RESUMO
Bufalin, a major cardiotonic compound of the traditional Chinese medicine Chanshu has been used for cancer treatment for several years. However, the molecular mechanisms of Bufalin-induced autophagy in osteosarcoma (OS) is not fully understood. In the present study, it was shown that Bufalin induced crosstalk between apoptosis and autophagy, which resulted in OS cell death. Mechanistically, Bufalin induced autophagy by increased the ratio of microtubule-associated protein 1A/1B-light chain 3 (LC3)-II/LC3-I, and inducing apoptosis via the caspase-dependent pathway. Inhibition of autophagy promoted Bufalin-induced cell death. In contrast, suppression of apoptosis enhanced Bufalin-induced autophagy. In addition, it was found that Bufalin activated the Ca2+ /calmodulin-dependent protein kinase ß/AMPK/Beclin1 pathway, which resulted in induction of autophagy. These findings provide a mechanistic understanding of the means by which Bufalin mediates autophagy and apoptosis in OS cells.
Assuntos
Quinase da Proteína Quinase Dependente de Cálcio-Calmodulina , Osteossarcoma , Humanos , Proteína Beclina-1 , Quinase da Proteína Quinase Dependente de Cálcio-Calmodulina/metabolismo , Proteínas Quinases Ativadas por AMP/metabolismo , Cálcio/metabolismo , Linhagem Celular Tumoral , Transdução de Sinais , Apoptose , Autofagia , Osteossarcoma/tratamento farmacológico , Osteossarcoma/metabolismoRESUMO
Tapeworms of the genus Dibothriocephalus are widely distributed throughout the world, some of which are agents of human diphyllobothriasis, one of the most important fish-borne zoonoses caused by a cestode parasite. Genomic and transcriptomic data can be used to develop future diagnostic tools and epidemiological studies. The present work focuses on a comparative analysis of the transcriptomes of adult and plerocercoid D. dendriticus and the identification of their differentially expressed genes (DEGs). Transcriptome assembly and analysis yielded and annotated 35,129 unigenes, noting that 16,568 (47%) unigenes were not annotated in known databases, which may indicate a unique set of expressed transcripts for D. dendriticus. A total of 8022 differentially expressed transcripts were identified, including 3225 upregulated and 4797 downregulated differentially expressed transcripts from the plerocercoid and adult animals. The analysis of DEGs has shown that among the most differentially expressed genes, there are important genes characteristic of each stage. Thus, several genes are characteristic of D. dendriticus plerocercoids, including fatty acid-binding protein and ferritin. Among the most highly expressed DEGs of the adult stage of D. dendriticus is the Kunitz-type serine protease inhibitor, in two putative isoforms. The analyses of GO and KEGG metabolic pathways revealed that a large number of the DEGs of D. dendriticus are associated with the biosynthesis of various substances such as arginine and folate, as well as with various metabolic pathways such as galactose metabolism, selenocompound metabolism, and phosphonate and phosphinate metabolism. This will contribute to further research aimed at identifying targets for new generation drugs and the development of specific vaccines.
Assuntos
Cestoides , Diphyllobothrium , Animais , Adulto , Humanos , Transcriptoma , Larva , Perfilação da Expressão Gênica , Cestoides/genéticaRESUMO
BACKGROUND: Breast cancer is the most diagnosed cancer among women, and its incidence and mortality are rapidly growing worldwide. In this regard, plant-derived natural compounds have been shown to be effective as chemotherapeutic and preventative agents. Apricot kernels are a rich source of nutrients including proteins, lipids, fibers, and phenolic compounds and contain the aromatic cyanogenic glycoside amygdalin that has been shown to exert a cytotoxic effect on cancer cells by affecting the cell cycle, inducing apoptosis, and regulating the immune function. METHODS: Here, we describe a previously unexplored proapoptotic mechanism of action of amygdalin in breast cancer (MCF7) cells that involves the modulation of intracellular proteolysis. For comparative purposes, the same investigations were also conducted upon cell treatment with two apricot kernel aqueous extracts from Prunus armeniaca L. RESULTS: We observed that both the 20S and 26S proteasome activities were downregulated in the MCF7 cells upon 24 h treatments. Simultaneously, the autophagy cascade resulted in being impaired due to cathepsin B and L inhibition that also contributed to a reduction in cancer cell migration. The inhibition of these proteolytic systems finally promoted the activation of apoptotic events in the MCF7 cells. CONCLUSION: Collectively, our data unveil a novel mechanism of the anticancer activity of amygdalin, prompting further investigations for potential application in cancer preventative strategies.
Assuntos
Amigdalina , Neoplasias da Mama , Prunus armeniaca , Feminino , Humanos , Amigdalina/farmacologia , Proteólise , Neoplasias da Mama/tratamento farmacológico , ApoptoseRESUMO
Oncogenic viruses are associated with approximately 15% of human cancers. In viral infections, microRNAs play an important role in host-pathogen interactions. miR-21 is a highly conserved non-coding RNA that not only regulates the development of oncogenic viral diseases, but also responds to the regulation of intracellular signal pathways. Oncogenic viruses, including HBV, HCV, HPV, and EBV, co-evolve with their hosts and cause persistent infections. The upregulation of host miR-21 manipulates key cellular pathways to evade host immune responses and then promote viral replication. Thus, a better understanding of the role of miR-21 in viral infections may help us to develop effective genetically-engineered oncolytic virus-based therapies against cancer.
Assuntos
Interações Hospedeiro-Patógeno/genética , MicroRNAs/fisiologia , Vírus Oncogênicos/patogenicidade , Infecções Tumorais por Vírus/genética , Animais , Humanos , Neoplasias/genética , Neoplasias/patologia , Neoplasias/virologia , Vírus Oncogênicos/genética , Vírus Oncogênicos/imunologia , Infecções Tumorais por Vírus/imunologia , Infecções Tumorais por Vírus/patologia , Infecções Tumorais por Vírus/virologia , Replicação Viral/genéticaRESUMO
Tapeworms (Cestoda) cause neglected diseases that can be fatal and are difficult to treat, owing to inefficient drugs. Here we present an analysis of tapeworm genome sequences using the human-infective species Echinococcus multilocularis, E. granulosus, Taenia solium and the laboratory model Hymenolepis microstoma as examples. The 115- to 141-megabase genomes offer insights into the evolution of parasitism. Synteny is maintained with distantly related blood flukes but we find extreme losses of genes and pathways that are ubiquitous in other animals, including 34 homeobox families and several determinants of stem cell fate. Tapeworms have specialized detoxification pathways, metabolism that is finely tuned to rely on nutrients scavenged from their hosts, and species-specific expansions of non-canonical heat shock proteins and families of known antigens. We identify new potential drug targets, including some on which existing pharmaceuticals may act. The genomes provide a rich resource to underpin the development of urgently needed treatments and control.
Assuntos
Adaptação Fisiológica/genética , Cestoides/genética , Genoma Helmíntico/genética , Parasitos/genética , Animais , Evolução Biológica , Cestoides/efeitos dos fármacos , Cestoides/fisiologia , Infecções por Cestoides/tratamento farmacológico , Infecções por Cestoides/metabolismo , Sequência Conservada/genética , Echinococcus granulosus/genética , Echinococcus multilocularis/efeitos dos fármacos , Echinococcus multilocularis/genética , Echinococcus multilocularis/metabolismo , Genes de Helmintos/genética , Genes Homeobox/genética , Proteínas de Choque Térmico HSP70/genética , Humanos , Hymenolepis/genética , Redes e Vias Metabólicas/genética , Terapia de Alvo Molecular , Parasitos/efeitos dos fármacos , Parasitos/fisiologia , Proteoma/genética , Células-Tronco/citologia , Células-Tronco/metabolismo , Taenia solium/genéticaRESUMO
MicroRNAs (miRNAs) are short noncoding RNAs, involved in the regulation of parasite diseases. However, a role of miRNAs in Echinococcus multilocularis infection remains largely unknown. In this study, we first found the expression levels of key genes involved in miRNA biogenesis and function, including Ago2, Xpo5, Tarbp2 and DgcR8, were obviously altered in the macrophage RAW264·7 cells exposed to E. multilocularis metacestodes. Compared with the control, 18 and 32 known miRNAs were found to be differentially expressed (P 2) in the macrophages exposed to E. multilocularis metacestodes for 6 and 12 h, respectively. Among these, several are known to be involved in regulating cytokine activities and immune responses. Quantitative real-time polymerase chain reaction results showed that the expression of nine selected miRNAs was consistent with the sequencing data at each treatment time points. Moreover, there were statistically significant correlations between the expression levels of miRNAs and their corresponding targeted genes. Our data give us some clues to pinpoint a role of miRNAs in the course of infection and immunity of E. multilocularis.
Assuntos
Echinococcus multilocularis/genética , Macrófagos/parasitologia , MicroRNAs/genética , Animais , Citocinas/genética , Equinococose/parasitologia , Echinococcus multilocularis/imunologia , Interações Hospedeiro-Patógeno/genética , Interações Hospedeiro-Patógeno/imunologia , Macrófagos/imunologia , Camundongos , MicroRNAs/imunologia , Células RAW 264.7 , Reação em Cadeia da Polimerase em Tempo RealRESUMO
Hydatigera taeniaeformis (formerly known as Taenia taeniaeformis) is a parasitic tapeworm that has a worldwide distribution. H. taeniaeformis is naturally transmitted between mice and cats and threatens to human health, especially those who are in close contact with pets. MicroRNAs (miRNAs) are a class of small regulatory non-coding RNAs involved in the regulation of parasite growth and development, parasite infection and immunology, and host-pathogen interactions. The miRNA profile of H. taeniaeformis remains to be elucidated. Herein, 47 conserved miRNAs (grouped into 34 miRNA families) and 4 novel miRNAs were identified in H. taeniaeformis metacestodes using deep sequencing approach. Among them, hta-miR-71, -let-7, and-miR-87 was absolutely predominant in H. taeniaeformis metacestodes. Moreover, comparative analysis revealed the presence of miR-71/2 and miR-4989/277 clusters in H. taeniaeformis. Nucleotide bias analysis of identified miRNAs showed that the adenine (A) was the dominant nucleotide at the beginning of the miRNAs, particularly at the positions of third and 7th nucleotides. The study provides rich data for further understandings of H. taeniaeformis biology.
Assuntos
MicroRNAs/química , MicroRNAs/isolamento & purificação , Taenia/genética , Animais , Sequência de Bases , Sequenciamento de Nucleotídeos em Larga Escala/veterinária , Humanos , Fígado/parasitologia , MicroRNAs/classificação , Família Multigênica , RNA de Helmintos/química , RNA de Helmintos/classificação , RNA de Helmintos/isolamento & purificação , Doenças dos Roedores/parasitologia , Roedores , Teníase/parasitologia , Teníase/veterináriaRESUMO
OBJECTIVE: To evaluate the effects of L-lysine (Lys)/L-arginine (Arg) on lipid and protein oxidation of emulsion sausage during storage and its possible mechanism. METHODS: Four samples were prepared based on the presence or absence of additional sodium isoascorbate, Lys, or Arg: sample A (control), sample B (0.05 g of sodium isoascorbate), sample C (0.4 g of Lys), and sample D (0.4 g of Arg). Peroxide value (POV), thiobarbituric reactive substances (TBARS), protein carbonyls and thiols were measured. 2,2-Diphenyl-1-picrylhydrazyl (DPPH) and hydroxyl radical-scavenging, ferrous ion-chelating ability were also measured. RESULTS: Compared with the control, the sample treated with sodium isoascorbate, Lys or Arg had significantly lower POV during the initial 20 days, TBARS during the initial 15 days. Protein carbonyls were significantly lower compared Sample B, C, and D with A during the later storage (10 to 25 days); basically, protein thiols became lower during storage when the samples were treated with sodium isoascorbate, Lys, or Arg. Both Lys and Arg had weak reducing power but strong ferrous ion-chelating activity and DPPH radical- and hydroxyl radical-scavenging activity. CONCLUSION: Both Lys and Arg effectively inhibited the oxidation of lipids and proteins in emulsion sausage by scavenging free radicals and chelating ferrous ions. The results obtained may be favorable for the prevention of lipid and protein oxidation during processing and storage of meat products.
RESUMO
Echinococcus multilocularis is a most pathogenic zoonotic tapeworm that causes devastating echinococcosis in both humans and animals. Circulating microRNAs (miRNAs) are stably existed in the serum/plasma of mammalian hosts during helminthic infection. In this study, we compared the host-circulating miRNA expression in the sera from the E. multilocularis-infected and uninfected mice. A total of 58 host-origin serum miRNAs were differentially expressed (2 ⩾ fold change, P < 0·05), of which 21 were upregulated and 37 were significantly downregulated. Consistent with the sequencing data, quantitative polymerase chain reaction (PCR) results showed that the expression levels of four miRNAs were elevated gradually and one decreased gradually at the E. multilocularis infection time points. Moreover, seven of E. multilocularis specific miRNAs were identified in the sera. Real-time PCR analyses further demonstrated that only two parasite-derived miRNAs (emu-miR-10 and emu-miR-227) were specifically amplified in all the sera from mice infected with E. multilocularis. These findings will be helpful to understand the roles of miRNAs in host-parasite interaction and to potentiate serum miRNAs as diagnostic targets for echinococcosis.
Assuntos
MicroRNA Circulante/genética , Equinococose/imunologia , Echinococcus multilocularis/fisiologia , RNA de Helmintos/genética , Animais , Regulação para Baixo , Equinococose/parasitologia , Echinococcus multilocularis/genética , Feminino , Interações Hospedeiro-Parasita , Camundongos , Camundongos Endogâmicos DBA , Reação em Cadeia da Polimerase em Tempo Real , Regulação para CimaRESUMO
Echinococcus multilocularis metacestodes are a causative pathogen for alveolar echinococcosis in human beings, and have been found to express miRNAs including emu-miR-71. miR-71 is evolutionarily conserved and highly expressed across platyhelminths, but little is known about its role. Here it was shown that emu-miR-71 was differentially expressed in protoscoleces and was unlikely to be expressed in neoblasts. The results of the luciferase assay indicated that emu-miR-71 was able to bind in vitro to the 3'-UTR of emu-nlk, encoding a key regulator of cell division, causing significant downregulation of luciferase activity (p < 0.01) compared to the negative control and the construct with mutations in the binding site. Consistent with the decreased luciferase activity, transfection of emu-miR-71 mimics into protoscoleces notably repressed emu-NLK (p < 0.05). These results demonstrate the suppression of emu-nlk by emu-miR-71, potentially involved in the protoscolex development.
Assuntos
Echinococcus multilocularis/genética , MicroRNAs/fisiologia , Proteínas Quinases Ativadas por Mitógeno/metabolismo , Regiões 3' não Traduzidas/imunologia , Animais , Anticorpos Anti-Helmínticos/metabolismo , Regulação para Baixo , Echinococcus multilocularis/enzimologia , Echinococcus multilocularis/crescimento & desenvolvimento , Echinococcus multilocularis/imunologia , Regulação da Expressão Gênica , Imuno-Histoquímica , Hibridização In Situ , Luciferases/metabolismo , Camundongos , Camundongos Endogâmicos DBA , Microscopia de Fluorescência , Proteínas Quinases Ativadas por Mitógeno/imunologia , Plasmídeos , RNA de Helmintos/isolamento & purificação , CoelhosRESUMO
Objective: To screen for the optimal qPCR primers for Echinococcus multilocularis apomucin gene (Em-apo) and analyze Em-apo expression. Methods: Primers were designed based on 4 Em-apo sequences from GeneDB. Primer specificity and PCR efficiency were determined, based on which the optimal primer pairs were selected. Alterations of Em-apo expression in 1 000 E. multilocularis protoscoleces treated with albendazoleï¼5 µg/mlï¼ and insulinï¼100 ng/mlï¼ were separately assessed using the selected primers. DMSO used in albendazole dilution and in PBS insulin dilution were used as the control. Results: Specific primers for Em-apo-1, Em-apo-2/3, Em-apo-4 and actin were selected. qPCR melting curves revealed a single peak for each primer pair and an amplification efficiency from 95% to 101%. The qPCR showed increased expression of Em-apo-1ï¼1.51±0.27ï¼, Em-apo-2/3 ï¼1.39±0.30ï¼ and Em-apo-4ï¼1.14±0.18ï¼ after albendazole treatment in comparison to the DMSO controlï¼1.00ï¼ï¼P>0.05 among the three genesï¼; and an unaltered Em-apo-1 expression, slightly decreased Em-apo-4 expression, and significantly decreased Em-apo-2/3 expressionï¼0.73±0.09ï¼ after insulin treatment in comparison to the PBS control (P>0.05 among the three genesï¼. Conclusion: The selected specific primers for Em-apo genes can be used to analyze the gene expression by qPCR. Treatment with albendazole and insulin show certain effects on the expression of Em-apo genes in E. multilocularis protoscoleces.
Assuntos
Echinococcus multilocularis , Albendazol , Animais , Equinococose , Mucinas Gástricas , Reação em Cadeia da Polimerase em Tempo RealRESUMO
BACKGROUND: Cysticercosis remains a major neglected tropical disease of humanity in many regions, especially in sub-Saharan Africa, Central America and elsewhere. Owing to the emerging drug resistance and the inability of current drugs to prevent re-infection, identification of novel vaccines and chemotherapeutic agents against Taenia solium and related helminth pathogens is a public health priority. The T. solium genome and the predicted proteome were reported recently, providing a wealth of information from which new interventional targets might be identified. In order to characterize and classify the entire repertoire of protease-encoding genes of T. solium, which act fundamental biological roles in all life processes, we analyzed the predicted proteins of this cestode through a combination of bioinformatics tools. Functional annotation was performed to yield insights into the signaling processes relevant to the complex developmental cycle of this tapeworm and to highlight a suite of the proteases as potential intervention targets. RESULTS: Within the genome of this helminth parasite, we identified 200 open reading frames encoding proteases from five clans, which correspond to 1.68% of the 11,902 protein-encoding genes predicted to be present in its genome. These proteases include calpains, cytosolic, mitochondrial signal peptidases, ubiquitylation related proteins, and others. Many not only show significant similarity to proteases in the Conserved Domain Database but have conserved active sites and catalytic domains. KEGG Automatic Annotation Server (KAAS) analysis indicated that ~60% of these proteases share strong sequence identities with proteins of the KEGG database, which are involved in human disease, metabolic pathways, genetic information processes, cellular processes, environmental information processes and organismal systems. Also, we identified signal peptides and transmembrane helices through comparative analysis with classes of important regulatory proteases. Phylogenetic analysis using Bayes approach provided support for inferring functional divergence among regulatory cysteine and serine proteases. CONCLUSION: Numerous putative proteases were identified for the first time in T. solium, and important regulatory proteases have been predicted. This comprehensive analysis not only complements the growing knowledge base of proteolytic enzymes, but also provides a platform from which to expand knowledge of cestode proteases and to explore their biochemistry and potential as intervention targets.
Assuntos
Biologia Computacional/métodos , Proteínas de Helminto/classificação , Peptídeo Hidrolases/classificação , Taenia solium/genética , Animais , Teorema de Bayes , Mineração de Dados , Genoma Helmíntico , Estudo de Associação Genômica Ampla , Proteínas de Helminto/genética , Proteínas de Helminto/metabolismo , Peptídeo Hidrolases/genética , Peptídeo Hidrolases/metabolismo , Filogenia , Análise de Sequência de DNA , Taenia solium/enzimologiaRESUMO
Argonaute proteins (AGOs) are mediators of gene silencing via recruitment of small regulatory RNAs to induce translational regression or degradation of targeted molecules. Platyhelminths have been reported to express microRNAs but the diversity of AGOs in the phylum has not been explored. Phylogenetic relationships of members of this protein family were studied using data from six platyhelminth genomes. Phylogenetic analysis showed that all cestode and trematode AGOs, along with some triclad planarian AGOs, were grouped into the Ago subfamily and its novel sister clade, here referred to as Cluster 1. These were very distant from Piwi and Class 3 subfamilies. By contrast, a number of planarian Piwi-like AGOs formed a novel sister clade to the Piwi subfamily. Extensive sequence searching revealed the presence of an additional locus for AGO2 in the cestode Echinococcus granulosus and exon expansion in this species and E. multilocularis. The current study suggests the absence of the Piwi subfamily and Class 3 AGOs in cestodes and trematodes and the Piwi-like AGO expansion in a free-living triclad planarian and the occurrence of exon expansion prior to or during the evolution of the most-recent common ancestor of the Echinococcus species studied.
Assuntos
Proteínas Argonautas/genética , Família Multigênica/genética , Filogenia , Platelmintos/genética , Sequência de Aminoácidos , Animais , Sequência de Bases , Biologia Computacional , Funções Verossimilhança , Modelos Genéticos , Dados de Sequência Molecular , Platelmintos/classificação , Alinhamento de SequênciaRESUMO
Orf virus (ORFV) is an enveloped virus with a double-stranded DNA genome, causing a contagious pustular dermatitis, mainly in goats and sheep. In this study, two strains of ORFV were isolated from sheep and goat samples in Xinjiang and Shaanxi, China. The B2L and virus interferon resistance (VIR) genes of these two isolates were sequenced and analyzed after PCR amplification. Phylogenetic analysis showed that the two isolates clustered with other ORFV strains but were separated into different subgroups. The Xinjiang strain shared the highest homology with the Gansu strain, whereas the Shaanxi strain shared higher homology with the Taiwan and Hubei strains. This is the first report of the molecular characterization of ORFV in Northwest China, and it provides new information on the genotyping of the causative agents responsible for contagious ecthyma dermatitis outbreaks in China.
Assuntos
Ectima Contagioso/virologia , Vírus do Orf/classificação , Vírus do Orf/genética , Filogenia , Proteínas Virais/genética , Animais , China , Análise por Conglomerados , DNA Viral/química , DNA Viral/genética , Genótipo , Cabras , Dados de Sequência Molecular , Vírus do Orf/isolamento & purificação , Reação em Cadeia da Polimerase , Análise de Sequência de DNA , OvinosRESUMO
miRNAs, a subclass of small regulatory RNAs, are present from ancient unicellular protozoans to parasitic helminths and parasitic arthropods. The miRNA-silencing mechanism appears, however, to be absent in a number of protozoan parasites. Protozoan miRNAs and components of their silencing machinery possess features different from other eukaryotes, providing some clues on the evolution of the RNA-induced silencing machinery. miRNA functions possibly associate with neoblast biology, development, physiology, infection and immunity of parasites. Parasite infection can alter host miRNA expression that can favor both parasite clearance and infection. miRNA pathways are, thus, a potential target for the therapeutic control of parasitic diseases.
Assuntos
MicroRNAs/genética , Parasitos/genética , Doenças Parasitárias/genética , Doenças Parasitárias/parasitologia , Interferência de RNA , RNA Nucleolar Pequeno/metabolismo , Animais , Antiparasitários/farmacologia , Evolução Molecular , Regulação da Expressão Gênica , Humanos , MicroRNAs/metabolismo , Parasitos/metabolismo , Doenças Parasitárias/tratamento farmacológico , RNA de Helmintos/genética , RNA de Helmintos/metabolismo , RNA de Protozoário/genética , RNA de Protozoário/metabolismo , RNA Nucleolar Pequeno/genética , Transdução de Sinais/efeitos dos fármacosRESUMO
Most species of the genus Taenia are of considerable medical and veterinary significance. In this study, complete nuclear 18S rRNA gene sequences were obtained from seven members of genus Taenia [Taenia multiceps, Taenia saginata, Taenia asiatica, Taenia solium, Taenia pisiformis, Taenia hydatigena, and Taenia taeniaeformis] and a phylogeny inferred using these sequences. Most of the variable sites fall within the variable regions, V1-V5. We show that sequences from the nuclear 18S ribosomal RNA gene have considerable promise as sources of phylogenetic information within the genus Taenia. Furthermore, given that almost all the variable sites lie within defined variable portions of that gene, it will be appropriate and economical to sequence only those regions for additional species of Taenia.
Assuntos
DNA de Helmintos/genética , DNA Ribossômico/genética , Filogenia , RNA Ribossômico 18S/genética , Taenia/classificação , Taenia/genética , Animais , Análise por Conglomerados , DNA de Helmintos/química , DNA Ribossômico/química , Cães , Dados de Sequência Molecular , Análise de Sequência de DNA , Taenia/isolamento & purificaçãoRESUMO
The gut-brain axis (GBA) is a complex bidirectional communication network connecting the gut and brain. It involves neural, immune, and endocrine communication pathways between the gastrointestinal (GI) tract and the central nervous system (CNS). Perturbations of the GBA have been reported in many neurodegenerative disorders (NDDs), such as Alzheimer's disease (AD), Parkinson's disease (PD), and amyotrophic lateral sclerosis (ALS), among others, suggesting a possible role in disease pathogenesis. The gut microbiota is a pivotal component of the GBA, and alterations in its composition, known as gut dysbiosis, have been associated with GBA dysfunction and neurodegeneration. The gut microbiota might influence the homeostasis of the CNS by modulating the immune system and, more directly, regulating the production of molecules and metabolites that influence the nervous and endocrine systems, making it a potential therapeutic target. Preclinical trials manipulating microbial composition through dietary intervention, probiotic and prebiotic supplementation, and fecal microbial transplantation (FMT) have provided promising outcomes. However, its clear mechanism is not well understood, and the results are not always consistent. Here, we provide an overview of the major components and communication pathways of the GBA, as well as therapeutic approaches targeting the GBA to ameliorate NDDs.
Assuntos
Doença de Alzheimer , Microbioma Gastrointestinal , Doenças Neurodegenerativas , Doença de Parkinson , Humanos , Eixo Encéfalo-Intestino , Doenças Neurodegenerativas/terapia , Doença de Alzheimer/terapia , Doença de Parkinson/terapia , Encéfalo , Disbiose/terapiaRESUMO
Background: Insufficient sleep is a serious public health problem in modern society. It leads to increased risk of chronic diseases, and it has been frequently associated with cellular oxidative damage and widespread low-grade inflammation. Probiotics have been attracting increasing interest recently for their antioxidant and anti-inflammatory properties. Here, we tested the ability of probiotics to contrast oxidative stress and inflammation induced by sleep loss. Methods: We administered a multi-strain probiotic formulation (SLAB51) or water to normal sleeping mice and to mice exposed to 7 days of chronic sleep restriction (CSR). We quantified protein, lipid, and DNA oxidation as well as levels of gut-brain axis hormones and pro and anti-inflammatory cytokines in the brain and plasma. Furthermore, we carried out an evaluation of microglia morphology and density in the mouse cerebral cortex. Results: We found that CSR induced oxidative stress and inflammation and altered gut-brain axis hormones. SLAB51 oral administration boosted the antioxidant capacity of the brain, thus limiting the oxidative damage provoked by loss of sleep. Moreover, it positively regulated gut-brain axis hormones and reduced peripheral and brain inflammation induced by CSR. Conclusions: Probiotic supplementation can be a possible strategy to counteract oxidative stress and inflammation promoted by sleep loss.
Assuntos
Probióticos , Distúrbios do Início e da Manutenção do Sono , Camundongos , Animais , Antioxidantes/farmacologia , Antioxidantes/metabolismo , Estresse Oxidativo , Inflamação/etiologia , Privação do Sono/complicações , Anti-Inflamatórios/farmacologia , Distúrbios do Início e da Manutenção do Sono/complicações , Hormônios/farmacologiaRESUMO
Chronic parasite infections in the liver pose a global threat to human and animal health, often occurring with liver fibrosis that leads to cirrhosis, liver failure, and even cancer. Hepatic fibrogenesis is a complex yet reversible process of tissue repair and is associated with various factors, including immune cells, microenvironment, gut microbiome, and interactions of the different liver cells. As a profibrogenic or antifibrogenic driver, microRNAs (miRNAs) are closely involved in parasite-induced hepatic fibrosis. This article updates the current understanding of the roles of miRNAs in hepatic fibrogenesis by parasite infections and discusses the strategies using miRNAs as candidates for diagnostics and therapeutics.