scholarly journals The Challenge of CRISPR-Cas Toward Bioethics

2021 ◽  
Vol 12 ◽  
Author(s):  
Luis Uriel Gonzalez-Avila ◽  
Juan Manuel Vega-López ◽  
Leda Ivonne Pelcastre-Rodríguez ◽  
Omar Alejandro Cabrero-Martínez ◽  
Cecilia Hernández-Cortez ◽  
...  
Keyword(s):  
Double Helix ◽  
Treatment Options ◽  
Fundamental Rights ◽  
Contemporary Science ◽  
New Findings ◽  
Scientific Technical ◽  
New Treatment ◽  
Dna Double Helix ◽  
Van Rensselaer Potter

Since determining the structure of the DNA double helix, the study of genes and genomes has revolutionized contemporary science; with the decoding of the human genome, new findings have been achieved, including the ability that humans have developed to modify genetic sequences in vitro. The discovery of gene modification mechanisms, such as the CRISPR-Cas system (Clustered Regularly Interspaced Short Palindromic Repeats) and Cas (CRISPR associated). Derived from the latest discoveries in genetics, the idea that science has no limits has exploded. However, improvements in genetic engineering allowed access to new possibilities to save lives or generate new treatment options for diseases that are not treatable by using genes and their modification in the genome. With this greater knowledge, the immediate question is who governs the limits of genetic science? The first answer would be the intervention of a legislative branch, with adequate scientific advice, from which the logical answer, bioethics, should result. This term was introduced for the first time by Van Rensselaer Potter, who in 1970 combined the Greek words bios and ethos, Bio-Ethik, which determined the study of the morality of human behavior in science. The approach to this term was introduced to avoid the natural tension that results from the scientific technical development and the ethics of limits. Therefore, associating the use of biotechnology through the CRISPR-Cas system and the regulation through bioethics, aims to monitor the use of techniques and technology, with benefits for humanity, without altering fundamental rights, acting with moral and ethical principles.

Mesenchymal stem cell-derived extracellular vesicles in the failing heart: past, present, and future

2021 ◽  
Author(s):  
Catherine Karbasiafshar ◽  
Frank W. Sellke ◽  
M. Ruhul Abid
Keyword(s):  
Stem Cell ◽  
Extracellular Vesicles ◽  
Treatment Options ◽  
Current Treatment ◽  
Lifestyle Changes ◽  
Challenges And Opportunities ◽  
Artery Disease ◽  
New Treatment

Cardiovascular disease (CVD) is the leading cause of death globally. Current treatment options include lifestyle changes, medication, and surgical intervention. However, many patients are unsuitable candidates for surgeries due to comorbidities, diffuse coronary artery disease or advanced stages of heart failure. The search for new treatment options has recently transitioned from cell-based therapies to stem-cell derived extracellular vesicles (EVs). A number of challenges remain in the EV field, including the effect of comorbidities, characterization, and delivery, However, recent revolutionary developments and insight into the potential of 'personalizing' EV contents by bioengineering methods to alter specific signaling pathways in the ischemic myocardium hold promise. Here, we discuss the past limitations of cell-based therapies, and recent EV studies involving in vivo, in vitro, and omics, and future challenges and opportunities in EV-based treatments in CVD.

scholarly journals (E)-N′-(4-Fluorobenzylidene)-5-methyl-2-(pyridin-3-yl)thiazole-4-carbohydrazide

Molbank ◽  
10.3390/m1058 ◽  
2019 ◽  
Vol 2019 (2) ◽  
pp. M1058
Author(s):  
Vinuta Kamat ◽  
Rangappa Santosh ◽  
Suresh Nayak
Keyword(s):  
Escherichia Coli ◽  
Double Helix ◽  
Catalytic Amount ◽  
Target Compound ◽  
Addition Compound ◽  
E Coli ◽  
In Vitro Antibacterial Activity ◽  
Ft Ir ◽  
Dna Double Helix

5-methyl-2-(pyridin-3-yl)-1,3-thiazole-4-carbohydrazide (1) on treatment with 4-fluorobenzaldehyde in presence of catalytic amount of acetic acid, accessed the target compound (2) with the yield of 79%. The target compound was confirmed by 1H-NMR, 13C-NMR, FT-IR and LCMS. In vitro antibacterial activity against Staphylococcus aureus (S. Aureus), Bacillus subtilis (B. subtilis), Escherichia coli (E. coli), and Pseudomonas aeruginosa (P. aeruginosa) were carried out and compound 2 showed promising activity against B. subtilis. In addition, compound 2 was analyzed for DNA binding study. It revealed that compound 2 has a promising affinity towards DNA double helix.

scholarly journals In VitroandIn VivoEfficacies of Mefloquine-Based Treatment against Alveolar Echinococcosis

2010 ◽  
Vol 55 (2) ◽  
pp. 713-721 ◽  
Author(s):  
Tatiana Küster ◽  
Britta Stadelmann ◽  
Corina Hermann ◽  
Sabrina Scholl ◽  
Jennifer Keiser ◽  
...  
Keyword(s):  
Alveolar Echinococcosis ◽  
Severe Disease ◽  
Treatment Options ◽  
Drug Candidate ◽  
Combined Application ◽  
New Treatment ◽  
Complete Detachment ◽  
Laminated Layer

ABSTRACTAlveolar echinococcosis (AE) is caused by the metacestode stage of the fox tapewormEchinococcus multilocularisand causes severe disease in the human liver, and occasionally in other organs, that is fatal when treatment is unsuccessful. The present chemotherapy against AE is based on mebendazole and albendazole. Albendazole treatment has been found to be ineffective in some instances, is parasitostatic rather than parasiticidal, and usually involves the lifelong uptake of large doses of drugs. Thus, new treatment options are urgently needed. In this study we investigated thein vitroandin vivoefficacy of mefloquine againstE. multilocularismetacestodes. Treatment using mefloquine (20 μM) againstin vitrocultures of metacestodes resulted in rapid and complete detachment of large parts of the germinal layer from the inner surface of the laminated layer within a few hours. Thein vitroactivity of mefloquine was dependent on the dosage.In vitroculture of metacestodes in the presence of 24 μM mefloquine for a period of 10 days was parasiticidal, as determined by murine bioassays, while treatment with 12 μM was not. Oral application of mefloquine (25 mg/kg of body weight administered twice a week for a period of 8 weeks) inE. multilocularis-infected mice was ineffective in achieving any reduction of parasite weight, whereas treatment with albendazole (200 mg/kg/day) was highly effective. However, when the same mefloquine dosage was applied intraperitoneally, the reduction in parasite weight was similar to the reduction seen with oral albendazole application. Combined application of both drugs did not increase the treatment efficacy. In conclusion, mefloquine represents an interesting drug candidate for the treatment of AE, and these results should be followed up in appropriatein vivostudies.

Rapamycin blocks hepatoblastoma growth in vitro and in vivo implicating new treatment options in high-risk patients

2012 ◽  
Vol 48 (15) ◽  
pp. 2442-2450 ◽  
Author(s):  
Ferdinand Wagner ◽  
Bente Henningsen ◽  
Christine Lederer ◽  
Melanie Eichenmüller ◽  
Jan Gödeke ◽  
...  
Keyword(s):  
High Risk ◽  
Treatment Options ◽  
High Risk Patients ◽  
Risk Patients ◽  
New Treatment

Polyamine derivatives as potential bisintercalators with antiproliferative activity

2016 ◽  
Vol 4 ◽  
pp. 9-15
Author(s):  
Marta Szumilak
Keyword(s):  
Ethidium Bromide ◽  
Antiproliferative Activity ◽  
Double Helix ◽  
Structural Features ◽  
Discovery Studio ◽  
Polycyclic Aromatic ◽  
Ic50 Values ◽  
Dna Double Helix ◽  
Polyamine Derivatives

Bisntercalators are very interesting group of compounds with potential antitumor activity. They interact reversibly with DNA double helix. These agents share common structural features such as the presence of two, planar, polycyclic aromatic or heteroaromatic systems separated by a spacer chain which must be long enough to enable double intercalation between base pairs. The unique chemical structure of these compounds provides numerous modifications within their structure resulting either in higher activity or increased selectivity toward tumor cells. Within the framework of the project, new polyamine derivatives containing dimeric phthalimide, quinoline, cinnoline and chromone moieties were obtained. Three different polyamines: 1,4-bis(3-aminopropyl)piperazine, 4,9-dioxa-1,12-dodecanediamine, 3,3’-diamino-N-methyldipropylamine were used as linkers. The biological activity of compounds was assessed in vitro in a highly aggressive melanoma cell line A375. Quinoline derivatives were found to have a higher antiproliferative activity than cinnoline ones. The lowest IC50 values, below 20 μM, were obtained for quinoline and 2H-chromene-2,4(3H)-dione derivatives. Quinoline diamides were more efficient than cinnoline ones. Polyamine diimides containing phthalimide moieties demonstrated no inhibitory activities against melanoma cells. Preliminary studies of mechanism of action have shown that obtained derivatives were capable of quenching the fluorescence of ethidium bromide-DNA complex, indicating that they bound to ds-DNA in competition with ethidium bromide for binding sites. All the compounds were also subjected to preliminary in silico ADME screening by evaluating their theoretical drug-likeness and physicochemical properties using Discovery Studio 3.0 obtained from Accelrys. Compounds meeting the required ADME and drug-likeness criteria were selected.

scholarly journals In Vitro Activity of New Tetracycline Analogs Omadacycline and Eravacycline against Drug-Resistant Clinical Isolates of Mycobacterium abscessus

2019 ◽  
Vol 63 (6) ◽  
Author(s):  
Amit Kaushik ◽  
Nicole C. Ammerman ◽  
Olumide Martins ◽  
Nicole M. Parrish ◽  
Eric L. Nuermberger
Keyword(s):  
Salvage Therapy ◽  
Treatment Options ◽  
Oral Formulation ◽  
Mycobacterium Abscessus ◽  
Clinical Isolates ◽  
Drug Resistant ◽  
In Vitro Activity ◽  
Content Type ◽  
New Treatment

ABSTRACT Tigecycline is used in multidrug regimens for salvage therapy of Mycobacterium abscessus infections but is often poorly tolerated and has no oral formulation. Here, we report similar in vitro activity of two newly approved tetracycline analogs, omadacycline and eravacycline, against 28 drug-resistant clinical isolates of M. abscessus complex. Since omadacycline and eravacycline appear to be better tolerated than tigecycline and since omadacycline is also formulated for oral dosing, these tetracycline analogs may represent new treatment options for M. abscessus infections.

scholarly journals ATP-Dependent Chromatin Remodeling by the Cockayne Syndrome B DNA Repair-Transcription-Coupling Factor

2000 ◽  
Vol 20 (20) ◽  
pp. 7643-7653 ◽  
Author(s):  
Elisabetta Citterio ◽  
Vincent Van Den Boom ◽  
Gavin Schnitzler ◽  
Roland Kanaar ◽  
Edgar Bonte ◽  
...  
Keyword(s):  
Dna Repair ◽  
Chromatin Remodeling ◽  
Chromatin Structure ◽  
Excision Repair ◽  
Double Helix ◽  
Coupling Factor ◽  
Cockayne Syndrome ◽  
Direct Role ◽  
Dna Double Helix

ABSTRACT The Cockayne syndrome B protein (CSB) is required for coupling DNA excision repair to transcription in a process known as transcription-coupled repair (TCR). Cockayne syndrome patients show UV sensitivity and severe neurodevelopmental abnormalities. CSB is a DNA-dependent ATPase of the SWI2/SNF2 family. SWI2/SNF2-like proteins are implicated in chromatin remodeling during transcription. Since chromatin structure also affects DNA repair efficiency, chromatin remodeling activities within repair are expected. Here we used purified recombinant CSB protein to investigate whether it can remodel chromatin in vitro. We show that binding of CSB to DNA results in an alteration of the DNA double-helix conformation. In addition, we find that CSB is able to remodel chromatin structure at the expense of ATP hydrolysis. Specifically, CSB can alter DNase I accessibility to reconstituted mononucleosome cores and disarrange an array of nucleosomes regularly spaced on plasmid DNA. In addition, we show that CSB interacts not only with double-stranded DNA but also directly with core histones. Finally, intact histone tails play an important role in CSB remodeling. CSB is the first repair protein found to play a direct role in modulating nucleosome structure. The relevance of this finding to the interplay between transcription and repair is discussed.

scholarly journals In VitroActivity of the New Fluoroketolide Solithromycin (CEM-101) against a Large Collection of Clinical Neisseria gonorrhoeae Isolates and International Reference Strains, Including Those with High-Level Antimicrobial Resistance: Potential Treatment Option for Gonorrhea?

2012 ◽  
Vol 56 (5) ◽  
pp. 2739-2742 ◽  
Author(s):  
Daniel Golparian ◽  
Prabhavathi Fernandes ◽  
Makoto Ohnishi ◽  
Jörgen S. Jensen ◽  
Magnus Unemo
Keyword(s):  
Neisseria Gonorrhoeae ◽  
Treatment Option ◽  
Treatment Options ◽  
Effective Treatment Option ◽  
Content Type ◽  
New Treatment ◽  
High Level ◽  
Drug Resistant Strains ◽  
Reference Strains

ABSTRACTGonorrhea may become untreatable, and new treatment options are essential. We investigated thein vitroactivity of the first fluoroketolide, solithromycin. ClinicalNeisseria gonorrhoeaeisolates and reference strains (n= 246), including the two extensively drug-resistant strains H041 and F89 and additional isolates with clinical cephalosporin resistance and multidrug resistance, were examined. The activity of solithromycin was mainly superior to that of other antimicrobials (n= 10) currently or previously recommended for gonorrhea treatment. Solithromycin might be an effective treatment option for gonorrhea.

scholarly journals In VitroActivity of Ertapenem versus Ceftriaxone against Neisseria gonorrhoeae Isolates with Highly Diverse Ceftriaxone MIC Values and Effects of Ceftriaxone Resistance Determinants: Ertapenem for Treatment of Gonorrhea?

2012 ◽  
Vol 56 (7) ◽  
pp. 3603-3609 ◽  
Author(s):  
Magnus Unemo ◽  
Daniel Golparian ◽  
Athena Limnios ◽  
David Whiley ◽  
Makoto Ohnishi ◽  
...  
Keyword(s):  
Treatment Options ◽  
Genetic Resistance ◽  
Effective Treatment Option ◽  
Content Type ◽  
Therapy Regimen ◽  
Resistance Determinants ◽  
Clinical Resistance ◽  
New Treatment ◽  
High Level

ABSTRACTClinical resistance to the currently recommended extended-spectrum cephalosporins (ESCs), the last remaining treatment options for gonorrhea, is being reported. Gonorrhea may become untreatable, and new treatment options are crucial. We investigated thein vitroactivity of ertapenem, relative to ceftriaxone, againstN. gonorrhoeaeisolates and the effects of ESC resistance determinants on ertapenem. MICs were determined using agar dilution technique or Etest for international reference strains (n= 17) and clinicalN. gonorrhoeaeisolates (n= 257), which included the two extensively drug-resistant (XDR) strains H041 and F89 and additional isolates with high ESC MICs, clinical ESC resistance, and other types of clinical high-level and multidrug resistance (MDR). Genetic resistance determinants for ESCs (penA,mtrR, andpenB) were sequenced. In general, the MICs of ertapenem (MIC50= 0.032 μg/ml; MIC90= 0.064 μg/ml) paralleled those of ceftriaxone (MIC50= 0.032 μg/ml; MIC90= 0.125 μg/ml). The ESC resistance determinants mainly increased the ertapenem MIC and ceftriaxone MIC at similar levels. However, the MIC ranges for ertapenem (0.002 to 0.125 μg/ml) and ceftriaxone (<0.002 to 4 μg/ml) differed, and the four (1.5%) ceftriaxone-resistant isolates (MIC = 0.5 to 4 μg/ml) had ertapenem MICs of 0.016 to 0.064 μg/ml. Accordingly, ertapenem hadin vitroadvantages over ceftriaxone for isolates with ceftriaxone resistance. Thesein vitroresults suggest that ertapenem might be an effective treatment option for gonorrhea, particularly for the currently identified ESC-resistant cases and possibly in a dual antimicrobial therapy regimen. However, further knowledge regarding the genetic determinants (and their evolution) conferring resistance to both antimicrobials, and clear correlates between genetic and phenotypic laboratory parameters and clinical treatment outcomes, is essential.

scholarly journals Untersuchungen über die Bindung pflanzlicher Wuchsstoffe an verschiedene Komponenten des Chromatins in vitro. I. Bindung an DNS / Investigations Upon the Binding of Plant Growth Substances to Several Components of the Chromatin in vitro. I. Binding to DNA

1971 ◽  
Vol 26 (6) ◽  
pp. 607-612 ◽  
Author(s):  
Günter Fellenberg
Keyword(s):  
Hydrogen Bonds ◽  
Absorption Maximum ◽  
Double Helix ◽  
Specific Effect ◽  
Growth Substance ◽  
Growth Substances ◽  
Plant Growth Substances ◽  
The Stability ◽  
Dna Double Helix

At pH 9,5 the DNA absorption maximum at 190 nm was shifted to 212 nm. This absorption maximum showed a bathochrome effect in the presence of IAA, GA and KI. The amplitude of this maximum was reduced at the same time. By addition of urea (0.1 —2.0 moles/l) the bathochrome effect, induced by the growth substances, was completely reversed, whereas application of NaCl (0.1 — 2.0 moles/l) did not affect the bathochrome movement of this DNA maximum. At pH 6.0 in the presence of 0.9% NaCl this DNA maximum did not show any visible bathochrome movement in the presence of the growth substances investigated. The DNA maximum at 260 nm did not show any alteration in the presence of growth substances.The thermal denaturation of DNA-complexes with IAA and GA showed, that with increasing concentration of these growth substances, the Tm-value of the DNA was reduced. On the other hand, KI increased the Tm-point of DNA. By biphasic melting at 260 nm and 280 nm no specific effect of the investigated growth substances on the stability of the A — T or G—C pairs was detected.Tryptophan and β-NAA closely related in structure to the auxins IAA and α-NAA did not reduce the Tm-value of DNA.At pH &lt; 7 IAA, GA and KI did not show any detectable influence on the Tm-value of DNA.The data presented show that at a pH &gt; 7 IAA, GA and KI are obviously bound to DNA by hydrogen bonds. There is evidence that these bonds are very unstable. Nevertheless, IAA and GA can loosen part of the hydrogen bonds of DNA double helix while KI cannot. Possible consequences of these growth substance effects on DNA are discussed.

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