RESUMO
Previous studies have highlighted the toxicity of pharmaceuticals and personal care products (PPCPs) in plants, yet understanding their spatial distribution within plant tissues and specific toxic effects remains limited. This study investigates the spatial-specific toxic effects of carbamazepine (CBZ), a prevalent PPCP, in plants. Utilizing desorption electrospray ionization mass spectrometry imaging (DESI-MSI), CBZ and its transformation products were observed predominantly at the leaf edges, with 2.3-fold higher concentrations than inner regions, which was confirmed by LC-MS. Transcriptomic and metabolic analyses revealed significant differences in gene expression and metabolite levels between the inner and outer leaf regions, emphasizing the spatial location's role in CBZ response. Notably, photosynthesis-related genes were markedly downregulated, and photosynthetic efficiency was reduced at leaf edges. Additionally, elevated oxidative stress at leaf edges was indicated by higher antioxidant enzyme activity, cell membrane impairment, and increased free fatty acids. Given the increased oxidative stress at the leaf margins, the study suggests using in situ Raman spectroscopy for early detection of CBZ-induced damage by monitoring reactive oxygen species levels. These findings provide crucial insights into the spatial toxicological mechanisms of CBZ in plants, forming a basis for future spatial toxicology research of PPCPs.
Assuntos
Carbamazepina , Carbamazepina/toxicidade , Folhas de Planta/efeitos dos fármacos , Estresse Oxidativo , MultiômicaRESUMO
The actual DOM in Chaohu Lake was used to feed cyanobacterial to explore the changes of microbial communities, fluorescence spectral characteristics and molecular composition of DOM during the degradation of cyanobacteria. It is found that cyanobacterial grow periodically depending on the concentration of nutrients with the decreasing concentration of nutrient salts. Both Bacteroidetes and Actinobacteria have strong correlation with algae growth. Bacteroidetes has a positive correlation with algae growth, relationship on the contrary, Actinobacteria has a negative relationship. The humus-like components in the four groups are similar, but the protein-like component (C3) shows periodic changes with the life process of cyanobacteria. The average molecular weight of each sample detected by Orbitrap high-resolution mass spectrometer increases slightly and the DOM increase aromaticity in the end. In this study, the molecule of Carboxyl-Rich Alicyclic Molecules (CRAM) is difficult to be done by photodegradation and biodegradation in the early periods, but some molecules of CRAM are selectively degraded by microorganisms in the final period. The growth of cyanobacterial lead to increasing the concentration of protein-like and carbohydrate-like molecule of DOM in the water. In the final stage, the molecule group of CHO disappear significantly and the molecule group of heteroatomic group increase.
Assuntos
Actinobacteria , Cianobactérias , Matéria Orgânica Dissolvida , Lagos , ChinaRESUMO
Endoplasmic reticulum (ER) stress plays an important role in metabolic diseases like obesity and type 2 diabetes mellitus (T2DM), although the underlying mechanisms and regulatory pathways remain to be elucidated. Here, we induced chronic low-grade ER stress in lean mice to levels similar to those in high-fat diet (HFD)-fed obese mice and found that it promoted hyperglycemia due to enhanced hepatic gluconeogenesis. Mechanistically, sustained ER stress up-regulated the deubiquitinating enzyme ubiquitin-specific peptidase 14 (USP14), which increased the stability and levels of 3',5'-cyclic monophosphate-responsive element binding (CREB) protein (CBP) to enhance glucagon action and hepatic gluconeogenesis. Exogenous overexpression of USP14 in the liver significantly increased hepatic glucose output. Consistent with this, liver-specific knockdown of USP14 abrogated the effects of ER stress on glucose metabolism, and also improved hyperglycemia and glucose intolerance in obese mice. In conclusion, our findings show a mechanism underlying ER stress-induced disruption of glucose homeostasis, and present USP14 as a potential therapeutic target against T2DM.
Assuntos
Estresse do Retículo Endoplasmático/fisiologia , Glucagon/metabolismo , Hiperglicemia/patologia , Obesidade/patologia , Ubiquitina Tiolesterase/metabolismo , Animais , Diabetes Mellitus Tipo 2/patologia , Dieta Hiperlipídica/efeitos adversos , Retículo Endoplasmático/patologia , Técnicas de Silenciamento de Genes , Gluconeogênese/fisiologia , Glucose/metabolismo , Intolerância à Glucose/genética , Camundongos , Camundongos Endogâmicos C57BL , Camundongos Obesos , Ubiquitina Tiolesterase/genéticaRESUMO
Chronic myeloid leukemia (CML) is associated with chromosomal translocation t(9; 22), which results in formation of the BCR-ABL oncogene. CML is treated with tyrosine kinase inhibitors (TKIs), which target BCR-ABL, to eradicate BCR-ABL + cells. However, the TKI imatinib (IM) fails to eliminate quiescent leukemia stem cells (LSCs) in CML. In this study, we demonstrate that transcription factor TAL1 is down-regulated in CML LSCs by BCR-ABL, and IM triggers TAL1 mRNA expression. In addition, loss of TAL1 abrogates IM-induced CML cell apoptosis. RNA-seq analysis suggests that TAL1 expression may affect PI3K/AKT pathway. Moreover, depletion of TAL1 inhibits the expression of PTEN, which is a negative regulator of the PI3K/AKT pathway. Our results reveal an unexpected involvement of TAL1 in CML etiology and demonstrate that TAL1 may regulate PTEN expression and lead to inhibition of the PI3K/AKT pathway in the response of CML cells to TKI. These results implicate regulation of PTEN expression as a novel mechanism for the transcriptional regulatory networks of TAL1 in CML.
Assuntos
Antineoplásicos/farmacologia , Apoptose/efeitos dos fármacos , Mesilato de Imatinib/farmacologia , Leucemia Mielogênica Crônica BCR-ABL Positiva/tratamento farmacológico , Inibidores de Proteínas Quinases/farmacologia , Proteína 1 de Leucemia Linfocítica Aguda de Células T/metabolismo , Células Cultivadas , Humanos , Leucemia Mielogênica Crônica BCR-ABL Positiva/metabolismo , Leucemia Mielogênica Crônica BCR-ABL Positiva/patologia , PTEN Fosfo-Hidrolase/metabolismo , Fosfatidilinositol 3-Quinases/metabolismo , Proteínas Proto-Oncogênicas c-akt/metabolismo , RNA Mensageiro/genética , RNA Mensageiro/metabolismo , Proteína 1 de Leucemia Linfocítica Aguda de Células T/deficiência , Proteína 1 de Leucemia Linfocítica Aguda de Células T/genéticaRESUMO
Four new hybrid peptide-polyketide cyclic tridepsipeptides, colletopeptides A-D (1-4), were isolated and characterized from the endophytic fungus Colletotrichum sp. S8 derived from the stems of Rubia podantha with the guidance of LC-UV-MS detection. Their structures were elucidated by extensive spectroscopic analysis and X-ray crystallography. Compounds 1-4 are rare natural 12-membered cyclic tridepsipeptides containing a 3,5,11-trihydroxy-2-methyl dodecanoic acid unit in their structures. 1-4 inhibited lipopolysaccharide-induced nitric oxide production in RAW264.7 macrophages with the IC50 values of 8.3, 38.7, 13.5, and 22.2 µM, respectively. 1 also inhibited the production of inflammatory factors IL-6 and TNF-α, and decreased the phosphorylation of NF-κB-associated proteins IκBα and p65.
Assuntos
Anti-Inflamatórios/farmacologia , Colletotrichum/química , Depsipeptídeos/farmacologia , Lipopolissacarídeos/farmacologia , Macrófagos/química , Inibidor de NF-kappaB alfa/metabolismo , NF-kappa B/química , Óxido Nítrico/biossíntese , Fator de Necrose Tumoral alfa/química , Anti-Inflamatórios/química , Depsipeptídeos/química , Depsipeptídeos/isolamento & purificação , Lipopolissacarídeos/química , Macrófagos/metabolismo , Estrutura Molecular , Inibidor de NF-kappaB alfa/química , NF-kappa B/metabolismo , Fosforilação , Fator de Necrose Tumoral alfa/metabolismoRESUMO
Using the TLC cyclopeptide protosite detection method, a new cyclohexapeptide named rubipodanin B (1), together with 11 known Rubiaceae-type cyclopeptides (RAs), RA-X-OMe (2), RA-IV (3), RA-XI (4), RA-XIII-OMe (5), rubiyunnanin C (6), RA-I (7), RA-III (8), RA-V (9), RA-VII (10), RA-XII (11) and rubipodanin A (12), were obtained from the roots and rhizomes of Rubia podantha Diels. The structures were determined using various spectroscopic methods. Among them, 2 was firstly identified as a natural product, and 3-6 were firstly isolated from this species. Cytotoxicity and NF-κB signaling pathway activity of 1, 2, 4, 6, 7 and 9 were evaluated. All these compounds showed cytotoxic activities against three human tumor cell lines, MDA-MB-231, SW620 and HepG2, with the IC50 values between 0.015 and 10.27â µm, and only 7 and 9 possessed NF-κB inhibitory activities with the IC50 values of 2.42 and 0.046â µm, respectively, which demonstrated that 2-alanine amino acid plays a key role to maintain the RAs bioactivity.
Assuntos
Antineoplásicos Fitogênicos/isolamento & purificação , Antineoplásicos Fitogênicos/farmacologia , Peptídeos Cíclicos/isolamento & purificação , Peptídeos Cíclicos/farmacologia , Rubia/química , Espectroscopia de Ressonância Magnética Nuclear de Carbono-13 , Linhagem Celular Tumoral , Ensaios de Seleção de Medicamentos Antitumorais , Humanos , Concentração Inibidora 50 , NF-kappa B/metabolismo , Raízes de Plantas/química , Espectroscopia de Prótons por Ressonância Magnética , Rizoma/química , Transdução de Sinais , Espectrometria de Massas por Ionização por ElectrosprayRESUMO
BACKGROUND: Vitamin D deficiency was reported to be associated with diabetic peripheral neuropathy. But the association in Chinese population and the screening value of vitamin D deficiency for diabetic peripheral neuropathy were unknown. METHODS: A total of 861 patients with type 2 diabetes were recruited in this cross-sectional study. Vitamin D deficiency was defined as serum circulating 25-hydroxyvitamin D(25(OH)D) level < 20 ng/mL. Peripheral neuropathy was evaluated by neurological symptoms, neurological signs, neurothesiometer and electromyogram. RESULTS: The patients with diabetic peripheral neuropathy had significantly lower serum 25(OH)D concentration (15.59 ± 7.68 ng/mL) and higher prevalence of vitamin D deficiency (80%) than patients with signs of diabetic peripheral neuropathy (17.66 ± 7.50 ng/mL; 64.5%) and non-DPN patients (18.35 ± 6.60; 61.7%) (all p < 0.01). Spearman's correlation analysis showed that serum circulating 25(OH)D level was closely associated with DPN (r = 0.121) and signs of DPN (r = 0.111) (both p < 0.01). After adjusting for all potential confounders, VDD was still linked with increased risk of DPN [odds ratio 2.59 (1.48-4.53)] (p < 0.01). Logistical regression analysis further revealed that VDD was an independent risk factor for DPN (ß = 0.88) (p < 0.01). Receiver operating characteristic analysis indicated that serum 25(OH)D < 17.22 ng/mL hinted the signs of DPN and serum 25(OH)D < 16.01 ng/mL predicted the occurrence of DPN (both p < 0.01). CONCLUSIONS: Vitamin D deficiency is an independent risk factor for diabetic peripheral neuropathy and may be a potential biomarker for peripheral neuropathy in Chinese patients with type 2 diabetes. Copyright © 2016 John Wiley & Sons, Ltd.
Assuntos
Diabetes Mellitus Tipo 2/fisiopatologia , Neuropatias Diabéticas/etiologia , Deficiência de Vitamina D/complicações , Idoso , Estudos Transversais , Feminino , Seguimentos , Humanos , Masculino , Pessoa de Meia-Idade , Prognóstico , Curva ROC , Fatores de RiscoRESUMO
OBJECTIVE: To investigate the relationship between the serum level of miR-9 and the progression of diabetic nephropathy (DN) and related molecular mechanisms. RESULTS: Thirty-five healthy subjects and 140 DN patients were divided into five groups: control, DN I-II, DN III, DN IV and DN V. Serum level of miR-9 was measured by real-time qPCR. Serum levels of vascular endothelial growth factor (VEGF), pigment epithelium-derived factor (PEDF) lipids, fasting glucose, insulin, hemoglobin A1c (HBA1c), creatinine, fibrinogen and insulin resistance (HOMA-IR) were also measured. The results show that the levels of miR-9, PEDF and VEGF are increased with DN progression (P < 0.05). miR-9, VEGF and PEDF are independent risk factors of DN (R2 = 0.430). Spearman rank correlation analysis showed that miR-9 level is positively related to the levels of VEGF, PEDF, cholesterol, triglyceride, fasting glucose, fasting insulin, HBA1c, creatinine, fibrinogen and HOMA-IR (P < 0.05). CONCLUSIONS: Serum miR-9 is a potential marker for conferring a poor prognosis in DN and associated with the levels of VEGF, PEDF and biochemical indices.
Assuntos
Nefropatias Diabéticas/genética , Proteínas do Olho/sangue , MicroRNAs/sangue , Fatores de Crescimento Neural/sangue , Serpinas/sangue , Fator A de Crescimento do Endotélio Vascular/sangue , Adulto , Idoso , Idoso de 80 Anos ou mais , Creatinina/sangue , Nefropatias Diabéticas/sangue , Feminino , Hemoglobinas Glicadas/metabolismo , Humanos , Resistência à Insulina , Masculino , Pessoa de Meia-Idade , Prognóstico , Triglicerídeos/sangue , Regulação para CimaRESUMO
We investigated the relationship between serum cystatin C levels and the prognosis of diabetic foot ulcerations (DFU). A population-based cohort study involving 1018 patients with type 2 diabetes was conducted. These patients recruited and divided into two groups: nondiabetic foot ulcer group (NDF, n = 865, 85.5%) and diabetic foot ulcer group (DFU, n = 147, 14.5%).After a 1-year-follow-up, DFUs were grouped into healing (n = 110, 74.8%) and nonhealing (n = 37, 25.2%) group based on the clinical prognosis. Compared with the healing group, the nonhealing group were older, had long diabetic duration and had significantly increased serum cystatin C concentrations in DFU (p < 0.01). After adjustments for age, diabetes duration, renal function and infection control, multiple logistical regression analysis revealed that cystatin C remained associated increased risk of undesirable DFU outcome (OR = 7.279, 95% CI: 1.299-40.784, p < 0.05). When divided into quartiles according to cystatin C levels, the healing rate of Quartile 4 was significantly lower (57.9%) compared with other groups (p < 0.01). The odd is ratio (OR) analysis showed that the risk of undesirable DFU outcome in Quartile 4 was significantly higher (OR = 4.554, 95% CI: 3.14-5.12, p < 0.05) compared with that in Quartile 1. We concluded that there was a strong and independent association between serum cystatin C and diabetic foot ulceration prognosis, cystatin C > 1.35 mg/L predicts more than sixfold increased risk of incurable foot ulceration.
Assuntos
Cistatina C/sangue , Pé Diabético/sangue , Pé Diabético/diagnóstico , Idoso , Povo Asiático , Biomarcadores/sangue , China/epidemiologia , Pé Diabético/fisiopatologia , Feminino , Seguimentos , Humanos , Masculino , Pessoa de Meia-Idade , Exame Físico , Valor Preditivo dos Testes , Prognóstico , Estudos Prospectivos , Fatores de Risco , Cicatrização/fisiologiaRESUMO
BACKGROUND: Fibroblast growth factor 21 (FGF21) is an emerging metabolic regulator associated with glucose and lipid metabolism, and it is still unclear whether FGF21 is related to atherosclerosis. Here, we explored the potential link between FGF21 and lower extremity atherosclerotic disease (LEAD) in type 2 diabetic patients. METHODS: A cross-sectional study was conducted on 504 type 2 diabetic patients (283 men, 221 women). LEAD was defined by Ankle-brachial index (ABI) <0.9 and lower extremity arterial plaque evaluated by color Doppler ultrasound. Serum FGF21 concentrations were quantified by a sandwich enzyme-linked immunosorbent assay. RESULTS: The total FGF21 levels of male and female patients had no significant differenence ((299.14(177.31-534.49) vs 362.50(214.01-578.73), P=0.516). Serum FGF21 levels in LEAD group were significantly higher than non-LEAD group in females (385.34(243.89-661.54) vs 313.13(156.38-485.79), P=0.006), while not in male patients (295.52(177.09-549.64) vs 342.09 (198.70-549.87), P=0.613). In diabetic women, subjects with LEAD had significantly higher serum FGF21 regardless of non-alcoholic fatty liver disease (NAFLD) (P < 0.05). And serum FGF21 levels were positively correlated with waist circumference and systolic blood pressure after adjusted for age and BMI (r=0.198, P=0.004; r=0.152, P=0.027; respectively). Moreover, FGF21 was independently tied to femoral intima-media thickness (FIMT) (ß=0.208, P=0.031). After adjusted for other LEAD risk factors, FGF21 was demonstrated to be an independent risk factor for LEAD in type 2 diabetic women (OR, 1.106; 95%CI 1.008-1.223; P=0.028). In addition, FGF21 was negatively correlated with estradiol in premenopausal diabetic women (r=-0.368, P=0.009). After adjusted for estradiol, serum FGF21 levels were still positively associated with FIMT in premenopausal diabetic women (r=0.381, P=0.007). In diabetic men, serum FGF21 levels were correlated with triglyceride and C-reactive protein even after adjusted for age and BMI (r=0.204, P=0.001; r=0.312, P < 0.001; respectively). However, serum FGF21 was not an independent impact factor for LEAD in men (P > 0.05). CONCLUSIONS: Serum FGF21 level independently and positively links LEAD in Chinese women with type 2 diabetes. The gender difference may be due to different estrogen levels.
Assuntos
Povo Asiático , Aterosclerose/sangue , Diabetes Mellitus Tipo 2/sangue , Fatores de Crescimento de Fibroblastos/sangue , Extremidade Inferior , Caracteres Sexuais , Idoso , Aterosclerose/diagnóstico , Aterosclerose/epidemiologia , Biomarcadores/sangue , Estudos Transversais , Diabetes Mellitus Tipo 2/diagnóstico , Diabetes Mellitus Tipo 2/epidemiologia , Feminino , Humanos , Extremidade Inferior/patologia , Masculino , Pessoa de Meia-IdadeRESUMO
OBJECTIVE: We investigated the relationship between vibration perception threshold and diabetic retinopathy and verified the screening value of vibration perception threshold for severe diabetic retinopathy. METHODS: A total of 955 patients with type 2 diabetes were recruited and divided into three groups according to their fundus oculi photography results: no diabetic retinopathy (n = 654, 68.48%), non-sight-threatening diabetic retinopathy (n = 189, 19.79%) and sight-threatening diabetic retinopathy (n = 112, 11.73%). Their clinical and biochemical characteristics, vibration perception threshold and the diabetic retinopathy grades were detected and compared. RESULTS: There were significant differences in diabetes duration and blood glucose levels among three groups (all p < 0.05). The values of vibration perception threshold increased with the rising severity of retinopathy, and the vibration perception threshold level of sight-threatening diabetic retinopathy group was significantly higher than both non-sight-threatening diabetic retinopathy and no diabetic retinopathy groups (both p < 0.01). The prevalence of sight-threatening diabetic retinopathy in vibration perception threshold >25 V group was significantly higher than those in 16-24 V group (p < 0.01). The severity of diabetic retinopathy was positively associated with diabetes duration, blood glucose indexes and vibration perception threshold (all p < 0.01). Multiple stepwise regression analysis proved that glycosylated haemoglobin (ß = 0.385, p = 0.000), diabetes duration (ß = 0.275, p = 0.000) and vibration perception threshold (ß = 0.180, p = 0.015) were independent risk factors for diabetic retinopathy. Receiver operating characteristic analysis further revealed that vibration perception threshold higher than 18 V was the optimal cut point for reflecting high risk of sight-threatening diabetic retinopathy (odds ratio = 4.20, 95% confidence interval = 2.67-6.59). CONCLUSION: There was a close association between vibration perception threshold and the severity of diabetic retinopathy. vibration perception threshold was a potential screening method for diabetic retinopathy, and its optimal cut-off for prompting high risk of sight-threatening retinopathy was 18 V.
Assuntos
Diabetes Mellitus Tipo 2/complicações , Retinopatia Diabética/diagnóstico , Programas de Rastreamento/métodos , Percepção do Tato/fisiologia , Vibração , Idoso , Cegueira/etiologia , Cegueira/prevenção & controle , Diabetes Mellitus Tipo 2/diagnóstico , Diabetes Mellitus Tipo 2/fisiopatologia , Retinopatia Diabética/etiologia , Retinopatia Diabética/fisiopatologia , Técnicas de Diagnóstico Endócrino , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Pacientes Ambulatoriais , Índice de Gravidade de DoençaRESUMO
Micro(nano)plastics widely detected in aquatic environments have caused serious threat to water quality security. However, as a potential important source of micro(nano)plastics in surface water during the COVID-19 pandemic, the ecological risks of face mask waste to aquatic environments remain poorly understood. Herein, we comprehensively characterized the micro(nano)plastics and organic compounds released from four daily used face masks in aqueous environments and further evaluated their potential impacts on aquatic ecosystem safety by quantitative genotoxicity assay. Results from spectroscopy and high-resolution mass spectrum showed that plastic microfibers/particles (â¼11%-83%) and leachable organic compounds (â¼15%-87%) were dominantly emitted pollutants, which were significantly higher than nanoplastics (< â¼5%) based on mass of carbon. Additionally, a toxicogenomics approach using green fluorescence protein-fused whole-cell array revealed that membrane stress was the primary response upon the exposure to micro(nano)plastics, whereas the emitted organic chemicals were mainly responsible for DNA damage involving most of the DNA repair pathways (e.g., base/nucleotide excision repair, mismatch repair, double-strand break repair), implying their severe threat to membrane structure and DNA replication of microorganisms. Therefore, the persistent release of discarded face masks derived pollutants might exacerbate water quality and even adversely affect aquatic microbial functions. These findings would contribute to unraveling the potential effects of face mask waste on aquatic ecosystem security and highlight the necessity for more developed management regulations in face mask disposal.
Assuntos
COVID-19 , Poluentes Ambientais , Poluentes Químicos da Água , Humanos , Ecossistema , Plásticos/toxicidade , Máscaras , Pandemias , Toxicogenética , Compostos Orgânicos , Poluentes Químicos da Água/análiseRESUMO
BACKGROUND: Acute myeloid leukemia (AML) is an aggressive heterogeneous hematological malignancy with remarkably heterogeneous outcomes. This study aimed to identify potential biomarkers for AML risk stratification via analysis of gene expression profiles. METHODS: RNA sequencing data from 167 adult AML patients in the Cancer Genome Atlas (TCGA) database were obtained for overall survival (OS) analysis, and 52 bone marrow (BM) samples from our clinical center were used for validation. Additionally, siRNA was used to investigate the role of prognostic genes in the apoptosis and proliferation of AML cells. RESULTS: Co-expression of 103 long non-coding RNAs (lncRNAs) and mRNAs in the red module that were positively correlated with European Leukemia Network (ELN) risk stratification and age was identified by weighted gene co-expression network analysis (WGCNA). After screening by uni- and multivariate Cox regression, Kaplan-Meier survival, and protein-protein interaction analysis, four genes including the lncRNA LOC541471, GDAP1, SOD1, and STK25 were incorporated into calculating a risk score from coefficients of the multivariate Cox regression model. Notably, GDAP1 expression was the greatest contributor to OS among the four genes. Interestingly, the risk score, ELN risk stratification, and age were independent prognostic factors for AML patients, and a nomogram model constructed with these factors could illustrate and personalize the 1-, 3-, and 5-year OS rates of AML patients. The calibration and time-dependent receiver operating characteristic curves (ROCs) suggested that the nomogram had a good predictive performance. Furthermore, new risk stratification was developed for AML patients based on the nomogram model. Importantly, knockdown of LOC541471, GDPA1, SOD1, or STK25 promoted apoptosis and inhibited the proliferation of THP-1 cells compared to controls. CONCLUSIONS: High expression of LOC541471, GDAP1, SOD1, and STK25 may be biomarkers for risk stratification of AML patients, which may provide novel insight into evaluating prognosis, monitoring progression, and designing combinational targeted therapies.
Assuntos
Leucemia Mieloide Aguda , RNA Longo não Codificante , Adulto , Humanos , Superóxido Dismutase-1 , Biomarcadores Tumorais/metabolismo , Leucemia Mieloide Aguda/patologia , Prognóstico , Perfilação da Expressão Gênica , RNA Longo não Codificante/metabolismo , Proteínas Serina-Treonina Quinases/genética , Peptídeos e Proteínas de Sinalização Intracelular/genéticaRESUMO
Objective: It is generally believed that gait characteristics of diabetic neuropathic patients differ from those of non-diabetic ones. However, it is still unclear how the abnormal foot sensation influences the gait during walking in type 2 diabetes mellitus (T2DM). For the purpose of gaining a better insight into the alterations of detailed gait parameters and figuring out important aspects in the gait indexes by peripheral neuropathy in elder T2DM patients, we compared the gait features in participants with normal glucose tolerance (NGT) controls and diabetic individuals complicated by peripheral neuropathy or not. Subjects and methods: Gait parameters were observed during the 10-m walk on flat land among different conditions of diabetes in 1,741 participants from three clinical centers. Subjects were divided into four groups: persons with NGT were taken as the control group; patients with T2DM included three subgroups: DM control (no chronic complications), DM-DPN (DM complicated by only peripheral neuropathy), and DM-DPN+LEAD (DM complicated by both neuropathy and artery disease). The clinical characteristics and gait parameters were assessed and compared among these four groups. Analyses of variance were employed to verify possible differences of gait parameters between groups and conditions. Stepwise multivariate regression analysis was performed to reveal possible predictors of gait deficits. Receiver operating characteristic (ROC) curve analysis was employed to find any discriminatory power of diabetic peripheral neuropathy (DPN) for the step time. Results: In participants burdened with DPN, whether complicated by lower extremity arterial disease (LEAD) or not, step time increased sharply (p < 0.05). Stepwise multivariate regression models showed that independent variables of gait abnormality were sex, age, leg length, vibration perception threshold (VPT), and ankle-brachial index (ABI) (p < 0.01). Meanwhile, VPT was a significant independent predictor of step time, spatiotemporal variability (SDA), and temporal variability (SDB) (p < 0.05). ROC curve analysis was explored to find the discriminatory power of DPN for the occurrence of increased step time. The area under the curve (AUC) value was 0.608 (95% CI: 0.562-0.654, p < 0.01), and the cutoff point was 538.41 ms accompanied by a higher VPT. A significant positive association was observed between increased step time and the highest VPT group [odds ratio (OR) = 1.83, 95% CI: 1.32-2.55, p< 0.01]. In female patients, this OR value elevated to 2.16 (95% CI: 1.25-3.73, p< 0.01). Conclusions: In addition to sex, age, and leg length, VPT was a distinct factor that associated with altered gait parameters. DPN is associated with increased step time, and the step time increases with worsening VPT in type 2 diabetes.
Assuntos
Diabetes Mellitus Tipo 2 , Neuropatias Diabéticas , Doenças Vasculares , Humanos , Feminino , Idoso , Diabetes Mellitus Tipo 2/complicações , Vibração , Percepção , Neuropatias Diabéticas/complicações , Sensação , Marcha , Doenças Vasculares/complicaçõesRESUMO
Dissolved organic matter (DOM) is an abundant and critical component of aquatic ecosystems, participating in many physicochemical and biogeochemical processes. The Paihe River is the only inflow river in the Jianghuai section of "Yangtze-Huaihe water diversion" clear water gallery project; however, its DOM molecular composition information and characteristics are still unclear. In this study, the molecular characterization of DOM in the Paihe River and Guangming Dayan River was determined using Orbitrap mass spectrometry. The Pearson's correlation and principal component analysis (PCA) were used to study the relationship between molecular composition information, characteristics, and sources of DOM in two rivers. The results showed that the molecular weight and oxygen content of DOM molecules in the Paihe River were relatively low; the molecular weight, aromaticity, and unsaturation of DOM molecules in the Guangming Dayan River were relatively high. From the element composition and compound composition of the two rivers' DOM, both rivers were mainly composed of CHO-compounds, lignin, and tannins derived from land plants, which indicates that both rivers were severely affected by terrestrial input. There were high percentages of CHOS, protein, and lipid compounds of DOM in the Paihe River. According to the results of the Pearson's correlation and PCA analyses, the DOM molecules of the Paihe River were also influenced by wastewater from sewage treatment plants, urbanization processes, and microbial activity. Molecular composition information and characteristics of DOM can provide a detailed reference to improve the theoretical support for the Paihe River clear water gallery project.
Assuntos
Matéria Orgânica Dissolvida , Rios , Ecossistema , Urbanização , Qualidade da ÁguaRESUMO
Rubia yunnanensis is an important medicinal plant with various bioactive secondary metabolites. In order to reduce the dependence on wild populations of the species, we aim to establish in vitro culture system that can produce Rubiaceae-type cyclopeptides (RAs) and quinones. Agrobacterium rhizogenes-mediated transformation of stem segments of in vitro grown R. yunnanensis plants using four A. rhizogenes strains was studied and transformation conditions were optimized. Hairy roots appeared with the highest frequency (68.89%) when stem segments (with leaves) without pre-culture were immersed in A. rhizogenes A4 strain bacterial suspension for 30 min, co-cultured on Murashige and Skoog (MS) solid medium in the dark for three days, and afterwards incubated in darkness. PCR analysis of rolB and rolC genes confirmed transformed nature of six hairy root clones. The hairy roots grew rapidly, especially showing the highest accumulation of biomass in MS liquid medium compared to in vitro grown plants and calli. Histological observation of hairy root revealed anatomical difference in vascular cylinder, where the cells exhibited high mitotic activity characterized by vigorous growth. The UPLC-MS/MS analysis revealed that the amount of RAs in the hairy roots grown in ½MS liquid medium (4.611 µg g-1 DW) was higher than that in in vitro grown plants (0.331 and 4.096 µg g-1 DW for shoots and roots respectively) and calli (1.082 µg g-1 DW), but still far lower than that in the roots of seed-borne plants (80.296 µg g-1 DW). However, the hairy roots accumulated high level of quinones (2320.923 and 5067.801 µg g-1 DW for MS and ½MS liquid media respectively), of the same order of magnitude as the roots of seed-borne plants (7409.973 µg g-1 DW). Hairy root culture of R. yunnanensis, with high accumulation of biomass and production of quinones, may offer an attractive perspective for the production of the RAs and quinones that could be further optimized for pharmaceutical use.
Assuntos
Rubia , Rubiaceae , Agrobacterium , Cromatografia Líquida , Meios de Cultura , Peptídeos Cíclicos , Raízes de Plantas , Quinonas , Espectrometria de Massas em TandemRESUMO
Imidazolium based ionic liquids (ILs) have been extensively used in the various industrial fields, however, the dependence of their structure on toxicity and bioavailability by plants is not clear. Thus, in this study, uptake of imidazolium based ILs with different alkyl chain lengths (e.g., [C2mim]+ and [C8mim]+) by ryegrass and their toxicity to plant growth were investigated. Results show that the two ILs could be removed by ryegrass with high efficiencies, and a higher uptake efficiency and accumulation was observed for [C2mim]+ with shorter chain length compared with that for [C8mim]+. A higher growth inhibition of ryegrass by [C8mim]+ was observed compared with that by [C2mim]+, indicating the long alkyl chain length of ILs had a negative effect on the plant growth. ILs taken up by ryegrass was retained in the roots and their translocation from roots to shoots was restricted. The IL concentration in roots was 0.68 mg/g-fresh weight for [C2mim]+ and 0.08 mg/g- fresh weight for [C8mim]+ when the ryegrass was exposed to 10 mg/L ILs. This study proved that plant assimilation of ILs depended on their alky chain lengths, which would be useful for understanding the fate of ILs with various structures in phytoremediation for ILs-contaminated water.
Assuntos
Líquidos Iônicos , Lolium , Biodegradação Ambiental , Transporte Biológico , Imidazóis/toxicidade , Líquidos Iônicos/toxicidadeRESUMO
Ciprofloxacin (CIP), a widely used fluoroquinolone antibiotic, is frequently detected in aqueous environments, and could be assimilated by vegetable plants to possess potential threats to human and animal health through food chains. However, plant uptake of CIP in different chemical speciation has still far from clear now. Thus, the toxicity and uptake of CIP by rice plants were investigated under different solution pH, owing to its contribution to different chemical speciation of CIP. Results display that high pH-driven changes of CIP from cation (CIP+) to anion (CIP-) decreased its adsorption and uptake by excised roots and intact plants, respectively. However, CIP concentrations in roots, stems and leaves all exhibited no significant differences with increasing solution pH. Moreover, six intermediates of CIP were detected and two possible transformation pathways were proposed in rice plants, including firstly oxidation and following consecutive cleavage of piperazine ring. After accumulated in plant tissues, CIP significantly inhibited the plant growth, decreased the photosynthetic pigments contents and enhanced the antioxidant enzyme activities in a concentration-dependent manner. Besides, high pH exacerbated the growth inhibition and changed the oxidative damage responses of rice plants to CIP. These findings indicate that the uptake and toxicity of CIP in rice plants were influenced by solution pH-driven changes of its chemical speciation.
Assuntos
Ciprofloxacina , Oryza , Adsorção , Ciprofloxacina/toxicidade , Fluoroquinolonas , Humanos , ÁguaRESUMO
Investigations on the molecular composition of coal pyrolysis products can help us to improve nonfuel utilization of coal. Meanwhile, the molecular composition of coal pyrolysis products is also influenced by the characteristics and depositional environment of coal. However, due to the extremely complex nature of coal, direct investigation of the molecular composition of coal pyrolysis products is still a challenge. In the present work, the data of the molecular composition of bituminous coal pyrolysis products are obtained by online pyrolysis coupled to comprehensive two-dimensional gas chromatography and mass spectrometry (online py-GC×GC-MS) and are divided into nine molecular groups depending on the aromaticity of the pyrolysis products and separating power of the GC×GC-MS. Chemometric tools, hierarchical cluster analysis, and principal component analysis are employed to reveal the correlations among the molecular composition of coal pyrolysis products and coal characteristics. The results show that the nine molecular groups of bituminous coal pyrolysis products can be divided into two clusters, the "aromatic group" and the "aliphatic group", and that the eight coals are divided into three clusters, all of which can be interpreted by the depositional environments and δ13CVPDB values of coals. Moreover, a simple and empirical equation for estimation of coal tar from hydropyrolysis can be obtained depending on the chemometric results of the molecular composition of the coal pyrolysis products. By application of chemometrics, the molecular composition of coal pyrolysis products can provide preference to industrial utilization of coal.
RESUMO
A high-efficiency approach for the synthesis of molecularly imprinted polymers has been developed and further for the solid-phase extraction of sulfonylurea herbicides in food samples. Molecular simulation approach combined chemometric selected metsulfuron-methyl (MSM) and 2-trifluoromethyl acrylic acid (TFMAA) as the template and the monomer to synthesize the molecularly imprinted polymers (MIPs). Experimental validation confirmed that the MSM-imprinted polymers showed a higher selectivity and affinity to sulfonylurea herbicides. The optimized molecularly imprinted solid-phase extraction (MISPE) conditions, including loading, washing, and eluting conditions, were established. The developed MISPE technology combined HPLC-MSMS was successfully used for the determination of sulfonylurea herbicides in foods. Compared with commercial SPE columns, MISPE showed high affinity, excellent selectivity and low matrix effect. The recoveries of sulfonylurea herbicides spiked in four matrices were between 86.4% and 100.2%, with the relative standard deviations (RSD) in the range of 0.9%-10.5%.