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1.
BMC Genomics ; 23(1): 17, 2022 Jan 08.
Artigo em Inglês | MEDLINE | ID: mdl-34996357

RESUMO

BACKGROUND: Schisandra chinensis, an ancient member of the most basal angiosperm lineage which is known as the ANITA, is a fruit-bearing vine with the pharmacological effects of a multidrug system, such as antioxidant, anti-inflammatory, cardioprotective, neuroprotective, anti-osteoporosis effects. Its major bioactive compound is represented by lignans such as schisandrin. Molecular characterization of lignan biosynthesis in S. chinensis is of great importance for improving the production of this class of active compound. However, the biosynthetic mechanism of schisandrin remains largely unknown. RESULTS: To understand the potential key catalytic steps and their regulation of schisandrin biosynthesis, we generated genome-wide transcriptome data from three different tissues of S. chinensis cultivar Cheongsoon, including leaf, root, and fruit, via long- and short-read sequencing technologies. A total of 132,856 assembled transcripts were generated with an average length of 1.9 kb and high assembly completeness. Overall, our data presented effective, accurate gene annotation in the prediction of functional pathways. In particular, the annotation revealed the abundance of transcripts related to phenylpropanoid biosynthesis. Remarkably, transcriptome profiling during fruit development of S. chinensis cultivar Cheongsoon revealed that the phenylpropanoid biosynthetic pathway, specific to coniferyl alcohol biosynthesis, showed a tendency to be upregulated at the postfruit development stage. Further the analysis also revealed that the pathway forms a transcriptional network with fruit ripening-related genes, especially the ABA signaling-related pathway. Finally, candidate unigenes homologous to isoeugenol synthase 1 (IGS1) and dirigent-like protein (DIR), which are subsequently activated by phenylpropanoid biosynthesis and thus catalyze key upstream steps in schisandrin biosynthesis, were identified. Their expression was increased at the postfruit development stage, suggesting that they may be involved in the regulation of schisandrin biosynthesis in S. chinensis. CONCLUSIONS: Our results provide new insights into the production and accumulation of schisandrin in S. chinensis berries and will be utilized as a valuable transcriptomic resource for improving the schisandrin content.


Assuntos
Lignanas , Schisandra , Antioxidantes , Frutas/química , Frutas/genética , Lignanas/análise , Transcriptoma
2.
MAbs ; 14(1): 2013594, 2022.
Artigo em Inglês | MEDLINE | ID: mdl-35000569

RESUMO

The ongoing SARS-CoV-2 coronavirus pandemic of 2020-2021 underscores the need for manufacturing platforms that can rapidly produce monoclonal antibody (mAb) therapies. As reported here, a platform based on Nicotiana benthamiana produced mAb therapeutics with high batch-to-batch reproducibility and flexibility, enabling production of 19 different mAbs of sufficient purity and safety for clinical application(s). With a single manufacturing run, impurities were effectively removed for a representative mAb product (the ZMapp component c4G7). Our results show for the first time the reproducibility of the platform for production of multiple batches of clinical-grade mAb, manufactured under current Good Manufacturing Practices, from Nicotiana benthamiana. The flexibility of the system was confirmed by the results of release testing of 19 different mAbs generated with the platform. The process from plant infection to product can be completed within 10 days. Therefore, with a constant supply of plants, response to the outbreak of an infectious disease could be initiated within a matter of weeks. Thus, these data demonstrated that this platform represents a reproducible, flexible system for rapid production of mAb therapeutics to support clinical development.


Assuntos
Anticorpos Monoclonais , Anticorpos Antivirais , COVID-19/imunologia , Plantas Geneticamente Modificadas , SARS-CoV-2/imunologia , Tabaco , Anticorpos Monoclonais/biossíntese , Anticorpos Monoclonais/química , Anticorpos Monoclonais/genética , Anticorpos Monoclonais/imunologia , Anticorpos Antivirais/biossíntese , Anticorpos Antivirais/química , Anticorpos Antivirais/genética , Anticorpos Antivirais/imunologia , COVID-19/tratamento farmacológico , Humanos , Plantas Geneticamente Modificadas/química , Plantas Geneticamente Modificadas/genética , Plantas Geneticamente Modificadas/crescimento & desenvolvimento , Plantas Geneticamente Modificadas/imunologia , Proteínas Recombinantes/biossíntese , Proteínas Recombinantes/química , Proteínas Recombinantes/genética , Proteínas Recombinantes/imunologia , Tabaco/química , Tabaco/genética , Tabaco/crescimento & desenvolvimento , Tabaco/imunologia
3.
World J Microbiol Biotechnol ; 38(1): 18, 2022 Jan 03.
Artigo em Inglês | MEDLINE | ID: mdl-34977979

RESUMO

Lantibiotics are a promising class of natural antimicrobial peptides. Lichenicidin is a two-peptide lantibiotic in which two mature peptides act synergistically to exhibit full bioactivity. Considering the two-peptide lantibiotics described so far, only cytolysin has been deeply characterized in terms of toxicity towards eukaryotic cells and it was found to be hemolytic and cytotoxic. This work aimed to improve the production of lichenicidin in vivo and characterize its antibacterial activity and toxicity against human cells. Peptides were purified and minimal inhibitory concentration (MIC) was determined against several strains; a time-kill assay was performed with Staphylococcus aureus. The hemolytic effect of lichenicidin was evaluated on blood samples from healthy donors and its toxicity towards human fibroblasts. The quantity of purified peptides was 1 mg/l Bliα and 0.4 mg/l Bliß. MIC for methicillin-sensitive and resistant S. aureus (MSSA and MRSA) strains were 16-32 µg/ml and 64-128 µg/ml, respectively. At the MIC, lichenicidin took less than 3 h to eliminate MSSA, indicating a strong bactericidal effect. It induces cell lysis at the highest concentration, an effect that might be potentiated by Bliß. Lichenicidin was not cytotoxic to human erythrocytes and fibroblasts. In this work, we evaluated the therapeutic potential of lichenicidin as a possible antimicrobial alternative.


Assuntos
Anti-Infecciosos/farmacologia , Bactérias/efeitos dos fármacos , Infecções Bacterianas/tratamento farmacológico , Bacteriocinas/farmacologia , Fibroblastos/efeitos dos fármacos , Peptídeos/farmacologia , Sequência de Aminoácidos , Anti-Infecciosos/química , Anti-Infecciosos/isolamento & purificação , Bacteriocinas/química , Bacteriocinas/isolamento & purificação , Linhagem Celular , Relação Dose-Resposta a Droga , Sinergismo Farmacológico , Hemólise , Humanos , Testes de Sensibilidade Microbiana
4.
Microb Cell Fact ; 21(1): 2, 2022 Jan 04.
Artigo em Inglês | MEDLINE | ID: mdl-34983520

RESUMO

Epidemic diseases and antibiotic resistance are urgent threats to global health, and human is confronted with an unprecedented dilemma to conquer them by expediting development of new natural product related drugs. C-nucleoside antibiotics, a remarkable group of microbial natural products with diverse biological activities, feature a heterocycle base linked with a ribosyl moiety via an unusual C-glycosidic bond, and have played significant roles in healthcare and for plant protection. Elucidating how nature biosynthesizes such a group of antibiotics has provided the basis for engineered biosynthesis as well as targeted genome mining of more C-nucleoside antibiotics towards improved properties. In this review, we mainly summarize the recent advances on the biosynthesis of C-nucleoside antibiotics, and we also tentatively discuss the future developments on rationally accessing C-nucleoside diversities in a more efficient and economical way via synthetic biology strategies.


Assuntos
Actinobacteria/metabolismo , Antibacterianos/biossíntese , Nucleosídeos/biossíntese , Biologia Sintética/métodos , Actinobacteria/genética , Produtos Biológicos/química , Streptomyces/genética , Streptomyces/metabolismo , Biologia Sintética/tendências
5.
Microb Cell Fact ; 21(1): 4, 2022 Jan 04.
Artigo em Inglês | MEDLINE | ID: mdl-34983528

RESUMO

Given a serious threat of multidrug-resistant bacterial pathogens to global healthcare, there is an urgent need to find effective antibacterial compounds to treat drug-resistant bacterial infections. In our previous studies, Bacillus velezensis CB6 with broad-spectrum antibacterial activity was obtained from the soil of Changbaishan, China. In this study, with methicillin-resistant Staphylococcus aureus as an indicator bacterium, an antibacterial protein was purified by ammonium sulfate precipitation, Sephadex G-75 column, QAE-Sephadex A 25 column and RP-HPLC, which demonstrated a molecular weight of 31.405 kDa by SDS-PAGE. LC-MS/MS analysis indicated that the compound was an antibacterial protein CB6-C, which had 88.5% identity with chitosanase (Csn) produced by Bacillus subtilis 168. An antibacterial protein CB6-C showed an effective antimicrobial activity against gram-positive bacteria (in particular, the MIC for MRSA was 16 µg/mL), low toxicity, thermostability, stability in different organic reagents and pH values, and an additive effect with conventionally used antibiotics. Mechanistic studies showed that an antibacterial protein CB6-C exerted anti-MRSA activity through destruction of lipoteichoic acid (LTA) on the cell wall. In addition, an antibacterial protein CB6-C was efficient in preventing MRSA infections in in vivo models. In conclusion, this protein CB6-C is a newly discovered antibacterial protein and has the potential to become an effective antibacterial agent due to its high therapeutic index, safety, nontoxicity and great stability.


Assuntos
Antibacterianos/farmacologia , Proteínas de Bactérias/farmacologia , Staphylococcus aureus Resistente à Meticilina/efeitos dos fármacos , Animais , Antibacterianos/uso terapêutico , Bacillus/química , Bacillus/enzimologia , Proteínas de Bactérias/química , Proteínas de Bactérias/isolamento & purificação , China , Cromatografia Líquida , Farmacorresistência Bacteriana Múltipla , Feminino , Camundongos , Camundongos Endogâmicos BALB C , Testes de Sensibilidade Microbiana , Infecções Estafilocócicas/tratamento farmacológico , Espectrometria de Massas em Tandem
7.
BMC Plant Biol ; 22(1): 10, 2022 Jan 03.
Artigo em Inglês | MEDLINE | ID: mdl-34979934

RESUMO

BACKGROUND: Kudzu is a term used generically to describe members of the genus Pueraria. Kudzu roots have been used for centuries in traditional Chinese medicine in view of their high levels of beneficial isoflavones including the unique 8-C-glycoside of daidzein, puerarin. In the US, kudzu is seen as a noxious weed causing ecological and economic damage. However, not all kudzu species make puerarin or are equally invasive. Kudzu remains difficult to identify due to its diverse morphology and inconsistent nomenclature. RESULTS: We have generated sequences for the internal transcribed spacer 2 (ITS2) and maturase K (matK) regions of Pueraria montana lobata, P. montana montana, and P. phaseoloides, and identified two accessions previously used for differential analysis of puerarin biosynthesis as P. lobata and P. phaseoloides. Additionally, we have generated root transcriptomes for the puerarin-producing P. m. lobata and the non-puerarin producing P. phaseoloides. Within the transcriptomes, microsatellites were identified to aid in species identification as well as population diversity. CONCLUSIONS: The barcode sequences generated will aid in fast and efficient identification of the three kudzu species. Additionally, the microsatellites identified from the transcriptomes will aid in genetic analysis. The root transcriptomes also provide a molecular toolkit for comparative gene expression analysis towards elucidation of the biosynthesis of kudzu phytochemicals.


Assuntos
Código de Barras de DNA Taxonômico , Isoflavonas/análise , Plantas Daninhas/classificação , Pueraria/classificação , Transcriptoma , Perfilação da Expressão Gênica , Raízes de Plantas/química , Plantas Daninhas/genética , Pueraria/genética
8.
Curr Microbiol ; 79(2): 59, 2022 Jan 04.
Artigo em Inglês | MEDLINE | ID: mdl-34982214

RESUMO

Dermatophytoses representing a major global health problem and dermatophyte species with reduced susceptibility to antifungals are increasingly reported. Therefore, we investigated for the first time the antidermatophyte activity and phytochemical properties of the sequential extracts of the Egyptian privet Henna (Lawsonia inermis) leaves. Total phenolic content (TPC), total flavonoids (TF), and antioxidant activity of chloroform, diethyl ether, acetone, ethanol 80%, and aqueous extracts were evaluated. The antifungal activity of henna leaves extracts (HLE) toward 30 clinical dermatophytes isolates, including Trichophyton mentagrophytes, Microsporum canis, and T. rubrum, was determined. Morphological changes in hyphae were investigated using scanning electron microscopy (SEM) analysis. Following the polarity of ethanol and acetone, they exhibited distinct efficiency for the solubility and extraction of polyphenolic polar antioxidants from henna leaves. Fraxetin, lawsone, and luteolin-3-O-glucoside were the major phenolic compounds of henna leaves, as assessed using high-performance liquid chromatography analysis. A high and significant positive correlation was found between TPC, TF, the antioxidants, and the antidermatophyte activities of HLE. Acetone and ethanol extracts exhibited the highest antifungal activity toward the tested dermatophyte species with minimum inhibitory concentration (MIC) ranges 12.5-37.5 and 25-62.5 µg/mL, respectively. Structural changes including collapsing, distortion, inflating, crushing of hyphae with corrugation of walls, and depressions on hyphal surfaces were observed in SEM analysis for dermatophyte species treated with MICs of griseofulvin, acetone, and ethanol extracts. In conclusion, acetone and ethanolic extracts of henna leaves with their major constituent fraxetin exhibited effective antifungal activity toward dermatophyte species and may be developed as an alternative for dermatophytosis treatment. These findings impart a useful insight into the development of an effective and safe antifungal agent for the treatment of superficial fungal infections caused by dermatophytes.


Assuntos
Antifúngicos , Arthrodermataceae/efeitos dos fármacos , Lawsonia (Planta)/química , Microsporum/efeitos dos fármacos , Extratos Vegetais , Antifúngicos/farmacologia , Testes de Sensibilidade Microbiana , Extratos Vegetais/farmacologia , Folhas de Planta/química
9.
PLoS One ; 17(1): e0261344, 2022.
Artigo em Inglês | MEDLINE | ID: mdl-34982782

RESUMO

With more than 1400 chiropteran species identified to date, bats comprise one-fifth of all mammalian species worldwide. Many studies have associated viral zoonoses with 45 different species of bats in the EU, which cluster within 5 families of bats. For example, the Serotine bats are infected by European Bat 1 Lyssavirus throughout Europe while Myotis bats are shown infected by coronavirus, herpesvirus and paramyxovirus. Correct host species identification is important to increase our knowledge of the ecology and evolutionary pattern of bat viruses in the EU. Bat species identification is commonly determined using morphological keys. Morphological determination of bat species from bat carcasses can be limited in some cases, due to the state of decomposition or nearly indistinguishable morphological features in juvenile bats and can lead to misidentifications. The overall objective of our study was to identify insectivorous bat species using molecular biology tools with the amplification of the partial cytochrome b gene of mitochondrial DNA. Two types of samples were tested in this study, bat wing punches and bat faeces. A total of 163 bat wing punches representing 22 species, and 31 faecal pellets representing 7 species were included in the study. From the 163 bat wing punches tested, a total of 159 were genetically identified from amplification of the partial cyt b gene. All 31 faecal pellets were genetically identified based on the cyt b gene. A comparison between morphological and genetic determination showed 21 misidentifications from the 163 wing punches, representing ~12.5% of misidentifications of morphological determination compared with the genetic method, across 11 species. In addition, genetic determination allowed the identification of 24 out of 25 morphologically non-determined bat samples. Our findings demonstrate the importance of a genetic approach as an efficient and reliable method to identify bat species precisely.


Assuntos
Quirópteros/classificação , Quirópteros/genética , DNA Mitocondrial/análise , Animais , Monitoramento Epidemiológico , Fezes/química , França , Raiva/veterinária , Asas de Animais/química , Zoonoses
10.
Environ Monit Assess ; 194(2): 58, 2022 Jan 06.
Artigo em Inglês | MEDLINE | ID: mdl-34989878

RESUMO

This study utilized switchable solvent liquid-phase microextraction (SS-LPME) to enrich eleven nervous system active pharmaceutical ingredients (APIs) from aqueous samples for their determination at trace levels by gas chromatography mass spectrometry. The analytes selected for the study included APIs utilized in antidepressant, antipsychotic, antiepileptic, and anti-dementia drugs. Parameters of the microextraction method including switchable solvent volume, concentration and volume of the trigger agent (sodium hydroxide), and sample agitation period were optimized univariately to boost extraction efficiency. Under the optimum conditions, the detection limits calculated for the analytes were in the range of 0.20-8.0 ng/mL, and repeatability for six replicate measurements as indicated by percent relative standard deviation values were below 10%. Matrix matching calibration strategy was used to enhance quantification accuracy for the analytes. The percent recovery results calculated for the eleven analytes ranged between 86 and 117%.


Assuntos
Microextração em Fase Líquida , Preparações Farmacêuticas , Poluentes Químicos da Água , Calibragem , Monitoramento Ambiental , Cromatografia Gasosa-Espectrometria de Massas , Limite de Detecção , Sistema Nervoso/química , Solventes , Poluentes Químicos da Água/análise
11.
Commun Biol ; 5(1): 1421, 2022 01 06.
Artigo em Inglês | MEDLINE | ID: mdl-34992214

RESUMO

As the SARS-CoV-2 (severe acute respiratory syndrome coronavirus 2) pandemic continues to spread, several variants of the virus, with mutations distributed all over the viral genome, are emerging. While most of the variants present mutations having little to no effects at the phenotypic level, some of these variants are spreading at a rate that suggests they may present a selective advantage. In particular, these rapidly spreading variants present specific mutations on the spike protein. These observations call for an urgent need to characterize the effects of these variants' mutations on phenotype features like contagiousness and antigenicity. With this aim, we performed molecular dynamics simulations on a selected set of possible spike variants in order to assess the stabilizing effect of particular amino acid substitutions on the molecular complex. We specifically focused on the mutations that are both characteristic of the top three most worrying variants at the moment, i.e the English, South African, and Amazonian ones, and that occur at the molecular interface between SARS-CoV-2 spike protein and its human ACE2 receptor. We characterize these variants' effect in terms of (i) residue mobility, (ii) compactness, studying the network of interactions at the interface, and (iii) variation of shape complementarity via expanding the molecular surfaces in the Zernike basis. Overall, our analyses highlighted greater stability of the three variant complexes with respect to both the wild type and two negative control systems, especially for the English and Amazonian variants. In addition, in the three variants, we investigate the effects a not-yet observed mutation in position 501 could provoke on complex stability. We found that a phenylalanine mutation behaves similarly to the English variant and may cooperate in further increasing the stability of the South African one, hinting at the need for careful surveillance for the emergence of these mutations in the population. Ultimately, we show that the proposed observables describe key features for the stability of the ACE2-spike complex and can help to monitor further possible spike variants.


Assuntos
Substituição de Aminoácidos , Enzima de Conversão de Angiotensina 2/genética , Mutação , SARS-CoV-2/fisiologia , Enzima de Conversão de Angiotensina 2/química , Enzima de Conversão de Angiotensina 2/metabolismo , Simulação de Dinâmica Molecular , Ligação Proteica
12.
Arch Microbiol ; 204(2): 133, 2022 Jan 09.
Artigo em Inglês | MEDLINE | ID: mdl-34999965

RESUMO

Biofilm formation of the opportunistic pathogen Pseudomonas (P). aeruginosa is one of the major global challenges to control nosocomial infections due to their high resistance to antimicrobials and host defense mechanisms. The present study aimed to assess the antibacterial and the antibiofilm activities of Peganum (P). harmala seed extract against multidrug-resistant P. aeruginosa isolates. Chemical identification of the active compound and determination of its molecular mechanism of action were also investigated. Results showed that P. harmala n-butanol "n-BuOH" extract exhibited antibacterial activity against multidrug-resistant P. aeruginosa isolates. This extract was even more active than conventional antibiotics cefazolin and vaamox when tested against three P. aeruginosa multidrug-resistant isolates. In addition, P. harmala n-BuOH extract exhibited potent bactericidal activity against PAO1 strain at MIC value corresponding to 500 µg/mL and attained 100% killing effect at 24 h of incubation. Furthermore, P. harmala n-BuOH extract showed an antibiofilm activity against P. aeruginosa PAO1 and exhibited 80.43% inhibition at sub-inhibitory concentration. The extract also eradicated 83.99% of the biofilm-forming bacteria. The active compound was identified by gas chromatography-mass spectrometry as an indole alkaloid harmaline. Transcriptomic analysis showed complete inhibition of the biofilm-related gene pilA when PAO1 cells were treated with harmaline. Our results revealed that P. harmala seed extract and its active compound harmaline could be considered as a candidate for a new treatment of multidrug-resistant P. aeruginosa pathogens-associated biofilm infections.


Assuntos
Antibacterianos , Biofilmes/efeitos dos fármacos , Peganum , Extratos Vegetais , Pseudomonas aeruginosa/efeitos dos fármacos , Antibacterianos/farmacologia , Farmacorresistência Bacteriana Múltipla , Peganum/química , Extratos Vegetais/farmacologia
13.
Environ Int ; 158: 106987, 2022 01.
Artigo em Inglês | MEDLINE | ID: mdl-34991249

RESUMO

OBJECTIVE: To examine whether selected endocrine disrupting chemicals were present in pregnant women and passed through the placental barrier to amniotic fluid, potentially exposing the developing fetus. METHODS: Paired samples of maternal serum, urine and amniotic fluid were concurrently collected (<1 h) from 200 pregnant women (age >18 years) with a singleton pregnancy and undergoing amniocentesis between gestational weeks 12 - 36. The concentration of six different parabens, seven phenols, 31 metabolites from 15 phthalate diesters and the polychlorinated substance triclocarban were analyzed by isotope diluted TurboFlow-liquid chromatography-tandem mass spectrometry. RESULTS: Concentrations of all included compounds were highest in maternal urine followed by serum, and lowest in amniotic fluid. Of the six parabens measured in amniotic fluid, methylparaben (MeP) and ethylparaben (EtP) were detectable most often (87% and 33% of the samples, respectively). Of the seven phenols measured, three (2,4-dichlorphenol, 2,5-dichlorphenol, 2-propylphenol) were detectable in the range of 14-21% of the amniotic fluid samples, at low concentrations (<0.12 ng/ml). Two secondary phthalates metabolites, mono-(2-carboxymethyl-hexyl) phthalate and mono-carboxy-iso-octyl phthalate were each present in ≤15% of the amniotic fluid samples at concentrations 2-5 times lower than in maternal serum and 20-100 times lower than in maternal urine. A modest statistically significant correlation between the levels of MeP and EtP was detected in paired maternal urine-amniotic fluid samples was detected (Spearman rMeP: 0.246; rEtP: 0.364). Likewise, the concentration of mono-ethyl phthalate (MEP) in paired maternal urine and amniotic fluid samples indicated a modest statistically significant correlation (Spearman rMEP: 0.264), driven by detectable levels of MEP in only 3% of the amniotic fluid samples. CONCLUSIONS: In general, the included parabens, phenols and phthalates were effectively metabolized and excreted via the urine, which was the matrix that reflected the highest detectable levels. The detectable levels of several included parabens and phthalates in human amniotic fluid calls for further investigations of the toxicokinetic and potential endocrine disrupting properties of individual and multiple endocrine disruptors in order to better assess the risk to the developing fetus.


Assuntos
Parabenos , Ácidos Ftálicos , Líquido Amniótico/química , Feminino , Humanos , Lactente , Exposição Materna , Parabenos/análise , Fenóis , Placenta/química , Gravidez
14.
Environ Int ; 158: 106996, 2022 01.
Artigo em Inglês | MEDLINE | ID: mdl-34991256

RESUMO

A multi-specimen, multi-mycotoxin approach involving ultra-sensitive LC-MS/MS analysis of breast milk, complementary food and urine was applied to examine mycotoxin co-exposure in 65 infants, aged 1-18 months, in Ogun state, Nigeria. Aflatoxin M1 was detected in breast milk (4/22 (18%)), while six other classes of mycotoxins were quantified; including dihydrocitrinone (6/22 (27%); range: 14.0-59.7 ng/L) and sterigmatocystin (1/22 (5%); 1.2 ng/L) detected for the first time. Seven distinct classes of mycotoxins including aflatoxins (9/42 (21%); range: 1.0-16.2 µg/kg) and fumonisins (12/42 (29%); range: 7.9-194 µg/kg) contaminated complementary food. Mycotoxins covering seven distinct classes with diverse structures and modes of action were detected in 64/65 (99%) of the urine samples, demonstrating ubiquitous exposure. Two aflatoxin metabolites (AFM1 and AFQ1) and FB1 were detected in 6/65 (9%), 44/65 (68%) and 17/65 (26%) of urine samples, respectively. Mixtures of mycotoxin classes were common, including 22/22 (100%), 14/42 (33%) and 56/65 (86%) samples having 2-6, 2-4, or 2-6 mycotoxins present, for breast milk, complementary food and urine, respectively. Aflatoxin and/or fumonisin was detected in 4/22 (18%), 12/42 (29%) and 46/65 (71%) for breast milk, complimentary foods and urine, respectively. Furthermore, the detection frequency, median concentrations and occurrence of mixtures were typically greater in urine of non-exclusively breastfed compared to exclusively breastfed infants. The study provides novel insights into mycotoxin co-exposures in early-life. Albeit a small sample set, it highlights transition to higher levels of infant mycotoxin exposure as complementary foods are introduced, providing impetus to mitigate during this critical early-life period and encourage breastfeeding.


Assuntos
Citrinina , Micotoxinas , Monitoramento Biológico , Biomarcadores , Aleitamento Materno , Criança , Cromatografia Líquida , Feminino , Contaminação de Alimentos/análise , Humanos , Lactente , Leite Humano/química , Nigéria , Espectrometria de Massas em Tandem
15.
Environ Int ; 158: 107018, 2022 01.
Artigo em Inglês | MEDLINE | ID: mdl-34991270

RESUMO

In 2011, phthalates, mainly di-(2-ethylhexyl) phthalate (DEHP), were found to have been added to a variety of foods in Taiwan, increasing the risk of microalbuminuria in children. Exposure to melamine perhaps modifies that risk. This prospective cohort study investigates whether renal injury resulting from exposure to DEHP-tainted foods from the 2011 Taiwan Food Scandal is reversed over time. The temporal and interactive effects of past daily DEHP intake, current daily DEHP intake, and urinary melamine levels on oxidative stress and renal injury were also examined. Two hundred possibly DEHP-affected children (aged < 18 years) were enrolled in the first survey wave (August 2012-January 2013), with 170 and 159 children in the second (July 2014-February 2015) and third waves (May 2016-October 2016), respectively. The first wave comprised questionnaires that were used to collect information about possible past daily DEHP intake from DEHP-tainted foods. One-spot first morning urine samples were collected to measure melamine levels, phthalate metabolites, and markers indicating oxidative stress (malondialdehyde and 8-oxo-2'-deoxyguanosine), and renal injury (albumin/creatinine ratio (ACR) and N-acetyl-beta-D-glucosaminidase) in all three waves. Generalized estimating equation (GEE) modeling revealed that both past daily DEHP intake and time might affect urinary ACR. However, most interactions were negative and significant correlation was observed only during the second wave (P for interaction = 0.014) in the group with the highest past daily DEHP intake (>50 µg/kg/day). Urinary melamine levels were found to correlate significantly with both urinary ACR and oxidative stress markers. The highest impact associated with exposure to DEHP-tainted foods in increasing urinary ACR of children was observed during the first wave, and the effect may partially diminish over time. These results suggest that continuous monitoring of renal health and other long-term health consequences is required in individuals who were affected by the scandal in 2011.


Assuntos
Dietilexilftalato , Ácidos Ftálicos , Criança , Dietilexilftalato/toxicidade , Exposição Ambiental/efeitos adversos , Contaminação de Alimentos , Humanos , Rim/química , Estresse Oxidativo , Estudos Prospectivos , Taiwan , Triazinas
16.
J Nanobiotechnology ; 20(1): 6, 2022 Jan 04.
Artigo em Inglês | MEDLINE | ID: mdl-34983543

RESUMO

BACKGROUND: Gold nanoparticles (AuNPs) have been widely used in local surface plasmon resonance (LSPR) immunoassays for biomolecule sensing, which is primarily based on two conventional methods: absorption spectra analysis and colorimetry. The low figure of merit (FoM) of the LSPR and high-concentration AuNP requirement restrict their limit of detection (LOD), which is approximately ng to µg mL-1 in antibody detection if there is no other signal or analyte amplification. Improvements in sensitivity have been slow in recent for a long time, and pushing the boundary of the current LOD is a great challenge of current LSPR immunoassays in biosensing. RESULTS: In this work, we developed spectral image contrast-based flow digital nanoplasmon-metry (Flow DiNM) to push the LOD boundary. Comparing the scattering image brightness of AuNPs in two neighboring wavelength bands near the LSPR peak, the peak shift signal is strongly amplified and quickly detected. Introducing digital analysis, the Flow DiNM provides an ultrahigh signal-to-noise ratio and has a lower sample volume requirement. Compared to the conventional analog LSPR immunoassay, Flow DiNM for anti-BSA detection in pure samples has an LOD as low as 1 pg mL-1 within only a 15-min detection time and 500 µL sample volume. Antibody assays against spike proteins of SARS-CoV-2 in artificial saliva that contained various proteins were also conducted to validate the detection of Flow DiNM in complicated samples. Flow DiNM shows significant discrimination in detection with an LOD of 10 pg mL-1 and a broad dynamic detection range of five orders of magnitude. CONCLUSION: Together with the quick readout time and simple operation, this work clearly demonstrated the high sensitivity and selectivity of the developed Flow DiNM in rapid antibody detection. Spectral image contrast and digital analysis further provide a new generation of LSPR immunoassay with AuNPs.


Assuntos
Teste Sorológico para COVID-19/métodos , COVID-19/diagnóstico , SARS-CoV-2/isolamento & purificação , Ressonância de Plasmônio de Superfície/métodos , Anticorpos Antivirais/imunologia , COVID-19/imunologia , Teste Sorológico para COVID-19/instrumentação , Desenho de Equipamento , Ouro/química , Humanos , Imunoensaio/instrumentação , Imunoensaio/métodos , Nanopartículas Metálicas/química , SARS-CoV-2/imunologia , Saliva/virologia , Glicoproteína da Espícula de Coronavírus/imunologia , Ressonância de Plasmônio de Superfície/instrumentação
17.
Food Chem ; 374: 131808, 2022 Apr 16.
Artigo em Inglês | MEDLINE | ID: mdl-35021581

RESUMO

This work evaluated the impact of high temperature short time (HTST, 72 °C, 15 s), high hydrostatic pressure (HHP, 400-600 MPa at 5 and 10 min) and Holder pasteurization (HoP, 62.5 °C, 30 min) on protein profile and aggregation in a human milk protein concentrate (HMPC). The structural changes induced in milk proteins were investigated in HMPC as well as in sedimentable and non-sedimentable fractions recovered after ultracentrifugation. The results showed that heat treatments induced more protein denaturation and aggregation than did HHP treatments. Indeed, heat-induced protein aggregates observed in HMPC and the sedimentable fraction were mainly composed of lactoferrin and α-lactalbumin. More specifically, the concentration of lactoferrin in HMPC decreased by 86% after HTST and HoP whereas no effect was observed after HHP treatment. These results show the potential of HHP processing as a pasteurization method for HMPC since it minimizes the impact on protein structure, which generally correlates to protein quality and bioactivity.


Assuntos
Proteínas do Leite , Pasteurização , Temperatura Alta , Humanos , Pressão Hidrostática , Proteínas do Leite/análise , Leite Humano/química , Temperatura
18.
Gene ; 812: 146111, 2022 Feb 20.
Artigo em Inglês | MEDLINE | ID: mdl-34902512

RESUMO

Stem cell differentiation towards various somatic cells and body organs has proven to be an effective technique in the understanding and progression of regenerative medicine. Despite the advances made, concerns regarding the low efficiency of differentiation and the remaining differences between stem cell products and their in vivo counterparts must be addressed. Biomaterials that mimic endogenous growth conditions represent one recent method used to improve the quality and efficiency of stem cell differentiation, though the mechanisms of this improvement remain to be completely understood. The effectiveness of various biomaterials can be analyzed through a multidisciplinary approach involving bioinformatics and systems biology tools. Here, we aim to use bioinformatics to accomplish two aims: 1) determine the effect of different biomaterials on stem cell growth and differentiation, and 2) understand the effect of cell of origin on the differentiation potential of multipotent stem cells. First, we demonstrate that the dimensionality (2D versus 3D) and the degradability of biomaterials affects the way that the cells are able to grow and differentiate at the transcriptional level. Additionally, according to transcriptional state of the cells, the particular cell of origin is an important factor in determining the response of stem cells to same biomaterial. Our data demonstrates the ability of bioinformatics to understand novel molecular mechanisms and context by which stem cells are most efficiently able to differentiate. These results and strategies can be used to suggest proper combinations of biomaterials and stem cells to achieve high differentiation efficiency and functionality of desired cell types.


Assuntos
Materiais Biocompatíveis/farmacologia , Perfilação da Expressão Gênica/métodos , Células-Tronco/citologia , Comunicação Celular , Diferenciação Celular/efeitos dos fármacos , Proliferação de Células/efeitos dos fármacos , Regulação da Expressão Gênica/efeitos dos fármacos , Sequenciamento de Nucleotídeos em Larga Escala , Humanos , Medicina Regenerativa , Análise de Sequência de RNA , Células-Tronco/química , Células-Tronco/efeitos dos fármacos
19.
Adv Drug Deliv Rev ; 180: 114079, 2022 01.
Artigo em Inglês | MEDLINE | ID: mdl-34902516

RESUMO

Polyethylene glycol or PEG has a long history of use in medicine. Many conventional formulations utilize PEG as either an active ingredient or an excipient. PEG found its use in biotechnology therapeutics as a tool to slow down drug clearance and shield protein therapeutics from undesirable immunogenicity. Nanotechnology field applies PEG to create stealth drug carriers with prolonged circulation time and decreased recognition and clearance by the mononuclear phagocyte system (MPS). Most nanomedicines approved for clinical use and experimental nanotherapeutics contain PEG. Among the most recent successful examples are two mRNA-based COVID-19 vaccines that are delivered by PEGylated lipid nanoparticles. The breadth of PEG use in a wide variety of over the counter (OTC) medications as well as in drug products and vaccines stimulated research which uncovered that PEG is not as immunologically inert as it was initially expected. Herein, we review the current understanding of PEG's immunological properties and discuss them in the context of synthesis, biodistribution, safety, efficacy, and characterization of PEGylated nanomedicines. We also review the current knowledge about immunological compatibility of other polymers that are being actively investigated as PEG alternatives.


Assuntos
Portadores de Fármacos , Nanomedicina , Polietilenoglicóis/química , Animais , Vacinas contra COVID-19/química , Vacinas contra COVID-19/imunologia , Sistemas de Liberação de Medicamentos , Humanos
20.
Gene ; 812: 146099, 2022 Feb 20.
Artigo em Inglês | MEDLINE | ID: mdl-34906645

RESUMO

Nasopharyngeal Carcinoma (NPC) found to be dependent on geographical and racial variation and is more prevalent in Northeast (NE) India. WES-based study was conducted in three states (tribes); Nagaland (Naga), Mizoram (Mizo) and Manipur (Manipuri), which provided an overview of germline variants involved inthemajor signaling pathways. Validation and recurrence assessment of WES data confirmed the risk effect of STEAP3_rs138941861 and JAG1_rs2273059, and the protective role of PARP4_rs17080653 and TGFBR1_rs11568778 variants, where STEAP3_rs138941861conferring Arg290His substitution was the only exonic non-synonymous variant and to be located in proximity to the linking region between the transmembrane and oxidoreductasedomainsof STEAP3 protein, andaffectedits structural and functional dynamics by altering the Electrostatic Potential around this connecting region. Moreover, these significantly associated variants having deleterious effect were observed to have interactions in p53 signaling pathway which emphasizes the importance of this pathway in the causation of NPC.


Assuntos
Proteínas de Ciclo Celular/genética , Proteína Jagged-1/genética , Carcinoma Nasofaríngeo/genética , Neoplasias Nasofaríngeas/genética , Proteínas Nucleares/genética , Oxirredutases/genética , Receptor do Fator de Crescimento Transformador beta Tipo I/genética , Sequenciamento Completo do Exoma/métodos , Adulto , Substituição de Aminoácidos , Estudos de Casos e Controles , Proteínas de Ciclo Celular/química , Feminino , Predisposição Genética para Doença , Sequenciamento de Nucleotídeos em Larga Escala , Humanos , Índia , Masculino , Pessoa de Meia-Idade , Modelos Moleculares , Oxirredutases/química , Polimorfismo de Nucleotídeo Único , Conformação Proteica , Domínios Proteicos
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