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1.
Purinergic Signal ; 2024 Feb 02.
Artigo em Inglês | MEDLINE | ID: mdl-38305986

RESUMO

Acupuncture is a traditional medicinal practice in China that has been increasingly recognized in other countries in recent decades. Notably, several reports have demonstrated that acupuncture can effectively aid in pain management. However, the analgesic mechanisms through which acupuncture provides such benefits remain poorly understood. Purinergic signaling, which is mediated by purine nucleotides and purinergic receptors, has been proposed to play a central role in acupuncture analgesia. On the one hand, acupuncture affects the transmission of nociception by increasing adenosine triphosphate dephosphorylation and thereby decreasing downstream P2X3, P2X4, and P2X7 receptors signaling activity, regulating the levels of inflammatory factors, neurotrophic factors, and synapsin I. On the other hand, acupuncture exerts analgesic effects by promoting the production of adenosine, enhancing the expression of downstream adenosine A1 and A2A receptors, and regulating downstream inflammatory factors or synaptic plasticity. Together, this systematic overview of the field provides a sound, evidence-based foundation for future research focused on the application of acupuncture as a means of relieving pain.

2.
J Sci Food Agric ; 104(10): 6149-6156, 2024 Aug 15.
Artigo em Inglês | MEDLINE | ID: mdl-38445560

RESUMO

BACKGROUND: Whole wheat steamed bread has been recommended for its potential nutritional benefits to human health. Given the positive role of both organic acid and alkali in improving dough development and product quality, the present study investigated the effects of neutralization by addition of alkali (Na2CO3) after dough acidification with traditional Jiaozi starter on the properties of whole wheat dough. RESULTS: The population of yeast and lactic acid bacteria and the acidification level of the dough increased significantly after fermentation with Jiaozi. Incorporation of alkali greatly improved the leavening capacity of the remixed dough and the quality of steamed bread. Jiaozi fermentation and alkali addition changed the water distribution patterns (T2) and affected the secondary structures of gluten protein, starch crystallinity and pasting properties. The storage modulus (G') of the dough increased significantly with the alkali addition, which could be attributed to the promoted cross-linking of the gluten structure and the altered hydration state of the macromolecules. CONCLUSION: The results of the present study indicate that a combination of Jiaozi fermentation and alkali addition could improve the technological properties of whole wheat dough and the quality of steamed bread. The results will help us to further explore the potential application of moderate acidification and alkali addition in the production of leavened whole wheat products. © 2024 Society of Chemical Industry.


Assuntos
Pão , Fermentação , Farinha , Glutens , Triticum , Triticum/química , Pão/análise , Farinha/análise , Concentração de Íons de Hidrogênio , Glutens/química , Manipulação de Alimentos/métodos , Lactobacillales/metabolismo , Lactobacillales/química , Álcalis/química , Leveduras/química , Leveduras/metabolismo , Carbonatos
3.
Mol Pain ; 19: 17448069231202882, 2023.
Artigo em Inglês | MEDLINE | ID: mdl-37678839

RESUMO

Acupuncture, as a traditional treatment, has been extensively used in China for thousands of years. According to the World Health Organization (WHO), acupuncture is recommended for the treatment of 77 diseases. And 16 of these diseases are related to inflammatory pain. As a combination of traditional acupuncture and modern electrotherapy, electroacupuncture (EA) has satisfactory analgesic effects on various acute and chronic pain. Because of its good analgesic effects and no side effects, acupuncture has been widely accepted all over the world. Despite the increase in the number of studies, the mechanisms via which acupuncture exerts its analgesic effects have not been conclusively established. A literature review of related research is of great significance to elaborate on its mechanisms and to inform on further research directions. We elucidated on its mechanisms of action on inflammatory pain from two levels: peripheral and central. It includes the mechanisms of acupuncture in the periphery (immune cells and neurons, purinergic pathway, nociceptive ion channel, cannabinoid receptor and endogenous opioid peptide system) and central nervous system (TPRV1, glutamate and its receptors, glial cells, GABAergic interneurons and signaling molecules). In this review, we collected relevant recent studies to systematically explain the mechanisms of acupuncture in treating inflammatory pain, with a view to providing direction for future applications of acupuncture in inflammatory pain and promoting clinical development.


Assuntos
Analgesia por Acupuntura , Dor Crônica , Eletroacupuntura , Humanos , Manejo da Dor , Peptídeos Opioides , Dor Crônica/terapia , Analgésicos
4.
Rheumatology (Oxford) ; 62(2): 575-582, 2023 02 01.
Artigo em Inglês | MEDLINE | ID: mdl-35689616

RESUMO

OBJECTIVE: We aimed to examine the relationship between serum 25-hydroxyvitamin D and all-cause, cause-specific mortality of patients with RA. METHODS: This cohort study included 1466 patients with RA from The National Health and Nutrition Examination Survey (NHANES) 2001-14. Mortality status was obtained according to death certificate records from the National Death Index. Cox proportional risk models were used to estimate hazard ratios (HR) and 95% CI for mortality. A generalized additive model, smooth curve fitting and 2-piecewise Cox proportional hazards models were established to address the nonlinearity between serum 25-hydroxyvitamin D and mortality. RESULTS: A total of 1466 patients [mean (s.d.) 59.89 (14.14) years old; 58.94% female] were enrolled. The weighted mean level of 25-hydroxyvitamin D was 59.26 (24.99) nmol/l and 38.95% were found with deficient (or severe deficient) vitamin D (<50.00 nmol/l). During 10453 person-years of follow-up, 268 patients were documented for all-cause death, including 52 cardiovascular disease (CVD)deaths and 48 cancer deaths. Compared with patients with serum 25-hydroxyvitamin D <25.00 nmol/l, patients with higher serum 25-hydroxyvitamin D were more likely to have lower rate of all-cause mortality. Nonlinear and L-shaped association between serum 25-hydroxyvitamin D and all-cause mortality was found, and decreased serum 25-hydroxyvitamin D was significantly associated with increased risk of all-cause mortality in patients with serum 25-hydroxyvitamin D <37.30 nmol/l [HR 0.95 (0.92, 0.98); P < 0.01]. CONCLUSION: An L-shaped association between serum 25-hydroxyvitamin D and all-cause mortality was found among patients with RA, indicating that serum 25-hydroxyvitamin D should be improved to a certain level for the prevention of premature death.


Assuntos
Artrite Reumatoide , Doenças Cardiovasculares , Deficiência de Vitamina D , Humanos , Feminino , Adolescente , Masculino , Estudos de Coortes , Inquéritos Nutricionais , Vitamina D , Deficiência de Vitamina D/complicações , Fatores de Risco , Mortalidade
5.
Rheumatology (Oxford) ; 62(12): 3984-3992, 2023 12 01.
Artigo em Inglês | MEDLINE | ID: mdl-37042723

RESUMO

OBJECTIVE: Spontaneous serum uric acid (SUA) decrease has been found in many patients during acute gout attacks, but its mechanism remains unclear. METHODS: The spontaneous regulation of SUA during a gout attack and its possible causes were evaluated in patients with gout. The mechanism of the spontaneous SUA decrease was further studied in Caco2 cells and a monosodium urate (MSU)-induced gout model of wild-type mice and ABCG2-/- mice. The urate transport function of intestinal epithelial cells was detected by transwell culture of Caco2 cells. Expression of ATP-binding cassette super-family G member 2 (ABCG2), IL-1ß and phosphoinositide 3-kinase (PI3K)/Akt was analysed using real-time PCR, western blotting, or immunofluorescence assays. RESULTS: SUA decreased during acute gout attacks in both the gout patients and MSU-induced gouty mice. Increased serum CRP and IL-1ß levels were correlated with the SUA decrease. Intestinal uric acid excretion and expression of ABCG2 were upregulated in the mice during acute gout attacks. In the ABCG2-/- mice, intestinal uric acid excretion significantly decreased during gout attacks. In an in vitro study of a transwell culture, ABCG2 and its upstream PI3K/Akt pathway were significantly upregulated in intestinal epithelial cells. However, ABCG2 expression and its associated intestinal uric acid transport were inhibited when PI3K/Akt was blocked by a PI3K inhibitor, LY294002. CONCLUSIONS: Increased intestinal urate excretion resulted in spontaneous SUA downregulation during acute gout attacks. Inflammation-induced PI3K/Akt activation and ABCG2 expression in epithelial cells might contribute to the upregulation of intestinal uric acid excretion.


Assuntos
Artrite Gotosa , Gota , Hiperuricemia , Humanos , Animais , Camundongos , Ácido Úrico , Fosfatidilinositol 3-Quinases/metabolismo , Proteínas Proto-Oncogênicas c-akt/metabolismo , Células CACO-2 , Transportadores de Cassetes de Ligação de ATP
6.
Plant Cell Environ ; 46(2): 635-649, 2023 02.
Artigo em Inglês | MEDLINE | ID: mdl-36451539

RESUMO

Cassava bacterial blight (CBB) is one of the most serious diseases in cassava production, so it is essential to explore the underlying mechanism of immune responses. Histone acetylation is an important epigenetic modification, however, its relationship with cassava disease resistance remains unclear. Here, we identified 10 histone acetyltransferases in cassava and found that the transcript of MeHAM1 showed the highest induction to CBB. Functional analysis showed that MeHAM1 positively regulated disease resistance to CBB through modulation of salicylic acid (SA) accumulation. Further investigation revealed that MeHAM1 directly activated SA biosynthetic genes' expression via promoting lysine 9 of histone 3 (H3K9) acetylation and lysine 5 of histone 4 (H4K5) acetylation of these genes. In addition, molecular chaperone MeDNAJA2 physically interacted with MeHAM1, and MeDNAJA2 also regulated plant immune responses and SA biosynthetic genes. In conclusion, this study illustrates that MeHAM1 and MeDNAJA2 confer immune responses through transcriptional programming of SA biosynthetic genes via histone acetylation. The MeHAM1 & MeDNAJA2-SA biosynthesis module not only constructs the direct relationship between histone acetylation and cassava disease resistance, but also provides gene network with potential value for genetic improvement of cassava disease resistance.


Assuntos
Manihot , Ácido Salicílico , Ácido Salicílico/metabolismo , Resistência à Doença/genética , Histonas/metabolismo , Manihot/genética , Manihot/metabolismo , Histona Acetiltransferases/genética , Histona Acetiltransferases/metabolismo , Lisina/metabolismo , Acetilação
7.
Purinergic Signal ; 19(1): 245-254, 2023 03.
Artigo em Inglês | MEDLINE | ID: mdl-35000074

RESUMO

Pain is a common clinical symptom that seriously affects the quality of life in a variety of patient populations. In recent years, research on the role of adenosine signaling in pain modulation has made great progress. Adenosine is a purine nucleoside and a neuromodulator, and regulates multiple physiological and pathophysiological functions through the activation of four G protein-coupled receptors, which are classified as A1, A2A, A2B, and A3 adenosine receptors (ARs). Adenosine and its receptors that are widespread in the central nervous system (CNS) play an important role in the processing of nociceptive sensory signals in different pain models. A1Rs have the highest affinity to adenosine, and the role in analgesia has been well investigated. The roles of A2ARs and A2BRs in the modulation of pain are controversial because they have both analgesic and pronociceptive effects. The analgesic effects of A3Rs are primarily manifested in neuropathic pain. In this article, we have reviewed the recent studies on ARs in the modulation of neuropathic pain, inflammatory pain, postoperative pain, and visceral pain in the CNS. Furthermore, we have outlined the pathways through which ARs contribute to pain regulation, thereby shedding light on how this mechanism can be targeted to provide effective pain relief.


Assuntos
Adenosina , Neuralgia , Humanos , Adenosina/farmacologia , Qualidade de Vida , Sistema Nervoso Central , Analgésicos , Dor Pós-Operatória
8.
J Pineal Res ; 74(3): e12861, 2023 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-36750349

RESUMO

Melatonin participates in plant growth and development and biotic and abiotic stress responses. Histone acetylation regulates many plant biological processes via transcriptional reprogramming. However, the direct relationship between melatonin and histone acetylation in plant disease resistance remains unclear. In this study, we identified cassava bacterial blight (CBB) responsive histone deacetylase 9 (HDA9), which negatively regulated disease resistance to CBB by reducing melatonin content. In addition, exogenous melatonin alleviated disease sensitivity of MeHDA9 overexpressed plants to CBB. Importantly, MeHDA9 inhibited the expression of melatonin biosynthetic genes through decreasing lysine 5 of histone 4 (H4K5) acetylation at the promoter regions of melatonin biosynthetic genes, thereby modulating melatonin accumulation in cassava. Furthermore, protein phosphatase 2C 12 (MePP2C12) interacted with MeHDA9 in vivo and in vitro, and it was involved in MeHDA9-mediated disease resistance via melatonin biosynthetic pathway. In summary, this study highlights the direct interaction between histone deacetylation and melatonin biosynthetic genes in cassava disease resistance via histone deacetylation, providing new insights into the genetic improvement of disease resistance via epigenetic regulation of melatonin level in tropical crops.


Assuntos
Manihot , Melatonina , Melatonina/metabolismo , Histonas/genética , Histonas/metabolismo , Manihot/genética , Manihot/metabolismo , Resistência à Doença/genética , Epigênese Genética , Plantas/metabolismo , Histona Desacetilases/genética , Histona Desacetilases/metabolismo , Regulação da Expressão Gênica de Plantas
9.
Br J Anaesth ; 131(1): 113-121, 2023 07.
Artigo em Inglês | MEDLINE | ID: mdl-37202261

RESUMO

BACKGROUND: The analgesic effect of intravenous lidocaine varies with the duration of lidocaine infusion and surgery type. We tested the hypothesis that prolonged lidocaine infusion alleviates postoperative pain in patients recovering from hepatectomy over the first 3 postoperative days. METHODS: Patients undergoing elective hepatectomy were randomly assigned to receive prolonged i.v. lidocaine treatment or placebo. The primary outcome was incidence of moderate-to-severe movement-evoked pain at 24 h postoperatively. The secondary outcomes included incidence of moderate-to-severe pain during movement and at rest throughout the first 3 postoperative days, postoperative opioid consumption, and pulmonary complications. Plasma lidocaine concentration was also monitored. RESULTS: We enrolled 260 subjects. Intravenous lidocaine lowered the incidence of moderate-to-severe movement-evoked pain at 24 h and 48 h postoperatively (47.7% vs 67.7%, P=0.001; 38.5% vs 58.5%, P=0.001) and reduced movement-evoked pain scores (3.7 [1.7] vs 4.2 [1.6]; mean difference 0.5 [95% confidence interval {CI}: 0.1-0.9]; P=0.018) and morphine equivalent consumption (47.2 [16.7] mg vs 52.6 [19.2] mg; mean difference 5.4 mg [95% CI: 1.0-9.8]; P=0.016) at 24 h postoperatively. Lidocaine also lowered the incidence of postoperative pulmonary complications (23.1% vs 38.5%; P=0.007). Median plasma lidocaine concentrations were 1.5, 1.9, and 1.1 µg ml-1 (inter-quartile ranges: 1.1-2.1, 1.4-2.6, and 0.8-1.6, respectively) after bolus injection, at the end of the surgery, and 24 h postoperatively. CONCLUSIONS: Prolonged intravenous lidocaine infusion reduced the incidence of moderate-to-severe movement-evoked pain for 48 h after hepatectomy. However, the reduction in pain scores and opioid consumption by lidocaine was below the minimal clinically important difference. CLINICAL TRIAL REGISTRATION: NCT04295330.


Assuntos
Analgésicos Opioides , Hepatectomia/efeitos adversos , Método Duplo-Cego , Dor Pós-Operatória/tratamento farmacológico , Dor Pós-Operatória/etiologia , Dor Pós-Operatória/prevenção & controle , Lidocaína/uso terapêutico , Complicações Pós-Operatórias , Anestésicos Locais/uso terapêutico , Analgésicos Opioides/uso terapêutico
10.
Eur Spine J ; 32(11): 4020-4029, 2023 11.
Artigo em Inglês | MEDLINE | ID: mdl-37747546

RESUMO

INTRODUCTION: Adult degenerative scoliosis (ADS) is a 3D deformity that greatly affects the quality of life of patients and is closely related to the quality of paraspinal muscles (PSMs), but the specific degenerative characteristics have not been described. METHODS: This study included ADS patients who were first diagnosed in our hospital from 2018 to 2022. Muscle volume (MV) and fat infiltration (FI) of PSM were measured by 3D reconstruction, and spinal parameters were assessed by X-ray. The values of convex side (CV) and concave side (CC) were compared. RESULTS: Fifty patients were enrolled with a mean age of 64.1 ± 5.8 years old. There were significant differences in MV, FI, and Cobb angle between male and female groups. The MV of MF and PS on the CC was significantly larger than that on the CV. In the apex and the segments above the apex, the FI of the MF on the CC is greater than the CV, and in the CV of the segment below the apex, the FI of the MF is greater than the CC. Besides, there was a significant positive correlation between the FI and Cobb angle in the MF of the CC-CV. CONCLUSION: There were significant differences in the MV and FI of PSM on both sides of the spine in ADS patients. It was determined that the PSM of ADS showed different degrees of degeneration in different levels of the lumbar spine and were positively correlated with Cobb angle.


Assuntos
Escoliose , Humanos , Masculino , Adulto , Feminino , Pessoa de Meia-Idade , Idoso , Escoliose/complicações , Escoliose/diagnóstico por imagem , Escoliose/patologia , Músculos Paraespinais/diagnóstico por imagem , Músculos Paraespinais/patologia , Qualidade de Vida , Radiografia , Vértebras Lombares/diagnóstico por imagem , Atrofia Muscular/diagnóstico por imagem
11.
J Thromb Thrombolysis ; 53(2): 523-531, 2022 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-34476733

RESUMO

OBJECTIVE: Risk factors of left atrial thrombus (LAT) or spontaneous echo contrast (LASEC) in non-valvular atrial fibrillation (NVAF) had been reported. However, information in the subgroup of NVAF patients with low CHA2DS2-VASc scores was limited. Here, we evaluated the risk factors of LAT/LASEC in NVAF patients with low CHA2DS2-VASc scores. METHODS: Transesophageal echocardiography (TEE) file of NVAF patients with low CHA2DS2-VASc scores was reviewed (between June 2009 and Feb 2019) in this retrospective observational study. Binary logistic regression analysis was performed to identify risk factors other than the CHA2DS2-VASc score. Propensity score matching (PSM) was used to further evaluate independent risk markers for LAT/LASEC. The newly discovered factors were added to the CHA2DS2-VASc score, and receiver operating characteristic analysis was used to evaluate the ability of the model to predict LAT/LASEC. RESULTS: TEE files of 3056 NVAF patients with low CHA2DS2-VASc scores were reviewed. Regression analysis revealed elevated fibrinogen and enlarged left atrium (LA) were risk factors for LAT/LASEC. Further PSM analysis confirmed that elevated fibrinogen and enlarged LA were independent risk factors for LAT/LASEC. After including fibrinogen and left atrial diameter (LAD), the CHA2DS2-VASc score was more accurate for LAT/LASEC prediction in NVAF patients with low CHA2DS2-VASc scores (area under the curve difference is 0.241, 95% confidence interval (CI) 0.188-0.294, Z = 8.890, P < 0.0001). CONCLUSIONS: Elevated fibrinogen and enlarged LA were independent risk factors for LAT/LASEC in NVAF patients with low CHA2DS2-VASc scores. Taking fibrinogen and LAD into consideration may help improve LAT/LASEC risk evaluation, which warrants further validation studies.


Assuntos
Fibrilação Atrial , Trombose , Fibrilação Atrial/complicações , Humanos , Valor Preditivo dos Testes , Estudos Retrospectivos , Medição de Risco , Fatores de Risco , Trombose/etiologia
12.
BMC Psychiatry ; 21(1): 3, 2021 01 05.
Artigo em Inglês | MEDLINE | ID: mdl-33402153

RESUMO

BACKGROUND: Based on social comparison theory, two experiments were conducted to explore the effects of depression and social comparison on adolescents, using the ultimatum game (UG). METHODS: Before the formal experiment began, a preliminary experiment tested the effectiveness of social comparison settings. This study used the UG paradigm to explore adolescents' social decision-making in the context of gain and loss through two experiments. These experiments were designed as a 2 (group: depressive mood group, normal mood group) × 2 (social comparison: upward, downward) × 3 (fairness level: fair 5:5, unfair 3:7, extremely unfair 1:9) three-factor hybrid study. RESULTS: (1) The fairer the proposal was, the higher the sense of fairness participants felt, and the higher their acceptance rate. (2) The acceptance rate of the participants for downward social comparison was significantly higher than that for upward social comparison, but there was no difference in fairness perception between the two social comparisons. (3) Under the context of gain, the acceptance rate of the depressive mood group was higher than that of the normal mood group, but there was no difference in the acceptance rate between the depressive mood group and the normal mood group under the loss context. Depressive mood participants had more feelings of unfairness in the contexts of both gain and loss. (4) The effects of depressive mood, social comparison and the fairness level of distribution on social decision-making interact. CONCLUSIONS: The interaction of social comparison, depressive mood and proposal type demonstrates that besides one's emotion, cognitive biases and social factors can also have an effect on social decision-making. These findings indicate that behavioral decision boosting may provide an avenue for appropriate interventions in helping to guide adolescents to make social decisions.


Assuntos
Depressão , Comparação Social , Adolescente , Afeto , Tomada de Decisões , Humanos , Comportamento Social
13.
J Thromb Thrombolysis ; 51(1): 129-135, 2021 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-32562102

RESUMO

The aim of this study was to evaluate the risk factors and characteristics of long-term postoperative left atrial (LA) thrombi after mitral valve replacement. Transthoracic echocardiography (TTE) file of 3117 consecutive patients with mitral valve replacement history was reviewed (between Jan 2006 and Feb 2019). 45 LA thrombi cases (1.4%) was identified and matched to 180 thrombi-free cases by random sampling. The median detection time of LA thrombi was 58 months (IQR, 17-144) after MV replacement. Distribution of LA thrombi included roof (n = 10), posterior wall (n = 9), appendage (n = 7), lateral wall (n = 6), anterior wall (n = 2), septum (n = 1) and multiple site (n = 10). All thrombi were sessile and immobile. The independent predictors for LA thrombi development by stepwise multiple regression analysis were the larger LA size (> 55 mm), the increased of mitral valve pressure gradient (MVPG > 6 mmHg), and the reduced of left ventricular ejection fraction (LVEF < 50%). Long-term thrombi incidence after mitral valve replacement is somewhat low. In individuals with mitral prosthetic valves, larger LA size, increased MVPG and reduced LVEF were three promising independent predictors of the insistence of LA thrombi. Furthermore, LA thrombi were sessile, immobile and widespread in the long-term postoperative period after mitral valve replacement. Close monitoring should be applied in these patients with thrombi risk.


Assuntos
Átrios do Coração/patologia , Implante de Prótese de Valva Cardíaca/efeitos adversos , Próteses Valvulares Cardíacas/efeitos adversos , Valva Mitral/cirurgia , Trombose/etiologia , Idoso , Ecocardiografia , Feminino , Seguimentos , Átrios do Coração/diagnóstico por imagem , Humanos , Masculino , Pessoa de Meia-Idade , Fatores de Risco , Trombose/diagnóstico por imagem , Trombose/patologia
14.
Ecotoxicol Environ Saf ; 220: 112309, 2021 Sep 01.
Artigo em Inglês | MEDLINE | ID: mdl-34015629

RESUMO

Tebuconazole, the most widely used fungicide, is reported to cause various environmental problems and have serious health risks in humans. Despite numerous advances in toxicity studies, its internal metabolic process and the underlying mechanisms have not been systemically studied. The present study administered low doses (0.02 g/kg bw and 0.06 g/kg bw) of tebuconazole to C57BL/6 mice in vivo. The high performance liquid chromatography-tandem mass spectrometry (HPLC-MS/MS) was developed and validated to analyze the tebuconazole in different organs, and our data revealed that tebuconazole mainly accumulated in the liver and that histopathological damage were exhibited in this organ. Tebuconazole significantly dysregulated phase Ⅰ- and phase II-metabolizing enzymes, ATP-binding cassette (ABC) efflux transporters (Abcc2 and Abcc3) and fatty acid metabolism-related genes (Cdkn1a and Fasn), thereby directly causing liver hypertrophy and steatosis. Importantly, the excessive induction of reactive oxygen species (ROS) and oxidative stress partially accounted for the metabolic abnormalities mediated by tebuconazole. Moreover, these alterations were related to the abnormal transcriptional levels of peroxisome proliferator-activated receptor α (PPAR-α) and liver x receptor α (LXR-α), which were predicted to bind to tebuconazole via hydrogen bonding interactions. The current findings provide new insight into the molecular mechanisms of metabolic abnormalities induced by tebuconazole at low concentration, and are conducive to a better understanding of the environmental risk posed by this fungicide.


Assuntos
Bioacumulação , Fungicidas Industriais/toxicidade , Metabolismo dos Lipídeos , Fígado/efeitos dos fármacos , Triazóis/toxicidade , Animais , Fígado/fisiologia , Masculino , Camundongos , Camundongos Endogâmicos C57BL , Proteína 2 Associada à Farmacorresistência Múltipla
15.
J Hepatol ; 73(4): 906-917, 2020 10.
Artigo em Inglês | MEDLINE | ID: mdl-32407813

RESUMO

BACKGROUND & AIMS: Neutrophils are one of the most abundant components in human hepatocellular carcinoma (HCC) and have been shown to play important roles in regulating disease progression. However, neutrophils are very short-lived cells in circulation, and mechanisms regulating their accumulation and functions in HCC are not yet fully understood. METHODS: Monocytes were purified from non-tumor or paired tumor tissues of patients with HCC, and their production of neutrophil-attracting chemokines was evaluated. Mechanisms regulating the expression of CXCL2/8 by tumor monocytes, and the role of tumor monocyte-derived chemokines and cytokines in modulating neutrophil accumulation and functions were studied with both ex vivo analyses and in vitro experiments. RESULTS: Monocyte-derived CXCL2 and CXCL8 were major factors in regulating the recruitment of neutrophils into tumor milieus. These chemokines, in addition to tumor-derived soluble factors, could inhibit apoptosis and sustain survival of neutrophils, thus leading to neutrophil accumulation in tumor tissues. Moreover, monocyte-derived TNF-α acted synergistically with tumor-derived soluble factors to induce the production of the pro-metastasis factor OSM by neutrophils. Further, the glycolytic switch in tumor-infiltrating monocytes mediated their production of CXCL2 and CXCL8 via the PFKFB3-NF-κB signaling pathway. Accordingly, levels of PFKFB3, CXCL2/CXCL8 production in monocytes and infiltration of OSM-producing neutrophils were positively correlated in human HCC tissues. CONCLUSIONS: Our results unveiled a previously unappreciated link between monocytes and neutrophils in human HCC, identifying possible targets that could be therapeutically exploited in the future. LAY SUMMARY: Neutrophils constitute a major but poorly understood component of human hepatocellular carcinoma (HCC). Herein, we unveil a novel mechanism by which metabolic switching in monocytes promotes the accumulation of neutrophils in the tumors of patients with HCC. Both monocyte-produced chemokines and signals from the tumor microenvironment promote the production of the pro-metastatic factor OSM by neutrophils. These data identify potential targets for immune-based anticancer therapies for HCC.


Assuntos
Carcinoma Hepatocelular/metabolismo , Glicólise/fisiologia , Neoplasias Hepáticas/metabolismo , Monócitos/metabolismo , Neutrófilos/metabolismo , Carcinoma Hepatocelular/patologia , Linhagem Celular Tumoral , Progressão da Doença , Feminino , Humanos , Neoplasias Hepáticas/patologia , Masculino , Monócitos/patologia , Neutrófilos/patologia , Estudos Retrospectivos , Transdução de Sinais
17.
Pacing Clin Electrophysiol ; 43(1): 133-145, 2020 01.
Artigo em Inglês | MEDLINE | ID: mdl-31682014

RESUMO

Obesity plays an important role in the pathogenesis of atrial fibrillation (AF). Recently, rather than general fat distribution, epicardial adipose tissue (EAT) gains a growing concern. EAT is the local adipose deposition between myocardium and pericardium. Accumulated evidence revealed several distinguishing characteristics of EAT. It lies contiguously with the myocardium and could infiltration into myocardium, actively secrets cytokines and adipokines mediating inflammation or remodeling, and contains abundant ganglionated plexi. Clinical research also found EAT may be an independent risk factor of AF. Volume or thickness of EAT measured on CT or MRI could be applied as a predictor of presence, severity, and recurrence of AF. Some drugs, like antidiabetic drugs and lipid-lowing drugs, show ability to reduce EAT. Additional surgical ablation of EAT was also proved that it could improve outcome of pulmonary vein isolation for AF. In present review, we summarize recent epidemic, biological, and clinical findings about EAT and its possible role in AF.


Assuntos
Tecido Adiposo/patologia , Fibrilação Atrial/etiologia , Fibrilação Atrial/prevenção & controle , Obesidade/complicações , Pericárdio/patologia , Fibrilação Atrial/fisiopatologia , Previsões , Humanos , Fatores de Risco
18.
J Cardiovasc Electrophysiol ; 30(3): 332-338, 2019 03.
Artigo em Inglês | MEDLINE | ID: mdl-30575204

RESUMO

OBJECTIVE: There are scarce comparative data on efficacy and procedural safety between radiofrequency catheter ablation (RFCA) and surgical ablation (SA) combined with mitral valve (MV) surgery for patients with nonparoxysmal atrial fibrillation (AF) and moderate mitral regurgitation (MR). METHODS AND RESULTS: This single-center, retrospective, and observational study enrolled 155 consecutive patients with nonparoxysmal AF and moderate MR, of which 98 underwent RFCA and 57 underwent SA combined with MV surgery. Circumferential pulmonary vein ablation, bidirectional block of lines, and disappearance of complex fractionated atrial electrograms were the endpoints of RFCA, while pulmonary vein isolation and left and right atrial incisions were performed in SA. At median 24-month follow-up, the primary outcome of atrial tachyarrhythmia (ATa) recurrence-free rate estimated by Kaplan-Meier analysis was higher in SA + MV surgery vs RFCA groups (64.2% vs 38.3%; P = 0.002), and comparable between patients with and without MV prolapse in SA + MV surgery group (64.7% vs 63.1%; P = 0.972). In adjusted Cox model, RFCA was associated with a hazard ratio for ATa recurrence of 2.27 (95% confidence interval, 1.02-5.05; P = 0.045). Patients with higher MR jet/LA (left atrial) area ratio had a higher risk of ATa recurrence in RFCA ( P = 0.037) but not SA + MV ( P = 0.529) groups. CONCLUSION: SA + MV surgery yielded more favorable outcomes than RFCA for treating nonparoxysmal AF in patients with moderate MR. The MR jet/LA area ratio was positively associated with ATa recurrence rate in patients undergoing RFCA. MV prolapse did not affect prognosis in patients undergoing SA + MV surgery.


Assuntos
Fibrilação Atrial/cirurgia , Procedimentos Cirúrgicos Cardíacos , Ablação por Cateter , Insuficiência da Valva Mitral/cirurgia , Valva Mitral/cirurgia , Veias Pulmonares/cirurgia , Potenciais de Ação , Idoso , Fibrilação Atrial/diagnóstico , Fibrilação Atrial/fisiopatologia , Procedimentos Cirúrgicos Cardíacos/efeitos adversos , Ablação por Cateter/efeitos adversos , Feminino , Frequência Cardíaca , Humanos , Masculino , Pessoa de Meia-Idade , Valva Mitral/diagnóstico por imagem , Valva Mitral/fisiopatologia , Insuficiência da Valva Mitral/diagnóstico por imagem , Insuficiência da Valva Mitral/fisiopatologia , Intervalo Livre de Progressão , Veias Pulmonares/fisiopatologia , Recidiva , Estudos Retrospectivos , Fatores de Risco , Índice de Gravidade de Doença , Fatores de Tempo
19.
J Org Chem ; 84(13): 8423-8439, 2019 07 05.
Artigo em Inglês | MEDLINE | ID: mdl-31136177

RESUMO

Various functional secondary and tertiary phosphines, or their derivatives, containing stationary chiral phosphorus and flexible chiral axis were prepared, which could be further modified to afford diversely chelating ligands. The flexible axial chirality was fixed by stereogenic phosphorus via a cyclic linkage of chemical bonds or coordination with a metallic ion.

20.
Cardiol Young ; 29(5): 643-648, 2019 May.
Artigo em Inglês | MEDLINE | ID: mdl-31104644

RESUMO

BACKGROUND: To assess the effectiveness of radiofrequency catheter ablation for lone atrial fibrillation in young adults. METHODS: This single-centre, retrospective, observational study enrolled 75 consecutive patients (86.7% men) under 35 (median, 30) years old with lone atrial fibrillation (68% paroxysmal, 26.7% persistent, and 5.3% long-standing persistent) without other cardiopulmonary diseases who underwent catheter ablation between April 2009 and May 2017. Procedural endpoints were circumferential pulmonary vein ablation for atrial fibrillation with pulmonary vein trigger, and target ablation or bidirectional block of lines and disappearance of complex fractionated atrial electrograms for atrial fibrillation with clear and unclear non-pulmonary vein triggers, respectively. RESULTS: Main study outcome was rate of survival free from atrial tachyarrhythmia recurrence, which at median 61 (range, 5-102) months follow-up was 62.7% (64.7 and 58.3% for paroxysmal and non-paroxysmal atrial fibrillation, respectively) after single ablation, and 69.3% (68.6 and 70.8% for paroxysmal and non-paroxysmal atrial fibrillation, respectively) after mean 1.2 ablations (two and three ablations in 11 and 2 patients, respectively). In multivariate analysis, non-pulmonary vein trigger was a significant independent predictor of recurrent atrial tachyarrhythmia (OR, 10.60 [95%CI, 2.25-49.96]; p = 0.003). There were no major periprocedural adverse events. CONCLUSIONS: In patients under 35 years old with lone atrial fibrillation, radiofrequency catheter ablation appeared effective particularly for atrial fibrillation with pulmonary vein trigger and regardless of left atrial size or atrial fibrillation duration or type. Atrial tachyarrhythmia recurrence after multiple ablations warrants further study.


Assuntos
Fibrilação Atrial/cirurgia , Ablação por Cateter , Veias Pulmonares/cirurgia , Adulto , Ablação por Cateter/efeitos adversos , China , Técnicas Eletrofisiológicas Cardíacas , Feminino , Humanos , Estimativa de Kaplan-Meier , Modelos Logísticos , Masculino , Análise Multivariada , Recidiva , Estudos Retrospectivos , Taquicardia/etiologia , Fatores de Tempo , Resultado do Tratamento , Adulto Jovem
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