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The chemophysical properties of a peptide isolated from Olivancillaria hiatula were combined with computational tools to design new antimicrobial peptides (AMPs). The in silico peptide design utilized arbitrary sequence shuffling, AMP sequence prediction and alignments such that putative sequences mimicked those of proline-rich AMPs (PrAMPs) and were potentially active against bacteria. Molecular modelling and docking experiments were used to monitor peptide binding to some intracellular targets like bacteria ribosome, DnaK and LasR. Peptide candidates were tested in vitro for antibacterial and antivirulence activities. Chemophysical studies of peptide extract suggested hydrophobic, acidic and proline-rich peptide properties. The amino acid signature of the extract matched that of AMPs that inhibit intracellular targets. Two of the designed PrAMP peptides (OhPrP-3 and OhPrP-5) had high affinity for the ribosome and DnaK. OhPrP-1, 2 and 4 also had favorable interactions with the biomolecular targets investigated. Peptides had bactericidal activity at the minimum inhibitory concentration against Pseudomonas aeruginosa. The designed peptides docked strongly to LasR suggesting possible interference with quorum sensing, and this was corroborated by in vitro data where sub-inhibitory doses of all peptides reduced pyocyanin and pyoverdine expression. The designed peptides can be further studied for the development of new anti-infective agents.
RESUMO
Bisphenol AF (BPAF) is a structural counterpart of bisphenol A that is utilized in the food and beverage industry. The present study investigated the potential mechanisms in BPAF-induced neurotoxicity in zebrafish embryos. The BPAF concentrations (0.03, 0.1, 0.3, and 1.0 µM) had no obvious effect on hatching, mortality, and body length of zebrafish larvae, while curved tail and pericardial edema were observed in the 1.0 µM group at 72 and 96 h postfertilization (hpf). Locomotor activity of the larvae (at 120 hpf) significantly decreased from dark to light but increased from light to dark transitions in BPAF groups (0.1, 0.3, and 1.0 µM). Acridine orange showed that BPAF significantly increased green fluorescence protein intensity (22.6%) in the 1.0 µM group. Consistently, the induced apoptosis significantly up-regulated caspase 3 at 0.3 µM (1.95-fold) and 1.0 µM (2.26-fold) and bax at 0.3 µM (1.60-fold) and 1.0 µM (1.78-fold), whereas bcl-2 expression was significantly decreased at 0.3 µM (0.72-fold) and 1.0 µM (0.53-fold). In addition, increased reactive oxygen species concentrations at 0.3 µM (27%) and 1.0 µM (61.4%) resulted in suppressed superoxide dismutase and catalase activities. Moreover, quantitative polymerase chain reaction results showed that BPAF (0.3 and 1.0 µM) significantly altered normal dopaminergic signaling where dat was up-regulated, while drd2a and th1 were down-regulated, in a concentration-dependent manner. Aberrations in dopamine-related genes were congruous with the dysregulations in neurodevelopment genes (sox11b, pax6a, syn2a, and rob2). Our findings suggest that BPAF-evoked oxidative stress and apoptosis could translate into phenotypical behavioral and neurodevelopmental abnormalities. These highlights could provide theoretical reference for risk assessment and act as an early indicator to BPAF exposure. Environ Toxicol Chem 2022;41:2273-2284. © 2022 SETAC.
Assuntos
Compostos Benzidrílicos , Peixe-Zebra , Animais , Apoptose , Compostos Benzidrílicos/metabolismo , Compostos Benzidrílicos/toxicidade , Fluorocarbonos , Larva , Estresse Oxidativo , Peixe-Zebra/metabolismoRESUMO
Bisphenol A (BPA) and bisphenol S (BPS) are implicated in the development of metabolic disorders, such diabetes mellitus. However, the epigenetic mechanism underlying the pancreatic ß-cell dysregulation for both BPA/BPS needs clarification. This exploratory study was designed to investigate whether embryonic exposure to low BPA/BPS concentrations impair early pancreatic ß-cell differentiation as well as DNA methylation in its gene expression profile using an in vivo model, zebrafish. Zebrafish embryos were exposed to 0, 0.01, 0.03, 0.1, 0.3, and 1.0 µM BPA/BPS at 4-h post fertilization (hpf) until 120 hpf. BPA/BPS-induced effects on pancreatic-related genes, insulin gene, and DNA methylation-associated genes were assessed at developmental stages (24-120 hpf), while glucose level was measure at the 120 hpf. The insulin expression levels decreased at 72-120 hpf for 1.0 µM BPA, while 0.32 and 0.24-fold of insulin expression were elicited by 0.3 and 1 µM BPS respectively at 72 hpf. Significant elevation of glucose levels; 16.3% (for 1.0 µM BPA), 7.20% (for 0.3 µM BPS), and 74.09% (for 1.0 µM BPS) higher than the control groups were observed. In addition, pancreatic-related genes pdx-1, foxa2, ptfla, and isl1 were significantly interfered compared with the untreated group. Moreover, the maintenance methylation gene, dnmt1, was monotonically and significantly decreased at early stage of development following BPA exposure but remained constant for BPS treatment relative to the control group. DNMT3a and DNMT3b orthologs were distinctively altered following BPA/BPS embryonic exposure. Our data indicated that embryonic exposure to low concentration of BPA/BPS can impair the normal expressions of pancreatic-associated genes and DNA methylation pattern of selected genes in zebrafish early development.
Assuntos
Compostos Benzidrílicos/toxicidade , Fenóis/toxicidade , Sulfonas/toxicidade , Poluentes Químicos da Água/toxicidade , Animais , Diferenciação Celular , DNA/metabolismo , DNA (Citosina-5-)-Metiltransferases , Metilação de DNA , Peixe-Zebra/embriologia , Peixe-Zebra/fisiologia , DNA Metiltransferase 3BRESUMO
The Barekese reservoir has seen persistent degradation for decades through anthropogenic activities within its catchment. In spite of this, heavy metal pollution profile of fish species of the reservoir is not well studied. Total concentrations of Hg, Cd, Ni, and Cr were analyzed in muscle tissues of 45 edible fish species comprising (Tilapia zilli, Oreochromis niloticus, and Heterotis niloticus) from the reservoir. The examined fish species showed varying bioaccumulative factors for detected metals. A PCA biplot revealed that Cd showed association with all examined fish species used in the study indicating that Cd in the reservoir is biologically available for uptake by all examined fish species. A dendrogram of cluster analysis also revealed that Cd and Cr are in one cluster indicating their associations and similarities to a common anthropogenic source. The study suggests that anthropogenic activities are possible sources of heavy metal pollution in the Barekese reservoir and, hence, the examined fish species could be used to monitor the levels of Ni, Cr, Hg, and Cd in the reservoir.
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Monitoramento Ambiental/métodos , Metais Pesados/análise , Alimentos Marinhos/análise , Poluentes Químicos da Água/análise , Animais , Ciclídeos/metabolismo , Gana , Análise Multivariada , Músculos/química , Tilápia/metabolismoRESUMO
BACKGROUND: Historical proven wood species have no reported adverse health effect associated with its past use. Different historical proven species have traditionally been used to manufacture different wooden food contact items. This study uses survey questionnaires to assess suppliers', manufacturers', retailers' and consumers' (end-users') preferences for specific wood species, to examine the considerations that inform these preferences and to investigate the extent of awareness of the chemical benefits and chemical hazards associated with wooden food contact material use. METHODS: Through the combined use of a cross sectional approach and a case study design, 25 suppliers, 25 manufacturers, 25 retailers and 125 consumers (end-users) of wooden food contact materials in four suburbs in Kumasi Metropolitan Area (Anloga junction, Ahinsan Bus Stop, Ahwia-Pankrono and Race Course) and Ashanti Akyim Agogo in the Ashanti Akyim North District of the Ashanti Region were administered with closed ended questionnaires. The questionnaires were prepared in English, but local language, Twi, was used to translate and communicate the content of the questionnaire where necessary. RESULTS: Suppliers', manufacturers' and retailers' preferences for specific wood species for most wooden cookware differed from that of consumers (end-users). But all respondent groups failed to indicate any awareness of chemical benefits or chemical hazards associated with either the choice of specific wood species for specific wooden cookware or with the general use of wooden food contact materials. The lack of appreciation of chemical benefits or hazards associated with active principles of wooden cookware led to heavy reliance of consumers (end-users) on the wood density, price, attractive grain pattern and colour or on the judgement of retailers in their choice of specific species for a wooden cookware. CONCLUSION: This study contributes some practical suggestions to guide national policy development on improvement in quality of available wooden food contact materials in Ghana.