Combined gene and cell therapy are promising strategies for cancer treatment. Given the complexity of cancer, several approaches are actively studied to fight this disease. Using mesenchymal stem ...cells (MSCs) has demonstrated dual antitumor and protumor effects as they exert massive immune/regulatory effects on the tissue microenvironment. MSCs have been widely investigated to exploit their antitumor target delivery system. They can be genetically modified to overexpress genes and selectively or more efficiently eliminate tumor cells. Current approaches tend to produce more effective and safer therapies using MSCs or derivatives; however, the effect achieved by engineered MSCs in solid tumors is still limited and depends on several factors such as the cell source, transgene, and tumor target. This review describes the progress of gene and cell therapy focused on MSCs as a cornerstone against solid tumors, addressing the different MSC-engineering methods that have been approached over decades of research. Furthermore, we summarize the main objectives of engineered MSCs against the most common cancers and discuss the challenges, limitations, risks, and advantages of targeted treatments combined with conventional ones.
Neurofilament light chain (NfL) is a promising biomarker of active axonal injury and neuronal degeneration. We aimed to characterise cross-sectional and longitudinal plasma NfL measurements and ...determine the age at which NfL concentrations begin to differentiate between carriers of the presenilin 1 (PSEN1) E280A (Glu280Ala) mutation and age-matched non-carriers from the Colombian autosomal dominant Alzheimer's disease kindred.
In this cross-sectional and longitudinal cohort study, members of the familial Alzheimer's disease Colombian kindred aged 8–75 years with no other neurological or health conditions were recruited from the Alzheimer's Prevention Initiative Registry at the University of Antioquia (Medellín, Colombia) between Aug 1, 1995, and Dec 15, 2018. We used a single molecule array immunoassay and log-transformed data to examine the relationship between plasma NfL concentrations and age, and establish the earliest age at which NfL concentrations begin to diverge between mutation carriers and non-carriers.
We enrolled a cohort of 1070 PSEN1 E280A mutation carriers and 1074 non-carriers with baseline assessments; of these participants, longitudinal measures (with a mean follow-up of 6 years) were available for 242 mutation carriers and 262 non-carriers. Plasma NfL measurements increased with age in both groups (p<0·0001), and began to differentiate carriers from non-carriers when aged 22 years (22 years before the estimated median age at mild cognitive impairment onset of 44 years), although the ability of plasma NfL to discriminate between carriers and non-carriers only reached high sensitivity close to the age of clinical onset.
Our findings further support the promise of plasma NfL as a biomarker of active neurodegeneration in the detection and tracking of Alzheimer's disease and the evaluation of disease-modifying therapies.
National Institute on Aging, National Institute of Neurological Disorders and Stroke, Banner Alzheimer's Foundation, COLCIENCIAS, the Torsten Söderberg Foundation, the Swedish Research Council, the Swedish Alzheimer Foundation, the Swedish Brain Foundation, and the Swedish state under the ALF-agreement.
El objetivo principal de este artículo es describir la estabilidad de sistemas lineales positivos mediante politopos invariantes en el espacio de estados, de forma que a cada sistema estable le ...corresponde una familia de politopos invariantes. Además, para el caso del plano, presentamos una manera de estabilizar sistemas lineales positivos mediante el diseño de controles lineales.
The development of active food packaging based on natural polymers and pigments is of interest to the food industry. Pigments to make this type of packaging can be extracted from waste and ...by-products, giving added value and reducing production costs. Therefore, the objective of this work was to study the physicochemical, structural, mechanical and antioxidant properties of zein films with non-ultrafiltered (Z-NUBE for films or NUBE for extract) and ultrafiltered betalain extract (Z-UBE for films and UBE for extract) from beet bagasse as active food packaging. SEM analysis showed that the films with Z-UBE showed a more uniform and smoother surface compared to Z-NUBE. FTIR analysis showed that the possible interaction of zein with betalains was due to physical forces, mains by hydrogen bonds. TGA analysis showed that the average degradation temperature for all films was around 313 °C, giving a greater weight loss due to the interaction between zein and betalains. Analysis by contact angle determined that films with Z-UBE were the most hydrophobic that films with Z-NUBE. Also, as the concentration of betalains increases, their hydrophobicity increases. Regarding antioxidant properties, Z-NUBE showed better antioxidant activity than films with NUBE, mainly by the FRAP method, Z-NUBE1 and Z-UBE1 (both with 1% extract) were 251.161 ± 16.45 and 523.49 ± 26.04 μM T/g, respectively. For the phytochemical content, Z-UBE showed a higher amount of betalains (specifically betacyanins) with increasing concentration between 56.05 and 76.43%, but similar content of phenolic compounds, less than 0.1 mEq GA/g. Therefore, it is concluded that the addition of UBE to zein films has a potential application in the food industry as active food packaging in refrigerated meats and products stored at room temperature.
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•Waste from the beet juice industry can be used.•Compounds from beet waste have added value as antioxidants.•Morphological, physicochemical and mechanical properties of zein films were improved with Ulltrafiltered Betalain Extract.•Antioxidant activity of zein films increase with the incorporation of ultrafiltered extract.•Incorporation of beet waste extract to zein films has potential as an active food packaging.
To develop and compare contrast material injection protocols suitable for hepatic helical computed tomography (CT).
Monophasic and biphasic helical CT were performed with contrast material with an ...iodine load of 50 g at 3 mL/sec for 60 seconds or at 5 mL/sec for 10 seconds and 2 mL/sec for 65 seconds, respectively. In 58 men and 51 women, aged 22-77 years, aortic and hepatic enhancement curves were constructed from a cluster acquisition with a slip-ring scanner operating in a nonhelical mode.
The monophasic protocol produced a higher peak aortic enhancement (180 HU +/- 47 +/- 1 standard deviation) than the biphasic protocol (150 HU +/- 24). Peak hepatic enhancement (63-64 HU +/- 15) was equivalent. Calculated equilibrium time for the monophasic protocol was 95.1 seconds and for the biphasic protocol was 101.4 seconds. The contrast enhancement index differed only marginally between the two protocols (P < .4).
Monophasic and biphasic protocols produced equivalent results when tailored for the shorter temporal window of a rapid-sequence helical acquisition.
This work provides the first description of the synthesis and characterization of water-soluble chitosan (Cs) derivatives based on the conjugation of both diethylaminoethyl (DEAE) and catechol groups ...onto the Cs backbone (Cs–DC) in order to obtain a Cs derivative with antioxidant and antimicrobial properties. The degree of substitution DS (%) was 35.46% for DEAE and 2.53% for catechol, determined by spectroscopy. Changes in the molecular packing due to the incorporation of both pendant groups were described by X-ray diffraction and thermogravimetric analysis. For Cs, the crystallinity index was 59.46% and the maximum decomposition rate appeared at 309.3 °C, while for Cs–DC, the values corresponded to 16.98% and 236.4 °C, respectively. The incorporation of DEAE and catechol groups also increases the solubility of the polymer at pH > 7 without harming the antimicrobial activity displayed by the unmodified polymer. The catecholic derivatives increase the radical scavenging activity in terms of the half-maximum effective concentration (EC50). An EC50 of 1.20 μg/mL was found for neat hydrocaffeic acid (HCA) solution, while for chitosan–catechol (Cs–Ca) and Cs–DC solutions, concentrations equivalent to free HCA of 0.33 and 0.41 μg/mL were required, respectively. Cell culture results show that all Cs derivatives have low cytotoxicity, and Cs–DC showed the ability to reduce the activity of reactive oxygen species by 40% at concentrations as low as 4 μg/mL. Polymeric nanoparticles of Cs derivatives with a hydrodynamic diameter (D h) of around 200 nm, unimodal size distributions, and a negative ζ-potential were obtained by ionotropic gelation and coated with hyaluronic acid in aqueous suspension, providing the multifunctional nanoparticles with higher stability and a narrower size distribution.
Pig farming is an important activity in the economic development of Mexico with millions of tons of meat produced annually. Antibiotics are used in therapeutic dose to prevent diseases, and sometimes ...as growth promoters. These compounds are not completely metabolized; they are carried into the environment in its active form at concentrations that could induce antibiotic resistance in bacteria, which could be transferred to human pathogens by horizontal gene transfer. The objective of this work was to develop methods of analysis for simultaneous quantification of the antibiotics Oxytetracycline (OXT), Chlortetracycline (CLT), Enrofloxacin (ENRO) and Ciprofloxacin (CIPRO) by field-amplified sampling injection in capillary zone electrophoresis (FASI-CZE). The method was validated by parameters of (1) linearity, obtaining a lineal range of 0.05 at 1 μg mL−1 for ENRO and CIPRO, and from 0.1 to 1 μg mL−1 for OXT and CLT; (2) precision, obtaining values <5% of standard deviation for CIPRO and ENRO and <10% of standard deviation for OXT and CLT; (3) accuracy, with recovery values from 93 to 115%; (4) selectivity, with values of resolution >2 for the all antibiotics tested. To prove the method, a sample of wastewater from a local pig farm was analyzed, detecting a concentration of 0.140 ± 0.009 for OXT. This concentration was higher than the minimal selective concentration, indicating the point in which resistance to a determined antibiotic could develop. The methods were validated with precision and sensitivity comparable to chromatographic methods, which can be used to analyze wastewater from pig farms directly.
Objective
The examination of individuals who carry fully penetrant genetic alterations that result in familial Alzheimer's disease (FAD) provides a unique model for studying the early presymptomatic ...disease stages. In AD, deficits in episodic and associative memory have been linked to structural and functional changes within the hippocampal system. This study used functional MRI (fMRI) to examine hippocampal function in a group of healthy, young, cognitively‐intact presymptomatic individuals (average age 33.7 years) who carry the E280A presenilin‐1 (PS1) genetic mutation for FAD. These PS1 subjects will go on to develop the first symptoms of the disease around the age of 45 years. Our objective was to examine hippocampal function years before the onset of clinical symptoms.
Methods
Twenty carriers of the Alzheimer's‐associated E280A PS1 mutation and 19 PS1‐negative control subjects participated. Both groups were matched for age, sex, education level, and neuropsychological test performance. All participants performed a face‐name associative encoding task while in a Phillips 1.5T fMRI scanner. Analysis focused on the hippocampal system.
Results
Despite identical behavioral performance, presymptomatic PS1 mutation carriers exhibited increased activation of the right anterior hippocampus during encoding of novel face‐name associations compared to matched controls.
Interpretation
Our results demonstrate that functional changes within the hippocampal memory system occur years before cognitive decline in FAD. These presymptomatic changes in hippocampal physiology in FAD suggest that hippocampal fMRI patterns during associative encoding may also provide a preclinical biomarker in sporadic AD. ANN NEUROL 2010
There is an urgent need to find effective presymptomatic Alzheimer's disease (AD) treatments that reduce the risk of AD symptoms or prevent them completely. It currently takes too many healthy ...people, too much money and too many years to evaluate the range of promising presymptomatic treatments using clinical endpoints. We have used brain imaging and other measurements to track some of the earliest changes associated with the predisposition to AD. We have proposed the Alzheimer's Prevention Initiative (API) to evaluate investigational amyloid-modifying treatments in healthy people who, based on their age and genetic background, are at the highest imminent risk of developing symptomatic AD using brain imaging, cerebrospinal fluid (CSF), and cognitive endpoints. In one trial, we propose to study AD-causing presenilin 1 PS1 mutation carriers from the world's largest early-onset AD kindred in Antioquia, Colombia, close to their estimated average age at clinical onset. In another trial, we propose to study apolipoprotein E (APOE) ε4 homozygotes (and possibly heterozygotes) close to their estimated average age at clinical onset. The API has several goals: 1) to evaluate investigational AD-modifying treatments sooner than otherwise possible; 2) to determine the extent to which the treatment's brain imaging and other biomarker effects predict a clinical benefit-information needed to help qualify biomarker endpoints for use in pivotal prevention trials; 3) to provide a better test of the amyloid hypothesis than clinical trials in symptomatic patients, when these treatments may be too little too late to exert their most profound effect; 4) to establish AD prevention registries needed to support these and other presymptomatic AD trials; and 5) to give those individuals at highest imminent risk of AD symptoms access to the most promising investigational treatments in clinical trials.
Celotno besedilo
Dostopno za:
DOBA, IZUM, KILJ, NUK, PILJ, PNG, SAZU, UILJ, UKNU, UL, UM, UPUK
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