RÉSUMÉ
BACKGROUND: Schisandra chinensis lignan (SCL), a major active component of the traditional functional Chinese medicine Schisandra chinensis, has been reported to have antidepressant effects. Its mechanisms include alleviating intestinal barrier injury (IBI) by resolving intestinal microflora, anti-inflammation, and neuroprotection. SCL also regulates endogenous cannabinoid system, and it is closely related to the onset and development of depression. PURPOSE: We investigated a new treatment strategy for depression, i.e., alleviating IBI by regulating the endogenous cannabinoid system for antidepressant effects, as well as conducted in-depth research to explore the specific mechanism. METHODS: Behavioral analysis was conducted to detect the occurrence of depressive-like behavior in C57BL/6 mice. We used hematoxylin-eosin staining, periodic acid-Schiff staining, and immunofluorescence to evaluate IBI. Network pharmacology and Western blotting (WB) were used to predict and confirm that the amelioration effect of SCL was associated with anti-inflammation and anti-apoptosis. Combined with the levels of anandamide (AEA) and 2-arachidonoylglycerol (2-AG), we conducted the Pearson analysis between the AEA, 2-AG levels and the major targets identified and validated by network pharmacology and WB. Subsequently, URB-597, a fatty acid amide hydrolase (FAAH) antagonist with an AEA hydrolase-inhibiting effect, was administered to the mice, and behavioral analysis and apoptotic proteins were verified. Plasma endocannabinoid levels after URB-597 supplementation were measured via 6470 Triple Quadrupole LC/MS. Finally, the cannabinoid receptor type 2 (CB2R) antagonist AM630 was administered to mice, and immunofluorescence and WB were performed to assess the proteins of IBI and anti-inflammation. RESULTS: The study demonstrated that SCL alleviated depressive-like behaviours and ameliorated IBI. Network pharmacology and WB confirmed that the improvement of IBI was related to the anti-inflammatory and anti-apoptotic pathways. Pearson results showed that AEA levels were positively correlated with inflammation and apoptosis, with a greater contribution to apoptosis. In-depth studies validated that the URB-597 administration reversed the positive effects of SCL on depressive-like behavior and anti-apoptosis. Similarly, URB-597 counteracted AEA levels reduced by SCL and decreased 2-AG levels. Furthermore, AM630 supplementation antagonized SCL's effect of improving IBI by reactivating the MAPK/NF-κB inflammation pathway. CONCLUSION: Overall, SCL, in collaboration with the endogenous cannabinoid system regulated by SCL, alleviates depression associated IBI. The specific mechanism involes SCL decreasing AEA levels to inhibit colon tissue cell apoptosis by up-regulating FAAH. Simultaneously, it directly triggers CB2R to reduce inflammation responses, further alleviating IBI.
RÉSUMÉ
Diabetic peripheral neuropathy (DPN) is the most prevalent complication of type 2 diabetes mellitus (T2DM), and it seriously affects the quality of life of patients. Tauroursodeoxycholic acid (TUDCA) is a bile acid that plays a protective role against various diseases. However, the function of TUDCA in DPN progression needs to be elucidated. Hence, this study clarified the action of TUDCA on DPN development and explored its mechanism of action. Fecal samples were collected from 50 patients with T2DM or DPN. Schwann cells induced by high levels were constructed to simulate an uncontrolled diabetic state. Cell viability and migration were measured using the CCK-8 and wound-healing assays, respectively. Reactive oxygen species and pyroptosis were detected using flow cytometry. Parabacteroides goldsteinii and Parabacteroides distasonis levels were decreased in the feces of patients with DPN. TUDCA enhanced the viability and migration ability of high glucose-stimulated Schwann cells. In addition, Schwann cell pyroptosis stimulated by high glucose levels was inhibited by TUDCA. Furthermore, the protective roles of TUDCA in cell viability, migration ability, and pyroptosis of Schwann cells stimulated by high glucose were suppressed by the overexpression of NLRP3. TUDCA enhanced cell viability and migration and suppressed pyroptosis in Schwann cells stimulated by high glucose levels by modulating NLRP3 expression. Thus, TUDCA may be a promising drug for DPN therapy.
Sujet(s)
Diabète de type 2 , Pyroptose , Acide taurochénodésoxycholique , Humains , Protéine-3 de la famille des NLR contenant un domaine pyrine , Glucose/toxicité , Glucose/métabolisme , Diabète de type 2/traitement médicamenteux , Diabète de type 2/métabolisme , Qualité de vie , Cellules de Schwann/métabolisme , Mouvement cellulaireRÉSUMÉ
Based on the current results, they showed that Schisandra chinensis lignans (SCL) ameliorated depressive-like behaviors in chronic unpredictable mild stress (CUMS) mice, alleviated neuroinflammation, and improved neuronal injury. This study aimed to explore whether SCL exerted antidepressant effects through inhibiting neuroinflammation, in turn improving neuronal injury. In vitro studies revealed that SCL blocked lipopolysaccharide-increased BV2 microglial M1 but promoted the M2 phenotype. The BV2-N2a interaction model suggested that increasing the M2 phenotype of BV2 played neuroprotective effects. The current studies demonstrated that SCL up-regulated the expression of CUMS- and LPS-decreased cannabinoid receptor type-2 (CB2R) mRNA. In vitro studies showed that the transfection of BV2 with siCrn2 blocked the SCL-increased M2 phenotype via the inactivating signal transducer and activator of transcription 6 (STAT6) pathway, further decreasing the viability of N2a cells. Finally, the possible pharmacodynamic compounds, γ-schisandrin and schisantherin A, were indicated by AutoDuck analysis. Overall, our study showed that SCL promoted microglia polarization toward the M2 phenotype, in turn exerting neuroprotective effects by activating CB2R-STAT6 signaling further to play antidepressant roles.
Sujet(s)
Lignanes , Neuroprotecteurs , Schisandra , Souris , Animaux , Microglie/métabolisme , Schisandra/métabolisme , Neuroprotecteurs/métabolisme , Facteur de transcription STAT-6/métabolisme , Lignanes/pharmacologie , Lignanes/métabolisme , Lipopolysaccharides/pharmacologie , Antidépresseurs/pharmacologie , Antidépresseurs/métabolisme , Phénotype , Récepteurs de cannabinoïdes/métabolismeRÉSUMÉ
BACKGROUND: The present study aimed to investigate the protective effects and mechanism of salidroside (SAL) on hypoxia/reoxygenation (H/R)-induced cardiomyocyte apoptosis and myocardial ischemia/reperfusion (I/R) injury. METHODS: We set up an H/R H9c2 cell model in vitro and an I/R rat model in vivo. Cell viability, apoptosis and histopathologic evaluation were conducted. RESULTS: The cell viability of H/R-induced cardiomyocytes was increased by pretreatment of SAL, whereas the release of lactate dehydrogenase, reactive oxygen species production, and apoptosis were decreased accompanied with reduced Cleaved-caspase-3 and Bax, and increased Bcl-2 expressions. The SAL restored mitochondrial membrane potential both in vitro and in vivo, and improved electrocardiographic abnormality, and attenuated myocardial apoptosis and injury in I/R-induced rats. The transfection of miR-378a-3p inhibitor counteracted the effects of SAL-induced increase of cell viability and decrease of cell apoptosis and mitochondrial membrane potential. SAL reduced the expression of insulin-like growth factor 1 receptor (IGF1R), and increased the expressions of PI3K and Akt, however, these alterations were blocked by miR-378a-3p inhibitor. CONCLUSIONS: miR-378a-3p might participate in the protective effect of SAL in I/R-induced myocardial apoptosis via the IGF1R/PI3K/AKT signaling pathway.
Sujet(s)
microARN , Lésion de reperfusion myocardique , Rats , Animaux , Phosphatidylinositol 3-kinases/métabolisme , Protéines proto-oncogènes c-akt/métabolisme , Lésion de reperfusion myocardique/génétique , Lésion de reperfusion myocardique/prévention et contrôle , Lésion de reperfusion myocardique/métabolisme , microARN/métabolisme , Apoptose , Transduction du signal , Myocytes cardiaques/métabolisme , Hypoxie/métabolisme , Reperfusion , Ischémie/métabolismeRÉSUMÉ
Herein, we aim to investigate the effect of Alpinae Oxyphyllae Fructus (AOF) on cognitive impairments and neuroinflammation in a lipopolysaccharide (LPS)-induced models of AD. Mice were injected intracerebroventricularly with LPS, and then administrated AOF using a gavage for 6 weeks. Spatial working memory was assessed using the Y-maze and Morris water maze test, whereas the levels of PI3K, AKT, p-AKT, p-GSK3ß, GSK3ß, NF-κB, IL-1ß, IL-6, and TNF-α were evaluated using western blot and ELISA assay. Our data showed that AOF was able to significantly alleviate the memory decline in LPS-induced AD mice. Moreover, AOF was able to protect neurons through the PI3K/AKT signaling pathway and significantly decrease NF-κB, IL-6, IL-1ß, and TNF-α levels in the hippocampal and cortex tissues, which were reversed through the use of LY294002. Additionally, we discovered that AOF could significantly decrease the high expression of cytokines as well as the expression and translocation of NF-κB induced by LPS in PC12 cells. These results demonstrate the anti-neuroinflammatory effect of AOF in both cell and animal models of AD, thereby slowing down the process and development of the disease.
Sujet(s)
Dysfonctionnement cognitif , Lipopolysaccharides , Animaux , Dysfonctionnement cognitif/induit chimiquement , Lipopolysaccharides/toxicité , Souris , Facteur de transcription NF-kappa B/métabolisme , Phosphatidylinositol 3-kinases/métabolisme , Protéines proto-oncogènes c-akt/métabolisme , Rats , Transduction du signalRÉSUMÉ
Parkinson's disease (PD) is a progressive neurodegenerative disorder characterized by a disorder of both the motor and nonmotor systems due to a loss of dopaminergic (DA) neurons. Herein, we aimed to investigate the potential neuroprotective role of Schisandra chinensis (Sch) and to determine the mechanism by which Sch functions to ameliorate PD in a 6-hydroxydopamin (6-OHDA)-induced PD model. The open field test, sucrose preference test, and Y-maze test were utilized to evaluate the motor and nonmotor symptoms. We found that administration of Sch improved both disorders and DA neurodegeneration in 6-OHDA-induced mice. Additional data confirmed that Sch treatment significantly increased BDNF expression and decreased the activity of GSK-3ß in the striatum and hippocampus. Moreover, Sch was able to alleviate the abnormal levels of ROS and increase SOD by boosting Nrf2 expression. The nuclear translocation of NF-κB was inhibited by Sch, which subsequently led to a downregulation of proinflammatory cytokines. Sch effectively suppressed apoptosis by decreasing expressions of caspase 3, caspase 9, and p53 in the PD mouse model. Our findings demonstrate that Sch protects against DA neurodegeneration in 6-OHDA-induced PD mice by suppressing oxidative stress, neuroinflammation and apoptosis through the involvement of the BDNF/Nrf2/NF-κB signaling pathway.
Sujet(s)
Neurones dopaminergiques/physiologie , Médicaments issus de plantes chinoises/usage thérapeutique , Neuroprotecteurs/usage thérapeutique , Syndromes parkinsoniens/traitement médicamenteux , Syndromes parkinsoniens/physiopathologie , Schisandra , Animaux , Apoptose , Facteur neurotrophique dérivé du cerveau/métabolisme , Corps strié/métabolisme , Cytokines/métabolisme , Modèles animaux de maladie humaine , Dopamine/métabolisme , Hippocampe/métabolisme , Souris , Souris de lignée C57BL , Facteur-2 apparenté à NF-E2/métabolisme , Facteur de transcription NF-kappa B/métabolisme , Stress oxydatif , Oxidopamine , Syndromes parkinsoniens/induit chimiquement , Phytothérapie , Transduction du signalRÉSUMÉ
A new regeneration method of ion exchange resin named Adjacent Bed Electrically Regenerated Ion-exchange (ABERI) was proposed to eliminate the environmental impact of traditional chemical regeneration and improve the economy of replacing chemical regeneration with electrical regeneration. The desalting operation of ABERI was the same as the conventional mixed bed. When the resins were exhausted, anion and cation resins were separated and then packed in a dedicated regenerator adjacently. The resins were regenerated by the H+ and OH- ions produced from a pair of electrodes installed on both sides of the resin bed. By optimizing the regeneration time, current, and feed water flow rate, the energy consumption of ABERI was 0.38 kWh/m3 water; that is, 54% of that of another electrical regeneration technology, membrane-free electrodeionization (MFEDI). Compared with MFEDI, the quality and quantity of purified water produced after regeneration were improved. In ABERI, the average conductivity and the volume (times of bed volumes) of the purified water are 0.9 µS/cm and 109; that is, 75 and 133% of that of MFEDI, respectively. The preliminary economic analysis showed that ABERI offers the potential to regenerate ion exchange resin in an eco-friendly and cost-effective manner.
Sujet(s)
Polluants chimiques de l'eau , Purification de l'eau , Échange ionique , Résines échangeuses d'ions , Eau , Polluants chimiques de l'eau/analyseRÉSUMÉ
Herein, a carbon membrane and Au nanoparticles were combined to improve the efficiency of photoelectrocatalytic water splitting over a TiO2 nanotube arrays film (TiO2 NTAF). Two different ternary nanostructures were constructed by hydrothermal and photochemical deposition processes. One was carbon membrane bridged Au nanoparticles and TiO2 nanotube arrays (Au/C/TiO2 NTAF), while the other was Au nanoparticles sandwiched between carbon membrane and TiO2 nanotube arrays (C/Au/TiO2 NTAF). The two structures exhibited enhanced visible light harvesting ability, but they showed distinctly different photoelectric properties. The unique microstructure of C/Au/TiO2 NTAF resulted in a much higher reduction of the electron cloud density of Au nanoparticles as carrier recombination centers, which were responsible for its poor photoelectrochemical performance. However, a champion photocurrent of Au/C/TiO2 NTAF was observed (0.984 mA cm-2), indicating superior ability of the photoelectrocatalytic water splitting. The great enhancement was attributed to multiple carriers transport paths, which can efficiently utilize the sensitization of the carbon membrane and the surface plasmon resonance effect of the Au nanoparticles.
RÉSUMÉ
BACKGROUND: Tick-borne rickettsioses are considered important emerging zoonoses worldwide, but their etiological agents, rickettsiae, remain poorly characterized in northeastern China, where many human cases have been reported during the past several years. Here, we determined the characteristics of Rickettsia spp. infections in ticks in this area. METHODS: Ticks were collected by flagging vegetation from Jilin and Heilongjiang provinces of northeastern China followed by morphological identification. The presence of Rickettsia spp. in ticks was detected by PCR targeting the 23S-5S ribosomal RNA intergenic spacer, citrate synthase (gltA) gene, and 190-kDa outer membrane protein gene (ompA). The newly-generated sequences were subjected to phylogenetic analysis using the software MEGA 6.0. RESULTS: The overall infection rate of Rickettsia spp. was 6.12 %. Phylogenetic analyses based on the partial gltA and ompA genes demonstrated that rickettsiae detected in the ticks belong to four species, including "Candidatus Rickettsia tarasevichiae", Rickettsia heilongjiangensis, Rickettsia raoultii, and a potential new species isolate. The associated tick species were also identified, i.e. Dermacentor nuttalli and Dermacentor silvarum for R. raoultii, Haemaphysalis concinna and Haemaphysalis longicornis for R. heilongjiangensis, and Ixodes persulcatus for "Ca. R. tarasevichiae". All Rickettsia spp. showed significantly high infection rates in ticks from Heilongjiang when compared to Jilin Province. CONCLUSION: Rickettsia heilongjiangensis, R. raoultii and "Ca. R. tarasevichiae" are widely present in the associated ticks in northeastern China, but more prevalent in Heilongjiang Province. The data of this study increase the information on the distribution of Rickettsia spp. in northeastern China, which have important public health implications in consideration of their recent association with human diseases.
Sujet(s)
Rickettsia/génétique , Rickettsia/isolement et purification , Tiques/microbiologie , Animaux , Chine , Nymphe/microbiologie , PhylogenèseRÉSUMÉ
The rabies virus (RABV) glycoprotein (G) is responsible for inducing neutralizing antibodies against rabies virus. Development of recombinant vaccines using the G genes from attenuated strains rather than street viruses is a regular practice. In contrast to this scenario, we generated three human adenovirus type 5 recombinants using the G genes from the vaccine strains SRV9 and Flury-LEP, and the street RABV strain BD06 (nrAd5-SRV9-G, nrAd5-Flury-LEP-G, and nrAd5-BD06-G). These recombinants were non-replicative, but could grow up to ~10(8) TCID50/ml in helper HEK293AD cells. Expression of the G protein was verified by immunostaining, quantitative PCR and cytometry. Animal experiments revealed that immunization with nrAd5-BD06-G can induce a higher seroconversion rate, a higher neutralizing antibody level, and a longer survival time after rabies virus challenge in mice when compared with the other two recombinants. Moreover, the expression of granulocyte-macrophage colony-stimulating factor (GM-CSF) was significantly higher in mice immunized with nrAd5-BD06-G, which might also contribute to the increased protection. These results show that the use of street RABV G for non-replicative systems may be an alternative for developing effective recombinant rabies vaccines.