bluuebunny/crossref_metadata_2025 huggingface dataset:
Diabetic neuropathy in the elderly
Authors: Cherdak Maria А. , Mkhitaryan E. А.
Published: August 2020

The increase in the diabetes mellitus (DM) prevalence and incidence has taken on the features of the epidemic. Particularly often, DM occurs in the elderly and senile patients, while at least half of the cases of diabetes in this population remain undiagnosed. DM contributes to the deterioration of the quality of life, causes formation of dependence and progression of various geriatric syndromes leading to increased mortality. Elderly age is an independent risk factor for diabetic neuropathy. The main clinical forms of which are represented by chronic sensorimotor and autonomic impairments, complicated by impaired cardiovascular, gastrointestinal and urogenital functions, as well as chronic neuropathic pain syndrome. Progression of diabetic neuropathy aggravates walking and balance disorders, increases the risk of falls and loss of mobility, and significantly increases the risk of adverse diabetes outcomes. The article discusses in detail risk factors, pathogenesis, differential diagnosis and the possibilities of clinical and non-clinical evaluation of patients with suspected diabetic neuropathy. Possibilities for pain assessment in elderly people with communicative disorders or concomitant cognitive impairment are demonstrated. The article presents an algorithm for management of diabetic neuropathy in elderly ones, ways for optimization of risk and benefit balance, as well as the possibility of etiopathogenetic and symptomatic treatment of pain, autonomic disorders and prevention of late complications of diabetes with use of alpha-lipouc acid, taking into account key characteristics of discussed population.
Personalized, interdisciplinary approach to the treatment of chronic low back pain: clinical observation
Authors: Golovacheva V. A. , Golovacheva A. A.
Published: August 2020

Nonspecific (musculoskeletal) pain is the most common cause of low back pain (LBP). Chronic nonspecific LBP is a particular problem, as it significantly reduces the quality of life and functional activity of the patient. The diagnosis of chronic non-specific LBP is made after exclusion of a specific cause of pain, discogenic radiculopathy and lumbar stenosis. Unfortunately, patients with chronic non-specific LBP are often misdiagnosed, pain chronization factors (“yellow flags”) are ignored and ineffective treatment is prescribed. Clinical observation of a patient with chronic non-specific LBP, who was initially wrongly diagnosed with spinal osteochondrosis and the treatment was ineffective, is presented. A personalized, multidisciplinary approach to treatment allowed the patient to cope with back pain and to return to his previous daily activities. The patient’s treatment plan included non-drug methods of treatment (educational conversation, physical activity, mindfulness, cognitive-behavioural therapy) and rational pharmacotherapy (non-steroidal anti-inflammatory drug, NSAID). Clinical observation showed the efficacy and good tolerability of NSAID - dexketoprofen (in the form of Dexalgin and Dexalgin 25), which was administered in a stepwise scheme for 5 days. According to modern recommendations, NSAIDs are first-line drugs in chronic non-specific LBP. The results of clinical studies on efficacy and safety in back pain of such NSAIDs as dexketoprofen and nimesulide are presented. In case of prolonged exacerbation the possibility of dexketoprofen prescription with subsequent transition to nimesulide is discussed.
Modern approaches to the pharmacotherapy of postpartum depression
Authors: Ovchinnikov A. V. , Vazagaeva T. I.
Published: August 2020

Postpartum or postnatal depression (PDD) is a common disorder that has serious negative effects on a woman’s health and increases the risk for a child’s emotional, social, and cognitive development outcomes. There are a few unresolved problems in the PDD pharmacotherapy caused by the lack of evidence about drug safety and effectiveness. This review provides a timely update on the current understanding of approaches to the diagnosis and treatment of patients with PDD as part of recurrent depression and bipolar disorder, the features of pharmacotherapy in the postpartum period depending on the manifestations and course of the disease. In accordance with the current guidelines, the treatment of PDD requires the use of the same standard approaches, as in the treatment of depression not associated with pregnancy and childbirth, while it is recommended to refuse breastfeeding in most cases, which runs somewhat contrary to the literature. Several clinical studies have shown that some psychotropic drugs are safe to use in breastfeeding mothers as they demonstrate low transfer into breast milk and rarely cause adverse events in infants. With this respect, sertraline is regarded as the first choice among antidepressants (AD), and quetiapine and valproate among normotimics, however, the limited amount of data does not allow us to make final conclusions about short-term and long-term risks for children. The article also outlines promising directions in the development of new neurosteroid-based antidepressant drugs for the treatment of PDD. Their mechanism of action is mainly associated with a modulating effect on GABAergic neurotransmission.
Production of peptides and amino acids from microbial biomass in food and feed industries: biotechnological aspects
Authors: Serba Elena , Rimareva Liubov , Overchenko Marina , Ignatova Nadezhda , Tadzhibova Polina , Zorin Sergey
Published: August 2020

Introduction. Microbial biomass is a popular source of food ingredients and feed additives. Its high use has made it focus of many relevant studies. Yeast and fungal biomasses proved to be useful substrates that improve the quality and biological value of functional products. They differ in the content and composition of proteins and polysaccharides. The present research dealt with the enzymatic decomposition of proteins found in a novel fungal and yeast biomass. The research objective was to describe the peptide and amino acid composition of their enzymatic hydrolysates.

Study objects and methods. The research featured a new fungal and yeast biomass mix. Aspergillus oryzae is a mycelial fungus and a popular industrial producer of hydrolytic enzymes in food industry. As for the yeast, it was the Saccharomyces cerevisiae strain, which is often used in baking.

Results and discussion. The total content of identified amino acids in the fungal and yeast biomass was 306.0 mg/g, which was 1.5 times higher than in the fungal biomass alone. The biomass mix demonstrated a higher biological value of proteins than the yeast biomass. A set of experiments made it possible to compile a scheme for the biocatalytic destruction of polymers in the fungal and yeast biomass under the effect of fungal intracellular and endogenous enzymes. The article also contains a thorough description of the obtained enzymatic hydrolysates with various fractional compositions of peptides and free amino acids. Peptides with the molecular weight in the range of up to 29.0 kDa decreased by 2.1 times after 5 h of hydrolysis and by 10.7 times after 18 h. The designed conditions doubled the release of amino acids and increased the content of low-molecular-weight peptides up to 75.3%.

Conclusion. The research provided a new algorithm for the biocatalytic conversion of microbial biomass. Regulating the conditions of enzymatic hydrolysis made it possible to obtain enzymatic hydrolysates with a desired degree of protein degradation. They could serve as peptides and amino acids in functional food and feed products.
Edible Nuts for Memory
Authors: Arslan Jamshed , Gilani Anwar-ul-Hassan , Jamshed Humaira , Khan Sumaiya F. , Kamal Mohammad A.
Published: August 2020

Nuts hold prime significance throughout the world as they offer multiple health benefits owing to their
highly nutritious profile. A number of scientific studies have demonstrated their actions against inflammation,
oxidative damage, the aging process, as well as dementia or memory loss. However, only walnuts, followed by
almonds, hazelnuts and pistachios, have shown promising results in empirical studies for memory improvements.
So, the current review focuses on presenting hypotheses regarding anti-dementia property of nine different nuts:
almond, walnut, pistachio, Brazil nut, peanut, pecans, cashew, hazelnut, and chestnut. The nutritious profile of
nuts contains essential fats (mostly mono- and poly-unsaturated fatty acids), proteins (source for arginine, lysine
and tryptophan), vitamins (riboflavin, folate, and various tocopherols), fibers, minerals (calcium, sodium, magnesium,
phosphorus and potassium) and trace elements (copper, zinc, and selenium). Interestingly, the constituents
of natural products, nuts being an excellent example, work synergistically and/or in a side-effect neutralizing
manner. These latter properties can make nuts an alternate therapy for humankind to fight against memory loss.
The Identification of Three Key Genes Related to Stemness in Thyroid Carcinoma through Comprehensive Analysis
Authors: Zhang Tonglong , Yan Chunhong , Ye Zhengdu , Yin Xingling , Jiang Tian-an
Published: August 2020

Background:

Tumor heterogeneity imposes great challenges on cancer treatment.
Cancer stem cells (CSCs) are a leading factor contributing to tumor occurrence. However, the
mechanisms underlying the growth of thyroid cancer (TCHA) are still unclear.

Methods:

Key genes regulating the characteristics of THCA, such as stemness were identified by
combining gene expressions of samples downloaded from the Cancer Genome Atlas (TCGA) and
were used to establish an mRNA expression stemness index (mRNAsi) through machine learningbased
methods. The relationships of mRNAsi, THCA clinical features and molecular subtypes
were analyzed. Weighted Gene Co-Expression Network Analysis (WGCNA) was performed to
obtain mRNAsi-related gene modules and determine mRNAsi-related differentially co-expressed
genes. Key genes related to mRNAsi were screened by protein interaction network. Functional
analysis was conducted and expressions of key genes were verified in multiple external data sets.

Results:

The mRNAsi score, which was found to be lower in the TCHA tissues than that in
normal tissues (p<0.05), was positively correlated with a slow progression of tumor prognosis
(p=0.0085). We screened a total of 83 differentially co-expressed genes related to mRNAsi and
multiple tumor pathways such as apoptosis, tight junction, cytokine-cytokine receptor interaction, and
cAMP signaling pathway (p<0.05). Finally, 28 protein interaction networks incorporating 32 genes
were established, and 3 key genes were identified through network mining. 3 core genes were finally
determined, as their low expressions were strongly correlated with the progression of THCA.

Conclusion:

The study found that NGF, FOS, and GRIA1 are closely related to the characteristics
of THCA stem cells. These genes, especially FOS, are highly indicative of the prognosis of THCA
patients. Thus, screening therapy could be used to inhibit the stemness of TCHA.
Theoretical Study of the Molecular Mechanism of Maxingyigan Decoction Against COVID-19: Network Pharmacology-based Strategy
Authors: Wang Mingzhu , Fu Deyu , Yao Lei , Li Jianhua
Published: August 2020

Aim and Objective:

Maxingyigan (MXYG) decoction is a traditional Chinese medicine
(TCM) prescription. However, how MXYG acts against coronavirus disease 2019 (COVID-19) is
not known. We investigated the active ingredients and the therapeutic targets of MXYG decoction
against COVID-19.

Methods:

A network pharmacology strategy involving drug-likeness evaluation, prediction of oral
bioavailability, network analyses, and virtual molecular docking was used to predict the
mechanism of action of MXYG against COVID-19.

Results:

Thirty-three core COVID-19-related targets were identified from 1023 gene targets
through analyses of protein–protein interactions. Eighty-six active ingredients of MXYG decoction
hit by 19 therapeutic targets were screened out by analyses of a compound–compound target
network. Via network topology, three “hub” gene targets (interleukin (IL-6), caspase-3, IL-4) and
three key components (quercetin, formononetin, luteolin) were recognized and verified by
molecular docking. Compared with control compounds (ribavirin, arbidol), the docking score of
quercetin to the IL-6 receptor was highest, with a score of 5. Furthermore, the scores of three key
components to SARS-CoV-2 are large as 4, 5, and 5, respectively, which are even better than those
of ribavirin at 3. Bioinformatics analyses revealed that MXYG could prevent and treat COVID-19
through anti-inflammatory and immunity-based actions involving activation of T cells,
lymphocytes, and leukocytes, as well as cytokine–cytokine-receptor interaction, and chemokine
signaling pathways.

Conclusion:

The hub genes of COVID-19 helped to reveal the underlying pathogenesis and
therapeutic targets of COVID-19. This study represents the first report on the molecular
mechanism of MXYG decoction against COVID-19.
Evaluation of Microbiological Contamination of Dummies Used in Cardiopulmonary Resuscitation in Korea
Authors: Cho Seung-Hak , Kim Jung-Beom , Kim Cheorl-Ho , Bak Young-Seok
Published: August 2020

Objectives:

In order to prevent infections through dummies used during Cardiopulmonary
Resuscitation (CPR) training, we analyzed the microbiological contamination on dummies used in CPR
institutions.

Methods:

A total of 31 dummy samples were collected from 13 different institutions in Korea, and
were evaluated for the number of contaminating bacteria and fungi on the surface. PCR and biochemical
tests were performed to identify pathogenic bacteria and fungi, including Methicillin-Resistant
Staphylococcus aureus (MRSA). Moreover, we further assessed the survival rate of microorganisms on
the surface of the dummies.

Results:

We assessed the total number of microorganisms on the surface to be 77,752CFU/cm2
(±50,047CFU), which is up to 188 times higher than the required surface contamination level. Grampositive
cocci such as Micrococcus spp. and Staphylococcus spp. accounted for the highest proportion
(55.3%). Especially, we detected three MRSA strains. Considering the isolated fungi and yeast, Aspergillus
spp. and Candidia spp. accounted for the highest proportion. Assessing the contamination level
simulation and survival rate on the humanoid surface showed that within two weeks of training, the
level of contamination on the dummy’s surface exceeded the standard, and artificially contaminated
pathogenic strains on the surface of the dummy survived for at least 40 days.

Conclusion:

To minimize the possibility of secondary infections during CPR training, there is a requirement
for a standardized protocol for proper microbiological management of dummies.
Comparative Inhibitory Efficacy on the iNOS/NO System of Curcuminand Tetrahydrocurcumin-Self-Microemulsifying Liquid Formulation in Chronic Gastric Ulcer Model
Authors: Mahattanadul Sirima , Kongpuckdee Sonsawan , Wiwattanapatapee Ruedeekorn , Tansakul Pimpimon , Nitiruangjaras Anupong , Hansakul Pintusorn
Published: August 2020

Background:

Curcumin was found to accelerate gastric ulcer healing by the main mechanism, i.e., the suppression of iNOS mediated inflammation. Although Tetrahydrocurcumin (THC) is claimed to be an active antioxidant element of curcumin, its antiulcer activity has not been systematically examined. The utility of Self-Microemulsifying Drug Delivery Systems (SMEDDSs) for curcumin and THC formulations in the liquid form was also found to increase the rate and extent of release of curcumin- and THC-SMEDDS. Nevertheless, the beneficial antiulcer effect of these nanoproducts has not yet been evaluated.

Objective:

This study aimed to evaluate and compare the antiulcer efficacy of curcumin- and THCSMEDDS through the inhibition of the iNOS/NO system in the rat model.

Methods:

Antiulcer efficacy was compared in terms of the ability to accelerate healing of gastric ulcer including the efficient inhibitory action on inflammatory NO production in activated macrophages and iNOS mRNA expression at the ulcerated area.

Results:

THC was found to have less ulcer healing capacity than curcumin with a lack of significant inhibitory effect on the iNOS/NO system. The SMEDDS used in the study significantly increased the inhibitory efficacy of THC on iNOS/NO production and iNOS mRNA expression compared to the inhibitory potency of curcumin. An oral administration of curcumin- or THC-SMEDDS once a day was appropriate for exerting a comparable curative efficacy to a twice-daily oral administration of curcumin or THC.

Conclusion:

The SMEDDS used in the study was observed to enhance the inhibitory efficacy of the antiulcer drug on the iNOS/NO system, leading to a reduction of daily dosing and dosing frequency.
LC-MS/MS Determination of Apigenin in Rat Plasma and Application to Pharmacokinetic Study
Authors: Zhu Shixing , Zhang Jiayuan , Lv Zhihua , Yu Mingming
Published: August 2020

Background:

Apigenin, a natural plant flavone, has been shown to possess a variety of biological
properties.

Objective:

In this report, a highly selective and sensitive LC-MS/MS method was developed and validated
for the determination of apigenin in rat plasma.

Methods:

Analysts were separated on the HSS T3 column (1.8 μm 2.1×100 mm) using acetonitrile and
0.1% formic acid in 2mM ammonium acetate buffer at a supply rate of 0.200 mL/min as eluent in gradient
model.

Results:

Plasma samples were treated by protein precipitation using acetonitrile for the recovery ranging
from 86.5% to 90.1% for apigenin. The calibration curves followed linearity in the concentration
range of 0.50-500ng/mL. The inter-day and intra-day precisions at different QC levels within 13.1%
and the accuracies ranged from -10.6% to 8.6%.

Conclusion:

The assay has been successfully applied to the pharmacokinetic study of apigenin in rats.
Ginseng Omics for Ginsenoside Biosynthesis
Authors: Yin Xianmei , Hu Haoyu , Shen Xiaofeng , Li Xiangyan , Pei Jin , Xu Jiang
Published: August 2020

Ginseng, also known as the king of herbs, has been regarded as an important traditional
medicine for several millennia. Ginsenosides, a group of triterpenoid saponins, have been characterized
as bioactive compounds of ginseng. The complexity of ginsenosides hindered ginseng research
and development both in cultivation and clinical research. Therefore, deciphering the ginsenoside biosynthesis
pathway has been a focus of interest for researchers worldwide. The new emergence of biological
research tools consisting of omics and bioinformatic tools or computational biology tools are
the research trend in the new century. Ginseng is one of the main subjects analyzed using these new
quantification tools, including tools of genomics, transcriptomics, and proteomics. Here, we review the
current progress of ginseng omics research and provide results for the ginsenoside biosynthesis pathway.
Organization and expression of the entire pathway, including the upstream MVA pathway, the
cyclization of ginsenoside precursors, and the glycosylation process, are illustrated. Regulatory gene
families such as transcriptional factors and transporters are also discussed in this review.
Potential of Gold Candidates against Human Colon Cancer
Authors: Abbasi Mahvish , Yaqoob Munazzah , Haque Rosenani A. , Iqbal Muhammad Adnan
Published: August 2020

Development of novel metallodrugs with pharmacological profile plays a significant role in
modern medicinal chemistry and drug design. Metal complexes have shown remarkable clinical results
in current cancer therapy. Gold complexes have attained attention due to their high antiproliferative
potential. Gold-based drugs are used for the treatment of rheumatoid arthritis. Gold-containing compounds
with selective and specific targets are capable to assuage the symptoms of a range of human
diseases. Gold (I) species with labile ligands (such as Cl in TEPAuCl) interact with isolated DNA;
therefore, this biomolecule has been considered as a target for gold drugs. Gold (I) has a high affinity
towards sulfur and selenium. Due to this, gold (I) drugs readily interact with cysteine or selenocysteine
residue of the enzyme to form protein-gold(I) thiolate or protein-gold (I) selenolate complexes that
lead to inhibition of the enzyme activity. Au(III) compounds due to their square-planner geometriesthe
same as found in cisplatin, represent a good source for the development of anti-tumor agents. This
article aims to review the most important applications of gold products in the treatment of human colon
cancer and to analyze the complex interplay between gold and the human body.
Modulation of Calcium Signaling in Glioblastoma Multiforme: A Therapeutic Promise for Natural Products
Authors: Afshari Amir R. , Mollazadeh Hamid , Soukhtanloo Mohammad , Hosseini Azar , Mohtashami Elmira , Jalili-Nik Mohammad , Modaresi Seyed Mohamad Sadegh , Soltani Arash , Sahebkar Amirhossein
Published: August 2020

Glioblastoma multiforme (GBM) continues as one of the most lethal cerebral cancers despite standard therapeutic modalities, such as maximum surgical resection and chemoradiation. The minimal effectiveness of existing therapies necessitates the development of additional drug candidates that could improve the prognosis of GBM patients. Accumulating evidence suggests that calcium (Ca2+) is involved in the processes of cell proliferation, metastasis, angiogenesis, migration, and invasiveness. Therefore, Ca2+could serve as a crucial regulator of tumorigenesis and a potential treatment target in GBM. In this context, specific natural products are known to modulate Ca2+signaling pathways implicated in tumor growth, apoptosis, angiogenesis, and development of GBM. Here, the focus is on the function of Ca2+as a therapeutic target in GBM and reviewing certain natural products that affect the signaling pathways of Ca2+.
Gene Therapy for Hemophilia A: Where We Stand
Authors: Zhou Miaojin , Hu Zhiqing , Zhang Chunhua , Wu Lingqian , Li Zhuo , Liang Desheng
Published: August 2020

Hemophilia A (HA) is a hereditary hemorrhagic disease caused by a deficiency of coagulation
factor VIII (FVIII) in blood plasma. Patients with HA usually suffer from spontaneous and recurrent
bleeding in joints and muscles, or even intracerebral hemorrhage, which might lead to disability
or death. Although the disease is currently manageable via delivery of plasma-derived or recombinant
FVIII, this approach is costly, and neutralizing antibodies may be generated in a large portion of patients,
which render the regimens ineffective and inaccessible. Given the monogenic nature of HA and
that a slight increase in FVIII can remarkably alleviate the phenotypes, HA has been considered to be
a suitable target disease for gene therapy. Consequently, the introduction of a functional F8 gene copy
into the appropriate target cells via viral or nonviral delivery vectors, including gene correction
through genome editing approaches, could ultimately provide an effective therapeutic method for HA
patients. In this review, we discuss the recent progress of gene therapy for HA with viral and nonviral
delivery vectors, including piggyBac, lentiviral and adeno-associated viral vectors, as well as new
raising issues involving liver toxicity, pre-existing neutralizing antibodies of viral approach, and the
selection of the target cell type for nonviral delivery.
Understanding the Obstacles to Uptake of Intervention Programmes and Services for Persons with Dementia
Authors: Lien Ha N.H. , Koh Emily J. , Yap Philip L.K.
Published: August 2020

Background:

Utilisation of intervention programmes and services for Persons with Dementia
(PWD) has been generally modest despite the growing numbers. One reason has been the lack of
knowledge about dementia and information on such services.

Objective:

We sought to close this gap by providing caregivers with an information session about
dementia and the importance and availability of related services. We explored the uptake of intervention
programmes and services and reasons for non-uptake thereafter.

Methods:

Two hundred and seventy-five PWD and caregiver dyads attended the Dyad Education and
Empowerment Programme (DEEP). At the DEEP, while caregivers underwent an information session,
PWD were assessed by a multidisciplinary team on their need and suitability for programmes and
services such as daycare, cognitive engagement programmes and physical rehabilitation. The dyads then
received individualized recommendations on the appropriate services, if any. Follow-up through medical
records review and phone calls was conducted one month after DEEP to ascertain if the dyads had acted
upon the recommendations and if not, what difficulties they encountered.

Results:

One hundred and eleven PWD received recommendations, of which 40 (36.0%) agreed and
enrolled in the services while 71 (64%) declined. Thematic analysis of the reasons for non-uptake
revealed 3 themes: PWD-related factors (e.g., refusal, functional improvement or decline), caregiverrelated
factors (adequacy of care at home, other care arrangements), and service-related factors (e.g.,
cost, timing).

Conclusion:

Despite adequate information, there are other reasons for non-uptake of dementia- related
services, some of which should be addressed to improve service updates and to provide better care for
PWD.
Nanotherapeutics in Neuropathologies: Obstacles, Challenges and Recent Advancements in CNS Targeted Drug Delivery Systems
Authors: Patel Vimal , Chavda Vishal , Shah Jigar
Published: August 2020

Neurology and associated nanotherapeutics are a complex field in terms of therapeutics
and neurological disorder complexity. The brain is an intricate appendage and requires more precise
embattled treatment for the particular diseases and hence it is a broad scale for developing
more targeted drug deliveries. The brain is one of the most inaccessible tissues of the body due to
the existence of the blood-brain barrier (BBB), thus delivery of drugs inside the brain is a striking
dare and it is also tricky to treat central nervous system (CNS) complications pharmacologically.
The therapeutic aspiration is to accomplish the lowest drug meditation in the brain tissues so as to
gain favoured therapeutic results. To devastate this obstacle, nanotechnology is engaged in the
field of targeted brain drug delivery and neuropathology targeting. These carriers hold myriad abilities
as they may augment the drug delivery into the brain by shielding them from degradation and
prolonging their transmission in the blood, as well as promoting their transport through the BBB.
Nanopharmaceuticals are quickly sprouting as a new avenue that is engaged with the drug-loaded
nanocarriers to demonstrate unique physicochemical properties and tiny size range for penetrating
the central nervous system. The enchantment behind their therapeutic achievement is the condensed
drug dose and inferior toxicity, whereby restricting the therapeutic compound to the specific
site. Therefore, in this article, we have tried to recapitulate the advances of the novel scopes for
the brain targeted drug delivery for complex neurological disorders.
Insights into Machine Learning-based Approaches for Virtual Screening in Drug Discovery: Existing Strategies and Streamlining Through FP-CADD
Authors: Hussain Waqar , Rasool Nouman , Khan Yaser Daanial
Published: August 2020

Background:

Machine learning is an active area of research in computer science by the availability of big data collection of all sorts prompting interest in the development of novel tools for data mining. Machine learning methods have wide applications in computer-aided drug discovery methods. Most incredible approaches to machine learning are used in drug designing, which further aid the process of biological modelling in drug discovery. Mainly, two main categories are present which are Ligand-Based Virtual Screening (LBVS) and Structure-Based Virtual Screening (SBVS), however, the machine learning approaches fall mostly in the category of LBVS.

Objectives:

This study exposits the major machine learning approaches being used in LBVS. Moreover, we have introduced a protocol named FP-CADD which depicts a 4-steps rule of thumb for drug discovery, the four protocols of computer-aided drug discovery (FP-CADD). Various important aspects along with SWOT analysis of FP-CADD are also discussed in this article.

Conclusions:

By this thorough study, we have observed that in LBVS algorithms, Support vector machines (SVM) and Random forest (RF) are those which are widely used due to high accuracy and efficiency. These virtual screening approaches have the potential to revolutionize the drug designing field. Also, we believe that the process flow presented in this study, named FP-CADD, can streamline the whole process of computer-aided drug discovery. By adopting this rule, the studies related to drug discovery can be made homogeneous and this protocol can also be considered as an evaluation criterion in the peer-review process of research articles.
In Silico Evaluation of Various Signal Peptides to Improve Secretion of Humulin Protein in E. coli Host
Authors: Kavousipour Soudabe , Barazesh Mahadi , Mohammadi Shiva , Abdollahpour- Alitappeh Meghdad , Fallahi Shirzad , Shakarami Amir , Hajmohammadi Zeynab
Published: August 2020

Background:

Escherichia coli host has been the workhorse for the production of heterologous
proteins due to simplicity of use, low cost, availability of various expression vectors, and a
plethora of knowledge on its genetic characteristics, but without a suitable signal sequence, this
host cannot be used for the production of secretory proteins. Humulin is a form of insulin used to
treat hyperglycemia caused by types 1 and 2 diabetes. To improve expression and make a straightforward
production of Humulin protein, we chose a series of signal peptides.

Objective:

The aim of this study was to predict the most excellent signal peptides to express secretory
Humulin in E. coli organism.

Methods:

Therefore, to forecast the most excellent signal peptides for expression of Humulin in
Escherichia coli, 47 signal sequences from bacteria organisms were elected and the most imperative
elements of them were studied. Hence, signal peptide probability along with physicochemical
features was evaluated by signal 4.1, and Portparam, PROSO II servers respectively. Later, the in-
-silico cloning in a known pET28a plasmid system also estimated the possibility of best signal peptide+
Humulin expression in E. coli.

Results:

The outcomes demonstrated that among 47 signal peptides only 2 signal peptides can be
considered as suitable signal peptides.

Conclusion:

Ultimately protein yebF precursor (YEBF_ECOLI) and protein yebF precursor
(YEBF_YERP3) were suggested as the most excellent signal peptides to express Humulin (With D
scores 0.812 and 0.623, respectively). Although verification of these results warrants experimental
analysis.
BCl3 Catalyzed, Solvent Free Protocol for the Synthesis of Dihydropyrano[ 3,2-b] Chromenediones
Authors: Suryawanshi Vikas B. , Momin Kalimoddin I. , Dawle Jairaj K. , Mathapati Sushil R.
Published: August 2020

:

Solvent free synthesis of dihydropyrano[3,2-b]chromenediones was formulated via multicomponent
reactions of kojic acid, dimedone and several substituted aromatic aldehydes catalyzed with
BCl3. Reactions progressed efficiently and the corresponding heterocyclic products were obtained in
good to high yields within short period. The developed protocol is one of the better and efficient alternative
methods for the synthesis of dihydropyrano[3,2-b]chromenediones. The simple reaction procedure,
easy separation of products, radially available catalyst are certain benefits of this reported protocol.
Warm Reactive Anti-A1 Agglutinin in an A2B individual: A Rare Case with Review of Literature
Authors: Raturi Manish , Kusum Anuradha
Published: August 2020

The prevalence of the major subgroup of A as A1 in almost 80% of the A group population
is a known fact. A2 and the remaining subgroups such as Aend, Am, Ax etc comprise the remaining
population, based on erythrocyte agglutinability and various serological reactions. These A subgroups
can often result in an ABO typing discrepancy. Anti-A1 antibody often appears as an irregular
cold agglutinin in the sera of A2 or A2B individuals who lack the corresponding antigen. Rather
notably, the literature suggests that 1% to 8% of A2 and 22% to 35% of A2B individuals possess an
allo-anti-A1 in their sera, which reacts at a temperature below 25°C. Although routinely, it does not
pose any problem either during or post blood transfusion, however, the literature reports of hemolysis
happening in procedures that are performed at lower temperatures, particularly in hypothermic
situations. We report herein, a case of a massively bleeding A2B Indian lady after the expulsion of
her dead fetus and an underlying uterine fibroid having a warm reactive allo-anti-A1 agglutinin that
warranted an urgent blood transfusion management.
Fatty Acids Recommendations: Controversies and Updates
Authors: Abdelhadi Nadine N. , Ahmad Mousa N.
Published: August 2020

Background:

The reduction in the intake of dietary fat has traditionally been the cornerstone
of dietary recommendations of many of the leading health organizations as a key measure to
prevent cardiometabolic diseases. However, dietary fat recommendations are sometimes contrasting.
In addition, many consumers and food manufacturers are still confused about the effects of fatty
acids on coronary heart disease after decades of focus on the low-fat diet.

Objectives:

To provide an overview of the recently available evidence on the effect of fatty acids
on cardiometabolic risk and the various dietary recommendations related to reducing fat in the diet.
It will also highlight the effect of the isocaloric substitution of fat by other macronutrients.

Methodology:

The Cochrane Central Register of Controlled Trials, PubMed, Medline, Clinical
trials.gov, Google Scholar, Science Direct, ADI, and WHO database were searched through to
March 2020.

Results:

Recent evidence demonstrates that higher dietary intakes of saturated fatty acids are associated
with an increased risk of coronary heart disease which is consistent with the previous scientific
evidence. In addition, recent findings indicate that replacing total saturated fatty acids with polyunsaturated
fatty acids, monosaturated fatty acids and high-quality carbohydrates reduces cardiometabolic
risk.

Conclusion:

Higher dietary intakes of saturated fatty acids are associated with an increased coronary
heart disease risk. Recent scientific evidence highlights the importance of replacing total saturated
fat with more healthy alternatives including polyunsaturated fatty acids, monosaturated fatty
acids, and high-quality carbohydrates which is consistent with the latest recommendations of the
updated guidelines.
Integrated Quality by Design (QbD) Approach for Stability Indicating RPHPLC Method for the Estimation of Tadalafil Hydrochloride in Bulk Drug and Pharmaceutical Formulations
Authors: Patil Prajakta H. , Gurupadayya Bannimath , Hamrapurkar Poornima
Published: August 2020

Background:

In view of the current FDA standardization and product quality control criteria,
Quality by design approach for analytical methods is gaining importance to develop a robust analytical
method. A new Quality by Design approach by RP-HPLC was developed and validated for the
quantification and purification of Tadalafil hydrochloride and its tablet formulations.

Objective:

The objective of the study was to develop and validate a simple, robust, and accurate method by QbD approach
for detection Tadalafil hydrochloride and its degradation products in bulk drug and tablet formulation.

Methods:

The chromatographic separation was performed on JASCO Crest Pack RPC18 column
(250mm×4.6mm, 5μm) with mobile phase A consisting of a mixture of Acetonitrile: Methanol (40:20
v/v); and mobile phase B: 0.01M Ammonium acetate in water pH adjusted to 3.50± 0.05 with glacial
acetic acid with 1.0ml/min flow rate at 285nm. Box-Behnken's three-level, 3-factorial design was employed
to create and analyze a "Design Space" (DoE). This design was statistically analyzed by ANOVA,
counter-plot, and 3D response surfaces plots, which demonstrated that the model was statistically
significant. The developed method was validated as per the ICH guidelines Q2 (R1).

Results and Discussion:

The tadalafil hydrochloride showed good regression (R2>0.9995) within tested
ranges, and the percent recovery was found to be 98% in the marketed formulation.

Conclusion:

The method was found to be highly specific without the interference of impurities and degradation products
of tadalafil hydrochloride. For quantification and routine quality control of tadalafil and its marketed formulation, the
stability-indicating the RP-HPLC method could thus be extended.
Elaboration and Validation of HPLC/DAD Method for Quality Control of Products Containing Cannabidiol
Authors: Andonova Lily , Ivanov Ervin , Pencheva Ivanka , Konstantinov Spiro
Published: August 2020

Background:

Cannabidiol (CBD) is the main, physiologically active, but psycho-inactive
constituent of the glandular hairs of Cannabis sativa. CBD exhibits diverse pharmacological activities
and it is used as an anticonvulsant, sedative and hypnotic agent. Other biological properties shown by
CBD are antipsychotic, anti-inflammatory and neuroprotective.

Objective:

The aim of this study is to develop, validate and apply high performance liquid chromatography
(HPLC/DAD) method with diode array detection for identification and assay of CBD in food
supplements obtained by different types of extraction and purification.

Method:

HPLC method with isocratic elution using column C18 ODS, 250 x 4.6, 100 Å, 5 μm, mobile
phase - a mixture of acetonitrile and water in ratio 80:20 v/v, a flow rate of 1.0 ml/min and DAD detection
at 220 nm, was used.

Results:

The method was developed and validated according to European Pharmacopoeia and International
Council for Harmonisation of Technical Requirements for Pharmaceuticals for Human Use
(ICH). For the analytical purposes, parameters like repeatability, linearity, accuracy, LOD, LOQ, specificity
and system suitability were studied. The developed method was successfully applied on a series
of food supplements containing CBD.

Conclusion:

The developed method is of practical importance for the determination of purity, identification
and assay tests of food supplements containing CBD extract in accordance with EU regulation
concerning food authorizations because it is useful for analytical tests for identification, purity determination
and assay of products containing CBD extract and could serve as part of the testing process in
the pharmaceutical industry.
Thymoquinone Inhibits Proliferation and Migration of MDA-MB-231 Triple Negative Breast Cancer Cells by Suppressing Autophagy, Beclin-1 and LC3
Authors: Ünal Tuba D. , Hamurcu Zuhal , Delibaşı Nesrin , Çınar Venhar , Güler Ahsen , Gökçe Sevda , Nurdinov Nursultan , Ozpolat Bulent
Published: August 2020

Background:

Triple Negative Breast Cancer (TNBC) is an aggressive and highly heterogeneous subtype of breast cancer associated with poor prognosis. A better understanding of the biology of this complex cancer is needed to develop novel therapeutic strategies for the improvement of patient survival. We have previously demonstrated that Thymoquinone (TQ), the major phenolic compound found in Nigella sativa, induces anti-proliferative and anti-metastatic effects and inhibits in vivo tumor growth in orthotopic TNBC models in mice. Also, we have previously shown that Beclin-1 and LC3 autophagy genes contributes to TNBC cell proliferation, migration and invasion, suggesting that Beclin-1 and LC3 genes provide proto-oncogenic effects in TNBC. However, the role of Beclin-1 and LC3 in mediating TQ-induced anti-tumor effects in TNBC is not known.

Objective:

To investigate the effects of TQ on the major autophagy mediators, Beclin-1 and LC3 expression, as well as autophagic activity in TNBC cells.

Methods:

Cell proliferation, colony formation, migration and autophagy activity were evaluated using MTS cell viability, colony formation assay, wound healing and acridine orange staining assays, respectively. Western blotting and RT-PCR assays were used to investigate LC3 and Beclin-1 protein and gene expressions, respectively, in MDA-MB-231 TNBC cells in response to TQ treatments.

Results:

TQ treatment significantly inhibited cell proliferation, colony formation, migration and autophagic activity of MDA-MB-231 cells and suppressed LC3 and Beclin-1 expressions. Furthermore, TQ treatment led to the inhibition of Integrin-β1, VEGF, MMP-2 and MMP-9 in TNBC cells.

Conclusion:

TQ inhibits autophagic activity and expression of Beclin-1 and LC3 in TNBC cells and suppresses pathways related to cell migration/invasion and angiogenesis, including Integrin-β1, VEGF, MMP-2 and MMP- 9, suggesting that TQ may be used to control autophagic activity and oncogenic signaling in TNBC.
Iterative Framework and Privacy Preservation in Reciprocal Recommendation
Authors: Tabassum Nazia , Ahmad Tanvir
Published: August 2020

Although there are many reciprocal recommenders based on different strategies which
have found applications in different domains but in this paper we aim to design a common framework
for both symmetric as well as asymmetric reciprocal recommendation systems (in Indian context),
namely Job recommendation (asymmetric) and Online Indian matrimonial system (symmetric).
The contributions of this paper is multifold: i) Iterative framework for Reciprocal Recommendation
for symmetric as well as asymmetric systems. ii) Useful information extracted from explicit
as well as implicit sources which were not explored in the existing system (Free-text mining in Indian
Matchmaking System). iii) Considering job-seekers’ personal information like his marital status,
kids, current location for suggesting recommendation. iv) Proposed Privacy preservation in the proposed
framework for Reciprocal Recommendation system. These parameters are very important
from practical viewpoint of a user and we have achieved improved efficiency through our framework
as compared to the existing system.
Stability and Thermal Conductivity of Tri-hybrid Nanofluids for High Concentration in Water-ethylene Glycol (60:40)
Authors: Ramadhan Anwar I. , Azmi Wan H. , Mamat Rizalman
Published: August 2020

Background:

Research has been focused on improving the thermal properties of single
nanofluid components for recent years. Therefore, hybrid nanofluids or composites have been developed
to improve heat transfer performance. Stability and thermal conductivity of Al2O3-TiO2-
SiO2 nanoparticles are suspended in the fluid base of water (W) and ethylene glycol (EG) mixture
with volume ratio of 60:40.

Methods:

Experiments were tri-hybrid nanofluid stability was investigated for volume concentration
of 0.5 ~ 3.0%, and temperature conditions from 30 to 70°C for thermal conductivity measurements
using a KD2 Pro Thermal Properties Analyzer. The experimental results show that the
tri-hybrid nanofluid stability analysis was performed using a stable UV-Vis method for up to 30
days after preparation with 10 hour sonication time.

Results:

Comparison of data concentration ratios with sedimentation for single, hybrid, and trihybrid
nanofluids yielding a stable tri-hybrid nanofluid with 80-90% value. Evaluation of zeta potential
for tri-hybrid nanofluids yielded 63.72 mV in excellent stability classification. Sedimentation
of this visual observation is influenced by the gravity of the movement of particles in the tube
after 30 days.

Conclusion:

The highest thermal conductivity for tri-hybrid nanofluids was obtained at 3.0% and a
maximum increase of up to 27% higher than that of the basic fluid (EG/W). Tri-hybrid nanofluids
with a concentration of 0.5% gave the lowest effective thermal conductivity of 13.4% at 70°C.
Does the Oxazolidinone Derivatives Constitute a Functional Approach for Cancer Therapy?
Authors: Ramalho Eduardo Augusto Vasconcelos de Freitas , Pitta Marina Galdino da Rocha , Neto Hernando de Barros Siqueira , Pitta Ivan da Rocha
Published: August 2020

In the last four decades, the emphasis was laid on the research of small organic molecules
with potential anti-cancer activity. Linezolid was the first oxazolidinone derivative approved by FDA
for MRSA treatment. Despite its major role in antimicrobial activity, these molecules display other
properties, also serving as an antitumor agent. The importance of drug repurposing could be highlighted
by the use of Oxazolidinone derivatives in pre-clinical studies, which are able to act through
different pathways, such as partial agonist of transcription factor PPAR-γ, an inhibitor of key enzymes
related to hormone-dependent disorders and even on sphingolipid metabolism as well. The purpose of
this short review is to discuss the application of oxazolidinone derivatives as an antitumor agent by
highlighting the most promising molecules studied by many research groups worldwide. Main biological
activity against several tumor cell lines, including hematopoietic and solid cancer cell lines have
been discussed. In addition, this study intends to report how different types of oxazolidinone derivatives
can act as antitumor agents describing their distinct mechanisms of action based on their targets.
Maximum Temperature Through a Yttrium Stabilized Zirconia Ceramic After Er,Cr:YSGG Laser Irradiation
Authors: Stringer Laurel , Malley Sarah , Hutto Darrell M. , Griggs Jason A. , Salazar Marocho Susana M.
Published: August 2020

Background:

The most common approach to remove yttria stabilized zirconia (YSZ)
fixed-dental prostheses (FDPs) is by means of diamond burs attached to a high-speed handpiece.
This process is time-consuming and destructive. The use of lasers over mechanical instrumentation
for removal of FDPs can lead to efficient and predictable restoration retrievability. However, the
heat produced might damage the tooth pulp (>42˚C).

Objective:

The purpose of this study was to determine the maximum temperature (T) reached during
the use of different settings of the erbium, chromium:yttrium-scandium-gallium-garnet
Er,Cr:YSGG laser through a YSZ ceramic.

Methods:

YSZ slices (1 mm thick) were assigned to 7 groups. For the control group, a diamond
bur was used to cut a 1 mm groove into the YSZ slices. For the 6 experimental groups, the laser
was operated at a constant combination of 33% water and 66% air during 30 s with two different
power settings (W) at three frequencies (PPS), as follows (W/PPS): 2.5/20, 2.5/30, 2.5/45, 4.5/20,
4.5/30, 4.5/45. The T through the YSZ slice was recorded in degrees Celsius by using a digital thermometer
with a K thermocouple.

Results:

The median T of the control group was 26.5˚C. The use of 4.5 W resulted in the median T
(˚C) of 44.2 at 20 PPS, 53.3 at 30 PPS, and 58.9 at 45 PPS, while 2.5 W showed 34.6, 31.6, and
25.0 at 20, 30, and 45 PPS, respectively. Kruskal-Wallis one-way ANOVA showed that within
each power setting, the T was similar. The high power and lowest frequency (4.5/20) showed no
significant difference from the 2.5 W settings and the control group.

Conclusion:

The lower power setting (2.5 W) is a potential method for the use of the Er,Cr:YSGG
laser to debond YSZ structures. The higher power (4.5 W) with high frequencies (30 and 45 PPS)
is unsuitable.