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1.
Int Ophthalmol ; 44(1): 314, 2024 Jul 04.
Artigo em Inglês | MEDLINE | ID: mdl-38965086

RESUMO

BACKGROUND: Oxidative stress-induced retinal pigment epithelium (RPE) cell damage is a major factor in age-related macular degeneration (AMD). Vitamin D3 (VD3) is a powerful antioxidant and it has been suggested to have anti-aging properties and potential for treating AMD. This study aimed to investigate the effect of VD3 on RPE cell oxidative apoptosis of RPE cells in order to provide experimental evidence for the treatment of AMD. METHODS: Human retinal pigment epithelial cell 19 (ARPE-19) cells were divided into four groups: blank group (untreated), model group (incubated in medium with 400 µmol/L H2O2 for 1 h), VD3 group (incubated in medium with 100 µmol/L VD3 for 24 h), and treatment group (incubated in medium with 400 µmol/L H2O2 for 1 h and 100 µmol/L VD3 for 24 h). Cell viability, cell senescence, ROS content, expression levels of vitamin D specific receptors, Akt, Sirt1, NAMPT, and JNK mRNA expression levels, SOD activity, and MDA, GSH, and GPX levels were measured. RESULTS: We first established an ARPE-19 cell stress model with H2O2. Our control experiment showed that VD3 treatment had no significant effect on ARPE-19 cell viability within 6-48 h. Treating the stressed ARPE-19 cells with VD3 showed mixed results; caspase-3 expression was decreased, Bcl-2 expression was increased, MDA level of ARPE-19 cells was decreased, GSH-PX, GPX and SOD levels were increased, the relative mRNA expression levels of Akt, Sirt1, NAMPT were increased (P < 0.05), and the relative mRNA expression level of JNK was decreased (P < 0.05). CONCLUSION: VD3 can potentially slow the development of AMD.


Assuntos
Apoptose , Sobrevivência Celular , Estresse Oxidativo , Epitélio Pigmentado da Retina , Humanos , Estresse Oxidativo/efeitos dos fármacos , Epitélio Pigmentado da Retina/efeitos dos fármacos , Epitélio Pigmentado da Retina/metabolismo , Epitélio Pigmentado da Retina/patologia , Sobrevivência Celular/efeitos dos fármacos , Apoptose/efeitos dos fármacos , Degeneração Macular/metabolismo , Vitaminas/farmacologia , Vitamina D/farmacologia , Antioxidantes/farmacologia , Espécies Reativas de Oxigênio/metabolismo , Células Cultivadas , Sirtuína 1/metabolismo , Sirtuína 1/genética , Senescência Celular/efeitos dos fármacos , Linhagem Celular , Peróxido de Hidrogênio/farmacologia , Peróxido de Hidrogênio/toxicidade
2.
Nature ; 548(7668): 434-438, 2017 08 23.
Artigo em Inglês | MEDLINE | ID: mdl-28836603

RESUMO

Semiconductor nanowires are ideal for realizing various low-dimensional quantum devices. In particular, topological phases of matter hosting non-Abelian quasiparticles (such as anyons) can emerge when a semiconductor nanowire with strong spin-orbit coupling is brought into contact with a superconductor. To exploit the potential of non-Abelian anyons-which are key elements of topological quantum computing-fully, they need to be exchanged in a well-controlled braiding operation. Essential hardware for braiding is a network of crystalline nanowires coupled to superconducting islands. Here we demonstrate a technique for generic bottom-up synthesis of complex quantum devices with a special focus on nanowire networks with a predefined number of superconducting islands. Structural analysis confirms the high crystalline quality of the nanowire junctions, as well as an epitaxial superconductor-semiconductor interface. Quantum transport measurements of nanowire 'hashtags' reveal Aharonov-Bohm and weak-antilocalization effects, indicating a phase-coherent system with strong spin-orbit coupling. In addition, a proximity-induced hard superconducting gap (with vanishing sub-gap conductance) is demonstrated in these hybrid superconductor-semiconductor nanowires, highlighting the successful materials development necessary for a first braiding experiment. Our approach opens up new avenues for the realization of epitaxial three-dimensional quantum architectures which have the potential to become key components of various quantum devices.

4.
BMC Cardiovasc Disord ; 22(1): 153, 2022 04 07.
Artigo em Inglês | MEDLINE | ID: mdl-35392805

RESUMO

BACKGROUND: Nerve injury-induced protein 1 (Ninj1) is elevated in various inflammatory diseases. The soluble form of Ninj1 yield by matrix metalloproteinase cleavage is a secreted protein and inhibits cell adhesion and inflammation. However, the role of plasma Ninj1 in atrial fibrillation (AF) has not been reported. The present study aimed to investigate the correlation between plasma Ninj1 levels and AF. METHODS: A total of 96 AF patients [age 66.00 (60.00, 72.00) years, male 56 (58.33%)] and 51 controls without AF [age 65.00 (55.00, 68.00) years, male 21 (41.18%)] were enrolled in this study. Plasma Ninj1 concentrations were detected using enzyme-linked immunosorbent assay. Also, the clinical characteristics, left atrial volume index (LAVI), CHA2DS2-VASc score, and HAS-BLED score were evaluated. RESULTS: Plasma Ninj1 levels were significantly higher in patients with AF than in controls (P < 0.001). Plasma Ninj1 levels were positively correlated with LAVI (P = 0.019) and CHA2DS2-VASc score (P = 0.024). Logistic regression analysis confirmed that the Ninj1 plasma levels were associated with AF (P = 0.009). The receiver operating characteristic analysis showed that plasma Ninj1 had a predictive value for AF (P < 0.001). CONCLUSIONS: Plasma Ninj1 levels were elevated in patients with AF, associated with left atrial enlargement and thromboembolic risk in AF.


Assuntos
Fibrilação Atrial , Remodelamento Atrial , Moléculas de Adesão Celular Neuronais , Fatores de Crescimento Neural , Acidente Vascular Cerebral , Tromboembolia , Idoso , Fibrilação Atrial/complicações , Moléculas de Adesão Celular Neuronais/sangue , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Fatores de Crescimento Neural/sangue , Valor Preditivo dos Testes , Medição de Risco , Fatores de Risco , Acidente Vascular Cerebral/complicações , Tromboembolia/diagnóstico , Tromboembolia/etiologia
5.
Int J Clin Pract ; 2022: 7942605, 2022.
Artigo em Inglês | MEDLINE | ID: mdl-35685549

RESUMO

Background: In our previous studies, we found a disordered taxonomic composition and function of gut microbiota (GM) in atrial fibrillation (AF) patients. However, direct evidence about the association between dysbiotic microbiota and thromboembolic risk in AF is lacking. Aims: In this study, we analyzed the interaction of GM and related functional patterns in AF with different CHA2DS2-VASc scores to assess its potential as a biomarker for predicting stroke risk. Patients and Methods. The CHA2DS2-VASc score was used for thromboembolic risk stratification in AF according to American Heart Association (AHA) guidelines. We investigated the taxonomic and functional annotation of GM based on metagenomic data from 50 AF patients (32 with high thromboembolic risk (CHA2DS2-VASc score ≥2 (males) or CHA2DS2-VASc score ≥3 (females)) and 18 individuals with low thromboembolic risk (CHA2DS2-VASc score <2 (males) or CHA2DS2-VASc score <3 (females))). Results: The gut microbial diversity, composition, and function in AF were different in high and low CHA2DS2-VASc score groups. In high thromboembolic risk group, the abundance of Prevotella, Lachnospiraceae, and Eubacterium rectale, related to the production of short-chain fatty acids and anti-inflammatory were reduced (all P < 0.05). Furthermore, annotated by Kyoto Encyclopedia of Genes and Genomes (KEGG), a database of genes and genomes, the KEGG orthology-based scoring approach exhibited a significant association with thromboembolic risk in AF patients. Conclusions: Imbalance of GM and microbial dysfunction are involved in aggravated thromboembolic risk of AF.


Assuntos
Fibrilação Atrial , Microbioma Gastrointestinal , Acidente Vascular Cerebral , Tromboembolia , Fibrilação Atrial/complicações , Disbiose/complicações , Feminino , Humanos , Masculino , Medição de Risco , Fatores de Risco , Acidente Vascular Cerebral/complicações , Tromboembolia/etiologia
6.
BMC Genomics ; 22(1): 634, 2021 Aug 31.
Artigo em Inglês | MEDLINE | ID: mdl-34465304

RESUMO

BACKGROUND: The gut microbiota provides health benefits in humans by producing short-chain fatty acids (SCFAs), whose deficiency causes multiple disorders and inflammatory diseases. However, gut bacteria producing SCFAs in patients with atrial fibrillation (AF), an arrhythmia with increasing prevalence, have not been reported. To investigate major gut microbial organisms related to SCFA synthesis, SCFAs-associated KEGG orthologues (KOs), enzymatic genes, and potential producers were examined according to metagenomic data-mining in a northern Chinese cohort comprising 50 non-AF control and 50 AF patients. RESULTS: Compared with non-AF controls, individuals with AF had marked differences in microbial genes involved in SCFA-related synthesis, including 125 KOs and 5 SCFAs-related enzymatic genes. Furthermore, there were 10 species that harbored SCFA-synthesis related enzymatic genes, and were markedly decreased in the gut of AF patients. Notably, discriminative features about SCFA-synthesis related function, including 8 KOs (K01752, K01738, K00175, K03737, K01006, K01653, K01647 and K15023), 4 genes (menI, tesB, yciA and CO dehydrogenase acetyl-CoA synthase complex) and 2 species (Coprococcus catus and Firmicutes bacterium CAG:103), were selected as key factors based on LASSO analysis. Furthermore, PLS-SEM analysis showed that 72.8 and 91.14 % of the overall effects on gut microbiota diversity and key species on AF, respectively, were mediated by the key KOs. Meanwhile, 46.31 % of the total effects of SCFA-synthesis related function on left atrial enlargement was mediated by hsCRP. Upon incorporation of clinical properties in AF, the KO score was still significantly associated with AF incidence (OR = 0.004, P = 0.001). CONCLUSIONS: The current study revealed that dysbiotic gut microbiota in AF is coupled with disrupted SCFA-synthesis related genes, characterized by decreased abundances of KEGG orthologues, synthesis enzymatic genes and harboring species.


Assuntos
Fibrilação Atrial , Fibrilação Atrial/genética , Clostridiales , Disbiose , Ácidos Graxos Voláteis , Humanos
7.
BMC Microbiol ; 21(1): 128, 2021 04 26.
Artigo em Inglês | MEDLINE | ID: mdl-33902467

RESUMO

BACKGROUND: Hypertension (HTN) is one of the major cardiovascular risk factors, which contributes to increasing target organ damages and cardiovascular morbidity and mortality worldwide. Isolated systolic HTN (ISH) and isolated diastolic HTN (IDH) are two important subtypes of HTN. Previous researches have demonstrated the alteration of fecal bacteria in HTN, but not down to these two sub-types. In order to identify whether the composition of bacterial taxa and functional modules shift in ISH and IDH, we performed a metagenomic sequencing analysis of fecal samples from 15 controls, 14 ISH, and 11 IDH. RESULTS: Compared with control and ISH, IDH patients showed decreased gene number, bacterial richness, and evenness, although the bacterial alterations did not reach statistical significance in the Shannon index. Also, at the genus level, the ß-diversity for intestinal flora in IDH was distinguishable from those with ISH. Furthermore, the taxonomic composition of ISH or IDH was different from that of healthy control at genus and species levels. Patients with IDH or ISH were confirmed to be enriched with Rothia mucilaginosa, along with reduced Clostridium sp. ASBs410. Lastly, the altered KEGG modules were significantly decreased in IDH compared with the control group, such as sodium transport system; while for ISH, functions relevant to biotin biosynthesis were decreased. CONCLUSIONS: Overall, our results showed the disordered fecal bacteria profiles in subjects with ISH and especially IDH, emphasizing the significance of early intervention for IDH.


Assuntos
Biodiversidade , Fezes/microbiologia , Hipertensão/microbiologia , Microbiota/fisiologia , Genes Bacterianos/genética , Humanos
8.
J Cell Mol Med ; 24(22): 13356-13369, 2020 11.
Artigo em Inglês | MEDLINE | ID: mdl-33058365

RESUMO

Alternations of gut microbiota (GM) in atrial fibrillation (AF) with elevated diversity, perturbed composition and function have been described previously. The current work aimed to assess the association of GM composition with AF recurrence (RAF) after ablation based on metagenomic sequencing and metabolomic analyses and to construct a GM-based predictive model for RAF. Compared with non-AF controls (50 individuals), GM composition and metabolomic profile were significantly altered between patients with recurrent AF (17 individuals) and non-RAF group (23 individuals). Notably, discriminative taxa between the non-RAF and RAF groups, including the families Nitrosomonadaceae and Lentisphaeraceae, the genera Marinitoga and Rufibacter and the species Faecalibacterium spCAG:82, Bacillus gobiensis and Desulfobacterales bacterium PC51MH44, were selected to construct a taxonomic scoring system based on LASSO analysis. After incorporating the clinical factors of RAF, taxonomic score retained a significant association with RAF incidence (HR = 2.647, P = .041). An elevated AUC (0.954) and positive NRI (1.5601) for predicting RAF compared with traditional clinical scoring (AUC = 0.6918) were obtained. The GM-based taxonomic scoring system theoretically improves the model performance, and the nomogram and decision curve analysis validated the clinical value of the predicting model. These data provide novel possibility that incorporating the GM factor into future recurrent risk stratification.


Assuntos
Fibrilação Atrial/microbiologia , Fibrilação Atrial/patologia , Microbioma Gastrointestinal , Perfilação da Expressão Gênica , Metaboloma , Idoso , Área Sob a Curva , Bacillus , Faecalibacterium , Feminino , Humanos , Incidência , Estimativa de Kaplan-Meier , Masculino , Metabolômica , Pessoa de Meia-Idade , Nitrosomonadaceae , Recidiva , Medição de Risco , Resultado do Tratamento
9.
BMC Genomics ; 21(1): 526, 2020 Jul 30.
Artigo em Inglês | MEDLINE | ID: mdl-32731896

RESUMO

BACKGROUND: The gut bacteria-derived metabolite trimethylamine-N-oxide (TMAO) has been discussed in various cardiometabolic diseases. However, evidence characterizing the microbial population responsible for TMAO accumulation in patients with atrial fibrillation (AF), an increasingly prevalent arrhythmia, is yet lacking. In order to understand the key gut microorganisms that produce TMAO in AF, trimethylamine (TMA)-synthesis enzymes and metabolic pathways, as well as the potential TMA-producers in gut microbiome were assessed based on metagenomic data-mining in a northern Chinese cohort consisting of 50 non-AF controls and 50 patients with different types of AF. RESULTS: Compared to the control subjects, AF patients showed a marked increase in the microbial genes underlying TMA formation in the gut, which included 12 potential TMA-synthesis functional orthologs and 1 module. The specific bacterial genes, including choline-TMA lyase, carnitine monooxygenase, glycine betaine reductase, and TMAO reductase, were elevated in the gut of AF patients. Furthermore, 16 genera were assigned and significantly correlated with TMA-enzymatic genes, where 9 genera were remarkably enriched in the gut communities of AF patients. Neither of these TMA-synthesis pathways nor the microbial players showed a significant discrepancy between different types of AF in the current cohort. These gut microbes might participate in the formation of TMA by activating the key TMA-synthesis enzymes and contributing to the functional pathways in AF patients. CONCLUSIONS: The present study provides an in-depth insight into the potential bacteria and metabolic pathways involved in TMA production in the gut of AF patients. These findings emphasize a key role of the gut bacteria in driving TMAO formation during AF pathogenesis, thereby indicating its therapeutic potential as an intervention strategy of AF by targeting TMA-synthesis pathways and dysbiotic gut microbiota.


Assuntos
Fibrilação Atrial , Microbioma Gastrointestinal , Mineração de Dados , Humanos , Metilaminas , Óxidos
10.
Cardiology ; 145(5): 324-332, 2020.
Artigo em Inglês | MEDLINE | ID: mdl-32235120

RESUMO

OBJECTIVE: Atrial fibrosis plays a critical role in atrial fibrillation (AF). A key event in the pathogenesis of fibrosis is the activation of fibroblasts (FBs) into myofibroblasts (MFBs). Paracrine factors released from MFBs lead to ion channel expression changes in cardiomyocytes (CMs). Downregulation of L-type calcium channel Cav1.2 expression is a hallmark of AF-associated ionic remodeling. However, whether exosome (Exo)-mediated crosstalk between MFBs and CMs regulates Cav1.2 expression remains unknown. METHODS: Atrial FBs and CMs were isolated and cultured from neonatal rats by enzymatic digestion. The activation of FBs into MFBs was induced by angiotensin II. Co-culture assay and in vitro Exo treatment were used to determine the effect of MFB-derived Exos on Cav1.2 expression. Confocal Ca2+ imaging was performed to examine the adrenergic stimulation-elicited Ca2+ influx signals. The levels of potential Cav1.2-inhibitory microRNAs (miRNAs) were measured by qRT-PCR. RESULTS: Untreated FBs expressed limited amounts of alpha smooth muscle actin (α-SMA), while angiotensin II induced a significant upregulation of α-SMA-expressing MFBs. Co-cultures of MFBs and CMs resulted in downregulation of Cav1.2 expression in CMs, which was largely abolished by pretreatment of MFBs with exosomal inhibitor GW4869. More importantly, treatment with MFB-derived Exos caused repression of Cav1.2 expression in CMs. Additionally, the adrenergic receptor agonist-elicited Ca2+ influx signals in CMs were remarkably attenuated by pretreatment with MFB-derived Exos, corresponding to the paralleled change in Cav1.2 expression. Finally, miR-21-3p, a potential Cav1.2-inhibitory miRNA, was enriched in MFB-derived Exos and upregulated in CMs in response to MFB-derived Exos. CONCLUSION: We uncover an Exo-mediated crosstalk between MFBs and CMs, contributing to increased vulnerability to AF by reducing the expression of Cav1.2 in CMs.


Assuntos
Fibrilação Atrial/metabolismo , Canais de Cálcio Tipo L/metabolismo , Exossomos/metabolismo , MicroRNAs/metabolismo , Miócitos Cardíacos/metabolismo , Miofibroblastos/citologia , Actinas/metabolismo , Animais , Remodelamento Atrial , Células Cultivadas , Ratos , Ratos Sprague-Dawley
11.
J Cardiovasc Electrophysiol ; 30(7): 1117-1124, 2019 07.
Artigo em Inglês | MEDLINE | ID: mdl-31042327

RESUMO

INTRODUCTION: Advanced age is the foremost risk factor for atrial fibrillation (AF). Telomere length is a surrogate for biological aging, but the association between shortened leukocyte telomere length (LTL) and recurrence of AF (RAF) after ablation remains inconclusive. METHODS: In this prospective analysis, 282 patients underwent an initial catheter ablation for paroxysmal or persistent AF. The association between RAF and LTL was analyzed by univariate and multivariate Cox regression, as well as time-dependent receiver operating characteristic (ROC) analysis and Kaplan-Meier analysis. RESULTS: After a mean follow-up of 14.20 ± 5.04 months, RAF was documented in 78 of the 277 patients who completed the study (28.16%). In Cox proportional hazards models, LTL, age, diagnosis to ablation time (DTAT), N-terminal pronatriuretic peptide, and CHA2DS2-VASc score were significantly associated with RAF. After multivariable adjustment, LTL and DTAT were predicted as independent risk factors for RAF with hazard ratio (HR) of 3.17 (95% confidence interval [CI]: 1.23-8.15, P = 0.017) and 1.43 (95% CI: 1.10-1.86, P = 0.007), respectively. In addition, ROC analysis indicated the potential diagnostic value of LTL with an area under the curve of 0.64 (P < 0.001; sensitivity = 60.3%, specificity = 57.8%), and an optimum cut-off value of 1.040. LTL less than or equal to 1.040 was defined as shortened LTL, while LTL greater than 1.040 nonshortened LTL. Kaplan-Meier analysis showed RAF rate curve was separated significantly between two groups (21.2% vs 35.9%, log-rank test result P = 0.007). Patients with shortened LTL might have a higher risk for RAF with HR = 1.84 (P = 0.008). CONCLUSIONS: Shortened LTL is an independent risk factor for AF recurrence. Shortened LTL could be a potential biomarker in predicting RAF after ablation.


Assuntos
Fibrilação Atrial/cirurgia , Ablação por Cateter/efeitos adversos , Encurtamento do Telômero , Telômero/genética , Idoso , Fibrilação Atrial/diagnóstico , Fibrilação Atrial/genética , Fibrilação Atrial/fisiopatologia , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Estudos Prospectivos , Recidiva , Sistema de Registros , Medição de Risco , Fatores de Risco , Fatores de Tempo , Resultado do Tratamento
12.
Nano Lett ; 17(4): 2690-2696, 2017 04 12.
Artigo em Inglês | MEDLINE | ID: mdl-28355877

RESUMO

Topological superconductivity is a state of matter that can host Majorana modes, the building blocks of a topological quantum computer. Many experimental platforms predicted to show such a topological state rely on proximity-induced superconductivity. However, accessing the topological properties requires an induced hard superconducting gap, which is challenging to achieve for most material systems. We have systematically studied how the interface between an InSb semiconductor nanowire and a NbTiN superconductor affects the induced superconducting properties. Step by step, we improve the homogeneity of the interface while ensuring a barrier-free electrical contact to the superconductor and obtain a hard gap in the InSb nanowire. The magnetic field stability of NbTiN allows the InSb nanowire to maintain a hard gap and a supercurrent in the presence of magnetic fields (∼0.5 T), a requirement for topological superconductivity in one-dimensional systems. Our study provides a guideline to induce superconductivity in various experimental platforms such as semiconductor nanowires, two-dimensional electron gases, and topological insulators and holds relevance for topological superconductivity and quantum computation.

13.
Phys Rev Lett ; 119(18): 187704, 2017 Nov 03.
Artigo em Inglês | MEDLINE | ID: mdl-29219554

RESUMO

Junctions created by coupling two superconductors via a semiconductor nanowire in the presence of high magnetic fields are the basis for the potential detection, fusion, and braiding of Majorana bound states. We study NbTiN/InSb nanowire/NbTiN Josephson junctions and find that the dependence of the critical current on the magnetic field exhibits gate-tunable nodes. This is in contrast with a well-known Fraunhofer effect, under which critical current nodes form a regular pattern with a period fixed by the junction area. Based on a realistic numerical model we conclude that the Zeeman effect induced by the magnetic field and the spin-orbit interaction in the nanowire are insufficient to explain the observed evolution of the Josephson effect. We find the interference between the few occupied one-dimensional modes in the nanowire to be the dominant mechanism responsible for the critical current behavior. We also report a strong suppression of critical currents at finite magnetic fields that should be taken into account when designing circuits based on Majorana bound states.

14.
Arch Virol ; 160(3): 787-94, 2015 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-25387862

RESUMO

The genetic diversity and population structure of citrus tristeza virus (CTV) isolates from China were investigated based on partial sequences spanning the C-terminal end of p61 and the complete sequences of the CPm and CP genes. Phylogenetic analysis revealed five known groups (RB, T30, T36, HA and VT) and one new group (VI) consisting of only Chinese CTV isolates. Incongruent phylogenetic trees coupled with recombination analysis suggested several recombination events in the CPm gene. Positive selection was detected at codon 9 of CPm and codons 31, 41 and 68 of CP. The widespread CTV subpopulation AT-1 found in China has a unique amino acid insertion at the C-terminus of p61, which could increase CTV population complexity with implications for the evolutionary history of the virus. Our results suggest relevant roles for gene flow, purifying selection and recombination in shaping the CTV population in China.


Assuntos
Proteínas do Capsídeo/genética , Citrus/virologia , Closterovirus/classificação , Closterovirus/genética , Evolução Molecular , Variação Genética , China , Closterovirus/isolamento & purificação , Análise por Conglomerados , Fluxo Gênico , Dados de Sequência Molecular , Filogenia , Doenças das Plantas/virologia , RNA Viral/genética , Recombinação Genética , Seleção Genética , Análise de Sequência de DNA , Homologia de Sequência de Aminoácidos
15.
Eur J Med Res ; 29(1): 233, 2024 Apr 15.
Artigo em Inglês | MEDLINE | ID: mdl-38622672

RESUMO

BACKGROUND: Atrial fibrillation (AF) is associated with circulating inflammation. Short-chain fatty acids (SCFAs) derived from gut microbiota (GM) regulate leukocyte function and inhibit the release of inflammatory cytokines, which are partly mediated by the G-protein-coupled receptor 43 (GPR43) signaling. This study aimed to investigate the expression of GPR43/NOD-like receptors family pyrin domain containing 3 (NLRP3) in leukocytes and the interaction with intestinal SCFAs levels in AF patients. METHODS: Expressions of GPR43 and NLRP3 mRNA in peripheral blood leukocytes from 23 AF patients and 25 non-AF controls were detected by quantitative reverse transcription-polymerase chain reaction (qRT-PCR). Expressions of leukocyte GPR43 and NLRP3 protein were evaluated by western blot analysis. The levels of plasma IL-1ß were measured by enzyme-linked immunosorbent assay (ELISA). The fecal SCFAs levels based on GC/MS metabolome of corresponding 21 controls and 14 AF patients were acquired from our published dataset. To evaluate the expression of NLRP3 and GPR43 and the release of IL-1ß, human THP-1 cells were stimulated with or without SCFAs (acetate, propionate, and butyrate), lipopolysaccharide (LPS), and nigericin in vitro, respectively. RESULTS: Compared to the controls, the mRNA expression in peripheral leukocytes was significantly reduced in AF patients (P = 0.011) coupled with the increase in downstream leukocyte NLRP3 mRNA expression (P = 0.007) and plasma IL-1ß levels (P < 0.001), consistent with changes in GPR43 and NLRP3 protein expression. Furthermore, leukocyte GPR43 mRNA levels were positively correlated with fecal GM-derived acetic acid (P = 0.046) and negatively correlated with NLRP3 mRNA expression (P = 0.024). In contrast to the negative correlation between left atrial diameter (LAD) and GPR43 (P = 0.008), LAD was positively correlated with the leukocyte NLRP3 mRNA levels (P = 0.024). Subsequent mediation analysis showed that 68.88% of the total effect of intestinal acetic acid on AF might be mediated by leukocyte GPR43/NLRP3. The constructed GPR43-NLRP3 score might have a predictive potential for AF detection (AUC = 0.81, P < 0.001). Moreover, SCFAs treatment increased GPR43 expression and remarkably reduced LPS/nigericin-induced NLRP3 expression and IL-1ß release in human THP-1 cells in vitro. CONCLUSIONS: Disrupted interactions between GPR43 and NLRP3 expression in peripheral blood leukocytes, associated with reduced intestinal GM-derived SCFAs, especially acetic acid, may be involved in AF development and left atrial enlargement by enhancing circulating inflammation.


Assuntos
Fibrilação Atrial , Proteína 3 que Contém Domínio de Pirina da Família NLR , Humanos , Acetatos/metabolismo , Ácidos Graxos Voláteis/metabolismo , Inflamação/metabolismo , Leucócitos/metabolismo , Lipopolissacarídeos/farmacologia , Nigericina/metabolismo , Proteína 3 que Contém Domínio de Pirina da Família NLR/genética , Proteína 3 que Contém Domínio de Pirina da Família NLR/metabolismo , RNA Mensageiro/genética , RNA Mensageiro/metabolismo
16.
Front Public Health ; 12: 1372758, 2024.
Artigo em Inglês | MEDLINE | ID: mdl-38898891

RESUMO

Introduction: A growing body of evidence suggests that alcohol use disorders coexist with depression. However, the causal relationship between alcohol consumption and depression remains a topic of controversy. Methods: We conducted a two-sample two-way Mendelian randomization analysis using genetic variants associated with alcohol use and major depressive disorder from a genome-wide association study. Results: Our research indicates that drinking alcohol can reduce the risk of major depression (odds ratio: 0.71, 95% confidence interval: 0.54~0.93, p = 0.01), while increasing the frequency of drinking can increase the risk of major depression (odds ratio: 1.09, 95% confidence interval: 1.00~1.18, p = 0.04). Furthermore, our multivariate MR analysis demonstrated that even after accounting for different types of drinking, the promoting effect of drinking frequency on the likelihood of developing major depression still persists (odds ratio: 1.13, 95% confidence interval: 1.04~1.23, p = 0.005). Additionally, mediation analysis using a two-step MR approach revealed that this effect is partially mediated by the adiposity index, with a mediated proportion of 37.5% (95% confidence interval: 0.22 to 0.38). Discussion: In this study, we found that alcohol consumption can alleviate major depression, while alcohol intake frequency can aggravate it.These findings have important implications for the development of prevention and intervention strategies targeting alcohol-related depression.


Assuntos
Consumo de Bebidas Alcoólicas , Transtorno Depressivo Maior , Estudo de Associação Genômica Ampla , Análise da Randomização Mendeliana , Humanos , Transtorno Depressivo Maior/genética , Transtorno Depressivo Maior/epidemiologia , Consumo de Bebidas Alcoólicas/epidemiologia , Masculino , Fatores de Risco , Feminino , Adulto , Polimorfismo de Nucleotídeo Único
17.
Front Pharmacol ; 15: 1414635, 2024.
Artigo em Inglês | MEDLINE | ID: mdl-39221146

RESUMO

The dried root and rhizome of Alpinia officinarum Hance (A. officinarum) have been widely used in traditional Chinese medicine for thousands of years to alleviate pain, promote digestion, warm the stomach, and disperse cold. This review aims to comprehensively and in-depth summarize the most recent research on the traditional uses, phytochemistry, pharmacokinetics, and pharmacology of A. officinarum. By searching various databases including Web of Science, PubMed, Google Scholar, Elsevier, Springer, ScienceDirect, and China National Knowledge Infrastructure (CNKI) for literature on "A. officinarum Hance," as well as relevant textbooks and digital documents, an overall and critical review of the subject was conducted. The traditional uses of A. officinarum were summarized, and 337 compounds from A. officinarum were summarized, including flavonoids, diarylheptanoids, volatile oils, and other compounds. Studies have found that the crude extract of A. officinarum and its compounds has a wide range of biological activities, such as improving gastrointestinal function, anti-inflammatory properties, anti-tumor activity, antibacterial properties, memory enhancement, and analgesic effects. Modern pharmacological studies have provided strong evidence and explanations for the traditional medicinal uses of A. officinarum, which brings a broad prospect for its medicinal use. However, more research is needed to explore the structure-activity relationship and potential mechanisms of action of its bioactive chemicals. Furthermore, it is essential to conduct more clinical trials in order to accelerate research and development of the drug.

18.
J Cardiothorac Surg ; 19(1): 18, 2024 Jan 23.
Artigo em Inglês | MEDLINE | ID: mdl-38263200

RESUMO

INTRODUCTION: The left partial anomalous pulmonary vein connection is a rare congenital heart disease, especially with intact atrial septum. Now we reported a case of the left superior pulmonary vein drainage to left innominate vein through a vertical vein, and corrected with video assisted thoracoscopy. CASE PRESENTATION: A-59-years old man diagnosed left anomalous partial pulmonary vein connection with presentation of short breathiness and palpation, and diagnosed with computer tomography pulmonary angiography. The operation was carried out under video assisted thoracoscopy with one manipulation incision and one observational incision, the vertical vein was dissected and anastomosis with left atrial appendage. The patients recovered smoothly and postoperative CTPA showed anastomosis ostium was unobstructed. CONCLUSION: The left lateral thoracotomy and video assisted thoracoscopic surgery is a feasible for correction of left PAPVC with intact interatrial septum without using CPB.


Assuntos
Septo Interatrial , Coração , Masculino , Humanos , Anastomose Cirúrgica , Angiografia , Veias Braquiocefálicas
19.
J Cardiothorac Surg ; 19(1): 209, 2024 Apr 15.
Artigo em Inglês | MEDLINE | ID: mdl-38616243

RESUMO

Uterine leiomyoma invading internal iliac vein and consequently disseminating into the right atrium is an extremely rare condition, and surgical strategy is controversial. Here, we reported a specific case with successful surgical resection through one-stage total hysterectomy, bilateral oophorectomy, and the intracardiovascular lesion. This procedure would be an optimal choice for uterine leiomyoma invading inferior vena cava and spreading to right atrium.


Assuntos
Leiomiomatose , Feminino , Humanos , Leiomiomatose/complicações , Leiomiomatose/diagnóstico por imagem , Leiomiomatose/cirurgia , Histerectomia , Átrios do Coração/cirurgia , Doenças Raras , Síncope
20.
Artigo em Inglês | MEDLINE | ID: mdl-38632049

RESUMO

OBJECTIVES: The study was designed to evaluate the superiority of the subxiphoid approach compared with the lateral intercostal approach during the operation and other perioperative indices. METHODS: Patients diagnosed with anterior mediastinal disease in our hospital between January 2018 and October 2019 were prospectively assigned to 2 groups; 1 group underwent the lateral intercostal approach and 1 group underwent the subxiphoid approach of video-assisted thoracoscopic surgery to resect the diseased tissue. The PaCO2, SaO2, PaO2 and circulation changes were recorded during the operation; the neutrophil-to-lymphocyte ratio and other perioperative outcomes, including clinical and surgical results, operating time, blood loss, postoperative complication and postoperative pain score were compared. RESULTS: A total of 59 patients diagnosed with an anterior mediastinal tumour or myasthenia gravis underwent a video-assisted thoracoscopic resection. Thirty-one patients were treated via the subxiphoid approach, and 28 patients were treated via the lateral intercostal approach. The PaCO2 increased significantly and the SaO2 remained stable in the subxiphoid group during the operation, whereas PaCO2 increased significantly and SaO2 decreased at the same time in the lateral intercostal group. Operations were more frequently interrupted for the hypoxia or circulation disturbance during the process of dissecting the thymus in the lateral intercostal approach. Compared with the lateral intercostal approach, patients treated via the subxiphoid approach experienced less inflammation and exhibited lower pain scores and shorter postoperative hospital stays. There were no significant differences in postoperative complications between the 2 groups. All of the patients recovered well when discharged. CONCLUSIONS: Our study results suggested that the subxiphoid approach has less of an influence on the pulmonary circulation than the lateral intercostal approach, that the whole procedure is safer and easier and that the subxiphoid approach may be the ideal choice for patients with anterior mediastinal disease.

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