bluuebunny/crossref_metadata_2025_split huggingface dataset:
MicroRNAs and long non-coding RNAs as potential candidates to target specific motifs of SARS-CoV-2
Authors: Natarelli Lucia , Parca Luca , Virgili Fabio , Mazza Tommaso , Weber Christian , Fratantonio Deborah 
Published: September 2020

Abstract
The novel Coronavirus, SARS-CoV-2 disease (COVID-19) was defined as a global pandemic and induced a severe public health crisis in 2020. Covid-19 viral infection targets the human respiratory system and, at present, no specific treatment has been identified even though certain drugs have been studied and considered apparently effective in viral progression by reducing the complications in the lung epithelium. Researchers and clinicians are still struggling to find a vaccine or a specific innovative therapeutic strategy to counter COVID-19 infection.Here we describe our study indicating that SARS-CoV-2 genome contains motif sequences in the 5´UTR leader sequence that can be selectively recognized by specific human non-coding RNAs (ncRNAs), such as micro and long non-coding RNAs (miRNAs and lncRNA). Notably, some of these ncRNAs have been already utilized as oligo-based drugs in pulmonary and virus-associated diseases. We identified three selective motifs at the 5´UTR leader sequence of SARS-CoV-2 that allow viral recognition and binding of a specific group of miRNAs, some of them characterized by “GU” seed alignments. Additionally, one seed motif within miRNAs has been found to be able to bind the 5’UTR leader sequence. Among miRNAs having thermodynamically stable binding site against leader sequence and that are able interacted with Spike transcript some are involved in pulmonary arterial hypertension and anti-viral response, i.e. miR-204, miR-3661, and miR-1343. Moreover, several miRNA candidates have been already validated in vivo and specific oligo sequence are indeed available for their inhibition or overexpression.Four lncRNAs (H19, Hotair, Fendrr, and LINC05) directly interact with spike transcript (mRNA) and viral genome.In conclusion, we suggest that specific miRNAs and lncRNAs can be potential candidates to design oligonucleotide-drugs to treat COVID-19 and that our study can provide candidate hypothesis to be eventually tested in further experimental studies.
Hypercaloric diets impair ovarian follicular development by inducing hyperinsulinemia and hyperlipidemia in female mice
Authors: Zhang Qiaoli , Wang Yan , Liu Jiansheng , Chen Zi-Jiang , Du Yanzhi 
Published: September 2020

Abstract
Long-term hypercaloric diets adversely impact ovarian follicular development and fecundity. We investigated the effects of high sugar (HS), high fat low sugar (HFLS), and high fat normal sugar (HFNS) diets on ovarian follicular development by feeding mice for up to 180 days. Body weight, gonadal fat, glucose, lipid, insulin, estrous cycle, sex hormones, ovarian tissues, and follicle ultrastructure were examined, and the expression of metabolism-related proteins was evaluated immunoblotting in ovarians. The mice on hypercaloric diets showed hyperinsulinemia and hyperlipidemia and exhibited heavier body and gonadal fat weights, longer estrous cycles, and fewer numbers of preantral and antral follicles; and the follicles that did form had impaired organelle morphology. The sex hormone levels in blood were similar to controls, excepting significantly elevated estradiol levels for the HS diet. In ovarian tissues, AMPKα phosphorylation was reduced while AKT phosphorylation and caspase-3 were increased in ovarian tissues in mice on all three hypercaloric diets. The data from our study collectively indicates possible mechanisms through which long-term exposure to unhealthy hypercaloric diets may impair ovarian follicular development: hyperinsulinemia and hyperlipidemia.
A hybrid model based on mBA-ANFIS for COVID 19 confirmed cases prediction and forecast
Authors: Saif Sohail , Das Priya , Biswas Suparna 
Published: September 2020

Abstract
In India, the first confirmed case of novel corona virus (COVID-19) was discovered on 30 January, 2020. The number of confirmed cases is increasing day by day and it crossed 21,53,010 on 09 August, 2020. In this paper a hybrid forecasting model has been proposed to determine the number of confirmed cases for upcoming 10 days based on the earlier confirmed cases found in India. The proposed modelis based on adaptive neuro-fuzzy inference system (ANFIS) and mutation based Bees Algorithm (mBA). ThemetaheuristicBees Algorithm (BA) has been modified applying 4 types of mutation and Mutation based Bees Algorithm (mBA) is applied to enhance the performance of ANFIS by optimizing its parameters. Proposed mBA-ANFIS model has been assessed using COVID-19 outbreak dataset for India and USAand the number of confirmed cases in next 10 days in Indiahas been forecasted. Proposed mBA-ANFIS model has been compared to standard ANFIS model as well as other hybrid models such as GA-ANFIS, DE-ANFIS, HS-ANFIS, TLBO-ANFIS, FF-ANFIS, PSO-ANFIS and BA-ANFIS. All these models have been implemented using Matlab 2015 with 10 iterations each. Experimental results showthat the proposed model has achieved better performance in terms of Root Mean squared error (RMSE), Mean Absolute Percentage Error (MAPE), Mean absolute error (MAE) and Normalized Root Mean Square Error (NRMSE).It has obtained RMSE of 1280.24, MAE of 685.68, MAPE of 6.24 and NRMSE of 0.000673 for India Data.Similarly, for USA the values are 4468.72, 3082.07, 6.1, 0.000952 for RMSE, MAE, MAPE, NRMSE respectively.
The Role of Ego Integrity and Despair in Older Adults’ Well-being during the Covid-19 Crisis: The Mediating Role of Need-based Experiences
Authors: Kaap-Deeder Jolene van der , Vermote Branko , Waterschoot Joachim , Soenens Bart , Morbee Sofie , Vansteenkiste Maarten 
Published: September 2020

Abstract
The Covid-19 pandemic has affected people across the world, with older adults being particularly at risk for the negative (side) effects associated with this crisis. Relying on a cross-fertilization between Erikson’s personality theory and Self-Determination Theory, this study aimed to examine possible sources of resilience (i.e., ego integrity and need satisfaction) and vulnerability (i.e., despair and need frustration) in older adults’ (mal)adjustment, thereby additionally considering the role of multiple risk and protective factors (e.g., gender and marital status). During the second month of the lockdown period in Belgium, 693 older adults (Mage = 70.06, SD = 4.48, range: 65 – 89 years, 62.1% female) filled out online questionnaires concerning the study variables, while also completing assessments of several important sociodemographic factors. Structural equation modeling showed that both ego integrity and despair related to indicators of well-being and ill-being through experienced need satisfaction and need frustration. Additionally, we found several factors to protect (e.g., higher perceived income) or diminish (e.g., being widowed) older adults’ well-being during these challenging times, with little evidence for a moderating role of these factors in associations between the psychological variables. Theoretical and practical implications of these results are discussed.
The Expression of the Cold Shock Protein RNA Binding Motif Protein 3 is Transcriptionally Responsive to Organ Temperature in Mice
Authors: Ushio Ayako , Eto Ko 
Published: September 2020

Background:
Mild hypothermia, i.e. maintenance of organ temperature by up to 8°C
lower than body temperature, is a critical strategy for exerting some functions of the cells and organs
normally, and is an useful therapy for recovering properly from some diseases, including myocardial
infarction, cardiac arrest, brain injury, and ischemic stroke. Nevertheless, there were no focusses
so far on organ temperature and potential responses of gene expression to organ temperature
in organs of homeothermic animals that survive under normal conditions.

Objective:
The present study aimed to assess organ temperature in homeothermic animals and evaluate
the effect of their organ temperature on the expression of the cold shock protein RNA binding
motif protein 3 (RBM3), and to gain insights into the organ temperature-mediated regulation of RBM3
gene transcription via Nuclear factor β-light-chain-enhancer of activated B cells (NF-κB) p65,
which had been identified as a transcription factor that is activated by undergoing the Ser276 phosphorylation
and promotes the RBM3 gene expression during mild hypothermia.

Methods:
We measured the temperature of several organs, where RBM3 expression was examined,
in female and male mice. Next, in male mice, we tested NF-κB p65 expression and its Ser276 phosphorylation
in organs that have their lower temperature than body temperature and compared them
with those in organs that have their temperature near body temperature.

Results:
Organ temperature was around 32°C in the brain and reproductive organs, which is lower
than the body temperature, and around 37°C in the heart, liver, and kidney, which is comparable to
the body temperature. The expression of RBM3 was detected greatly in the brain and reproductive
organs with their organ temperature of around 32°C, and poorly in the heart, liver, and kidney with
their organ temperature of around 37°C. In accordance with the changes in the RBM3 expression,
the NF-κB p65 Ser276 phosphorylation was detected more greatly in the testis and brain with their
organ temperature of around 32°C, than in the heart, liver, and kidney with their organ temperature
of around 37°C, although the NF-κB p65 expression was unchanged among all the organs tested.

Discussion:
Our data suggested that organ temperature lower than body temperature causes the expression
of RBM3 in the brain and reproductive organs of mice, and that lower organ temperature
causes the NF-κB p65 activation through the Ser276 phosphorylation, resulting in an increase in
the RBM3 gene transcription, in the brain and reproductive organs of mice.

Conclusion:
The study may present the possibility that organ temperature-induced alterations in
gene expression are organ specific in homeotherms and the possibility that organ temperature-induced
alterations in gene expression are transcriptionally regulated in some organs of
homeotherms.
Moringa oleifera Leaf Extract Attenuates Pb Acetate-induced Testicular Damage in Rats
Authors: Albasher Gadah , Alrajhi Rola , Alshammry Entesar , Almeer Rafa 
Published: September 2020

Background:
Lead (Pb) remains a common contaminant in the environment in many
parts of the world. Pb exposure adversely affects many human organs, including the gonads, via
oxidant and inflammatory marker propagation in affected tissues. Moringa oleifera leaf extract
(MOE) is a rich source of antioxidants, reported to have robust anti-inflammatory properties.

Aims:
This investigation assessed whether MOE could mitigate testicular damage caused by Pb acetate treatment in rats.

Methods:
Four experimental groups were used: control animals (saline only), MOE (MOE only),
PbAc (Pb acetate injection only), and MOE+PbAc. All treatments were administered for two
weeks, after which animals were sacrificed, and tissues and serum were examined. To confirm the
potential antioxidant effect of MOE, the total polyphenolic (TP) and flavonoid (TF) concentrations
were determined.

Results:
The obtained results revealed that the TP concentration was 17.4 mg gallic acid equivalents
per gram MOE dried weight and the TF concentration was 5.6 mg of quercetin equivalents
per gram MOE dried weight. Moreover, MOE partially restored levels of luteinizing hormone (LH)
and follicle-stimulating hormone (FSH) and testosterone and significantly attenuated oxidative
stress biomarkers, malondialdehyde (MDA) and nitric oxide (NO), compared to levels observed in
the PbAc-only group. MOE significantly increased the enzymatic and non-enzymatic antioxidant
molecules superoxide dismutase (SOD) and catalase (CAT), glutathione peroxidase (GPx) and glutathione
reductase (GR), and glutathione (GSH). Testicular levels of inflammatory cytokines tumor
necrosis factor-alpha (TNFα) and interleukin-1beta (IL-1β) were significantly decreased in
MOE+PbAc compared to PbAc. MOE also significantly decreased pro-apoptotic Bax and caspase-
3 mRNA and protein levels and increased anti-apoptotic Bcl-2 mRNA and protein levels.

Conclusion:
MOE extract was associated with significant antioxidant, anti-inflammatory, and anti-apoptotic activity that
ameliorated testicular damage induced by Pb acetate. We propose MOE as a favorable adjuvant to existing treatments for
Pb-induced toxicity.
Directing the Antiretroviral Drugs to the Brain Reservoir: A Nanoformulation Approach for NeuroAIDS
Authors: Nabi Bushra , Rehman Saleha , Pottoo Faheem H. , Baboota Sanjula , Ali Javed 
Published: September 2020

Background:
Human immunodeficiency virus (HIV)/AIDS is one of the principal concerns contributing
to the global burden and the accompanying deleterious outcomes could not be left unattended. Despite
significant advances and innovative research being conducted throughout the globe in order to improve the therapeutic
profile of conventionally available antiretroviral (ARV) drugs in the eradication of HIV virus reservoirs,
its penetration across the blood-brain barrier (BBB) is still a formidable mission. This makes the central
nervous system a dominant and vulnerable site for virus propagation, which ultimately affects the therapeutic
potential of the drug administered. Therefore there is an upsurge in the prerequisite of novel technologies to
come into play, paving the way for nanotechnology.

Methods:
This review primarily provides a comprehensive outline and emphasizes on the nanotechnological
techniques employed for the delivery of ARV drugs and their stupendous advantages in overcoming the hurdles
associated with the same.

Results:
The nanotechnological approach bears the potential of site-specific delivery across the BBB via targeting
explicit transport processes and provides a sustained release mechanism. Furthermore, different routes of administration
explored have also yielded beneficial outcomes for the delivery of ARV drugs.

Conclusion:
The futuristic holistic nanotechnology methods, however, should focus on increasing drug trafficking
and permeability across the BBB to ameliorate the therapeutic effect of ARV drugs. Additionally, the domain
warrants clinical studies to be undertaken to make the technology commercially viable and a success to
deal with the problems of the treatment strategy.
Assessment of Biochemical Determinants in Multiple Sclerosis Patients Following the Oral Administration of β-D-Mannuronic Acid (M2000)
Authors: Nikouei Moghaddam Mohamad Reza , Movahedi Monireh , Bananej Maryam , Najafi Soheil , Moghadam Nahid Beladi , Saadat Payam , Mokhtarian Fariba , Mirshafiey Abbas 
Published: September 2020

Background:
Multiple sclerosis is an autoimmune chronic inflammatory disease of the
central nervous system that can lead to some serious disabilities. Despite using various immunomodulatory
and anti-inflammatory drugs that have therapeutic effects, they cannot reduce its progression
completely and have some unwanted side effects too. The immunomodulatory and anti-inflammatory
effects of the β-D-Mannuronic acid (M2000) have been proven in several surveys, and the
present research was designed to determine its toxicity and therapeutic effects in MS patients.

Methods:
This study was performed on 15 MS patients who took 25 mg/kg/day the oral form of
the β-D-Mannuronic acid for six months, and 15 healthy people as a control group. Serum levels of
Urea, Creatinine, GGT, Vitamin D3, Uric acid, and Anti-Phospholipids were compared to evaluate
the therapeutic and possible toxic effects of this drug after this period.

Results:
Non- toxic effects through the study of urea, creatinine, GGT, and non-significant changes
in uric acid and anti-Phospholipids levels, besides a significant rise in vitamin, D3 levels in the
M2000 treated cases were found.

Conclusions:
Our results suggested that β-D-Mannuronic acid is a safe drug and has no toxicity
when administered orally and also has some therapeutic effects in MS patients.
NiFe2O4@SiO2 n Pr@glucose Catalyzed Synthesis of Novel 5-pyrazolin-1,2,4- triazazolidine-3-ones (thiones)
Authors: Nikpassand Mohammad , Pourkarim Zahra 
Published: September 2020

Introduction:
NiFe2O4@SiO2nPr@glucose catalyzed synthesis of novel 5-pyrazolin-1,2,4-triazazolidine-
3-ones (thiones).

Materials and Methods:
Amino glucose-functionalized silica-coated NiFe2O4 nanoparticles (NiFe2O4@SiO2
nPr@glucose amine or NiFe2O4@SiP@GA) were synthesized and characterized by X-ray powder diffraction
(XRD), X-ray spectroscopy (EDX), transmission electron microscope (TEM), field emission scanning electron
microscope (FE-SEM), vibrating sample magnetometry (VSM) and fourier transform infrared spectroscopy (FTIR).

Results and Discussion:
NiFe2O4@SiP@GA supply an eco-friendly procedure for the synthesis of some novel 5-
pyrazolin-1,2,4-triazazolidine-3-ones or thiones through one-pot reaction of thiosemicarbazide (hydrazinecarbothioamide)
and synthetized pyrazole carbaldehydes. These compounds were obtained in high yields in short
reaction times. The catalyst could be easily recovered and reused for six cycles with almost consistent activity.
The structures of the synthesized 5-pyrazolin-1,2,4-triazazolidine-3-ones or thiones were confirmed by 1H NMR,
13C NMR and FTIR spectral data and elemental analyses.

Conclusion:
In conclusion, we have investigated NiFe2O4@SiO2nPr@amino glucose as a new, eco-friendly,
inexpensive, mild and reusable catalyst for the synthesis of 5-pyrazolin-1,2,4-triazazolidine-3-ones or thiones.
High yield, a simple work.up procedure, adherence to the basics of green chemistry, environmental friendly and
based on natural ingredients, ease of separation and recyclability of the magnetic catalyst and waste reduction are
some advantages of this method.
Chemical IN04 Inhibits the Kinase Domain not the ROC Domain of LRRK1: Results from Homology Modeling and Molecular Docking
Authors: Chen Zhenhang , Xing Weirong , Fan Li 
Published: September 2020

Background:
Bone loss is the most common reason for broken bones among the elderly.
An ideal agent for the treatment of bone loss should have both osteoclast inhibitory and osteoblast
stimulatory functions. Leucine-rich repeat kinase 1 (LRRK1) is a novel target for alternative antiresorptive
drugs to treat osteoporosis and osteoporotic fractures. Recently a chemical IN04, Methyl
3-[(([5-(3,5-dimethoxyphenyl)-1,3,4-oxadiazol-2-yl]-thio-acetyl)-amino]-benzoate, has been identified
as a potential LRRK1 inhibitor.

Objective:
The aim of this work is to investigate how the chemical IN04 interacts with LRRK1 and
inhibits its activity.

Methods:
A structural model of the LRRK1 kinase domain was constructed with SWISS-MODEL.
The human protein kinase ROCO4 (PDB ID: 4YZN) was chosen as the template based on sequence
homology, structural and phylogenetic analysis. In addition, a homology model of the LRRK1 ROC
domain was also prepared based on the LRRK2 ROC domain structure (PDB ID: 2ZEJ). The interactions
of IN04 with the active sites in the LRRK1 kinase domain and ROC domain were investigated
by SwissDock.

Results:
IN04 was docked into the active site of the LRRK1 kinase domain with similar interactions
as ATP comparable to the ligand bound to homologous kinases. Many rational binding modes of
IN04 to LRRK1 kinase domain were investigated and the most likely binding pose containing multiple
hydrogen bonds and a salt bridge was discovered. However, IN04 cannot fit into the GDP-binding
site of the ROC domain.

Conclusion:
Chemical IN04 inhibits LRRK1 by binding to the active site of the kinase domain but
not the ROC domain.
Evaluation of the Laxative Activity of Saponin Enriched Hydroethanolic Pericarp Extract of Sapindus emarginatus in Animal Models
Authors: Vivekanandan Lalitha , Mandere Roxanne Gekonge , Thangavel Sivakumar 
Published: September 2020

Background:
Constipation is a common, predominant, chronic gastrointestinal functional
disorder. The drugs available to treat constipation are limited because of their side effects for
long term use. Therefore, we need effective drug to treat constipation. Sapindus emarginatus Vahl
belongs to the family Sapindaceae, commonly known as soapnut. It is traditionally used as an antipruritic,
antifertility, laxative, and anti-inflammatory agent.

Objective:
The present study was conducted to evaluate the laxative activity of hydroethanolic pericarp
extract of Sapindus emarginatus (HESE) in animal models.

Methods:
The saponin content in the extract was measured by the gravimetric analysis. The laxative
activity of hydroethanolic pericarp extract of Sapindus emarginatus was evaluated by the
weight of feces matter, charcoal meal hyperperistalsis test, and loperamide induced constipation
model.

Results:
The saponin content of the soapnut pericarp was 13.48% and the extract was found to be
11.92%. The results obtained from these models showed a significant dose-dependent increase in
fecal weight, peristalsis index, and moisture content compared to control animals.

Conclusion:
The present study concluded that the oral administration of HESE showed a significant
laxative activity in different animal models. The presence of triterpene saponins is supposed to
be responsible for this activity. Further studies are needed to confirm their mechanism behind the
laxative effect. The administration of the extract was found to be effective in constipation therapy.
Design and In-silico Screening of Peptide Nucleic Acid (PNA) Inspired
Novel Pronucleotide Scaffolds Targeting COVID-19
Authors: Sahu Bichismita , Behera Santosh Kumar , Das Rudradip , Dalvi Tanay , Chowdhury Arnab , Dewangan Bhaskar , Kalia Kiran , Shard Amit 
Published: September 2020

Introduction:
The outburst of the novel coronavirus COVID-19, at the end of December 2019 has turned itself
into a pandemic taking a heavy toll on human lives. The causal agent being SARS-CoV-2, a member of the
long-known Coronaviridae family, is a positive sense single-stranded enveloped virus and quite closely related to
SARS-CoV. It has become the need of the hour to understand the pathophysiology of this disease, so that drugs,
vaccines, treatment regimens and plausible therapeutic agents can be produced.

Methods:
In this regard, recent studies uncovered the fact that the viral genome of SARS-CoV-2 encodes nonstructural proteins like RNA dependent RNA polymerase (RdRp) which is an important tool for its transcription
and replication process. A large number of nucleic acid based anti-viral drugs are being repurposed for treating
COVID-19 targeting RdRp. Few of them are in the advanced stage of clinical trials including Remdesivir. While
performing close investigation of the large set of nucleic acid based drugs, we were surprised to find that the
synthetic nucleic acid backbone is explored very little or rare.

Results:
We have designed scaffolds derived from peptide nucleic acid (PNA) and subjected them for in-silico
screening systematically. These designed molecules have demonstrated excellent binding towards RdRp.
Compound 12 was found to possess similar binding affinity as Remdesivir with comparable pharmacokinetics.
However, the in-silico toxicity prediction indicates compound 12 may be a superior molecule which can be
explored further due to its excellent safety-profile with LD50 (12,000mg/kg) as opposed to Remdesivir (LD50
=1000mg/kg).

Conclusion:
Compound 12 falls in the safe category of class 6. Synthetic feasibility, equipotent binding and
very low toxicity of this peptide nucleic acid derived compounds can serve as a leading scaffold to design,
synthesize and evaluate many of similar compounds for the treatment of COVID-19.