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1.
Nature ; 596(7871): 227-231, 2021 08.
Artigo em Inglês | MEDLINE | ID: mdl-34381235

RESUMO

Topological superfluidity is an important concept in electronic materials as well as ultracold atomic gases1. However, although progress has been made by hybridizing superconductors with topological substrates, the search for a material-natural or artificial-that intrinsically exhibits topological superfluidity has been ongoing since the discovery of the superfluid 3He-A phase2. Here we report evidence for a globally chiral atomic superfluid, induced by interaction-driven time-reversal symmetry breaking in the second Bloch band of an optical lattice with hexagonal boron nitride geometry. This realizes a long-lived Bose-Einstein condensate of 87Rb atoms beyond present limits to orbitally featureless scenarios in the lowest Bloch band. Time-of-flight and band mapping measurements reveal that the local phases and orbital rotations of atoms are spontaneously ordered into a vortex array, showing evidence of the emergence of global angular momentum across the entire lattice. A phenomenological effective model is used to capture the dynamics of Bogoliubov quasi-particle excitations above the ground state, which are shown to exhibit a topological band structure. The observed bosonic phase is expected to exhibit phenomena that are conceptually distinct from, but related to, the quantum anomalous Hall effect3-7 in electronic condensed matter.

2.
Ann Hematol ; 2024 Apr 30.
Artigo em Inglês | MEDLINE | ID: mdl-38684510

RESUMO

Hematopoietic stem cells (HSCs) are an ideal source for the treatment of many hematological diseases and malignancies, as well as diseases of other systems, because of their two important features, self-renewal and multipotential differentiation, which have the ability to rebuild the blood system and immune system of the body. However, so far, the insufficient number of available HSCs, whether from bone marrow (BM), mobilized peripheral blood or umbilical cord blood, is still the main restricting factor for the clinical application. Therefore, strategies to expand HSCs numbers and maintain HSCs functions through ex vivo culture are urgently required. In this review, we outline the basic biology characteristics of HSCs, and focus on the regulatory factors in BM niche affecting the functions of HSCs. Then, we introduce several representative strategies used for HSCs from these three sources ex vivo expansion associated with BM niche. These findings have deepened our understanding of the mechanisms by which HSCs balance self-renewal and differentiation and provided a theoretical basis for the efficient clinical HSCs expansion.

3.
Mol Cell Probes ; 76: 101966, 2024 Jun 15.
Artigo em Inglês | MEDLINE | ID: mdl-38866345

RESUMO

Platelet-derived growth factor receptor ß (PDGFRß) plays a crucial role in murine haematopoiesis. Baicalein (BAI), a naturally occurring flavonoid, can alleviate disease damage through anti-oxidative, anti-apoptotic, and anti-inflammatory mechanisms. However, whether BAI attenuates oxidative damage in murine haematopoietic cells by PDGFRß remains unexplored. In this study, we utilized a tert-butyl hydroperoxide (TBHP)-induced BaF3 cell injury model and an ionising radiation (IR)-induced mice injury model to investigate the impact of the presence or absence of PDGFRß on the pharmacological effects of BAI. In addition, the BAI-PDGFRß interaction was characterized by molecular docking and dynamics simulations. The results show that a specific concentration of BAI led to increased cell viability, reduced reactive oxygen species (ROS) content, upregulated nuclear factor erythroid 2-related factor 2 (NRF2) expression, and its downstream target genes heme oxygenase 1 (HO-1) and NAD(P)H Quinone Dehydrogenase 1 (NQO1), and activated protein kinase B (AKT) pathway in cells expressing PDGFRß plasmid and experiencing damage. Similarly, BAI elevated lineage-Sca1+cKIT+ (LSK) cell proportion, promoted haematopoietic restoration, enhanced NRF2-mediated antioxidant response in PDGFRß+/+ mice. However, despite BAI usage, PDGFRß knockout mice (PDGFRß-/-) showed lower LSK proportion and less antioxidant capacity than the total body irradiation (TBI) group. Furthermore, we demonstrated an interaction between BAI and PDGFRß at the molecular level. Collectively, our results indicate that BAI attenuates oxidative stress injury and helps promote haematopoietic cell recovery through regulation of PDGFRß.

4.
Prostate ; 83(1): 97-108, 2023 01.
Artigo em Inglês | MEDLINE | ID: mdl-36164668

RESUMO

BACKGROUND: The PI3K/AKT/mTOR signaling pathway is essential for initiation and progression of prostate cancer. However, there has been no a comprehensive comparison for the role of these signaling nodes in prostate tumor initiation and progression. METHODS: With genetically engineered animal models, we compared the impact of prostate-specific deletions of Pten, Tsc1, and Tsc2 and activation of Akt1 on tumor initiation and progression. Also, we assessed the expression and genetic alterations of PTEN, AKT1, TSC1, and TSC2 in human primary prostate cancers. RESULTS: For the genetically engineered mice, prostate conditional knockout (cKO) of Pten, Tsc1, and Tsc2 led to initiation and progression of mouse prostatic neoplasia hyperplasia (mPIN). Akt1 transgenic mice developed more aggressive mPINs than mice with Tsc1 or Tsc2 single-cKO, but the effect was more moderate than that for Pten single-cKO or Tsc1/Tsc2 double-cKO mice. Functional analyses showed that Pten single-cKO, AKT1 activation, and Tsc1/Tsc2 double-cKO induced cell proliferation more than Tsc1 or Tsc2 single-cKO, but only Pten single-cKO and AKT1 activation reduced epithelial adhesion. All cKO or AKT1 activation enhanced the phosphorylation of p-S6 (S235/236) but only Pten single-cKO and Tsc1/Tsc2 double-cKO enhanced the phosphorylation of p-AKT (S473) and p-4EBP1 (T37/46/70). In human prostate cancers, PTEN, but not AKT1, TSC1, or TSC2 had frequent genetic alterations. However, as key signaling nodes, AKT1, TSC1, and TSC2 may be responsible for PTEN loss-mediated tumor initiation and progression. CONCLUSION: Our results for genetically engineered mouse models suggest a differential role of the PI3K/AKT/mTOR signaling nodes in prostate cancer initiation and progression, but the underlying molecular mechanisms remain unaddressed.


Assuntos
Fosfatidilinositol 3-Quinases , Neoplasias da Próstata , Masculino , Humanos , Camundongos , Animais , Mutação , Transdução de Sinais , Neoplasias da Próstata/genética , Modelos Animais , Serina-Treonina Quinases TOR
5.
Phys Rev Lett ; 131(22): 226001, 2023 Dec 01.
Artigo em Inglês | MEDLINE | ID: mdl-38101378

RESUMO

Understanding strongly correlated quantum materials, such as high-T_{c} superconductors, iron-based superconductors, and twisted bilayer graphene systems, remains as one of the outstanding challenges in condensed matter physics. Quantum simulation with ultracold atoms in particular optical lattices, which provide orbital degrees of freedom, is a powerful tool to contribute new insights to this endeavor. Here, we report the experimental realization of an unconventional Bose-Einstein condensate of ^{87}Rb atoms populating degenerate p orbitals in a triangular optical lattice, exhibiting remarkably long coherence times. Using time-of-flight spectroscopy, we observe that this state spontaneously breaks the rotational symmetry and its momentum spectrum agrees with the theoretically predicted coexistence of exotic stripe and loop-current orders. Like certain strongly correlated electronic systems with intertwined orders, such as high-T_{c} cuprate superconductors, twisted bilayer graphene, and the recently discovered chiral density-wave state in kagome superconductors AV_{3}Sb_{5} (A=K, Rb, Cs), the newly demonstrated quantum state, in spite of its markedly different energy scale and the bosonic quantum statistics, exhibits multiple symmetry breakings at ultralow temperatures. These findings hold the potential to enhance our comprehension of the fundamental physics governing these intricate quantum materials.

6.
Vox Sang ; 118(11): 913-920, 2023 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-37831598

RESUMO

Haematopoietic stem cell transplantation (HSCT) is considered an effective treatment for some haematopoietic malignancies, haematopoietic failure and immunodeficiency. Compared with bone marrow and mobilized peripheral blood, cord blood has the advantages of easy access, being harmless to donors and low requirement for HLA matching. In addition, umbilical cord blood transplantation (UCBT) has achieved remarkable clinical success in the past 30 years due to the low recurrence rate of malignancies treated by UCBT, mild degree of chronic graft-versus-host disease (GVHD) and good quality of life for patients after transplantation. However, the number of cells in a single cord blood is too small for rapid bone marrow implantation. We summarize the various factors involved that need to be considered in the expansion of haematopoietic stem cells (HSCs) in vitro, which all avoid complex operations, such as vector construction and virus transfection. We also found it necessary to identify a new molecule as the carrier of HSCs cultured in vitro, which not only would provide a three-dimensional structure conducive to the self-renewal of HSCs but also prevent their differentiation.


Assuntos
Doença Enxerto-Hospedeiro , Transplante de Células-Tronco Hematopoéticas , Humanos , Sangue Fetal , Qualidade de Vida , Doença Enxerto-Hospedeiro/prevenção & controle , Transplante de Células-Tronco Hematopoéticas/métodos , Células-Tronco Hematopoéticas
7.
Environ Res ; 229: 115981, 2023 07 15.
Artigo em Inglês | MEDLINE | ID: mdl-37100365

RESUMO

Alpine rivers originating from the Tibetan Plateau (TP) contain large amounts of water resources with high environmental sensitivity and eco-fragility. To clarify the variability and controlling factors of hydrochemistry on the headwater of the Yarlung Tsangpo River (YTR), the large river basin with the highest altitude in the world, water samples from the Chaiqu watershed were collected in 2018, and major ions, δ2H and δ18O of river water were analyzed. The values of δ2H (mean: -141.4‰) and δ18O (mean: -18.6‰) were lower than those in most Tibetan rivers, which followed the relationship: δ2H = 4.79*δ18O-52.2. Most river deuterium excess (d-excess) values were lower than 10‰ and positively correlated with altitude controlled by regional evaporation. The SO42- in the upstream, the HCO3- in the downstream, and the Ca2+ and Mg2+ were the controlling ions (accounting for >50% of the total anions/cations) in the Chaiqu watershed. Stoichiometry and principal component analysis (PCA) results revealed that sulfuric acid stimulated the weathering of carbonates and silicates to produce riverine solutes. This study promotes understanding water source dynamics to inform water quality and environmental management in alpine regions.


Assuntos
Monitoramento Ambiental , Poluentes Químicos da Água , Tibet , Monitoramento Ambiental/métodos , Rios , Qualidade da Água , Carbonatos/análise , Poluentes Químicos da Água/análise
8.
Neoplasma ; 70(3): 350-360, 2023 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-37498064

RESUMO

We have identified that NUDT21 plays a vital role in MDS transformations, while the transcription factor RUNX1 is essential for normal hematopoiesis, which is a high expression in acute myeloid leukemia (AML) and myelodysplastic syndromes (MDS), and we aim to explore the linkage between the two genes and new pathways for MDS transformation to AML. Prediction of RUNX1 expression levels and its relationship with NUDT21 in AML and MDS patients was performed using bioinformatics techniques and validated in patients. Using lentiviral packaging technology, NUDT21 knockdown and overexpression models were developed in AML and MDS cell lines. These models were validated using quantitative polymerase chain reaction (qPCR) and western blotting. The cell cycle, apoptosis, differentiation, and cytokines were examined by flow cytometry, CCK-8 analyzed proliferation, and the intracellular localization of NUDT21 and RUNX1 was examined by immunofluorescence. mRNA transcriptome sequencing was performed on THP-1, MUTZ-1, and Dapars analyzed SKM-1 cell lines and the sequencing data to observe the knockdown effect of NUDT21 on RUNX1. qPCR and western blot revealed a positive correlation between NUDT21 and RUNX1; both were located in the nucleus. Overexpression of NUDT21 reduced apoptosis, promoted cell proliferation, and possibly increased the invasive ability of cells. It also altered the APA site in the RUNX1 3'-UTRs region. NUDT21 regulates RUNX1 gene expression and promotes AML transformation in MDS through an APA mechanism.


Assuntos
Leucemia Mieloide Aguda , Síndromes Mielodisplásicas , Humanos , Apoptose , Proliferação de Células , Subunidade alfa 2 de Fator de Ligação ao Core/genética , Leucemia Mieloide Aguda/genética , Síndromes Mielodisplásicas/genética
9.
J Environ Manage ; 325(Pt B): 116588, 2023 Jan 01.
Artigo em Inglês | MEDLINE | ID: mdl-36308954

RESUMO

Nowadays, groundwater quality has deteriorated because of intensive human activities. It is important to accurately identify the pollution source for controlling the deterioration of groundwater quality. However, the accuracy of the current source analysis method needs to be improved. In this study, we combined hydrochemical method, isotope tracing technique and PMF model, for the first time, to trace the source of groundwater pollution in Beichuan River basin, Qinghai Province, China. According to the results, there were 35.8% of Fe, 34.1% of total hardness, 24.3% of SO42- and 8.09% of NO3- samples exceeded the Grade III standards for Groundwater quality in China, which indicated that the groundwater in the study area has been significantly affected by human activities. Hydrochemical method suggested that the chemical component originated from rock weathering, cation exchange and mineral dissolution. Based on isotope tracing technique (δ15N-NO3-, δ18O-NO3-, δ34S-SO42- and δ18O-SO42-), the primary sources of nitrate and sulfate in groundwater were soil nitrogen and oxidation of sulfide minerals in the forest area, domestic sewage and oxidation of sulfide minerals in the urban and industrial area, and mixed sources in the village and agricultural area. Finally, the pollution source of groundwater was distinguished by combining the PMF model, isotope tracing technique and hydrochemical method. Results showed that the main pollutant of groundwater is domestic sewage in the urban, village and industrial area. The contribution rates to groundwater pollution were 60.7%, 60.8% and 57.8%, respectively. However, in the forest and agricultural area, the main source changed to water-rock interaction and chemical fertilizer, and the contribution rates to groundwater quality were 53.5% and 61.0%, respectively. Our results suggested that the coupling tracing methodology can improve the accuracy of source resolution in the water environment and it can be applied to other areas of the world.


Assuntos
Água Subterrânea , Poluentes Químicos da Água , Humanos , Esgotos/análise , Monitoramento Ambiental/métodos , Poluentes Químicos da Água/análise , Isótopos de Nitrogênio/análise , Nitratos/análise , Sulfetos/análise , Água/análise , China
10.
Mol Cancer ; 21(1): 38, 2022 02 07.
Artigo em Inglês | MEDLINE | ID: mdl-35130925

RESUMO

BACKGROUND: Unlike autosomal tumor suppressors, X-linked tumor suppressors can be inactivated by a single hit due to X-chromosome inactivation (XCI). Here, we argue that targeted reactivation of the non-mutated allele from XCI offers a potential therapy for female breast cancers. METHODS: Towards this goal, we developed a dual CRISPR interference and activation (CRISPRi/a) approach for simultaneously silencing and reactivating multiple X-linked genes using two orthogonal, nuclease-deficient CRISPR/Cas9 (dCas9) proteins. RESULTS: Using Streptococcus pyogenes dCas9-KRAB for silencing XIST and Staphylococcus aureus dCas9-VPR for activating FOXP3, we achieved CRISPR activation of FOXP3 in various cell lines of human female breast cancers. In human breast cancer HCC202 cells, which express a synonymous heterozygous mutation in the coding region of FOXP3, simultaneous silencing of XIST from XCI led to enhanced and prolonged FOXP3 activation. Also, reactivation of endogenous FOXP3 in breast cancer cells by CRISPRi/a inhibited tumor growth in vitro and in vivo. We further optimized CRISPRa by fusing dCas9 to the demethylase TET1 and observed enhanced FOXP3 activation. Analysis of the conserved CpG-rich region of FOXP3 intron 1 confirmed that CRISPRi/a-mediated simultaneous FOXP3 activation and XIST silencing were accompanied by elevated H4 acetylation, including H4K5ac, H4K8ac, and H4K16ac, and H3K4me3 and lower DNA methylation. This indicates that CRISPRi/a targeting to XIST and FOXP3 loci alters their transcription and their nearby epigenetic modifications. CONCLUSIONS: The simultaneous activation and repression of the X-linked, endogenous FOXP3 and XIST from XCI offers a useful research tool and a potential therapeutic for female breast cancers.


Assuntos
Neoplasias da Mama , Genes Ligados ao Cromossomo X , Neoplasias da Mama/genética , Linhagem Celular , Metilação de DNA , Feminino , Fatores de Transcrição Forkhead/genética , Humanos , Oxigenases de Função Mista , Proteínas Proto-Oncogênicas
11.
Opt Express ; 30(25): 44375-44384, 2022 Dec 05.
Artigo em Inglês | MEDLINE | ID: mdl-36522863

RESUMO

Hexagonal optical lattices offer a tunable platform to study exotic orbital physics in solid state materials. Here, we present a versatile high-precision scheme to implement a hexagonal optical lattice potential, which is engineered by overlapping two independent triangular optical sublattices generated by laser beams with slightly different wavelengths around 1064 nm. This enables us to precisely control the detailed structure of the hexagonal lattice by adjusting the relative position and the relative lattice depth of the two triangular optical sublattices. Taking advantage of the sensitive dependence of the second Bloch band on small lattice deformations, we propose a strategy to optimize the optical lattice geometry with an extremely high precision. This method can also be extended to other lattice configurations involving more than two sublattices. Our work provides the experimental requirements in the search for novel orbital physics of ultracold atoms, for example, in the flat p-band of the hexagonal optical lattice.

12.
Phys Rev Lett ; 129(18): 185301, 2022 Oct 28.
Artigo em Inglês | MEDLINE | ID: mdl-36374672

RESUMO

The anomalous Hall effect has had a profound influence on the understanding of many electronic topological materials but is much less studied in their bosonic counterparts. We predict that an intrinsic anomalous Hall effect exists in a recently realized bosonic chiral superfluid, a p-orbital Bose-Einstein condensate in a 2D hexagonal boron nitride optical lattice [Wang et al., Nature (London) 596, 227 (2021)NATUAS0028-083610.1038/s41586-021-03702-0]. We evaluate the frequency-dependent Hall conductivity within a multi-orbital Bose-Hubbard model that accurately captures the real experimental system. We find that in the high frequency limit, the Hall conductivity is determined by finite loop current correlations on the s-orbital residing sublattice, the latter a defining feature of the system's chirality. In the opposite limit, the dc Hall conductivity can trace its origin back to the noninteracting band Berry curvature at the condensation momentum, although the contribution from atomic interactions can be significant. We discuss available experimental probes to observe this intrinsic anomalous Hall effect at both zero and finite frequencies.

13.
Environ Sci Technol ; 56(7): 4610-4619, 2022 04 05.
Artigo em Inglês | MEDLINE | ID: mdl-35294176

RESUMO

The Tibetan Plateau is sensitive to climate change, but the feedbacks of nitrogen (N) cycling to climate conditions on this plateau are not well-understood, especially under varying degrees of anthropogenic disturbances. The Nujiang River Basin, the last undammed large river basin on the Tibetan Plateau, provides an opportunity to reveal the feedbacks at a broad river basin scale. The isotopic compositions revealed that the conservative mixing of multiple sources controlled the nitrate (NO3-) loadings during the low-flow season, while biological removal processes (assimilation and denitrification) occurred in the high-flow season. During the high-flow season, soil sources, sewage, and atmospheric precipitation contributed 76.3%, 15.6%, and 8.1% to the riverine NO3-. In the low-flow season, the contribution of soil sources decreased while that of sewage increased. The relationship between d-excess and δ15N-NO3- suggests that the hydrological conditions largely controlled the N cycling dynamics in the basin, causing the high spatiotemporal heterogeneity of the riverine NO3- sources and transformation mechanisms. During the high-flow season, the precipitation and evaporation patterns controlled the in-soil processes and soil leaching. In contrast, in-stream nitrification became more evident during the low-flow season, which was related to the long water residence time. This study illustrates hydrology dominated control on N cycling over a large basin scale, which has implications for understanding the N cycling dynamics in the Tibetan Plateau.


Assuntos
Rios , Poluentes Químicos da Água , China , Monitoramento Ambiental , Hidrologia , Nitratos/análise , Nitrogênio/análise , Isótopos de Nitrogênio/análise , Tibet , Poluentes Químicos da Água/análise
14.
J Clin Lab Anal ; 36(2): e24221, 2022 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-34979042

RESUMO

OBJECTIVES: Platelet (PLT) recovery after chemotherapy is associated with the prognosis of patients with acute myeloid leukaemia (AML). This study aimed to explore the prognostic significance of early high PLT values in patients with de novo non-M3 AML who achieved first complete remission (CR). METHODS: A total of 206 patients with de novo non-M3 AML were analysed in this retrospective study. A receiver operating characteristic (ROC) curve was used to determine the optimal PLT cut-off. The overall survival (OS) and relapse-free survival (RFS) were assessed using Kaplan-Meier and Cox regression analyses. RESULTS: 312×109 /L was confined as the cut-off of the PLT count. The estimated 3-year OS of patients with high PLT was higher than that of their counterparts (72.3% vs. 34.6%, p = 0.001). In subgroup analysis, patients with high PLT had better OS in the favourable- and intermediate-risk (non-adverse-risk) AML (p = 0.001). The estimated 3-year RFS for the high and low PLT groups was 75.1% and 45.7% respectively (p = 0.078). Multivariate analyses revealed that high PLT count was an independent favourable variable for OS (HR = 0.264, p < 0.001) and RFS (HR = 0.375, p = 0.011) in the non-adverse-risk group. CONCLUSION: Our results showed that early high PLT count recovery at first CR in non-adverse-risk AML patients is a positive prognostic marker for survival outcomes.


Assuntos
Quimioterapia de Indução , Leucemia Mieloide/sangue , Contagem de Plaquetas , Adolescente , Adulto , Idoso , Criança , Feminino , Seguimentos , Humanos , Estimativa de Kaplan-Meier , Leucemia Mieloide/tratamento farmacológico , Leucemia Mieloide/mortalidade , Masculino , Pessoa de Meia-Idade , Prognóstico , Curva ROC , Indução de Remissão , Estudos Retrospectivos
15.
Environ Res ; 194: 110721, 2021 03.
Artigo em Inglês | MEDLINE | ID: mdl-33421426

RESUMO

To date, basin-scale understanding of nitrogen (N) cycling is lacking, which undermines riverine N pollution control efforts. Applying a multiple-isotopic approach, this study provided insights into the impacts of climate and anthropogenic activities on the N cycling at a basin scale. The isotopic compositions of the river water were regulated by a simple mixing process in winter, while unconservative processes (nitrification and denitrification) occurred in warm seasons. Denitrification dominated the N transformations in summer, while coupled nitrification-denitrification in soils after fertilization was responsible for the isotopic fractionations in spring and autumn. While at least 58.7% of the nitrate (NO3-) was removed from the basin, the NO3- loadings in the river remained high, suggesting that the ecosystem services could not balance the anthropogenic pollution. After correcting the isotopic fractionations, the sources of the riverine NO3- were quantified by a Markov chain Monte Carlo isotope mixing model. The contributions of point sources versus non-point sources changed dynamically with the precipitation and fertilization patterns. In summer and autumn, the soil organic N and chemical fertilizer dominated the riverine NO3-, with total contributions of 75.9% and 74.6%, respectively. The contributions from sewage and manure significantly increased during spring (47.9%) and winter (50.2%). Overall, the annual NO3- fluxes were from SON (28.7%), CF (28.1%), DS (18.2%), MA (23.9%), and AP (1.1%). In addition, we presented the large uncertainties in source apportionment that arose from the ignorance of isotope fractionations, highlighting the importance of considering the effect of isotopic fractionations in N source apportionment studies.


Assuntos
Rios , Poluentes Químicos da Água , China , Ecossistema , Monitoramento Ambiental , Nitratos/análise , Nitrogênio/análise , Isótopos de Nitrogênio/análise , Poluentes Químicos da Água/análise
16.
Neural Plast ; 2021: 9926445, 2021.
Artigo em Inglês | MEDLINE | ID: mdl-34221005

RESUMO

Parkinson's disease (PD) is a chronic and progressive neurodegenerative disease caused by degeneration of dopaminergic neurons in the substantia nigra. Existing pharmaceutical treatments offer alleviation of symptoms but cannot delay disease progression and are often associated with significant side effects. Clinical studies have demonstrated that acupuncture may be beneficial for PD treatment, particularly in terms of ameliorating PD symptoms when combined with anti-PD medication, reducing the required dose of medication and associated side effects. During early stages of PD, acupuncture may even be used to replace medication. It has also been found that acupuncture can protect dopaminergic neurons from degeneration via antioxidative stress, anti-inflammatory, and antiapoptotic pathways as well as modulating the neurotransmitter balance in the basal ganglia circuit. Here, we review current studies and reflect on the potential of acupuncture as a novel and effective treatment strategy for PD. We found that particularly during the early stages, acupuncture may reduce neurodegeneration of dopaminergic neurons and regulate the balance of the dopaminergic circuit, thus delaying the progression of the disease. The benefits of acupuncture will need to be further verified through basic and clinical studies.


Assuntos
Terapia por Acupuntura , Neurônios Dopaminérgicos/fisiologia , Doença de Parkinson/terapia , Antiparkinsonianos/uso terapêutico , Apoptose , Gânglios da Base/fisiopatologia , Bibliometria , Ensaios Clínicos como Assunto , Terapia Combinada , Dopamina/metabolismo , Humanos , Rede Nervosa/fisiopatologia , Doenças Neuroinflamatórias , Estresse Oxidativo , Doença de Parkinson/tratamento farmacológico , Doença de Parkinson/fisiopatologia , Agregação Patológica de Proteínas , Resultado do Tratamento , alfa-Sinucleína/análise
17.
Neural Plast ; 2021: 8881557, 2021.
Artigo em Inglês | MEDLINE | ID: mdl-33531894

RESUMO

Although pain is regarded as a global public health priority, analgesic therapy remains a significant challenge. Pain is a hypersensitivity state caused by peripheral and central sensitization, with the latter considered the culprit for chronic pain. This study summarizes the pathogenesis of central sensitization from the perspective of neuroglial crosstalk and synaptic plasticity and underlines the related analgesic mechanisms of acupuncture. Central sensitization is modulated by the neurotransmitters and neuropeptides involved in the ascending excitatory pathway and the descending pain modulatory system. Acupuncture analgesia is associated with downregulating glutamate in the ascending excitatory pathway and upregulating opioids, 𝛾-aminobutyric acid, norepinephrine, and 5-hydroxytryptamine in the descending pain modulatory system. Furthermore, it is increasingly appreciated that neurotransmitters, cytokines, and chemokines are implicated in neuroglial crosstalk and associated plasticity, thus contributing to central sensitization. Acupuncture produces its analgesic action by inhibiting cytokines, such as interleukin-1ß, interleukin-6, and tumor necrosis factor-α, and upregulating interleukin-10, as well as modulating chemokines and their receptors such as CX3CL1/CX3CR1, CXCL12/CXCR4, CCL2/CCR2, and CXCL1/CXCR2. These factors are regulated by acupuncture through the activation of multiple signaling pathways, including mitogen-activated protein kinase signaling (e.g., the p38, extracellular signal-regulated kinases, and c-Jun-N-terminal kinase pathways), which contribute to the activation of nociceptive neurons. However, the responses of chemokines to acupuncture vary among the types of pain models, acupuncture methods, and stimulation parameters. Thus, the exact mechanisms require future clarification. Taken together, inhibition of central sensitization modulated by neuroglial plasticity is central in acupuncture analgesia, providing a novel insight for the clinical application of acupuncture analgesia.


Assuntos
Analgesia por Acupuntura/métodos , Neuroglia/metabolismo , Plasticidade Neuronal/fisiologia , Manejo da Dor/métodos , Dor/metabolismo , Analgesia por Acupuntura/tendências , Animais , Citocinas/imunologia , Citocinas/metabolismo , Humanos , Neuroglia/imunologia , Dor/imunologia
18.
Blood Cells Mol Dis ; 81: 102393, 2020 03.
Artigo em Inglês | MEDLINE | ID: mdl-31918382

RESUMO

We analyzed the characteristics of coagulopathy in cytogenetically and molecularly distinct acute leukemias. We retrospectively analyzed 211 adult patients with de novo non-acute promyelocytic leukemia (APL) and acute myeloid leukemia (AML), and 105 newly diagnosed patients with B-cell acute lymphoblastic leukemia (B-ALL). Disseminated intravascular coagulation (DIC) occurrence was assessed according the International Society of Thrombosis and Haemostasis (ISTH) criteria. Further, we analyzed the associations of the cytogenetics and mutations with DIC development and coagulation profile. Significant differences were observed between APL and non-APL AML (P = 0.001), APL and B-ALL (P = 0.002), and non-APL AML and B-ALL (P = 0.009) in the distribution of ISTH DIC scores of the acute leukemia patients that met the criteria for diagnosis of DIC. Except for the elevated leukocyte count, a normal karyotype with NPM1 mutations or/and FLT3-ITD mutations was independently associated with the development of DIC in non-APL AML, characterized by significant PT prolongation and significantly elevated D-Dimers. The P210BCR-ABL1 transcript strongly predicted hypofibrinogenemia in B-ALL in the final multivariate model, but Philadelphia chromosome negatively affected elevated D-dimers. In conclusion, DIC occurrence and the coagulation profile were associated with the cytogenetics and mutations in acute leukemia.


Assuntos
Coagulação Intravascular Disseminada/etiologia , Leucemia/complicações , Leucemia/genética , Doença Aguda , Adulto , Citogenética , Feminino , Humanos , Leucemia/sangue , Leucemia de Células B , Leucemia Mieloide Aguda , Leucemia Promielocítica Aguda , Masculino , Mutação , Nucleofosmina , Leucemia-Linfoma Linfoblástico de Células Precursoras , Estudos Retrospectivos
19.
J Clin Lab Anal ; 34(6): e23241, 2020 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-32052899

RESUMO

BACKGROUND: Blast transformation of chronic myelogenous leukemia (CML) to T lymphoblastic lymphoma/acute lymphoblastic leukemia (T-LBL/ALL) is rare, and the molecular mechanism is still unclear. CASE REPORT: A 28-year-old woman who developed T-ALL with coexpressing both p210 and p190 BCR-ABL transcripts five years after the initial diagnosis of CML in chronic phase. The proliferation of bone marrow was extremely active with blast cells over 20%. Chromosome analysis revealed t(9;22)(q34;q11) and t(10;11)(q25;p15). Flow immunophenotyping showed that blasts expressed CD4, CD7, CD11b, CD38, CD34, CD33, and cCD3. CONCLUSION: It is the first T-cell blast of CML case with coexisting p210 and p190 as well as additional chromosome translocations. Through review this case and previous reports, we will reveal that CML patients with T-lymphocyte transformation depend on potential molecular and pathological mechanism.


Assuntos
Crise Blástica/genética , Crise Blástica/patologia , Genes abl , Leucemia-Linfoma Linfoblástico de Células T Precursoras/genética , Leucemia-Linfoma Linfoblástico de Células T Precursoras/patologia , Translocação Genética , Adulto , Feminino , Proteínas de Fusão bcr-abl/genética , Regulação Leucêmica da Expressão Gênica , Humanos , Leucemia Mielogênica Crônica BCR-ABL Positiva/genética
20.
Neural Plast ; 2020: 8890655, 2020.
Artigo em Inglês | MEDLINE | ID: mdl-33061954

RESUMO

Spinal cord injury (SCI) is a structural event with devastating consequences worldwide. Due to the limited intrinsic regenerative capacity of the spinal cord in adults, the neural restoration after SCI is difficult. Acupuncture is effective for SCI-induced neurologic deficits, and the potential mechanisms responsible for its effects involve neural protection by the inhibition of inflammation, oxidation, and apoptosis. Moreover, acupuncture promotes neural regeneration and axon sprouting by activating multiple cellular signal transduction pathways, such as the Wnt, Notch, and Rho/Rho kinase (ROCK) pathways. Several studies have demonstrated that the efficacy of combining acupuncture with mesenchymal stem cells (MSCs) transplantation is superior to either procedure alone. The advantage of the combined treatment is dependent on the ability of acupuncture to enhance the survival of MSCs, promote their differentiation into neurons, and facilitate targeted migration of MSCs to the spinal cord. Additionally, the differentiation of MSCs into neurons overcomes the problem of the shortage of endogenous neural stem cells (NSCs) in the acupuncture-treated SCI patients. Therefore, the combination of acupuncture and MSCs transplantation could become a novel and effective strategy for the treatment of SCI. Such a possibility needs to be verified by basic and clinical research.


Assuntos
Terapia por Acupuntura , Transplante de Células-Tronco Mesenquimais , Neurônios/fisiologia , Traumatismos da Medula Espinal/prevenção & controle , Traumatismos da Medula Espinal/fisiopatologia , Animais , Humanos , Plasticidade Neuronal , Recuperação de Função Fisiológica
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