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1.
Prog Brain Res ; 273(1): 117-143, 2022.
Artigo em Inglês | MEDLINE | ID: mdl-35940712

RESUMO

Mammalian retinas contain three specialized photoreceptors: the rods and cones in the outer retina, whose primary function is to support visual perception in dim and bright environments, respectively, and a small subset of retinal ganglion cells ("intrinsically photosensitive" retinal ganglion cells; ipRGCs), which are directly light-responsive owing to their expression of the photopigment melanopsin. Melanopsin photoreception is optimized to encode low-frequency changes in the light environment and, as a result, extends the temporal and spatial range over which light is detected by the retina. ipRGCs innervate many brain areas, and this allows melanopsin light responses to be used for diverse purposes, ranging from the synchronization of the circadian clock with the solar day to light's regulation of mood, alertness, and neuroendocrine and cognitive functions. In this review, we discuss the methods and findings that have contributed to our understanding of melanopsin across biology. We particularly focus on the approaches that allow melanopsin to be studied at a systems/whole animal level and how these methods have illuminated the role of melanopsin in diverse physiological outputs.


Assuntos
Luz , Opsinas de Bastonetes , Animais , Mamíferos/metabolismo , Modelos Animais , Células Ganglionares da Retina/metabolismo , Opsinas de Bastonetes/metabolismo
2.
Prog Brain Res ; 273(1): 71-95, 2022.
Artigo em Inglês | MEDLINE | ID: mdl-35940725

RESUMO

Light is an important environmental stimulus that exerts a powerful influence on physiology and behavior across multiple timescales. Organisms have adapted to respond to the predictable 24-h light/dark cycle imposed by the solar day using this light information to appropriately time physiological and behavioral functions while acute changes in the light environment provide important salient cues to induce rapid responses. Variations in the light environment caused by seasonal changes in daylength as well as those prevalent in modern day life (artificial lighting, transmeridian travel) have made the light environment more irregular and unpredictable. Alterations in the regular timing of light input can have dramatic physiological and behavioral effects including a significant impact on mental health and increased prevalence of mood disorders. While the relationship between light and mood has been well established, the neuronal mechanisms underlying this relationship have remained unclear. Animal models paired with advanced technology have allowed scientists to perform detailed studies about light- dependent effects on mood-related behaviors that are not possible in human subjects. The contributions of these studies have provided novel insight into the features of light information (e.g., timing, wavelength, etc.) that are responsible for observed changes in mood-related behaviors while uncovering the brain regions, neurons, and molecules involved. In this chapter, we discuss the advancements made in deciphering neuronal mechanisms mediating light-dependent effects on mood using animal models.


Assuntos
Afeto , Ritmo Circadiano , Animais , Encéfalo , Ritmo Circadiano/fisiologia , Humanos , Modelos Animais , Transtornos do Humor/etiologia
3.
Biomed Res Int ; 2022: 1440996, 2022.
Artigo em Inglês | MEDLINE | ID: mdl-35909475

RESUMO

Background: Efflux pumps are transmembrane proteins that expel drugs out of a bacterial cell contributing to microorganism drug resistance. Several studies addressing the use of natural products with medicinal properties have intensified given the above. Thus, the aim of the present study was to investigate the antibacterial activity and the O-eugenol potential in Staphylococcus aureus resistance reversal by efflux pump inhibition, as well as to evaluate its toxicity in the Drosophila melanogaster arthropod model. The broth microdilution method was used to determine the minimum inhibitory concentration (MIC) and the O-eugenol efflux pump inhibition. For the D. melanogaster toxicity assays, mortality and locomotor system damage were performed using the fumigation method. Results: O-eugenol presented a MIC of 1024 µg/mL against S. aureus. The association of this compound with the antibiotic tetracycline demonstrated a synergistic effect (p < 0.0001), this also being observed when the antibiotic was associated with ethidium bromide (p < 0.0001); thus, these results may be attributable to an efflux pump inhibition. The D. melanogaster mortality and geotaxis assays revealed the compound is toxic, with an EC50 of 18 µg/mL within 48 hours of exposure. Conclusions: While we can conclude that the tested product has an efflux pump inhibitory effect, further studies are needed to elucidate its mechanisms of action, in addition to assays using other strains to verify whether the substance has the same inhibitory effect.


Assuntos
Infecções Estafilocócicas , Staphylococcus aureus , Animais , Antibacterianos/metabolismo , Antibacterianos/farmacologia , Proteínas de Bactérias/metabolismo , Drosophila melanogaster/metabolismo , Eugenol/farmacologia , Testes de Sensibilidade Microbiana , Modelos Animais , Proteínas Associadas à Resistência a Múltiplos Medicamentos , Infecções Estafilocócicas/tratamento farmacológico
5.
Adv Exp Med Biol ; 1400: 15-33, 2022.
Artigo em Inglês | MEDLINE | ID: mdl-35930223

RESUMO

Schizophrenia is a complex and heterogeneous neurodevelopmental psychiatric disorder characterized by a variety of symptoms classically grouped into three main domains: positive (hallucinations, delusions, and thought disorder) and negative symptoms (social withdrawal, lack of affect) and cognitive dysfunction (attention, working and episodic memory functions, and processing speed). This disorder places an immense emotional and economic pressure on the individual and society-at-large. Although the etiology of schizophrenia is not completely known, it is proposed to involve abnormalities in neurodevelopmental processes and dysregulation in the signaling mediated by several neurotransmitters, such as dopamine, glutamate, and GABA. Preclinical research using animal models are essential in our understanding of disease development and pathology as well as the discovery and advance of novel treatment choices. Here we describe rodent models for studying schizophrenia, including those based on the effects of drugs (pharmacological models), neurodevelopmental disruption, demyelination, and genetic alterations. The advantages and limitations of such models are highlighted. We also discussed the great potential of proteomic technologies in unraveling the molecular mechanism of schizophrenia through animal models.


Assuntos
Esquizofrenia , Animais , Atenção , Modelos Animais de Doenças , Dopamina , Humanos , Modelos Animais , Proteômica , Esquizofrenia/diagnóstico
6.
Age Ageing ; 51(8)2022 Aug 02.
Artigo em Inglês | MEDLINE | ID: mdl-35932241

RESUMO

Many common chronic diseases and syndromes are ageing-related. This raises the prospect that therapeutic agents that target the biological changes of ageing will prevent or delay multiple diseases with a single therapy. Gerotherapeutic drugs are those that target pathways involved in ageing, with the aims of reducing the burden of ageing-related diseases and increasing lifespan and healthspan. The approach to discovering gerotherapeutic drugs is similar to that used to discover drugs for diseases. This includes screening for novel compounds that act on receptors or pathways that influence ageing or repurposing of drugs currently available for other indications. A novel approach involves studying populations with exceptional longevity, in order to identify genes variants linked with longer lifespan and could be targeted by drugs. Metformin, rapamycin and precursors of nicotinamide adenine dinucleotide are amongst the frontrunners of gerotherapeutics that are moving into human clinical trials to evaluate their effects on ageing. There are also increasing numbers of potential gerotherapeutic drugs in the pipeline or being studied in animal models. A key hurdle is designing clinical trials that are both feasible and can provide sufficient clinical evidence to support licencing and marketing of gerotherapeutic drugs.


Assuntos
Envelhecimento , Longevidade , Envelhecimento/genética , Animais , Humanos , Expectativa de Vida , Longevidade/genética , Modelos Animais
7.
NPJ Biofilms Microbiomes ; 8(1): 51, 2022 07 02.
Artigo em Inglês | MEDLINE | ID: mdl-35780244

RESUMO

In adult animals, acute viral infections only temporarily alter the composition of both respiratory and intestinal commensal microbiota, potentially due to the intrinsic stability of this microbial ecosystem. In stark contrast, commensal bacterial communities are rather vulnerable to perturbation in infancy. Animal models proved that disruption of a balanced microbiota development e.g., by antibiotics treatment early in life, increases the probability for metabolic disorders in adults. Importantly, infancy is also a phase in life with high incidence of acute infections. We postulated that acute viral infections in early life might pose a similarly severe perturbation and permanently shape microbiota composition with long-term physiological consequences for the adult host. As a proof of concept, we infected infant mice with a sub-lethal dose of influenza A virus. We determined microbiota composition up to early adulthood (63 days) from small intestine by 16S rRNA gene-specific next-generation sequencing. Infected mice underwent long-lasting changes in microbiota composition, associated with increase in fat mass. High-fat-high-glucose diet promoted this effect while co-housing with mock-treated animals overwrote the weight gain. Our data suggest that in the critical phase of infancy even a single silent viral infection could cast a long shadow and cause long-term microbiota perturbations, affecting adult host physiology.


Assuntos
Microbiota , Infecções Respiratórias , Viroses , Adulto , Animais , Humanos , Camundongos , Modelos Animais , RNA Ribossômico 16S/genética
8.
Front Cell Infect Microbiol ; 12: 907314, 2022.
Artigo em Inglês | MEDLINE | ID: mdl-35782148

RESUMO

Staphylococcus aureus (S. aureus) is a common and virulent human pathogen causing several serious illnesses including skin abscesses, wound infections, endocarditis, osteomyelitis, pneumonia, and toxic shock syndrome. Antibiotics were first introduced in the 1940s, leading to the belief that bacterial illnesses would be eradicated. However, microorganisms, including S. aureus, began to develop antibiotic resistance from the increased use and abuse of antibiotics. Antibiotic resistance is now one of the most serious threats to global public health. Bacteria like methicillin-resistant Staphylococcus aureus (MRSA) remain a major problem despite several efforts to find new antibiotics. New treatment approaches are required, with bacteriophage treatment, a non-antibiotic strategy to treat bacterial infections, showing particular promise. The ability of S. aureus to resist a wide range of antibiotics makes it an ideal candidate for phage therapy studies. Bacteriophages have a relatively restricted range of action, enabling them to target pathogenic bacteria. Their usage, usually in the form of a cocktail of bacteriophages, allows for more focused treatment while also overcoming the emergence of resistance. However, many obstacles remain, particularly in terms of their effects in vivo, necessitating the development of animal models to assess the bacteriophage efficiency. Here, we provide a review of the animal models, the various clinical case treatments, and clinical trials for S. aureus phage therapy.


Assuntos
Bacteriófagos , Staphylococcus aureus Resistente à Meticilina , Terapia por Fagos , Infecções Estafilocócicas , Animais , Antibacterianos/uso terapêutico , Modelos Animais , Infecções Estafilocócicas/microbiologia , Staphylococcus aureus
9.
Front Immunol ; 13: 878463, 2022.
Artigo em Inglês | MEDLINE | ID: mdl-35784312

RESUMO

Purpose: Although respiratory diseases (RD) are rapidly becoming a global health issue due to their high mortality and prevalence, there are limitations to the currently available treatments. Acupuncture has been recognized to mitigate many diseases by reducing inflammation and modulating cytokines. However, no systematic analysis has been performed to examine the effects of acupuncture on RD. We aimed to evaluate the effects of acupuncture on rodent animal models of RD. Methods: PubMed, EMBASE, MEDLINE, and the Research Information Service System were searched to retrieve studies that met our inclusion/exclusion criteria. The quality of each included study was evaluated using a 10-item checklist modified from the Collaborative Approach to Meta-Analysis and Review of Animal Data from Experimental Studies. With adequate data extracted, meta-analysis was performed using RevMan software. Results: A total of 18 studies were included, and the mean quality assessment was 5.7. The meta-analysis revealed that acupuncture had a significant effect on changing the cytokine levels, including pro-/anti-inflammatory, Th1-, Th2- and Th17- specific cytokines. Conclusion: Although there were limitations in the number of included studies, the results suggest that acupuncture can be a possible treatment for RD through its modulation of various cytokines, leading to reduced inflammation.


Assuntos
Terapia por Acupuntura , Citocinas , Terapia por Acupuntura/métodos , Animais , Inflamação , Modelos Animais , Roedores
10.
J Med Life ; 15(5): 685-697, 2022 May.
Artigo em Inglês | MEDLINE | ID: mdl-35815074

RESUMO

Ischemic reperfusion injury (IRI) of the kidneys is a direct sequela of surgical procedures associated with the interruption of blood supply. The pathophysiology of IRI is complicated, and several inflammatories, apoptosis, and oxidative stress pathways are implicated. Among the major receptors directly involved in renal IRI are the toll-like receptors (TLRs), specifically TLR2 and TLR4. In this study, we investigated the effects of Lipopolysaccharide from Rhodobacter Sphaeroides (TLR2 and TLR4 antagonist, LPS-RS) and the ultrapure form (pure TLR4 antagonist, ULPS-RS) on the histopathological changes and TLRs expression in an animal model of bilateral renal IRI. Forty-eight adult male rats were allocated into six groups (N=8) as follows: sham group (negative control without IRI), control group (rats underwent bilateral renal ischemia for 30 minutes and 2 hours of reperfusion), vehicle group (IRI+ vehicle), LPS-RS group (IRI+ 0.5 mg/kg of LPS-RS), ULPS-RS group (IRI+ 0.1 mg/kg of ULPS-RS), ULPS-RSH group (IRI+ 0.2 mg/kg of ULPS-RS). Significant improvement in the histopathological damages induced by renal IRI was found in the ULPS-RS treated groups at both doses compared with the control group. The protective effect of ULPS-RS was associated with significantly reduced TLR4 expression without affecting TLR2. Regarding LPS-RS, the tested dose adversely affected the renal tissues as manifested by the histopathological findings, although it similarly affected TLRs expression as ULPS-RS. Our results demonstrated that ULPS-RS was renoprotective while LPS-RS had no protective effect against the tissue damages induced by renal IRI.


Assuntos
Lipopolissacarídeos , Traumatismo por Reperfusão , Animais , Rim/irrigação sanguínea , Lipopolissacarídeos/farmacologia , Lipopolissacarídeos/uso terapêutico , Masculino , Modelos Animais , Ratos , Traumatismo por Reperfusão/complicações , Traumatismo por Reperfusão/tratamento farmacológico , Traumatismo por Reperfusão/metabolismo , Rhodobacter/metabolismo , Receptor 2 Toll-Like/metabolismo , Receptor 4 Toll-Like/metabolismo , Receptor 4 Toll-Like/uso terapêutico , Receptores Toll-Like/uso terapêutico
11.
Nat Commun ; 13(1): 4069, 2022 Jul 13.
Artigo em Inglês | MEDLINE | ID: mdl-35831300

RESUMO

Non-human primates are attractive laboratory animal models that accurately reflect both developmental and pathological features of humans. Here we present a compendium of cell types across multiple organs in cynomolgus monkeys (Macaca fascicularis) using both single-cell chromatin accessibility and RNA sequencing data. The integrated cell map enables in-depth dissection and comparison of molecular dynamics, cell-type compositions and cellular heterogeneity across multiple tissues and organs. Using single-cell transcriptomic data, we infer pseudotime cell trajectories and cell-cell communications to uncover key molecular signatures underlying their cellular processes. Furthermore, we identify various cell-specific cis-regulatory elements and construct organ-specific gene regulatory networks at the single-cell level. Finally, we perform comparative analyses of single-cell landscapes among mouse, monkey and human. We show that cynomolgus monkey has strikingly higher degree of similarities in terms of immune-associated gene expression patterns and cellular communications to human than mouse. Taken together, our study provides a valuable resource for non-human primate cell biology.


Assuntos
Transcriptoma , Animais , Macaca fascicularis/genética , Camundongos , Modelos Animais , Transcriptoma/genética
12.
Sci Rep ; 12(1): 11649, 2022 Jul 08.
Artigo em Inglês | MEDLINE | ID: mdl-35803983

RESUMO

Autologous bone graft substitute (ABGS) containing rhBMP6 in autologous blood coagulum (Osteogrow) is a novel therapeutic solution for bone regeneration. This study is aimed to investigate the long-term outcome of ABGS with synthetic ceramics (Osteogrow-C) in rabbit posterolateral spinal fusion (PLF) model. Osteogrow-C implants were implanted bilaterally between rabbit lumbar transverse processes. We compared the outcome following implantation of ABGS with ceramic particles of different chemical composition (TCP and biphasic ceramics containing both TCP and HA) and size (500-1700 µm and 74-420 µm). Outcome was analyzed after 14 and 27 weeks by microCT, histology, and biomechanical analyses. Successful bilateral spinal fusion was observed in all animals at the end of observation period. Chemical composition of ceramic particles has impact on the PLF outcome via resorption of TCP ceramics, while ceramics containing HA were only partially resorbed. Moreover, persistence of ceramic particles subsequently resulted with an increased bone volume in implants with small particles containing high proportion of HA. ABGS (rhBMP6/ABC) with various synthetic ceramic particles promoted spinal fusion in rabbits. This is the first presentation of BMP-mediated ectopic bone formation in rabbit PLF model with radiological, histological, and biomechanical features over a time course of up to 27 weeks.


Assuntos
Substitutos Ósseos , Doenças da Coluna Vertebral , Fusão Vertebral , Animais , Substitutos Ósseos/farmacologia , Transplante Ósseo/métodos , Fosfatos de Cálcio/uso terapêutico , Cerâmica/farmacologia , Vértebras Lombares/patologia , Modelos Animais , Coelhos , Doenças da Coluna Vertebral/patologia , Fusão Vertebral/métodos
13.
Molecules ; 27(13)2022 Jul 01.
Artigo em Inglês | MEDLINE | ID: mdl-35807505

RESUMO

Zingiber ottensii (ZO) Valeton, a local plant in Northern Thailand, has been widely used in traditional medicine. Many studies using in vitro models reveal its pharmacological activities, including the anti-inflammatory activity of ZO essential oil, extracted from ZO rhizomes. However, the scientific report to confirm its anti-inflammatory activity using animal models is still lacking. The present study aimed to evaluate the anti-inflammatory activity and explore the possible mechanisms of action of ZO essential oil in rats. The results revealed that ZO essential oil significantly reduced the ear edema formation induced by ethyl phenylpropiolate. Pre-treatment with ZO essential oil significantly reduced the carrageenan-induced hind paw edema and the severity of inflammation in paw tissue. In addition, pre-treatment with ZO essential oil exhibited decreased COX-2 and pro-inflammatory cytokine TNF-α expression in paw tissue, as well as PGE2 levels in serum. On this basis, our study suggests that ZO essential oil possesses anti-inflammatory activity in animal models. Its possible mechanisms of action may involve the inhibition of TNF-α expression as well as the inhibition of COX-2 and PGE2 production. These findings provide more crucial data of ZO essential oil that may lead to new natural anti-inflammatory product development in the future.


Assuntos
Óleos Voláteis , Zingiberaceae , Animais , Anti-Inflamatórios/uso terapêutico , Carragenina/efeitos adversos , Ciclo-Oxigenase 2/metabolismo , Dinoprostona/metabolismo , Edema/induzido quimicamente , Edema/tratamento farmacológico , Modelos Animais , Óleos Voláteis/uso terapêutico , Extratos Vegetais/uso terapêutico , Ratos , Fator de Necrose Tumoral alfa/metabolismo , Zingiberaceae/metabolismo
14.
Radiol Imaging Cancer ; 4(4): e210098, 2022 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-35838531

RESUMO

Animal models play a crucial role in developing and testing new therapies for hepatocellular carcinoma (HCC), providing preclinical evidence prior to exploring human safety and efficacy outcomes. The interventional radiologist must weigh the advantages and disadvantages of various animal models available when testing a new local-regional therapy. This review highlights the currently available animal models for testing local-regional therapies for HCC and details the importance of considering animal genetics, tumor biology, and molecular mechanisms when ultimately choosing an animal model. Keywords: Animal Studies, Interventional-Vascular, Molecular Imaging-Clinical Translation, Molecular Imaging-Cancer, Chemoembolization, Liver © RSNA, 2022.


Assuntos
Carcinoma Hepatocelular , Quimioembolização Terapêutica , Neoplasias Hepáticas , Animais , Carcinoma Hepatocelular/diagnóstico por imagem , Carcinoma Hepatocelular/terapia , Humanos , Neoplasias Hepáticas/diagnóstico por imagem , Neoplasias Hepáticas/terapia , Modelos Animais , Tomografia Computadorizada por Raios X
15.
Science ; 377(6606): eabq0839, 2022 08 05.
Artigo em Inglês | MEDLINE | ID: mdl-35857620

RESUMO

To combat future severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) variants and spillovers of SARS-like betacoronaviruses (sarbecoviruses) threatening global health, we designed mosaic nanoparticles that present randomly arranged sarbecovirus spike receptor-binding domains (RBDs) to elicit antibodies against epitopes that are conserved and relatively occluded rather than variable, immunodominant, and exposed. We compared immune responses elicited by mosaic-8 (SARS-CoV-2 and seven animal sarbecoviruses) and homotypic (only SARS-CoV-2) RBD nanoparticles in mice and macaques and observed stronger responses elicited by mosaic-8 to mismatched (not on nanoparticles) strains, including SARS-CoV and animal sarbecoviruses. Mosaic-8 immunization showed equivalent neutralization of SARS-CoV-2 variants, including Omicrons, and protected from SARS-CoV-2 and SARS-CoV challenges, whereas homotypic SARS-CoV-2 immunization protected only from SARS-CoV-2 challenge. Epitope mapping demonstrated increased targeting of conserved epitopes after mosaic-8 immunization. Together, these results suggest that mosaic-8 RBD nanoparticles could protect against SARS-CoV-2 variants and future sarbecovirus spillovers.


Assuntos
COVID-19 , Nanopartículas , Animais , Anticorpos Neutralizantes , Anticorpos Antivirais , COVID-19/prevenção & controle , Epitopos , Camundongos , Modelos Animais , SARS-CoV-2 , Glicoproteína da Espícula de Coronavírus
16.
Int J Mol Sci ; 23(15)2022 Jul 25.
Artigo em Inglês | MEDLINE | ID: mdl-35897770

RESUMO

The coronavirus disease 2019 (COVID-19) pandemic, caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), has been a major public health challenge worldwide. Owing to the emergence of novel viral variants, the risks of reinfections and vaccine breakthrough infections has increased considerably despite a mass of vaccination. The formation of cytokine storm, which subsequently leads to acute respiratory distress syndrome, is the major cause of mortality in patients with COVID-19. Based on results of preclinical animal models and clinical trials of acute lung injury and acute respiratory distress syndrome, the immunomodulatory, tissue repair, and antiviral properties of MSCs highlight their potential to treat COVID-19. This review article summarizes the potential mechanisms and outcomes of MSC therapy in COVID-19, along with the pathogenesis of the SARS-CoV-2 infection. The properties of MSCs and lessons from preclinical animal models of acute lung injury are mentioned ahead. Important issues related to the use of MSCs in COVID-19 are discussed finally.


Assuntos
Lesão Pulmonar Aguda , COVID-19 , Transplante de Células-Tronco Mesenquimais , Células-Tronco Mesenquimais , Síndrome do Desconforto Respiratório , Lesão Pulmonar Aguda/etiologia , Lesão Pulmonar Aguda/terapia , Animais , COVID-19/terapia , Imunomodulação , Transplante de Células-Tronco Mesenquimais/métodos , Modelos Animais , Síndrome do Desconforto Respiratório/etiologia , Síndrome do Desconforto Respiratório/terapia , SARS-CoV-2
17.
Cent Eur J Public Health ; 30 Suppl: S27-S31, 2022 06.
Artigo em Inglês | MEDLINE | ID: mdl-35841222

RESUMO

Celiac disease (CD) is a disorder that affects both children and adults. Over the few last decades, several new atypical cases have been identified through improved diagnostic tools. On the other hand, the onset of CD at a later age, including atypical CD forms whose clinical picture overlaps with other autoimmune diseases, shows that currently there are several unknown gene mutations, which could be responsible for the disease development. Non-celiac gluten sensitivity (NCGS) is entity included by the ingestion of gluten leading to intestinal, or extraintestinal symptoms that improve once the gluten is removed from the nutrition. In this article relationships between genetically modified rodent animals with previously unknown multiple organ changes and CD, respectively NCGS are reviewed. Relationships between the small bowel histological changes and other organs pathology are discussed. Results of research document that changes have similar genetic background and can develop to serious autoimmune systematic diseases, including small bowel inflammation resembling atypical CD or NCGS. These may have extra-intestinal symptomatology but without a clear explanation of causes and differences in their manifestations. Research on animal models helps to discover links between several disorders associated with gastrointestinal damage. New methods based on individual gene mutations can help in atypical adult CD and NCGS recognitions in the future.


Assuntos
Doença Celíaca , Roedores , Animais , Doença Celíaca/genética , Glutens , Modelos Animais
18.
Int J Mol Sci ; 23(14)2022 Jul 09.
Artigo em Inglês | MEDLINE | ID: mdl-35886959

RESUMO

Inflammatory bowel diseases (IBD) are chronic inflammatory disorders of the gastrointestinal tract that encompass two main phenotypes, namely Crohn's disease and ulcerative colitis. These conditions occur in genetically predisposed individuals in response to environmental factors. Epigenetics, acting by DNA methylation, post-translational histones modifications or by non-coding RNAs, could explain how the exposome (or all environmental influences over the life course, from conception to death) could influence the gene expression to contribute to intestinal inflammation. We performed a scoping search using Medline to identify all the elements of the exposome that may play a role in intestinal inflammation through epigenetic modifications, as well as the underlying mechanisms. The environmental factors epigenetically influencing the occurrence of intestinal inflammation are the maternal lifestyle (mainly diet, the occurrence of infection during pregnancy and smoking); breastfeeding; microbiota; diet (including a low-fiber diet, high-fat diet and deficiency in micronutrients); smoking habits, vitamin D and drugs (e.g., IBD treatments, antibiotics and probiotics). Influenced by both microbiota and diet, short-chain fatty acids are gut microbiota-derived metabolites resulting from the anaerobic fermentation of non-digestible dietary fibers, playing an epigenetically mediated role in the integrity of the epithelial barrier and in the defense against invading microorganisms. Although the impact of some environmental factors has been identified, the exposome-induced epimutations in IBD remain a largely underexplored field. How these environmental exposures induce epigenetic modifications (in terms of duration, frequency and the timing at which they occur) and how other environmental factors associated with IBD modulate epigenetics deserve to be further investigated.


Assuntos
Expossoma , Doenças Inflamatórias Intestinais , Animais , Epigenoma , Inflamação/genética , Doenças Inflamatórias Intestinais/epidemiologia , Doenças Inflamatórias Intestinais/genética , Modelos Animais
19.
PLoS One ; 17(7): e0271232, 2022.
Artigo em Inglês | MEDLINE | ID: mdl-35853079

RESUMO

BACKGROUND: Cysticercosis and Neurocysticercosis (NCC) can be studied using several animal species in experimental models which contributes to the understanding of the human form of the disease. Experimental infections of Taenia spp. are vital in explaining the modes of transmission of the parasite and helps the understanding of transmission of the parasite in humans and thus may be useful in designing therapeutic and immune-prophylactic studies to combat the disease. Thus, this systematic review aims to explore the existing experimental animal models to the understanding of cysticercosis in both humans and animals and elucidate the risk factors of cysticercosis and identify the Taenia spp. used in these models. METHODOLOGY: We systematically identified all publications from the Web of Science, Google Scholar, and Pubmed regarding experimental animal models using Taenia spp. that cause cysticercosis in both humans and animals. 58 studies were identified for eligibility. Of these, only 48 studies met the inclusion criteria from which data extraction was done and presented descriptively. RESULTS: Pigs, cattle, gerbils, mice, rats, voles, monkeys, cats, dogs, and goats were used in which T. solium, T. saginata, T. saginata asiatica, T. crassiceps and T. asiatica were studied. The routes used to induce disease were; oral, intravenous, subcutaneous, intramuscular, intraperitoneal, intraarterial, intracranial, intraduodenal, and surgical routes using eggs, oncospheres, and proglottids. Besides, the establishment of infection using eggs and oncospheres was affected by the route used to induce infection in the experimental animals. The cysticerci recovery rate in all the experimental studies was low and the number of animals used in these experiments varied from 1 to 84. Although not analysed statistically, sex, age, and breed of animals influenced the cysticerci recovery rate. Additionally, the cysticerci recovery rate and antibody-antigen levels were shown to increase with an increase in the dose of oncospheres and eggs inoculated in the animals. Contrasting results were reported in which the cysticerci recovery rate decreased with an increase in the dose of eggs inoculated. CONCLUSION: This review describes the various animal experiments using Taenia species that cause cysticercosis highlighting the animals used, age and their breed, the routes of infection used to induce disease and the sample size used, and the cysticerci recovery rate in these animal models.


Assuntos
Cisticercose , Neurocisticercose , Taenia solium , Taenia , Animais , Bovinos , Cisticercose/parasitologia , Cysticercus , Cães , Humanos , Camundongos , Modelos Animais , Ratos , Suínos
20.
Biosens Bioelectron ; 214: 114521, 2022 Oct 15.
Artigo em Inglês | MEDLINE | ID: mdl-35820254

RESUMO

Balance disorders affect approximately 30% of the population throughout their lives and result in debilitating symptoms, such as spontaneous vertigo, nystagmus, and oscillopsia. The main cause of balance disorders is peripheral vestibular dysfunction, which may occur as a result of hair cell loss, neural dysfunction, or mechanical (and morphological) abnormality. The most common cause of vestibular dysfunction is arguably vestibular hair cell damage, which can result from an array of factors, such as ototoxicity, trauma, genetics, and ageing. One promising therapy is the vestibular prosthesis, which leverages the success of the cochlear implant, and endeavours to electrically integrate the primary vestibular afferents with the vestibular scene. Other translational approaches of interest include stem cell regeneration and gene therapies, which aim to restore or modify inner ear receptor function. However, both of these techniques are in their infancy and are currently undergoing further characterization and development in the laboratory, using animal models. Another promising translational avenue to treating vestibular hair cell dysfunction is the potential development of artificial biocompatible hair cell sensors, aiming to replicate functional hair cells and generate synthetic 'receptor potentials' for sensory coding of vestibular stimuli to the brain. Recently, artificial hair cell sensors have demonstrated significant promise, with improvements in their output, such as sensitivity and frequency selectivity. This article reviews the history and current state of bioelectronic devices to interface with the labyrinth, spanning the vestibular implant and artificial hair cell sensors.


Assuntos
Técnicas Biossensoriais , Células Ciliadas Vestibulares , Animais , Terapia Genética/métodos , Células Ciliadas Vestibulares/fisiologia , Modelos Animais , Sistema Vestibular
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