RESUMO
The reproductive process in Octopus maya was analyzed to establish the amount of reactive oxygen species that the embryos inherit from females, during yolk synthesis. At the same time, respiratory metabolism, ROS production, and the expression of some genes of the antioxidant system were monitored to understand the ability of embryos to neutralize maternal ROS and those produced during development. The results indicate that carbonylated proteins and peroxidized lipids (LPO) were transferred from females to the embryos, presumably derived from the metabolic processes carried out during yolk synthesis in the ovary. Along with ROS, females also transferred to embryos glutathione (GSH), a key element of the antioxidant defense system, thus facilitating the neutralization of inherited ROS and those produced during development. Embryos are capable of neutralizing ROS thanks to the early expression of genes such as catalase (CAT) and superoxide dismutase (SOD), which give rise to the synthesis of enzymes when the circulatory system is activated. Also, it was observed that the levels of the routine metabolic rate of embryos are almost as high as those of the maximum activity metabolism, which leads, on the one hand, to the elevated production of ROS and suggests that, at this stage of the life cycle in octopuses, energy production is maximum and is physically limited by the biological properties inherent to the structure of embryonic life (oxygen transfer through the chorion, gill surface, pumping capacity, etc.). Due to its role in regulating vascularization, a high expression of HIf-1A during organogenesis suggests that circulatory system development has begun in this phase of embryo development. The results indicate that the routine metabolic rate and the ability of O. maya embryos to neutralize the ROS are probably the maximum possible. Under such circumstances, embryos cannot generate more energy to combat the free radicals produced by their metabolism, even when environmental factors such as high temperatures or contaminants could demand excess energy.
Assuntos
Embrião não Mamífero , Metabolismo Energético , Octopodiformes , Espécies Reativas de Oxigênio , Animais , Espécies Reativas de Oxigênio/metabolismo , Octopodiformes/metabolismo , Octopodiformes/genética , Embrião não Mamífero/metabolismo , Feminino , Regulação da Expressão Gênica no Desenvolvimento , Antioxidantes/metabolismo , Superóxido Dismutase/metabolismo , Superóxido Dismutase/genética , Catalase/metabolismo , Catalase/genética , Glutationa/metabolismoRESUMO
BACKGROUND: The genes involved in cephalopod development and their association with hatching and survival during early life stages have been extensively studied. However, few studies have investigated the paralarvae transcriptome of the East Asian common octopus (Octopus sinen sis). OBJECTIVE: This study aimed to identify the genes related to embryonic development and hatching in O. sinensis using RNA sequencing (RNA-seq) and verify the genes most relevant to different embryonic stages. METHODS: RNA samples from hatched and 25 days post-hatching (dph) O. sinensis paralarvae were used to construct cDNA libraries. Clean reads from individual samples were aligned to the reference O. sinensis database to identify the differentially expressed genes (DEGs) between the 0- and 25-dph paralarvae libraries. Real-time quantitative polymerase chain reaction (RT-qPCR) was used to supplement the RNA-seq data for embryogenic developmental stages. RESULTS: A total of 12,597 transcripts were annotated and 5,468 DEGs were identified between the 0- and 25-dph O. sinensis paralarvae, including 2,715 upregulated and 2,753 downregulated transcripts in the 25-dph paralarvae. Several key DEGs were related to transmembrane transport, lipid biosynthesis, monooxygenase activity, lipid transport, neuropeptide signaling, transcription regulation, and protein-cysteine S-palmitoyltransferase activity during the post-hatching development of O. sinensis paralarvae. RT-qPCR analysis further revealed that SLC5A3A, ABCC12, and NPC1 transcripts in 20 and/or 30 days post-fertilization (dpf) embryos were significantly higher (p < 0.05) than those in 10-dpf embryos. CONCLUSION: Transcriptome profiles provide molecular targets to understand the embryonic development, hatching, and survival of O. sinensis paralarvae, and enhance octopus production.
Assuntos
Octopodiformes , Transcriptoma , Animais , Octopodiformes/genética , Octopodiformes/crescimento & desenvolvimento , Transcriptoma/genética , Regulação da Expressão Gênica no Desenvolvimento , Perfilação da Expressão Gênica/métodos , População do Leste AsiáticoRESUMO
Cephalopods receive a great deal of attention due to their socioeconomically important fisheries and aquaculture industries as well their unique biological features. However, basic information about their physiological responses under stress conditions is lacking. This study investigated the impact of a simple stressor, exercise to exhaustion, on the activity levels of antioxidant enzymes and the concentrations of molecules involved in oxidative stress response in the pale octopus (Octopus pallidus). Eight biochemical assays were measured in the humoral (plasma) and cellular (hemocyte) components of O. pallidus haemolymph, the invertebrate analogue to vertebrate blood. Overall, exercise resulted in an increase in activity of plasma catalase (CAT) and glutathione-S-transferase (GST) and the decrease in activity of plasms glutathione reductase (GR). In the hemocytes, the exercise elicited a different response, with a reduction in the activity of superoxide dismutase (SOD), GR, and glutathione peroxidase (GPX) and a reduction in nitric oxide (NO) concentration. Malondialdehyde (MDA) activity was similar in the plasma and haemocytes in control and exercised treatments, indicating that exercise did not induce lipid peroxidation. These results provide an important baseline for understanding oxidative stress in octopus, with exercise to exhaustion serving as a simple stressor which will ultimately inform our ability to detect and understand physiological responses to more complex stressors.
Assuntos
Octopodiformes , Animais , Octopodiformes/metabolismo , Antioxidantes , Estresse Oxidativo , Catalase/metabolismo , Superóxido Dismutase/metabolismo , Glutationa Peroxidase/metabolismo , Peroxidação de Lipídeos , Glutationa Redutase/metabolismo , Glutationa Transferase/metabolismo , Glutationa/metabolismoRESUMO
Enzymes from ectotherms living in chronically cold environments have evolved structural innovations to overcome the effects of temperature on catalysis. Cold adaptation of soluble enzymes is driven by changes within their primary structure or the aqueous milieu. For membrane-embedded enzymes, like the Na+/K+-ATPase, the situation is different because changes to the lipid bilayer in which they operate may also be relevant. Although much attention has been focused on thermal adaptation within lipid bilayers, relatively little is known about the contribution of structural changes within membrane-bound enzymes themselves. The identification of specific mutations that confer temperature compensation is complicated by the presence of neutral mutations, which can be more numerous. In the present study, we identified specific amino acids in a Na+/K+-ATPase from an Antarctic octopus that underlie cold resistance. Our approach was to generate chimeras between an Antarctic clone and a temperate ortholog and then study their temperature sensitivities in Xenopus oocytes using an electrophysiological approach. We identified 12 positions in the Antarctic Na+/K+-ATPase that, when transferred to the temperate ortholog, were sufficient to confer cold tolerance. Furthermore, although all 12 Antarctic mutations were required for the full phenotype, a single leucine in the third transmembrane segment (M3) imparted most of it. Mutations that confer cold resistance are mostly in transmembrane segments, at positions that face the lipid bilayer. We propose that the interface between a transmembrane enzyme and the lipid bilayer is a critical determinant of temperature sensitivity and, accordingly, has been a prime evolutionary target for thermal adaptation.
Assuntos
Bicamadas Lipídicas , Octopodiformes , ATPase Trocadora de Sódio-Potássio , Aclimatação/genética , Aminoácidos , Regiões Antárticas , ATPase Trocadora de Sódio-Potássio/metabolismo , Octopodiformes/enzimologia , AnimaisRESUMO
Intratissue topical medication is important for the treatment of cutaneous, mucosal or splanchnic diseases. However, penetrating surface barriers to providing adequate and controllable drug delivery while guaranteeing adhesion in bodily fluids remains challenging. Here, the predatory behavior of the blue-ringed octopus inspired us with a strategy to improve topical medication. For effective intratissue drug delivery, the active injection microneedles were prepared in a manner inspired by the teeth and venom secretion of blue-ringed octopus. With on demand release function guided by temperature-sensitive hydrophobic and shrinkage variations, these microneedles can supply adequate drug delivery at an early stage and then achieve the long-term release stage. Meanwhile, the bionic suction cups were developed to facilitate microneedles to stay firmly in place (>10 kilopascal) when wet. With wet bonding ability and multiple delivery mode, this microneedle patch achieved satisfactory efficacy, such as accelerating the ulcers' healing speed or halting early tumor progression.
Assuntos
Octopodiformes , Animais , Sistemas de Liberação de Medicamentos , Pele , Administração Cutânea , Fenômenos FísicosRESUMO
In poikilotherms, temperature changes challenge the integration of physiological function. Within the complex nervous systems of the behaviorally sophisticated coleoid cephalopods, these problems are substantial. RNA editing by adenosine deamination is a well-positioned mechanism for environmental acclimation. We report that the neural proteome of Octopus bimaculoides undergoes massive reconfigurations via RNA editing following a temperature challenge. Over 13,000 codons are affected, and many alter proteins that are vital for neural processes. For two highly temperature-sensitive examples, recoding tunes protein function. For synaptotagmin, a key component of Ca2+-dependent neurotransmitter release, crystal structures and supporting experiments show that editing alters Ca2+ binding. For kinesin-1, a motor protein driving axonal transport, editing regulates transport velocity down microtubules. Seasonal sampling of wild-caught specimens indicates that temperature-dependent editing occurs in the field as well. These data show that A-to-I editing tunes neurophysiological function in response to temperature in octopus and most likely other coleoids.
Assuntos
Octopodiformes , Proteoma , Animais , Proteoma/metabolismo , Octopodiformes/genética , Edição de RNA , Temperatura , Sistema Nervoso/metabolismo , Adenosina Desaminase/metabolismo , RNA/metabolismoRESUMO
This research aimed to chemically synthesize and evaluate the antiproliferative and anti-inflammatory potential of ozopromide (OPC), a novel compound recently isolated from O. vulgaris ink. After chemical synthesis, OPC structural characterization was confirmed by COSY2D, FTIR, and C-/H-NMR. OPC inhibited the growth of human breast (MDA-MB-231), prostate (22Rv1), cervix (HeLa), and lung (A549) cancerous cells, being the highest effect on the latter (IC50: 53.70 µM). As confirmed by flow cytometry, OPC induced typical apoptosis-derived morphological features on A549 cells, mostly at early and late apoptosis stages. OPC generated a dose-dependent effect inhibiting IL-6 and IL-8 on LPS-stimulated peripheral mononuclear cells (PBMCs). A major affinity of OPC to Akt-1 and Bcl-2 proteins in silico agreed with the observed pro-apoptotic mechanisms. Results suggested that OPC has the potential to alleviate inflammation and be further studied for anticancer activity. Marine-derived food products such as ink contains bioactive metabolites exhibiting potential health benefits.
Assuntos
Antineoplásicos , Neoplasias , Octopodiformes , Masculino , Feminino , Animais , Humanos , Antineoplásicos/química , Linhagem Celular Tumoral , Células A549 , Tinta , Apoptose , Proliferação de CélulasRESUMO
The blue-ringed octopus species complex (Hapalochlaena spp.), known to occur from Southern Australia to Japan, currently contains four formally described species (Hapalochlaena maculosa, Hapalochlaena fasciata, Hapalochlaena lunulata and Hapalochlaena nierstraszi). These species are distinguished based on morphological characters (iridescent blue rings and/or lines) along with reproductive strategies. However, the observation of greater morphological diversity than previously captured by the current taxonomic framework indicates that a revision is required. To examine species boundaries within the genus we used mitochondrial (12S rRNA, 16S rRNA, cytochrome c oxidase subunit 1 [COI], cytochrome c oxidase subunit 3 [COIII] and cytochrome b [Cytb]) and genome-wide SNP data (DaRT seq) from specimens collected across its geographic range including variations in depth from 3 m to >100 m. This investigation indicates substantially greater species diversity present within the genus Hapalochlaena than is currently described. We identified 10,346 SNPs across all locations, which when analysed support a minimum of 11 distinct clades. Bayesian phylogenetic analysis of the mitochondrial COI gene on a more limited sample set dates the diversification of the genus to â¼30 mya and corroborates eight of the lineages indicated by the SNP analyses. Furthermore, we demonstrate that the diagnostic lined patterning of H. fasciata found in North Pacific waters and NSW, Australia is polyphyletic and therefore likely the result of convergent evolution. Several "deep water" (>100 m) lineages were also identified in this study with genetic convergence likely to be driven by external selective pressures. Examination of morphological traits, currently being undertaken in a parallel morphological study, is required to describe additional species within the complex.
Assuntos
Octopodiformes , Animais , Filogenia , Octopodiformes/genética , RNA Ribossômico 16S/genética , Complexo IV da Cadeia de Transporte de Elétrons/genética , Teorema de Bayes , Polimorfismo de Nucleotídeo Único , ÁsiaRESUMO
The common octopus is a cephalopod species subject to active fisheries, with great potential in the aquaculture and food industry, and which serves as a model species for biomedical and behavioral studies. The analysis of the skin mucus allows us to study their health in a non-invasive way, by using a hardly exploited discard of octopus in the fishing sector. A shotgun proteomics approach combined with liquid chromatography coupled with tandem mass spectrometry (LC-MS/MS) using an Orbitrap-Elite instrument was used to create a reference dataset from octopus skin mucus. The final proteome compilation was investigated by integrated in-silico studies, including Gene Ontology (GO), the Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway, network studies, and prediction and characterization analysis of potential bioactive peptides. This work presents the first proteomic analysis of the common octopus skin mucus proteome. This library was created by merging 5937 identified spectra of 2038 different peptides. A total of 510 non-redundant proteins were identified. Obtained results show proteins closely related to the defense, which highlight the role of skin mucus as the first barrier of defense and the interaction with the environment. Finally, the potential of the bioactive peptides with antimicrobial properties, and their possible application in biomedicine, pharmaceutical, and nutraceutical industry was addressed.
Assuntos
Octopodiformes , Proteogenômica , Animais , Proteômica/métodos , Proteoma/metabolismo , Octopodiformes/química , Octopodiformes/metabolismo , Cromatografia Líquida , Espectrometria de Massas em Tandem , Peptídeos/metabolismo , Muco/metabolismoRESUMO
The common octopus (Octopus vulgaris) is nowadays the most demanded cephalopod species for human consumption. This species was also postulated for aquaculture diversification to supply its increasing demand in the market worldwide, which only relies on continuously declining field captures. In addition, they serve as model species for biomedical and behavioral studies. Body parts of marine species are usually removed before reaching the final consumer as by-products in order to improve preservation, reduce shipping weight, and increase product quality. These by-products have recently attracted increasing attention due to the discovery of several relevant bioactive compounds. Particularly, the common octopus ink has been described as having antimicrobial and antioxidant properties, among others. In this study, the advanced proteomics discipline was applied to generate a common octopus reference proteome to screen potential bioactive peptides from fishing discards and by-products such as ink. A shotgun proteomics approach by liquid chromatography coupled with tandem mass spectrometry (LC-MS/MS) using an Orbitrap Elite instrument was used to create a reference dataset from octopus ink. A total of 1432 different peptides belonging to 361 non-redundant annotated proteins were identified. The final proteome compilation was investigated by integrated in silico studies, including gene ontology (GO) term enrichment, pathways, and network studies. Different immune functioning proteins involved in the innate immune system, such as ferritin, catalase, proteasome, Cu/Zn superoxide dismutase, calreticulin, disulfide isomerase, heat shock protein, etc., were found in ink protein networks. Additionally, the potential of bioactive peptides from octopus ink was addressed. These bioactive peptides can exert beneficial health properties such as antimicrobial, antioxidant, antihypertensive, and antitumoral properties and are therefore considered lead compounds for developing pharmacological, functional foods or nutraceuticals.
Assuntos
Octopodiformes , Proteoma , Animais , Humanos , Proteoma/metabolismo , Proteômica/métodos , Octopodiformes/química , Cromatografia Líquida , Antioxidantes/farmacologia , Antioxidantes/metabolismo , Tinta , Espectrometria de Massas em Tandem , Peptídeos/químicaRESUMO
Background: To explore the correlation between visual field (VF) defect values and retinal nerve fiber layer (RNFL) thickness for intracranial tumor and glaucoma patients. Methods: Retrospective analysis is performed for the intracranial and glaucoma patients, whose VF defect values were measured with Octopus perimeter cluster analysis, RNFL thickness, ganglion cell layer (GCL) thickness, and optic disk parameters measured with swept-source OCT. The differences between VF and RNFL (including the data of optic disc) are calculated. The correlation between VF defect values and RNFL and GCL thickness are explored. Results: In total 43 eyes of 29 patients with intracranial tumor and 31 eyes of 19 patients with glaucoma were enrolled. The thickness of RNFL not only for the whole (360°), but also for the four quadrants was thinner in the glaucoma group than those of the intracranial tumor group (p<0.05), and similar to the thickness of GCL without significance (p>). There is no significant difference in VF for those two groups except glaucoma having lower sLV (p<0.05). A stronger correlation for mean deviations (MD)s of VF ten clusters and RNFL thickness of OCT twelve sectors is found in the glaucoma patients, but few in the intracranial tumor patients. Logistic regression also shows the loss of RNFL or increasing of vertical CDR and cup volume tending to the diagnosis of glaucoma and the irregular VF damage is inclined to the diagnosis of intracranial tumor. Conclusions: Intracranial tumor has a weak correlation between the RNFL thickness and Octopus VF MD, compared with that of glaucoma. OCT and Octopus VF might provide more helpful information for the differential diagnosis of intracranial tumor and glaucoma.
Assuntos
Neoplasias Encefálicas , Glaucoma , Octopodiformes , Animais , Neoplasias Encefálicas/diagnóstico por imagem , Neoplasias Encefálicas/patologia , Análise por Conglomerados , Glaucoma/diagnóstico , Glaucoma/patologia , Humanos , Fibras Nervosas/patologia , Células Ganglionares da Retina/patologia , Estudos Retrospectivos , Tomografia de Coerência Óptica , Transtornos da Visão/patologia , Testes de Campo Visual , Campos VisuaisRESUMO
Mitochondrial respirometry is key to understand how environmental factors model energetic cellular process. In the case of ectotherms, thermal tolerance has been hypothesized to be intimately linked with mitochondria capability to produce enough adenosine triphosphate (ATP) to respond to the energetic demands of animals in high temperatures. In a recent study made in Octopus maya was proposed the hypothesis postulating that high temperatures could restrain female reproduction due to the limited capacity of the animals' heart to sustain oxygen flow to the body, affecting in this manner energy production in the rest of the organs, including the ovarium Meza-Buendia AK et al. (2021). Unfortunately, until now, no reports have shown temperature effects and other environmental variables on cephalopod mitochondria activity because of the lack of a method to evaluate mitochondrial respiratory parameters in those species' groups. In this sense and for the first time, this study developed a method to obtain mitochondrial respirometry data of adult Octopus maya's heart. This protocol illustrates a step-by-step procedure to get high yield and functional mitochondria of cephalopod heart and procedure for determining the corresponding respiratory parameters. The procedure described in this paper takes approximately 3 to 4 hours from isolation of intact mitochondria to measurement of mitochondrial oxygen consumption.
Assuntos
Octopodiformes , Trifosfato de Adenosina/metabolismo , Animais , Feminino , Coração , Mitocôndrias/metabolismo , Mitocôndrias Cardíacas/metabolismo , Consumo de OxigênioRESUMO
Bioinspired soft devices, which possess high adaptability to targeted objects, provide promising solutions for a variety of industrial and medical applications. However, achieving stable and switchable attachment to objects with curved, rough, and irregular surfaces remains difficult, particularly in dry and underwater environments. Here, a highly adaptive soft microstructured switchable adhesion device is presented, which is inspired by the geometric and material characteristics of the tiny denticles on the surface of an octopus sucker. The contact interface of the artificial octopus sucker (AOS) is imprinted with soft, microscale denticles that interact adaptably with highly rough or curved surfaces. Robust and controllable attachment of the AOS with soft microdenticles (AOS-sm) to dry and wet surfaces with diverse morphologies is achieved, allowing conformal attachment on curved and soft objects with high roughness. In addition, AOS-sms assembled with an octopus-arm-inspired soft actuator demonstrate reliable grasping and the transport of complex polyhedrons, rough objects, and soft, delicate, slippery biological samples.
Assuntos
Materiais Biomiméticos , Calcificações da Polpa Dentária , Octopodiformes , Animais , Fenômenos Físicos , Força da MãoRESUMO
BACKGROUND AND PURPOSE: Over past decades, targeted therapies and immunotherapy have improved survival and reduced the morbidity of patients with BRAF-mutated melanoma. However, drug resistance and relapse hinder overall success. Therefore, there is an urgent need for novel compounds with therapeutic efficacy against BRAF-melanoma. This prompted us to investigate the antiproliferative profile of a tachykinin-peptide from the Octopus kaurna, Octpep-1 in melanoma. EXPERIMENTAL APPROACH: We evaluated the cytotoxicity of Octpep-1 by MTT assay. Mechanistic insights on viability and cellular damage caused by Octpep-1 were gained via flow cytometry and bioenergetics. Structural and pharmacological characterization was conducted by molecular modelling, molecular biology, CRISPR/Cas9 technology, high-throughput mRNA and calcium flux analysis. In vivo efficacy was validated in two independent xerograph animal models (mice and zebrafish). KEY RESULTS: Octpep-1 selectively reduced the proliferative capacity of human melanoma BRAFV600E -mutated cells with minimal effects on fibroblasts. In melanoma-treated cells, Octpep-1 increased ROS with unaltered mitochondrial membrane potential and promoted non-mitochondrial and mitochondrial respiration with inefficient ATP coupling. Molecular modelling revealed that the cytotoxicity of Octpep-1 depends upon the α-helix and polyproline conformation in the C-terminal region of the peptide. A truncated form of the C-terminal end of Octpep-1 displayed enhanced potency and efficacy against melanoma. Octpep-1 reduced the progression of tumours in xenograft melanoma mice and zebrafish. CONCLUSION AND IMPLICATIONS: We unravel the intrinsic anti-tumoural properties of a tachykinin peptide. This peptide mediates the selective cytotoxicity in BRAF-mutated melanoma in vitro and prevents tumour progression in vivo, providing a foundation for a therapy against melanoma.
Assuntos
Antineoplásicos , Melanoma , Trifosfato de Adenosina , Animais , Antineoplásicos/farmacologia , Cálcio , Linhagem Celular Tumoral , Humanos , Melanoma/tratamento farmacológico , Melanoma/patologia , Camundongos , Mutação , Octopodiformes/química , Peptídeos/farmacologia , Proteínas Proto-Oncogênicas B-raf/genética , Proteínas Proto-Oncogênicas B-raf/uso terapêutico , RNA Mensageiro , Espécies Reativas de Oxigênio , Taquicininas/genética , Taquicininas/uso terapêutico , Peixe-Zebra/genéticaRESUMO
Rigid suckers commonly used in surgical procedures often cause absorption damage, while their soft counterparts are difficult to handle due to their weak anchoring. Alternatively, the octopus sucker is both soft and has strong suction power. Further observation revealed that its structure is self-sealing and that the tissues are layered in hardness. Inspired by said structure and the characteristics of associated materials, a bionic soft sucker with stiffness gradient and acetabular roof structure was proposed, made of silicone with varying hardness including structures such as acetabular roof and circle muscles. The automatic tensile force measurement system was used to experimentally analyze the adsorption performance of the suckers to the soft curved contact surface. Both dry and wet conditions were tested, along with practical tests on organisms. The bionic sucker adsorption force was increased by 25.1% and 34.6% on the cylindrical surface, and 45.2% and 7.3% on the spherical surface for dry and wet conditions, respectively. During the experiment, the bionic suckers did not cause notable suction damage to the contact surfaces. Thus, this type of bionic sucker shows good application prospects in the field of surgery.
Assuntos
Octopodiformes , Adsorção , Animais , Biônica , Fenômenos Mecânicos , Octopodiformes/fisiologia , SucçãoRESUMO
INTRODUCTION: Cardiothoracic surgical outcomes are poorer in people with diabetes compared with those without diabetes. There are two important uncertainties in the management of people with diabetes undergoing major surgery: (1) how to improve diabetes management in the weeks leading up to an elective procedure and (2) whether that improved management leads to better postoperative outcomes. We previously demonstrated the feasibility of delivering the Optimising Cardiac Surgery ouTcOmes in People with diabeteS (OCTOPuS) intervention, an outpatient intervention delivered by diabetes healthcare professionals for people with suboptimally managed diabetes over 8-12 weeks before elective cardiac surgery. The present study will assess the clinical and cost-effectiveness of the intervention in cardiothoracic centres across the UK. METHODS AND ANALYSIS: A multicentre, parallel group, single-blinded 1:1 individually randomised trial comparing time from surgery until clinically fit for discharge in adults with suboptimally managed type 1 diabetes or type 2 diabetes undergoing elective surgery between the OCTOPuS intervention and usual care (primary endpoint). Secondary endpoints will include actual time from surgery to discharge from hospital; days alive and either out of hospital or judged as clinically fit for discharge; mortality; time on intensive therapy unit (ITU)/ventilator; infections; acute myocardial infarction; change in weight; effect on postoperative renal function and incidence of acute kidney injury; change in HbA1c; frequency and severity of self-reported hypoglycaemia; operations permanently cancelled for suboptimal glycaemic levels; cost-effectiveness; psychosocial questionnaires. The target sample size will be 426 recruited across approximately 15 sites. The primary analysis will be conducted on an intention-to-treat population. A two-sided p value of 0.05 or less will be used to declare statistical significance for all analyses and results will be presented with 95% CIs. ETHICS AND DISSEMINATION: The trial was approved by the South Central-Hampshire A Research Ethics Committee (20/SC/0271). Results will be disseminated through conferences, scientific journals, newsletters, magazines and social media. TRIAL REGISTRATION NUMBER: ISRCTN10170306.
Assuntos
Procedimentos Cirúrgicos Cardíacos , Diabetes Mellitus Tipo 1 , Diabetes Mellitus Tipo 2 , Octopodiformes , Adulto , Animais , Humanos , Estudos Multicêntricos como Assunto , Pacientes Ambulatoriais , Ensaios Clínicos Controlados Aleatórios como AssuntoRESUMO
Underutilized marine food products such as cephalopods' ink could be sources of bioactive compounds providing health benefits. This study aimed to assess the anti-proliferative and anti-inflammatory effects from Octopus vulgaris ink extracts (hexane-, ethyl acetate-, dichloromethane- (DM), and water extracts) using human colorectal (HT-29/HCT116) and breast (MDA-MB-231) cancer cells, and LPS-challenged murine RAW 264.7 cells. Except by ethyl-acetate, all of the extracts exhibited anti-proliferative effects without being cytotoxic to ARPE-19 and RAW 264.7 cells. Among DM fractions (F1/F2/F3), DM-F2 showed the highest anti-proliferative effect (LC50 = 52.64 µg/mL), inducing pro-apoptotic morphological disruptions in HCT116 cells. On RAW 264.7 cells, DM-F2 displayed the lowest nitrites reduction and up-regulation of key-cytokines from the JAK-STAT, PI3K-Akt, and IL-17 pathways. Compared to control, DM-F2 increased IL-4 and decreased NF-κB fluorometric expression in peripheral blood mononuclear cells (PBMCs). Metabolomic analysis of DM-F2 highlighted hexadecanoic acid and 1-(15-methyl-1-oxohexadecyl)-pyrrolidine as the most important metabolites. These compounds also exhibited high in silico binding affinity (-4.6 to -5.8 kcal/mol) to IL-1α, IL-1ß, and IL-2. Results suggested the joint immuno-modulatory and anti-proliferative effect derived from selected compounds of underutilized marine food products such as ink. This is the first report of such biological activities in extracts from O. vulgaris ink.
Assuntos
Anti-Inflamatórios/farmacologia , Proliferação de Células/efeitos dos fármacos , Octopodiformes/química , Animais , Citocinas/metabolismo , Células HCT116 , Humanos , Mediadores da Inflamação/metabolismo , Macrófagos/efeitos dos fármacos , Macrófagos/metabolismo , Metabolômica , Cloreto de Metileno/química , Camundongos , Nitritos/metabolismo , Células RAW 264.7 , Transdução de SinaisRESUMO
The novelty of the present research is conducting a new method in the systemic resistance of plant diseases by using distinct marine extracts. The ability of two octopus extracts to reduce the wilt disease caused by Fusarium oxysporum was observed. The applied methods are soaked roots (SR) and foliar shoots (FS). The antioxidant enzyme activities, percent disease index (PDI), and growth parameters were measured. In vitro antifungal potential of the octopus extracts against F. oxysporum was examined. The obtained result shows that SR extracts reduced PDI. Additionally, all the tested treatments promoted the growth and photosynthetic pigments of the infected plants. SR (in ethanolic extracts) was the most prominent inducer which offered a high advancement in the total soluble protein contents. Also, SR (in methanolic extracts) was the most suitable inducer which provided a very necessary development not only in the total phenol but also in the peroxidase (POD) and polyphenol oxidase (PPO) activities. GC-MS investigation of the octopus extracts exhibited that the compounds which possess antifungal activity were furoscrobiculin B and/or eugenol. They demonstrated a notable antifungal potential against F. oxysporum with a maximum activity of 38.5 and 12.7 mm ZOI after the treatment with the ethanolic and methanolic extract, respectively. FTIR results illustrated the functional group of the compound responsible for the antifungal activity. Additionally, an atomic absorption result reveals that there are traces of metals detected such as Pb, Ag, Cu, Zn, and Mg. The antifungal activity was decreased as the concentrations were reduced. Accordingly, the present extracts may be used as the vital agents in the agricultural field to restrain the plant pathogenic fungi, especially F. oxysporum from a proliferation.