bluuebunny/crossref_metadata_2025_split huggingface dataset:
Negative Correlation Between Serum Levels of Homocysteine and Apolipoprotein M
Authors: Wei J. , Yu Y. , Feng Y. , Zhang J. , Jiang Q. , Zheng L. , Zhang X. , Xu N. , Luo G. 
Published: March 2019

Background:
Homocysteine (Hcy) has been suggested as an independent
risk factor for atherosclerosis. Apolipoprotein M (apoM) is a constituent of the HDL
particles. The goal of this study was to examine the serum levels of homocysteine and
apoM and to determine whether homocysteine influences apoM synthesis.

Methods:
Serum levels of apoM and Hcy in 17 hyperhomocysteinemia (HHcy) patients
and 19 controls were measured and their correlations were analyzed. Different
concentrations of homocysteine (Hcy) and LY294002, a specific phosphoinositide 3-
kinase (PI3K) inhibitor, were used to treat HepG2 cells. The mRNA levels were
determined by RT-PCR and the apoM protein mass was measured by western blot.

Results:
We found that decreased serum apoM levels corresponded with serum HDL
levels in HHcy patients, while the serum apoM levels showed a statistically significant
negative correlation with the serum Hcy levels. Moreover, apoM mRNA and protein
levels were significantly decreased after the administration of Hcy in HepG2 cells, and
this effect could be abolished by addition of LY294002.

Conclusions:
resent study demonstrates that Hcy downregulates the expression of
apoM by mechanisms involving the PI3K signal pathway.
The Mitochondrial tRNAHis G12192A Mutation May Modulate the Clinical Expression of Deafness-Associated tRNAThr G15927A Mutation in a Chinese Pedigree
Authors: Ding Yu , Teng Yao-Shu , Zhuo Guang-Chao , Xia Bo-Hou , Leng Jian-Hang 
Published: March 2019

Background:Mutations in mitochondrial tRNA (mt-tRNA) genes have been found to be associated with both syndromic and non-syndromic hearing impairment. However, the pathophysiology underlying mt-tRNA mutations in clinical expression of hearing loss remains poorly understood.Objective:The aim of this study was to explore the potential association between mttRNA mutations and hearing loss.Methods and Results:We reported here the molecular features of a pedigree with maternally transmitted non-syndromic hearing loss. Among 12 matrilineal relatives, five of them suffered variable degree of hearing impairment, but none of them had any medical history of using aminoglycosides antibiotics (AmAn). Genetic screening of the complete mitochondrial genomes from the matrilineal relatives identified the coexistence of mt-tRNAHis G12192A and mt-tRNAThr G15927A mutations, together with a set of polymorphisms belonging to human mitochondrial haplogroup B5b1b. Interestingly, the G12192A mutation occurred 2-bp from the 3’ end of the TψC loop of mt-tRNAHis, which was evolutionarily conserved from various species. In addition, the well-known G15927A mutation, which disrupted the highly conserved C-G base-pairing at the anticodon stem of mt-tRNAThr, may lead to the failure in mt-tRNA metabolism.:Furthermore, a significant decreased in ATP production and an increased ROS generation were observed in polymononuclear leukocytes (PMNs) which were isolated from the deaf patients carrying these mt-tRNA mutations, suggested that the G12192A and G15927A mutations may cause mitochondrial dysfunction that was responsible for deafness. However, the absence of any functional mutations/variants in GJB2, GJB3, GJB6 and TRMU genes suggested that the nuclear genes may not play important roles in the clinical expression of non-syndromic hearing loss in this family.Conclusion:Our data indicated that mt-tRNAHis G12192A mutation may increase the penetrance and expressivity of deafness-associated m-tRNAThr G15927A mutation in this family.
The Prognostic and Clinicopathologic Characteristics of OCT4 and Lung Cancer: A Meta-Analysis
Authors: Li Hui , Wang Liwen , Shi Shupeng , Xu Yadong , Dai Xuejiao , Li Hongru , Wang Jing , Zhang Qiong , Wang Yonggang , Sun Shuming , Li Yanping 
Published: March 2019

Objective:The relationship between OCT4 and clinicopathological features in lung cancer is shown to be controversial in recent publications. Therefore, we conducted this meta-analysis to quantitatively investigate the prognostic and clinicopathological characteristics of OCT4 in lung cancer.Methods:A comprehensive literature search of the PubMed, EMBASE, Cochrane Library, WOS, CNKI and Wanfang databases was performed to identify studies. Correlations between OCT4 expression and survival outcomes or clinicopathological features were analyzed using meta-analysis methods.Results:Twenty-one studies with 2523 patients were included. High OCT4 expression showed a poorer overall survival (OS) (univariate: HR= 2.00, 95% CI = (1.68, 2.39), p<0.0001; multivariate: HR= 2.43, 95% CI = (1.67, 3.55), p<0.0001) and median overall survival (MSR = 0.51, 95% CI = (0.44, 0.58), p < 0.0001), disease-free survival (DFS) (HR= 2.18, 95% CI = (1.30, 3.67), p = 0.003) and poorer disease-specific survival (DSS) (HR= 2.23, 95% CI = (1.21, 4.11), p = 0.010). Furthermore, high OCT4 expression was found to be related with lower 5 year disease-specific survival rate (OR= 0.24, 95% CI = (0.14, 0.41), p<0.0001) and 10 year overall survival rate (OR= 0.22, 95% CI = (0.12, 0.40), p=0.0001). Additionally, OCT4-high expression was also strongly associated with higher clinical TNM stage, lymph node metastasis, tumor distant metastasis, higher histopathologic grade, but not related with gender, smoking status, tumor size and histologic type of lung cancer.Conclusion:OCT4 over-expression in lung cancer was strongly related to poorer clinicopathological features and worse survival outcomes, which suggests that OCT4 could be a valuable prognostic marker in lung cancer.
Pharmaceutical Inhibition of Neddylation as Promising Treatments for Various Cancers
Authors: Yin Lina , Xue Yuanyuan , Shang Qiannan , Zhu Haichao , Liu Meihua , Liu Yingxiang , Hu Qingzhong 
Published: March 2019

Background:
Neddylation is an important post-translational modification of proteins, in
which a NEDD8 (neural-precursor-cell-expressed developmentally down-regulated 8) is covalently
introduced onto the substrate proteins to regulate their functions and homeostasis. As neddylation is
frequently up-regulated in various cancers, its interference was proposed as a promising therapy of
related diseases.

Objective:
The recent advances in developing neddylation interfering agents were summarized to provide
an overview of current achievements and perspectives for future development.

Methods:
Reports on neddylation interfering agents were acquired from Pubmed as well as the EPO
and clinicaltrials.gov websites, which were subsequently analyzed and summarized according to targets,
chemical structures and biological activities.

Results:
Neddylation as a sophisticated procedure comprises proteolytic processing of NEDD8 precursor,
deploying conjugating enzymes E1 (NAE), E2 (UBE2M and UBE2F) and various E3, as well as
translocating NEDD8 along these conjugating enzymes sequentially and finally to substrate proteins.
Among these nodes, NAE, UBE2M and the interaction between UBE2M-DCN1 have been targeted by
small molecules, metal complexes, peptides and RNAi. A NAE inhibitor pevonedistat (MLN4924) is
currently under evaluation in clinical trials for the treatment of various cancers.

Conclusion:
With multiple inhibitory approaches of neddylation being introduced, the development of
neddylation interference as a novel cancer therapy is significantly boosted recently, although its efficacy
and the best way to achieve that are still to be demonstrated in clinical trials.
Synthesis and Antioxidant Evaluation of Dihydropyrimidinone Integrated Pyrazoles
Authors: Padmavathy Krishnaraj , Sutha Peramasivan , Krishnan Kannan G. , Kumar Chandran U. , Iniyaval Shunmugam , Ramalingan Chennan 
Published: March 2019

:
A series of novel ethyl 6-[2-(3-aryl-1-phenyl-1H-pyrazol-4-yl)vinyl]-2-oxo-4-phenyl-
1,2,3,4-tetrahydropyrimidine-5-carboxylates (9a-9d) has been synthesized by adopting a multistep synthetic
strategy. The structure of the targets was confirmed on the basis of physical and spectral techniques.
The synthetically achieved targets were evaluated for their antioxidant activity by in-vitro
DPPH free radical scavenging assay. Of the chemical entities screened, most of them exhibit good to
better radical scavenging profile and among those, the nitro substituent bearing molecule 9c displayed
the highest activity (82%) with IC50 value 621.6 μM. Further, as a representative molecule, compound
9a has been subjected to density functional theory calculations employing B3LYP method with
6311(++G) basis set to optimize its structure.
Molecular Hybrids of N-Phthaloylglycyl Hydrazide and Hydrazinecarbothioamide with Anti-inflammatory and Anti-oxidant Activities
Authors: Gera Ankur , Mohan Chander , Madan Jitender , Arora Sandeep 
Published: March 2019

Background:Oxidative stress due to high levels of reactive organic species is the cause of the progression of inflammation in various diseases. The molecules possessing both anti-inflammatory and antioxidant activity can be the promising key to treat inflammatory diseases. Phthalimide and hydrazinecarbothioamide are anti-inflammatory and anti-oxidant pharmacophores.Objective:Molecular hybrids possessing above two pharmacophores were designed. A series of N-phenyl substituted 2-(2-(1,3-dioxoisoindolin-2-yl)acetyl)-N-phenylhydrazine-1-carbothioamide (CGS compounds) was synthesized and evaluated for biological activities.Methods:N-phthaloylglycyl hydrazide was reacted with unsubstituted/substituted phenyl isothiocyanates to yield CGS compounds. Synthesized compounds were evaluated for in vivo anti-inflammatory activity in carrageenan rat paw edema model, and in vitro anti-oxidant activity by DPPH assay. Levels of TNF-α and oxidative stress at the site of inflammation were measured. The genetic algorithm-PLS regression based QSAR model correlating the effect of N-phenyl substituent on the anti-inflammatory activity was developed. Further, the interaction of the active compound in the TNF-α binding pocket was studied by in silico docking.Results:Compound containing the 2-OCH3, 4-NO2 (CGS-5); 4-CF3 (CGS-9); 4-NO2 (CGS-3) showed significant anti-inflammatory activity (percentage inhibition of paw edema after 3 hour = 58.24, 50.38, 40.05, respectively) and potent anti-oxidant activity (IC50 =0.045, 0.998, 0.285 μg/ml, respectively). Reduced levels of TNF- α and increased levels of GSH were observed for the above three compounds. Descriptors for QSAR model identified by GA-PLS were WPSA1, Weta1unity, WDunity, SC3, VC5, MlogP, and WTPT3. The identified model was highly predictive, and value of root mean square error of prediction for internal (leave one out) and external validation was: 1.579, 1.325.Conclusion:Molecular hybrids of phthalimide and hydrazinecarbothioamide were synthesized. Some of the compounds possessed promising anti-inflammatory and anti-oxidant activities.
Anti-Trypanosoma cruzi Activity and Molecular Docking Studies of 1Hpyrazolo[ 3, 4-b]pyridine Derivatives
Authors: da Silva Lima Camilo Henrique , de Araujo Vanelis Soares Júlio César , de Sousa Ribeiro Joana Lucius , Muri Estela Maris Freitas , de Albuquerque Sérgio , Dias Luiza Rosaria Sousa 
Published: March 2019

Background:
Untargeted studies led to the development of some pyrazolopyridine
derivatives for the antiparasitic profile, particularly the derivatives containing the structural
carbohydrazide subunit. In this work, we proceeded in the biological screening of 27 N’- (substitutedphenylmethylene)-
4-carbohydrazide-3-methyl-1-phenyl-1H-pyrazolo[3, 4-b]pyridine derivatives against
T. cruzi as well as the cytotoxic evaluation. To obtain more information about the trypanocidal
activity of this class of compounds, we carried out molecular docking simulations to get an insight
into putative targets in T. cruzi.

Methods:
The assays were evaluated against both trypomastigote and amastigote forms of T. cruzi
and cytotoxicity assays on LLCMK2 cells. The predominant conformational compounds were
analyzed and molecular docking simulations performed.

Results:
The results from trypanocidal activity screening of this series showed that just the
compounds with phenyl group at C-6 position exhibited activity and the N’-4-hydroxyphenylmethylene
derivative presented the best profile against both trypomastigote and amastigote
forms of T. cruzi. Docking simulation results showed that this compound has a binding affinity with
both CYP51 and cruzain targets of T. cruzi.

Conclusion:
Our results indicate that the hydroxyl substituent at the N’-substituted-phenylmethylene
moiety and the phenyl ring at C-6 of 1H-pyrazolo[3,4-b]pyridine system are relevant for the
trypanocidal activity of this class of compounds. Also, docking simulations showed that activity
presented can be related to more than one target of the parasite.
Effects of Coenzyme Q10 Supplementation on Serum Adiponectin Levels: A Systematic Review and Meta-Analysis of Randomized Controlled Trials
Authors: Nazary-Vannani Ali , Ghaedi Ehsan , Salamat Shekoufeh , Sayyaf Afsaneh , Varkaneh Hamed K. , Mohammadi Hamed , Djalali Mahmoud 
Published: March 2019

Background:
Adiponectin, a well-known adipokine plays a number of regulatory actions
in human body metabolism. Decreased levels of adiponectin have been reported in type 2 diabetes
mellitus, cardiovascular diseases, metabolic syndrome and hypertension. Coenzyme Q10 (Co Q10)
is a fat-soluble antioxidant substance which has been reported to be effective in several metabolic
disturbances such as insulin resistance and inflammation.

Objective:
Present systematic review and meta-analysis were performed to assess the effects of
CoQ10 supplementation on adiponectin serum level.

Methods:
A comprehensive search was performed in electronic databases including EMBASE,
Google scholar, and PubMed up to January 2018. A meta-analysis of eligible studies was performed
using random effects model to estimate pooled effect size of CoQ10 supplementation on adiponectin.

Results:
A total of 209 subjects were recruited from 5 eligible studies. Meta-analysis did not suggest
any significant effect of CoQ10 supplementation on adiponectin serum level (0.240 mg/dl,
95%CI: -0.216, 0.696, P= 0.303), without significant heterogeneity between included studies (I2=
40.9%, p= 0.149).

Conclusion:
Although present meta-analysis did not indicate any significant effects of CoQ10 supplementation
on serum adiponectin levels but future long-term dose-response trials are needed before
any firm conclusion.
Adverse Drug Reactions of Anti-Epileptic Drugs in Children with Epilepsy: A Cross-Sectional Study
Authors: Kaushik Sundeep , Chopra Deepti , Sharma Suvasini , Aneja Satinder 
Published: March 2019

Background:
Adverse drug reactions (ADRs) due to antiepileptic drugs (AEDs) in children
contribute to poorer patient outcomes. However, reliable data ragarding such ADRs is not
available.

Objectives:
Thus, the aim of the present study was to determine the incidence and patterns of ADRs
of antiepileptic drugs in children aged 2-17 years presenting to a tertiary care teaching hospital.

Methods:
An observational study was conducted in the Department of Pediatrics, Kalawati Saran
Children’s Hospital for a period of one year. Two hundred consecutive eligible patients (aged 2-17
yrs with epilepsy on AED) with consenting parents were enrolled. ADRs were noted using Paediatric
Epilepsy Side Effect Questionnaire (PESQ) at clinic visits and any other ADRs reported by parents
were also recorded. Causality, severity and avoidability assessments were done.

Results:
The mean age was 10.5 ± 3.6 years. A total of 139 ADRs occurred in 97 patients. One
hundred and nine ADRs were reported by use of PESQ, in addition, 30 ADRs were reported by parents.
Poor school result (33.8%) was the commonest ADR. Valproate (61.9%) was the main drug
causing ADRs. Valproate, when used in polytherapy, was associated with more number of children
experiencing ADRs (72.2%). The most common add on drug was clobazam (42.3%). Children with
poorly controlled epilepsy were associated with more ADRs. Causality assessment revealed that
91.3% of the ADRs were probable. Most (94.9%) ADRs were of ‘mild’ category and 95.7% were
probably preventable. Treatment was discontinued only in 6 patients of phenytoin toxicity.R

Conclusion:
Cognitive and neurological problems were the most common ADRs seen in children
with epilepsy. Polytherapy significantly increases the likelihood of ADRs in children.
Optimization of Microemulgel for Tizanidine Hydrochloride
Authors: Jagdale Swati , Brahmane Sujata , Chabukswar Anuruddha 
Published: March 2019

Background:
Tizanidine hydrochloride acts centrally as a muscle relaxant. It is
used for the treatment of painful muscle spasm, spasticity associated with multiple sclerosis
or spinal cord injury and treatment of muscle spasticity in spinal cord disease. Tizanidine
hydrochloride belongs to BCS class II. It has low oral bioavailability and short halflife.
Incorporating this drug in microemulgel is an excellent way to overcome problems associated
with the drug.

Objective:
Present research work was aimed to develop and optimize a microemulsion
based gel system for tizanidine hydrochloride.

Methods:
Screening of oil, surfactant and co-surfactant was carried out. Ternary phase diagram
was constructed to obtain concentration range of components. The prepared microemulsion
was evaluated for pH, globule size, zeta potential, conductivity, density and viscosity.
32 level factorial design was applied to study the effect of concentration of carbopol
934 and HPMC K15M on % cumulative drug release and viscosity of microemulgel using
software Design Expert. Microemulgel was evaluated for pH, spreadability, viscosity, syneresis,
drug content, bioadhesive strength, in-vitro as well as ex-vivo diffusion study.

Results:
Microemulsion was prepared by using isopropyl myristate as oil, tween 80 as a
surfactant and transcutol P as cosurfactant. Largest transparent microemulsion region was
found with Smix ratio of 1:1. FE-SEM showed globule size 28μm for batch B1 and zeta
potential was -1.27mV indicating good stability of the microemulsion. Optimised batch
was F6 which showed 92% drug release within 8 hours. It followed the Korsmeyer-Peppas
model.

Conclusion:
A stable, effective and elegant microemulgel formulation, exhibiting good
in-vitro and ex-vivo drug release was formulated.
Thrombotic Events in Homozygotes with a Proven or Highly Probable Arg304Gln Factor VII Mutation (FVII Padua)1): Only Limited Replacement Therapy is Needed in Case of Surgery
Authors: Girolami Antonio , Cosi Elisabetta , Ferrari Silvia , Girolami Bruno , Randi Maria L. 
Published: March 2019

Objective:To investigate the prevalence of thrombotic events among patients with proven or highly probable homozygosis for the Arg304Gln (Factor VII Padua) defect or compound heterozygosis containing the Arg304Gln mutation.Methods:Homozygotes and compound heterozygotes proven by molecular studies to have the Arg304Gln mutation were gathered from personal files and from two PubMed searches. In addition, patients with probable homozygosis on the basis of clotting tests (discrepancies among Factor VII activity levels according to the tissue thromboplastin used) were also gathered.Results:30 proven homozygotes and 17 probable ones were gathered together with 8 compound heterozygotes. In the latter use, the associated mutation was Cys135Arg (twice), Gly180Arg, Arg304Trp, Arg315Trp, His348Gln, Gly365Cys. The prevalence of venous thrombotic events was 16.6, 11.8 and 11.1 percent, respectively for the three groups of patients. Heterozygotes showed no thrombotic event. The difference for proven homozygotes was statistically significant, while for the other groups only a trend was present.Conclusion:proven homozygous or compound heterozygous patients with the Arg304Gln mutation showed a higher than expected incidence of thrombotic events. The same is true for probable cases gathered only on the basis of clotting tests. These patients, because of their frequent lack of bleeding and for their relatively high prevalence of thrombosis should probably receive only limited replacement therapy in case of surgical procedures.
Development of a Novel Magnetic Brake Shoe for Mine Hoists Based on Nano-Fe3O4 and Nd-Fe-B Additive
Authors: Bao Jiusheng , Zhao Shaodi , Yin Yan , Xiao Xingming , Tuttle Mark E. , Liu Tonggang 
Published: March 2019

Background:
The brake is an important safety protection device for mine hoists, in which
the performance of the brake shoe affects directly the safe operation of the hoist system. In order to
solve problems such as high wear rate and unstable friction coefficient of brake shoe under high temperature,
this paper indicated that adding magnetic powder to the composite material of traditional
mine hoist’s brake shoe will be a creative and effective approach to improve its properties.

Methods:
Based on relevant China patents of the authors, several new formulas of brake shoe material
were designed in the presence of Nano-Fe3O4 and Nd-Fe-B, and the methods of both preparation and
performance testing of the magnetic brake shoes were introduced. The experiment of formula design
was carried out by uniform prescription design, and the friction coefficient and wear rate of each kind
of brake shoes made through different formulas were measured. Furthermore, the formula was optimized
by application of fuzzy comprehensive evaluation method and analytic hierarchy process.

Results:
Compared with ordinary formulas, the optimized formula is higher totally and changes more
steadily as well. Its wear rate is far lower than the national standard. Namely, its comprehensive properties
are better. Few relevant patents to the topic have been reviewed and cited.

Conclusion:
This paper proved that it is practically valuable and feasible to improve the properties of
hoist brake shoes by adding magnetic powder to its composite material.
Medicinal Plant Compounds for Combating the Multi-drug Resistant Pathogenic Bacteria: A Review
Authors: Mulat Mulugeta , Pandita Archana , Khan Fazlurrahman 
Published: March 2019

Background:Globally, people utilize plants as the main source of remedy to heal various ailments. Medicinal plants have been utilized to treat ailments since the invention of modern scientific systems of medicine. The common remedy of infectious diseases mainly depends on the inhibition capacity of compounds or killing potential. The issue may give a clue for the development of a novel antimicrobial agent.Methods:Currently, microorganisms which are resistant towards antibiotics are probably a matter of serious concern for the overall well-being of health. At the moment, new therapeutic targets aside from the microorganism wall-based activities are in progress. For instance, the autoinducer molecules produced by the quorum sensing system are used to control antibiotic resistance and biofilm formation.Results:This therapeutic target is well-studied worldwide, however, the scientific data are not updated and only current studies started to gain insight into its perspective as a target to struggle against infectious diseases. Microbial resistance against antimicrobial compounds is a topic of serious concern in recent time.Conclusion:Hence, this paper aims to confer a current overview of the novel compounds, quorum sensing, quorum quenching, biofilm formation in the development of antibiotic resistance and an update on their importance as a potential target for natural substances.