Your browser doesn't support javascript.
loading
Mostrar: 20 | 50 | 100
Resultados 1 - 20 de 680
Filtrar
1.
Comput Intell Neurosci ; 2021: 7388825, 2021.
Artigo em Inglês | MEDLINE | ID: mdl-34630552

RESUMO

In order to effectively optimize the machine online translation system and improve its translation efficiency and translation quality, this study uses the deep separable convolution neural network algorithm to construct a machine online translation model and evaluates the quality on the basis of pseudo data learning. In order to verify the performance of the model, the regression performance experiment of the model, the method performance experiment of generating pseudo data for specific tasks, the sorting task performance experiment of the model, and the machine translation quality comparison experiment are designed. RMSE and MAE were used to evaluate the regression task performance of the model. Spearman rank correlation coefficient and delta AVG value were used to evaluate the sorting task performance of the model. The experimental results show that the MAE and RMSE values of the model are decreased by 2.28% and 1.39%, respectively, compared with the baseline system under the same experimental conditions, and the Spearman and delta AVG values are increased by 132% and 100.7%, respectively, compared with the baseline system. The method of generating pseudo data for specific tasks needs less data and can make the translation system reach a better level faster. When the number of instances is more than 10, the quality score of the model output is higher than that of Google translation whose similarity is more than 0.8.


Assuntos
Algoritmos , Redes Neurais de Computação , Sistemas On-Line , Traduções
2.
Clin Pharmacol Ther ; 2021 Oct 08.
Artigo em Inglês | MEDLINE | ID: mdl-34625956

RESUMO

Bilirubin has antioxidant and anti-inflammatory properties in vitro and in animal studies and protects against inflammatory, cardiovascular, and other diseases in observational studies; therefore, bilirubin has potential as a therapeutic agent. However, observational studies could be confounded by many factors. We used a genetic (n=61,281) and clinical (n=234,670) approach to define the association between bilirubin and 19 conditions with a putative protective signal in observational studies. We also tested if individuals with genetically higher bilirubin levels underwent more diagnostic tests. We used a common variant in UGT1A1 (rs6742078) associated with an 26% increase in bilirubin levels in the genetic studies. Carriers of the variant had higher bilirubin levels (P= 2.2x10-16 ) but there was no significant association with any of the 19 conditions. In a phenome-wide association study (pheWAS) to seek undiscovered genetic associations, the only significant finding was increased risk of "jaundice - not of newborn". Carriers of the variant allele were more likely to undergo an abdominal ultrasound (OR=1.04 [1.00, 1.08], P=0.03). In contrast, clinically measured bilirubin levels were significantly associated with 15 of the 19 conditions (P< 0.003) and with 431 clinical diagnoses in the pheWAS (P<1x10-5 adjusted for sex, age, and follow-up). With additional adjustment for smoking and body mass index, 7 of 19 conditions and 260 pheWAS diagnoses remained significantly associated with bilirubin levels. In conclusion, bilirubin does not protect against inflammatory or other diseases using a genetic approach; the many putative beneficial associations reported clinically are likely due to confounding.

3.
Curr Microbiol ; 2021 Oct 20.
Artigo em Inglês | MEDLINE | ID: mdl-34668992

RESUMO

Grey mould caused by Botrytis cinerea leads to severe economic loss on commercial tomato production. Application of beneficial microorganism offers an eco-friendly alternative for mitigation of tomato fungal disease damage, considering negative influences of fungicides. In the present study, an antagonistic Trichoderma afroharzianum isolate TM24 was evaluated for its biocontrol potential on tomato grey mould. The isolate TM24 showed obviously antagonistic effect on B. cinerea mycelium growth and production of glucanase and chitinase. Leaf spraying with spore suspension of isolate TM24 showed a biocontrol efficiency of over 54% against tomato grey mould in greenhouse pot experiment. The activities of plant defense-related enzymes including polyphenol oxidase, phenylalanine ammonialyase, superoxide dismutase, and peroxidase were all increased to varying degrees in tomato leaves after isolate TM24 treatment. Transcriptome analysis showed that, a total of 1941, 1753 and 38 differentially expressed genes (DEGs) were obtained at 24, 48 and 72 hpi, respectively, in tomato leaves pretreated with T. afroharzianum TM24, and then challenged with B. cinerea inoculation. The DEGs were mainly enriched in MAPK signaling pathway and plant hormones signal transduction pathway. Multiple genes that regulated crucial nodes of defense-related pathways, like flavonoid, phenylpropanoid, jasmonic acid and ethylene metabolisms were also identified, which may have positive correlations with the biocontrol potential of isolate TM24 in tomato plants. These promising results provided valuable information on using T. afroharzianum TM24 as a beneficial biocontrol agent in tomato grey mould management.

4.
Front Immunol ; 12: 712351, 2021.
Artigo em Inglês | MEDLINE | ID: mdl-34504494

RESUMO

Hepatocellular carcinoma (HCC) is an aggressive liver tumor that occurs due to chronic liver disease, and it has a high mortality rate and limited treatment options. Immune checkpoint inhibitors have been successfully introduced and used in cancer therapy, among which inhibitors of programmed death ligand-1 (PD-L1) and its receptor programmed death-1 (PD-1) are commonly administered for HCC as combination therapy, including combined anti-angiogenic and immunotherapy combination therapy. We report a case of a primary massive HCC patient with portal hepatic vein tumor thrombus who had a good response to atezolizumab in combination with bevacizumab, following progression of disease on combined immunotherapy with pembrolizumab and lenvatinib. This case demonstrates for the first time that an HCC patient who is resistant to anti-PD-1 antibody immunotherapy can benefit from anti-PD-L1 antibody immunotherapy, providing a potentially promising strategy for the treatment of HCC.

5.
mBio ; : e0109721, 2021 Sep 07.
Artigo em Inglês | MEDLINE | ID: mdl-34488443

RESUMO

The Epstein-Barr virus (EBV) protein LMP1 serves as a paradigm that engages complicated ubiquitination-mediated mechanisms to activate multiple transcription factors. p62 is a ubiquitin sensor and a signal-transducing adaptor that has multiple functions in diverse contexts. However, the interaction between p62 and oncogenic viruses is poorly understood. We recently reported a crucial role for p62 in oncovirus-mediated oxidative stress by acting as a selective autophagy receptor. In this following pursuit, we further discovered that p62 is upregulated in EBV type 3 compared to type 1 latency, with a significant contribution from NF-κB and AP1 activities downstream of LMP1 signaling. In turn, p62 participates in LMP1 signal transduction through its interaction with TRAF6, promoting TRAF6 ubiquitination and activation. As expected, short hairpin RNA (shRNA)-mediated knockdown (KD) of p62 transcripts reduces LMP1-TRAF6 interaction and TRAF6 ubiquitination, as well as p65 nuclear translocation, which was assessed by Amnis imaging flow cytometry. Strikingly, LMP1-stimulated NF-κB, AP1, and Akt activities are all markedly reduced in p62-/- mouse embryo fibroblasts (MEFs) and in EBV-negative Burkitt's lymphoma (BL) cell lines with CRISPR-mediated knockout (KO) of the p62-encoding gene. However, EBV-positive BL cell lines (type 3 latency) with CRISPR-mediated KO of the p62-encoding gene failed to survive. In consequence, shRNA-mediated p62 KD impairs the ability of LMP1 to regulate its target gene expression, promotes etoposide-induced apoptosis, and reduces the proliferation of lymphoblastic cell lines (LCLs). These important findings have revealed a previously unrecognized novel role for p62 in EBV latency and oncogenesis, which advances our understanding of the mechanism underlying virus-mediated oncogenesis. IMPORTANCE As a ubiquitin sensor and a signal-transducing adaptor, p62 is crucial for NF-κB activation, which involves the ubiquitin machinery, in diverse contexts. However, whether p62 is required for EBV LMP1 activation of NF-κB is an open question. In this study, we provide evidence that p62 is upregulated in EBV type 3 latency and, in turn, p62 mediates LMP1 signal transduction to NF-κB, AP1, and Akt by promoting TRAF6 ubiquitination and activation. In consequence, p62 deficiency negatively regulates LMP1-mediated gene expression, promotes etoposide-induced apoptosis, and reduces the proliferation of LCLs. These important findings identified p62 as a novel signaling component of the key viral oncogenic signaling pathway.

6.
Pain Ther ; 2021 Sep 04.
Artigo em Inglês | MEDLINE | ID: mdl-34482533

RESUMO

INTRODUCTION: Pain in ankylosing spondylitis is currently considered an inflammatory pain (IP). However, it was found that some patients still had the sensation of pain even without inflammation. Our study was to investigate the prevalence and characteristics of neuropathic pain (NeP) in Chinese Han ankylosing spondylitis (AS) patients. METHODS: The study consisted of three parts. Firstly, we assessed the prevalence and clinical data of NeP in 182 AS patients. Secondly, we evaluated pain improvement after etanercept therapy in 63 patients. Finally, serum neurotransmitters were measured for 20 AS patients and ten healthy controls (HC). RESULTS: Out of 182 AS patients, our study showed that 14 patients (7.70%) had likely NeP and 55 (30.21%) had uncertain NeP. There were significant differences among the three groups with respect to nocturnal pain (NP), peripheral pain (PP), total back pain (TBP), BASDAI, ASDAS-CRP, HAD-A, HAD-D, and BASDAI-fatigue except fort CRP concentrations. Principal component analysis (PCA) of AS pain revealed that the weight of NeP was greater than PP in the first principal component (0.703 vs. 0.639). Structural equation modeling (SEM) revealed that NeP altered disease activity (ß = 0.62, P < 0.001), which influenced psychological status (ß = 0.42, P < 0.001). Of 63 patients who used etanercept for 3 months, significant improvement was found in NP, TBP, and PP (all P < 0.0001) but not in PDQ (10.60 ± 6.85 vs. 9.98 ± 6.40, P = 0.0671). Serum norepinephrine concentrations in patients with PDQ > 19 were higher than those in patients with PDQ ≤ 19 and HC. CONCLUSIONS: We conclude that NeP contributes to pain in AS patients.

7.
J Hazard Mater ; 423(Pt B): 127159, 2021 Sep 12.
Artigo em Inglês | MEDLINE | ID: mdl-34537633

RESUMO

Melatonin, a regulatory molecule, performs pleiotropic functions in plants, including aluminum (Al) stress mitigation. Here, we conducted transcriptomic and physiological analyses to identify metabolic processes associated with the alleviated Al-induced growth inhibition of the melatonin-treated (MT) maize (Zea mays L.) seedlings. Melatonin decreased Al concentration in maize roots and leaves under Al stress. Al stress reduced the total dry weight (DW) by 41.2% after 7 days of treatment. By contrast, the total DW was decreased by only 19.4% in MT plants. According to RNA-Seq, enzyme activity, and metabolite content data, MT plants exhibited a higher level of relatively stable carbon and nitrogen metabolism than non-treated (NT) plants. Under Al stress, MT plants showed higher photosynthetic rate and sucrose content by 29.9% and 20.5% than NT plants, respectively. Similarly, the nitrate reductase activity and protein content of MT plants were 34.0% and 15.0% higher than those of NT plants, respectively. Furthermore, exogenous supply of melatonin mitigated Al-induced oxidative stress. Overall, our results suggest that melatonin alleviates aluminum-induced growth inhibition through modulating carbon and nitrogen metabolism, and reestablishing redox homeostasis in maize. Graphical Abstarct.

8.
Hum Gene Ther ; 2021 Sep 24.
Artigo em Inglês | MEDLINE | ID: mdl-34555961

RESUMO

Hemophilia A (HA) is a monogenic disease characterized by plasma clotting factor 8 (F8) deficiency due to F8 mutation. We have been attempting to cure HA permanently using a CRISPR-Cas9 gene-editing strategy. Here, we induced targeted integration of BDDF8 (B-domain-deleted F8) gene into the albumin locus of HA mice by hydrodynamic tail vein injection of editing plasmid vectors. One week after treatment, a high F8 activity ranging from 70% to 280% of normal serum levels was observed in all treated HA mice but dropped to background levels 3-5 weeks later. We found that the humoral immune reaction targeting F8 is the predominant cause of the decreased F8 activity. We hypothesized that hydrodynamic injection-induced liver damage triggered the release of large quantities of inflammatory cytokines. However, co-injection of plasmids expressing a dozen immunomodulatory factors failed to curtail the immune reaction and stabilize F8 activity. The spCas9 plasmid carrying a miR-142-3p target sequence alleviated the cellular immune response but was unable to deliver therapeutic efficacy. Strikingly, immunosuppressant cyclo-phosphamide virtually abolished the immune response, leading to a year-long stable F8 level. Our findings should have important implications in developing therapies in mouse models using the hydrodynamic gene delivery approach, highlighting the ne-cessity of modulating the innate immune response triggered by liver damage.

10.
Mech Ageing Dev ; 199: 111571, 2021 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-34517021

RESUMO

Age is a major risk factor for developing metabolic diseases such as obesity and diabetes. There is an unprecedented rise in obesity and type 2 diabetes in recent decades. A convincing majority of brain-gut peptides are associated with a higher risk to develop metabolic disorders, and may contribute to the pathophysiology of age-related metabolic diseases. Accumulating basic studies revealed an intriguing role of kisspeptin and galanin involved in the amelioration of insulin resistance in different ways. In patients suffered from obesity and diabetes a significant, sex-related changes in the plasma kisspeptin and galanin levels occurred. Kisspeptin is anorexigenic to prevent obesity, its level is negatively correlative with obesity and insulin resistance. While galanin is appetitive to stimulate food intake and body weight, its level is positively correlative with obesity, HOMA-IR and glucose/triglyceride concentration. In turn, kisspeptin and galanin also distinctly increase glucose uptake and utilization as well as energy expenditure. This article reviews recent evidence dealing with the role of kisspeptin and galanin in the pathophysiology of age-related metabolic diseases. It should be therefore taken into account that the targeted modulation of those peptidergic signaling may be potentially helpful in the future treatment of age-related metabolic diseases.

12.
Plant Physiol Biochem ; 167: 958-969, 2021 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-34571389

RESUMO

Melatonin is a pleiotropic regulatory molecule in plants and is involved in regulating plant tolerance to drought stress. Here, we conducted transcriptomic and physiological analyses to identify metabolic processes associated with the enhanced tolerance of the melatonin-treated maize (Zea mays L.) seedlings to water deficit. Maize seedlings were foliar sprayed with either 50 µM melatonin or water and exposed to drought stress for 12 d in growth chambers. Drought stress significantly suppressed seedling growth, and melatonin application partially alleviated this growth inhibition. RNA-Seq analysis revealed that genes whose expression was significantly altered by melatonin were mainly related to carbon (C) and nitrogen (N) metabolism. Analysis of transcriptomics, enzyme activity, and metabolite content data, melatonin-treated plants exhibited a higher level of relatively stable C and N metabolism than untreated plants; this phenotype of melatonin-treated plants was associated with their higher photosynthesis, sucrose biosynthesis, N assimilation, and protein biosynthesis capacities under drought stress. Overall, our results suggest that melatonin enhances drought stress tolerance in maize through coordinated regulation of C and N metabolism.


Assuntos
Secas , Melatonina , Carbono/metabolismo , Regulação da Expressão Gênica de Plantas , Melatonina/farmacologia , Nitrogênio/metabolismo , Plântula/metabolismo , Estresse Fisiológico , Zea mays/metabolismo
13.
J Neuroophthalmol ; 2021 Aug 17.
Artigo em Inglês | MEDLINE | ID: mdl-34417770

RESUMO

BACKGROUND: Current research has not provided a consistent and qualitative description of MRI features in Leber hereditary optic neuropathy (LHON). Our study aims to investigate the MRI findings in the pregeniculate visual pathway and discuss their clinical significance in LHON. METHODS: Orbital MRI was retrospectively analyzed for 53 patients with LHON (101 afflicted eyes) admitted to the Department of Neurology, Beijing Tongren Hospital, Capital Medical University, from 2014 to 2019. We described the imaging abnormalities and discussed their associations with the time interval from the onset of vision loss to the performance of MRI (TIOVP), prevalence of m.11778G>A, and best-corrected visual acuity (BCVA). RESULTS: T2 hyperintense signal (HS) was determined in 82 afflicted eyes, with 34 located in the intraorbital segment (IO) of the optic nerve (ON), 26 in the IO concurrent with intracanalicular segment (ICn), 14 in the IO and ICn concurrent with intracranial segment (ICr) of the ON, 4 in the IO, ICn, and ICr concurrent with optic chiasm (OCh), and 4 in the IO, ICn, ICr, and OCh concurrent with optic tract (OTr). MRI was normal in the remaining 19 afflicted eyes. Among the 6 groups, no statistical differences were found in the TIOVP (P = 0.071), prevalence of m.11778G>A (P = 0.234), and BCVA (P = 0.076). As T2 HS extended, the BCVA gradually decreased. Nineteen of the 54 afflicted eyes revealed contrast enhancement, with the TIOVP ranging from 0.25 to 6 months. CONCLUSIONS: T2 HS was common in the pregeniculate visual pathway in LHON. It was not correlated with the prevalence of m.11778G>A and did not benefit in disease staging. As it extended, the BCVA gradually decreased. Contrast enhancement was relatively rare, always occurring in the subacute stage.

14.
J Agric Food Chem ; 69(31): 8634-8648, 2021 Aug 11.
Artigo em Inglês | MEDLINE | ID: mdl-34339211

RESUMO

The monocot lineage-specific miR528 was previously established as a multistress regulator. However, it remains largely unclear how miR528 participates in response to salinity stress in rice. Here, we show that miR528 positively regulates rice salt tolerance by down-regulating a gene encoding l-ascorbate oxidase (AO), thereby bolstering up the AO-mediated abscisic acid (ABA) synthesis and ROS scavenging. Overexpression of miR528 caused a substantial increase in ascorbic acid (AsA) and ABA contents but a significant reduction in ROS accumulation, resulting in the enhanced salt tolerance of rice plants. Conversely, knockdown of miR528 or overexpression of AO stimulated the expression of the AO gene, hence lowering the level of AsA, a critical antioxidant that promotes the ABA content but reduces the ROS level, and then compromising rice tolerance to salinity. Together, the findings reveal a novel mechanism of the miR528-AO module-mediated salt tolerance by modulating the processes of AsA and ABA metabolism as well as ROS detoxification, which adds a new regulatory role to the miR528-AO stress defense pathway in rice.


Assuntos
Ácido Abscísico/metabolismo , Ácido Ascórbico/metabolismo , MicroRNAs/genética , Oryza , Tolerância ao Sal , Ascorbato Oxidase , Regulação da Expressão Gênica de Plantas , Oryza/genética , Oryza/metabolismo , Proteínas de Plantas/genética , Proteínas de Plantas/metabolismo , Plantas Geneticamente Modificadas/genética , Plantas Geneticamente Modificadas/metabolismo , Espécies Reativas de Oxigênio/metabolismo , Tolerância ao Sal/genética , Estresse Fisiológico
15.
J Neuroinflammation ; 18(1): 176, 2021 Aug 10.
Artigo em Inglês | MEDLINE | ID: mdl-34376208

RESUMO

BACKGROUND: Cathepsin H (CatH) is a lysosomal cysteine protease with a unique aminopeptidase activity. Its expression level is increased in activated immune cells including dendritic cells, macrophages, and microglia. We have previously reported that CatH deficiency impairs toll-like receptor 3 (TLR3)-mediated activation of interferon regulatory factor 3 (IRF3), and the subsequent secretion of interferon (IFN)-ß from dendritic cells. Furthermore, there is increasing evidence that IFN-ß secreted from microglia/macrophages has neuroprotective effects. These observations prompted further investigation into the effects of CatH deficiency on neuropathological changes. METHODS: In this study, neuropathological changes were examined using histochemical staining (both hematoxylin-eosin (H&E) and Nissl) of the hippocampus of wild-type (WT) and CatH-deficient (CatH-/-) mice after hypoxia-ischemia (HI). The density and the localization of CatH and TLR3 were examined by immunofluorescent staining. CatH processing in microglia was assayed by pulse-chase experiments, while immunoblotting was used to examine TLR3 expression and IRF3 activation in microglia/macrophages in the presence of poly(I:C). Microglial cell death was examined by fluorescence-activated cell sorting (FACS), and primary astrocyte proliferation in the presence of IFN-ß was examined using scratch wound assay. RESULTS: WT mice displayed severe atrophy in association with neuronal death and moderate astrogliosis in the hippocampus following neonatal HI. Somewhat surprisingly, CatH-/- mice showed marked neuronal death without severe atrophy in the hippocampus following HI. Furthermore, there was notable microglia/macrophages cell death and strong astrogliosis in the hippocampus. The TLR3 and phosphorylated IRF3 expression level in the hippocampus or splenocytes (mainly splenic macrophages); from CatH-/- mice was lower than in WT mice. In vitro experiments demonstrated that recombinant IFN-ß suppressed HI-induced microglial cell death and astrocyte proliferation. CONCLUSION: These observations suggest that CatH plays a critical role in the proteolytic maturation and stabilization of TLR3, which is necessary for IFN-ß production. Therefore, impaired TLR3/IFN-ß signaling resulting from CatH deficiency may induce microglial cell death after activation and astrogliosis/glial scar formation in the hippocampus following HI injury, leading to suppression of hippocampal atrophy.

16.
Transl Psychiatry ; 11(1): 437, 2021 08 21.
Artigo em Inglês | MEDLINE | ID: mdl-34420033

RESUMO

Magnetic seizure therapy (MST) has established efficacy in the treatment of depression and a growing evidence base in the treatment of depression. We conducted the first systematic review and meta-analysis of the efficacy of MST in anti-depressive treatment and its impact on cognitive function (INPLASY registration number: INPLASY202170061). We searched for controlled trials published in English between 1 January 2001 to 31 December 2020 in PubMed, EMBASE, Cochrane Library, Web of Science, and PsycINFO databases. The evaluation process strictly followed the Cochrane bias risk assessment tool into the literature, and Meta-analysis was performed according to the Cochrane System Reviewer's Manual. Data from a total of 285 patients from 10 studies were retained in the quantitative synthesis. The results showed no significant difference between MST and ECT in the antidepressant effect (SDM -0.13 [-0.78;0.52]). Compared with ECT, MST showed shorter recovery time (MD -5.67 [-9.75; -1.60]) and reorientation time (MD -14.67 [-27.96; -1.41]); and MST showed less cognitive impairment on the immediate recall of words (SDM 0.80 [0.35;1.25]), delayed recall of words (SDM 0.99 [0.01;0.74]), visual-spatial immediate memory (SDM 0.51 [0.20;0.83]), visual-spatial delayed memory (SDM 0.57 [0.11;1.02]), and the verbal fluency (SDM 0.51 [0.20;0.83]). Our evidence-based study is the first meta-analysis on the efficacy of MST in anti-depressive treatment and its effect on cognitive function. It showed that the curative effect of MST in anti-depressive treatment is equivalent to that of ECT. Besides, depressive patients with MST benefit more from cognitive function compared with ECT.


Assuntos
Transtorno Depressivo Maior , Eletroconvulsoterapia , Cognição , Transtorno Depressivo Maior/terapia , Humanos , Memória , Convulsões
17.
Biomed Pharmacother ; 142: 111995, 2021 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-34435595

RESUMO

The clinical application of cisplatin was mainly limited by severe nephrotoxicity. Danshensu was the main pharmacological active diterpenoids which extracted from the roots of Salvia milthiorriza Bunge. This study is aimed to investigate the protective effects and potential mechanisms of Danshensu against cisplatin-induced nephrotoxicity. After fasting for 12 h, all mice groups except the control group were administered a single intraperitoneal injection of 25 mg/kg cisplatin. 1 h later, cisplatin (25 mg/kg) + Danshensu (15 mg/kg, 30 mg/kg, 60 mg/kg) groups were treated with corresponding doses of Danshensu once a day for 7 consecutive days. Blood urea nitrogen (BUN), creatinine, reactive oxygen species (ROS), superoxide dismutase (SOD), Glutathione peroxidase (GPx), Catalase (CAT) and malondialdehyde (MDA) were assayed in this study. The expression of inflammatory cytokines TNF-α, IL-6 and IL-1ß were examined by ELISA. The results showed that Danshensu could improve kidney damage, attenuate serum BUN, creatinine, cytokines and oxidative stress markers. Further studies showed that Danshensu can induce Nrf2/HO-1 activation and inhibition of NF-κB pathway. In conclusion, Danshensu exerts the protective effects on cisplatin-induced nephrotoxicity, which may be related to the activation of Nrf2/HO-1 and inhibition of NF-ĸB pathway.

18.
Neuroscience ; 473: 119-129, 2021 10 01.
Artigo em Inglês | MEDLINE | ID: mdl-34455011

RESUMO

Major depressive disorder (MDD) is one of the most common psychiatric disorders. However, the effective drugs for MDD have not yet been developed. WS6 is originally designed with a similar structure as Resveratrol and Pterostilbene. The present study aims to investigate the neuroprotective and ameliorating effects of WS6 treatment in a rat model of chronic unpredictable mild stress (CUMS) induced depression. The results show that CUMS is effective in producing depressive-like behavior in rats as indicated by decreased responses in the locomotor activity, sucrose preference test and increased immobility time. However, WS6 treatment significantly ameliorated these behavioral alterations associated with CUMS-induced depression. Moreover, the reduction in neurogenesis, GABAergic neurons, dendrite complexity, spine density and synaptic plasticity-associate protein 95 (PSD95) by CUMS can be reversed by treatment with WS6. Taken together, this study highlights the neuroprotective and antidepressant-like effects of WS6 against CUMS-induced depression, and suggest a possible mechanism for this protection via changes in neurogenesis within the hippocampus. These finding reveal the therapeutic protection of WS6 for use in clinical trials in the treatment of neuronal deterioration in MDD.


Assuntos
Transtorno Depressivo Maior , Animais , Antidepressivos/farmacologia , Antidepressivos/uso terapêutico , Depressão/tratamento farmacológico , Depressão/etiologia , Transtorno Depressivo Maior/tratamento farmacológico , Modelos Animais de Doenças , Hipocampo , Neurogênese , Ratos , Estresse Psicológico/complicações , Estresse Psicológico/tratamento farmacológico
19.
Mol Med Rep ; 24(4)2021 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-34328202

RESUMO

A number of drugs and other triggers can cause acute liver injury (ALI) in clinical practice. Therefore, identifying a safe drug for the prevention of liver injury is important. The aim of the present study was to investigate the potential preventive effect and regulatory mechanism of urantide on carbon tetrachloride (CCl4)­induced ALI by investigating the expression of components of the MAPK signalling pathway and the urotensin II (UII)/urotensin receptor (UT) system. Liver oedema and severe fatty degeneration of the cytoplasm were observed in ALI model rats, and the serum alanine aminotransferase (ALT) and aspartate aminotransferase (AST) levels were found to be significantly increased. Compared with those in the ALI model group, ALT and AST levels and the liver index did not significantly increase in each group given the preventive administration of urantide, and the liver tissue morphology was correspondingly protected. Moreover, the gene and protein expression levels of UII, G protein­coupled receptor (GPR14) and the oxidative stress­sensitive cytokines, α­smooth muscle actin and osteopontin were decreased, indicating that the protein translation process was effectively maintained. However, the expression levels of MAPK signalling pathway­related proteins and genes were decreased. It was found that urantide could effectively block the MAPK signalling pathway by antagonizing the UII/UT system, thus protecting the livers of ALI model rats. Therefore, it was suggested that ALI may be associated with the MAPK signalling pathway, and effective inhibition of the MAPK signalling pathway may be critical in protecting the liver.


Assuntos
Doença Hepática Induzida por Substâncias e Drogas/metabolismo , Doença Hepática Induzida por Substâncias e Drogas/prevenção & controle , Sistema de Sinalização das MAP Quinases/efeitos dos fármacos , Fragmentos de Peptídeos/farmacologia , Urotensinas/farmacologia , Actinas/genética , Actinas/metabolismo , Animais , Tetracloreto de Carbono/toxicidade , Modelos Animais de Doenças , MAP Quinases Reguladas por Sinal Extracelular/genética , MAP Quinases Reguladas por Sinal Extracelular/metabolismo , MAP Quinase Quinase 4/genética , MAP Quinase Quinase 4/metabolismo , Masculino , Osteopontina/genética , Osteopontina/metabolismo , Fragmentos de Peptídeos/uso terapêutico , Ratos Sprague-Dawley , Receptores Acoplados a Proteínas G/genética , Receptores Acoplados a Proteínas G/metabolismo , Urotensinas/uso terapêutico , Proteínas Quinases p38 Ativadas por Mitógeno/genética , Proteínas Quinases p38 Ativadas por Mitógeno/metabolismo
20.
Br J Nutr ; : 1-13, 2021 Jul 29.
Artigo em Inglês | MEDLINE | ID: mdl-34321122

RESUMO

The present study evaluated effects of dietary supplementation with tryptophan (Trp) on muscle growth, protein synthesis and antioxidant capacity in hybrid catfish Pelteobagrus vachelli♀ × Leiocassis longirostris♂. Fish were fed six different diets containing 2·6 (control), 3·1, 3·7, 4·2, 4·7 and 5·6 g Trp/kg diet for 56 d, respectively. Results showed that dietary Trp significantly (1) improved muscle protein content, fibre density and frequency of fibre diameter; (2) up-regulated the mRNA levels of PCNA, myf5, MyoD1, MyoG, MRF4, IGF-I, IGF-II, IGF-IR, PIK3Ca, TOR, 4EBP1 and S6K1; (3) increased phosphorylation levels of AKT, TOR and S6K1; (4) decreased contents of MDA and PC, and increased activities of CAT, GST, GR, ASA and AHR; (5) up-regulated mRNA levels of CuZnSOD, CAT, GST, GPx, GCLC and Nrf2, and decreased Keap1 mRNA level; (6) increased nuclear Nrf2 protein level and the intranuclear antioxidant response element-binding ability, and reduced Keap1 protein level. These results indicated that dietary Trp improved muscle growth, protein synthesis as well as antioxidant capacity, which might be partly related to myogenic regulatory factors, IGF/PIK3Ca/AKT/TOR and Keap1/Nrf2 signalling pathways. Finally, based on the quadratic regression analysis of muscle protein and MDA contents, the optimal Trp requirements of hybrid catfish (21·82-39·64 g) were estimated to be 3·94 and 3·93 g Trp/kg diet (9·57 and 9·54 g/kg of dietary protein), respectively.

SELEÇÃO DE REFERÊNCIAS
DETALHE DA PESQUISA
...