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1.
Anal Biochem ; 678: 115271, 2023 10 01.
Artigo em Inglês | MEDLINE | ID: mdl-37543277

RESUMO

With the development of genomic technologies, the isolation of genomic DNA (gDNA) from clinical samples is increasingly required for clinical diagnostics and research studies. In this study, we explored the potential of utilizing various leftover blood samples obtained from routine clinical tests as a viable source of gDNA. Using an automated method with optimized pre-treatments, we obtained gDNA from seven types of clinical leftover blood, with average yields of gDNA ranging from 3.11 ± 0.45 to 22.45 ± 4.83 µg. Additionally, we investigated the impact of storage conditions on gDNA recovery, resulting in yields of 8.62-68.08 µg when extracting gDNA from EDTA leftover blood samples stored at 4 °C for up to 13 weeks or -80 °C for up to 78 weeks. Furthermore, we successfully obtained sequenceable gDNA from both Serum Separator Tube and EDTA Tube using a 96-well format extraction, with yields ranging from 0.61 to 71.29 µg and 3.94-215.98 µg, respectively. Our findings demonstrate the feasibility of using automated high-throughput platforms for gDNA extraction from various clinical leftover blood samples with the proper pre-treatments.


Assuntos
DNA , Genoma , Ácido Edético , DNA/genética , Coleta de Amostras Sanguíneas , Genômica
2.
Pain Med ; 24(Suppl 1): S71-S80, 2023 08 04.
Artigo em Inglês | MEDLINE | ID: mdl-36525387

RESUMO

The Biospecimen Collection and Processing Working Group of the National Institutes of Health (NIH) HEAL Initiative BACPAC Research Program was charged with identifying molecular biomarkers of interest to chronic low back pain (cLBP). Having identified biomarkers of interest, the Working Group worked with the New York University Grossman School of Medicine, Center for Biospecimen Research and Development-funded by the Early Phase Pain Investigation Clinical Network Data Coordinating Center-to harmonize consortium-wide and site-specific efforts for biospecimen collection and analysis. Biospecimen collected are saliva, blood (whole, plasma, serum), urine, stool, and spine tissue (paraspinal muscle, ligamentum flavum, vertebral bone, facet cartilage, disc endplate, annulus fibrosus, or nucleus pulposus). The omics data acquisition and analyses derived from the biospecimen include genomics and epigenetics from DNA, proteomics from protein, transcriptomics from RNA, and microbiomics from 16S rRNA. These analyses contribute to the overarching goal of BACPAC to phenotype cLBP and will guide future efforts for precision medicine treatment.


Assuntos
Dor Lombar , Humanos , RNA Ribossômico 16S , Biomarcadores , Dor Lombar/terapia , Fenótipo , New York
3.
Intervirology ; 2022 Dec 01.
Artigo em Inglês | MEDLINE | ID: mdl-36455522

RESUMO

BACKGROUND: Emerging virus infections provoke health problems in people and animals, which generate social, and economic issues worldwide. This has spurred the search for new pharmacological strategies to confront them. SUMMARY: The purpose of this review is to draw the reader's attention to pharmacological evaluations of glycyrrhizic acid (GA) and its analogs on the broad range of viruses known in human and veterinary medicine. GA is the main water-soluble constituent extracted from the roots of plants from the genus Glycyrrhiza, commonly known as licorice root. It has long been used due to its broad spectrum of bioactivities, including anti-inflammatory, antiulcer, and antitumor properties. It has also been proposed as an antiviral agent. Medicines derived from GA are currently being used to combat acute and chronic hepatitis and herpes viruses. KEY MESSAGES: This review suggests that GA could be a new broad-spectrum antiviral due to its ability to inhibit DNA or RNA viruses both in vitro and in vivo. GA could be a potential drug for preventing and/or treating various viral diseases.

4.
J Transl Med ; 18(1): 219, 2020 06 01.
Artigo em Inglês | MEDLINE | ID: mdl-32487093

RESUMO

The outbreak of the novel coronavirus disease 2019 (COVID-19) and consequent social distancing practices have disrupted essential clinical research functions worldwide. Ironically, this coincides with an immediate need for research to comprehend the biology of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) and the pathology of COVID-19. As the global crisis has already led to over 15,000 deaths out of 175,000 confirmed cases in New York City and Nassau County, NY alone, it is increasingly urgent to collect patient biospecimens linked to active clinical follow up. However, building a COVID-19 biorepository amidst the active pandemic is a complex and delicate task. To help facilitate rapid, robust, and regulated research on this novel virus, we report on the successful model implemented by New York University Langone Health (NYULH) within days of outbreak in the most challenging hot spot of infection globally. Using an amended institutional biobanking protocol, these efforts led to accrual of 11,120 patients presenting for SARS-CoV-2 testing, 4267 (38.4%) of whom tested positive for COVID-19. The recently reported genomic characterization of SARS-CoV-2 in the New York City Region, which is a crucial development in tracing sources of infection and asymptomatic spread of the novel virus, is the first outcome of this effort. While this growing resource actively supports studies of the New York outbreak in real time, a worldwide effort is necessary to build a collective arsenal of research tools to deal with the global crisis now, and to exploit the virus's biology for translational innovation that outlasts humanity's current dilemma.


Assuntos
Betacoronavirus/fisiologia , Bancos de Espécimes Biológicos , Pesquisa Biomédica , Infecções por Coronavirus/epidemiologia , Pandemias , Pneumonia Viral/epidemiologia , COVID-19 , Bases de Dados como Assunto , Humanos , SARS-CoV-2
5.
Sensors (Basel) ; 20(18)2020 Sep 09.
Artigo em Inglês | MEDLINE | ID: mdl-32916964

RESUMO

Currently, a high percentage of the world's population lives in urban areas, and this proportion will increase in the coming decades. In this context, indoor positioning systems (IPSs) have been a topic of great interest for researchers. On the other hand, Visible Light Communication (VLC) systems have advantages over RF technologies; for instance, they do not need satellite signals or the absence of electromagnetic interference to achieve positioning. Nowadays, in the context of Indoor Positioning (IPS), Visible Light Positioning (VLP) systems have become a strong alternative to RF-based systems, allowing the reduction in costs and time to market. This paper shows a low cost VLP solution for indoor systems. This includes multiple programmable beacons and a receiver which can be plugged to a smartphone running a specific app. The position information will be quickly and securely available through the interchange between the receiver and any configurable LED-beacon which is strategically disposed in an area. The implementation is simple, inexpensive, and no direct communication with any data server is required.

6.
J Food Sci Technol ; 56(7): 3177-3184, 2019 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-31274885

RESUMO

In order to identify pigmented corn with nutraceutical potential, the secondary metabolite content, the antioxidant capacity and antimutagenic activity of red, and blue corn were analyzed. The ranges of total phenolic, flavonoid and anthocyanin contents of the corn samples were from 69.4 to 212.8 mg gallic ac. equiv./100 g DW, 0.07 to 12.19 mg (+) catechin eq./100 g DW and 3.89 to 34.17 mg cyanidin-3-O-glucoside eq./100 g DW, respectively. The phenolic extracts demonstrated the highest antioxidant capacity evaluated by the ABTS assay displaying values from 2.06 to 7.34 mmol Trolox/100 g DW. None of the extracts was toxic to the tested bacteria strains TA98 and TA100. For TA98 tester strain, percentage inhibition values against AFB1 mutagenicity from 61 to 93, and 38 to 75 for flavonoid and anthocyanin extracts were obtained. The total phenol and anthocyanin contents correlate with the observed antioxidant capacity. The most biological active corn samples were the blue color while the least actives were the red ones. The results show that the studied blue corn samples are good sources of antioxidant and antimutagenic compounds, which could use to develop products that contribute to human health.

7.
Ann Bot ; 121(6): 1257-1264, 2018 05 11.
Artigo em Inglês | MEDLINE | ID: mdl-29471370

RESUMO

Background and Aims: Capsella is a model genus for studying the transition from outcrossing to selfing, with or without change in ploidy levels. The genomic consequences and changes in reproductive traits (selfing syndrome) associated with these shifts have been studied in depth. However, potential ecological divergence among species of the genus has not been determined. Among ecological traits, competitive ability could be relevant for selfing evolution, as selfing has been shown to be statistically associated with reduced competitiveness in a recent meta-analysis. Methods: We assessed the effect of competition on three Capsella species differing in their mating system and ploidy level. We used an experimental design where fitness related traits were measured in focal individuals with and without competitors. Key Results: The diploid selfer (C. rubella) was most sensitive to competition, whereas the tetraploid selfer (C. bursa-pastoris) performed the best, with the diploid outcrosser (C. grandiflora) being intermediate. Conclusions: These results add to the detailed characterization of Capsella species and highlight the possible roles of ecological context and ploidy in the evolutionary trajectories of selfing species.


Assuntos
Capsella/fisiologia , Ploidias , Evolução Biológica , Capsella/genética , Flores/fisiologia , Polinização/genética , Polinização/fisiologia , Reprodução , Autofertilização/genética , Autofertilização/fisiologia
9.
J Food Sci Technol ; 53(10): 3787-3794, 2016 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-28017994

RESUMO

Most of antimicrobial peptides interact with food components decreasing their activity, which limit their successful incorporation into packaging material, functional foods and edible films. The aim of this work was to develop a nisin carrier. Nanofibers of amaranth protein and pullulan (50:50) loaded with nisin were obtained by electrospinning. The nanofibers morphology was determined by scanning electron microscopy and fluorescent microscopy. The molecular interactions were characterized by infrared spectroscopy, X-ray diffraction, differential scanning calorimetry, and thermogravimetric analysis. The nisin loading efficiency as well as the antimicrobial activity against Leuconostoc mesenteroides were evaluated. The micrographs of the obtained materials exhibited smooth and continuous fibers with no defects characterized by diameters between 124 and 173 nm. The FTIR analysis showed intermolecular interactions mainly by hydrogen bonding. The electrospinning process improved the thermal properties of the polymeric mixture displacing the Tm peak to higher temperatures and increasing crystallinity. The antimicrobial activity of nisin in broth and agar against L. mesenteroides was maintained after incorporation into fibers. The results presented an outlook for the potential use of protein amaranth nanofibers when incorporating antimicrobials as a food preservation strategy.

10.
Plant Foods Hum Nutr ; 70(2): 146-52, 2015 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-25680741

RESUMO

Mexico has the highest per capita consumption of corn in the world, which is consumed mainly as tortilla. However, only a few in vivo studies have demonstrated the anticarcinogenic potential of some maize components against colon cancer, but not as a whole food product. Therefore, our objective was to evaluate the protective effect of corn tortillas against the development of colon cancer. First, blue, red, yellow and white corn grains were lime-cooked and processed to elaborate tortillas. Then, tortillas were administered into the diet (27% w/w) to male Sprague-Dawley rats induced with the colon carcinogen 1,2-dimethylhydrazine (DMH). Our results indicated that consumption of tortillas, particularly from white and blue corns, significantly decreased adenocarcinoma incidence (up to 77.5%) and mean number compared to DMH-treated animals. In addition, an inhibition of ß-glucuronidase activity, and induction of detoxifying enzymes in liver and colon, as well as a decrease in the expression of the two most important proliferative proteins (K-ras and ß-catenin) involved in colon carcinogenesis, were also observed. These results highlight some of the molecular mechanisms related to the chemopreventive effect of tortillas, thus indicating that corn products retain their biological properties even after nixtamalization and tortilla processing.


Assuntos
1,2-Dimetilidrazina/toxicidade , Anticarcinógenos/farmacologia , Neoplasias do Colo/prevenção & controle , Manipulação de Alimentos , Zea mays/química , Animais , Colo/efeitos dos fármacos , Colo/enzimologia , Neoplasias do Colo/induzido quimicamente , Glucuronidase/antagonistas & inibidores , Glucuronidase/metabolismo , Glutationa Transferase/metabolismo , Fígado/efeitos dos fármacos , Fígado/enzimologia , Masculino , NAD(P)H Desidrogenase (Quinona)/metabolismo , Proteínas Proto-Oncogênicas p21(ras)/metabolismo , Ratos , Ratos Sprague-Dawley , beta Catenina/metabolismo
11.
ScientificWorldJournal ; 2014: 837215, 2014.
Artigo em Inglês | MEDLINE | ID: mdl-24995363

RESUMO

Natural food antimicrobials are bioactive compounds that inhibit the growth of microorganisms involved in food spoilage or food-borne illness. However, stability issues result in degradation and loss of antimicrobial activity. Nanoencapsulation allows protection of antimicrobial food agents from unfavorable environmental conditions and incompatibilities. Encapsulation of food antimicrobials control delivery increasing the concentration of the antimicrobials in specific areas and the improvement of passive cellular absorption mechanisms resulted in higher antimicrobial activity. This paper reviews the present state of the art of the nanostructures used as food antimicrobial carriers including nanoemulsions, nanoliposomes, nanoparticles, and nanofibers.


Assuntos
Anti-Infecciosos/administração & dosagem , Indústria Alimentícia/normas , Conservação de Alimentos/normas , Nanopartículas/administração & dosagem , Animais , Indústria Alimentícia/métodos , Conservação de Alimentos/métodos , Humanos
12.
Electrophoresis ; 34(14): 2129-35, 2013 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-23595251

RESUMO

A SU-8/Pyrex single-channel microchip integrating three 100 µm Pt electrodes (MCE-ED) for class-selective electrochemical index determination (CSEID) of phenolic acids and flavonoids in complex extracts of Tagetes lucida (Tl), Mentha piperita (Mp), Cymbopogon citratus (Cc), Calendula officinalis (Co), and Cynara scolymus (Cs) is proposed. Under strategic conditions controlled by a MES buffer (pH 5.0; 25 mM) and accordingly to the antioxidant acid-base properties, the simultaneous measurement of total acids and flavonoids indexes was achieved in less than 100 s with excellent analytical performance. The reliability of MCE-ED approach was demonstrated toward the high agreement between the total phenolic content obtained using microchip approach with those obtained by the well-established HPLC-DAD; revealing both identical order regarding the total phenolic content in the target samples. In addition, further comparison of MCE-ED with the traditional Folin-Ciocalteu antioxidant capacity assay, showed that MCE-ED approach could become a class-selective antioxidant capacity assay revealing that the sample antioxidant capacity was decreasing as Tl > Mp > Cs > Cc > Co according to their endogenous polyphenol content. These results suggested that the microchip approach is not only a reliable method for fast assessment of class-selective antioxidants constituting a very good alternative to the long analysis times and the using of toxic solvents required in HPLC but a novel truly antioxidant capacity assay. This excellent analytical performance is connected with the key-features of the "ready-to-use" system employed in this work such as portability, full integration of electrochemical detection, easy-operation, and potential MCE-ED disposability.


Assuntos
Antioxidantes/análise , Eletroforese em Microchip/instrumentação , Flavonoides/análise , Fenóis/análise , Extratos Vegetais/química , Plantas/química , Compostos de Epóxi/química , Desenho de Equipamento , Polímeros/química , Reprodutibilidade dos Testes
13.
Pharmaceuticals (Basel) ; 16(4)2023 Mar 23.
Artigo em Inglês | MEDLINE | ID: mdl-37111239

RESUMO

Traditional medicine in Latin America and mainly in Mexico represents an essential alternative for treating different diseases. The use of plants as medicine is the product of a rich cultural tradition of the indigenous peoples, in which a great variety of species are used for the treatment of gastrointestinal, respiratory, and mental diseases and some other sicknesses; the therapeutic efficacy that they possess is due to the properties that derive from the active ingredients of plants principally antioxidants, such as phenolic compounds, flavonoids, terpenes, and tannins. An antioxidant is a substance that, at low concentrations, delays or prevents substrate oxidation through the exchange of electrons. Different methods are used to determine the antioxidant activity and the most commonly used are described in the review. Cancer is a disease in which some cells multiply uncontrollably and spread to other parts of the body, a process known as metastasis. These cells can lead to the formation of tumors, which are lumps of tissue that can be cancerous (malignant) or noncancerous (benign). Generally, the treatment of this disease consists of surgery, radiotherapy, or chemotherapy, which have side effects that decrease the quality of life of patients, so new treatments, focusing on natural resources such as plants, can be developed. This review aims to gather scientific evidence on the antioxidant compounds present in plants used in traditional Mexican medicine, specifically as antitumor treatment in the most common cancer types worldwide (e.g., breast, liver, and colorectal cancer).

14.
Eur Endod J ; 8(1): 20-36, 2023 01.
Artigo em Inglês | MEDLINE | ID: mdl-36748442

RESUMO

Inflammatory radicular cysts (IRCs) are chronic lesions that follow the development of periapical granulomas (PGs). IRCs result from multiple inflammatory reactions led initially by several pro-inflammatory interleukins and growth factors that provoke the proliferation of epithelial cells derived from epithelial cell rests of Malassez present in the granulomatous tissue, followed by cyst formation and growth processes. Multiple theories have been proposed to help explain the molecular process involved in the development of the IRC from a PG. However, although multiple studies have demonstrated the presence of epithelial cells in most PGs, it is still not fully understood why not all PGs turn into IRCs, even though both are stages of the same inflammatory phenomenon and receive the same antigenic stimulus. Histopathological examination is currently the diagnostic gold standard for differentiating IRCs from PGs. Although multiple studies have evaluated the accuracy of non-invasive or minimally invasive methods in assessing the histopathological nature of the AP before the intervention, these studies' results are still controversial. This narrative review addresses the biological insights into the complex molecular mechanisms of IRC formation and its histopathological features. In addition, the relevant inflammatory molecular mediators for IRC development and the accuracy of non-invasive or minimally invasive diagnostic approaches are summarised. (EEJ-2022-03-041).


Assuntos
Granuloma Periapical , Cisto Radicular , Humanos , Cisto Radicular/diagnóstico , Cisto Radicular/metabolismo , Células Epiteliais/metabolismo , Células Epiteliais/patologia , Inflamação/patologia , Granuloma Periapical/metabolismo , Granuloma Periapical/patologia , Peptídeos e Proteínas de Sinalização Intercelular
15.
Pharmaceutics ; 14(10)2022 Sep 28.
Artigo em Inglês | MEDLINE | ID: mdl-36297503

RESUMO

Gold nanoparticles (AuNPs) are promising nanomaterials exhibiting anti-cancer effects. Green AuNPs synthesis using plant extracts can be used to achieve stable and beneficial nanoparticles due to their content of bioactive compounds. This research aimed to synthesize and evaluate the antiproliferative and caspase-3 activity induction of green AuNPs synthesized with common mullein (V. thapsus) flowers (AuNPsME) and castor bean (R. communis) leaves (AuNPsCE) ethanolic extracts in human HT29 and SW480 colorectal cancer cells. Their effect was compared with chemically synthesized AuNPs (AuNPsCS). The extracts mainly contained p-coumaric acid (71.88-79.93 µg/g), ferulic acid (19.07-310.71 µg/g), and rutin (8.14-13.31 µg/g). The obtained nanoparticles presented typical FT-IR bands confirming the inclusion of polyphenols from V. thapsus and R. communis and spherical/quasi-spherical morphologies with diameters in the 20.06-37.14 nm range. The nanoparticles (20-200 µg/mL) showed antiproliferative effects in both cell lines, with AuNPsCE being the most potent (IC50 HT29: 110.10 and IC50SW480: 64.57 µg/mL). The AuNPsCS showed the lowest intracellular reactive oxygen species (ROS) generation in SW480 cells. All treatments induced caspase 3/7 activity to a similar or greater extent than 30 mM H2O2-treated cells. Results indicated the suitability of V. thapsus and R. communis extracts to synthesize AuNPs, displaying a stronger antiproliferative effect than AuNPsCS.

16.
Biomolecules ; 12(11)2022 11 07.
Artigo em Inglês | MEDLINE | ID: mdl-36358999

RESUMO

Pomegranate (PMG; Punica granatum L.) fruits possess a well-balanced nutrient/phytochemical composition, with proven adjuvant benefits in experimental cancer chemotherapy; however, such bioactivity could be affected by PMG's phenogenotype (varietal). Here, the chemical and phytochemical (UPLC-DAD-MS2) composition, antioxidant capacity and anticancer potential [in vitro (MTT assay) and in silico (foodinformatics)] of three PMG fruits of different aryl color [red (cv. Wonderful), pink (cv. Molar de Elche), and white (cv. Indian)] were evaluated. The macro/micronutrient (ascorbic acid, tocols, carotenoids), organic acid (citric/malic), and polyphenol content were changed by PMG's varietal and total antioxidant activity (ABTS, alcoholic > hexane extract) in the order of red > pink > white. However, their in vitro cytotoxicity was the same (IC50 > 200 µg.mL-1) against normal (retinal) and cancer (breast, lung, colorectal) cell lines. Sixteen major phytochemicals were tentatively identified, four of them with a high GI absorption/bioavailability score [Ellagic (pink), vanillic (red), gallic (white) acids, D-(+)-catechin (white)] and three of them with multiple molecular targets [Ellagic (52) > vanillic (32) > gallic (23)] associated with anticancer (at initiation and promotion stages) activity. The anticancer potential of the PMG fruit is phenogenotype-specific, although it could be more effective in nutraceutical formulations (concentrates).


Assuntos
Lythraceae , Punica granatum , Frutas/química , Lythraceae/química , Polifenóis/análise , Compostos Fitoquímicos/química , Antioxidantes/química , Extratos Vegetais/química
17.
Lancet Infect Dis ; 22(5): 636-648, 2022 05.
Artigo em Inglês | MEDLINE | ID: mdl-35090638

RESUMO

BACKGROUND: We evaluated our SARS-CoV-2 prefusion spike recombinant protein vaccine (CoV2 preS dTM) with different adjuvants, unadjuvanted, and in a one-injection and two-injection dosing schedule in a previous phase 1-2 study. Based on interim results from that study, we selected a two-injection schedule and the AS03 adjuvant for further clinical development. However, lower than expected antibody responses, particularly in older adults, and higher than expected reactogenicity after the second vaccination were observed. In the current study, we evaluated the safety and immunogenicity of an optimised formulation of CoV2 preS dTM adjuvanted with AS03 to inform progression to phase 3 clinical trial. METHODS: This phase 2, randomised, parallel-group, dose-ranging study was done in adults (≥18 years old), including those with pre-existing medical conditions, those who were immunocompromised (except those with recent organ transplant or chemotherapy) and those with a potentially increased risk for severe COVID-19, at 20 clinical research centres in the USA and Honduras. Women who were pregnant or lactating or, for those of childbearing potential, not using an effective method of contraception or abstinence, and those who had received a COVID-19 vaccine, were excluded. Participants were randomly assigned (1:1:1) using an interactive response technology system, with stratification by age (18-59 years and ≥60 years), rapid serodiagnostic test result (positive or negative), and high-risk medical conditions (yes or no), to receive two injections (day 1 and day 22) of 5 7mu;g (low dose), 10 7mu;g (medium dose), or 15 7mu;g (high dose) CoV2 preS dTM antigen with fixed AS03 content. All participants and outcome assessors were masked to group assignment; unmasked study staff involved in vaccine preparation were not involved in safety outcome assessments. All laboratory staff performing the assays were masked to treatment. The primary safety objective was to describe the safety profile in all participants, for each candidate vaccine formulation. Safety endpoints were evaluated for all randomised participants who received at least one dose of the study vaccine (safety analysis set), and are presented here for the interim study period (up to day 43). The primary immunogenicity objective was to describe the neutralising antibody titres to the D614G variant 14 days after the second vaccination (day 36) in participants who were SARS-CoV-2 naive who received both injections, provided samples at day 1 and day 36, did not have protocol deviations, and did not receive an authorised COVID-19 vaccine before day 36. Neutralising antibodies were measured using a pseudovirus neutralisation assay and are presented here up to 14 days after the second dose. As a secondary immunogenicity objective, we assessed neutralising antibodies in non-naive participants. This trial is registered with ClinicalTrials.gov (NCT04762680) and is closed to new participants for the cohort reported here. FINDINGS: Of 722 participants enrolled and randomly assigned between Feb 24, 2021, and March 8, 2021, 721 received at least one injection (low dose=240, medium dose=239, and high dose=242). The proportion of participants reporting at least one solicited adverse reaction (injection site or systemic) in the first 7 days after any vaccination was similar between treatment groups (217 [91%] of 238 in the low-dose group, 213 [90%] of 237 in the medium-dose group, and 218 [91%] of 239 in the high-dose group); these adverse reactions were transient, were mostly mild to moderate in intensity, and occurred at a higher frequency and intensity after the second vaccination. Four participants reported immediate unsolicited adverse events; two (one each in the low-dose group and medium-dose group) were considered by the investigators to be vaccine related and two (one each in the low-dose and high-dose groups) were considered unrelated. Five participants reported seven vaccine-related medically attended adverse events (two in the low-dose group, one in the medium-dose group, and four in the high-dose group). No vaccine-related serious adverse events and no adverse events of special interest were reported. Among participants naive to SARS-CoV-2 at day 36, 158 (98%) of 162 in the low-dose group, 166 (99%) of 168 in the medium-dose group, and 163 (98%) of 166 in the high-dose group had at least a two-fold increase in neutralising antibody titres to the D614G variant from baseline. Neutralising antibody geometric mean titres (GMTs) at day 36 for participants who were naive were 2189 (95% CI 1744-2746) for the low-dose group, 2269 (1792-2873) for the medium-dose group, and 2895 (2294-3654) for the high-dose group. GMT ratios (day 36: day 1) were 107 (95% CI 85-135) in the low-dose group, 110 (87-140) in the medium-dose group, and 141 (111-179) in the high-dose group. Neutralising antibody titres in non-naive adults 21 days after one injection tended to be higher than titres after two injections in adults who were naive, with GMTs 21 days after one injection for participants who were non-naive being 3143 (95% CI 836-11 815) in the low-dose group, 2338 (593-9226) in the medium-dose group, and 7069 (1361-36 725) in the high-dose group. INTERPRETATION: Two injections of CoV2 preS dTM-AS03 showed acceptable safety and reactogenicity, and robust immunogenicity in adults who were SARS-CoV-2 naive and non-naive. These results supported progression to phase 3 evaluation of the 10 7mu;g antigen dose for primary vaccination and a 5 7mu;g antigen dose for booster vaccination. FUNDING: Sanofi Pasteur and Biomedical Advanced Research and Development Authority.


Assuntos
Vacinas contra COVID-19 , COVID-19 , Adjuvantes Imunológicos , Adolescente , Adulto , Idoso , Anticorpos Neutralizantes , Anticorpos Antivirais , COVID-19/prevenção & controle , Vacinas contra COVID-19/efeitos adversos , Método Duplo-Cego , Feminino , Humanos , Imunogenicidade da Vacina , Lactação , Pessoa de Meia-Idade , Proteínas Recombinantes , SARS-CoV-2 , Vacinas Sintéticas , Adulto Jovem
18.
Pediatr Res ; 70(5): 480-3, 2011 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-21775922

RESUMO

Familial dysautonomia (FD) is caused by an intronic splice mutation in the IKBKAP gene that leads to partial skipping of exon 20 and tissue-specific reduction in I-κ-B kinase complex-associated protein/elongation protein 1 (IKAP/ELP-1) expression. Kinetin (6-furfurylaminopurine) has been shown to improve splicing and increase WT IKBKAP mRNA and IKAP protein expression in FD cell lines and carriers. To determine whether oral kinetin treatment could alter mRNA splicing in FD subjects and was tolerable, we administered kinetin to eight FD individuals homozygous for the splice mutation. Subjects received 23.5 mg/Kg/d for 28 d. An increase in WT IKBKAP mRNA expression in leukocytes was noted after 8 d in six of eight individuals; after 28 d, the mean increase compared with baseline was significant (p = 0.002). We have demonstrated that kinetin is tolerable in this medically fragile population. Not only did kinetin produce the desired effect on splicing in FD patients but also that effect seems to improve with time despite lack of dose change. This is the first report of a drug that produces in vivo mRNA splicing changes in individuals with FD and supports future long-term trials to determine whether kinetin will prove therapeutic in FD patients.


Assuntos
Proteínas de Transporte/metabolismo , Disautonomia Familiar/fisiopatologia , Regulação da Expressão Gênica/efeitos dos fármacos , Cinetina/farmacologia , Splicing de RNA/efeitos dos fármacos , RNA Mensageiro/metabolismo , Administração Oral , Adulto , Análise de Variância , Área Sob a Curva , Proteínas de Transporte/genética , Disautonomia Familiar/genética , Feminino , Humanos , Cinetina/administração & dosagem , Cinetina/sangue , Cinetina/farmacocinética , Masculino , New York , Splicing de RNA/fisiologia , Fatores de Elongação da Transcrição
19.
Environ Sci Pollut Res Int ; 28(28): 37130-37141, 2021 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-33710485

RESUMO

Nowadays, the use of different nanoscale structures has been introduced to a large number of research areas. One of these is the treatment and remediation of water through photocatalytic processes, seeking to reuse wastewater for agriculture. In this paper, Lactuca sativa, Coriandrum sativum, and Capsicum annuum were used as crop models to observe the effects in plant growth and the secondary metabolism of different water qualities and types used in the watering process. Initial results show that the photocatalytic process's water maintains a pH and ion concentration within the allowed limits, significantly reducing the number of bacteria. Along the growth process, an influence on germination times, appearance of true leaves, maturation, and fruit production depending on the type of water used is observed, obtaining the best results in both growth times and quantity of fruits, for the 50% and 70% disinfected water/tap water (DW/TAW) study groups. Secondary metabolites, such as phenols, flavonoids, and antioxidant activity, were studied to evaluate changes in the vegetables' composition, showing increased concentration for the disinfected water groups in most specimens. Additionally, no traces of metals and microorganisms were detected, concluding that the crops are viable to be consumed by human beings.


Assuntos
Capsicum , Coriandrum , Nanopartículas , Humanos , Lactuca , Prata , Titânio , Água
20.
J Child Psychol Psychiatry ; 51(8): 935-43, 2010 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-20406333

RESUMO

BACKGROUND: Although adolescent major depressive disorder (MDD) is acknowledged to be a heterogeneous disorder, no studies have reported on biological correlates of its clinical subgroups. This study addresses this issue by examining whether adolescent MDD with and without melancholic features (M-MDD and NonM-MDD) have distinct biological features in the kynurenine pathway (KP). The KP is initiated by pro-inflammatory cytokines via induction of the enzyme indoleamine 2,3-dioxygenase (IDO), which degrades tryptophan (TRP) into kynurenine (KYN). KYN is further metabolized into neurotoxins linked to neuronal dysfunction in MDD. Hypotheses were that, compared to healthy controls and to NonM-MDD adolescents, adolescents with M-MDD would exhibit: (i) increased activation of the KP [i.e., increased KYN and KYN/TRP (reflecting IDO activity)]; (ii) greater neurotoxic loads [i.e., increased 3-hydroxyanthranilic acid (3-HAA, neurotoxin) and 3-HAA/KYN (reflecting production of neurotoxins)]; and (iii) decreased TRP. We also examined relationships between severity of MDD and KP metabolites. METHODS: Subjects were 20 adolescents with M-MDD, 30 adolescents with NonM-MDD, and 22 healthy adolescents. MDD episode duration had to be >or= 6 weeks and Children's Depression Rating Scale-Revised (CDRS-R) scores were >or= 36. Blood samples were collected at AM after an overnight fast and analyzed using high-performance liquid chromatography. Group contrasts relied on analysis of covariance based on ranks, adjusted for age, gender, and CDRS-R scores. Analyses were repeated excluding medicated patients. Fisher's protected least significant difference was used for multiple comparisons. RESULTS: As hypothesized, KYN/TRP ratios were elevated and TRP concentrations were reduced in adolescents with M-MDD compared to NonM-MDD adolescents (p = .001 and .006, respectively) and to healthy controls (p = .008 and .022, respectively). These findings remained significant when medicated patients were excluded from the analyses. Significant correlations were obtained exclusively in the M-MDD group between KYN and 3-HAA/KYN and CDRS-R. CONCLUSIONS: Findings support the notion that adolescent M-MDD may represent a biologically distinct clinical syndrome.


Assuntos
Transtorno Depressivo Maior/fisiopatologia , Transtorno Depressivo/fisiopatologia , Cinurenina/sangue , Ácido 3-Hidroxiantranílico/metabolismo , Adolescente , Criança , Citocinas/sangue , Transtorno Depressivo/diagnóstico , Transtorno Depressivo/psicologia , Transtorno Depressivo Maior/diagnóstico , Transtorno Depressivo Maior/psicologia , Indução Enzimática , Feminino , Humanos , Indolamina-Pirrol 2,3,-Dioxigenase/sangue , Mediadores da Inflamação/sangue , Masculino , Neurotoxinas/sangue , Valores de Referência , Triptofano/sangue , Adulto Jovem
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