RESUMO
BACKGROUND: Sepsis often leads to significant morbidity and mortality due to severe myocardial injury. As is known, the activation of NOD-like receptor family pyrin domain-containing 3 (NLRP3) inflammasome crucially contributes to septic cardiomyopathy (SCM) by facilitating the secretion of interleukin (IL)-1ß and IL-18. The removal of palmitoyl groups from NLRP3 is a crucial step in the activation of the NLRP3 inflammasome. Thus, the potential inhibitors that regulate the palmitoylation and inactivation of NLRP3 may significantly diminish sepsis-induced cardiac dysfunction. PURPOSE: The present study sought to explore the effects of the prospective flavonoid compounds targeting NLRP3 on SCM and to elucidate the associated underlying mechanisms. STUDY DESIGN: The palmitoylation and activation of NLRP3 were detected in H9c2 cells and C57BL/6 J mice. METHODS/RESULTS: Echocardiography, histological staining, western blotting, co-immunoprecipitation, qPCR, ELISA and network pharmacology were used to assess the impact of vaccarin (VAC) on SCM in mice subjected to lipopolysaccharide (LPS) injection. From the collection of 74 compounds, we identified that VAC had the strongest capability to suppress NLRP3 luciferase report gene activity in cardiomyocytes, and the anti-inflammatory characteristics of VAC were further ascertained by the network pharmacology. Exposure of LPS triggered apoptosis, inflammation, oxidative stress, mitochondrial disorder in cardiomyocytes. The detrimental alterations were significantly reversed upon VAC treatment in both septic mice and H9c2 cells exposed to LPS. In vivo experiments demonstrated that VAC treatment alleviated septic myocardial injury, indicated by enhanced cardiac function parameters, preserved cardiac structure, and reduced inflammation/oxidative response. Mechanistically, VAC induced NLRP3 palmitoylation to inactivate NLRP3 inflammasome by acting on zDHHC12. In support, the NLRP3 agonist ATP and the acylation inhibitor 2-bromopalmitate (2-BP) prevented the effects of VAC. CONCLUSION: Our findings suggest that VAC holds promise in protecting against SCM by mitigating cardiac oxidative stress and inflammation via priming NLRP3 palmitoylation and inactivation. These results lay the solid basis for further assessment of the therapeutic potential of VAC against SCM.
Assuntos
Cardiomiopatias , Inflamassomos , Camundongos Endogâmicos C57BL , Proteína 3 que Contém Domínio de Pirina da Família NLR , Sepse , Proteína 3 que Contém Domínio de Pirina da Família NLR/metabolismo , Animais , Cardiomiopatias/tratamento farmacológico , Sepse/tratamento farmacológico , Sepse/complicações , Camundongos , Masculino , Inflamassomos/metabolismo , Inflamassomos/efeitos dos fármacos , Lipoilação/efeitos dos fármacos , Ratos , Estresse Oxidativo/efeitos dos fármacos , Linhagem Celular , Lipopolissacarídeos , Miócitos Cardíacos/efeitos dos fármacos , Miócitos Cardíacos/metabolismo , Interleucina-1beta/metabolismo , Interleucina-18/metabolismoRESUMO
BACKGROUND: The inflammatory cascade mediated by macrophages and T cells is considered to be an important factor in promoting the progression of rheumatoid arthritis (RA). Our previous study found that berberine (BBR) can therapeutically impact adjuvant arthritis (AA) in rats through the regulation of macrophage polarization and the balance of Th17/Treg. However, whether BBR's effects on CD4+T cells response are related to its suppression of M1 macrophage still unclear. PURPOSE: The study aimed to estimate the mechanism of BBR in regulating the immunometabolism and differentiation of CD4+T cells are related to exosome derived from M1-macrophage (M1-exo). STUDY-DESIGN/METHODS: Mice model of collagen-induced arthritis (CIA) was established to investigate the antiarthritic effect of BBR was related with regulation of M1-exo to balance T cell subsets. Bioinformatics analysis using the GEO database and meta-analysis. In vitro, we established the co-culture system involving M1-exo and CD4+ T cells to examine whether BBR inhibits CD4+T cell activation and differentiation by influencing M1-exo-miR155. Exosome was characterized using transmission electron microscopy and western blot analysis, macrophage and CD4+T cell subpopulation were detected by flow cytometry. Further, the metabolic profiles of CD4+T cells were assessed by ECAR, OCR, and the level of glucose, lactate, intracellular ATP. RESULT: BBR reinstates CD4+ T cell homeostasis and reduces miR155 levels in both M1-exo and CD4+ T cells obtained from mice with CIA. In vitro, we found exosomes are indispensable for M1-CM on T lymphocyte activation and differentiation. BBR reversed M1-exo facilitating the activation and differentiation of CD4+T cells. Furthermore, BBR reversed glycolysis reprogramming of CD4+T cells induced by M1-exo, while these regulation effects were significantly weakened by miR155 mimic. CONCLUSION: The delivery of miR-155 by M1-exo contributes to CD4+ T cell immunometabolism dysfunction, a process implicated in the development of RA. The anti-arthritic effect of BBR is associated with the suppression of glycolysis and the disruption of CD4+ T cell subsets balance, achieved by reducing the transfer of M1-exo-miR155 into T cells.
Assuntos
Artrite Experimental , Artrite Reumatoide , Berberina , MicroRNAs , Animais , Camundongos , Ratos , Artrite Experimental/tratamento farmacológico , Artrite Experimental/metabolismo , Artrite Reumatoide/metabolismo , Berberina/farmacologia , Linfócitos T CD4-Positivos , Modelos Animais de Doenças , Macrófagos , MicroRNAs/metabolismoRESUMO
High prevalence and metastasis rates are characteristics of lung cancer. Glycolysis provides energy for the development and metastasis of cancer cells. The 1,25-dihydroxy vitamin D3 (1,25(OH)2 D3 ) has been linked to reducing cancer risk and regulates various physiological functions. We hypothesized that 1,25(OH)2 D3 could be associated with the expression and activity of Na+ /H+ exchanger isoform 1 (NHE1) of Lewis lung cancer cells, thus regulating glycolysis as well as migration by actin reorganization. Followed by online public data analysis, Vitamin D3 receptor, the receptor of 1,25(OH)2 D3 has been proved to be abundant in lung cancers. We demonstrated that 1,25(OH)2 D3 treatment suppressed transcript levels, protein levels, and activity of NHE1 in LLC cells. Furthermore, 1,25(OH)2 D3 treatment resets the metabolic balance between glycolysis and OXPHOS, mainly including reducing glycolytic enzymes expression and lactate production. In vivo experiments showed the inhibition effects on tumor growth as well. Therefore, we concluded that 1,25(OH)2 D3 could amend the NHE1 function, which leads to metabolic reprogramming and cytoskeleton reconstruction, finally inhibits the cell migration.
Assuntos
Neoplasias Pulmonares , Humanos , Neoplasias Pulmonares/tratamento farmacológico , Neoplasias Pulmonares/genética , Movimento CelularRESUMO
Dysfunction of macrophage polarization majorly contributes to the progression of rheumatoid arthritis (RA). Polarization and functions of activated macrophages are closely associated with the reprogramming of intracellular metabolisms. Previously, we demonstrated that the anti-arthritis effect of berberine (BBR) in rats with adjuvant-induced arthritis (AA) may be related to AMP-activated protein kinase (AMPK) activation (a key regulator in the biological energy metabolism), and balanced macrophage polarization. However, the specific molecular mechanism of BBR in macrophage metabolism is yet to be elucidated. In this study, we clarified that BBR ameliorated articular inflammation and restored M1/M2 ratio in collagen-induced arthritis (CIA) mice in an AMPK-dependent manner. Mechanistically, BBR reversed the effects of mTORC1 agonist leucine (Leu) on regulating macrophage polarization through activation of AMPK to switch glycolytic reprogramming. Furthermore, BBR inhibition of mTORC1 rely on activation of AMPK to phosphorylate raptor and TSC2 instead of destroying its structure. Our study revealed that the activation of AMPK is required for the BBR-mediated anti-arthritis effect by downregulating mTORC1/HIF-1α and inhibiting the glycolysis in M1 macrophages.
Assuntos
Artrite Experimental , Berberina , Camundongos , Ratos , Animais , Artrite Experimental/tratamento farmacológico , Artrite Experimental/metabolismo , Proteínas Quinases Ativadas por AMP/metabolismo , Berberina/farmacologia , Berberina/uso terapêutico , Alvo Mecanístico do Complexo 1 de Rapamicina/metabolismo , Macrófagos , GlicóliseRESUMO
The aim of this study was to investigate the protective function and mechanism of TCP3 (PKK), TCP6 (YEGGD) and TCP9 (GPGLM) from skipjack tuna cardiac arterial bulbs on skin photoaging using UVB-irradiated HaCaT cell model. The present results indicated that TCP3 (PKK), TCP6 (YEGGD) and TCP9 (GPGLM) had significant cytoprotective effect on UVB-irradiated HaCaT cells (p < 0.001). Hoechst 33342 staining showed that apoptosis of UV-irradiated HaCaT cells could be significantly reduced by the treatment of TCP3 (PKK), TCP6 (YEGGD) and TCP9 (GPGLM); JC-1 staining showed that TCP3 (PKK), TCP6 (YEGGD) and TCP9 (GPGLM) could protect HaCaT cells from apoptosis by restoring mitochondrial membrane potential (MMP); Furthermore, TCP3 (PKK), TCP6 (YEGGD) and TCP9 (GPGLM) could significantly down-regulate the ratio of Bax/Bcl-2 and reduce the expression level of the apoptosis-executing protein Caspase-3 by decreasing the expression of protein Caspase-8 and Caspase-9 (p < 0.05). The action mechanism indicated that TCP3 (PKK), TCP6 (YEGGD) and TCP9 (GPGLM) could up-regulate the expression levels of Nrf2, NQO1 and HO-1 (p < 0.05), which further increased the activity of downstream proteases (SOD, CAT and GSH-Px), and scavenged reactive oxygen species (ROS) and decreased the intracellular levels of malondialdehyde (MDA). In addition, molecular docking indicated that TCP3 (PKK) and TCP6 (YEGGD) could competitively inhibit the Nrf2 binding site because they can occupy the connection site of Nrf2 by binding to the Kelch domain of Keap1 protein. TCP9 (GPGLM) was inferred to be non-competitive inhibition because it could not bind to the active site of the Kelch domain of Keap1 protein. In summary, the antioxidant peptides TCP3 (PKK), TCP6 (YEGGD) and TCP9 (GPGLM) from cardiac arterial bulbs of skipjack tuna can effectively protect HaCaT cells from UVB-irradiated damage and can be used in the development of healthy and cosmetic products to treat diseases caused by UV radiation.
Assuntos
Antioxidantes , Queratinócitos , Animais , Humanos , Antioxidantes/farmacologia , Células HaCaT , Proteína 1 Associada a ECH Semelhante a Kelch/metabolismo , Atum/metabolismo , Fator 2 Relacionado a NF-E2/metabolismo , Simulação de Acoplamento Molecular , Peptídeos/farmacologia , Espécies Reativas de Oxigênio/metabolismo , Apoptose , Raios UltravioletaRESUMO
High-performance pervaporation membranes have potential in industrial separation applications, but overcoming the permeability-selectivity trade-off is a challenge. We report a strategy to create highly flexible metal-organic framework nanosheet (MOF-NS) membranes with a faveolate structure on polymer substrates for alcohol-water separation. The controlled growth followed by a surface-coating method effectively produced flexible and defect-free superhydrophobic MOF-NS membranes. The reversible deformation of the flexible MOF-NS and the vertical interlamellar pathways were captured with electron microscopy. Molecular simulations confirmed the structure and revealed transport mechanism. The ultrafast transport channels in MOF-NS exhibited an ultrahigh flux and a separation factor of 8.9 in the pervaporation of 5 weight % ethanol-water at 40°C, which can be used for biofuel recovery. MOF-NS and polydimethylsiloxane synergistically contribute to the separation performance.
RESUMO
Cardiac arterial bulbs of Skipjack tuna (Katsuwonus pelamis) are rich in elastin, and its hydrolysates are high quality raw materials for daily cosmetics. In order to effectively utilizing Skipjack tuna processing byproducts-cardiac arterial bulbs and to prepare peptides with high antioxidant activity, pepsin was selected from six proteases for hydrolyzing proteins, and the best hydrolysis conditions of pepsin were optimized. Using ultrafiltration and chromatographic methods, eleven antioxidant peptides were purified from protein hydrolysate of tuna cardiac arterial bulbs. Four tripeptides (QGD, PKK, GPQ and GLN) were identified as well as seven pentapeptides (GEQSN, GEEGD, YEGGD, GEGER, GEGQR, GPGLM and GDRGD). Three out of them, namely the tripeptide PKK and the pentapeptides YEGGD and GPGLM exhibited the highest radical scavenging activities on 2,2-diphenyl-1-picrylhydrazyl (DPPH), hydroxyl, 2,2'-azino-bis-3-ethylbenzothiazoline-6-sulfonic acid (ABTS) and superoxide anion assays. They also showed to protect plasmid DNA and HepG2 cells against H2O2-induced oxidative stress. Furthermore, they exhibited high stability under temperature ranged from 20-100 °C, pH values ranged from 3-11, and they simulated gastrointestinal digestion for 240 min. These results suggest that the prepared eleven antioxidant peptides from cardiac arterial bulbs, especially the three peptides PKK, YEGGD, and GPGLM, could serve as promising candidates in health-promoting products due to their high antioxidant activity and their stability.
Assuntos
Antioxidantes , Hidrolisados de Proteína , Animais , Antioxidantes/química , Hidrolisados de Proteína/química , Atum/metabolismo , Elastina , Superóxidos/metabolismo , Peroxidação de Lipídeos , Pepsina A , Peróxido de Hidrogênio/metabolismo , Peptídeos/química , Peptídeo Hidrolases/metabolismo , Ácidos Sulfônicos , Concentração de Íons de Hidrogênio , Digestão , DNA/metabolismoRESUMO
The light-matter interaction between plasmonic nanocavity and exciton at the sub-diffraction limit is a central research field in nanophotonics. Here, we demonstrated the vertical distribution of the light-matter interactions at ~1 nm spatial resolution by coupling A excitons of MoS2 and gap-mode plasmonic nanocavities. Moreover, we observed the significant photoluminescence (PL) enhancement factor reaching up to 2800 times, which is attributed to the Purcell effect and large local density of states in gap-mode plasmonic nanocavities. Meanwhile, the theoretical calculations are well reproduced and support the experimental results.
RESUMO
Background: It has been established that the dipeptidyl peptidase-4 (DPP-4) inhibitor Diprotin A TFA can reduce vascular endothelial (VE)-cadherin disruption by inhibiting the increase in cleaved ß-catenin in response to hypoxia, thereby protecting the vascular barrier of human umbilical vein endothelial cells. In this study, we sought to investigate the possible effect of Diprotin A TFA on the VE barrier after cerebral ischemic stroke in mice. Methods: C57BL/6J mice were divided into five groups, namely, (1) sham, (2) stroke, (3) stroke + dimethyl sulfoxide (DMSO), (4) stroke + Diprotin A TFA, and (5) stroke + Diprotin A TFA + XAV-939. First, the cerebral ischemia model was established by photothrombotic ischemia, followed by intraperitoneal injection with Diprotin A TFA and XAV-939 at doses of 70 µg/kg and 40 mg/kg 30 min once in the morning and once in the evening for 3 days. Immunofluorescence staining and Western blot methods were used to analyze the expression of vascular and blood-brain barrier (BBB)-associated molecular markers in the peri-infarct area. Results: Compared with the vehicle control group, we found that mice injected with Diprotin A TFA exhibited reduced cerebral infarction volume, increased vascular area and length around the brain injury, increased pericyte and basement membrane coverage, upregulated expression of BBB tight junction proteins, and improved their BBB permeability, whereas the group injected with both drug and inhibitor exhibited significantly aggravated vascular injury and BBB permeability. Conclusion: Diprotin A TFA can reduce VE-cadherin disruption by inhibiting ischemia-hypoxia-induced ß-catenin cleavage to protect blood vessels.
RESUMO
The aim of this study was to investigate the effects of different types of exercise on intestinal mechanical barrier and related regulatory factors in mice with type 2 diabetes mellitus (T2DM). The model was established by high-fat diet feeding and intraperitoneal injection of streptozocin (STZ). The mice were divided into control group, model group (free exercise), resistance exercise group (tail load-bearing ladder climbing, 5 times a week), aerobic exercise group (non-load-bearing platform running, 5 times a week at a speed of 10-15 m/min), and combined exercise group (aerobic exercise was performed on the first, third and fifth days of each week, and resistance exercise on the second and fourth days of each week). After 8 weeks of intervention, the serum lipid levels and inflammatory cytokines were measured by corresponding kits. The pathological changes of ileum were detected by HE and PAS staining. The mRNA and protein expression levels of tight junction-related proteins were detected by real-time qPCR and Western blot, respectively. Moreover, the protein expression levels of hypoxia inducible factor-1α (HIF-1α) and myosin light chain kinase (MLCK) were detected by Western blot. The results showed that all three types of exercise decreased blood glucose and body weight compared to the model group. Aerobic exercise and combined exercise decreased serum lipid (triglycerides and total cholesterol) levels, up-regulated the expression levels of ileal tight junction-related proteins and HIF-1α, improved the intestinal alkaline phosphatase (AKP) activity, reduced serum lipopolysaccharide (LPS), interleukin-1ß (IL-1ß), tumor necrosis factor-α (TNF-α) and diamine oxidase (DAO) levels, and down-regulated MLCK protein expression level. These results suggest that all three types of exercise can reduce blood glucose and body weight of T2DM mice, and aerobic exercise and combined exercise can restore the damaged intestinal mechanical barrier by a mechanism involving HIF-1α-MLCK pathway.
Assuntos
Diabetes Mellitus Experimental , Diabetes Mellitus Tipo 2 , Animais , Glicemia , Peso Corporal , Lipopolissacarídeos , CamundongosRESUMO
AIMS: Hyperglycemia and insulin resistance drive intestinal barrier dysfunction in type 2 diabetes (T2DM). Vaccarin, the main active component in the semen of traditional Chinese medicine Vaccaria has a definite effect on T2DM mice. The purpose of this study was to investigate whether vaccarin can enhance the intestinal barrier function in T2DM. MAIN METHODS: The T2DM mice model was established by streptozocin and high-fat diet. Vaccarin at a dose of 1 mg/kg/day was administered. We evaluated the effects of vaccarin on gut microbiota and intestinal barrier function by 16S rRNA sequencing, Western blot, quantitative fluorescent PCR (qPCR), and morphological observation. Moreover, we constructed a single layer of the human intestinal epithelium model to determine the effect of vaccarin in vitro. RESULTS: The experimental results showed that vaccarin alleviated inflammatory mediators in serum and intestinal tissue of mice (P < 0.05), which may depend on the improvement of tight junctions and gut microbiota (P < 0.05). Activation of extracellular regulated protein kinases (Erk1/2) stimulated myosin light chain kinase (MLCK). By inhibiting ERK expression (P < 0.05), vaccarin had similar effects to ERK inhibitors. In addition, the regulation of tight junction barriers also involved the abovementioned pathways in vivo. CONCLUSION: Vaccarin could protect the intestinal barrier by inhibiting the ERK/MLCK signaling pathway and modulate the composition of the microbiota. These results suggested that vaccarin may be an effective candidate for improving intestinal barrier changes in T2DM.
Assuntos
Diabetes Mellitus Tipo 2 , Animais , Diabetes Mellitus Experimental , Camundongos , RNA Ribossômico 16SRESUMO
Many clinical studies have reported that patients diagnosed with cancer will suffer from sleep disturbance during their clinical process, especially among lung cancer patients, and this effect will not easily subside. 1,25-dihydroxy-vitamin-D3 [1,25(OH)2 D3 ], the activated form of vitamin D, can participate in neuronal differentiation and prevent damage to the nervous system. However, little is known about the potential therapeutic effects of cancer-related psychiatric symptoms. In light of this, we hypothesized that a low circulating level of vitamin D was related to sleep quality in the presence of a tumor, 1,25(OH)2 D3 may be an effective way to ameliorate sleep disturbance and neurochemical alterations along with the cancer progress. Male C57BL/6 mice were implanted with intracranial transmitters to monitor electroencephalogram and were subcutaneously inoculated with Lewis lung cancer cells. The results demonstrated that on Days 19-20, tumor-bearing mice displayed fragmented sleep, shortened wake phase, prolonged sleep in the non-rapid eye movement phase, and the levels of vitamin D-associated genes in the brain had changed a lot compared to control mice. Importantly, 1,25(OH)2 D3 treatment really effectively saved the sleep quality of tumor-bearing mice. We further explored and confirmed that 1,25(OH)2 D3 repressed tumor-induced neuroinflammation (IL-1ß, TNF-α, IL-6, IL-10, IFN-γ, and IL-2), enhanced neurotrophic factors (brain-derived neurotrophic factor [BDNF], glialcellline-derived neurotrophic factor) and 5-HT system in the hippocampus, hypothalamus or cortex. A molecular docking approah manifested the ability of 1,25(OH)2 D3 to affect the activity of tryptophan hydroxylase 2 and BDNF. Together, our results suggested that 1,25(OH)2 D3 treatment may attenuate sleep disturbance in Lewis lung cancer-bearing mice, and become a promising strategy for treating cancer symptom clusters to ameliorate the quality of life of patients with cancer.
Assuntos
Encéfalo/efeitos dos fármacos , Calcitriol/farmacologia , Transtornos do Sono-Vigília/tratamento farmacológico , Sono/efeitos dos fármacos , Animais , Encéfalo/metabolismo , Encéfalo/fisiopatologia , Fator Neurotrófico Derivado do Encéfalo/genética , Fator Neurotrófico Derivado do Encéfalo/metabolismo , Carcinoma Pulmonar de Lewis/complicações , Carcinoma Pulmonar de Lewis/metabolismo , Carcinoma Pulmonar de Lewis/patologia , Citocinas/genética , Citocinas/metabolismo , Modelos Animais de Doenças , Fator Neurotrófico Derivado de Linhagem de Célula Glial/genética , Fator Neurotrófico Derivado de Linhagem de Célula Glial/metabolismo , Mediadores da Inflamação/metabolismo , Masculino , Camundongos Endogâmicos C57BL , Serotonina/metabolismo , Transtornos do Sono-Vigília/etiologia , Transtornos do Sono-Vigília/metabolismo , Transtornos do Sono-Vigília/fisiopatologia , Triptofano Hidroxilase/genética , Triptofano Hidroxilase/metabolismoRESUMO
AIMS: SLC9A1 plays an important role in the growth, differentiation and glycolysis of tumor cells. The present study aimed to elucidate the correlation between SLC9A1 and tumor immune infiltration. MAIN METHODS: Expression level of SLC9A1 gene in tumors was identified in GEPIA. The correlation between SLC9A1 and survival in various types of cancers was analyzed by the PrognoScan. SLC9A1 immune infiltration levels and clinical correlation analysis was generated via TIMER and TIMER2.0. KEGG enrichment analysis of SLC9A1 expression was evaluated via STRING. KEY FINDINGS: We found that, in cancers such as liver hepatocellular carcinoma (LIHC), the expression of SLC9A1 was significantly higher in tumor tissues compared with normal tissues, and was significantly associated with poor prognosis. Further analysis showed that SLC9A1 expression in LIHC was significantly positively correlated with immune cell infiltration, and the correlation was the highest for LIHC among 40 cancers. The expression of SLC9A1 is significantly correlated with the immune marker set of most immune cells in LIHC. Furthermore, we found that the expression level of TGF-ß (TGFB1) in Tregs showed the highest correlation with the expression of SLC9A1 in LIHC. SIGNIFICANCE: The increased expression of SLC9A1 is positively correlated with the prognosis of cancer and the level of immune infiltration. Therefore, SLC9A1 is an important prognostic factor for immunotherapy against hepatocellular carcinoma.
Assuntos
Carcinoma Hepatocelular/imunologia , Neoplasias Hepáticas/imunologia , Trocador 1 de Sódio-Hidrogênio/imunologia , Carcinoma Hepatocelular/diagnóstico , Carcinoma Hepatocelular/genética , Regulação Neoplásica da Expressão Gênica , Humanos , Neoplasias Hepáticas/diagnóstico , Neoplasias Hepáticas/genética , Prognóstico , Trocador 1 de Sódio-Hidrogênio/genética , TranscriptomaRESUMO
PURPOSE: Rheumatoid arthritis (RA) is a chronic, systemic autoimmune disease with synovitis as pathological changes. The immune microenvironment of RA promotes metabolic reprogramming of immune cells and stromal cells, which leads to dysfunction and imbalance of immune homeostasis. Cell metabolism undergoes the switch from a static regulatory state to a highly metabolic active state, which changes the redox-sensitive signaling pathway and also leads to the accumulation of metabolic intermediates, which in turn can act as signaling molecules and further aggravate the inflammatory response. The reprogramming of immunometabolism affects the function of immune cells and is crucial to the pathogenesis of RA. In addition, mitochondrial dysfunction plays a key role in glycolytic reprogramming in RA. These metabolic changes may be potential therapeutic targets for RA. Therefore, we reviewed the metabolic reprogramming of RA immune cells and fibroblast-like synovium cells (FLS) and its relationship with mitochondrial dysfunction. METHODS: A computer-based online search was performed using the PubMed database and Web of Science database for published articles concerning immunometabolic reprogramming, mitochondrial dysfunction, and rheumatoid arthritis. RESULTS: This article reviews the metabolic reprogramming of immune cells and fibroblast-like synoviocytes in RA and their relationship to mitochondrial disfunction, as well as the key pro-inflammatory pathways associated with metabolic reprogramming and chemotherapy as a potential future therapeutic strategy for RA.
Assuntos
Artrite Reumatoide/imunologia , Artrite Reumatoide/metabolismo , Animais , Humanos , Macrófagos/imunologia , Macrófagos/metabolismo , Mitocôndrias/imunologia , Mitocôndrias/metabolismo , Transdução de Sinais , Sinoviócitos/imunologia , Sinoviócitos/metabolismo , Linfócitos T/imunologia , Linfócitos T/metabolismoRESUMO
Cancer-related fatigue (CRF) is one of the most common and serious complications in cancer patients, which greatly reduces the quality of life. The mechanism induced fatigue may be diverse. In this study, we tried to investigate the effect of 1,25(OH)2D3, the active metabolite of vitamin D on CRF in Lewis lung cancer-bearing mice. Network pharmacological analysis, behavioral testing, western blotting, ELISA and flow cytometry were used. We found that there was an interaction between proteins related to the role of 1,25(OH)2D3 and CRF-related proteins. The results of animal model experiments showed that 1,25(OH)2D3 could mitigate the CRF behavior of tumor-bearing mice, and the treatment of 1,25(OH)2D3 reduced the levels of inflammatory factors, changed the tryptophan metabolism direction, and caused changes in immune cells. Collectively, 1,25(OH)2D3 might improve CRF in tumor-bearing mice by changing the direction of tryptophan metabolism and inflammatory factor levels. This study provided a possible solution for patients with clinical CRF.
Assuntos
Comportamento Animal/efeitos dos fármacos , Calcitriol/farmacologia , Carcinoma Pulmonar de Lewis/tratamento farmacológico , Fadiga/prevenção & controle , Atividade Motora/efeitos dos fármacos , Mapas de Interação de Proteínas , Animais , Carcinoma Pulmonar de Lewis/metabolismo , Carcinoma Pulmonar de Lewis/psicologia , Linhagem Celular Tumoral , Bases de Dados de Proteínas , Fadiga/metabolismo , Fadiga/psicologia , Elevação dos Membros Posteriores , Humanos , Masculino , Camundongos Endogâmicos C57BL , Teste de Desempenho do Rota-RodRESUMO
Microbial reductive dechlorination of chlorinated aromatics frequently suffers from the long dechlorination period and the generation of toxic metabolites. Biocathode bioelectrochemical systems were verified to be effective in the degradation of various refractory pollutants. However, the electrochemical and microbial related working mechanisms for bio-dechlorination by electro-stimulation remain poorly understood. In this study, we reported the significantly improved 2,4,6-trichlorophenol dechlorination activity through the weak electro-stimulation (cathode potential of -0.36â¯V vs. SHE), as evidenced by the 3.1 times higher dechlorination rate and the complete dechlorination ability with phenol as the end dechlorination product. The high reductive dechlorination rate (20.8⯵M/d) could be maintained by utilizing electrode as an effective electron donor (coulombic efficiency of 82.3⯱â¯4.8%). Cyclic voltammetry analysis of the cathodic biofilm gave the direct evidences of the cathodic respiration with the improved and positive-shifted reduction peaks of 2,4,6-TCP, 2,4-DCP and 4-CP. The optimal 2,4,6-TCP reductive dechlorination rate (24.2⯵M/d) was obtained when a small amount of lactate (2â¯mM) was added, and the generation of H2 and CH4 were accompanied due to the biological fermentation and methanogenesis. The electrical stimulation significantly altered the cathodic biofilm structure and composition with some potential dechlorinators (like Acetobacterium) predominated. The microbial interactions in the ecological network of cathodic biofilm were more simplified than the planktonic community. However, some potential dechlorinators (Acetobacterium, Desulfovibrio, etc.) shared more positive interactions. The co-existence and possible cooperative relationships between potential dechlorinators and fermenters (Sedimentibacter, etc.) were revealed. Meanwhile, the competitive interrelations between potential dechlorinators and methanogens (Methanomassiliicoccus) were found. In the network of plankton, the fermenters and methanogens possessed the more positive interrelations. Electro-stimulation at the cathodic potential of -0.36â¯V selectively enhanced the dechlorination function, while it showed little influence on either fermentation or methanogenesis process. The study gave suggestions for the enhanced bioremediation of chlorinated aromatics, in views of the electro-stimulation capacity, efficiency and microbial interrelations related microbial mechanism.
Assuntos
Clorofenóis , Halogenação , Biodegradação Ambiental , Estimulação ElétricaRESUMO
OBJECTIVE: Vasculogenic mimicry (VM) is a novel mechanism of tumor blood supply distinct from endothelial vessel (EV). VM is associated with malignancy, invasion, metastasis, and poor prognosis. Hitherto a noninvasive method for the assessment of VM in vivo has been lacking. METHODS: Contrast-enhanced ultrasound (CEUS) was performed to evaluate the quantitative parameters of tumors in mice. CD31 immunohistochemistry-Periodic Acid-Schiff double staining was conducted to identify the VM or EV in tumor tissues. Correlations between perfusion parameters and VM density was analyzed by Pearson correlation test. RESULTS: By the 15th day after tumor inoculation, the EV and VM density was 31.15 ± 7.14 and 14.11 ± 2.99 per 200× field. The maximal intensity (IMAX) was 301.19 ± 191.56%, and the rise time (RT), time to peak (TTP) and mean transit time (mTT) were 17.38 ± 7.82 s, 20.27 ± 9.61 s and 58.09 ± 26.44 s, respectively. VM density positively correlated to RT (r = 0.3598, P = 0.0226), TTP (r = 0.3733, P = 0.0177) and mTT(r = 0.6483, P < 0.0001), whereas EV density positively correlated to IMAX (r = 0.4519, P = 0.0034). The vascular diameter of VM was substantially larger than that of EV (43.81 ± 5.88 µm vs 11.21 ± 4.13 µm). CONCLUSION: Three quantitative parameters related to VM were obtained and the relationships between CEUS and VM were established. CEUS might thus provide a novel noninvasive method to assess VM in vivo.
RESUMO
BACKGROUND: The infratemporal fossa (ITF) is located deep in the skull base. Recently, the endoscopic transoral approach has enabled maxillofacial surgeons to access the ITF using a less invasive approach compared to the traditional transfacial and endonasal endoscopic approaches. OBJECTIVE: The present study aims to provide maxillofacial surgeons with new data concerning direct endoscopic measurement and precise anatomical topography features of the endoscopic trans-lateral molar approach to ITF by comparing the endoscopic and regional anatomy of ITF. A clinical case receiving the proposed surgical approach is used to determine the feasibility of this technique. METHOD: The anatomical data were obtained by measuring the bone anatomical landmarks and analyzing the CT imaging data using GE's Advance Windows 4.1 software on 25 subjects (50 sides). Morphological pictures of the regional anatomy and endoscopic anatomy were obtained from 6 (12 sides) adult cadaver heads, and the anatomical features were described. The present study reports the management of one case using the proposed surgical approach. RESULTS: The proposed surgical approach clearly revealed neurovascular, muscular, and surgical landmarks in the ITF. The surgical case supports the minimally invasive treatment approach, which could rapidly access the ITF and completely excise benign tumors. CONCLUSION: The anatomical studies and surgical case presentation helps us understand the spatial relationship of surgical landmarks of the surgical approach to the ITF for the treatment of benign lesions in the deep cranial base area.
Assuntos
Endoscopia/métodos , Neurilemoma/cirurgia , Neoplasias da Base do Crânio/cirurgia , Osso Temporal/patologia , Idoso , Cadáver , Feminino , Humanos , Dente Molar , Neurilemoma/diagnóstico por imagem , Neoplasias da Base do Crânio/diagnóstico por imagemRESUMO
OBJECTIVE: An abnormal state of the central auditory system (CAS) likely plays a large role in the occurrence of phantom sound of tinnitus. Various tinnitus studies using resting-state functional MRI (RS-fMRI) have reported aberrant spontaneous brain activity in the non-auditory system and altered functional connectivity between the CAS and non-auditory system. This study aimed to investigate abnormal functional connections between the aberrant spontaneous activity in the CAS and the whole brain in tinnitus patients, compared to healthy controls (HC) using RS-fMRI. MATERIALS AND METHODS: RS-fMRI from 16 right-ear tinnitus patients with normal hearing (TNHs) and 15 HC individuals was collected, and the time series were extracted from different clusters of a CAS template, supplied by the Anatomy Toolbox of the Statistical Parametric Mapping software. These data were used to derive the smoothed mean amplitude of low-frequency fluctuation (smALFF) values and calculate the relationship between such values and the corresponding clinical data. In addition, clusters in the CAS identified by the smALFF maps were set as seed regions for calculating and comparing the brain-wide connectivity between TNH and HC. RESULTS: We identified the different clusters located in the left higher auditory cortex (HAC) and the right inferior colliculus (IC) from the smALFF maps that contained increased (HAC) and decreased (IC) activity when the TNH group was compared to the HC group, respectively. The value of increased smALFF cluster in the HAC was positively correlated with the tinnitus score, but the decreased smALFF cluster in the IC was not correlated with any clinical characters of tinnitus. The TNH group displayed increased connectivity, compared to the HC group, in brain regions that encompassed the left IC, bilateral Heschl gyrus, bilateral supplementary motor area, right insula, bilateral superior temporal gyrus, right middle temporal gyrus, left hippocampus, left amygdala, and right supramarginal gyrus. CONCLUSION: Tinnitus may be linked to abnormal spontaneous activity in the HAC, which can arise from the neural plasticity induced from the increased functional connectivity between the auditory network, cerebellum, and limbic system.
RESUMO
Academics researchers and "citizen scientists" from 22 countries confirmed that yellow mealworms, the larvae of Tenebrio molitor Linnaeus, can survive by eating polystyrene (PS) foam. More detailed assessments of this capability for mealworms were carried out by12 sources: five from the USA, six from China, and one from Northern Ireland. All of these mealworms digested PS foam. PS mass decreased and depolymerization was observed, with appearance of lower molecular weight residuals and functional groups indicative of oxidative transformations in extracts from the frass (insect excrement). An addition of gentamycin (30â¯mgâ¯g-1), a bactericidal antibiotic, inhibited depolymerization, implicating the gut microbiome in the biodegradation process. Microbial community analyses demonstrated significant taxonomic shifts for mealworms fed diets of PS plus bran and PS alone. The results indicate that mealworms from diverse locations eat and metabolize PS and support the hypothesis that this capacity is independent of the geographic origin of the mealworms, and is likely ubiquitous to members of this species.