Rare Germline GLMN Variants Identified from Blue Rubber Bleb Nevus Syndrome Might Impact mTOR Signaling

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Author(s): Jie Yin, Zhongping Qin, Kai Wu, Yufei Zhu, Landian Hu, Xiangyin Kong*.

Journal Name: Combinatorial Chemistry & High Throughput Screening
Accelerated Technologies for Biotechnology, Bioassays, Medicinal Chemistry and Natural Products Research

Abstract:

Backgrounds and Objective: Blue rubber bleb nevus syndrome (BRBN) or Bean syndrome is a rare venous malformation (VM)-associated disorder, which mostly affects the skin and gastrointestinal tract in early childhood. Somatic mutations in TEK have been identified from BRBN patients; however, the etiology of TEK mutation-negative patients of BRBN need further investigation.

Method: Two unrelated sporadic BRBNs and one sporadic VM were firstly screened for any rare non-silent mutation in TEK by Sanger sequencing and subsequently applied to whole exome sequencing to identify underlying disease causative variants. Overexpression assay and immunoblotting were used to evaluate the functional effect of the candidate disease causative variants.

Results: In the VM case, we identified the known causative somatic mutation in the TEK gene c.2740C>T (p.Leu914Phe). In the BRBN patients, we identified two rare germline variants in GLMN gene c.761C>G (p.Pro254Arg) and c.1630G>T(p.Glu544*). The GLMN-P254R-expressing and GLMN-E544X-expressing HUVECs exhibited increased phosphorylation of mTOR-Ser-2448 in comparison with GLMN-WT-expressing HUVECs, in vitro.

Conclusion: Our results demonstrated that rare germline variants in GLMN might contribute to the pathogenesis of BRBN. Moreover, abnormal mTOR signaling might be the pathogenesis mechanism underlying the dysfunction of GLMN protein.

Keywords: Blue Rubber Bleb Nevus Syndrome, Venous Malformation, GLMN, mTOR

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DOI: 10.2174/1386207322666191203110042
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Current Alzheimer Research

Editor-in-Chief:

Debomoy K. Lahiri  
Department of Psychiatry
Indiana University School of Medicine
Neuroscience Research Center
Indianapolis, IN 46202
USA

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Microextraction and Chromatographic Analysis of Budesonide Epimers in Exhaled Breath Condensate

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Author(s): Laleh Samini, Maryam Khoubnasabjafari, Mohamad M. Alimorad, Vahid Jouyban-Gharamaleki, Hak-Kim Chan, Abolghasem Jouyban*.

Journal Name: Current Analytical Chemistry

Abstract:

Background: Analysis of drug concentrations in biological fluids is required in clinical sciences for various purposes. Among other biological samples, exhaled breath condensate (EBC) is a potential sample for follow up of drug concentrations.

Methods: A dispersive liquid–liquid microextraction (DLLME) procedure followed by a validated liquid chromatography method was employed for determination of budesonide (BDS) in EBC samples collected using a home-made setup. EBC is a non-invasive biological sample with possible applications for monitoring drug concentrations. The proposed analytical method is validated according to the FDA guidelines using EBC-spiked samples. Its applicability is tested on EBC samples collected from healthy volunteers receiving a single puff of BDS. Results: The best DLLME conditions involved the use of methanol (1 mL) as a disperser solvent, chloroform (200 µL) as an extraction solvent, and centrifugation rate of 3500 rpm for 5 minutes. The method was validated over a concentration range of 21–210 µgL-1 in EBC. Inter- and intra-day precisions were less than 10 % where the acceptable levels are less than 20%. The validated method was successfully applied for the determination of BDS in EBC samples.

Conclusion: The findings of this study indicate that the developed method can be used for the extraction and quantification of BDS in EBC samples using a low cost method.

Keywords: Budesonide, Microextraction, Exhaled breath condensate, HPLC-UV, Determination

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DOI: 10.2174/1573411015666191203104522
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Mediterranean Diet and Osteoarticular Diseases

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Author(s): Eliana Rita Sanpaolo, Addolorata Corrado, Francesco Paolo Cantatore*.

Journal Name: Current Nutrition & Food Science

Abstract:

Background: Besides the well-known positive effect on the reduction the risk of cardiovascular diseases, in the latest decades a growing evidence has accumulated on the beneficial effects of MD on various aspect of health outcomes. Nevertheless, data concerning the existence of a direct positive effect of MD, irrespective of its beneficial effect on body weight, in osteo-articular diseases, are still controversial. In osteo-articular diseases a pro-inflammatory environment is highlighted, with an increased systemic levels of pro-inflammatory cytokines.

Objective: Our objective is to investigate the effects of adherence to the Mediterranean Diet and osteo-articular diseases.

Conclusion: Many food included in MD, have anti-inflammatory properties, due to the presence of nutrients such as polyunsaturated (PUFA) and monounsaturated (MUFA) fats. The two types of polyunsaturated fatty acids, omega-3 and omega-6, have opposing effects on the inflammatory process. Omega-6 stimulate the production of pro-inflammatory cytokines, while omega-3 fatty acids exert anti-inflammatory effects, including significant reductions in the release of pro-inflammatory cytokines. Some studies have shown that dietary pattern of MD consumption have an important role for the prevention development of inflammatory arthritis. Nevertheless, possible influence of MD on chronic osteo-articular diseases is very limited,this review updates the main experimental and clinical evidences concerning the potential beneficial effects of the Mediterranean Diet on the most diffuse osteo-articular chronic and degenerative joint disease.

Keywords: Mediterranean Diet, Osteo-Articular Diseases, Fatty Acids, Adipokines, Polyphenol

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DOI: 10.2174/1386207322666191203103530
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Review on Polymeric Citrate Precursor and Sono-chemical Methods for the Synthesis of Nanomaterials

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Author(s): Irfan H. Lone*, Jeenat Aslam, Nagi R. E. Radwan, Arifa Akhter, Ali Habib Bashal, Rayees Ahmad Shiekh.

Journal Name: Current Analytical Chemistry

Abstract:

Background: The manner in which the things are constructed with atoms and molecules essentially are important to know their properties and their respective interactions and hence it was on high demand to synthesis novel materials. The low temperature synthesis methods such as polymeric citrate precursor and sonochemical methods are efficient enough to control the preparation of novel nanoparticles with morphological differences that leads to the novel devices with desired technological performances. These methods are simple, very less expensive and are easy to handle to operate for the synthesis of nanoparticles as per the expected morphology and dimensions

Methods: Polymeric citrate precursor method, a chelate-based method involves the reaction between mixed cations with citric acid and then these cations are cross-linked with the help of ethylene glycol for the esterification process. Gel composites were heated which burns the organic moieties leaving behind the nanoparticles and burning gels becomes essential for the reduction of nanoparticles. Sonochemical method on the other hand uses ultrasonic irradiation results the acoustic cavitation and high intensity ultrasound has been exploited for the preparation of different series of nanoparticles.

Results: Commonly known for polymeric citrate method as Pechini gel pyrolysis method gives the evidence of versatile and elegant method for the synthesis of nanoparticles. Sonochemical method provides an unusual route of nanoparticle fabrication without bulk and that too with low temperature and pressure or less reaction time. These two methods have better control for the desired shape morphology and size and provide many opportunities for the use of these prepared nanoparticles in various aspects of science and technology.

Conclusion: Polymeric citrate precursor and sonochemical methods are efficient to reduce to promote desirable reaction conditions and reduce the metal ions for the fabrication of nanoparticles. The prepared nanoparticles by these two low cost elegant methods are uniform with small size distribution, reproducible with good yield as per the demanded applications.

Keywords: Citric acid and ethylene glycol ester bond, High degree of homogeneity, Less expensive, Ultrasound, Cavitation bubble, Sono chemical method, Nanoparticle synthesis

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DOI: 10.2174/1573411015666191203102837
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Alkylation of 2(3H)-Furanones: Inter- versus Intra-molecular

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Author(s): Sayed K. Ramadan*, Wael S. I. Abou-Elmagd, Ahmed I. Hashem.

Journal Name: Letters in Organic Chemistry

Abstract:

In this review, survey on the behavior of 2(3H)-furanones as alkylating agents are systematized. It is obvious that the direction of the reaction was mainly dependent on the solvent used. Furanones reacted with AlCl3 in excess benzene, toluene, or anisole to give the corresponding butadienecarboxylic acids via an intermolecular alkylation mode. Carrying out the reaction in tetrachloroethane and nitrobenzene as solvents; the reactions may lead to intramolecular alkylation mode or failed to give any product and the unreacted furanones were isolated, depending upon the electron density on C-2 at the aryl group situated at position-3.

Keywords: 2(3H)-Furanones, 2(5H)-Furanone, Friedel-Crafts Reaction, Intramolecular Alkylation, Intermolecular Alkylation, Butadienecarboxylic Acids

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DOI: 10.2174/1570178617666191203102528
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Inorganic Gold and Polymeric Poly(Lactide-co-glycolide) Nanoparticles as Novel Strategies to Ameliorate the Biological Properties of Antimicrobial Peptides

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Author(s): Bruno Casciaro, Francesca Ghirga, Deborah Quaglio, Maria Luisa Mangoni*.

Journal Name: Current Protein & Peptide Science

Abstract:

Cationic antimicrobial peptides (AMPs) are an interesting class of gene-encoded molecules endowed with a broad-spectrum of anti-infective activity and immunomodulatory properties. They represent promising candidates for the development of new antibiotics, mainly due to their membraneperturbing mechanism of action that very rarely induces microbial resistance. However, bringing AMPs into the clinical field is hampered by some intrinsic limitations, encompassing low peptide bioavailability at the target site and high peptide susceptibility to proteolytic degradation. In this regard, nanotechnologies represent an innovative strategy to circumvent these issues. According to the literature, a large variety of nanoparticulate systems have been employed for drug-delivery, bioimaging, biosensors or nanoantibiotics. The possibility of conjugating different types of molecules, including AMPs, to these systems, allows the production of nanoformulations able to enhance the biological profile of the compound while reducing its cytotoxicity and prolonging its residence time. In this minireview, inorganic gold nanoparticles (NPs) and biodegradable polymeric NPs made of poly(lactide-coglycolide) are described with particular emphasis on examples of the conjugation of AMPs to them, to highlight the great potential of such nanoformulations as alternative antimicrobials.

Keywords: Antimicrobial peptides, Antibiotic-resistance, Drug delivery, Nanoparticles

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DOI: 10.2174/1389203720666191203101947
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Therapeutic targets for the treatment of comorbidities associated with epilepsy

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Author(s): Kinjal Gangar, Lokesh Kumar Bhatt*.

Journal Name: Current Molecular Pharmacology

Abstract:

One of the most common neurological disorder occurs among 1% of population worldwide is epilepsy. Therapeutic failure is common with epilepsy and nearly about 30% of patient fall in this category. Seizure suppression should not be the only goal while treating epilepsy but associated comorbidities which can further worsen the condition should also be considered. Treatment of such comorbidities like depression, anxiety, cognition, attention deficit hyperactivity disorder and, various other disorder which co-exist with epilepsy or are caused due to epilepsy should also be treated. Novel targets or the existing targets needed to be explored for dual mechanism which can supress both the disease and the comorbidity. New therapeutic targets like IDO, nNOS, PAR1, NF-κb are being explored for their role in epilepsy and various comorbidities. This review explore recent therapeutic targets for the treatment of comorbidities associated with epilepsy.

Keywords: Epilepsy, Comorbidities, Therapeutic Targets, Depression, Anxiety, Cognition

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DOI: 10.2174/1874467212666191203101606
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Study on Chlorination by Sulfuryl Chloride of Benzene/Pyridine Carboxamides and Carbonitriles

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Author(s): Weiqing Yang, Yongjing Cao, Hongrui Cheng, Qingrong Sun, Menglin Ma*.

Journal Name: Letters in Organic Chemistry

Abstract:

In the chlorination of N-[2-aryl-1-(1-piperidinylcarbonyl)ethenyl]arenecarboxamides, it has been found that a derivative having two methoxy substituents on the arenecarbonyl ring undergoes chlorination on the same ring rather than converting into the expected enamine bond chlorination product. Based on the above results, the chlorination of benzamides/nicotinamides by sulfuryl chloride (SO2Cl2) has been studied. We developed a method of synthesizing aromatic chlorinated compounds by treating aromatic amides or nitriles with SO2Cl2 in dichloromethane at 0 oC without catalyst. This is a new mild method and give good yields, especially when benzene ring is substituted by amide or cyano group together with alkoxy group.

Keywords: Arylpropenamide, Benzamide, Benzonitrile, Chlorination, Sulfuryl dichloride

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DOI: 10.2174/1570178617666191203101254
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Geminiviruses: Taxonomic Structure and Diversity in Genomic Organization

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Author(s): Saurabh Kulshrestha*, Abhishek Bhardwaj, Vanshika.

Journal Name: Recent Patents on Biotechnology

Abstract:

Background: Geminiviridae is one of the best-characterized and hence, one of the largest plant-virus families with highest economic importance. It’s members characteristically have a circular ssDNA genome within the encapsidation of twinned quasi-icosaheadral virions (18-38 nm size-range).

Objective: Construction of a narrative review on geminiviruses, to have a clearer picture about their genomic structure and taxonomic status.

Methods: Thorough search was conducted for papers and patents regarding geminiviruses, where relevant information was used for studying their genomic organization, diversity and taxonomic structure. Results: Geminiviruses have been classified into nine genera (viz., genus Begomovirus, Mastrevirus, Curtovirus, Topocuvirus, Becurtovirus, Turncurtovirus, Capulavirus, Eragrovirus and Grablovirus) having distinct genomic organizations, host ranges and insect vectors. Genomic organization of all genera generally shows the presence of 4-6 ORFs encoding for various proteins. For now, Citrus chlorotic dwarf-associated virus (CCDaV), Camellia chlorotic dwarf-associated virus (CaCDaV) and few other geminiviruses are still unassigned to any genera. The monopartite begomoviruses (and few mastreviruses) have been found associated with aplhasatellites and betasatellites (viz., ~1.3 kb circular ssDNA satellites). Recent reports suggests that deltasatellites potentially reduce the accumulation of helper-Begomovirus species in host plants. Some patents have revealed the methods for generating transgenic plants resistant to geminiviruses.

Conclusion: Geminiviruses are rapidly evolving and highly diverse group of plant-viruses. However, research has shown new horizons in tackling the acute begomoviral diseases in plants by generating a novel bio-control methodology in which deltasatellites can be used as bio-control agents and generating transgenic plants resistant to geminiviruses.

Keywords: Geminiviridae, Begomoviruses, Aplhasatellites, Betasatellites, Deltasatellites, ssDNA

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DOI: 10.2174/1872208313666191203100851
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