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1.
J Hazard Mater ; 421: 126707, 2022 01 05.
Artigo em Inglês | MEDLINE | ID: mdl-34315018

RESUMO

Triclosan (TCS) is an antimicrobial ingredient that has been widely incorporated in consumer products. TCS can cause hepatic damage by disturbing lipid metabolism, which is often accompanied with gut microbiota dysbiosis. However, the effects of gut microbiota on the TCS-induced liver injury are still unknown. Therefore, we constructed a mouse model based on five-week-old male C57BL/6 mice to investigate the effects of dietary TCS exposure (40 ppm) on liver injury. We found that TCS treatment for 4 weeks dramatically disturbed gut microbiota homeostasis, resulting in overproduction of lipopolysaccharides (LPS) and deficiency of secondary bile acids such as deoxycholic acid (DCA) and lithocholic acid (LCA). In addition, TCS considerably increased intestinal permeability by reducing mucus excretion and expression of tight junction proteins (ZO-1, occludin and claudin 4), which facilitated translocation of LPS. The LPS accumulation in blood contributed to liver injury by triggering the inflammatory response via TLR4 pathway. In summary, this study provides novel insights into the underlying mechanisms of TCS-associated liver injury induced by gut microbiota via the gut-liver axis, and contributes to better interpretation of the health impact of the environmentally emerging contaminant TCS.


Assuntos
Doença Hepática Crônica Induzida por Substâncias e Drogas , Microbioma Gastrointestinal , Triclosan , Animais , Fígado , Masculino , Camundongos , Camundongos Endogâmicos C57BL , Triclosan/toxicidade
2.
Behav Brain Res ; 417: 113630, 2022 01 24.
Artigo em Inglês | MEDLINE | ID: mdl-34656691

RESUMO

Social isolation gained discussion momentum due to the COVID-19 pandemic. Whereas many studies address the effects of long-term social isolation in post-weaning and adolescence and for periods ranging from 4 to 12 weeks, little is known about the repercussions of adult long-term social isolation in middle age. Thus, our aim was to investigate how long-term social isolation can influence metabolic, behavioural, and central nervous system-related areas in middle-aged mice. Adult male C57Bl/6 mice (4 months-old) were randomly divided into Social (2 cages, n = 5/cage) and Isolated (10 cages, n = 1/cage) housing groups, totalizing 30 weeks of social isolation, which ended concomitantly with the onset of middle age of mice. At the end of the trial, metabolic parameters, short-term memory, anxiety-like behaviour, and physical activity were assessed. Immunohistochemistry in the hippocampus (ΔFosB, BDNF, and 8OHDG) and hypothalamus (ΔFosB) was also performed. The Isolated group showed impaired memory along with a decrease in hippocampal ΔFosB at dentate gyrus and in BDNF at CA3. Food intake was also affected, but the direction depended on how it was measured in the Social group (individually or in the group) with no alteration in ΔFosB at the hypothalamus. Physical activity parameters increased with chronic isolation, but in the light cycle (inactive phase), with some evidence of anxiety-like behaviour. Future studies should better explore the timepoint at which the alterations found begin. In conclusion, long-term social isolation in adult mice contributes to alterations in feeding, physical activity pattern, and anxiety-like behaviour. Moreover, short-term memory deficit was associated with lower levels of hippocampal ΔFosB and BDNF in middle age.


Assuntos
Ansiedade/etiologia , COVID-19 , Comportamento Alimentar , Hipocampo/metabolismo , Locomoção , Transtornos da Memória/etiologia , Isolamento Social , Fatores Etários , Animais , Comportamento Animal/fisiologia , Fator Neurotrófico Derivado do Encéfalo , COVID-19/prevenção & controle , Modelos Animais de Doenças , Comportamento Alimentar/fisiologia , Abrigo para Animais , Hipotálamo/metabolismo , Locomoção/fisiologia , Masculino , Camundongos , Camundongos Endogâmicos C57BL , Proteínas Proto-Oncogênicas c-fos/metabolismo
3.
J Ethnopharmacol ; 283: 114701, 2022 Jan 30.
Artigo em Inglês | MEDLINE | ID: mdl-34606948

RESUMO

ETHNOPHARMACOLOGICAL RELEVANCE: Xuanfei Baidu Decoction (XFBD), one of the "three medicines and three prescriptions" for the clinically effective treatment of COVID-19 in China, plays an important role in the treatment of mild and/or common patients with dampness-toxin obstructing lung syndrome. AIM OF THE STUDY: The present work aims to elucidate the protective effects and the possible mechanism of XFBD against the acute inflammation and pulmonary fibrosis. METHODS: We use TGF-ß1 induced fibroblast activation model and LPS/IL-4 induced macrophage inflammation model as in vitro cell models. The mice model of lung fibrosis was induced by BLM via endotracheal drip, and then XFBD (4.6 g/kg, 9.2 g/kg) were administered orally respectively. The efficacy and molecular mechanisms in the presence or absence of XFBD were investigated. RESULTS: The results proved that XFBD can effectively inhibit fibroblast collagen deposition, down-regulate the level of α-SMA and inhibit the migration of fibroblasts. IL-4 induced macrophage polarization was also inhibited and the secretions of the inflammatory factors including IL6, iNOS were down-regulated. In vivo experiments, the results proved that XFBD improved the weight loss and survival rate of the mice. The XFBD high-dose administration group had a significant effect in inhibiting collagen deposition and the expression of α-SMA in the lungs of mice. XFBD can reduce bleomycin-induced pulmonary fibrosis by inhibiting IL-6/STAT3 activation and related macrophage infiltration. CONCLUSIONS: Xuanfei Baidu Decoction protects against macrophages induced inflammation and pulmonary fibrosis via inhibiting IL-6/STAT3 signaling pathway.


Assuntos
COVID-19/tratamento farmacológico , Medicamentos de Ervas Chinesas , Inflamação/tratamento farmacológico , Macrófagos/efeitos dos fármacos , SARS-CoV-2 , Transdução de Sinais/efeitos dos fármacos , Animais , Sobrevivência Celular/efeitos dos fármacos , Medicamentos de Ervas Chinesas/farmacologia , Medicamentos de Ervas Chinesas/uso terapêutico , Fibroblastos/efeitos dos fármacos , Regulação da Expressão Gênica/efeitos dos fármacos , Redes Reguladoras de Genes , Humanos , Interleucina-6/antagonistas & inibidores , Interleucina-6/genética , Interleucina-6/metabolismo , Masculino , Camundongos , Camundongos Endogâmicos C57BL , Células NIH 3T3 , Fitoterapia , Fibrose Pulmonar/patologia , Fibrose Pulmonar/prevenção & controle , Células RAW 264.7 , Fator de Transcrição STAT3/antagonistas & inibidores , Fator de Transcrição STAT3/genética , Fator de Transcrição STAT3/metabolismo
4.
J Sci Food Agric ; 102(1): 434-444, 2022 Jan 15.
Artigo em Inglês | MEDLINE | ID: mdl-34143895

RESUMO

BACKGROUND: The incidence of inflammatory bowel disease (IBD) continues to increase worldwide. Multiple factors, including diet, loss of the intestinal barrier function, and imbalance of the immune system can cause IBD. A balanced diet is important for maintaining a healthy bowel and preventing IBD from occurring. The effects of probiotic Lactobacillus gasseri-fermented Maillard reaction products (MRPs) prepared by reacting whey protein with galactose on anti-inflammation and intestinal homeostasis were investigated in this study, which compared MPRs and probiotics separately. RESULTS: In an animal colitis model induced by 2% dextran sulfate sodium (DSS), FWG administration alleviated colon length loss and maintained intestinal immune system homeostasis as reflected by down-regulated interleukin (IL)-6, IL-10, tumor necrosis factor (TNF)-α output, and metallopeptidase-9, and epithelial barrier balance as reflected by up-regulated occludin, E-cadherin, and zonula occludens-1 production in the colon. Furthermore, the expression of splenic cytokines such as IL-6, TNF-α, and IL-10 was up-regulated in the FWG-treated mice in a comparable amount to the control group to ensure the balance of immune responses. CONCLUSION: This study showed that the use of FWG protects the intestines from colitis caused by DSS and maintains immune balance. FWG increased antioxidant enzyme activity, increased intestinal permeability, and regulated the balance of pro- and anti-inflammatory cytokines in the intestines and spleen. Continued intake of FWG can alleviate IBD symptoms through the preservation of mucosal immune responses, epithelial junction and homeostasis through the regulated splenic cytokines. © 2021 Society of Chemical Industry.


Assuntos
Colite/tratamento farmacológico , Produtos Finais de Glicação Avançada/administração & dosagem , Lactobacillus gasseri/metabolismo , Probióticos/administração & dosagem , Animais , Anti-Inflamatórios/administração & dosagem , Colite/induzido quimicamente , Colite/imunologia , Colite/fisiopatologia , Colo/efeitos dos fármacos , Colo/imunologia , Sulfato de Dextrana/efeitos adversos , Modelos Animais de Doenças , Galactose/metabolismo , Produtos Finais de Glicação Avançada/metabolismo , Homeostase/efeitos dos fármacos , Humanos , Interleucina-10/genética , Interleucina-10/imunologia , Interleucina-6/genética , Interleucina-6/imunologia , Mucosa Intestinal/efeitos dos fármacos , Mucosa Intestinal/imunologia , Masculino , Camundongos , Camundongos Endogâmicos C57BL , Junções Íntimas/genética , Junções Íntimas/imunologia , Fator de Necrose Tumoral alfa/genética , Fator de Necrose Tumoral alfa/imunologia , Proteínas do Soro do Leite/metabolismo
5.
Braz Dent J ; 32(3): 32-43, 2021.
Artigo em Inglês | MEDLINE | ID: mdl-34755788

RESUMO

The aim of this study was to evaluate the M1 and M2 macrophage modulation after stimuli with different materials used during endodontic treatment. In bone marrow-derived macrophage cell culture, from males C57BL/6 wild-type (WT) mice, gene expression analysis of markers to M1 and M2 macrophages was performed by qRT-PCR (Cxcl10, CxCL9, iNOS, Arg1, Chil3, Retnla and MRC1) and cytokine quantification by Luminex® (GM-CSF, IL-10, IL-6, IL-1ß and TNF-α) after exposure to the five endodontic sealers: AH Plus, Sealapex Xpress, Endosequence BC Sealer, BioRoot RCS and a calcium hydroxide-based paste. For normal values, ANOVA test was used, followed by Tukey post-test. For non-normal values, the Kruskall-Wallis test was used. BioRootTM RCS and EndoSequence BC SealerTM stimulated the highest expression of markers for M1 macrophages, while calcium hydroxide-based paste stimulated the lowest expression of these gene markers. For M2 protein markers, BioRootTM RCS presented the highest stimulation while calcium hydroxide-based paste also presented the lowest stimulation. It was concluded that all the evaluated filling materials increased the genetic expression of pro- and anti-inflammatory markers: TNF-α and IL-10 respectively. The others proinflammatory mediators showed differences against the filling materials. However, this process did not induce the inflammatory response polarization, resulting in a hybrid macrophage.


Assuntos
Materiais Restauradores do Canal Radicular , Animais , Resinas Epóxi , Macrófagos , Masculino , Teste de Materiais , Camundongos , Camundongos Endogâmicos C57BL , Fenótipo
6.
J Med Food ; 24(11): 1213-1221, 2021 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-34792393

RESUMO

Immunosuppression occurs in response to a variety of external antigens. However, various immune cells and cytokines can activate the immune system. In this study, it was found that fermented deer velvet (FD) and fermented Eleutherococcus senticosus (FE) extract (FDE) mixtures regulated the immunity of animals that underwent induced immunosuppression through forced swimming exercise (FSE). Seven mouse treatment groups were included in the experiment: normal controls, FSE controls, positive controls (FSE+red ginseng 300 mg/kg body weight), FD200 (FSE+FD 200 mg/kg body weight), FE200 (FSE+FE 200 mg/kg body weight), FDE50 (FSE+FDE 50 mg/kg body weight), and FDE200 (FSE+FDE 200 mg/kg body weight). Oral intake of experimental and control substances lasted for 2 weeks. Oral FDE intake increased cell counts for major histocompatibility complex (MHC) I, MHC II, CD4(+) T cells, and CD8(+) T cells compared with controls. Moreover, FDE increased Th1 (interleukin [IL]-2 and interferon gamma) cytokine proliferation, T cell proliferation, IL-12 and IL-15 production, and natural killer cell activity compared with controls. In addition, FDE inhibited Th2 cytokines (IL-4, IL-6, IL-10, and tumor necrosis factor alpha) and nitric oxide production, increased B cell proliferation and leukocyte count, and promoted immunoglobulin A and G serum levels compared with controls. Thus, the finding that FDE increased immune function in an immunosuppression model suggests that FDE has immunomodulatory capacity.


Assuntos
Cervos , Eleutherococcus , Animais , Citocinas/genética , Imunossupressão , Ativação Linfocitária , Camundongos , Camundongos Endogâmicos C57BL , Natação
7.
Zhonghua Xin Xue Guan Bing Za Zhi ; 49(11): 1130-1138, 2021 Nov 24.
Artigo em Chinês | MEDLINE | ID: mdl-34775724

RESUMO

Objective: To explore the differential expression of circRNAs and their potential impact on the pathophysiological process in cardiac hypertrophy. Methods: Six SPF C57BL/6J male mice, aged 8 to 10 weeks, were randomly divided into transverse aortic constriction (TAC) group (n=3) or sham operation(sham) group (n=3) according to random number table method. TAC mouse model was used to induce cardiac hypertrophy. Four weeks after surgery, high-throughput sequencing analysis was performed to detect differentially expressed circRNA in left myocardial tissues of mice between TAC group and sham group, and principal component analysis of circRNA was performed by R language software. Enrichment analysis was performed by GO and KEGG databases to predict the basic functions of differentially expressed circRNA-derived genes and their biological pathways. The differentially expressed circRNAs in the sequencing results were verified by real-time fluorescence quantitative polymerase chain reaction. Cytoscape software was used to construct circRNA-microRNA (miRNA) network maps to predict their interactions by combining differentially expressed circRNA and TargetScan predicted miRNA sites. Results: Principal component analysis was performed on 4 580 circRNAs detected from 6 samples of mice in TAC group and sham group. The results of R language software indicated that the variance contribution rate of the first 3 principal components, namely the first, second and third principal components, was 91.01%, 3.19% and 2.01%, respectively, and the cumulative variance contribution rate of the 3 components was 96.21%. Among the differentially expressed circRNAs, 6 (19%) were up-regulated and 25 (81%) were down-regulated in the TAC group. GO analysis showed that differentially expressed circRNA was closely related to the occurrence and development of cardiac hypertrophy, and KEGG pathway analysis suggested that downregulated circRNA expression was involved in the regulation of actin cytoskeleton. Fifteen out of the 31 differentially expressed circRNAs were selected for real-time fluorescence quantitative polymerase chain reaction verification, and the results showed that 8 circRNAs were consistent with sequencing results. circRNA-miRNA co-expression network analysis results showed that chr11:65218529-65233184-interacts with mmu-miRNA-30e-3p and mmu-miRNA-30a-3p. Conclusions The differential expression of circRNA in hypertrophic myocardium mice is evidenced in TAC mouse model. circRNA may interact with the corresponding miRNA to influence the occurrence and development of cardiac hypertrophy through autophagy-related cellular hypertrophy pathway or apoptosis-related pathological phenotypes.


Assuntos
MicroRNAs , RNA Circular , Animais , Biologia Computacional , Hipertrofia , Masculino , Camundongos , Camundongos Endogâmicos C57BL , MicroRNAs/genética , Miocárdio
8.
ACS Chem Neurosci ; 12(22): 4249-4256, 2021 11 17.
Artigo em Inglês | MEDLINE | ID: mdl-34738783

RESUMO

Alzheimer's disease (AD), the most common neurodegenerative disease, has limited treatment options. As such, extensive studies have been conducted to identify novel therapeutic approaches. We previously reported that rhynchophylline (Rhy), a small molecule EphA4 inhibitor, rescues impaired hippocampal synaptic plasticity and cognitive dysfunctions in APP/PS1 mice, an AD transgenic mouse model. To assess whether Rhy can be developed as an alternative treatment for AD, it is important to examine its pharmacokinetics and effects on other disease-associated pathologies. Here, we show that Rhy ameliorates amyloid plaque burden and reduces inflammation in APP/PS1 mice. Transcriptome analysis revealed that Rhy regulates various molecular pathways in APP/PS1 mouse brains associated with amyloid metabolism and inflammation, specifically the ubiquitin proteasome system, angiogenesis, and microglial functional states. These results show that Rhy, which is blood-brain barrier permeable, is beneficial to amyloid pathology and regulates multiple molecular pathways.


Assuntos
Doença de Alzheimer , Doenças Neurodegenerativas , Doença de Alzheimer/tratamento farmacológico , Peptídeos beta-Amiloides , Precursor de Proteína beta-Amiloide/genética , Animais , Modelos Animais de Doenças , Inflamação/tratamento farmacológico , Camundongos , Camundongos Endogâmicos C57BL , Camundongos Transgênicos , Oxindóis , Placa Amiloide/tratamento farmacológico , Presenilina-1/genética
9.
ACS Chem Neurosci ; 12(22): 4319-4335, 2021 11 17.
Artigo em Inglês | MEDLINE | ID: mdl-34747594

RESUMO

Stress-induced dopaminergic (DAergic) neuronal death in the midbrain region is the primary cause of Parkinson's disease (PD). Following the discovery of l-dopa, multiple drugs have been developed to improve the lifestyle of PD patients; however, none have been suitable for clinical use due to their multiple side effects. Tinospora cordifolia has been used in traditional medicines to treat neurodegenerative diseases. Previously, we reported the neuroprotective role of Tc via inhibition of NF-κB-associated proinflammatory cytokines against MPTP-intoxicated Parkinsonian mice. In the present study, we investigated the neuroprotective molecular mechanism of Tc in a rotenone (ROT)-intoxicated mouse model, using a proteomics approach. Mice were pretreated with Tc extract by oral administration, followed by ROT intoxication. Behavioral tests were performed to check motor functions of mice. Protein was isolated, and label-free quantification (LFQ) was carried out to identify differentially expressed protein (DEP) in control vs PD and PD vs treatment groups. Results were validated by qRT-PCR with the expression of target genes correlating with the proteomics data. In this study, we report 800 DEPs in control vs PD and 133 in PD vs treatment groups. In silico tools demonstrate significant enrichment of biochemical and molecular pathways with DEPs, which are known to be important for PD progression including mitochondrial gene expression, PD pathways, TGF-ß signaling, and Alzheimer's disease. This study provides novel insights into the PD progression as well as new therapeutic targets. More importantly, it demonstrates that Tc can exert therapeutic effects by regulating multiple pathways, resulting in neuroprotection.


Assuntos
Fármacos Neuroprotetores , Tinospora , Animais , Modelos Animais de Doenças , Neurônios Dopaminérgicos , Humanos , Camundongos , Camundongos Endogâmicos C57BL , Fármacos Neuroprotetores/farmacologia , Proteômica
10.
Zhonghua Shao Shang Za Zhi ; 37(11): 1036-1047, 2021 Nov 20.
Artigo em Chinês | MEDLINE | ID: mdl-34794255

RESUMO

Objective: To prepare the modified hyaluronic acid viscous hydrogel loaded with sliver particles and to explore the roles and mechanism of the hydrogel in healing of full-thickness skin defect wounds with bacterial colonization in mice. Methods: The experimental research method was adopted. Dopamine modified hyaluronic acid (HA-DA) and phenylboric acid modified hyaluronic acid (HA-PBA) were prepared, and their characteristic peaks were detected by Fourier-transform infrared spectroscopy. Different mass of acrylamides was added to HA-DA and HA-PBA to prepare the viscous hydrogel with mass fraction of acrylamide in 10%, 15%, and 20%. The gelation of the viscous hydrogel with mass fraction of acrylamide in 20% was observed in the state of tilt and inversion at 37 ℃, and the storage modulus and loss modulus of the above 3 kinds of viscous hydrogels were detected by rotational rheometer. The sliver-loaded viscous hydrogel was prepared by adding nano silver ions to the viscous hydrogel with mass fraction of acrylamide in 20%. The concentration of silver ions released by sliver-loaded viscous hydrogel was measured by inductively coupled plasma mass spectrometer, and the cumulative release rate of silver ion was calculated (n=5). The mouse fibroblasts L929 were divided into phosphate buffered saline (PBS) group, viscous hydrogel group, and sliver-loaded viscous hydrogel group, which were dealt correspondingly, and the cell survival was detected by cell counting kit 8 method after 1, 2, and 3 d of culture (n=5). Twenty-four male C57BL/6 mice aged 6-8 weeks were selected, and forty-eight full-thickness skin defect wounds were inflicted and inoculated with the mixture of Escherichia coli and Staphylococcus aureus in the back of the mice, with two wounds in each mouse. The wounds were divided into normal saline group, viscous hydrogel group, and sliver-loaded viscous hydrogel group, which were dealt correspondingly, with 16 wounds in each group, and two wounds in each mouse were divided into different groups. On post injury day (PID) 3, 7, 10, and 14, the wound healing was observed and the wound healing rate was calculated. On PID 3, the colony forming units of Escherichia coli and Staphylococcus aureus in wounds were observed and counted. On PID 14, the epithelized epidermal thickness and the optical density of collagen fiber in wounds were observed and analyzed after hematoxylin eosin staining and Masson staining, respectively. On PID 3, 7, and 10, the expressions of tumor necrosis factor α (TNF-α), transforming growth factor ß1 (TGF-ß1), and vascular endothelial growth factor (VEGF) were detected by immunohistochemistry. The number of wounds in each index detecting at each time point was four. Data were statistically analyzed with analysis of variance for factorial design, one-way analysis of variance, and Bonferroni correction. Results: The characteristic peaks of HA-PBA were detected at the wave numbers of 1 369 and 1 425 cm-1, indicating that phenylboric acid had been successfully grafted on hyaluronic acid, and the characteristic peaks of HA-DA were detected at the wave numbers of 1 516 and 1 431 cm-1, indicating that dopamine had been successfully grafted on hyaluronic acid. The viscous hydrogel with mass fraction of acrylamide in 20% maintained the stable and no-flow condition of gelation in the state of tilt and inversion at 37 ℃. The storage modulus and loss modulus of the viscous hydrogel increased with the increase of acrylamide content, the storage modulus and loss modulus of the 3 kinds of viscous hydrogels had no obvious changes with the increase of the oscillation frequency or time, and the storage modulus of the 3 kinds of acrylamide hydrogels were greater than the loss modulus. The release of silver ion in the sliver-loaded viscous hydrogel lasted for 7 days, and the cumulative release rate of silver ion was up to 65%. After 1, 2, and 3 d of culture, the cell survival rates in sliver-loaded viscous hydrogel group were significantly lower than those in PBS group and viscous hydrogel group (P<0.05 or P<0.01), while after 1 d of culture, the cell survival rate in viscous hydrogel group was significantly lower than that in PBS group (P<0.01). With extension of time after injury, the wounds of mice in the 3 groups shrank gradually. On PID 3, 7, 10, and 14, the wound healing rates in sliver-loaded viscous hydrogel group were (53.0±3.6)%, (75.3±6.9)%, (93.3±1.2)%, and (96.7±0.8)%, which were significantly higher than (21.8±6.4)%, (53.9±8.2)%, (72.0±7.8)%, and (92.5±0.4)% in normal saline group (P<0.01). On PID 3 and 14, the wound healing rates in sliver-loaded viscous hydrogel group were significantly higher than (43.5±2.4)% and (94.1±1.5)% in viscous hydrogel group (P<0.05). On PID 3 and 10, the wound healing rates in viscous hydrogel group were significantly higher than those in normal saline group (P<0.01). On PID 3, the colony forming units of two bacteria in wound of sliver-loaded viscous hydrogel group were significantly less than those in normal saline group and viscous hydrogel group (P<0.01), while the colony forming units of two bacteria in wound of viscous hydrogel group were significantly less than those in normal saline group (P<0.05). On PID 14, the wounds were basically epithelialized and the epidermis was thicker, with collagen protein content being increased significantly and more orderly arranged collagen in sliver-loaded viscous hydrogel group compared with those in the other 2 groups. On PID 14, the epidermal thickness in wounds of sliver-loaded viscous hydrogel group was significantly increased compared with that in the other two groups (P<0.05), and the optical density of collagen fiber was significantly increased compared with those in normal saline group (P<0.05). On PID 3, the expressions of TGF-ß1 and VEGF in wounds of sliver-loaded viscous hydrogel group were significantly higher than those in normal saline group (P<0.05 or P<0.01), while the expression of VEGF in wounds of viscous hydrogel group was significantly higher than that in normal saline group (P<0.01). On PID 7, the expression of TGF-ß1 in wounds of sliver-loaded viscous hydrogel group was significantly higher than that in the other 2 groups (P<0.01), and the expression of VEGF was significantly higher than that in normal saline group (P<0.01). On PID 10, the expression of TNF-α in wounds of sliver-loaded viscous hydrogel group was significantly lower than that in normal saline group (P<0.05), the expressions of TGF-ß1 and VEGF in wounds of sliver-loaded viscous hydrogel group were significantly higher than those in normal saline group (P<0.05 or P<0.01), and the expression of VEGF in wounds of sliver-loaded viscous hydrogel group was significantly higher than that in viscous hydrogel group (P<0.05). Conclusions: The sliver-loaded viscous hydrogel prepared in this study has good stability and elasticity, which can continuously release silver ions and help to accelerate the healing of full-thickness defect wounds with bacterial colonization in mice. Besides, the sliver-loaded viscous hydrogel has low biological toxicity and can promote re-epithelialization, collagen deposition as well as angiogenesis of wounds, which may be related to the infiltration and regression of inflammatory cells.


Assuntos
Hidrogéis , Fator A de Crescimento do Endotélio Vascular , Animais , Bactérias , Masculino , Camundongos , Camundongos Endogâmicos C57BL , Cicatrização
11.
Zhongguo Yi Xue Ke Xue Yuan Xue Bao ; 43(5): 696-705, 2021 Oct.
Artigo em Chinês | MEDLINE | ID: mdl-34728030

RESUMO

Objective To obtain the proteome and acetylome profiles of livers in mice during normal aging.Methods We applied tandem mass tag labeling and liquid chromatography tandem mass spectrometry and achieved proteome and acetylome data in C57BL/6J male mice aged 2 and 18 months under physiological conditions.Results A total of 4712 proteins were quantified by proteome profiling,and 4818 acetylated sites in 1367 proteins by acetylome profiling.The proteome and acetylome revealed moderate differences in the livers of young and old mice.There were 195 differentially expressed proteins in the proteome and 113 differentially expressed acetylated sites corresponding to 76 proteins in the acetylome.Functional enrichment analysis for the proteome showed that aging-associated upregulated proteins were mainly involved in fatty acid metabolism,epoxygenase P450 pathway,drug catabolic process,organic hydroxy compound metabolic process,and arachidonic acid metabolic process,while the downregulated proteins were related to regulation of gene silencing,nucleosome assembly,protein heterotetramerization,response to interferon,protein-DNA complex assembly and other processes.For the acetylome,the proteins with aging-associated upregulated acetylated sites mainly participated in cofactor metabolism,small molecule catabolic process,ribose phosphate metabolic process,ribonucleotide metabolic process,and purine-containing compound metabolic process,while the proteins with downregulated acetylated sites were associated with sulfur compound metabolic process,response to unfolded protein,and amino acid metabolic process.Conclusion We profiled the proteome and acetylome of livers in mice during normal aging and generated datasets for further research on aging.


Assuntos
Lisina , Proteoma , Acetilação , Envelhecimento , Animais , Fígado , Lisina/metabolismo , Masculino , Camundongos , Camundongos Endogâmicos C57BL , Proteoma/metabolismo
12.
Front Immunol ; 12: 656419, 2021.
Artigo em Inglês | MEDLINE | ID: mdl-34745081

RESUMO

Tuberculosis (TB) is the global health problem with the second highest number of deaths from a communicable disease after COVID-19. Although TB is curable, poor health infrastructure, long and grueling TB treatments have led to the spread of TB pandemic with alarmingly increasing multidrug-resistant (MDR)-TB prevalence. Alternative host modulating therapies can be employed to improve TB drug efficacies or dampen the exaggerated inflammatory responses to improve lung function. Here, we investigated the adjunct therapy of natural immune-modulatory compound berberine in C57BL/6 mouse model of pulmonary TB. Berberine treatment did not affect Mtb growth in axenic cultures; however, it showed increased bacterial killing in primary murine bone marrow-derived macrophages and human monocyte-derived macrophages. Ad libitum berberine administration was beneficial to the host in combination with rifampicin and isoniazid. Berberine adjunctive treatment resulted in decreased lung pathology with no additive or synergistic effects on bacterial burdens in mice. Lung immune cell flow cytometry analysis showed that adjunctive berberine treatment decreased neutrophil, CD11b+ dendritic cell and recruited interstitial macrophage numbers. Late onset of adjunctive berberine treatment resulted in a similar phenotype with consistently reduced numbers of neutrophils both in lungs and the spleen. Together, our results suggest that berberine can be supplemented as an immunomodulatory agent depending on the disease stage and inflammatory status of the host.


Assuntos
Antituberculosos/uso terapêutico , Berberina/uso terapêutico , Fatores Imunológicos/uso terapêutico , Isoniazida/uso terapêutico , Rifampina/uso terapêutico , Tuberculose Pulmonar/tratamento farmacológico , Animais , Antituberculosos/farmacologia , Berberina/farmacologia , Citocinas/imunologia , Células Dendríticas/efeitos dos fármacos , Quimioterapia Combinada , Feminino , Humanos , Fatores Imunológicos/farmacologia , Isoniazida/farmacologia , Pulmão/efeitos dos fármacos , Pulmão/imunologia , Pulmão/microbiologia , Pulmão/patologia , Macrófagos/efeitos dos fármacos , Macrófagos/imunologia , Masculino , Camundongos Endogâmicos C3H , Camundongos Endogâmicos C57BL , Mycobacterium tuberculosis/efeitos dos fármacos , Mycobacterium tuberculosis/crescimento & desenvolvimento , Neutrófilos/efeitos dos fármacos , Neutrófilos/imunologia , Rifampina/farmacologia , Baço/efeitos dos fármacos , Baço/imunologia , Baço/microbiologia , Tuberculose Pulmonar/imunologia , Tuberculose Pulmonar/microbiologia , Tuberculose Pulmonar/patologia
13.
Artigo em Inglês | MEDLINE | ID: mdl-34769857

RESUMO

Autism spectrum disorder is a neurodevelopmental syndrome with a complicated etiology and could be responsible for disrupted gastrointestinal tract microbiota. The aim of this work was to study intestinal samples from an autistic animal model (BTBR mouse strain) to better describe gastrointestinal alterations. We performed a morphological and biological evaluation of small intestine samples. In terms of morphology, we studied the goblet cells, cells of intestinal mucosal responsible for the production and maintenance of the protective mucous blanket. Alterations in their secretion may indicate an altered rate of mucus synthesis and this is one of the possible causes of gastrointestinal problems. In terms of biological evaluation, impaired regulation of glucose homeostasis regulated by sodium-glucose transporters has been suggested as an important component of obesity and associated comorbidities; therefore, this study analyzed the expression of sodium/glucose transporter-1 and -3 in BTBR mice to better define their role. We demonstrated that, in BTBR mice as compared to C57BL/6J (B6) strain animals: (1) The goblet cells had different protein content in their vesicles and apparently a larger number of Golgi cisternae; (2) the expression and level of sodium/glucose transporters were higher. These findings could suggest new possible targets in autism spectrum disorder to maintain mucus barrier function.


Assuntos
Transtorno do Espectro Autista , Transtorno Autístico , Animais , Células Caliciformes , Camundongos , Camundongos Endogâmicos C57BL , Proteínas de Transporte de Sódio-Glucose
14.
Signal Transduct Target Ther ; 6(1): 389, 2021 11 10.
Artigo em Inglês | MEDLINE | ID: mdl-34759261

RESUMO

SARS-CoV-2 and SARS-CoV are genetically related coronavirus and share the same cellular receptor ACE2. By replacing the VSV glycoprotein with the spikes (S) of SARS-CoV-2 and SARS-CoV, we generated two replication-competent recombinant viruses, rVSV-SARS-CoV-2 and rVSV-SARS-CoV. Using wild-type and human ACE2 (hACE2) knock-in mouse models, we found a single dose of rVSV-SARS-CoV could elicit strong humoral immune response via both intranasal (i.n.) and intramuscular (i.m.) routes. Despite the high genetic similarity between SARS-CoV-2 and SARS-CoV, no obvious cross-neutralizing activity was observed in the immunized mice sera. In macaques, neutralizing antibody (NAb) titers induced by one i.n. dose of rVSV-SARS-CoV-2 were eight-fold higher than those by a single i.m. dose. Thus, our data indicates that rVSV-SARS-CoV-2 might be suitable for i.n. administration instead of the traditional i.m. immunization in human. Because rVSV-SARS-CoV elicited significantly stronger NAb responses than rVSV-SARS-CoV-2 in a route-independent manner, we generated a chimeric antigen by replacing the receptor binding domain (RBD) of SARS-CoV S with that from the SARS-CoV-2. rVSV expressing the chimera (rVSV-SARS-CoV/2-RBD) induced significantly increased NAbs against SARS-CoV-2 in mice and macaques than rVSV-SARS-CoV-2, with a safe Th1-biased response. Serum immunized with rVSV-SARS-CoV/2-RBD showed no cross-reactivity with SARS-CoV. hACE2 mice receiving a single i.m. dose of either rVSV-SARS-CoV-2 or rVSV-SARS-CoV/2-RBD were fully protected against SARS-CoV-2 challenge without obvious lesions in the lungs. Our results suggest that transplantation of SARS-CoV-2 RBD into the S protein of SARS-CoV might be a promising antigen design for COVID-19 vaccines.


Assuntos
Vacinas contra COVID-19/imunologia , COVID-19/prevenção & controle , Glicoproteína da Espícula de Coronavírus/imunologia , Animais , Anticorpos Neutralizantes/sangue , Anticorpos Antivirais/sangue , Técnicas de Introdução de Genes , Células HEK293 , Humanos , Camundongos , Camundongos Endogâmicos C57BL , Testes de Neutralização , Proteínas Recombinantes de Fusão/imunologia , SARS-CoV-2 , Glicoproteína da Espícula de Coronavírus/genética
15.
Phytomedicine ; 93: 153804, 2021 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-34735907

RESUMO

BACKGROUND: Mosla chinensis Maxim. cv. Jiangxiangru (JXR), a traditional Chinese medicine, commonly used for the therapy of cold, fever, diarrhea, digestive disorders, and other diseases. Inflammatory bowel disease (IBD) is a chronic disorder of the human gastrointestinal tract. Research about the effect of JXR on IBD and the active ingredient composition of JXR remains deficiency. PURPOSE: This study aims to determine the phytochemical composition and the anti-inflammatory property of JXR, as well as the possible anti-inflammatory mechanisms. METHODS: The bioactive profile of JXR extracts was determined by UPLC-LTQ-Orbitrap-MS. A DSS induced colitis mouse model was applied to explore the anti-inflammatory activity of JXR. The body weight, colon length and histopathological status of colon tissue were evaluated. The content of inflammatory mediators (nitric oxide (NO), prostaglandin E2 (PGE2)) and cytokines (tumor necrosis factor-α (TNF-α), interleukin-6 (IL-6) and interleukin-1ß (IL-1ß)), corresponding mRNA and protein expression levels were analyzed. Oxidation pressure and gut microbial composition were also explored. RESULTS: Totally 63 constitutes were identified from JXR, among them, phenolic acids and flavonoids comprised a large part, and rosmarinic acid (RA) was the main compound. The results of DSS-induced colitis mice model indicated that JXR effectively ameliorated inflammation, restore the redox balance in the gut. JXR treatment significantly reduced the production of reactive oxygen species (ROS), increased the activity of antioxidative enzyme, suppressed the secretion of inflammatory mediators (NO, PGE2) and cytokines (TNF-α, IL-6, IL-1ß). JXR also restrained the activation of mitogen-activated protein kinases (MAPKs) signaling pathway. Furthermore, JXR could restore the microbial diversity by suppressing Bacteroidaceae, increasing Bifidobacteriales and Melainabacteria in DSS colitis mouse model. CONCLUSIONS: This study demonstrated that JXR composed with various bioactive compounds, effectively ameliorated colitis, restored the redox balance and regulated gut microbiota. Results from the present study provide an insight of therapeutic potential of JXR in IBD based on its anti-inflammatory and antioxidant properties, also provide a scientific basis for using JXR as a functional ingredient to promote colon health.


Assuntos
Colite , Microbioma Gastrointestinal , Animais , Colite/induzido quimicamente , Colite/tratamento farmacológico , Colo , Citocinas , Sulfato de Dextrana , Modelos Animais de Doenças , Inflamação/tratamento farmacológico , Camundongos , Camundongos Endogâmicos C57BL
16.
Phytomedicine ; 93: 153812, 2021 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-34753029

RESUMO

BACKGROUND: Atherosclerosis is a progressive chronic disease characterised by aberrant lipid metabolism and a maladaptive inflammatory response. As atherosclerosis-driven cardiovascular disease remains the major cause of morbidity and mortality worldwide, more effective clinical therapies are urgently needed. Traditional Chinese Medicine (TCM) has demonstrated efficacy against atherosclerosis, with Qing-Xue-Xiao-Zhi formula (QXXZF) having been approved for clinical treatment of patients with atherosclerosis. However, the mechanisms underlying the anti-atherosclerotic activity of QXXZF remain unknown. PURPOSE: To investigate the anti-atherosclerotic effect of QXXZF and reveal its mechanisms using preclinical models. METHODS: In vivo, apolipoprotein E-deficient (ApoE-/-) mice were fed a high-fat and high-choline diet (HHD) to induce atherosclerosis. Serum metabolomic profiling was used to identify the concentration of trimethylamine N-oxide (TMAO) in mice. In vitro, RAW264.7 macrophages and bone marrow-derived macrophages (BMDMs) from WT and TLR4-/- C57BL/6 mice were used to explore the effects of QXXZF on macrophages. After confirming the therapeutic effects of QXXZF, mass spectrometry and network pharmacology analyses were used to predict and investigate the main components and the anti-atherogenic mechanisms of QXXZF in the context of atherosclerosis. RESULTS: Our results showed QXXZF significantly suppressed the development of atherosclerosis, as evidenced by the decreased atherosclerotic plaques in the aorta and aortic root, reduced plasma lipid levels and decreased serum TMAO content in HHD-fed ApoE-/- mice. Meanwhile, QXXZF effectively reduced foam cell formation in oxidized low-density lipoprotein (ox-LDL) and TMAO-stimulated RAW264.7 macrophages and BMDMs. Moreover, QXXZF facilitated reverse cholesterol transport (RCT) in macrophages by upregulating the expression of cholesterol efflux-related genes PPARγ/LXRα/ABCA1/ABCG1. Mechanistic studies revealed that QXXZF influenced cholesterol metabolism by inhibiting the TLR4-mediated nuclear factor kappa B (NF-κB) axis. Importantly, TLR4 knockout abolished the influence of QXXZF on macrophages. CONCLUSION: QXXZF promotes lipid efflux and inhibits macrophage-mediated inflammation, producing a therapeutic effect against atherosclerosis. Our study provides new insight into the mechanism of QXXZF against atherosclerosis.


Assuntos
Aterosclerose , NF-kappa B , Transportador 1 de Cassete de Ligação de ATP , Animais , Apolipoproteínas E/genética , Aterosclerose/tratamento farmacológico , Humanos , Macrófagos/metabolismo , Camundongos , Camundongos Endogâmicos C57BL , Camundongos Knockout , Fator 88 de Diferenciação Mieloide , NF-kappa B/metabolismo , Receptor 4 Toll-Like/metabolismo
17.
J Agric Food Chem ; 69(44): 13034-13044, 2021 Nov 10.
Artigo em Inglês | MEDLINE | ID: mdl-34723501

RESUMO

Dietary ethanolamine plasmalogen (PlsEtn) has been reported to have several health benefits; however, its functional role during colon pathophysiology remains elusive. The present study investigated the anticolitis effect of dietary ethanolamine glycerophospholipids (EtnGpls) with high PlsEtn from ascidian muscle (86.2 mol %) and low PlsEtn from porcine liver (7.7 mol %) in dextran sulfate sodium (DSS)-induced colitis in mice. Dietary EtnGpls lowered myeloperoxidase activity, thiobarbituric acid-reactive substances, proinflammatory cytokines and proapoptosis-related protein levels in colon mucosa after 16 days of DSS treatment, with ascidian muscle (0.1% EtnGpl in diet) showing higher suppression than porcine liver (0.1% EtnGpl in diet). Moreover, dietary EtnGpls suppressed DSS symptoms after 38 days of DSS treatment as evidenced by increased body weight, colon length, and ameliorated colon mucosa integrity. Additionally, dietary EtnGpls elevated short-chain fatty acid production in DSS-treated mice. Altogether, these results indicate the potential of utilizing diets with abundant PlsEtn for the prevention of colon inflammation-related disorders.


Assuntos
Colite , Animais , Anti-Inflamatórios/farmacologia , Colite/induzido quimicamente , Colite/tratamento farmacológico , Colite/genética , Colo/metabolismo , Sulfato de Dextrana/metabolismo , Dieta , Modelos Animais de Doenças , Mucosa Intestinal/metabolismo , Camundongos , Camundongos Endogâmicos C57BL , Estresse Oxidativo , Plasmalogênios , Suínos , Compostos de Vinila
18.
Elife ; 102021 11 01.
Artigo em Inglês | MEDLINE | ID: mdl-34723795

RESUMO

Previously we showed that the vitamin A metabolite all-trans retinoic acid (atRA) induces synaptic plasticity in acute brain slices prepared from the mouse and human neocortex (Lenz et al., 2021). Depending on the brain region studied, distinct effects of atRA on excitatory and inhibitory neurotransmission have been reported. Here, we used intraperitoneal injections of atRA (10 mg/kg) in adult C57BL/6J mice to study the effects of atRA on excitatory and inhibitory neurotransmission in the mouse fascia dentata-a brain region implicated in memory acquisition. No major changes in synaptic transmission were observed in the ventral hippocampus while a significant increase in both spontaneous excitatory postsynaptic current frequencies and synapse numbers were evident in the dorsal hippocampus 6 hr after atRA administration. The intrinsic properties of hippocampal dentate granule cells were not significantly different and hippocampal transcriptome analysis revealed no essential neuronal changes upon atRA treatment. In light of these findings, we tested for the metaplastic effects of atRA, that is, for its ability to modulate synaptic plasticity expression in the absence of major changes in baseline synaptic strength. Indeed, in vivo long-term potentiation (LTP) experiments demonstrated that systemic atRA treatment improves the ability of dentate granule cells to express LTP. The plasticity-promoting effects of atRA were not observed in synaptopodin-deficient mice, therefore, extending our previous results regarding the relevance of synaptopodin in atRA-mediated synaptic strengthening in the mouse prefrontal cortex. Taken together, our data show that atRA mediates synaptopodin-dependent metaplasticity in mouse dentate granule cells.


Assuntos
Giro Denteado/fisiologia , Proteínas dos Microfilamentos/genética , Plasticidade Neuronal/efeitos dos fármacos , Transmissão Sináptica/fisiologia , Tretinoína/administração & dosagem , Animais , Masculino , Camundongos , Camundongos Endogâmicos C57BL , Proteínas dos Microfilamentos/metabolismo
20.
DNA Cell Biol ; 40(11): 1396-1406, 2021 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-34767734

RESUMO

Sepsis has become a major public health problem worldwide. Methylprednisolone sodium succinate (MP) is a commonly used drug to prevent inflammation. However, the role and underlying mechanism of MP in sepsis remain vague. MP inhibited the lipopolysaccharide (LPS)-induced production of tumor necrosis factor-alpha (TNF-α) and interleukin (IL)-17 and suppressed cell growth in alveolar type II epithelial cells (ATII cells). Small nucleolar RNA host gene 5 (SNHG5) expression was inhibited by LPS and restored by MP. Upregulation of SNHG5 inhibited the cellular role of LPS in ATII cells, and further, downregulation of SNHG5 inhibited the cellular role of MP in ATII cells under LPS conditions. SNHG5 elevated the expression of Copine 1 (CPNE1) by enhancing the mRNA stability of CPNE1. Increasing CPNE1 expression restored the silenced SNHG5-induced inhibitor role of MP in ATII cells under LPS conditions. Finally, MP attenuated lung injury and TNF-α and IL-17 secretion in an LPS-induced sepsis mouse model. Overall, this study investigated the mechanism underlying the effect of MP treatment in sepsis and, for the first time, revealed the important role of the SNHG5/CPNE1 pathway in the development and treatment of sepsis and the potential to serve as a diagnostic and therapeutic target for sepsis.


Assuntos
Proteínas de Ligação ao Cálcio/metabolismo , Metilprednisolona/farmacologia , Sepse/tratamento farmacológico , Células Epiteliais Alveolares/efeitos dos fármacos , Células Epiteliais Alveolares/metabolismo , Animais , Apoptose/efeitos dos fármacos , Proteínas de Ligação ao Cálcio/efeitos dos fármacos , Proteínas de Ligação ao Cálcio/genética , Proteínas de Transporte , Ciclo Celular/efeitos dos fármacos , Proliferação de Células/genética , Feminino , Inflamação , Lipopolissacarídeos/farmacologia , Metilprednisolona/metabolismo , Camundongos , Camundongos Endogâmicos C57BL , MicroRNAs/genética , RNA Longo não Codificante/genética , RNA Nucleolar Pequeno/genética , Sepse/metabolismo , Transdução de Sinais/efeitos dos fármacos
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