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1.
Phytomedicine ; 94: 153822, 2022 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-34763313

RESUMO

BACKGROUND: Astragalus and Panax notoginseng are significant traditional Chinese medicines for treating ischemic stroke, with astragaloside IV (AST IV) and Panax notoginseng saponins (PNS) being the major effective compounds, respectively. These compounds can also be used in combination. We have previously shown that AST IV and PNS have an antagonistic effect on cerebral ischemia/reperfusion (I/R) injury, and the combination of these two drugs can elevate this effect; unfortunately, AST IV and PNS cannot easily enter the brain tissues through the blood brain barrier (BBB). Previous studies have confirmed that the combination of borneol with other agents could promote the penetration of the drug components through the BBB. However, it remains unclear whether borneol can promote entry of the active components of AST IV and PNS into the brain tissues and enhance their effect against cerebral ischemia. OBJECTIVE: This study aimed to investigate the effects of a combination of borneol with AST IV and PNS against I/R injury and explore the mechanisms of borneol-promoting penetration of drug components into the BBB based on the drug transport of brain tissues. METHODS: A rat model of focal cerebral I/R injury was established, and drugs, including borneol, AST IV, and PNS, as well as their combinations were intragastrically administered. Subsequently, drug efficacy was assessed, and the condition of AST IV and PNS active components (Rg1, Rb1, R1) delivered into the brain was analyzed. Moreover, BBB permeability was determined, and the expression of related drug transporters and their genes were evaluated. RESULTS: After treatment with borneol, AST IV, PNS, AST Ⅳ+PNS, and borneol+AST Ⅳ+PNS after cerebral I/R, the neurological function deficit scores, cerebral infarct rate, and brain water content markedly decreased. The effects of the three-drug-combination were better than those of the drugs used alone and those of AST Ⅳ+PNS. Moreover, after I/R in rats, AST IV and the components of PNS (Rg1, Rb1, R1) were mainly found in the cerebral cortex and in the cerebellum, respectively, when used alone. Borneol combined with AST IV and PNS increased the contents of AST IV, Rb1, Rg1, and R1 in the cerebral cortex and in the cerebellum, thus, promoting the enrichment of active components to the cerebral cortex, especially to the affected side. In addition, following I/R, diffuse distribution of lanthanum particles in the basement membrane, intercellular and intracellular locations of rat brain tissues indicated BBB destruction and increase in permeability, which were alleviated in each drug group. The effects of borneol combined with AST IV and PNS were stronger than those of the drug single-used and those of the AST IV+PNS group. Finally, the expression of effluent transporters (ET) and their genes, including P-glycoprotein (P-gp), multidrug resistance protein (MRP)-1, MRP-2, MRP-4, and MRP-5 in brain tissues, strikingly increased after I/R. Borneol remarkedly down-regulated the protein expression of P-gp, MRP-2, and MRP-4 in the brain, whereas PNS down-regulated MRP-4 and MRP-5 protein expression. AST IV, AST IV+PNS, and bornoel+AST IV+PNS effectively decreased the expression of P-gp, MRP-2, MRP-4, and MRP-5 proteins. The effects of the three-drug combination were significantly greater than those of the drug single-used and AST IV+PNS groups. The expression of each ET gene manifested corresponding results. Meanwhile, PNS, AST IV+PNS, and bornoel+AST IV+PNS significantly inhibited the down-regulation of the uptake transporter organic anion transporting polypeptide (OATP)-2 expression, and the effect of bornoel+AST IV+PNS was stronger than that of other groups. CONCLUSION: After I/R, the brain tissues were injured, BBB permeability increased, expression of critical ET and their genes were markedly up-regulated, and the main uptake transporters were down-regulated. We propose that the combination of borneol, AST IV and PNS could enhance the effect against cerebral I/R injury and protect BBB integrity. The potential mechanism might be the delivery of AST IV and active components of PNS to the brain tissues after treatment in combination with borneol, which could be effectively promoted by down-regulating the expression of ETs and up-regulating the expression of uptake transporters in the brain tissues. This study was the first to demonstrate that borneol combined with AST IV+PNS enhanced the effect against cerebral I/R injury through promoting the entry of AST and PNS active components to the brain tissues. Thus, this study proposes an instructive role in developing effective active ingredients combination of Chinese medicine with clear ingredients and synergistic effects in terms of the characteristic of borneol.

2.
Commun Biol ; 4(1): 1342, 2021 Nov 30.
Artigo em Inglês | MEDLINE | ID: mdl-34848815

RESUMO

Myotonic Dystrophy Type I (DM1) patients demonstrate widespread and variable brain structural alterations whose etiology is unclear. We demonstrate that inactivation of the Muscleblind-like proteins, Mbnl1 and Mbnl2, initiates brain structural defects. 2D FSE T2w MRIs on 4-month-old Mbnl1+/-/Mbnl2-/- mice demonstrate whole-brain volume reductions, ventriculomegaly and regional gray and white matter volume reductions. Comparative MRIs on 2-month-old Mbnl1-/-, Mbnl2-/- and Mbnl1-/-/Mbnl2+/- brains show genotype-specific reductions in white and gray matter volumes. In both cohorts, white matter volume reductions predominate, with Mbnl2 loss leading to more widespread alterations than Mbnl1 loss. Hippocampal volumes are susceptible to changes in either Mbnl1 or Mbnl2 levels, where both single gene and dual depletions result in comparable volume losses. In contrast, the cortex, inter/midbrain, cerebellum and hindbrain regions show both gene and dose-specific volume decreases. Our results provide a molecular explanation for phenotype intensification in congenital DM1 and the variability in the brain structural alterations reported in DM1.

3.
Chin J Integr Med ; 2021 Nov 26.
Artigo em Inglês | MEDLINE | ID: mdl-34826043

RESUMO

OBJECTIVE: To explore the effect and mechanism of action of bufalin in triple-negative breast cancer (TNBC) drug-resistant cell lines. METHODS: The normal human mammary epithelial cell line, TNBC cell line, TNBC adriamycin-resistant cell line, and TNBC docetaxel-resistant cell line were treated with different doses of bufalin (0-1,000 nmol/L) at different time points (0-72 h). Propidium iodide staining, AV-FITC/PI double staining, Hoechst 33342/PI double staining and transmission electron microscopy (TEM) were used to evaluate the death patterns of the cell lines. RESULTS: Bufalin killed the TNBC cell line and its drug-resistant cell lines in a dose/time-dependent manner (all P<0.01). After treatment with bufalin for 24 h, the adriamycin-resistant cell line showed a co-existing pattern of necroptosis and apoptosis. However, at 48 h, necroptosis was the main manifestation. After treatment with bufalin, the expressions of tumor necrosis factor α, phospho-tumor necrosis factor receptor 1, phospho-receptor interacting protein 1 and c-caspase 3 increased (all P<0.01), the killing effect of bufalin could be mostly inhibited by NEC-1, and by z-VAD-fmk (both P<0.01). Besides, the intracellular reactive oxygen species (ROS) levels increased considerably (P<0.01), the antioxidant N-acetyl cysteine or Nec-1 could inhibit the increase of ROS level and the killing effect of bufalin (all P<0.01). The adriamycin-resistant cell line exhibited necroptosis characteristic after 48 h of bufalin treatment under TEM. CONCLUSIONS: Bufalin could induce necroptosis through RIP1/ROS-mediated pathway to kill the drug-resistant TNBC cell lines. This finding provides critical experimental data and theoretical basis for the clinical application of bufalin to overcome the difficulties in the treatment of TNBC.

4.
Mol Cancer ; 20(1): 139, 2021 10 26.
Artigo em Inglês | MEDLINE | ID: mdl-34702297

RESUMO

BACKGROUND: Circular RNAs (circRNAs) constitute a family of transcripts with unique structures and have been confirmed to be critical in tumorigenesis and to be potential biomarkers or therapeutic targets. However, only a few circRNAs have been functionally characterized in pediatric acute myeloid leukemia (AML). METHODS: Here, we investigated the expression pattern of circRNAs in pediatric AML using a circRNA microarray. The characteristics, potential diagnostic value, and prognostic significance of circRNF220 were evaluated. A series of functional experiments were performed to investigate the role of circRNF220 in primary pediatric AML cells. Then we investigated the aberrant transcriptional networks regulated by circRNF220 in primary AML cells by RNA-seq. Furthermore, biotin RNA pulldown assays were implemented to verify the relationship between circRNF220 and miR-30a. RESULTS: We identified a circRNA, circRNF220, which was specifically abundant in and accumulated in the peripheral blood and bone marrow of pediatric patients with AML. It could distinguish AML from ALL and other hematological malignancies with high sensitivity and specificity. Significantly, circRNF220 expression independently predicted prognosis, while high expression of circRNF220 was an unfavorable prognostic marker for relapse. Furthermore, we characterized the function of circRNF220 and found that circRNF220 knockdown specifically inhibited proliferation and promoted apoptosis in AML cell lines and primary cells. Mechanistically, circRNF220 may act as an endogenous sponge of miR-30a to sequester miR-30a and inhibit its activity, which increases the expression of its targets MYSM1 and IER2 and implicated in AML relapse. CONCLUSIONS: Collectively, these findings demonstrated that circRNF220 could be highly efficient and specific for the accurate diagnosis of pediatric AML, with implications for relapse prediction.

5.
Front Public Health ; 9: 691554, 2021.
Artigo em Inglês | MEDLINE | ID: mdl-34631641

RESUMO

Objective: This paper aimed to systematically review the application methods and components of step counter-based physical activity (PA) promotion programs in patients with chronic obstructive pulmonary disease (COPD). The effects of longer-duration (≥12 weeks) programs on PA, exercise capacity, quality of life, and dyspnea were discussed. Methods: This review was performed in accordance with the preferred reporting items for systematic reviews and meta-analysis. Online data resources PubMed, Web of Science, Embase, and EBSCO were searched. The publication year was limited between January 2000 to August 2020. All randomized controlled trials with ≥12-week duration of step counter-based PA promotion programs of COPD were included. Two researchers independently assessed the quality of the included studies and extracted their characteristics. Results: Nine studies involving 1,450 participants were included. Step counters, counseling, exercise goals, diaries, and tele-communicational approaches were common components of these programs. The PA feedback tools were mostly pedometers (n = 8), whereas accelerometers were often used as assessment tools of PA (n = 5). All studies implemented counseling: five applied behavioral change theories, and three reported motivational interview techniques simultaneously. Six studies reported detailed exercise goals. The usual exercise goal was to reach a total of 8,000-10,000 steps/day. Three research studies used diaries, and five applied tele-communication approaches to deliver interventions. The programs could be implemented alone (n = 4), in combination with exercise training (n = 2), or with pulmonary rehabilitation (n = 2). All studies showed a significant increase in the PA (≥793 steps/day). Three studies observed a significant improvement in exercise capacity (≥13.4 m), and two reported a significant increase in the quality of life (p < 0.05). No study showed significant between-group differences in dyspnea. Conclusion: There are a few studies assessing the impact of long-duration (≥12 weeks) step counter-based interventions in COPD, with different methodologies, although all studies included counseling and exercise goal setting. These interventions seem to have a positive effect on PA. A few studies also showed benefit on exercise capacity and quality of life.


Assuntos
Doença Pulmonar Obstrutiva Crônica , Qualidade de Vida , Dispneia , Exercício Físico , Tolerância ao Exercício , Humanos , Doença Pulmonar Obstrutiva Crônica/terapia
6.
Glia ; 2021 Oct 29.
Artigo em Inglês | MEDLINE | ID: mdl-34713920

RESUMO

The integrity of blood-brain-barrier (BBB) is essential for normal brain functions, synaptic remodeling, and angiogenesis. BBB disruption is a common pathology during Parkinson's disease (PD), and has been hypothesized to contribute to the progression of PD. However, the molecular mechanism of BBB disruption in PD needs further investigation. Here, A53T PD mouse and a 3-cell type in vitro BBB model were used to study the roles of α-synuclein (α-syn) in BBB disruption with the key results confirmed in the brains of PD patients obtained at autopsy. The A53T PD mouse studies showed that the expression of tight junction-related proteins decreased, along with increased vascular permeability and accumulation of oligomeric α-syn in activated astrocytes in the brain. The in vitro BBB model studies demonstrated that treatment with oligomeric α-syn, but not monomeric or fibrillar α-syn, resulted in significant disruption of BBB integrity. This process involved the expression and release of vascular endothelial growth factor A (VEGFA) and nitric oxide (NO) from oligomeric α-syn treated astrocytes. Increased levels of VEGFA and iNOS were also observed in the brain of PD patients. Blocking the VEGFA signaling pathway in the in vitro BBB model effectively protected the barrier against the harmful effects of oligomeric α-syn. Finally, the protective effects on BBB integrity associated with inhibition of VEGFA signaling pathway was also confirmed in PD mice. Taken together, our study concluded that oligomeric α-syn is critically involved in PD-associated BBB disruption, in a process that is mediated by astrocyte-derived VEGFA.

7.
Toxicol Res (Camb) ; 10(4): 875-884, 2021 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-34484679

RESUMO

Cervical cancer (CC) is a type of pelvic malignant tumor that severely threatens women's health. Current evidence suggests that IER5, as a potential radiosensitizer, promotes irradiation-induced apoptosis in CC tissues in patients undergoing chemoradiotherapy. IER5 has been shown to be involved in the G2/M-phase transition. In the present study, we used Cdc25B as the breakthrough point to explore the underlying mechanism of IER5 in the cell cycle regulation of radiation-damaged HeLa cells. IER5 was evidently upregulated after irradiation, but Cdc25B was significantly downregulated. In monoclonal IER5-silenced HeLa cells, irradiation-induced downregulation of Cdc25B was attenuated. The effect of irradiation on Cdc25B promoter activity was determined by dual-luciferase reporter assays. The response elements on the Cdc25B promoter related to irradiation were predicted by JASPAR. These conserved sequences were mutated individually or in combination by splicing-by-overlap extension PCR, and their function was confirmed by dual-luciferase reporter assays. The enrichment efficiency of transcription factors after irradiation was determined by chromatin immunoprecipitation (ChIP) assay. Both Sp1/Sp3 and NF-YB binding sites were involved in irradiation-mediated regulation of Cdc25B. IER5 was involved in irradiation-mediated regulation of Cdc25B through the NF-YB binding site. Furthermore, ChIP assays showed that IER5 bound to the Cdc25B promoter, and the binding of IER5 to the Cdc25B promoter region in irradiation-induced HeLa cells induced the release of the coactivator p300 through interaction with NF-YB. Taken together, these findings indicate that IER5 is the transcriptional repressor that accelerates the downregulation of Cdc25B expression after irradiation.

8.
Front Oncol ; 11: 635251, 2021.
Artigo em Inglês | MEDLINE | ID: mdl-34568001

RESUMO

Objective: To reveal the contributing role of METTL3 gene SNPs in pediatric ALL risk. Patients and Methods: A total of 808 pediatric ALL cases and 1,340 cancer-free controls from five hospitals in South China were recruited. A case-control study by genotyping three SNPs in the METTL3 gene was conducted. Genomic DNA was abstracted from peripheral blood. Three SNPs (rs1263801 C>G, rs1139130 A>G, and rs1061027 A>C) in the METTL3 gene were chosen to be detected by taqman real-time polymerase chain reaction assay. Results: That rs1263801 C>G, rs1139130 A>G, and rs1061027 A>C polymorphisms were significantly associated with increased pediatric ALL risk was identified. In stratification analyses, it was discovered that rs1263801 CC, rs1061027 AA, and rs1139130 GG carriers were more likely to develop ALL in subgroups of common B-ALL, MLL gene fusion. Rs1263801 CC and rs10610257 AA carriers were more possible to increase the risk of ALL in subgroups of low hyperdiploid, and all of these three SNPs exhibited a trend toward the risk of ALL. All of these three polymorphisms were associated with the primitive/naïve lymphocytes and MRD in marrow after chemotherapy in ALL children. Rs1263801 CC and rs1139130 AA alleles provided a protective effect on MRD ≥0.01% among CCCG-treated children. As for rs1139130, AA alleles provided a protective effect on MRD in marrow ≥0.01% on 33 days and 12 weeks among CCCG-treated children, but provided a risk effect on MRD in the marrow ≥0.01% among SCCLG-treated children. As for rs1263801 CC and rs1139130 AA, these two alleles provided a protective effect on MRD in the marrow ≥0.01% among CCCG-treated children. Conclusion: In this study, we revealed that METTL3 gene polymorphisms were associated with increased pediatric ALL risk and indicated that METTL3 gene polymorphisms might be a potential biomarker for choosing ALL chemotherapeutics.

9.
Transgenic Res ; 30(6): 727-737, 2021 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-34460070

RESUMO

Salt stress is an important abiotic factor that causes severe losses in soybean yield and quality. Therefore, breeding salt-tolerant soybean germplasm resources via genetic engineering has gained importance. Aspergillus glaucus, a halophilic fungus that exhibits significant tolerance to salt, carries the gene AgGlpF. In this study, we used the soybean cotyledonary node transformation method to transfer the AgGlpF gene into the genome of the soybean variety Williams 82 to generate salt-tolerant transgenic soybean varieties. The results of PCR, Southern blot, ddPCR, and RT-PCR indicated that AgGlpF was successfully integrated into the soybean genome and stably expressed. When subjected to salt stress conditions via treatment with 250 mM NaCl for 3 d, the transgenic soybean plants showed significant tolerance compared with wild-type plants, which exhibited withering symptoms and leaf abscission after 9 d. The results of this study indicated that the transfer of AgGlpF into the genome of soybean plants produced transgenic soybean with significantly improved salt stress tolerance.

10.
Brain Res Bull ; 176: 76-84, 2021 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-34371139

RESUMO

OBJECTIVE: c-myc has been reported to attenuate ischemia stroke (IS). We initiated the research to uncover the molecular mechanism of c-myc with regard to microRNA (miR)-200b-5p/Sirtuin1 (SIRT1) axis. METHODS: An IS mouse model was prepared by middle cerebral artery occlusion (MCAO). Measurements of c-myc, miR-200b-5p and SIRT1 levels in MCAO mice were conducted. c-myc, miR-200b-5p and SIRT1 expression levels in MCAO mice were detected. The neurological function, production of inflammatory cytokines, neuronal apoptosis, brain tissue pathology and neuronal survival of MCAO mice were observed. RESULTS: c-myc and SIRT1 levels went downward while miR-200b-5p expression went upward in MCAO mice. Elevation of c-myc or suppression of miR-200b-5p improved neurological function, reduced inflammation and neuronal apoptosis, and attenuated brain tissue pathology and neuronal survival of MCAO mice. Enhancement of miR-200b-5p or knockdown of SIRT1 weakened c-myc-induced protection against MCAO-induced brain injury in mice. CONCLUSION: Overall, c-myc protects mice from IS through elevating miR-200b-5p-targeted SIRT1 expression.

11.
Int J Chron Obstruct Pulmon Dis ; 16: 2023-2037, 2021.
Artigo em Inglês | MEDLINE | ID: mdl-34262271

RESUMO

Introduction: Diaphragm dysfunction is a significant extrapulmonary effect in chronic obstructive pulmonary disease (COPD), which is manifested by changes in diaphragm structure and reduced diaphragm strength. Acupuncture is a traditional rehabilitation technique in China, which has been used in rehabilitation for COPD. But whether acupuncture can improve the diaphragm function of COPD patients remains to be verified. Objective: The objective of this study was to evaluate the rehabilitation effects of acupuncture on diaphragm dysfunction in patients with COPD. Methods: The authors retrieved in CNKI, VIP, SinoMed, PubMed, Ebsco, Web of Science, from inception to November 2020, for relevant randomized control trials. Two researchers independently screened the articles and extracted the data. The quality of the included studies was evaluated by Physiotherapy Evidence Database scale. The primary outcome measures were maximal inspiratory pressure and the scale for accessory respiratory muscle mobilization, the secondary outcome measures were pulmonary function-related indicators and arterial blood gas indicators. Results: Nine articles were finally obtained. Seven studies added acupuncture to standard treatment for patients with diaphragm dysfunction in COPD and found statistically significant changes in the maximum inspiratory pressure and the scale for accessory respiratory muscle mobilization. Two studies have proved that use acupuncture combined with other Traditional Chinese Medicine methods in the rehabilitation for COPD can effectively improve the diaphragm strength and diaphragmatic motor performance. Seven studies showed that acupuncture has obvious improvement in pulmonary ventilation function. Seven studies reported significant differences in arterial blood gas pre- to post-intervention. Conclusion: This systematic review found that acupuncture can effectively enhance the diaphragm strength, relieve respiratory muscle fatigue, it can also play a promoting role in improving lung function, hypoxia, and carbon dioxide retention, as well as preventing and alleviating respiratory failure. The generalizability of these results is limited by the design of the included studies.


Assuntos
Terapia por Acupuntura , Doença Pulmonar Obstrutiva Crônica , Diafragma , Humanos , Doença Pulmonar Obstrutiva Crônica/diagnóstico , Doença Pulmonar Obstrutiva Crônica/terapia , Respiração , Músculos Respiratórios
12.
J Hazard Mater ; 417: 126019, 2021 09 05.
Artigo em Inglês | MEDLINE | ID: mdl-34229378

RESUMO

Sulfidated microscale zero-valent iron (SmZVI) attracts much attention recently in remediation of contaminated groundwater, but whether polymer coating on SmZVI would impact on its reactivity and capacity is yet to be understood. In this work, SmZVI was prepared by milling mZVI with elemental sulfur, and its stability in agar solution was evaluated. The impact of polymer coating on SmZVI grains' capacity and reactivity for chromate reduction was then examined. Experimental results indicated that SmZVI having the best overall performance was attained by grinding mZVI with elemental sulfur at 0.05 S/Fe molar ratio for 10 h. SmZVI's stability can be substantially improved if dispersed in 2.0 g/L agar solution. Existence of agar films on the SmZVI grain (A-SmZVI) lowered the material's capacity for chromate reduction by 56%, and the associated reaction kinetics by 70.4%, as estimated by pseudo first-order reaction model using the early-stage experimental data. Analysis of XPS spectra of A-SmZVI post reaction with chromate indicated that multiple reductive species including Fe0, Fe(II), FeS, and S(-II) may have jointly participated in the redox reaction taking place on the A-SmZVI-water interface. Fitting of XPS data supported that S(-II) was oxidized to SO42-, S2O32-, and S0, in order of decreasing surface concentration.


Assuntos
Água Subterrânea , Poluentes Químicos da Água , Ágar , Cromatos , Ferro , Poluentes Químicos da Água/análise
13.
Sci Rep ; 11(1): 15077, 2021 07 23.
Artigo em Inglês | MEDLINE | ID: mdl-34302002

RESUMO

Quantitative in vivo monitoring of cell biodistribution offers assessment of treatment efficacy in real-time and can provide guidance for further optimization of chimeric antigen receptor (CAR) modified cell therapy. We evaluated the utility of a non-invasive, serial 89Zr-oxine PET imaging to assess optimal dosing for huLym-1-A-BB3z-CAR T-cell directed to Lym-1-positive Raji lymphoma xenograft in NOD Scid-IL2Rgammanull (NSG) mice. In vitro experiments showed no detrimental effects in cell health and function following 89Zr-oxine labeling. In vivo experiments employed simultaneous PET/MRI of Raji-bearing NSG mice on day 0 (3 h), 1, 2, and 5 after intravenous administration of low (1.87 ± 0.04 × 106 cells), middle (7.14 ± 0.45 × 106 cells), or high (16.83 ± 0.41 × 106 cells) cell dose. Biodistribution (%ID/g) in regions of interests defined over T1-weighted MRI, such as blood, bone, brain, liver, lungs, spleen, and tumor, were analyzed from PET images. Escalating doses of CAR T-cells resulted in dose-dependent %ID/g biodistributions in all regions. Middle and High dose groups showed significantly higher tumor %ID/g compared to Low dose group on day 2. Tumor-to-blood ratios showed the enhanced extravascular tumor uptake by day 2 in the Low dose group, while the Middle dose showed significant tumor accumulation starting on day 1 up to day 5. From these data obtained over time, it is apparent that intravenously administered CAR T-cells become trapped in the lung for 3-5 h and then migrate to the liver and spleen for up to 2-3 days. This surprising biodistribution data may be responsible for the inactivation of these cells before targeting solid tumors. Ex vivo biodistributions confirmed in vivo PET-derived biodistributions. According to these studies, we conclude that in vivo serial PET imaging with 89Zr-oxine labeled CAR T-cells provides real-time monitoring of biodistributions crucial for interpreting efficacy and guiding treatment in patient care.


Assuntos
Neoplasias/diagnóstico por imagem , Neoplasias/metabolismo , Oxiquinolina/metabolismo , Receptores de Antígenos de Linfócitos T/metabolismo , Receptores de Antígenos Quiméricos/metabolismo , Linfócitos T/metabolismo , Zircônio/metabolismo , Animais , Linhagem Celular Tumoral , Masculino , Camundongos , Camundongos Endogâmicos NOD , Camundongos SCID , Tomografia por Emissão de Pósitrons/métodos , Radioisótopos/metabolismo , Distribuição Tecidual/fisiologia
14.
Pain ; 162(7): 1960-1976, 2021 07 01.
Artigo em Inglês | MEDLINE | ID: mdl-34130310

RESUMO

ABSTRACT: The methyltransferase-like 3 (Mettl3) is a key component of the large N6-adenosine-methyltransferase complex in mammalian responsible for RNA N6-methyladenosine (m6A) modification, which plays an important role in gene post-transcription modulation. Although RNA m6A is enriched in mammalian neurons, its regulatory function in nociceptive information processing remains elusive. Here, we reported that Complete Freund's Adjuvant (CFA)-induced inflammatory pain significantly decreased global m6A level and m6A writer Mettl3 in the spinal cord. Mimicking this decease by knocking down or conditionally deleting spinal Mettl3 elevated the levels of m6A in ten-eleven translocation methylcytosine dioxygenases 1 (Tet1) mRNA and TET1 protein in the spinal cord, leading to production of pain hypersensitivity. By contrast, overexpressing Mettl3 reversed a loss of m6A in Tet1 mRNA and blocked the CFA-induced increase of TET1 in the spinal cord, resulting in the attenuation of pain behavior. Furthermore, the decreased level of spinal YT521-B homology domain family protein 2 (YTHDF2), an RNA m6A reader, stabilized upregulation of spinal TET1 because of the reduction of Tet1 mRNA decay by the binding to m6A in Tet1 mRNA in the spinal cord after CFA. This study reveals a novel mechanism for downregulated spinal cord METTL3 coordinating with YTHDF2 contributes to the modulation of inflammatory pain through stabilizing upregulation of TET1 in spinal neurons.


Assuntos
Adenosina , Metiltransferases , Animais , Dor/genética , RNA , RNA Mensageiro
15.
Front Physiol ; 12: 684453, 2021.
Artigo em Inglês | MEDLINE | ID: mdl-34163375

RESUMO

Chronic obstructive pulmonary disease (COPD) can cause extrapulmonary injury such as diaphragm dysfunction. Oxidative stress is one of the main factors causing diaphragm dysfunction in COPD. Exercise plays a positive role in the prevention and treatment of diaphragm dysfunction in COPD, and the changes in diaphragm structure and function induced by exercise are closely related to the regulation of oxidative stress. Therefore, on the basis of the review of oxidative stress and the changes in diaphragm structure and function in COPD, this article analyzed the effects of exercise on oxidative stress and diaphragm dysfunction in COPD and explored the possible mechanism by which exercise improves oxidative stress. Studies have found that diaphragm dysfunction in COPD includes the decline of muscle strength, endurance, and activity. Oxidative stress mainly affects the structure and function of the diaphragm in COPD through protein oxidation, protease activation and calcium sensitivity reduction. The effects of exercise on oxidative stress level and diaphragm dysfunction may differ depending on the intensity, duration, and style of exercise. The mechanism of exercise on oxidative stress in the diaphragm of COPD may include improving antioxidant capacity, reducing oxidase activity and improving mitochondrial function.

16.
Chemosphere ; 280: 130711, 2021 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-34162083

RESUMO

The intestine is the important bioaccumulation and target organ of Bisphenol F (BPF) and Bisphenol S (BPS). Morphological and functional abnormalities induced by BPS and BPF exposure in zebrafish intestine have been reported. However, the underlying mechanisms are not well understood, and the combined toxicities of BPS and BPF in the intestine have not been studied. Here, the zebrafish were treated by single and combined exposure of BPF and BPS at 1, 10, 100, 1000 µg/L. Oxidative damage, inflammation, and transcriptome profiles in the zebrafish intestine were determined. Changes in microbial community structure in zebrafish intestine were analyzed. Results showed that BPF, BPS, and BPF + BPS exposures significantly increased MDA, 8-OHdG, 1L-1ß, and TNF-α levels in the zebrafish intestine, indicating oxidative damage and inflammatory effects. Co-exposure of BPS and BPF did not cause synergistic effects on the above effects but induced more changes in gene expression profiles. The changes in the PPAR signaling pathway might be associated with oxidative damage and inflammation. The amino acid metabolism and steroid biosynthesis were specifically altered by co-exposure of BPF and BPS. Moreover, BPF and/or BPS exposures altered microbial community structure in the zebrafish intestine, which showed different influence patterns. Increased abundance of potentially pathogenic bacteria (such as Flavobacterium, Pseudomonas, and Stenotrophomonas) might indicate one of the potential health hazards in zebrafish intestine. The above results provide basic information for the health risk assessment of BPS and BPF in aquatic organisms.


Assuntos
Microbiota , Peixe-Zebra , Animais , Compostos Benzidrílicos/toxicidade , Intestinos , Fenóis , Sulfonas , Peixe-Zebra/genética
17.
Phys Rev Lett ; 126(17): 173902, 2021 Apr 30.
Artigo em Inglês | MEDLINE | ID: mdl-33988417

RESUMO

The quantum behavior of surface plasmons has received extensive attention, benefiting from the development of exquisite nanotechnology and the diverse applications. Blueshift, redshift, and nonshift of localized surface plasmon resonances (LSPRs) have all been reported as the particle size decreases and enters the quantum size regime, but the underlying physical mechanism to induce these controversial size dependences is not clear. Herein, we propose an improved semiclassical model for modifying the dielectric function of metal nanospheres by combining the intrinsic quantized electron transitions and surface electron injection or extraction to investigate the plasmon shift and LSPR size dependence of the charged Au nanoparticles. We experimentally observe that the nonmonotonic blueshift of LSPRs with size for Au nanoparticles is turned into an approximately monotonic blueshift by increasing the electron donor concentration in the reduction solution, and it can also be transformed to an approximately monotonic redshift after surface passivation by ligand molecules. Moreover, we demonstrate controlled blueshift and redshift for the electron and hole plasmons in Cu_{2-x}S@Au core-shell nanoparticles by injecting electrons. The experimental observations and the theoretical calculations clarify the controversial size dependences of LSPR reported in the literature, reveal the critical role of surface electron injection or extraction in the transformation between the different size dependences of LSPRs, and are helpful for understanding the nature of surface plasmons in the quantum size regime.

18.
Case Rep Womens Health ; 31: e00321, 2021 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-33968612

RESUMO

The effects of SARS-CoV-2 infection in the first trimester on the pregnant woman and the fetus remain unclear. We describe the complete follow-up of a pregnant woman with asymptomatic SARS-CoV-2 infection in the first trimester. The woman tested positive for SARS-CoV-2 viral RNA in nasopharyngeal swabs in her seventh week of gestation and was admitted to a local hospital for treatment. Although the woman had a BMI above 28 and a total gestational weight gain of 21 kg, no pregnancy complications or severe complications related to SARS-CoV-2 were reported. An ultrasound scan identified no fetal abnormalities at 22 weeks. The pregnancy ended at term (37 weeks), and the newborn's birth weight was 3100 g. Placental insufficiency was revealed by placental histology examination but this appeared not to be related to the SARS-CoV-2 infection. In-situ hybridisation and immunohistochemical tests for SARS-CoV-2 RNA, spike protein 1, and nucleocapsid proteins were negative. However, ACE-2 was positive in samples of the placenta, umbilical cord and fetal membrane. The baby was followed up through to 10 days after birth and grew normally. Our results suggest that asymptomatic SARS-CoV-2 infection in the first trimester of pregnancy might not have significant harmful effects on the mother and the developing fetus. This finding may be of interest to the general public, midwives and general practitioners. However, large population studies are needed to confirm our findings.

19.
Clin Respir J ; 15(9): 956-966, 2021 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-33998778

RESUMO

OBJECTIVES: This study was conducted to investigate the effect of water-based Liuzijue exercise on peak exercise capacity, functional exercise capacity, and quality of life in people with COPD. METHODS: The study included 50 participants randomly divided into three groups: a control group (CG = 17), a land-based Liuzijue exercise group (LG = 17), and a water-based Liuzijue exercise group (WG = 16). The LG and WG performed Liuzijue exercise in different environments, and the CG had no exercise intervention. All participants received prescribed medical treatment. Liuzijue exercise was performed according to the description of Health Qigong Liuzijue compiled by Chinese Health Qigong Association for 60 minutes, two times per week, for 12 weeks. RESULTS: After intervention, peak oxygen uptake and peak working rate were significantly improved in WG (P = .02). The results of the 6 minutes walking test (6MWT) and 30 seconds sit-to-stand test were significantly improved in both WG and LG (P < .05), and significant difference was found between WG and CG in 6MWT (P = .03). The St. George's Respiratory Questionnaire (SGRQ) activity score increased significantly in the CG (P = .03), while all domains of SGRQ significantly decreased in both training groups (P < .01). All SGRQ scores showed a significant difference between LG and CG (P < .05) and, except for the activity score, between WG and CG (P < .05). CONCLUSIONS: Water-based Liuzijue exercise can effectively improve peak exercise capacity, functional exercise capacity, and quality of life in people with COPD, especially with respect to increasing peak VO2 and 6MWD.


Assuntos
Doença Pulmonar Obstrutiva Crônica , Qigong , Tolerância ao Exercício , Humanos , Doença Pulmonar Obstrutiva Crônica/terapia , Qualidade de Vida , Água
20.
Acta Neuropathol Commun ; 9(1): 37, 2021 03 08.
Artigo em Inglês | MEDLINE | ID: mdl-33685516

RESUMO

Peripheral biomarkers indicative of brain pathology are critically needed for early detection of Parkinson's disease (PD). In this study, using NanoString and digital PCR technologies, we began by screening for alterations in genes associated with PD or atypical Parkinsonism in erythrocytes of PD patients, in which PD-related changes have been reported, and which contain ~ 99% of blood α-synuclein. Erythrocytic CHCHD2 mRNA was significantly reduced even at the early stages of the disease. A significant reduction in protein and/or mRNA expression of CHCHD2 was confirmed in PD brains collected at autopsy as well as in the brains of a PD animal model overexpressing α-synuclein, in addition to seeing a reduction of CHCHD2 in erythrocytes of the same animals. Overexpression of α-synuclein in cellular models of PD also resulted in reduced CHCHD2, via mechanisms likely involving altered subcellular localization of p300 histone acetyltransferase. Finally, the utility of reduced CHCHD2 mRNA as a biomarker for detecting PD, including early-stage PD, was validated in a larger cohort of 205 PD patients and 135 normal controls, with a receiver operating characteristic analysis demonstrating > 80% sensitivity and specificity.


Assuntos
Encéfalo/patologia , Proteínas de Ligação a DNA/sangue , Proteínas de Ligação a DNA/genética , Eritrócitos/metabolismo , Doença de Parkinson/genética , Doença de Parkinson/patologia , RNA Mensageiro , Fatores de Transcrição/sangue , Fatores de Transcrição/genética , Idoso , Idoso de 80 Anos ou mais , Animais , Autopsia , Biomarcadores , Encéfalo/metabolismo , Estudos de Coortes , Modelos Animais de Doenças , Feminino , Humanos , Masculino , Camundongos , Camundongos Transgênicos , Pessoa de Meia-Idade , Mitocôndrias/metabolismo , Mutação , Doença de Parkinson/sangue , Doença de Parkinson/metabolismo , RNA Mensageiro/genética , RNA Mensageiro/metabolismo , alfa-Sinucleína/sangue , alfa-Sinucleína/metabolismo , Fatores de Transcrição de p300-CBP/metabolismo
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