study.
Advances on Monosaccharides and Oligosaccharides: Structural Modifications and Bioactivities
Authors: Li Shaochen , Lv Min , Zhang Shaoyong , Xu Hui
Published: January 2021

Derivatives of monosaccharides and oligosaccharides play important roles in biological
processes. Monosaccharides are the single carbohydrate building blocks, such as glucose, xylose, and
fructose. Oligosaccharides are composed of 2-10 monosaccharides, including disaccharides and trisaccharides.
Moreover, monosaccharides, oligosaccharides and their derivatives are vital molecules
with various biological properties, including anticancer activity, antiviral activity, insecticidal activity,
antimicrobial activity, and antioxidant activity. This review covers a survey of structural modifications,
biological activities, and mechanisms of action of monosaccharides, oligosaccharides and their
derivatives. Additionally, their structure-activity relationships are also concluded.
Efficacy of Gene Therapy to Restore Cognition in Alzheimer’s Disease: A Systematic Review
Authors: Tedeschi Desyrre V. , da Cunha Anderson F , Cominetti Márcia R. , Pedroso Renata Valle
Published: January 2021

Background:

Alzheimer's disease (AD) is the main cause of dementia and it is a progressive neurogenerative disease characterized by the accumulation of neurofibrillary tangles and senile plaques. There is currently no cure; however, some treatments are available to slow down the progression of the disease, including gene therapy, which has been investigated to have great potential for the treatment of AD.

Objective:

The aim of this review was to identify the efficacy of gene therapy to restore cognition in AD.

Methods:

A systematic review was carried out using papers published up to May 2020 and available in the Web of Science, Scopus, and Medline/PUBMED databases. Articles were considered for inclusion if they were original researches that investigated the effects of gene therapy on cognition in AD. The methodological quality of the selected studies was evaluated using the Risk of Bias Tool for Animal Intervention Studies (SYRCLE’s Rob tool) and the Jadad Scale.

Results:

Most preclinical studies obtained positive results in improving memory and learning in mice that underwent treatment with gene therapy. On the other hand, clinical studies have obtained inconclusive results related to the delivery methods of the viral vector used in gene therapy.

Conclusion:

Gene therapy has shown a great potential for the treatment of AD in preclinical trials, but results should be interpreted with caution since preclinical studies presented limitations to predict the efficacy of the treatment outcome in humans.
Extracellular Vesicles from Stem and Progenitor Cells for Cell-Free
Regenerative Therapy
Authors: Haque Nazmul , Widera Darius , Govindasamy Vijayendran , Soesilawati Pratiwi , Abu Kasim Noor Hayaty
Published: January 2021

:

Cell-based regenerative therapies involving stem or progenitor cells are considered as possible therapeutic
modalities to treat non-communicable and degenerative diseases. Recently, regenerative outcomes of cell-based therapies
have been linked to paracrine factors and extracellular vesicles [EVs] released by the transplanted cells rather than the
transplanted cells themselves. EVs contain a cargo that includes microRNAs [miRNAs], mRNAs, as well as proteins. Their
role in mediating intercellular communication has been acknowledged in several studies. However, the regenerative
potential of the miRNAs, mRNAs, and proteins that are present in EVs is a matter of ongoing scientific debate. In this
review, we discuss EVs as an alternative to stem cell-based therapy to treat some of the non-communicable and
degenerative diseases. Moreover, we also propose that pre-treatment of the cells could help to produce EVs enriched with
particular miRNAs, mRNAs, and/or proteins that could support the successful regeneration of a targeted organ.
Preparation of Enzymatically Highly Active Pegylated-D-Amino Acid Oxidase and Its Application to Antitumor Therapy
Authors: Nakamura Hideaki , Enoch Appiah , Iwaya Shotaro , Furusho Sakura , Tsunoda Shoko , Haratake Mamoru
Published: January 2021

Background:

D-amino acid oxidase (DAO) is an H2O2-generating enzyme, and tumor growth suppression by
selective delivery of porcine DAO in tumors via the cytotoxic action of H2O2 has been reported. DAO isolated from
Fusarium spp. (fDAO) shows much higher enzyme activity than porcine DAO, although the application of fDAO for
antitumor treatment has not yet been determined.

Objective:

The purpose of this study was to prepare enzymatically highly active pegylated-fDAO, and to determine whether
it accumulates in tumors and exerts a potent antitumor effect in tumor-bearing mice.

Methods:

Polyethylene glycol (PEG; Mw. 2000) was conjugated to fDAO to form PEGylated fDAO (PEG-fDAO). PEGfDAO was intravenously administered into S180 tumor-bearing mice, and the body distribution and antitumor activity of
PEG-fDAO was determined.

Results:

The enzyme activity of PEG-fDAO was 26.1 U/mg, which was comparable to that of
fDAO. Intravenously administered PEG-fDAO accumulated in tumors with less distribution in normal
tissue except in the plasma. Enzyme activity in the tumor was 60-120 mU/g-tissue over 7-20 h
after i.v. injection of 0.1 mg of PEG-fDAO. To generate the H2O2 in the tumor tissue, PEG-fDAO
was intravenously administered, and then, D-phenylalanine was intraperitoneally administered after
a lag time. No remarkable tumor suppression effect was observed under conditions used in this
study, compared to the non-treated group.

Conclusion:

The results suggest that PEG-fDAO maintained high enzymatic activity after pegylation. Treatment with PEGfDAO conferred high enzyme activity on tumor tissue; 3–6 fold higher than that of previously reported pDAO; however,
high enzyme activity in the plasma limited repeated treatment owing to lethal toxicity, which seemingly led to poor
therapeutic outcome. Overall, the use of PEG-fDAO is promising for antitumor therapy, although the suppression of DAO
activity in the plasma would also be required rather than only the increase in DAO activity in the tumor for an antitumor
effect.
Dequalinium-Derived Nanoconstructs: A Promising Vehicle for Mitochondrial Targeting
Authors: Pawar Abhishek , Korake Swati , Gajbhiye Kavita R.
Published: January 2021

The cell's power house, mitochondrion, is a vital organelle for drug targeting in the treatment
of many diseases due to its fundamental duties and function related to cell proliferation and
death. The mitochondrial membrane comprises bilayer artifact and poses extremely negative potential,
creating hurdles for therapeutic molecules in reaching mitochondria. To accomplish mitochondrial
targeting, the scientific community has explored diverse pharmaceutical formulations like liposomes,
polymeric nanoparticles (NPs), and inorganic NPs. However, the game changing technology
was a modification of these carriers by mitochondriotropic moiety, dequalinium chloride
(DQA) or delivering the chemotherapeutics by DQAsomes. The DQA represents a distinctive mitochondriotropic
delocalized cation that displays their selectivity towards accumulation in mitochondria
of carcinoma cells. Attributed to this characteristics, DQAsomes have been formulated using
DQA and explored for successful mitochondrial targeting of bioactives. In this review, it is discussed
the effectiveness of DQA nanocarriers which efficiently and selectively transmit the cytotoxic
drug to the tumor cell. The DQA based nanoformulations have evidently displayed augmented
pharmacological and therapeutic outcomes than their counterparts both in vitro and in vivo. Thus,
DQAsomes symbolizes an ideal carrier with excellent potential as mitochondrial targeting agent.
The Efficacy of Vitamin K, A Member Of Naphthoquinones in the Treatment of Cancer: A Systematic Review and Meta-Analysis
Authors: Ganbat Dariimaa , Jugder Bat-Erdene , Ganbat Lkhamaa , Tomoeda Miki , Dungubat Erdenetsogt , Takahashi Yoshihisa , Mori Ichiro , Shiomi Takayuki , Tomita Yasuhiko
Published: January 2021

Background:

Redox dysregulation originating from metabolic alterations in cancer cells
contributes to their proliferation, invasion, and resistance to therapy. Conversely, these features represent
a specific vulnerability of malignant cells that can be selectively targeted by redox chemotherapeutics.
Amongst them, Vitamin K (VitK) carries the potential against cancer stem cells, in
addition to the rest of tumor mass.

Objectives:

To assess the possible benefits and safety of VitK for cancer treatment using a systematic
review and meta-analysis with a mixed-methods approach.

Methods:

We performed a systematic search on several electronic databases for studies comparing
VitK treatment with and without combination to the control groups. For quantitative studies, fully
or partially reported clinical outcomes such as recurrence rates, survival, overall response and adverse
reactions were assessed. For qualitative studies, a narrative synthesis was accomplished.

Results:

Our analysis suggested that the clinical outcome of efficacy, the pooled hazard ratio for
progression-free survival, and the pooled relative risk for overall survival, and overall response
were significantly higher in the VitK therapy group compared to the placebo group (p<0.05). We
did not observe any significant difference in the occurrence of adverse events between groups.
Among qualitative studies, VitK treatment targeting myelodysplastic syndrome and advanced solid
tumors resulted in 24.1% and 10% of clinical response, respectively.

Conclusion:

VitK not only exerts antitumor effects against a wide range of tumor types, but it also
has excellent synergism with other therapeutic agents.
Acid-Sensing Ion Channels: Focus on Physiological and Some Pathological Roles in the Brain
Authors: Storozhuk Maksim , Cherninskyi Andrii , Maximyuk Oleksandr , Isaev Dmytro , Krishtal Oleg
Published: January 2021

Acid-sensing ion channels (ASICs) are Na+-permeable ion channels activated by protons
and predominantly expressed in the nervous system. ASICs act as pH sensors leading to neuronal excitation.
At least eight different ASIC subunits (including ASIC1a, ASIC1b, ASIC2a, ASIC2b, ASIC3,
ASIC4, ASIC5) are encoded by five genes (ASIC1-ASIC5). Functional ASICs assembled in the plasma
membrane are homo- or heteromeric trimers. ASIC1a-containing trimers are of particular interest
as, in addition to sodium ions, they also conduct calcium ions and thus can trigger or regulate multiple
cellular processes. ASICs are widely but differentially expressed in the central and peripheral nervous
systems. In the mammalian brain, a majority of neurons express at least one ASIC subunit. Several recent
reviews have summarized findings of the role of ASICs in the peripheral nervous system, particularly
in nociception and proprioception, and the structure-function relationship of ASICs. However,
there is little coverage on recent findings regarding the role of ASICs in the brain. Here we review and
discuss evidence regarding the roles of ASICs: (i) as postsynaptic receptors activated by protons coreleased
with glutamate at glutamatergic synapses; (ii) as modulators of synaptic transmission at glutamatergic
synapses and GABAergic synapses; (iii) in synaptic plasticity, memory and learning; (iv) in
some pathologies such as epilepsy, mood disorders and Alzheimer's disease.
Piroxicam Analogs: Design, Synthesis, Docking Study and Biological Evaluation as Promising Anti-HIV-1 Agents
Authors: Imani Ali , Soleymani Sepehr , Vahabpour Rouhollah , Hajimahdi Zahra , Zarghi Afshin
Published: January 2021

Background:

Taking the well-known drug, Piroxicam as a lead compound, we designed and synthesized two series of 1,2-benzothiazines 1,1-dioxide derivatives to assay their ability in inhibition of HIV-1 replication in cell culture.

Objective:

In this study, we describe the synthesis, docking study and biological evaluation of 1,2-benzothiazines 1,1- dioxide derivatives.

Results:

Most of the new compounds were active in the cell-based anti-HIV-1 assay with EC50 < 50 M. Among them, compounds 7g was found to be the most active molecule. Docking study using 3OYA pdb code on the most active molecule 7g with EC50 values of 10 M showed a similar binding mode to the HIV integrase inhibitors.

Conclusion:

Since all the compounds showed no remarkable cytotoxicity (CC50> 500 M), the designed scaffold is promising structure for development of new anti-HIV-1 agents.
Smart Nanodevices for Point-of-Care Applications
Authors: Chokkareddy Rajasekhar , Kanchi Suvardhan , Inamuddin  , Altalhi Tariq A
Published: January 2021

Background::

While significant strides have been made to avoid mortality during the treatment of chronic
diseases, it is still one of the biggest health-care challenges that have a profound effect on humanity. The development of
specific, sensitive, accurate, quick, low-cost, and easy-to-use diagnostic tools is therefore still in urgent demand.
Nanodiagnostics is defined as the application of nanotechnology to medical diagnostics that can offer many unique
opportunities for more successful and efficient diagnosis and treatment for infectious diseases.

Methods::

In this review we provide an overview of infectious disease using nanodiagnostics platforms based on
nanoparticles, nanodevices for point-of-care (POC) applications.

Results::

Current state-of-the-art and most promising nanodiagnostics POC technologies, including miniaturized
diagnostic tools, nanorobotics and drug delivery systems have been fully examined for the diagnosis of diseases. It also
addresses the drawbacks, problems and potential developments of nanodiagnostics in POC applications for chronic
diseases.

Conclusions::

While progress is gaining momentum in this field and many researchers have dedicated their time in
developing new smart nanodevices for POC applications for various chronic diseases, the ultimate aim of achieving longterm,
reliable and continuous patient monitoring has not yet been achieved. Moreover, the applicability of the
manufactured nanodevices to rural patients for on-site diagnosis, cost, and usability are the crucial aspects that require
more research, improvements, and potential testing stations. Therefore, more research is needed to develop the
demonstrated smart nanodevices and upgrade their applicability to hospitals away from the laboratories.
Adverse Reactions Induced by Minocycline: A Review of Literature
Authors: Dominic Maria Rose
Published: January 2021

Background:

Minocycline is a tetracycline antibiotic that is widely used to treat infections
and is a first-line oral antibiotic in the treatment of moderate to severe inflammatory acne. Although
it has high efficacy, several adverse reactions, including life-threatening ones, have been reported
in association with its use.

Objective:

To identify all the potential adverse reactions due to minocycline and analyze them in
terms of the number of cases reported so far, salient features, severity and clinical outcome.

Methods:

Comprehensive PubMed search of English and non-English literature for case reports of
adverse reactions to minocycline was conducted.

Results:

A total of 550 cases were identified from over 200 publications. The major reported adverse
events caused by minocycline are drug reaction with eosinophilia and systemic symptoms syndrome,
autoimmune syndromes like hepatitis, lupus and vasculitis, acute eosinophilic pneumonia, pseudotumor
cerebri, hyperpigmentation, serum sickness-like reaction, Sweet’s syndrome and drug fever.
Several other reactions involving multiple organ systems have also been reported. These show an
overlap of clinical features and may be associated with multiple events causing considerable morbidity.
Eight of these cases resulted in the death of the patients.

Conclusion:

In view of the evident potential of minocycline to cause long-lasting and severe adverse
effects, significant morbidity and even mortality, it should be prescribed with caution in the first-line
treatment for moderate to severe acne.
Plasma-Rich in Growth Factor and its Clinical Application
Authors: Sheykhhasan Mohsen , Seifalian Amelia
Published: January 2021

The potential use of growth factors in stem cell-based therapies for the repair and regeneration
of tissues and organs offers a paradigm shift in regenerative medicine. Growth factors are
critical signalling molecules that play an important role in tissue development and remodelling.
Plasma rich in growth factor (PRGF) is a biotechnological strategy for the harvesting of the active
substances of platelets, including growth factors, from the patient’s blood. Because of their tremendous
essential growth factor and bioactive agents, as well as their paracrine mechanisms, PRGF
has been used as an efficacious option and adjuvant biological therapy in the repair and replacement
of damaged organs. This article provides an overview of PRGF extraction and its properties
and critically reviewed its clinical benefit and clinical trials in the treatment and regeneration of human
organs. Regenerative medicine is a multi-billion-dollar industry with huge interest to clinicians,
academics and industries, being considered as an emerging technology.
Exploring the Mitochondrial Apoptotic Cell Death Landscape and Associated Components Serving as Molecular Targets, Primarily for Synthetic and Natural Drugs Targeting Oncology Therapeutics
Authors: Kaur Ishnoor , Behl Tapan , Sachdeva Monika , Bungau Simona , Venkatachalam Thangavel
Published: January 2021

:

The role of mitochondria in apoptosis signaling cell death pathway is regulated by extrinsic and intrinsic
pathway, encompassing multiple components like Bcl-2 family of proteins, death receptors, caspases, Smac/DIABLO, IAPs,
Omi/HtrA2 and cytochrome c. These entities serve as effective molecular targets for numerous drugs targeting
mitochondrial apoptotic pathway, mainly emphasizing on oncology therapeutics. Defective apoptosis is an acquired
hallmark of cancer cells, which promotes establishment of apoptosis-targeting anti-cancer drugs in cancer treatment. The
review provides an overview of the Bcl-2 inhibiting, IAPs antagonizing, caspase inhibiting and BH3 mimicking actions,
mediated by anti-cancer drugs, rendering beneficial outcomes in different forms of cancer. The authors elaborate the
significance of synthetic and natural agents, targeting the mitochondrial apoptotic pathway, in ameliorating tumor cell
growth in the body, and the specificity and effectiveness of these agents, motivating the researchers to explore
mitochondrial apoptosis targeting of anti-tumor drugs, of both herbal and synthetic origin. Thus, the review aims to
prognosticate this dynamic approach in oncology, simultaneously highlighting the challenges and future prospects,
providing an opportunity to the experts, to “go over with a fine tooth comb” in understanding this “programmed cell death
pathway”, and establishing reliability and accuracy of this therapeutic paradigm in the upcoming future.
Nanostructured Lipid Carriers for Intranasal Administration of Olanzapine in the Management of Schizophrenia
Authors: Kaur Sarbjot , Nautiyal Ujjwal , Chawla Pooja A. , Chawla Viney
Published: January 2021

Background:

Olanzapine belongs to a new class of dual spectrum antipsychotic agents.
It is known to show promise in managing both the positive and negative symptoms of schizophrenia.
Drug delivery systems based on nanostructured lipid carriers (NLC) are expected to provide
rapid nose-to-brain transport of this drug and improved distribution into and within the brain.

Objective:

The present study deals with the preparation and evaluation of olanzapine loaded NLC
via the intranasal route for schizophrenia.

Methods:

Olanzapine-NLC were formulated through the solvent injection method using isopropyl
alcohol as the solvent, stearic acid as solid lipid, and oleic acid as liquid lipid, chitosan as a coating
agent, and Poloxamer 407 as a surfactant. NLC were characterized for particle size, polydispersity
index, entrapment efficiency, pH, viscosity, X-ray diffraction studies, in-vitro mucoadhesion study,
in- vitro release and ex-vivo permeation studies. The shape and surface morphology of the prepared
NLC was determined through transmission electron microscopy. To detect the interaction of the
drug with carriers, compatibility studies were also carried out.

Results:

Average size and polydispersity index of developed formulation S6 was 227.0±6.3 nm
and 0.460, respectively. The encapsulation efficiency of formulation S6 was found to be 87.25%.
The pH, viscosity, in-vitro mucoadhesion study, and in- vitro release of optimized olanzapine loaded
NLC were recorded as 5.7 ± 0.05, 78 centipoise, 15±2 min, and 91.96%, respectively. In ex-vivo
permeation studies, the percent drug permeated after 210 min was found to be 84.03%.

Conclusion:

These results reveal potential application of novel olanzapine-NLC in intranasal drug delivery system for
treatment of schizophrenia.
Science Up in Smoke: One Psychiatrist’s Journey Through the Politics of Cannabis Legalization
Authors: Rettew David C.
Published: January 2021

Background:

Many states are currently considering legislature that would legalize and commercialize cannabis
for medical and recreational purposes. Physicians and other health professionals are frequently called upon to offer an expert
opinion on the public health implications of these bills. For many, the role as a scientific expert and advocate in a political
process is new.

Objective 1:

To outline themes and lessons learned for science-minded clinicians engaged in deliberations over cannabis
legislation.

Objective 2:

To describe how science can get used and misused in the political process.

Method:

This article describes the experience of a psychiatrist who was actively involved in one state’s deliberations through
cannabis legalization bills.

Results:

Major themes that emerged during the process are described as are recommendations
for other health professionals who may find themselves involved in similar processes related to cannabis legalization and
other controversial initiatives that rely on the interpretation of scientific information.

Conclusion:

Psychiatrists and other clinicians can make important contributions to the political process for legislative
debates that involve science-based mental health information.
Biogenic Synthesis of Silver Nanoparticles using Azadirachta indica (Neem) Leaf Extract To Achieve Inhibitory Action Against Antibiotic-Resistant Bacteria
Authors: Moinuzzaman Md. , Jamal Mohammad Abu Hena Mostofa , Uddin Helal , Rahman Shahedur , Momin Abdul , Al Mashud Md. Abdullah
Published: January 2021

Background:

Nanotechnology is an emerging research field on nanoparticles. Nanoparticles
are 1-100 nm in one dimension and are important in biomedical science, medical chemistry,
atomic physics, and most other known fields. They are used because of their small size, orientation,
and physical properties.

Objectives:

This study was designed to synthesize silver nanoparticles (AgNPs) using Azadirachta
indica (Neem) leaf extract and evaluate their biomedical application.

Methods:

An aqueous extract of Azadirachta indica was used to synthesize AgNPs. 1 ml of the extract
was added drop by drop to 30-60 ml of a 1mM solution of silver nitrate. The AgNPs were
characterized by UV-Visible Spectroscopy, Fourier Transform Infrared Spectroscopy, Dynamic
Light Scattering Spectroscopy, X-ray Diffraction, Transmission Electron Microscopy, and antibacterial
activity studies. The biological synthesis of AgNPs was performed using the aqueous solution
of Azadirachta indica leaf extract and AgNO3. A fixed ratio of plant extract to metal ion was
used to prepare AgNPs and the formation of the nanoparticles was confirmed through the color
change. The nanoparticles were characterized by UV-vis spectrophotometer, FTIR, DLS, XRD and
TEM, and were found to range in size from 30-60 nm.

Results:

The biosynthesized AgNPs had a bactericidal effect against the antibiotic resistant pathogenic
microorganisms Bacillus subtilis, Pseudomonas aeruginosa, and Bacillus cereus.

Conclusion:

Silver nanoparticles were synthesized from Azadirachta indica leaf extract and can be
used as a therapeutic candidate for biomedical applications.
Role of Genetic Interactions in Lung Diseases Detection Using Computational
Approaches: A Review
Authors: Priya S. , Manavalan R.
Published: January 2021

:

Genome-wide Association Studies (GWAS) give special insight into genetic differences
and environmental influences that are part of different human disorders and provide prognostic
help to increase the survival of patients. Lung diseases such as lung cancer, asthma, and tuberculosis
are detected by analyzing Single Nucleotide Polymorphism (SNP) genetic variations. The key
causes of lung-related diseases are genetic factors, environmental and social behaviors.

:

The epistasis effects act as a blueprint for the researchers to observe the genetic variation associated
with lung diseases. The manual examination of the enormous genetic interactions is complicated
to detect the lung syndromes for diagnosis of acute respiratory diseases. Due to its importance,
several computational approaches have been modeled to infer epistasis effects. This article includes
a comprehensive and multifaceted review of all the relevant genetic studies published between
2006 and 2020. In this critical review, various computational approaches are extensively discussed
in detecting respondent epistasis effects for various lung diseases such as asthma, tuberculosis,
lung cancer, and nicotine drug dependence.

:

The analysis shows that different computational models identified candidate genes such as
CHRNA4, CHRNB2, BDNF, TAS2R16, TAS2R38, BRCA1, BRCA2, RAD21, IL4Ra, IL-13 and
IL-1β, have important causes for genetic variants linked to pulmonary disease. These computational
approaches' strengths and limitations are described. The issues behind the computational methods
while identifying the lung diseases through epistasis effects and the parameters used by various
researchers for their evaluation are also presented.
Preliminary Studies on the Content of Phytochemical Compounds On Skin of Salak Fruit (Salacca zalacca)
Authors:   Fakultas Farmasi, Pharmacy Academy of Kusuma Husada, Purwokerto, Indonesia, Setyawaty Rety , Aptuning B Ruli ,   Fakultas Farmasi, Pharmacy Academy of Kusuma Husada, Purwokerto, Indonesia, Dewanto Dewanto ,   Fakultas Farmasi, Pharmacy Academy of Kusuma Husada, Purwokerto, Indonesia
Published: January 2021

Salak (Salaccazalacca) is a native plant of Indonesia. Some Indonesians use zalacca as a traditional medicine. This plant belongs to the Palmae family. The purpose of this study is to reveal the structure of the active components that are efficacious and increase the economic value and efficacy that exist in the skin of zalacca (Salaccazalacca).The extraction method chosen was the maceration method using 96% ethanol solvent. A total of 1 kg of fresh zalacca skin (Salaccazalacca) is dried using the sun-heating method and produces 625 g of dried zalacca skin. The extraction-maceration process uses 100 grams of implicial. Simplisia is soaked and stirred occasionally in 96% ethanol for 3 days and filtered until a thick extract is obtained. Thick extract obtained was 10.69 g. The percentage of yield obtained was 10.69%. Phytochemical screening carried out is alkaloids, steroids, triterpenoids, saponins, tannins, and flavonoids by using chemical reactions and using thin layer chromatography. The mobile phase used in thin layer chromatography is toluene: ethyl acetate (9.3: 0.7). Determination of the mobile phase is done based on a trial and error approach to obtain a clear line of movement. The stationary phase uses silica gel GF 254.Based on phytochemical analysis, the skin of salak fruit (Salaccazalacca) contains alkaloids, triterpenoids, saponins, tannins, and flavonoids. In addition, based on analysis using thin layer chromatography it produces Rf 0.1875 and is thought to contain terpene alcohol.