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BACKGROUND: Patients with chronic kidney disease (CKD) possess a pronounced risk for cardiovascular events. A noninvasive left ventricular pressure-strain loop (LV-PSL) has recently been introduced to detect subtler changes in cardiac function. This study aims to investigate the value of LV-PSL for quantitative assessment of myocardial work (MW) in patients with CKD. METHODS: Seventy-five patients with CKD were enrolled retrospectively (37 patients with CKD Stages 2-3, and 38 patients with CKD Stages 4-5), and 35 healthy volunteers were included as controls. All subjects underwent transthoracic echocardiography. LV-PSL analysis was performed to estimate LV MW and efficiency. Global work index (GWI), global constructive work (GCW), global wasted work (GWW), and global work efficiency (GWE) were obtained by echocardiography, and the differences among the groups were compared. RESULTS: There was a significant increase in GWW and reduction in GWE in patients with CKD compared to normal controls (p < 0.05). No significant difference in GWI and GCW was observed among the three groups. Multiple linear regression revealed that increased GWW was significantly associated with age, serum creatinine, and systolic pressure, and decreased GWE was associated with age, serum creatinine, and GLS. CONCLUSION: LV-PSL can be used for noninvasive quantitative assessment of MW in patients with CKD, providing a new sensitive approach for the clinical assessment of myocardial function.
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Ecocardiografia , Insuficiência Renal Crônica , Disfunção Ventricular Esquerda , Humanos , Masculino , Feminino , Insuficiência Renal Crônica/fisiopatologia , Insuficiência Renal Crônica/complicações , Disfunção Ventricular Esquerda/fisiopatologia , Disfunção Ventricular Esquerda/diagnóstico por imagem , Disfunção Ventricular Esquerda/etiologia , Disfunção Ventricular Esquerda/complicações , Pessoa de Meia-Idade , Ecocardiografia/métodos , Estudos Retrospectivos , Reprodutibilidade dos Testes , Ventrículos do Coração/diagnóstico por imagem , Ventrículos do Coração/fisiopatologia , Pressão Ventricular/fisiologia , AdultoRESUMO
Orthosiphon aristatus is a well-known folkloric medicine and herb for Guangdong soup for the treatment of rheumatism in China. Eight isopimarane-type and migrated pimarane-type diterpenoids (1-8), including a new one with a rarely occurring α,ß-unsaturated diketone C-ring, were isolated from O. aristatus. Their structures were determined by spectroscopic methods and quantum chemical calculations. Furthermore, the most abundant compound, orthosiphol K, was structurally modified by modern synthetic techniques to give seven new derivatives (9-15). The anti-rheumatoid arthritis activity of these diterpenoids were evaluated on a TNF-α induced MH7A human rheumatoid fibroblast-like synoviocyte model. Compound 10 showed the most potent activity among these compounds. Based on their inhibitory effects on the release levels of IL-1ß, the preliminary structure-activity relationships were concluded. Furthermore, western blot analysis revealed that 10 could increase the expression of IκBα and decrease the expression of NF-κB p65, and the expression levels of COX-2 and NLRP3 proteins were consequently down-regulated.
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Artrite Reumatoide , Diterpenos , Orthosiphon , Humanos , Orthosiphon/química , Orthosiphon/metabolismo , Abietanos , Artrite Reumatoide/tratamento farmacológico , Fator de Necrose Tumoral alfa , Diterpenos/farmacologia , Diterpenos/química , NF-kappa B/metabolismoRESUMO
Leucine-rich repeat kinase 2 (LRRK2) is a known regulator of autophagy in a range of cell types. Here, we investigated the role of LRRK2-associated autophagy during acute kidney injury (AKI) and its underlying mechanism(s) of action. Male mice aged 8-weeks were treated with the LRRK2 inhibitor MLi-2 and exposed to lipopolysaccharide (LPS) through intraperitoneal injection or ischemia-reperfusion (IR) surgery. Mice were sacrificed 12 or 24 h post-LPS injection or IR operation and blood was collected for serum creatinine measurements. Kidney cortical tissues were collected for western blot analysis of podocyte-specific markers and autophagy-associated proteins. Renal histopathology was observed through hematoxylin-eosin staining. For cell-based assays, immortalized mouse podocytes were silenced for LRRK2 through siRNA transfection and exposed to LPS or cobalt chloride. Changes in cell viability were investigated using cell counting kit-8, flow cytometry and MTT assays. Expression of podocyte-specific markers and autophagy-associated proteins were analyzed by western blotting. We observed an increase in LRRK2 expression at 12 h post-LPS injection and IR surgery that was accompanied by enhanced autophagy. At 24 h post-treatment, both LRRK2 expression and autophagy declined. Kidney injury was most pronounced in mice treated with MLi-2. Podocytes silenced for LRRK2 showed a loss of cell viability, decreased levels of podocyte-specific protein expression and a suppression of autophagy. Together, these data reveal the protective effects of LRRK2 during AKI through enhanced podocyte autophagy and cell viability.
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Injúria Renal Aguda , Podócitos , Masculino , Camundongos , Animais , Podócitos/metabolismo , Podócitos/patologia , Leucina , Lipopolissacarídeos/farmacologia , Apoptose , Autofagia , Injúria Renal Aguda/metabolismo , Biomarcadores/metabolismoRESUMO
Our previous study demonstrated that guaiane-type sesquiterpenoid ludartin showed potent antihepatoma activity against two human hepatocellular carcinoma cell lines, HepG2 and Huh7, with IC50 values of 32.7 and 34.3 µM, respectively. In this study, 34 ludartin derivatives were designed, synthesized and evaluated for their cytotoxic activities against HepG2 and Huh7 cell lines using an MTT assay in vitro. As a result, 17 compounds increased the activity against HepG2 cells, and 20 compounds enhanced the activity against Huh7 cells; 14 derivatives 2, 4-7, 9, 11, 17, 24, 28-30 and 32-33 were superior to ludartin on both HepG2 and Huh7 cells. In particular, dimeric derivative 33 as the most active compound showed 20-fold and 17-fold enhancement of cytotoxicity against HepG2 and Huh7 cells compared to that of ludartin. These results suggested that compound 33 could serve as a promising lead compound against liver cancer. Graphical abstract.
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Liver fibrosis is a final result of extensive deposition of extracellular matrix (ECM) and starts with the activation and proliferation of hepatic stellate cells (HSCs). Our previous study showed that eudesmane sesquiterpenoid santamarin had cytotoxicity against hepatic stellate cell line LX2 (HSC-LX2) with IC50 values of 16.5 ± 0.7 µM. To explore the structure-activity relationships, twenty-six derivatives were synthesized by modifying the hydroxyl group, double-bond and unsaturated lactone. Cytotoxicity evaluation suggested that eight derivatives (6, 9, 13, 17, 20 and 25-27) increased activity against HSC-LX2. Especially, derivatives 17, 20 and 25 displayed obvious cytotoxicity with IC50 values of 6.4 ± 0.4, 4.6 ± 0.1, and 3.5 ± 0.1 µM, which were 3 to 5-fold higher than santamarin. Preliminary mechanisms study revealed that the active compound 20 exhibited more than 8-fold and 6-fold enhancement of inhibitory effect on the deposition of human hyaluronic acid (HA) and human laminin (HL) with IC50 values of 7.6 ± 0.6 and 3.3 ± 1.2 µM.
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Citotoxinas/farmacologia , Células Estreladas do Fígado/efeitos dos fármacos , Cirrose Hepática/tratamento farmacológico , Sesquiterpenos/farmacologia , Linhagem Celular , Citotoxinas/síntese química , Citotoxinas/química , Relação Dose-Resposta a Droga , Células Estreladas do Fígado/metabolismo , Células Estreladas do Fígado/patologia , Humanos , Cirrose Hepática/metabolismo , Cirrose Hepática/patologia , Estrutura Molecular , Sesquiterpenos/síntese química , Sesquiterpenos/química , Relação Estrutura-AtividadeRESUMO
BACKGROUND: Activated charcoal (AC) is highly adsorbent and is often used to promote seedling growth in plant tissue culture; however, the underlying molecular mechanism remains unclear. In this study, root and leaf tissues of 10-day-old seedlings grown via immature embryo culture in the presence or absence of AC in the culture medium were subjected to global transcriptome analysis by RNA sequencing to provide insights into the effects of AC on seedling growth. RESULTS: In total, we identified 18,555 differentially expressed genes (DEGs). Of these, 11,182 were detected in the roots and 7373 in the leaves. In seedlings grown in the presence of AC, 9460 DEGs were upregulated and 7483 DEGs were downregulated in the presence of AC as compared to the control. Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway analysis revealed 254 DEG-enriched pathways, 226 of which were common between roots and leaves. Further analysis of the major metabolic pathways revealed that AC stimulated the expression of nine genes in the phenylpropanoid biosynthesis pathway, including PLA, CYP73A, COMT, CYP84A, and 4CL, the protein products of which promote cell differentiation and seedling growth. Further, AC upregulated genes involved in plant hormone signaling related to stress resistance and disease resistance, including EIN3, BZR1, JAR1, JAZ, and PR1, and downregulated genes related to plant growth inhibition, including BKI1, ARR-B, DELLA, and ABF. CONCLUSIONS: Growth medium containing AC promotes seedling growth by increasing the expression of certain genes in the phenylpropanoid biosynthesis pathway, which are related to cell differentiation and seedling growth, as well as genes involved in plant hormone signaling, which is related to resistance.
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Carvão Vegetal , Perfilação da Expressão Gênica , Plântula/crescimento & desenvolvimento , Triticum/genética , Regulação da Expressão Gênica de Plantas , Fenilpropionatos/metabolismo , Plântula/genética , Transcriptoma , Triticum/crescimento & desenvolvimentoRESUMO
The preliminary assay suggested that the EtOH extract of Artemisia lavandulaefolia had cytotoxicity against hepatic stellate cell line LX2 (HSC-LX2) with an inhibitory ratio of 94.1% at 400 µg/mL. Bioassay-guided investigation led to eleven new sesquiterpenoids, artemilavanolides C-F (1-4) and artemlavandulolides A-G (5-11), as well as thirteen known compounds (12-24). Their structures were elucidated by extensive spectroscopic data and X-ray crystallographic analysis. Cytotoxicity evaluation suggested that fourteen compounds exhibited activity against HSC-LX2; compounds 22, 23 and 24 were comparable to the positive control, silybin (IC50, 162.3 µM); compounds 6, 9 and 16 showed moderate activity with IC50 values of 109.3, 114.0 and 124.2 µM. Importantly, compounds 14, 15 and 18 displayed significant cytotoxicity against HSC-LX2 with IC50 values of 52.1, 16.5 and 21.3 µM, and inhibitory activity on the deposition of human collagen type I (Col I) and human laminin (HL) with IC50 values ranging from 7.3 to 71.6 µM and from 18.6 to 72.9 µM.
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Artemisia/química , Sesquiterpenos/farmacologia , Sobrevivência Celular/efeitos dos fármacos , Células Cultivadas , Cristalografia por Raios X , Relação Dose-Resposta a Droga , Humanos , Modelos Moleculares , Estrutura Molecular , Sesquiterpenos/química , Sesquiterpenos/isolamento & purificação , Relação Estrutura-AtividadeRESUMO
BACKGROUND: To determine the impact of retinal pigment epithelium (RPE) pathology on intersession repeatability of retinal thickness and volume metrics derived from Spectralis spectral-domain optical coherence tomography (Heidelberg Engineering, Heidelberg, Germany). DESIGN: Prospective cross-sectional single centre study. PARTICIPANTS: A total of 56 eyes of 56 subjects were divided into three groups: (i) normal RPE band (25 eyes); (ii) RPE elevation: macular soft drusen (13 eyes); and (iii) RPE attenuation: geographic atrophy or inherited retinal diseases (18 eyes). METHODS: Each subject underwent three consecutive follow-up macular raster scans (61 B-scans at 119 µm separation) at 1-month intervals. MAIN OUTCOME MEASURES: Retinal thicknesses and volumes for each zone of the macular subfields before and after manual correction of segmentation error. Coefficients of repeatability (CR) were calculated. RESULTS: Mean (range) age was 57 (21-88) years. Mean central subfield thickness (CST) and total macular volume were 264 and 258 µm (P = 0.62), and 8.0 and 7.8 mm3 (P = 0.31), before and after manual correction. Intersession CR (95% confidence interval) for CST and total macular volume were reduced from 40 (38-41) to 8.3 (8.1-8.5) and 0.62 to 0.16 mm3 after manual correction of segmentation lines. CR for CST were 7.4, 23.5 and 66.7 µm before and 7.0, 10.9 and 7.6 µm after manual correction in groups i, ii and iii. CONCLUSIONS: Segmentation error in eyes with RPE disease has a significant impact on intersession repeatability of Spectralis spectral-domain optical coherence tomography macular thickness and volume metrics. Careful examination of each B-scan and manual adjustment can enhance the utility of quantitative measurement. Improved automated segmentation algorithms are needed.
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Atrofia Geográfica/diagnóstico , Macula Lutea/patologia , Drusas Retinianas/diagnóstico , Epitélio Pigmentado da Retina/patologia , Tomografia de Coerência Óptica , Adulto , Idoso , Idoso de 80 Anos ou mais , Estudos Transversais , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Estudos Prospectivos , Reprodutibilidade dos Testes , Adulto JovemRESUMO
Objective To observe the therapeutic efficacy and safety of Chinese herbal fumigation combined with leflunomide (LEF) and prednisone (Pred) in treatment of systemic sclerosis (SSc) complicated pulmonary arterial hypertension (PAH). Methods Totally 99 SSc patients complicated early PAH were randomly assigned to the Western drugs group (WD, 49 cases) and the integrative medicine group (IM, 50 cases). Patients in the WD group took LEF (20 mg) and Pred (15 mg) , once per day. In addition to routine WD program, those in the IM group additionally received Chinese herbal fumigation. All treatment lasted for 6 months. Raynaud's phenomenon (RP) was observed in each group before and after treatment. RP score, erythrocyte sedimentation rate (ESR), C reactive protein (CRP), pulmonary arterial systolic pressure (PASP) , and pulmonary function were compared between the two groups before and after treatment. The clinical efficacy and adverse reactions were evaluated. Results Thirteen cases were lost due to various reasons. A total of 86 patients completed this study, 41 in the WD group and 45 in the IM group. Compared with the same group before treatment, RP score, levels of ESR and CRP all decreased in the two groups after treatment (P <0. 05). Compared with the WM group after treatment, RP score, levels of ESR and CRP were obviously lowered in the IM group after treatment (P < 0. 05). Besides, lowered differences between post-pre-values of ESR, CRP, and PASP were more obviously higher, while elevated differences between post-pre-values of total lung capacity (TLC) and carbon monoxide diffusing capacity (DLCO) were more obviously higher in the IM group (P <0. 05). The total effective rate was 93. 33% (42/45) in the IM group, obviously higher than that in the WD group [70. 73% (29/41) , P <0. 05 ]. There was no statistical difference in total adverse reaction rate between the two groups (x² =0. 019, P =0. 891). Conclusion Chinese herbal fumigation combined with WD had obvious efficacy with less adverse reactions, so it was worth clinical spread.
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Medicamentos de Ervas Chinesas , Hipertensão Pulmonar , Medicina Integrativa , Esclerose , Fumigação , Humanos , Hipertensão Pulmonar/complicações , Hipertensão Pulmonar/terapia , Esclerose/complicações , Esclerose/terapiaRESUMO
BACKGROUND: Plasma miR-21 is widely investigated as biomarker in many diseases. Recent studies show that miR-21 participates in the development of systemic lupus erythematosus (SLE). The aim of this study was to evaluate the expression profile of miR-21 in the plasma of SLE patients. METHODS: Relative quantities of plasma miR-21 both in SLE patients and healthy controls were determined by relative qRT-PCR under endogenous and exogenous controls. The diagnostic value of plasma miR-21 was evaluated in SLE patients. Data of some SLE-associated clinical parameters were collected. RESULTS: Eighty participants from Central China were recruited. Forty-four participants were new-onset SLE patients and the others were healthy controls. Plasma miR-21 level in SLE patients was higher than that of healthy controls (P = 0.031). Receiver operating characteristic analysis of plasma miR-21 revealed an Area Under Curve (AUC) of 0.64 ± 0.06 (95% CI: 0.51-0.76, P = 0.03854) when differentiating SLE from healthy controls. The level of plasma miR-21 was not associated with the level of white blood cells (P = 0.4284), red blood cells (P = 0.4079), and platelets (P = 0.4961), but significantly correlated with the level of plasma complement C3 (r = -0.5297, P = 0.0004), C4 (r = -0.4732, P = 0.0020), and serum uric acid (r = 0.3932, P = 0.0121) in SLE patients. CONCLUSIONS: Plasma miR-21 in SLE patients from Central China is overexpressed. Since circulating miR-21 is aberrantly expressed in many diseases, the applying of it as a disease biomarker should be considered carefully.
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Lúpus Eritematoso Sistêmico/genética , MicroRNAs/sangue , Adolescente , Adulto , Idoso , Área Sob a Curva , Biomarcadores/sangue , Contagem de Células Sanguíneas , Complemento C3/metabolismo , Feminino , Humanos , Lúpus Eritematoso Sistêmico/diagnóstico , Masculino , Pessoa de Meia-Idade , Curva ROC , Ácido Úrico/sangueRESUMO
INTRODUCTION: Rheumatoid arthritis (RA) is a progressive inflammatory autoimmune disease characterised by chronic systemic inflammation, which can cause swelling, stiffening and destruction of articular cartilage and bone. Early diagnosis and treatment of RA can improve outcomes and slow the progression of joint damage. Preliminary exploratory research had hinted an expected effect of modified Zhiwang decoction (MZWD) in treating early RA. However, few randomised clinical trials have evaluated the effectiveness of MZWD in early RA. Therefore, a parallel-group randomised controlled trial was designed to evaluate the efficacy and safety of MZWD combined with methotrexate (MTX) on early RA. METHODS AND ANALYSIS: This is a prospective, parallel-group, single-centre randomised controlled clinical study. A total of 150 patients will be randomly assigned to either the treatment (n=75) or control group (n=75). The treatment group will receive MZWD and MTX, and the control group will receive MTX for 12 weeks. The primary outcome of this study is Disease Activity Score-28, and the secondary outcomes are Fatigue Scale-14, Visual Analogue Scale pain scores and traditional Chinese medicine symptom scores. Safety outcomes, including adverse events and results of ECG and laboratory tests, will be monitored. ETHICS AND DISSEMINATION: Ethics approval was obtained from the Clinical Research Ethics Committee of the China-Japan Friendship Hospital (no. 2022-KY-124) on 8 July 2022. The findings will be disseminated in peer-reviewed publications. TRIAL REGISTRATION NUMBER: ClinicalTrials.gov Registry (NCT05508815).
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Antirreumáticos , Artrite Reumatoide , Medicamentos de Ervas Chinesas , Humanos , Metotrexato/efeitos adversos , Estudos Prospectivos , Artrite Reumatoide/tratamento farmacológico , Artrite Reumatoide/induzido quimicamente , Medicina Tradicional Chinesa/métodos , Medicamentos de Ervas Chinesas/efeitos adversos , Resultado do Tratamento , Método Duplo-Cego , Antirreumáticos/efeitos adversos , Ensaios Clínicos Controlados Aleatórios como AssuntoRESUMO
OBJECTIVE: To investigate glucose metabolism status and its relationship with blood pressure, obesity, renal function and cardio-cerebral vascular events in Chinese essential hypertensive patients. METHODS: Essential hypertensive patients without diabetic history were enrolled in this cross-sectional survey. All patients filled in questionnaires and received physical examination and laboratory tests. Oral glucose tolerance test (OGTT, fasting and 2 hours glucose level after drinking the 75 g glucose solution) was performed in patients who signed the informed consent. RESULTS: (1) The control rate of systolic BP was lower in patients with dysglycemia than in patients without dysglycemia (41.0% vs. 46.4%, P = 0.000). (2) The albuminuria detection rate and the abnormal rate of estimated glumerular filtration rate (eGFR) increased significantly with the deterioration of glucose metabolism. (3) Multifactor-analysis showed that abnormal waist circumference, decreased eGFR and presence of albuminuria were independent risk factors for abnormal glucose metabolism. Cardiovascular events was significantly higher in patients with abnormal glucose metabolism than patients with normal glucose metabolism. CONCLUSION: Abnormal glucose metabolism is common in Chinese essential hypertensive patients. When complicated with abnormal glucose metabolism, essential hypertensive patients had poor blood pressure control rate and were related to higher cardiovascular risk.
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Glicemia/metabolismo , Transtornos do Metabolismo de Glucose/diagnóstico , Hipertensão/sangue , Idoso , Estudos Transversais , Hipertensão Essencial , Feminino , Transtornos do Metabolismo de Glucose/complicações , Teste de Tolerância a Glucose , Humanos , Hipertensão/complicações , Masculino , Pessoa de Meia-Idade , Fatores de RiscoRESUMO
BACKGROUND: Immune thrombocytopenic (ITP) is an autoimmune bleeding disease with genetic susceptibility. Twenty newly diagnosed active primary ITP patients who had not been treated with glucocorticosteroids, immune globulin or immunosuppressants prior to sampling were enrolled in this study. Bone marrow blood mononuclear cells were used for whole exome sequencing to further elucidation the variant genes of ITP. METHODS: High-molecular-weight genomic DNA was extracted from freshly frozen bone marrow blood mononuclear cells from 20 active ITP patients. Next, the samples were subjected to molecular genetic analysis by whole-exome sequencing, and the results were confirmed by Sanger sequencing. The signaling pathways and cellular processes associated with the mutated genes were identified with gene ontology and Kyoto Encyclopedia of Genes and Genomes pathway analyses. RESULTS: The results showed that there were 3998 missense mutations involving 2269 genes in more than 10 individuals. Unique genetic variants including phosphatase and tensin homolog, insulin receptor, and coagulation factor C homology were the most associated with the pathogenesis of ITP. Functional analysis revealed these mutation genes mainly affect Phosphatidylinositol 3 kinase/serine/threonine kinase B signaling pathways (signal transduction) and platelet activation (immune system). CONCLUSION: Our finding further demonstrates the functional connections between these variant genes and ITP. Although the substantial mechanism and the impact of genetic variation are required further investigation, the application of next generation sequencing in ITP in this paper is a valuable method to reveal the genetic susceptibility.
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Púrpura Trombocitopênica Idiopática , Trombocitopenia , Humanos , Proteínas Proto-Oncogênicas c-akt/genética , Fosfatidilinositol 3-Quinases/genética , Predisposição Genética para Doença , Transdução de Sinais/genética , MutaçãoRESUMO
Soil fungal community structure and diversity are highly sensitive to variations in the external environment, as well as soil improvement measures. In order to clarify the effects of soil improvement measures on topsoil fertility or quality, a field experiment was conducted in eroded forest of a red soil region. Organic fertilizer, biochar, and lime+microbial fertilizer were added to the topsoil, respectively. After four years, the chemistry properties and nutrients in the topsoil were measured, and the diversity and composition of fungi were analyzed. The results showed that the additions of organic fertilizer, biochar, and lime+microbial fertilizer reduced fungal richness in topsoil, compared to that with no fertilizer addition (CK). Among them, lime+microbial fertilizer had the most negative effect on fungal richness. The three soil improvement measures also affected the diversity of topsoil fungi, but the impacts were not significant. The dominant fungal phyla in the topsoil were Ascomycota (31.29%-46.55%) and Basidiomycota (30.07%-70.71%), and the dominant fungal genera were Amphinema and Archaeorhizomyces. The effects of soil improvement measures on fungal community structure in the topsoil were different; organic fertilizer increased the relative abundance of Ascomycetes and Archaeopteroides, and biochar enhanced the relative abundance of Basidiomycetes and Archaeopteroides, whereas lime+microbial fertilizer improved the relative abundance of Basidiomycetes and Archaeopteroides. Fungal diversity and community structure in the topsoil was affected by edaphic factors, and fungal richness was regulated by pH value, whereas fungal community structure was influenced by pH, total nitrogen, and organic carbon. This study provides scientific guidance for soil improvement and ecological restoration below the canopy in eroded forests of red soil regions.
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Micobioma , Solo , Solo/química , Florestas , Microbiologia do SoloRESUMO
BACKGROUND: Eosinophilic fasciitis (EF) is a rare connective tissue disease that can cause swelling and sclerosis of the extremities, and special attention is needed to differentiate EF from systemic sclerosis. Misdiagnosis or omission markedly delays treatment of EF, and severe skin sclerosis in advanced stages can cause joint contracture and tendon retraction, worsening the patient's prognosis and quality of life. CASE SUMMARY: We report a case of EF in a young woman diagnosed by tissue biopsy, confirming the difficulty of differential diagnosis with scleroderma. CONCLUSION: Focusing on skin manifestations, completing tissue biopsy and radiography can help diagnose EF effectively. Clinicians should enhance their understanding of the differences between EF and scleroderma, and early diagnosis and standardized treatment can improve the prognosis of patients with EF.
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Vasorelaxant properties of N-2-(ferulamidoethyl)-nitrate (ferulate nitrate, FLNT), a newly synthesized nitrate, were compared with those of isosorbide dinitrate, nicorandil, nitroglycerin, and 8-bromoguanosine 3,5-cyclic monophosphate (8-Br-cGMP) in rat aorta pre-contracted by phenylephrine. FLNT produced vasorelaxation in a concentration-dependent manner (0.1 - 100 µM). The degree of relaxation induced by FLNT was similar to that induced by isosorbide dinitrate. In addition, removal of endothelium did not affect the relaxant effect of FLNT. FLNT caused a rightward shift of the cumulative concentration-response curves of phenylephrine and reduced the maximal efficacy of contraction. 1H-[1,2,4]Oxadiazolo-[4,3-a]quinoxalin-1-one (ODQ, 10 µM) and K(+)-channel blockers charybdotoxin (CHT, 0.1 µM) and BaCl(2) (1 µM) reduced the relaxant effect of FLNT in the endothelium-denuded arteries, whereas glibenclamide (1 µM) and 4-aminopyridine (1 mM) failed to influence FLNT-induced vasorelaxation. Furthermore, in the presence of ODQ, both CHT (0.1 µM) and BaCl(2) (1 µM) still significantly reduced the relaxation evoked by FLNT. Pretreatment of vessels with hydroxocobalamin, a nitric oxide scavenger, abolished the FLNT effect. These findings demonstrate that FLNT induces relaxation of the rat aorta rings endothelium-independently. Furthermore, we demonstrated that FLNT-induced vasorelaxation is related to its stimulation of soluble guanylate cyclase and activation of K(+) channels.
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Aorta Torácica/efeitos dos fármacos , Aorta Torácica/enzimologia , Ácidos Cumáricos/farmacologia , Endotélio Vascular/efeitos dos fármacos , Endotélio Vascular/enzimologia , Guanilato Ciclase/fisiologia , Canais de Potássio/fisiologia , Vasodilatação/efeitos dos fármacos , Animais , Aorta Torácica/metabolismo , Endotélio Vascular/metabolismo , Masculino , Técnicas de Cultura de Órgãos , Ratos , Ratos Wistar , Vasodilatação/fisiologiaRESUMO
Acute viral myocarditis (AVMC) is characterized by virus-triggered myocardial inflammation, and Coxsackievirus B3 (CVB3) is the primary pathogen. We previously proved that Th17 cells, besides having proinflammatory effects, were involved in AVMC by enhancing humoral response. However, the relationship between Th17 cells and CVB3 replication remains unknown. In this experiment, we infected BALB/c mice with CVB3 for establishing AVMC models and then found that, with the increase of viral replication, the expressions of splenic Th17 cells, serum IL-17, and cardiac IL-17 mRNA were elevated significantly, accompanied by the progressive cardiac injuries of AVMC. Furthermore, on day 5, the peak time for viral replication, correlation was positive between cardiac IL-17 mRNA and CVB3 RNA (correlation index = 0.835; p < 0.01). Although the expressions of Th1 and CD8(+) T cells, which could secrete the antiviral cytokine IFN-γ and damage the heart, were also elevated, along with Th17 cells, in AVMC, the neutralization of IL-17 further upregulated the percentages of splenic Th1 and CD8(+) T cells and the levels of cardiac IFN-γ mRNA. The cardiac pathological changes were obviously improved after neutralization, with reduced viral replication followed by decreases in the cardiac inflammatory cytokines IL-17, TNF-α, and IL-1ß. These data suggest that Th17 cells contribute to CVB3 replication in AVMC, and that IL-17 might be an important target for regulating the balance of antiviral immunities.
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Infecções por Coxsackievirus/imunologia , Interleucina-17/imunologia , Miocardite/imunologia , Subpopulações de Linfócitos T/imunologia , Linfócitos T Auxiliares-Indutores/imunologia , Replicação Viral/imunologia , Animais , Western Blotting , Separação Celular , Infecções por Coxsackievirus/metabolismo , Infecções por Coxsackievirus/patologia , Enterovirus Humano B/fisiologia , Citometria de Fluxo , Interleucina-17/metabolismo , Masculino , Camundongos , Camundongos Endogâmicos BALB C , Miocardite/patologia , Miocardite/virologia , RNA Mensageiro/análise , Reação em Cadeia da Polimerase Via Transcriptase Reversa , Subpopulações de Linfócitos T/metabolismo , Linfócitos T Auxiliares-Indutores/metabolismoRESUMO
In the title complex, [La(C7H4BrO3)Cl2(C12H8N2)](n), the La(III) ion is eight-coordinated by two carboxyl-ate O atoms from two 5-bromo-salicylate ligands, two N atoms from a chelating 1,10-phenanthroline ligand and four bridging Cl atoms in a distorted square-anti-prismatic geometry. The La(III) ions are linked by bridging carboxyl-ate groups and chloride anions into a chain along [100]. An intra-molecular O-Hâ¯O hydrogen bond is formed in the 5-bromo-salicylate ligand. π-π inter-actions between the pyridine and benzene rings and between the benzene rings are observed [centroid-centroid distances = 3.794â (5) and 3.804â (4)â Å].
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Azahetereocycles constitute important structural components in many biologically active natural compounds and marketed drugs, and represent the most promising scaffolds in drug discovery. Accordingly, the development of efficient and general synthetic methods for the construction of diverse azaheterocycles is the major goal in synthetic chemistry. Herein, we report the efficient construction of a wide range of azaheterocycles via a Pd-catalyzed migratory cycloannulation strategy with unactivated alkenes. This strategy enables the rapid synthesis of a series of 6-, 7- and 8-membered azaheterocycles in high efficiency, and features a broad substrate scope, excellent functional group tolerance under redox-neutral conditions. The significance of this finding is demonstrated by the efficient synthesis of drug-like molecules with high step-economy. Preliminary mechanistic investigations reveal that this reaction underwent a sequentially migratory insertion to alkenes, metal migration process, and the aza-Michael addition to a quinone methide intermediate.
Assuntos
Alcenos , Paládio , Catálise , Estrutura MolecularRESUMO
Methylglyoxal (MG) is a novel signaling molecule with multiple functions in plants. To explore the effects of MG on Chinese chestnut (Castanea mollissima) under drought stress, two-year-old 'Huangpeng' chestnut seedlings were treated with 15% polyethylene glycol (PEG) coupled with MG or its scavenger N-acetyl-L-cys-teine (NAC). We measured the activities of antioxidant enzymes, including superoxide dismutase (SOD), peroxidase (POD), catalase (CAT), ascorbate peroxidase (APX) and glutathione reductase (GR), and glyoxalase enzymes, including glyoxalase â (Glyâ ) and glyoxalase â ¡(Glyâ ¡). Contents of antioxidants such as endogenous MG, malondialdehyde (MDA), H2O2, and O2-· as well as the osmotic adjustment substances including proline (Pro), soluble sugar (SS), glycine betaine (GB) were also detected. The results showed that 0.5 mmol·L-1 MG significantly increased the activities of antioxidant enzymes (SOD, POD, CAT, APX, GR) and glyoxalase enzymes (Glyâ , Glyâ ¡) in leaves of chestnut seedlings under drought stress, elevated the contents of osmotic adjustment substances (Pro, SS, GB) and antioxidant substances (ASA, GSH), and reduced the contents of MG, MDA, H2O2, O2-· and dehydroascorbate (DHA). Drought stress induced damages such as membrane lipid peroxidation and osmotic stress was alleviated by MG, leading to an overall improved adaptability of chestnut to drought stress. Moreover, the addition of MG scavenger NAC could reverse the effects induced by MG, indicating that MG had positive impacts on drought resistance of chestnut plants. Our study provided a theoretical basis for further exploring the mechanism of MG in alleviating drought stress induced symptoms in chestnut.