The characterization of virulent and drug-resistant Escherichia coli strains helps to control and provide more accurate information regarding infection and eradication. The aim of this study was to determine the relationship between antibiotic susceptibility, phylogroups and virulence factors of E. coli isolates from children with septicaemia. One hundred dereplicated E. coli isolates were collected from paediatric patients with septicaemia in five hospitals in Tehran (May 2015 to May 2018). The antibiotic susceptibility of isolates was performed as per the 2016 guidelines of the Clinical and Laboratory Standards Institute. Extended-spectrum β-lactamases and carbapenemase genes, phylogroups, serogroups and virulence encoding genes were detected by PCR. Phylogroup B2 was dominant (40%) among strains, followed by phylogroups D (30%), A (8%) and B1 (7%). CTX-M1 was significantly higher in the B2 group (n = 21, p 0.001). Furthermore, the virulence genes iutA (n = 27, p 0.002), csgA (n = 39, p <0.001), kpsMII (n = 39, p 0.002), ibeA (n = 4, p 0.004), vat (n = 5, p 0.003), traT (n = 24, p <0.001), sat (n = 12, p 0.001) and hlyA (n = 33, p <0.001) showed significantly higher rates in phylogroup B2. Three O25/CTXM1/OXA-48 and cnf, iutA, csgA and traT positive isolates belonged to phylogroup B2. Pulsed-field gel electrophoresis analysis showed 85% similarity among 25% of isolates. More than half of the isolates were multidrug-resistant E. coli. A significant relation was observed among iutA, csgA, kpsMII, ibeA, vat, traT, sat and hlyA genes and phylogroup B2. The characterization of virulent and drug-resistant strains helps control and properly eliminate infections. There was no genetic relation among strains in the pulsed-field gel electrophoresis pattern.
Nicotinamide adenine dinucleotide (NAD) is an important coenzyme that participates in various energy metabolism pathways, including glycolysis, β-oxidation, and oxidative phosphorylation. Besides, it is a required cofactor for post-translational modifications such as ADP-ribosylation and deacetylation by poly (ADP-ribose) polymerases (PARPs) and sirtuins, respectively. Thus, NAD regulates energy metabolism, DNA damage repair, gene expression, and stress response through these enzymes. Numerous studies have shown that NAD levels decrease with aging and under disturbed nutrient conditions, such as obesity. Additionally, a decline in NAD levels is closely related to the development of various metabolic disorders, including diabetes and fatty liver disease. In addition, many studies have revealed that administration of NAD precursors, such as nicotinamide mononucleotide (NMN) and nicotinamide riboside (NR), efficiently increase NAD levels in various tissues and prevent such metabolic diseases. These NAD precursors are contained in natural foods, such as cow milk, vegetables, and meats. Therefore, altered NAD metabolism can be a practical target for nutritional intervention. Recently, several human clinical trials using NAD precursors have been conducted to investigate the safety, pharmacokinetics, and efficacy against metabolic disorders such as glucose intolerance. In this review, we summarize current knowledge on the implications of NAD metabolism in metabolic diseases and discuss the outcomes of recent human clinical trials.
Mitochondrial transcription factor A (TFAM) is a key regulator of mitochondria biogenesis. Previous studies confirmed that reduced TFAM expression sensitized tumours cells to chemical therapy reagents and ionizing irradiation (IR). However, the underlying mechanisms remain largely unknown. In this study, we identified that decreased expression of TFAM impaired the proliferation of tumour cells by inducing G1/S phase arrest and reducing the expression of E2F1, phospo-Rb, PCNA and TK1. Furthermore, we proved that knockdown of TFAM enhanced the interaction between p53 and MDM2, resulting in decreased expression of p53 and the downstream target TIGAR, and thus leading to elevated level of mitochondrial superoxide and DNA double-strand break (DSB) which were exacerbated when treated the cell with ionizing radiation. Those indicated that knockdown of TFAM could aggravate radiation induced DSB levels through affecting the production of mitochondria derived reactive oxygen species. Our current work proposed a new mechanism that TFAM through p53/TIGAR signalling to regulate the sensitivity of tumour cells to ionizing radiation. This indicated that TFAM might be a potential target for increasing the sensitization of cancer cells to radiotherapy.
Resveratrol increases the production of nitric oxide (NO) in endothelial cells by upregulating the expression of endothelial NO synthase (eNOS), stimulating eNOS enzymatic activity, and preventing eNOS uncoupling. At the same time, resveratrol inhibits the synthesis of endothelin-1 and reduces oxidative stress in both endothelial cells and smooth muscle cells. Pathological stimuli-induced smooth muscle cell proliferation, vascular remodeling, and arterial stiffness can be ameliorated by resveratrol as well. In addition, resveratrol also modulates immune cell function, inhibition of immune cell infiltration into the vascular wall, and improves the function of perivascular adipose tissue. All these mechanisms contribute to the protective effects of resveratrol on vascular function and blood pressure in vivo. Sirtuin 1, AMP-activated protein kinase, and estrogen receptors represent the major molecules mediating the vascular effects of resveratrol.
Iberian primitive breeds exhibit a remarkable phenotypic diversity over a very limited geographical space. While genomic data are accumulating for most commercial cattle, it is still lacking for these primitive breeds. Whole genome data is key to understand the consequences of historic breed formation and the putative role of earlier admixture events in the observed diversity patterns.
As an allotetraploid, most genes have multiple copies that belong to At and Dt subgenomes in cotton. Different types of gene editing tools are desirable for the functional genomic research in cotton: a plant species with very complex genome (AADD, 2n=4x=52; genome size of 2.5 Gb). CRISPR/Cpf1 (Cas12a) is a novel member of CRISPR-Cas system from Alicyclobacillus acidoterrestris, and currently, there have three kinds of Cpf1 commonly used for genome editing, namely AsCpf1, LbCpf1 and FnCpf1. Recently, several groups have successfully applied the CRISPR/Cpf1 system in plant species such as rice, soybean, tobacco and maize. Here, we established an efficient CRISPR/Cpf1 system to expand the scope of genome editing in cotton. To my knowledge, this is the first report of the application of CRISPR/Cpf1 system for cotton genome editing with a very high efficiency (87%) and no off-target effects were detected in the most potential off-target sites. More importantly, the mutated phenotype and genotype in T0 generation were faithfully inherited to their progeny and some homozygous mutants were obtained in T1 generation. These results further support the finding that the CRISPR/Cpf1 system is highly specific and efficient system in plant genome editing, which will be a very promising alternative of CRISPR/Cas9 system for the genome editing in cotton. This article is protected by copyright. All rights reserved.
The question of whether anesthetic, analgesic or other perioperative intervention during cancer resection surgery might influence long-term oncologic outcomes has generated much attention over the past 13 years. A wealth of experimental and observational clinical data have been published, but the results of prospective, randomized clinical trials are awaited. The European Union supports a pan-European network of researchers, clinicians and industry partners engaged in this question (COST Action 15204: Euro-Periscope). In this narrative review, members of the Euro-Periscope network briefly summarize the current state of evidence pertaining to the potential effects of the most commonly deployed anesthetic and analgesic techniques and other non-surgical interventions during cancer resection surgery on tumor recurrence or metastasis.
Ultraselective conventional transarterial chemoembolization (cTACE), defined as cTACE at the most distal portion of the subsubsegmental hepatic artery, is mainly performed for hepatocellular carcinoma (HCC) ≤5 cm. Distal advancement of a microcatheter enables injection of a larger volume of iodized oil into the portal vein in the limited area under non-physiological hemodynamics. As a result, the reversed portal flow into the tumor through the drainage route of the tumor that occurs when the hepatic artery is embolized is temporarily blocked. By adding gelatin sponge slurry embolization, both the hepatic artery and portal vein are embolized and not only complete necrosis of the tumor but also massive peritumoral necrosis can be achieved. Ultraselective cTACE can cure small HCCs including less hypervascular tumor portions and replace surgical resection and radiofrequency ablation in selected patients.
- Turkish journal of haematology : official journal of Turkish Society of Haematology
- Published 11 days ago
Despite effective factor replacement and various treatment schedules, there remain several challenges and unmet needs in the prophylactic treatment of haemophilia limiting its adoption and thereby posing an increased risk of spontaneous bleeding. In this regard, extended half-life (EHL) recombinant factor VIII (rFVIII) and factor IX (rFIX) products promise optimal prophylaxis by decreasing the dose frequency, increasing the compliance and improving the quality of life without compromising on safety and efficacy. EHL products might lead to higher trough levels without increasing infusion frequency, or would facilitate ability to maintain trough levels while reducing infusion frequency. This paper aims to provide a comprehensive review on the rationale for developing EHL coagulation factors and their utility in the management of haemophilia, with special emphasis on optimal technique for half-life extension and criteria for defining EHL coagulation factors, as well as indications, efficacy and safety issues of the currently available EHL-rFVIII and EHL-rFIX products. Potential impact of these factors on quality of life, health economics and immune tolerance treatment will be also be discussed alongside the challenges in pharmacokinetic driven prophylaxis and difficulties in monitoring the EHL-products with laboratory assays.
To determine the volume recombination at high dose-per-pulse in liquid ionization chambers (LIC) and to ascertain whether existing calculation methods verified in air-filled chambers may be used to calculate a correction factor.