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1.
Ying Yong Sheng Tai Xue Bao ; 33(4): 972-980, 2022 Apr.
Artigo em Chinês | MEDLINE | ID: mdl-35543049

RESUMO

Soil acidification is an important factor leading to poor growth and root rot disease of Panax notoginseng in the understorey of forests. In this study, different amounts of quicklime (0, 500, 1000, 1500 and 2000 kg·hm-2) were amended into acid soil under forest. We evaluated the effect of quikelime addition on soil chemical properties, phenols, rhizosphere microorganisms and growth of P. notoginseng. The results showed that an appro-priate amount of quicklime addition (500-1000 kg·hm-2) could significantly increase soil pH, decrease the content of phenols (p-hydroxybenzoic acid, vanillin, syringic acid, ferulic acid and vanillic acid), promote P. notoginseng growth, and reduce the incidence of root rot disease. An appropriate amount of quicklime (500-1000 kg·hm-2) could significantly reduce the fungi:bacteria ratio, increase bacteria diversity, and increase the relative abundance of Ascomycota and Proteobacteria as well as Massilia and Sphingomonas. However, excessive quicklime addition (1500-2000 kg·hm-2) could reduce the content of available nitrogen and organic matter, and inhibit P. notoginseng growth. Therefore, 500-1000 kg·hm-2 of quicklime amendment could improve the chemical properties and microbial community of acid soil under forest, thereby promoting P. notoginseng growth, and reducing the incidence of root rot disease.


Assuntos
Ascomicetos , Panax notoginseng , Compostos de Cálcio , Florestas , Óxidos , Fenóis , Raízes de Plantas/microbiologia , Solo/química , Microbiologia do Solo
2.
Front Immunol ; 13: 862702, 2022.
Artigo em Inglês | MEDLINE | ID: mdl-35572527

RESUMO

Objective: To establish an artificial intelligence-based method to quantitatively evaluate subtle pathological changes in retinal nerve cells and synapses in monosodium glutamate (MSG) mice and provide an effective animal model and technique for quantitative evaluation of retinal neurocytopathies. Methods: ICR mice were subcutaneously injected with MSG to establish a model of metabolic syndrome. We then established a mouse model of type 1 diabetes, type 2 diabetes, and KKAy mouse model as control. The HE sections of the retina were visualized using an optical microscope. AI technology was used for quantitative evaluation of the retinal lesions in each group of rats. The surface area custom parameters of the retinal nerve fiber layer (RNFL), inner plexiform layer (IPL), inner nuclear layer (INL), and outer plexiform layer (OPL) were defined as SR, SIPL, SINL, and SOPL, respectively. Their heights were defined as HR, HIPL, HINL, and HOPL, and the number of ganglion cells was defined as A. Then, the attention-augmented fully convolutional Unet network was used to segment the retinal HE images, and AI technology to identify retinal neurocytopathies quantitatively. Results: The attention-augmented fully convolutional Unet network increased PA and IOU parameters for INL, OPL, RNFL, and ganglion cells and was superior in recognizing fine structures. A quantitative AI identification of the height of each layer of the retina showed that the heights of the IPL and INL of the MSG model were significantly less than those of the control groups; the retinas of the other diabetic models did not exhibit this pathological feature. The RNFLs of type 2 diabetes were thinner, and the characteristics of retinopathy were not obvious in the other animal models. The pathological changes seen on HE images were consistent with the results of the quantitative AI evaluation. Immunohistochemistry results showed that NMDAR2A, GluR2, and NRG1 were significantly downregulated in the retina of MSG mice. Conclusions: The MSG retinopathy model is closely associated with neurotransmitter abnormalities and exhibits important characteristics of retinal neurodegeneration, making it suitable for studying retinal neurocytopathies. The AI recognition technology for retinal images established in the present study can be used for the quantitative and objective evaluation of drug efficacy.

3.
Innovation (N Y) ; 3(3): 100243, 2022 May 10.
Artigo em Inglês | MEDLINE | ID: mdl-35519511

RESUMO

Consciousness lies at the heart of our existence and experience. To probe how perceptual consciousness emerges in the brain, we recorded brain-wide intracranial electroencephalography signals from human patients while their perceptual consciousness was effectively manipulated using the continuous flash suppression paradigm. We observed substantial differences in brain activities when visual information gradually enters consciousness. Specifically, the functional connectivity first increases and then decreases, oscillations in the low-frequency band reduce in power, and those in the high-frequency band remain unchanged. We employed random forest-based classification to characterize the transitions from no perception to subconsciousness and then to consciousness, which showed an increase in signal variance at the second transition rather than the first. Further, the frontal-parietal junction dominates the first transition, whereas the temporal-frontal lobes dominate the second transition. Finally, we identified the most relevant neuronal features associated with consciousness. Altogether, these findings shed fresh light on the emergence of visual consciousness.

4.
Bioengineered ; 13(5): 11732-11741, 2022 May.
Artigo em Inglês | MEDLINE | ID: mdl-35506298

RESUMO

Acute respiratory distress syndrome (ARDS) is a multifactorial inflammatory lung failure with a high incidence and a high cost burden. However, the underlying pathogenesis of ARDS is still unclear. Recently, microRNA has been shown to have critical function in regulating the pathogenesis of ARDS development and inflammation. To identify the important microRNA in the serum from patients with ARDS that may be potential biomarkers for the disease and explore the underlying disease mechanism. We found significant upregulation of miR-155-5p expression in serum samples from patients with ARDS compared with the control group (p < 0.01). The levels of interleukin receptors and inflammatory cytokines were significantly increased in blood samples from patients with ARDS (p < 0.05). In the cell model, miR-155-5p had a binding site in the 3'-UTR of the three interleukin receptors. In LPS-simulated BEAS-2B cells, transfection of miR-155-5p mimic inhibited the expression levels of these interleukin receptors, and was found to directly target the inflammatory response of leukocyte nodulin receptor through NF-kB signaling. In conclusion, miR-155-5p can alleviate LPS-simulated injury that induces the expression of IL17RB, IL18R1, and IL22RA2 by affecting the NF-kB pathway; however, it cannot change the occurrence of inflammatory storms. Collectively, this suggests that the progression of ARDS is the result of effects of the multiple regulatory pathways, providing novel evidence for the therapy of ARDS.


Assuntos
MicroRNAs , Síndrome do Desconforto Respiratório , Humanos , Lipopolissacarídeos , MicroRNAs/genética , MicroRNAs/metabolismo , NF-kappa B/metabolismo , Receptores de Interleucina/genética , Síndrome do Desconforto Respiratório/genética
5.
BMJ Open ; 12(5): e049225, 2022 May 02.
Artigo em Inglês | MEDLINE | ID: mdl-35501092

RESUMO

INTRODUCTION: The evidence on predictive value of lifestyle behaviours and dietary pattern on the prognosis of heart failure (HF) is limited. Our aim is to identify these factors in the setting of secondary prevention of HF. METHODS AND ANALYSIS: The Metabolic Abnormalities, Lifestyle and Dietary Pattern in Heart Failure study is an ongoing, prospective cohort, single-centre study that aims to recruit 1500 patients with HF from June 2016 to June 2021. At baseline, each participant completes a questionnaire on demographic characteristics, medical history, lifestyle behaviours, sleep duration and quality, bowel movements and regular diet. Biochemical measurements, blood pressure, carotid ultrasound, echocardiography, electrocardiography and cardiac magnetic resonance are obtained and analysed. Muscle strength is assessed using the handgrip dynamometer and the MicroFet2 hand-held dynamometer. Each patient is followed for 5 years or until the occurrence of death. The primary outcome is a composite of cardiovascular mortality or hospitalisation due to worsening heart failure. The secondary end points are cardiovascular deaths and the hospitalisations due to worsening HF. The incidence of mortality and cardiovascular events is documented biennially. ETHICS AND DISSEMINATION: The study protocol has been approved by the Ethics Committee of the Ruijin Hospital, Shanghai Jiao Tong University School of Medicine, and follows the norms of the World's Association Declaration of Helsinki. The results of this study will be disseminated in peer-reviewed journals and academic conferences. TRIAL REGISTRATION NUMBER: NCT03951311.


Assuntos
Força da Mão , Insuficiência Cardíaca , China/epidemiologia , Dieta , Insuficiência Cardíaca/epidemiologia , Humanos , Estilo de Vida , Estudos Prospectivos
6.
BMC Nephrol ; 23(1): 184, 2022 May 13.
Artigo em Inglês | MEDLINE | ID: mdl-35562673

RESUMO

BACKGROUND: Statins therapy has been primarily recommended for the prevention of cardiovascular risk in patients with chronic kidney diseases. Statins has also been proved some benefits in lipid-induced kidney diseases. The current study aims to investigate the protection and underlying mechanisms of statins on renal tubular injuries induced by cholesterol overloaded. METHODS: We used tubular suspensions of inner medullary collecting duct (IMCD) cells from rat kidneys and mouse collecting duct cell line mpkCCD cells to investigate the effect of statins on reactive oxygen species (ROS) production induced by cholesterol. Protein and mRNA expression of NADPH oxidase 2 (NOX2) /NOX4 was examined by Western blot and RT-PCR in vitro studies and in rats with 5/6 nephrectomy and high-fat diet. Mitochondrial morphology and membrane potential was observed by Mito-tracker and JC-1. RESULTS: Statins treatment was associated with decreased NOX2 and NOX4 protein expression and mRNA levels in 5/6Nx rats with high-fat diet. Statins treatment markedly reduced the ROS production in IMCD suspensions and mpkCCD cells. Also, statins reduced NOX2 and NOX4 protein expression and mRNA levels in cholesterol overload mpkCCD cells and improved mitochondrial morphology and function. CONCLUSION: Statins prevented ROS production induced by cholesterol in the kidney, likely through inhibiting NOXs protein expression and improving mitochondrial function. Statins may be a therapeutic option in treating obesity-associated kidney diseases.

7.
Neurobiol Dis ; 169: 105743, 2022 Apr 28.
Artigo em Inglês | MEDLINE | ID: mdl-35490927

RESUMO

Depression is one of the most prevalent mental illnesses in the world today, and the onset of depression is usually accompanied by neuroinflammation and impaired adult neurogenesis. As a new potential member of the endocannabinoid (eCB) system, G protein coupled receptor 55 (GPR55) has been associated with mood regulation. However, the role of GPR55 in the pathophysiology of depression remains poorly understood. Thus, a 10-day chronic social defeat stress (CSDS) paradigm was utilized as an animal model of depression to explore the potential role of GPR55 in depression. After CSDS, the protein level of GPR55 decreased significantly, but the mRNA expression did not change significantly, highlighting that although the GPR55 protein was involved in the progression of the depression- and anxiety-like phenotypes, its mRNA was not. Additionally, depression- and anxiety-like behaviors were also accompanied by neuroinflammation and impaired adult neurogenesis in the hippocampus. Interestingly, O-1602, a GPR55 agonist, remarkably prevented the development of depression- and anxiety-like behaviors as well as hippocampal neuroinflammation and neurogenesis deficits induced by CSDS. However, after electroacupuncture (EA) alleviated depression- and anxiety-like behaviors induced by CSDS, treatment with a GPR55 antagonist (CID16020046) reversed this effect. Our research demonstrated that downregulation of GPR55 expression in the hippocampus might mediate CSDS-induced depression- and anxiety-like phenotypes, and activation and upregulation of GPR55, which might be correlated with its anti-inflammatory and subsequent neuroprotective effects, could be a potential treatment for depression.

8.
Front Endocrinol (Lausanne) ; 13: 868105, 2022.
Artigo em Inglês | MEDLINE | ID: mdl-35528018

RESUMO

Objective: This study aimed to investigate the inhibition of human important phase II metabolic enzyme sulfotransferases (SULTs) by phthalate monoesters, which are important metabolites of phthalate esters (PAEs). Method: Recombinant SULT-catalyzed metabolism of p-nitrophenol (PNP) was employed as the probe reactions of SULTs to investigate the inhibition of 8 kinds of phthalate monoesters towards SULT isoforms. An in vitro incubation system was utilized for preliminary screening, and 100 µM of phthalate monoesters was used. Inhibition kinetics were carried out to determine the inhibition of SULTs by phthalate monoesters. Result: Multiple phthalate monoesters have been demonstrated to exert strong inhibition potential towards SULT1A1, SULT1B1, and SULT1E1, and no significant inhibition of phthalate monoesters towards SULT1A3 was found. The activity of SULT1A1 was strongly inhibited by mono-hexyl phthalate (MHP), mono-octyl phthalate (MOP), mono-benzyl phthalate (MBZP), and mono-ethylhexyl phthalate (MEHP). Monobutyl phthalate (MBP), MHP, MOP, mono-cyclohexyl phthalate (MCHP), and MEHP significantly inhibited the activity of SULT1B1. MHP, MOP, and MEHP significantly inhibited the activity of SULT1E1. MOP was chosen as the representative phthalate monoester to determine the inhibition kinetic parameters (K i) towards SULT1B1 and SULT1E1. The inhibition kinetic parameters (K i) were calculated to be 2.23 µM for MOP-SULT1B1 and 5.54 µM for MOP-SULT1E1. In silico docking method was utilized to understand the inhibition mechanism of SULT1B1 by phthalate monoesters. Conclusions: All these information will be beneficial for understanding the risk of phthalate monoester exposure from a new perspective.


Assuntos
Ésteres , Sulfotransferases , Humanos , Ácidos Ftálicos , Isoformas de Proteínas , Sulfotransferases/metabolismo
9.
J Nutr Biochem ; : 109038, 2022 May 06.
Artigo em Inglês | MEDLINE | ID: mdl-35533901

RESUMO

The radioresistance of glioma is related to the presence of glioma stem cells. Apigenin, a natural flavonoid compound present in numerous health foods and edible plants, has inhibitory effects on a variety of glioma cells. However, the effects of apigenin on glioma and radiotherapy remain unclear. Here, we used radioresistant SU3-5R stem cells-inoculated subcutaneous glioma model to investigate the effects of apigenin and potential mechanisms. The results showed that after treatment of mouse subcutaneous glioma with apigenin 20 mg/kg for 12 days, irradiation 8 Gray twice or their combination, the tumor volume and weight were significantly decreased, especially in the combined treatment group. Apigenin treatment inhibited the activities of glycolytic related enzymes and expressions of nuclear factor kappa B (NF-κB) p65, hypoxia inducible factor-lα (HIF-1α), glucose transporter (GLUT)-1/3 and pyruvate kinase isozyme type M2 (PKM2) proteins in tumor tissues. After treatment of SU3-5R cells with apigenin 7.5 µM, the fluorescence intensity of CD133 positive cells was decreased, the percentage of cells with comet tails caused by irradiation was increased, and the expressions of lipopolysaccharide-induced NF-κB p65, HIF-1α, GLUT-3 and PKM2 proteins were reduced. These results demonstrate that apigenin can sensitize the radiotherapy of subcutaneous glioma in nude mice, and its mechanisms may result from the attenuations of cell stemness and DNA damage repair by inhibiting NF-κB/HIF-1α-mediated glycolytic related enzymes and protein expressions. In conclusion, our findings suggest that apigenin and apigenin-rich health foods can be used in the radiotherapy of glioma as a radiosensitizer.

10.
BMC Neurol ; 22(1): 168, 2022 May 03.
Artigo em Inglês | MEDLINE | ID: mdl-35501818

RESUMO

BACKGROUND: HINT1 mutations cause an autosomal recessive axonal neuropathy with neuromyotonia. This is a first case report of coexistence of myasthenia gravis (MG) and HINT1-related motor axonal neuropathy without neuromyotonia. CASE PRESENTATION: A 32-year-old woman presented with recurrent ptosis for 8 years, diplopia for 2 years and limb weakness for 1 year and a half. Neostigmine test, elevated AChR antibody level and positive repetitive nerve stimulation supported the diagnosis of MG. Electroneurography (ENG) and electromyography (EMG) examinations revealed a motor axonal neuropathy without neuromyotonic or myokymic discharges. Next-generation sequencing and Sanger sequencing were performed to identify the gene responsible for suspected hereditary neuropathy. Genetic testing for a HINT1 mutation was performed and revealed a homozygous mutation at c.278G>T (p. G93V). The patient was treated with pyridostigmine, oral prednisolone and azathioprine. Her ptosis and diplopia have significantly improved at 6-month follow-up. CONCLUSIONS: Concurrence of MG and hereditary motor axonal neuropathy without neuromyotonia is quite rare. Detection of ptosis with or without ophthalmoplegia, distribution of limb weakness, and reflex can help in recognizing the combination of MG and peripheral neuropathy. Early diagnosis is important for initial treatment and prognosis. The novel homozygous variant c.278G>T(p.G93V) contributes to the pathogenic variants spectrum of the HINT1 gene.


Assuntos
Síndrome de Isaacs , Miastenia Gravis , Doenças do Sistema Nervoso Periférico , Adulto , Diplopia/complicações , Feminino , Humanos , Síndrome de Isaacs/complicações , Síndrome de Isaacs/diagnóstico , Síndrome de Isaacs/tratamento farmacológico , Debilidade Muscular/complicações , Miastenia Gravis/complicações , Miastenia Gravis/diagnóstico , Miastenia Gravis/tratamento farmacológico , Proteínas do Tecido Nervoso/genética , Doenças do Sistema Nervoso Periférico/complicações
11.
Chemistry ; : e202200869, 2022 May 11.
Artigo em Inglês | MEDLINE | ID: mdl-35543280

RESUMO

Aryl sulfides are in great demands in drugs and materials sciences. To avoid using nucleophilic and noxious thiols, many efforts have been focused on exploring novel sulfide resources. Herein, a reductive Pd-catalyzed, Ni-mediated method to synthesize aryl sulfides via a sulfide transfer reaction is developed. The utility and scope of this reaction is exemplified by various aryl electrophiles and aryl sulfides. Mechanistic studies reveal two competing catalytic cycles of sulfide transfer and aryl transfer in this reaction, where the former one is favored over the later one because of the large energy barrier difference during the transmetalation. Moreover, two important chemicals are late-stage functionalized by this method, exhibiting the potential applications in drugs and materials science.

12.
Front Nutr ; 9: 843357, 2022.
Artigo em Inglês | MEDLINE | ID: mdl-35558755

RESUMO

Introduction: Diabetes mellitus (DM) is a pathological hyperglycemic state related to the dysregulation of insulin. Chronic kidney disease (CKD) is a common chronic complication in diabetic patients. A vegetarian diet could be one of the preventive strategies for the occurrence of CKD in patients with diabetes mellitus. However, it is still unknown whether a vegetarian diet lowers the occurrence of CKD in DM patients. Research Design and Methods: This retrospective study was conducted at Taipei Tzu Chi Hospital from 5 September 2005 to 31 December 2016. Subjects with an HbA1c level > 6.5% or previous history of diabetes mellitus elder than 40 years were grouped based on self-reported dietary habits (vegetarians, lacto-ovo vegetarians and omnivores) in the structured questionnaire. Structural equation modeling (SEM) was applied to estimate the direct and indirect effects of variables on the occurrence of chronic kidney disease. Results: Among these 2,797 subjects, the participants were grouped into dietary habits as vegans (n = 207), lacto-ovo vegetarians (n = 941) and omnivores (n = 1,649). The incidence of overall CKD was higher in the omnivore group [36.6% vs 30.4% (vegans) and 28.5% (lacto-ovo vegetarian), p < 0.001]. In the SEM model, after adjusting for age and sex, the lacto-ovo vegetarian [OR: 0.68, 95% confidence interval (CI): 0.57-0.82] and vegan groups (OR 0.68, 95% CI: 0.49-0.94) were both associated with a lower risk of CKD occurrence than the omnivore group. The vegan diet and lacto-ovo diet lowered the risk related to a high BMI (OR: 0.45, p < 0.001, OR: 0.58, p < 0.001) and hyperuricemia (OR: 0.53, p < 0.001; OR: 0.55, p < 0.001) for the occurrence of CKD. Conclusion: Vegetarian dietary habits were associated with a lower occurrence of CKD in DM patients.

13.
NPJ Genom Med ; 7(1): 31, 2022 May 13.
Artigo em Inglês | MEDLINE | ID: mdl-35562572

RESUMO

Structural anomalies of the central nervous system (CNS) are one of the most common fetal anomalies found during prenatal imaging. However, the genomic architecture of prenatal imaging phenotypes has not yet been systematically studied in a large cohort. Patients diagnosed with fetal CNS anomalies were identified from medical records and images. Fetal samples were subjected to low-pass and deep whole-genome sequencing (WGS) for aneuploid, copy number variation (CNV), single-nucleotide variant (SNV, including insertions/deletions (indels)), and small CNV identification. The clinical significance of variants was interpreted based on a candidate gene list constructed from ultrasound phenotypes. In total, 162 fetuses with 11 common CNS anomalies were enrolled in this study. Primary diagnosis was achieved in 62 cases, with an overall diagnostic rate of 38.3%. Causative variants included 18 aneuploids, 17 CNVs, three small CNVs, and 24 SNVs. Among the 24 SNVs, 15 were novel mutations not reported previously. Furthermore, 29 key genes of diagnostic variants and critical genes of pathogenic CNVs were identified, including five recurrent genes: i.e., TUBA1A, KAT6B, CC2D2A, PDHA1, and NF1. Diagnostic variants were present in 34 (70.8%) out of 48 fetuses with both CNS and non-CNS malformations, and in 28 (24.6%) out of 114 fetuses with CNS anomalies only. Hypoplasia of the cerebellum (including the cerebellar vermis) and holoprosencephaly had the highest primary diagnosis yields (>70%), while only four (11.8%) out of 34 neural tube defects achieved genetic diagnosis. Compared with the control group, rare singleton loss-of-function variants (SLoFVs) were significantly accumulated in the patient cohort.

14.
Med Oncol ; 39(5): 72, 2022 May 15.
Artigo em Inglês | MEDLINE | ID: mdl-35568747

RESUMO

Renal cell carcinoma (RCC) is the most common form of malignancy affecting the kidneys. Circular RNAs (circRNAs) are non-coding RNAs that are derived from exonic or intronic sequences through a selective shearing process. There is growing evidence that these circRNAs can influence a range of biological pathways by serving as protein decoys, microRNA sponges, regulators of transcriptional activity, or templates for protein translation. The dysregulation of circRNA expression patterns is a hallmark of RCC and other cancer types, and there is strong evidence that these RNA species can play central roles in the onset and progression of RCC tumors. In the present review, we summarized recent findings on the functional roles and clinical impacts of circRNAs in RCC. Further, we discussed their potential utility as diagnostic biomarkers or targets for therapeutic intervention.

15.
Ann Transl Med ; 10(8): 472, 2022 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-35571434

RESUMO

Background: Airway inflammation produced by neutrophils is a critical factor in the development of chronic obstructive pulmonary disease (COPD). Poor or excessive neutrophil polarization and chemotaxis may lead to pathogen accumulation and tissue damage. However, it is unclear how cigarette smoke extract (CSE) attracts neutrophils and to what extent COPD is affected by the improper polarization of these abnormal neutrophils. This study sought to assess the polarization and migration dynamics of neutrophils isolated from patients with different severities of COPD compared to healthy smoking and non-smoking control subjects, and to detect how CSE triggers the polarization of neutrophils. Methods: The neutrophils were freshly isolated using standard isolation protocol. The polarization of the neutrophils was observed using a Zigmond chamber when stimulated by a linear concentration gradient of CSE or N-formyl-methionine-leucine-phenylalanine (fMLP). Confocal laser-scanning microscopy was used to observe the intracellular calcium of the neutrophils. The experimental data are presented as the mean ± standard deviation. SPSS 20.0 software was used for the statistical analysis. A P value <0.05 was considered statistically significant. Results: The neutrophils from the COPD patients showed a higher frequency of spontaneous polarization and a lower prevalence of directionality polarization than those from the healthy control (HC) and smoker subjects. The abnormal polarization of the neutrophils from the COPD patients was altered by the influence of store-operated calcium entry (SOCE) component matrix interaction molecules 1 and 2 and calcium release-activated calcium channel protein 1 [stromal interaction molecule 1 (STIM1), Stromal interaction molecule 2 (STIM2), and calcium release-activated calcium modulator 1 (ORAI1)]. Conclusions: The COPD neutrophils exhibited unique polarization and migration patterns compared to those of the cells examined from other populations. The attraction of CSEs to neutrophils was mediated by the SOCE/Akt/Src pathway.

16.
Nat Prod Res ; : 1-9, 2022 May 14.
Artigo em Inglês | MEDLINE | ID: mdl-35574640

RESUMO

Three new compounds, 4,5,6,7-tetramethoxy-3-benzoylbenzofuran (1), 4-hydroxy-3,5,6-trimethoxydihydrochalcone-2-O-ß-D-glucopyranoside (2) and 2-hydroxy-3,4,5,6-tetramethoxyphenylethyl benzoate (3) along with five known flavonoids were isolated from the dichloromethane fraction of the stems of Fissistigma acuminatissimum Merr.'s ethanol extracts. The compounds were obtained by chromatographic methods and the structure elucidation was completed primarily on the basis of spectroscopic analyses, all of these compounds were isolated from F. acuminatissimum for the first time. All the fractions and compounds were evaluated for their anti-inflammatory activity against lipopolysaccharide (LPS)-stimulated tumor necrosis factor α (TNF-α) production in RAW264.7 cells in vitro. The dichloromethane fraction showed the most potent inhibition(38.2%) at 60 µg/mL, compound 1 (70.2%) and 3 (65.2%) showed significant inhibition at 10 µM.

17.
J Nanobiotechnology ; 20(1): 186, 2022 Apr 12.
Artigo em Inglês | MEDLINE | ID: mdl-35413839

RESUMO

BACKGROUND: Sonodynamic therapy (SDT) is a burgeoning modality for cancer therapy owing to its high tissue-penetrating capability, controllability and safety. Whereas, the undesirable reactive oxygen species (ROS) yield of sonosensitizers and tumor hypoxia are two vulnerable spots of SDT. Therefore, it is an advisable strategy to augment ROS level and simultaneously relieve hypoxia for SDT to arrive its full potential in cancer treatment. RESULTS: In this work, the defected two-dimensional (2D) Pd/H-TiO2 nanosheets (NSs) with triple antineoplastic properties were dexterously elaborated and engineered using a facile one-pot Pd-catalyzed hydrogenation tactic by loading a tiny amount of Pd and then inletting hydrogen flow at atmospheric pressure and temperature. The 2D black Pd/H-TiO2 NSs with oxygen defects exerted eximious SDT effect based on the decreased bandgap that made it easier for the separation of electrons and holes when triggered by ultrasound as theoretically guided by density functional theory calculations. Additionally, Pd/H-TiO2 NSs could serve as Fenton-like agents because of the presence of oxygen defects, facilitating the conversion of hydrogen peroxide into hydroxyl radicals for exerting the chemodynamic therapy (CDT). Simultaneously, the introduced tiny Pd component possessed catalase-like activity responsible for oxygen production to ameliorate hypoxic condition and thus contributed to improving SDT and CDT efficacies. Both in vitro and in vivo results provided compelling evidences of high ROS yield and aggrandized sono-chemodynamic effect of Pd/H-TiO2 nanosonosensitizers with the detailed underlying mechanism investigation by RNA sequencing. CONCLUSION: This work delves the profound potential of Pd-catalyzed hydrogenated TiO2 on oncotherapy, and the effective antineoplastic performance and ignorable therapeutic toxicity make it a powerful competitor among a cornucopia of nanosonosensitizers.


Assuntos
Antineoplásicos , Neoplasias , Terapia por Ultrassom , Antineoplásicos/farmacologia , Antineoplásicos/uso terapêutico , Linhagem Celular Tumoral , Humanos , Hipóxia/tratamento farmacológico , Neoplasias/tratamento farmacológico , Oxigênio , Paládio/farmacologia , Paládio/uso terapêutico , Espécies Reativas de Oxigênio , Titânio , Terapia por Ultrassom/métodos
18.
BMC Pulm Med ; 22(1): 141, 2022 Apr 12.
Artigo em Inglês | MEDLINE | ID: mdl-35413899

RESUMO

BACKGROUND: Respiratory involvement is common in immunoglobulin G4-related disease (IgG4-RD). However, severe asthma as the initial clinical manifestation of IgG4-RD is rare and might be neglected by respiratory clinicians. We aimed to explore the clinical characteristics and prognoses of patients with immunoglobulin G4-related disease (IgG4-RD) manifesting as severe asthma. METHODS: A retrospective analysis of the clinical characteristics and prognoses of patients with severe asthma who were eventually diagnosed with IgG4-RD was performed in the Peking Union Medical College Hospital from 2013 to 2019. RESULTS: Twelve patients (5males, 7 females) were included. The mean age at enrollment and age of asthma onset were 59.4 ± 10.1 and 53.8 ± 10.4 years, respectively. The mean duration of asthma symptoms was 5.7 ± 2.0 years. In all patients, the proportion (25.1 ± 10.3%) and count (2.0 ± 1.1) × 109/L of eosinophils in peripheral blood increased. Additionally, all patients exhibited elevated total immunoglobulin E [IgE, (1279.3 ± 1257.9) KU/L] and IgG4 (9155.8 ± 9247.6) mg/dL. Bronchial wall thickening (n = 11) and mediastinal/hilar lymphadenopathy (n = 11) were major chest CT manifestations. All were pathologically diagnosed through surgical biopsy; submandibular gland (n = 8), supraclavicular lymph node (n = 2), stomach (n = 1), rashes (n = 1), lacrimal gland (n = 1) and thoracoscopic lung (n = 1) biopsies were performed. Asthma was well controlled by oral glucocorticoids (GCs), but some patients relapsed during tapering (n = 11). The refractory condition was controlled after increasing the dosage of GCs and add-on immunosuppressants. CONCLUSIONS: For patients with middle age-onset severe asthma with elevated eosinophils, total IgE and IgG4 levels and available salivary gland ultrasound imaging, ruling out IgG4-RD is recommended. GCs used in combination with immunosuppressants is recommended to prevent relapse.


Assuntos
Asma , Doença Relacionada a Imunoglobulina G4 , Linfadenopatia , Idoso , Asma/complicações , Feminino , Glucocorticoides/uso terapêutico , Humanos , Imunoglobulina E , Imunoglobulina G , Doença Relacionada a Imunoglobulina G4/complicações , Doença Relacionada a Imunoglobulina G4/diagnóstico , Imunossupressores , Pessoa de Meia-Idade , Estudos Retrospectivos
19.
Adv Sci (Weinh) ; : e2200974, 2022 Apr 30.
Artigo em Inglês | MEDLINE | ID: mdl-35488513

RESUMO

Variant modalities are quested and merged into the tumor nanotherapy by leveraging the excitation from external or intratumoral incentives. However, the ubiquitous hypoxia and the insufficient content of hydrogen peroxide (H2 O2 ) in tumor microenvironments inevitably hinder the effective production of reactive oxygen species (ROS). To radically extricate from the shackles, peroxymonosulfate (PMS: HSO5 - )-loaded hollow mesoporous copper sulfide (CuS) nanoparticles (NPs) are prepared as the distinct ROS donors for sulfate radical (•SO4 - )-mediated and stimuli-responsive tumor nanotherapy in an oxygen-independent manner. In this therapeutic modality, the second near-infrared laser irradiation, together with the released copper ions as well as the heat produced by CuS after illumination, work together to activate PMS thus triply ensuring the copious production of •SO4 - . Different from conventional ROS, the emergence of •SO4 - , possessing a longer half-life and more rapid reaction, is independent of the oxygen (O2 ) and H2 O2 content within the tumor. In addition, this engineered nanosystem also exerts the function of photoacoustic imaging and skin restoration on the corresponding animal models. This study reveals the enormous potential of sulfate radical in oncotherapy and broadens pave for exploring the application of multifunctional and stimuli-responsive nanosystems in biomedicine.

20.
Diabetes Metab Syndr Obes ; 15: 1165-1171, 2022.
Artigo em Inglês | MEDLINE | ID: mdl-35464260

RESUMO

Purpose: To establish a high-glucose (HG) stressed cell model and study the expression of main components of the Dll4/Notch-VEGF signaling pathway under high-glucose stimulation. Methods: A model of HG-conditioned cells (human umbilical vein endothelial cells, HUVECs) was first established, and then the expression of Dll4, Notch1, Notch4 and VEGF in HG-stressed cells with or without Notch pathway blockage was analyzed by RT-PCR and Western blot. To observe cell migration, we also evaluated the Transwell assay. Results: HUVECs stimulated with 30mmol/L HG was selected as a cell model. RT-PCR and Western blot results showed that HG stimulation induced the expression of Dll4, Notch1 and VEGF and downregulated Notch4. The expressions were reversed after Notch pathway blockage; meanwhile, the blockage of Notch pathway inhibited cell migration under HG condition. Conclusion: The function of Notch4 in responses to HG stimulation deserves further researching. Combination therapy by blocking Dll4/Notch and VEGF pathways may provide us with a new way for anti-neovascularization.

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