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1.
New Phytol ; 237(1): 177-191, 2023 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-36028981

RESUMO

Global warming has profound impact on growth and development, and plants constantly adjust their internal circadian clock to cope with external environment. However, how clock-associated genes fine-tune thermoresponsive growth in plants is little understood. We found that loss-of-function mutation of REVEILLE5 (RVE5) reduces the expression of circadian gene EARLY FLOWERING 4 (ELF4) in Arabidopsis, and confers accelerated hypocotyl growth under warm-temperature conditions. Both RVE5 and CIRCADIAN CLOCK ASSOCIATED 1 (CCA1) accumulate at warm temperatures and bind to the same EE cis-element presented on ELF4 promoter, but the transcriptional repression activity of RVE5 is weaker than that of CCA1. The binding of CCA1 to ELF4 promoter is enhanced in the rve5-2 mutant at warm temperatures, and overexpression of ELF4 in the rve5-2 mutant background suppresses the rve5-2 mutant phenotype at warm temperatures. Therefore, the transcriptional repressor RVE5 finetunes ELF4 expression via competing at a cis-element with the stronger transcriptional repressor CCA1 at warm temperatures. Such a competition-attenuation mechanism provides a balancing system for modulating the level of ELF4 and thermoresponsive hypocotyl growth under warm-temperature conditions.

2.
Bioresour Technol ; 368: 128266, 2023 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-36351531

RESUMO

A novel biobased composite was developed for the removal of phosphate (P) and atrazine from agricultural wastewater. A composite with strong P affinity and good biocompatibility, synthesized from La3+ and polydopamine (PDA), was immobilized onto an atrazine-degrading bacterium Acinetobacter lwoffii DNS32 (La/PDA/DNS32). Following Box-Behnken design optimization, the maximum removal rate of P (500 mg L-1) and atrazine (100 mg L-1) by La/PDA/DNS32 reached 28 % and 100 %, respectively. Density functional theory calculations revealed that La/PDA had more negative adsorption energy (-5.90 eV) than PDA alone and exhibited prominent electrophilic sites. Additionally, La/PDA-induced sorption of atrazine improved transmembrane transport and enhanced expression of degradation-associated genes in strain DNS32. La/PDA nanoparticles surrounding strain DNS32 provided a shielding effect and exhibited desirable biostability, thermal stability, and acid-alkaline resistance under contamination stress. This study demonstrates the promising potential of La/PDA/DNS32 in reducing the P and atrazine pollution caused by agricultural production.


Assuntos
Atrazina , Lantânio , Adsorção , Fosfatos
3.
Food Chem ; 402: 134232, 2023 Feb 15.
Artigo em Inglês | MEDLINE | ID: mdl-36137374

RESUMO

Noni fruit has certain anti-obesity effect. However, the bioactive ingredients in noni fruit that contribute to anti-obesity activity as well as the relation between its anti-obesity activity and gut microbiota remain unclear. In this study, obese mice induced by high-fat diet (HFD) and were intervened with noni fruit phenolic extract (NFE) for 10 weeks. The results showed NFE supplementation decreased body weight, lipid accumulation in liver andadiposetissues, ameliorated gut microbiota dysbiosis by increasing short-chain fatty acid (SCFA)-producing bacteria and decreasing lipopolysaccharide (LPS)-producing bacteria, and mitigated intestinal inflammation and oxidative stress. Moreover, NFE supplementation improved intestinal barrier dysfunction by elevating the protein expression levels of Claudin-1, Occludin and ZO-1, alleviated the HFD-induced intestinal inflammation by repressing the LPS/TLR4/NF-κB pathway. Collectively, the findings revealed NFE intervention inhibits obesity by improving gut microbiota disorder, barrier function, and inflammation. Hence, NFE may be an effective way to ameliorate HFD-induced damage.


Assuntos
Microbioma Gastrointestinal , Morinda , Camundongos , Animais , Dieta Hiperlipídica/efeitos adversos , Morinda/metabolismo , Lipopolissacarídeos/farmacologia , Frutas/metabolismo , Ocludina/metabolismo , Receptor 4 Toll-Like , NF-kappa B/genética , Claudina-1/farmacologia , Camundongos Endogâmicos C57BL , Obesidade/tratamento farmacológico , Obesidade/genética , Obesidade/metabolismo , Ácidos Graxos Voláteis/metabolismo , Fenóis/farmacologia , Inflamação/tratamento farmacológico , Inflamação/genética , Extratos Vegetais/farmacologia
4.
J Hazard Mater ; 441: 129872, 2023 01 05.
Artigo em Inglês | MEDLINE | ID: mdl-36084461

RESUMO

Decabromodiphenyl ethane (DBDPE), a new brominated flame retardant, could negatively affect neurobehavior and pose health risks to humans. Humans are also exposed to widely used nanomaterials. This study investigated the combined toxic effects and action types of DBDPE and Zinc oxide nanoparticles (ZnO NPs) on human neuroblastoma SK-N-SH cells and the toxicity mechanisms. DBDPE inhibited the viability of SK-N-SH cells by 21.87% at 25 mg/L. ZnO NPs synergistically exacerbated the toxic effects of DBDPE. DBDPE and ZnO NPs caused excessive ROS production and inhibition of antioxidant enzyme (SOD and GSH) activity in cells, thus causing oxidative cellular damage. Moreover, DBDPE and ZnO NPs caused apoptosis by disrupting mitochondrial kinetic homeostasis, reducing mitochondrial membrane potential (MMP), increasing cytochrome C release and regulating Bax/Bcl-2 and Caspase-3 mRNA and protein expression. DBDPE and ZnO NPs increased the mRNA expression of nuclear factor erythroid 2- related factor (Nrf2) and its downstream genes. The molecular mechanisms revealed that oxidative stress, apoptosis and mitochondrial dysfunction were the critical factors in combined cytotoxicity. The bioinformatics analysis further indicated that co-exposure affected Nrf2 activation, apoptotic factors expression and mitochondrial fusion. The findings enrich the risk perception of neurotoxicity caused by DBDPE and ZnO NPs.


Assuntos
Retardadores de Chama , Nanopartículas , Óxido de Zinco , Antioxidantes/metabolismo , Apoptose , Caspase 3/metabolismo , Citocromos c/metabolismo , Retardadores de Chama/metabolismo , Humanos , Mitocôndrias , Fator 2 Relacionado a NF-E2/genética , Fator 2 Relacionado a NF-E2/metabolismo , Nanopartículas/toxicidade , Estresse Oxidativo , RNA Mensageiro/metabolismo , Espécies Reativas de Oxigênio/metabolismo , Transdução de Sinais , Superóxido Dismutase/metabolismo , Óxido de Zinco/toxicidade , Proteína X Associada a bcl-2/metabolismo , Proteína X Associada a bcl-2/farmacologia
5.
Biochim Biophys Acta Mol Basis Dis ; 1869(1): 166569, 2023 Jan 01.
Artigo em Inglês | MEDLINE | ID: mdl-36243293

RESUMO

BACKGROUND: Hippocampus plays critical roles in drug addiction. Cocaine-induced modifications in dopamine receptor function and the downstream signaling are important regulation mechanisms in cocaine addiction. Rac regulates actin filament accumulation while Cdc42 stimulates the formation of filopodia and neurite outgrowth. Based on the region specific roles of small GTPases in brain, we focused on the hippocampal subregions to detect the regulation of Cdc42 signaling in long-term morphological and behavioral adaptations to cocaine. METHODS: Genetically modified mouse models of Cdc42, dopamine receptor D1 (D1R) and D2 (D2R) and expressed Cdc42 point mutants that are defective in binding to and activation of its downstream effector molecules PAK and N-WASP were generated, respectively, in CA1 or dentate gyrus (DG) subregion. RESULTS: Cocaine induced upregulation of Cdc42 signaling activity. Cdc42 knockout or mutants blocked cocaine-induced increase in spine plasticity in hippocampal CA1 pyramidal neurons, leading to a decreased conditional place preference (CPP)-associated memories and spatial learning and memory in water maze. Cdc42 knockout or mutants promoted cocaine-induced loss of neurogenesis in DG, leading to a decreased CPP-associated memories and spatial learning and memory in water maze. Furthermore, by using D1R knockout, D2R knockout, and D2R/Cdc42 double knockout mice, we found that D2R, but not D1R, regulated Cdc42 signaling in cocaine-induced neural plasticity and behavioral changes. CONCLUSIONS: Cdc42 acts downstream of D2R in the hippocampus and plays an important role in cocaine-induced neural plasticity through N-WASP and PAK-LIMK-Cofilin, and Cdc42 signaling pathway correlatively links specific brain regions (CA1, dentate gyrus) to cocaine-induced CPP behavior.


Assuntos
Transtornos Relacionados ao Uso de Cocaína , Cocaína , Animais , Camundongos , Cocaína/farmacologia , Cocaína/metabolismo , Transtornos Relacionados ao Uso de Cocaína/genética , Transtornos Relacionados ao Uso de Cocaína/metabolismo , Dopamina/metabolismo , Hipocampo/metabolismo , Camundongos Knockout , Receptores de Dopamina D2/genética , Receptores de Dopamina D2/metabolismo
6.
Food Chem ; 402: 134435, 2023 Feb 15.
Artigo em Inglês | MEDLINE | ID: mdl-36303381

RESUMO

This work was aimed to study the effects of the selenized yeast added in feed on selenium-containing proteins of egg yolk. Two groups of the same little hens were given the ordinary grain feed either unsupplemented selenized yeast (Group O) or supplemented with 0.15% selenized yeast (Group Y), respectively. The water-soluble Se-containing proteins were isolated and purified from the two group eggs yolk using the same conditions. SeP1-1 and SeP1-I were purified from the yolk of Group Y and Group O, respectively. Sequences identified by HPLC-MS/MS showed that SeP1-1 was a highly homologous Se-containing protein with Se-free YGP-42 with 83% match, in which Se species include methylselenocysteine and selenocysteine. SeP1-I was a highly homologous Se-containing protein with Se-free ovalbumin with 78.2% match, in which Se species include selenomethionine and selenocysteine. It can be concluded that the selenized yeast can change the compositions and structures of Se-containing proteins in egg yolk.


Assuntos
Selênio , Animais , Feminino , Selênio/química , Gema de Ovo/química , Saccharomyces cerevisiae/metabolismo , Selenocisteína/análise , Galinhas/metabolismo , Albuminas/análise , Espectrometria de Massas em Tandem , Suplementos Nutricionais/análise , Ração Animal/análise , Dieta
7.
Food Chem ; 401: 134126, 2023 Feb 01.
Artigo em Inglês | MEDLINE | ID: mdl-36088714

RESUMO

To clarify the role of Acetobacter sp. in fermented noni juice, the physiochemical properties, main active ingredients and volatile constituents were comprehensively analyzed. The sugar content and acidity tended to be stable after 12 days of fermentation. Acetobacter sp. had no significant influence on major active ingredients of products. The headspace-gas chromatography-ion mobility spectrometry (HS-GC-IMS) were performed to describe the characteristic flavor profiles during fermentation. A total of 55 flavor compounds were screened with odour threshold and Kruskal-Wallis p < 0.05. Among them, 14 different biomarkers were selected with Variable Importance in Projection (VIP) greater than 1. The concentrations of ketones and aldehydes increased significantly, mainly contributing to the floral, fruit and green features. The content of hexanoic acid, octanoic acid and butanoic acid as the main source of peculiar odor were significantly reduced, indicating Acetobacter sp. could improve the unpleasant odor of fermented noni juice.


Assuntos
Acetobacter , Morinda , Odorantes , Ácido Butírico , Cromatografia Gasosa-Espectrometria de Massas , Frutas/química , Açúcares/análise , Aldeídos/análise , Cetonas/análise
8.
J Colloid Interface Sci ; 630(Pt A): 1-10, 2023 Jan 15.
Artigo em Inglês | MEDLINE | ID: mdl-36215819

RESUMO

Wind power is a promising electricity source. Nevertheless, wind turbine blade icing can cause severe problems in turbine operation. In this study, SiO2 spherical nanoparticles (∼90 nm), produced by RF (radio frequency) plasma spheroidization, were mixed with E51, PDMS, and ethyl acetate, and sprayed on the surface of aluminum plates and regular power windmill fan blades which were already coated with polyurethane primer. XPS and IR spectroscopies revealed the development of SiC and SiPh (Ph = phenolic ring) bonds, whose formation should be favored by the ultrasound and curing processes at 50 °C. The integrity of the coating/substrate interface, whose strength is ascribed to hydrogen bonds, was maintained after 100 icing-melting cycles. The coatings display superhydrophobic behavior and excellent anti-icing performance, along with stability in abrasion, sunlight and self-cleaning ability towards solid pollutants.

9.
J Ethnopharmacol ; 301: 115818, 2023 Jan 30.
Artigo em Inglês | MEDLINE | ID: mdl-36220509

RESUMO

ETHNOPHARMACOLOGICAL RELEVANCE: Gentiana purpurea was one of the most important medicinal plants in Norway during the 18th and 19th centuries, and the roots were used against different types of gastrointestinal and airway diseases. AIM OF THE STUDY: To explore the content of bioactive compounds in a water extract from the roots, a preparation commonly used in traditional medicine in Norway, to assess the anti-inflammatory potential, and furthermore to quantify the major bitter compounds in both roots and leaves. MATERIALS AND METHODS: G. purpurea roots were boiled in water, the water extract applied on a Diaion HP20 column and further fractionated with Sephadex LH20, reverse phase C18 and normal phase silica gel to obtain the low molecular compounds. 1D NMR, 2D NMR, and ESI-MS were used for structure elucidation. HPLC-DAD analysis was used for quantification. The inhibition of TNF-α secretion in ConA stimulated peripheral blood mononuclear cells (PBMCs) was investigated. RESULTS: Eleven compounds were isolated and identified from the hot water extract of G. purpurea roots. Gentiopicrin, amarogentin, erythrocentaurin and gentiogenal showed dose-dependent inhibition of TNF-α secretion. Gentiopicrin is the major secondary metabolite in the roots, while sweroside dominates in the leaves. CONCLUSIONS: The present work gives a comprehensive overview of the major low-molecular weight compounds in the water extracts of G. purpurea, including metabolites produced during the decoction process, and show new anti-inflammatory activities for the native bitter compounds as well as the metabolites produced during preparation of the crude drug.


Assuntos
Gentiana , Gentiana/química , Fator de Necrose Tumoral alfa/análise , Água , Leucócitos Mononucleares , Extratos Vegetais , Raízes de Plantas/química , Anti-Inflamatórios , Compostos Fitoquímicos/análise
10.
Ultrason Sonochem ; 92: 106231, 2022 Nov 19.
Artigo em Inglês | MEDLINE | ID: mdl-36463783

RESUMO

In order to obtain noni juice with high yield and good quality, the effect of combined extraction technique of enzymatic treatment (EZ) and ultrasonication (US) on the overall quality of noni juice was investigated. Moreover, the extraction performance of the EZ-US combined extraction technique was compared with that of EZ-based extraction and the US-based extraction. Response surface methodology (RSM) was designed to optimize the parameters of ultrasonic treatment, by taking consideration of the extraction efficiency, quality parameters and bioactive ingredients of noni juice. The results indicated that combined ultrasonic and enzymatic treatment achieved a synergistic effect on promoting the quality of noni juice. The maximum juice yield of 67.95 % was obtained under ultrasonication for 10 min at 600 W after enzymatic treatment (EZU). In addition, EZU-treated juice exhibited the highest contents of total phenolic and flavonoid, which were 148.19 ± 2.53 mg gallic acid/100 mL and 47.19 ± 1.22 mg rutin/100 mL, respectively, thus contributing to better antioxidant activity. Moreover, the EZU treatment significantly reduced the particle size of noni juice, and improved its suspension stability and rheological properties. FTIR results indicated that the treatments did not bring major changes in the chemical structure and the functional groups of compounds in noni juice. Therefore, EZU treatment can be successfully applied to the extraction of noni juice with better nutritional properties and overall quality.

11.
Radiother Oncol ; 2022 Dec 01.
Artigo em Inglês | MEDLINE | ID: mdl-36464180

RESUMO

BACKGROUND AND PURPOSE: This multicenter retrospective study aimed to investigated the prognostic value of unequivocal radiologic extranodal extension (rENE) and the efficacy of chemotherapy for stage T1-2N1 nasopharyngeal carcinoma (NPC) in the IMRT era. MATERIALS AND METHODS: We included 1,082 patients treated in 2005-2017 from three centers. rENE was recorded as G1 (coalescent nodal mass comprising ≥2 inseparable nodes) or G2 (invading beyond perinodal fat to frankly infiltrate adjacent structures). Multivariable analysis (MVA) evaluated the prognostic value of rENE. The value of chemotherapy was assessed in rENE-positive (rENE+) and rENE-negative (rENE-) subset separately. RESULTS: Centers 1, 2, and 3 had 139/515 (27.0%), 100/365 (27.4%), and 43/202 (21.3%) cN+ patients with rENE, respectively. Compared to rENE-, rENE+ patients had a worse distant metastasis-free survival (DMFS) and overall survival (OS) (all p<0.001). MVA confirmed the prognostic of both G1-rENE and G2-rENE for distant metastasis [G1: hazard ratio (HR): 2.933, G2: HR: 6.942, all p<0.001] and death (G1: HR: 1.587, p=0.040; G2: HR: 6.162, p<0.001). There was no significant difference for DMFS and OS between chemo-radiotherapy and radiotherapy alone in rENE+ and rENE- groups (all p>0.1). However, rENE+ patients with a cumulative cisplatin/nedaplatin dose (CCND) of >160 mg/m2 had an improved DMFS (p=0.033) but no OS (p=0.197). CONCLUSION: Unequivocal rENE is prognostic in patients with T1-2N1 NPC. Addition of chemotherapy to radiotherapy did not affect DMFS and OS in rENE- patients. Chemotherapy with a CCND of >160mg/m2 improved DMFS in rENE+ patients.

12.
Sci Total Environ ; : 160617, 2022 Nov 30.
Artigo em Inglês | MEDLINE | ID: mdl-36462653

RESUMO

BACKGROUND: Evidence concerning associations of per- and polyfluoroalkyl substances (PFASs) exposure with bone mineral density (BMD) and osteoporosis is scarce. Additionally, no study has examined the effects of PFAS isomers and alternatives on bone health. OBJECTIVES: To evaluate the associations of PFASs and PFAS alternatives with BMD levels and osteoporosis prevalence. METHODS: A total of 1260 healthy adults from southern China were enrolled. Serum concentrations of 32 legacy PFASs, PFAS isomers, and alternatives were measured using modified liquid chromatography-tandem mass spectrometry. Logistic and linear regression models were applied to evaluate the associations of PFASs with osteoporosis prevalence and BMD levels, respectively, adjusting for confounding factors. We performed stratified analyses to assess potential effect modifications of age and sex. We further used sensitivity analyses to testify the robustness of the main findings. RESULTS: There were 204 (16.2 %) participants diagnosed with osteoporosis. Eleven of the studied PFASs (i.e., PFHpA, PFOA, PFBS, PFHpS, total-PFHxS, n-PFHxS, br-PFHxS, br-PFOS, 1m-PFOS, Σ3 + 4 + 5m-PFOS, and 6:2 Cl-PFESA) showed significant and inverse associations with BMD levels (mean differences ranged from -6.47 to -26.07 per one ln-unit increase in the PFASs). Additionally, we observed that each one ln-unit increase in PFHpA was significantly associated a 23 % (OR = 1.23, 95 % CI = 1.04, 1.45) greater odds of osteoporosis. The above associations were consistent in several sensitivity analyses we performed. Stratified analyses showed stronger associations among women and younger compared to their counterparts. CONCLUSIONS: Our findings suggested that greater PFAS exposure is associated with poorer bone health, especially in women and younger people.

13.
Front Endocrinol (Lausanne) ; 13: 993423, 2022.
Artigo em Inglês | MEDLINE | ID: mdl-36465620

RESUMO

Background: This study aims to develop a diabetic retinopathy (DR) hazard nomogram for a Chinese population of patients with type 2 diabetes mellitus (T2DM). Methods: We constructed a nomogram model by including data from 213 patients with T2DM between January 2019 and May 2021 in the Affiliated Hospital of Zunyi Medical University. We used basic statistics and biochemical indicator tests to assess the risk of DR in patients with T2DM. The patient data were used to evaluate the DR risk using R software and a least absolute shrinkage and selection operator (LASSO) predictive model. Using multivariable Cox regression, we examined the risk factors of DR to reduce the LASSO penalty. The validation model, decision curve analysis, and C-index were tested on the calibration plot. The bootstrapping methodology was used to internally validate the accuracy of the nomogram. Results: The LASSO algorithm identified the following eight predictive variables from the 16 independent variables: disease duration, body mass index (BMI), fasting blood glucose (FPG), glycated hemoglobin (HbA1c), homeostatic model assessment-insulin resistance (HOMA-IR), triglyceride (TG), total cholesterol (TC), and vitamin D (VitD)-T3. The C-index was 0.848 (95% CI: 0.798-0.898), indicating the accuracy of the model. In the interval validation, high scores (0.816) are possible from an analysis of a DR nomogram's decision curve to predict DR. Conclusion: We developed a non-parametric technique to predict the risk of DR based on disease duration, BMI, FPG, HbA1c, HOMA-IR, TG, TC, and VitD.


Assuntos
Diabetes Mellitus Tipo 2 , Retinopatia Diabética , Resistência à Insulina , Humanos , Retinopatia Diabética/diagnóstico , Retinopatia Diabética/epidemiologia , Retinopatia Diabética/etiologia , Diabetes Mellitus Tipo 2/complicações , Nomogramas , Hemoglobina A Glicada , Triglicerídeos , Vitamina D , Vitaminas
14.
Front Bioeng Biotechnol ; 10: 1057904, 2022.
Artigo em Inglês | MEDLINE | ID: mdl-36466342

RESUMO

Hydrogel-based tissue engineering has been widely used to repair cartilage injury. However, whether this approach can be applied to treat nasal septum cartilage defects remains unclear. In this study, three gelatin methacrylate-based scaffolds loaded with transforming growth factor (TGF)-ß1 (GelMA-T) were prepared, and their effects on repair of nasal septum cartilage defects were examined. In vitro, the GelMA-T scaffolds showed good biocompatibility and promoted the chondrogenic differentiation of bone mesenchymal stem cells. Among three scaffolds, the 10% GelMA-T scaffold promoted chondrogenic differentiation most effectively, which significantly improved the expression of chondrocyte-related genes, including Col II, Sox9, and ACAN. In vivo, 10% GelMA-T scaffolds and 10% GelMA-T scaffolds loaded with bone mesenchymal stem cells (BMSCs; 10% GelMA-T/BMSCs) were transplanted into a nasal septum cartilage defect site in a rabbit model. At 4, 12, and 24 weeks after surgery, the nasal septum cartilage defects exhibited more complete repair in rabbits treated with the 10% GelMA-T/BMSC scaffold as demonstrated by hematoxylin & eosin, safranine-O, and toluidine blue staining. We showed that GelMA-T/BMSCs can be applied in physiological and structural repair of defects in nasal septum cartilage, providing a potential strategy for repairing cartilage defects in the clinic.

15.
Top Spinal Cord Inj Rehabil ; 28(4): 33-43, 2022.
Artigo em Inglês | MEDLINE | ID: mdl-36457363

RESUMO

Background: About 69% of the 299,000 Americans living with spinal cord injury (SCI) experience long-term debilitating neuropathic pain. New treatments are needed because current treatments do not provide enough pain relief. We have found that insular-opercular brain network alterations may contribute to neuropathic pain and that restoring this network could reduce neuropathic pain. Here, we outline a study protocol using a physical therapy approach, cognitive multisensory rehabilitation (CMR), which has been shown to restore OP1/OP4 connections in adults post stroke, to test our hypothesis that CMR can normalize pain perception through restoring OP1/OP4 connectivity in adults with SCI and relieve neuropathic pain. Objectives: To compare baseline brain function via resting-state and task-based functional magnetic resonance imaging in adults with SCI versus uninjured controls, and to identify changes in brain function and behavioral pain outcomes after CMR in adults with SCI. Methods: In this phase I randomized controlled trial, adults with SCI will be randomized into two groups: Group A will receive 6 weeks of CMR followed by 6 weeks of standard of care (no therapy) at home. Group B will start with 6 weeks of standard of care (no therapy) at home and then receive 6 weeks of CMR. Neuroimaging and behavioral measures are collected at baseline, after the first 6 weeks (A: post therapy, B: post waitlist), and after the second 6 weeks (A: post-therapy follow-up, B: post therapy), with follow-up of both groups up to 12 months. Conclusion: The successful outcome of our study will be a critical next step toward implementing CMR in clinical care to improve health in adults with SCI.


Assuntos
Neuralgia , Traumatismos da Medula Espinal , Adulto , Humanos , Traumatismos da Medula Espinal/complicações , Encéfalo , Manejo da Dor , Cognição , Ensaios Clínicos Controlados Aleatórios como Assunto , Ensaios Clínicos Fase I como Assunto
16.
Front Pharmacol ; 13: 977582, 2022.
Artigo em Inglês | MEDLINE | ID: mdl-36467046

RESUMO

Background and objectives: The US FDA and Health Canada have successively published potential red flags for acute pancreatitis caused by sodium-dependent glucose transporter 2 inhibitors (SGLT-2i). However, existing studies have focused on case reports. We aimed to assess the possible association of SGLT-2i with acute pancreatitis by analyzing postmarketing adverse events reported in the FDA adverse event reporting system (FAERS), to explore risk factors for SGLT-2i-related acute pancreatitis death, and to build a nomogram. Methods and Results: We used a disproportionality analysis of suspected acute pancreatitis-related reports in the FAERS database of patients from the use of SGLT-2i from the first quarter of 2013 to the fourth quarter of 2021. Single-factor and multi-factor logistic regression analyses were performed using the relevant clinical information of patients, and risk factors were combined with the age of patients to construct a SGLT-2i risk prediction model for acute pancreatitis-related death. A total of 757 reports were retrieved. The largest number of acute pancreatitis-related cases were caused by canagliflozin (317 reports), which was also the strongest agent associated with acute pancreatitis, with the information component (IC 2.41, lower 95% one-sided confidence interval 2.16), the reporting odds ratio (ROR 5.37, 95% two-sided confidence interval 4.8-5.99), and the empirical Bayesian geometric mean (EBGM 5.32, lower 90% one-sided confidence interval 4.85). The median time to acute pancreatitis was 54 (interquartile range [IQR] 14-131) days, and approximately 83% of adverse events occurred within 6 months. Odds ratio(OR) adjusted by acute pancreatitis and the coadministration of SGLT-2i with dipeptidyl peptidase 4 inhibitor (DPP-4i), glucagon-like peptide 1 analog (GLP-1RA), and angiotensin converting enzyme inhibitor (ACEIs) was 1.39, 1.97, and 1.34, respectively, all of which were statistically significant. Logistic regression analysis showed that different SGLT-2i type and their combinations with statins were independent risk factors for acute pancreatitis mortality in the patients (p < 0.05). The mortality risk prediction model showed good discrimination and clinical applicability in both the training set (AUC 0.708) and the validation set (AUC 0.732). Conclusion: SGLT-2i may increase the risk of acute pancreatitis especially within the first 6 months of drug administration. Combination with DPP-4i, GLP-1RA or ACEIs significantly increases the risk of acute pancreatitis. In addition, different SGLT-2i type and their combination with statins are risk factors that can predict the risk of death following acute pancreatitis.

17.
Ann Transl Med ; 10(21): 1171, 2022 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-36467343

RESUMO

Background: Cervical cancer patients have a high risk of metastasis and a poor prognosis with shorter disease-free survival. Thus, novel biomarkers and feasible therapies urgently need to be discovered. Previous studies have shown that miR-95-3p plays crucial roles in several cancer types. However, the roles of miR-95-3p in cervical cancer remain unknown. Methods: The micro ribonucleic acid (miRNA) expression data and clinical characteristics of cervical cancer samples were downloaded from The Cancer Genome Atlas (TCGA) database. Univariate and multivariate Cox regression analyses were conducted to identify the prognostic-related miRNAs. The potential target genes of miR-95-3p were predicted by the TargetScan database. Gene Ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway enrichment analyses were conducted to explore the target gene of miR-95-3p. The effects of miR-95-3p inhibition and overexpression on cell proliferation were inspected by cell counting kit-8 (CCK-8) assays and cell colony formation assays. Wound-healing assays and transwell assays were also used to examine cell migration ability in HeLa and SiHa cells. Results: MiR-95-3p was the only miRNA significantly associated with the poor prognosis of cervical squamous cell carcinoma. A further analysis suggested that vascular cell adhesion molecule 1 (VCAM1) is a target gene of miR-95-3p in cervical cancer, and miR-95-3p promotes the malignant behavior of cervical cancer cells by inhibiting the expression of VCAM1. The CCK-8 and cell colony assays showed that miR-95-3p downregulation significantly suppressed cell proliferation in the HeLa and SiHa cells. The transwell and wound-healing assays showed that miR-95-3p inhibition suppressed cell migration in the HeLa and SiHa cells. Further the Western blot analysis and the quantitative real-time-polymerase chain reaction (qRT-PCR) showed that the knockdown of miR-95-3p in HeLa cells resulted in increased VCAM1 expression. And VCAM1 was highly expressed in the paired adjacent normal cervical epithelium tissue samples, but lowly expressed in the cervical tumor tissue samples. Conclusions: Our study was the first to show that miR-95-3p could serve as a prognostic biomarker of cervical cancer. Mechanistically, we discovered that miR-95-3p inhibited the expression of the cell adhesion molecule VCAM1 and thus promoted further tumor progression.

18.
Sci Rep ; 12(1): 20988, 2022 Dec 05.
Artigo em Inglês | MEDLINE | ID: mdl-36471094

RESUMO

Slash disposal changes soil quality by affecting soil properties and nutrient cycling, and the appropriate disposal approaches remain controversial. This work aimed to explore the impact of different slash disposal methods on soil qualities. For this purpose, a Eucalyptus grandis × Eucalyptus urophylla plantation that had been cultivated in 2002 and felled for the third time in 2016 was established in Hezhou City, China. Burning forest (BF, for moderate intensity fire) and no-burning forest (NF) were set in the plantation, and the native evergreen broadleaf forest near the plantation was used as the control (CK). Soils were sampled quarterly in 2017, and 27 indicators that represent soil physical, chemical, and biological properties were analyzed and compared through the analysis of the sustainability index (SI), which adopts five indices to calculate soil quality. The obtained data showed that the indicators of BF and NF, except for the total potassium content, were much lower than those of CK. The physical properties (Max-WHC, CWHC, Min-WHC, MMC, CPD, TPD) of NF were significantly better (29.07%, 30.98%, 29.61%, 52.08%, 21.89%, 19.76%) than those of BF, unlike the chemical properties of BF (SOM, TN, ACa, AFe, AMn, ACu, AZn) were significantly better than those of NF (45.61%, 81.33%, 12.78%, 23.18%, 96.13%, 144.30%, 114.04%). The enzymatic activities of NF (URE, APHO) were significantly better (43.33%, 156.58%)than those of BF, except the activities of INV (- 25.21%). Results of SI showed that the soil quality of CK was much better than that of BF, and NF the worst. But it exhibited the most unevenness of CK, followed by NF, and BF the best. The change rules of BF and NF were contrasting, and soil quality reached the same level after half a year. In summary, the soil qualities, either BF or CK, were not comparable to that of CK. BF increased the soil quality fleetly and transiently, and NF was sustainable for the eucalyptus plantation.

19.
Zhongguo Zhong Yao Za Zhi ; 47(21): 5838-5848, 2022 Nov.
Artigo em Chinês | MEDLINE | ID: mdl-36472002

RESUMO

Hd-Zip, a unique transcription factor in plant kingdom, influences the growth, development, and secondary metabolism of plants. Hd-zip Ⅳ is thought to play an important role in trichome development of Schizonepeta tenuifolia. This study aims to explore the functions of StHD1 and StHD8 in Hd-zip Ⅳ subfamily in peltate glandular trichome development. To be specific, the expression patterns of the two genes and interaction between the proteins encoded by them were analyzed based on transcriptome sequencing and two-hybrid screening. The subcellular localization was performed and functions of the genes were verified in tobacco and S. tenuifolia. The results showed that StHD1 and StHD8 had high similarity to HD-Zip Ⅳ proteins of other plants and they all had the characteristic conserved domains of HD-Zip Ⅳ subfamily. They were located in the nucleus. The two genes mainly expressed in young tissues and spikes, and StHD1 and StHD8 proteins interacted with each other. The density and length of glandular trichomes increased significantly in tobacco plants with the overexpression of StHD1 and StHD8. Inhibiting the expression of StHD1 and StHD8 by VIGS(virus-induced gene silencing) in S. tenuifolia resulted in the reduction in the density of peltate glandular trichomes, the expression of key genes related to mono-terpene synthesis, and the relative content of limonene and pulegone, the main components of monoterpene. These results suggested that StHD1 and StHD8 of S. tenuifolia formed a complex to regulate glandular trichomes and affect the biosynthesis of monoterpenes.

20.
Artigo em Inglês | MEDLINE | ID: mdl-36456428

RESUMO

BACKGROUND: Although transarterial chemoembolization (TACE) is the first-line therapy for intermediate-stage hepatocellular carcinoma (HCC), it is not suitable for all patients. This study aimed to determine how to select patients who are not suitable for TACE as the first treatment choice. METHODS: A total of 243 intermediate-stage HCC patients treated with TACE at three centers were retrospectively enrolled, of which 171 were used for model training and 72 for testing. Radiomics features were screened using the Spearman correlation analysis and the least absolute shrinkage and selection operator (LASSO) algorithm. Subsequently, a radiomics model was established using extreme gradient boosting (XGBoost) with 5-fold cross-validation. The Shapley additive explanations (SHAP) method was used to visualize the radiomics model. A clinical model was constructed using univariate and multivariate logistic regression. The combined model comprising the radiomics signature and clinical factors was then established. This model's performance was evaluated by discrimination, calibration, and clinical application. Generalization ability was evaluated by the testing cohort. Finally, the model was used to analyze overall and progression-free survival of different groups. RESULTS: A third of the patients (81/243) were unsuitable for TACE treatment. The combined model had a high degree of accuracy as it identified TACE-unsuitable cases, at a sensitivity, specificity, and area under the receiver operating characteristic curve (AUC) of 0.759, 0.885, 0.906 [95% confidence interval (CI): 0.859-0.953] in the training and 0.826, 0.776, and 0.894 (95% CI: 0.815-0.972) in the testing cohort, respectively. CONCLUSIONS: The high degree of accuracy of our clinical-radiomics model makes it clinically useful in identifying intermediate-stage HCC patients who are unsuitable for TACE treatment.

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