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Postpartum depression (PPD) is a severe mental disorder that affects approximately 10---20% of women after childbirth. The precise mechanism underlying PPD pathogenesis remains elusive, thus limiting the development of therapeutics. Gut microbiota dysbiosis is considered to contribute to major depressive disorder. However, the associations between gut microbiota and PPD remain unanswered. Here, we established a mouse PPD model by sudden ovarian steroid withdrawal after hormone-simulated pseudopregnancy-human (HSP-H) in ovariectomy (OVX) mouse. Ovarian hormone withdrawal induced depression-like and anxiety-like behaviors and an altered gut microbiota composition. Fecal microbiota transplantation (FMT) from PPD mice to antibiotic cocktail-treated mice induced depression-like and anxiety-like behaviors and neuropathological changes in the hippocampus of the recipient mice. FMT from healthy mice to PPD mice attenuated the depression-like and anxiety-like behaviors as well as the inflammation mediated by the NOD-like receptor protein (NLRP)-3/caspase-1 signaling pathway both in the gut and the hippocampus, increased fecal short-chain fatty acids (SCFAs) levels and alleviated gut dysbiosis with increased SCFA-producing bacteria and reduced Akkermansia in the PPD mice. Also, downregulation of NLRP3 in the hippocampus mitigated depression-like behaviors in PPD mice and overexpression of NLRP3 in the hippocampal dentate gyrus induced depression-like behaviors in naïve female mice. Intriguingly, FMT from healthy mice failed to alleviate depression-like behaviors in PPD mice with NLRP3 overexpression in the hippocampus. Our results highlighted the NLRP3 inflammasome as a key component within the microbiota-gut-brain axis, suggesting that targeting the gut microbiota may be a therapeutic strategy for PPD.
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Depressão Pós-Parto , Modelos Animais de Doenças , Disbiose , Transplante de Microbiota Fecal , Microbioma Gastrointestinal , Hipocampo , Proteína 3 que Contém Domínio de Pirina da Família NLR , Animais , Feminino , Disbiose/metabolismo , Hipocampo/metabolismo , Camundongos , Microbioma Gastrointestinal/fisiologia , Proteína 3 que Contém Domínio de Pirina da Família NLR/metabolismo , Transplante de Microbiota Fecal/métodos , Depressão Pós-Parto/metabolismo , Camundongos Endogâmicos C57BL , Depressão/metabolismo , Doenças Neuroinflamatórias/metabolismo , Comportamento Animal/fisiologia , Ansiedade/metabolismo , Eixo Encéfalo-Intestino/fisiologia , Inflamação/metabolismo , OvariectomiaRESUMO
Sevoflurane exposure during rapid brain development induces neuronal apoptosis and causes memory and cognitive deficits in neonatal mice. Exosomes that transfer genetic materials including long non-coding RNAs (lncRNAs) between cells play a critical role in intercellular communication. However, the lncRNAs found in exosomes derived from neurons treated with sevoflurane and their potential role in promoting neurotoxicity remain unknown. In this study, we investigated the role of cross-talk of newborn mouse neurons with microglial cells in sevoflurane-induced neurotoxicity. Mouse hippocampal neuronal HT22 cells were exposed to sevoflurane, and then co-cultured with BV2 microglial cells. We showed that sevoflurane treatment markedly increased the expression of the lncRNA growth arrest-specific 5 (Gas5) in neuron-derived extracellular vesicles, which inhibited neuronal proliferation and induced neuronal apoptosis by promoting M1 polarization of microglia and the release of inflammatory cytokines. We further revealed that the exosomal lncRNA Gas5 significantly upregulated Foxo3 as a competitive endogenous RNA of miR-212-3p in BV2 cells, and activated the NF-κB pathway to promote M1 microglial polarization and the secretion of inflammatory cytokines, thereby exacerbating neuronal damage. In neonatal mice, intracranial injection of the exosomes derived from sevoflurane-treated neurons into the bilateral hippocampi significantly increased the proportion of M1 microglia, inhibited neuronal proliferation and promoted apoptosis, ultimately leading to neurotoxicity. Similar results were observed in vitro in BV2 cells treated with the CM from HT22 cells after sevoflurane exposure. We conclude that sevoflurane induces the transfer of lncRNA Gas5-containing exosomes from neurons, which in turn regulates the M1 polarization of microglia and contributes to neurotoxicity. Thus, modulating the expression of lncRNA Gas5 or the secretion of exosomes could be a strategy for addressing sevoflurane-induced neurotoxicity.
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Exossomos , MicroRNAs , RNA Longo não Codificante , Animais , Camundongos , Sevoflurano/toxicidade , Microglia/metabolismo , Animais Recém-Nascidos , RNA Longo não Codificante/genética , RNA Longo não Codificante/metabolismo , Exossomos/metabolismo , Neurônios/metabolismo , Citocinas/metabolismo , MicroRNAs/genética , MicroRNAs/metabolismoRESUMO
Anaerobic biological treatment was regarded as one of promising options for realizing concurrent WAS reduction, stabilization and bioenergy/bioresource recycle. But the relatively low treatment efficiency limited its spreading application toward larger scale considerably in China. Aimed at such barrier, this study offered a novel enhancing strategy for achieving high-efficiency of bioenergy/bioresource recycle from WAS anaerobic treatment via improving bioelectrogenesis/acidogenesis using sludge source-redox mediators (SSRMs). SSRMs not only facilitated bioeletrogenesis with an increasing efficiency of 36% for voltage output and 39% for bioelectricity bioconversion, but also enhanced acidogenesis of WAS with a mean elevating efficiency of 37.5% of volatile fatty acids (VFAs) production within 5 d Mechanistic investigations indicated that SSRMs had a potential influence on improving the protein and carbohydrate metabolisms-related genes' expression for enhancing bioelectrogenesis and acidogenesis. Moreover, SSRMs exerted roles of electrochemical "catalysts" or as terminal electron acceptors with affecting functional proteins of complexes of â and â £ in electron transfer chains for improving electron transfer efficiency. Meanwhile, the core members' abundance, microbial diversity and community distributive evenness were prompted concurrently for carrying out superior bioelectrogenesis and acidogenesis. A schematic illustration was established for demonstrating the mechanism of SSRMs for enhancing bioelectrogenesis and acidogenesis via changing microbial metabolism functions, enhancing electron transfer efficiency, and regulating functional genes' expression of functional proteins (up-regulating cytochrome c oxidase and down-regulating-NADH dehydrogenase). This study provided an effective enhancing strategy for facilitating WAS bioconversion to bioenergy/bioresource with well-process sustainability.
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Ácidos Graxos Voláteis , Esgotos , Esgotos/química , Fermentação , Oxirredução , Proteínas , Anaerobiose , Concentração de Íons de Hidrogênio , Reatores BiológicosRESUMO
Mono-lactate glyceride (LG) is a short-chain fatty acid ester. It has been shown that short-chain fatty acid esters play an important role in maintaining intestinal structure and function. The aim of this study is to investigate the effects of mono-lactate glyceride on growth performance and intestinal morphology and function in weaned piglets. Sixteen 21-day-old weaned piglets of similar weight were distributed arbitrarily to two treatments: The control group (basal diet) and the LG group (basal diet + 0.6% mono-lactate glyceride). The experiment lasted for 21 days. On day 21 of the trial, piglets were weighed, and blood and intestinal samples were collected for further analysis. Results showed that dietary supplementation with 0.6% mono-lactate glyceride decreased (p < 0.05) the diarrhea rate and the contents of malondialdehyde and hydrogen peroxide in the ileum and jejunum and increased (p < 0.05) the expression of intestinal tight junction protein (Occludin) and the activities of superoxide dismutase and catalase in the ileum and colon. In addition, mono-lactate glyceride supplementation could enhance intestinal mucosal growth by increasing (p < 0.05) the mRNA levels of extracellular regulated protein kinases, promote intestinal mucosal water and nutrient transport and lipid metabolism by increasing (p < 0.05) the mRNA levels of b0,+ amino acid transporter, aquaporin 3, aquaporin 10, gap junction protein alpha 1, intestinal fatty acid-binding protein, and lipoprotein lipase, enhance antiviral and immune function by increasing (p < 0.05) the mRNA levels of nuclear factor kappa-B, interferon-ß, mucovirus resistance protein II, 2'-5'-oligoadenylate synthetase-like, interferon-γ, C-C motif chemokine ligand 2, and toll-like receptor 4, and enhance antioxidant capacity by increasing (p < 0.05) the mRNA levels of NF-E2-related factor 2 and glutathione S-transferase omega 2 and decreasing (p < 0.05) the mRNA level of NADPH oxidase 2. These results suggested that dietary supplementation with mono-lactate glyceride could decrease the diarrhea rate by improving intestinal antioxidant capacity, intestinal mucosal barrier, intestinal immune defense function, and intestinal mucosal water and nutrient transport. Collectively, dietary supplementation with 0.6% mono-lactate glyceride improved the intestinal function of weaned piglets.
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Cerebral ischemia is one of the leading causes of death and disability worldwide. Although revascularization via reperfusion combined with advanced anticoagulant therapy is currently a gold standard treatment for patients, the reperfusion itself also results in a serious dysfunction termed cerebral ischemia-reperfusion (I/R) injury. Silent information regulator 1 (sirtuin 1, SIRT1), is a classic NAD+-dependent deacetylase, which has been proposed as an important mediator in the alleviation of cerebral ischemia through modulating multiple physiological processes, including apoptosis, inflammation, DNA repair, oxidative stress, and autophagy. Recent growing evidence suggests that SIRT1-mediated autophagy plays a key role in the pathophysiological process of cerebral I/R injury. SIRT1 could both activate and inhibit the autophagy process by mediating different autophagy pathways, such as the SIRT1-FOXOs pathway, SIRT1-AMPK pathway, and SIRT1-p53 pathway. However, the autophagic roles of SIRT1 in cerebral I/R injury have not been systematically summarized. Here, in this review, we will first introduce the molecular mechanisms and effects of SIRT1 in cerebral ischemia and I/R injury. Next, we will discuss the involvement of autophagy in the pathogenesis of cerebral I/R injury. Finally, we will summarize the latest advances in the interaction between SIRT1 and autophagy in cerebral I/R injury. A good understanding of these relationships would serve to consolidate a framework of mechanisms underlying SIRT1's neuroprotective effects and provides evidence for the development of drugs targeting SIRT1.
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The conductive media was capable to enhance anaerobic digestion and promote direct interspecific electron transfer (DIET). In this study, the effects of activated carbon- and graphite-conductive media on promoting anaerobic digestion efficiency of waste activated sludge were experimentally studied. The results show that the 100 mesh-activated carbon group reactor produced a largest biogas yield of 468.2 mL/g VSS, which was 13.8% higher than the blank test. The graphite group reactor with 400-grain size produced a largest biogas yield of 462.9 mL/g VSS, which was 12.5% higher than the blank test. Moreover, the optimal particle size of such two carbon- conductive mediators were optimized for enhancing degradation efficiency of VSS, TCOD, total protein and total polysaccharide of waste sludge. Activated carbon was capable to promote the hydrolytic acidification stage in anaerobic digestion of waste sludge. When the particle size reduced to the optimal particle size, the promoting effect could be strengthened for producing more hydrolytic acidification products for methanogenesis. However, in the graphite group, the methane production is increased by promoting the consumption of hydrolysis and acidification products and is enhanced with the particle size reduction, thus promoting the methanogenesis process, and improving the anaerobic digestion efficiency. Microbial community analysis showed that both activated carbon and graphite cultivated the genera of Methanosaeta, Methanobacterium, Nitrososphaeraceae, which promoted the improvement of methane production through the acetate debris methanogenesis pathway.
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Enhancing anaerobic treatment efficiency of waste activated sludge (WAS) toward preferable resource recovery would be an important requirement for achieving carbon-emission reduction, biosolids minimization, stabilization and security concurrently. This study demonstrated the synergic effect of potassium ferrate (PF) and nitrite on prompting WAS solubilisation and acidogenic fermentation toward harvesting volatile fatty acids (VFAs). The results indicated the PF+NaNO2 co-pretreatment boosted 7.44 times and 1.32 times higher WAS solubilisation [peak soluble chemical oxygen demand (SCOD) of 2680 ± 52 mg/L] than that by the single nitrite- and PF-pretreatment, respectively, while about 2.77 times and 2.11 times higher VFAs production were achieved (maximum VFAs accumulation of 3536.25 ± 115.24 mg COD/L) as compared with the single pretreatment (nitrite and PF)-fermentations. Afterwards the WAS dewaterability was improved simultaneously after acidogenic fermentation. Moreover, a schematic diagram was established for illustrating mechanisms of the co-pretreatment of PF and nitrite for enhancing the VFAs generation via increasing key hydrolytic enzymes, metabolic functional genes expression, shifting microbial biotransformation pathways and elevating abundances of key microbes in acidogenic fermentation. Furthermore, the mechanistic investigations suggested that the PF addition was conducive to form a relatively conductive fermentation environment for enhancing electron transfer (ET) efficiency, which contributed to the VFAs biotransformation positively. This study provided an effective strategy for enhancing the biodegradation/bioconversion efficiency of WAS organic matters with potential profitable economic returns.
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Nitritos , Esgotos , Fermentação , Concentração de Íons de Hidrogênio , Ácidos Graxos Voláteis , ÁcidosRESUMO
Polyoxyethylene dehydration sorbitol monooleate (polysorbate-80) pretreatment enhanced volatile fatty acids (VFAs) production of waste activated sludge (WAS) in acidogenic fermentation. The results showed that polysorbate-80 ameliorated WAS solubilization obviously with a soluble chemical oxygen demand (SCOD) increasing to 1536 mg/L within 4 h. Within 2 days of acidogenic fermentation, the maximal VFAs arrived to 2958.35 mg COD/L via polysorbate-80-pretreatment. The polysorbate-80 pretreatment boosted microbial diversity and richness in fermentation process. The Clostridium, Macellibacteroides and Acidocella strengthened microbial cooperation for the metabolic functions enhancement (e.g. amino acid metabolism and carbohydrate metabolism) for VFAs generation from WAS organics. Overall, the polysorbate-80 could play positive roles on the transformation of organic matter from sludge solid matters to VFAs, which was turned out to become an effective enhancing strategy for future WAS treatment / bioresource recovery with relatively low cost.
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Polissorbatos , Esgotos , Metabolismo dos Carboidratos , Ácidos Graxos Voláteis , Fermentação , Concentração de Íons de Hidrogênio , Interações MicrobianasRESUMO
Introduction: Postpartum depression (PPD) is a common neuropsychiatric disorder characterized by depression and comorbid anxiety during the postpartum period. PPD is difficult to treat because of its elusive mechanisms. Epigallocatechin-3-gallate (EGCG), a component of tea polyphenols, is reported to exert neuroprotective effects in emotional disorders by reducing inflammation and apoptosis. However, the effect of EGCG on PPD and the underlying mechanism are unknown. Methods: We used a mouse model of PPD established by exposing pregnant mice to gestational stress. Open field, forced swimming and tail suspension tests were performed to investigate the anxiety and depression-like behaviors. Immunohistochemical staining was used to measure the c-fos positive cells. The transcriptional levels of hippocampal semaphorin3A(sema3A), (glycogen synthase kinase 3-beta)GSK3ß and collapsin response mediator protein 2(CRMP2) were assessed by RT-PCR. Alterations in protein expression of Sema3A, GSK3ß, p-GSK3ß, CRMP2 and p-CRMP2 were quantified by western blotting. EGCG was administrated to analyze its effect on PPD mice. Results: Gestational stress induced anxiety and depression-like behaviors during the postpartum period, increasing Sema3A expression while decreasing that of phosphorylated GSK3ß as well as c-Fos in the hippocampus. These effects were reversed by systemic administration of EGCG. Conclusions: Thus, EGCG may alleviate anxiety and depression-like behaviors in mice by downregulating Sema3A and increasing GSK3ß phosphorylation in the hippocampus, and has potential application in the treatment of PPD.
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Long non-coding RNA (lncRNA) X-inactive specific transcript (Xist) is involved in apoptosis and inflammatory injury. This study aimed to assess the role of lncRNA Xist in sevoflurane-induced social and emotional impairment and neuronal apoptosis in neonatal mice and hippocampal neuronal cells. The performance in social and emotional tests and the expression levels of lncRNA Xist and microRNA (miR)-98-5p after sevoflurane exposure were measured. Moreover, the effects of suppression of lncRNA Xist on neuronal apoptosis and endoplasmic reticulum (ER) stress were determined. Subsequently, the association among lncRNA Xist, miR-98-5p, and ER degradation-enhancing α-mannosidase-like 1 protein (EDEM1) was explored. Our results showed that lncRNA Xist increased, miR-98-5p decreased, and social and emotional impairment appeared after sevoflurane exposure. Furthermore, suppression of lncRNA Xist improved sevoflurane-induced social and emotional impairment and reduced sevoflurane-induced neuronal apoptosis and ER stress in vivo and in vitro. Moreover, lncRNA Xist negatively regulated miR-98-5p expression, and it contributed to sevoflurane-induced neuronal apoptosis and ER stress by sponging miR-98-5p. Additionally, EDEM1 was identified as a target of miR-98-5p. Our findings revealed that the knockdown of lncRNA Xist ameliorates sevoflurane-induced social and emotional impairment through inhibiting neuronal apoptosis and ER stress by targeting the miR-98-5p/EDEM1 axis.
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The secondary metabolites of endophytic fungus Cerrena sp.A593 from Pogostemon cablin and their cytotoxic activities were investigated. Eight sesquiterpenoids were isolated from the fermentation broth of the strain A593 by silica gel, reverse phase silica gel, Sephadex LH-20, HPLC and so on. Their structures were identified as chloriolin B(1), chloriolin C(2), pleurocybellone A(3), dihydrohypnophilin(4), cucumin F(5), antrodin A(6), 10α-hydroxyamorphan-4-en-3-one(7), and connatusin A(8). Compounds 1- 8 were firstly found from the genus Cerrena. All isolated sesquiterpenoids were evaluated for in vitro cytotoxic activities against HepG-2, SF-268, MCF-7 and NCI-H460 tumor cell lines. Compounds 1-3 showed inhibitory activities against the four tumor cell lines with IC50 values ranging from 20.33 to 63.13 µmolâ¢L⻹.
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Antineoplásicos/isolamento & purificação , Pogostemon/microbiologia , Polyporales/química , Sesquiterpenos/isolamento & purificação , Antineoplásicos/farmacologia , Linhagem Celular Tumoral , Endófitos/química , Humanos , Sesquiterpenos/farmacologiaRESUMO
Porcine epidemic diarrhea virus (PEDV) infects the intestine of young pigs, but effective measures for prevention and treatment are lacking. N-Acetylcysteine (NAC) has been shown to reduce endotoxin-induced intestinal dysfunction. This study was conducted with the PEDV-infected neonatal piglet model to determine the effect of NAC supplementation on intestinal function. Thirty-two 7-day-old piglets were randomly allocated to one of four treatments in a 2 × 2 factorial design consisting of two liquid diets (0 or 50 mg/kg BW NAC supplementation) and oral administration of 0 or 104.5 TCID50 (50% tissue culture infectious dose) PEDV. On day 7 of the trial, half of the pigs (n = 8) in each dietary treatment received either sterile saline or PEDV (Yunnan province strain) solution at 104.5 TCID50 per pig. On day 10 of the trial, D-xylose (0.1 g/kg BW) was orally administrated to all pigs. One hour later, jugular vein blood samples were collected, and then all pigs were killed to obtain the small intestine. PEDV infection increased diarrhea incidence, while reducing ADG. PEDV infection also decreased plasma D-xylose concentration, small intestinal villus height, mucosal I-FABP and villin mRNA levels but increased mucosal MX1 and GCNT3 mRNA levels (P < 0.05). Dietary NAC supplementation ameliorated the PEDV-induced abnormal changes in all the measured variables. Moreover, NAC reduced oxidative stress, as indicated by decreases in plasma and mucosal H2O2 levels. Collectively, these novel results indicate that dietary supplementation with NAC alleviates intestinal mucosal damage and improves the absorptive function of the small intestine in PEDV-infected piglets.