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1.
Blood Cells Mol Dis ; 107: 102858, 2024 Jul.
Artículo en Inglés | MEDLINE | ID: mdl-38796983

RESUMEN

Immune thrombocytopenia (ITP) is an autoimmune disease caused by the loss of immune tolerance to platelet autoantigens, resulting in reduced platelet production and increased platelet destruction. Impaired megakaryocyte differentiation and maturation is a key factor in the pathogenesis and treatment of ITP. Sarcandra glabra, a plant of the Chloranthaceae family, is commonly used in clinical practice to treat ITP, and daucosterol (Dau) is one of its active ingredients. However, whether Dau can treat ITP and the key mechanism of its effect are still unclear. In this study, we found that Dau could effectively promote the differentiation and maturation of megakaryocytes and the formation of polyploidy in the megakaryocyte differentiation disorder model constructed by co-culturing Dami and HS-5 cells. In vivo experiments showed that Dau could not only increase the number of polyploidized megakaryocytes in the ITP rat model, but also promote the recovery of platelet count. In addition, through network pharmacology analysis, we speculated that the JAK2-STAT3 signaling pathway might be involved in the process of Dau promoting megakaryocyte differentiation. Western blot results showed that Dau inhibited the expression of P-JAK2 and P-STAT3. In summary, these results provide a basis for further studying the pharmacological mechanism of Dau in treating ITP.


Asunto(s)
Diferenciación Celular , Janus Quinasa 2 , Megacariocitos , Púrpura Trombocitopénica Idiopática , Factor de Transcripción STAT3 , Transducción de Señal , Animales , Humanos , Masculino , Ratas , Diferenciación Celular/efectos de los fármacos , Modelos Animales de Enfermedad , Janus Quinasa 2/metabolismo , Megacariocitos/metabolismo , Megacariocitos/efectos de los fármacos , Megacariocitos/citología , Púrpura Trombocitopénica Idiopática/metabolismo , Púrpura Trombocitopénica Idiopática/tratamiento farmacológico , Púrpura Trombocitopénica Idiopática/patología , Transducción de Señal/efectos de los fármacos , Sitoesteroles/farmacología , Factor de Transcripción STAT3/metabolismo
2.
Zhongguo Zhong Yao Za Zhi ; 49(13): 3636-3643, 2024 Jul.
Artículo en Zh | MEDLINE | ID: mdl-39041136

RESUMEN

To explore the effect and mechanism of Gegen Qinlian Decoction(GQD) in inhibiting M1 polarization of macrophages under inflammatory hypoxia by simulating intestinal hypoxia microenvironment in vitro. A tri-gas incubator was used to simulate normal physiological hypoxia of the colon and inflammatory hypoxia microenvironments of ulcerative colitis(UC). RAW264.7 macrophages were divided into 18.5% O_(2 )(normoxia group), 4% O_2(physiological hypoxia group), and 1% O_2(inflammatory hypoxia group), and they were induced by lipopolysaccharide(LPS) for 24 h. M1 polarization was detected by flow cytometry. Under the condition of 1% inflammatory hypoxia, they were divided into blank group, model group, and GQD-containing serum low, medium, and high dose groups. Flow cytometry was used to detect M1 polarization marker CD86, and ELISA was used to detect the expression of tumor necrosis factor-α(TNF-α) and interleukin-1ß(IL-1ß) in cell supernatant. The mRNA expression of hypoxia-inducible factor-1α(HIF-1α), TNF-α, and IL-1ß was detected by qRT-PCR. Western blot was used to detect the expression of HIF-1α/nuclear transcription factor-κB(NF-κB) signaling pathway-related proteins. The nuclear translocation of NF-κB p65 was detected by immunofluorescence. The results showed that the positive rate of CD86 in the 1% O_2 group was the highest. Under the condition of 1% inflammatory hypoxia, compared with the blank group, the expression of CD86, TNF-α, IL-1ß, and HIF-1α in the model group increased. Compared with the model group, each group of GQD could reduce the expression of CD86, TNF-α, IL-1ß, and HIF-1α. Compared with the blank group, the protein expression of HIF-1α, NF-κB p65, p-IKKα/ß, and p-IκBα in the model group increased. Compared with the model group, the protein expression of HIF-1α, NF-κB p65, p-IKKα/ß, and p-IκBα in GQD groups was significantly decreased. Compared with the blank group, NF-κB p65 in the model group entered the nucleus significantly. Compared with the model group, the nuclear expression of NF-κB p65 was decreased in each GQD group. Studies have shown that GQD may protect the intestine by down-regulating the HIF-1α/NF-κB signaling pathway to inhibit M1 polarization of macrophages and secretion of related inflammatory factors under 1% inflammatory hypoxia.


Asunto(s)
Medicamentos Herbarios Chinos , Subunidad alfa del Factor 1 Inducible por Hipoxia , Interleucina-1beta , Macrófagos , Animales , Ratones , Macrófagos/efectos de los fármacos , Macrófagos/inmunología , Macrófagos/metabolismo , Medicamentos Herbarios Chinos/farmacología , Células RAW 264.7 , Subunidad alfa del Factor 1 Inducible por Hipoxia/genética , Subunidad alfa del Factor 1 Inducible por Hipoxia/metabolismo , Interleucina-1beta/genética , Interleucina-1beta/metabolismo , Factor de Necrosis Tumoral alfa/genética , Factor de Necrosis Tumoral alfa/metabolismo , Inflamación/tratamiento farmacológico , Inflamación/genética , FN-kappa B/genética , FN-kappa B/metabolismo , Hipoxia/genética , Hipoxia/metabolismo , Transducción de Señal/efectos de los fármacos
3.
Cell Biol Int ; 41(3): 258-266, 2017 Mar.
Artículo en Inglés | MEDLINE | ID: mdl-28032386

RESUMEN

In the higher eukaryotic nucleolus, fibrillar centers (FCs), the dense fibrillar components (DFCs), and the granular components (GCs) are functional domains structurally relatively well-defined by electron microscopy (EM). However, ultrastructural alterations in FC, DFC, and GC during the cell cycle and their associated cellular functions are still largely unclear. Based on synchronized HeLa cells, we followed the structural dynamics of nucleolus during cell cycle by EM. We found that nucleolus structure shifted from tripartite to bipartite organization and FC/DFCs were reorganized in S phase with three distinct stages: (1) In early-S phase, FC/DFC structures were disassembled. (2) In mid-S phase, a transition from FC/DFC disruption to restoration occurred. As FC/DFC structures were completely disassembled, nucleoli became structurally homogenous. (3) In late-S phase, the number of small FC/DFCs increased and subsequently large FC/DFCs were constructed. Our data demonstrated that nucleolar FC/DFCs in interphase are presented in two different forms or states due to disassembly and reassembly. FC/DFCs in G1 are nucleolar structures constructed concomitantly with the establishment of nucleoli derived from the nucleolar organizer region (NOR). FC/DFCs in G2 are nucleolar components reconstituted after the global reassembly in mid-S phase. Dynamic nucleolus structures revealed in this study may serve as ultrastructural characteristics to reflect distinct stages of the cell cycle. By providing evidence for the temporal and spatial regulation of nucleolus, our findings contribute to the coupling of nucleolus structures to cell cycle dependent functions.


Asunto(s)
Nucléolo Celular/fisiología , Nucléolo Celular/ultraestructura , Fase S/fisiología , Células HeLa , Humanos
4.
Front Pharmacol ; 14: 1291195, 2023.
Artículo en Inglés | MEDLINE | ID: mdl-38322702

RESUMEN

Background and objectives: Autophagy is a cellular process where damaged organelles or unwanted proteins are packaged into a double-membrane structure and transported to lysosomes for degradation. Autophagy plays a regulatory role in various hematologic malignancies, including acute myeloid leukemia (AML). However, there are few bibliometric studies on the role of autophagy in AML. The purpose of this study is to clarify the role of autophagy in acute myeloid leukemia through bibliometric analysis. Methods: The literature on autophagy and AML research from 2003 to 2023 was searched in Web of Science Core Collection, and bibliometric tools such as VOSviewer 1.6.18, Cite Space (6.1.R3), RStudio (R package bibliometrix), and Scimago Graphica were used to understand the current status and hotspots of autophagy and AML research. The study conducted an analysis of various dimensions including the quantity of publications, countries, institutions, journals, authors, co-references, keywords, and to predict future development trends in this field by drawing relevant visualization maps. Results: A total of 343 articles were obtained, published in 169 journals, written by 2,323 authors from 295 institutions in 43 countries. The journals with the most publications were Blood and Oncotarget. China had the most publications, and Chongqing Medical University and Sun Yat-sen University had the most publications. The author with the highest number of publications was Tschan, Mario P. The main types of research included clinical research, in vitro experiments, in vivo experiments, public database information, and reviews, and the forms of therapeutic effects mainly focused on genetic regulation, traditional Chinese medicine combination, autophagy inhibitors, and drug targets. The research hotspots of autophagy and AML in the past 17 years have focused on genetic regulation, autophagy inhibition, and targeted drugs. Chemotherapy resistance and mitochondrial autophagy will be the forefront of research. Conclusion: The gradual increase in the literature on autophagy and AML research and the decline after 2022 could be a result of authors focusing more on the type of research and the quality of the literature. The current research hotspots are mainly genetic regulation, autophagy inhibition, and autophagy-related targeted drugs. In future, autophagy will remain the focus of the AML field, with research trends likely to focus more on AML chemotherapy resistance and mitochondrial autophagy.

5.
Medicine (Baltimore) ; 100(13): e24530, 2021 Apr 02.
Artículo en Inglés | MEDLINE | ID: mdl-33787570

RESUMEN

BACKGROUND: At present, Liver Cirrhosis (LC) is common in most later liver and gallbladder diseases that its morbidity and mortality seriously affect human health. The limitation and effectiveness of western medicine on LC have become a huge clinical challenge. However, a large number of clinical studies have shown that Yi-guan decoction has become a complementary treatment for LC. Therefore, this systematic review will aim to explore the safety and feasibility of Yi-guan decoction in the treatment of LC. METHODS: We will conduct a comprehensive literature search in Medline, PubMed, Cochrane Database of Systematic Reviews, Embase, Chinese Biomedical Literatures Database, China National Knowledge Infrastructure, Wang Fang Database, Chinese Scientific Journal Database from inception to December 2020 without any language restriction, In addition, relevant literature will be searched manually. The main subject terms searched: "Yi-guan decoction" "cirrhosis" "LC". Data entry will be performed by 2 researchers separately. Primary outcomes will be concluded: Liver function indicators: Total bilirubin, Alanine transaminase, Aspartate aminotransferase, etc. Secondary outcome indicators: Total effective rate, Nutrition index, Survival analysis, Adverse events; All randomized controlled trials collected in this study will be evaluated and rated using the Cochrane risk-of-biasassessment tool. Meta-analysis will be performed using RevMan 5.4.0 software. The heterogeneity test will be conducted between the studies, P < .1 and I2 > 50% are the thresholds for the tests. Using solid effect model or random effect model will be based on its heterogeneity value. RESULTS: This systematic review provides a theoretical basis for Yi-guan decoction to treat LC, we will report this result soon. CONCLUSION: This study will explore Yi-guan decoction can will be used as one of the non drug therapies to prevent or treat LC. TRIAL REGISTRATION NUMBER: INPLASY2020120114.


Asunto(s)
Medicamentos Herbarios Chinos/uso terapéutico , Cirrosis Hepática/tratamiento farmacológico , Humanos , Metaanálisis como Asunto , Ensayos Clínicos Controlados Aleatorios como Asunto , Proyectos de Investigación , Revisiones Sistemáticas como Asunto , Resultado del Tratamiento
6.
Chin J Integr Med ; 24(10): 758-762, 2018 Oct.
Artículo en Inglés | MEDLINE | ID: mdl-28914439

RESUMEN

OBJECTIVE: To investigate the impact of dampness-heat (DH) on the development of mammary tumors in 7,12-dimethylbenz(a)anthracene (DMBA)-induced rats. METHODS: Forty rats were randomly divided into 3 groups in a randomized block design, including the control group (n=13), DMBA group (n=14), and DMBA plus DH group (n=13). Rats in the DMBA group and DMBA plus DH group were intragastrically administrated with DMBA (100 mg/kg) for twice, once per week, while rats in the control group were treated with equivalent volumes of sesame oil. After DMBA administration, rats in the DMBA plus DH group were exposed to a simulated climate chamber with ambient temperature (33.0±0.5°C) and humidity (90%±5%) for 8 weeks, 8 h per day. The body weight, time of tumor formation, and number of tumors were measured weekly to calculate tumor incidence, average latency period, average number of tumors, and average tumor weight. At the end of the experiment, the levels of matrix metalloproteinase 9 (MMP-9) and tissue inhibitor of metalloproteinases 1 (TIMP-1) in serum, and the contents of tumor necrosis factor-α (TNF-α) and interleukin (IL)-1ß in serum and tumor tissue were measured, respectively. Some tumor tissues were processed for hematoxylin-eosin staining to determine the histopathological changes. RESULTS: Compared with DMBA, DMBA plus DH significantly increased the average number of tumors, average tumor weight, levels of serum MMP-9, TIMP-1, TNF-α and IL-1ß, and contents of tumor tissue TNF-α and IL-1ß (P<0.05 or P<0.01). CONCLUSION: DH could accelerate the development of mammary tumors through increasing the expressions of MMP-9, TIMP-1, TNF-α and IL-1ß in DMBA-induced rats.


Asunto(s)
Calor , Neoplasias Mamarias Animales/patología , 9,10-Dimetil-1,2-benzantraceno , Animales , Peso Corporal , Femenino , Interleucina-1beta/sangre , Neoplasias Mamarias Animales/sangre , Metaloproteinasa 9 de la Matriz/sangre , Ratas Sprague-Dawley , Inhibidor Tisular de Metaloproteinasa-1/sangre , Carga Tumoral , Factor de Necrosis Tumoral alfa/sangre
7.
Micron ; 49: 15-20, 2013 Jun.
Artículo en Inglés | MEDLINE | ID: mdl-23602556

RESUMEN

In higher eukaryotes ribosome production starts at the end of mitosis, increases during G1, is maximal in G2 (Sirri et al., 2000) and stops during prophase (Gébrane-Younès et al., 1997). But the mechanism of the change is still uncovered. Especially in the actively growing mammalian somatic cells usually contain one or several giant fibrillar centres (GFCs) with many tiny fibrillar centre (FCs) (Koberna et al., 2002; Raska et al., 2004; Casafont et al., 2007). The process how the giant fibrillar centre (GFC) and the many tiny fibrillar centres (FCs) were formed is unknown. The present results showed there were processes of FCs fusion in G1 phase and FCs regeneration in S phase respectively in the nucleoli of A 375 cells. A few FCs fused each other in late G1 phase when the process of nucleoli fusion was completed. In S phase, a lot of tiny FCs were regenerated from the periphery of GFC, separated and scattered into nucleolar matrix in late S phase and early G2 phase. The GFC was found to be coexisted with numerous tiny FCs in the nucleolus in G2 phase. The present study provided a new evidence of nucleolar dynamic change during interphase: fibrillar centre (FC) was not to be a stable state subunit of nucleolar compartment but a highly dynamic process that may be the bases of nucleolar morphological architecture organization and its function taking place.


Asunto(s)
Nucléolo Celular/metabolismo , Nucléolo Celular/ultraestructura , Fase G1 , Fase S , Línea Celular Tumoral , Humanos , Microscopía Electrónica de Transmisión
8.
Micron ; 40(4): 449-54, 2009 Jun.
Artículo en Inglés | MEDLINE | ID: mdl-19231208

RESUMEN

To investigate the correlation between subnucleolar structure and function, the precise distribution and configuration of nucleolar DNA during the cell cycle of Allium sativum were determined using the NAMA-Ur DNA-specific staining technique. We showed that nucleolar DNA is present in two forms: compacted chromatin clumps and a decondensed DNA cloud. The form of the DNA within the nucleolus varied greatly as the cell cycle progressed. During telophase, chromosomes extended into the prenucleolar body. In early G1 phase, DNA was only located in the fibrillar centers in the form of the condensed chromatin clump, while in mid-G1, S and G2 phases, the two forms of DNA were distributed in the fibrillar centers (FC) and dense fibrillar component (DFC). In prophase of mitosis, nucleolar DNA, along with FC and DFC, was linked into a network structure and condensed into a large chromatin clump. The area of the DNA cloud in the dense fibrillar component changed during different phases of the cell cycle. Our results demonstrated that the configuration of nucleolar DNA undergoes a series of decondensations and condensations during the cell cycle to fulfill the function of the nucleoli during the different phases.


Asunto(s)
Ciclo Celular , Nucléolo Celular/química , ADN de Plantas/química , Ajo/fisiología , Conformación de Ácido Nucleico , Cromatina/metabolismo , ADN de Plantas/metabolismo , Coloración y Etiquetado/métodos
9.
Cell Biol Int ; 30(10): 836-40, 2006 Oct.
Artículo en Inglés | MEDLINE | ID: mdl-16879987

RESUMEN

In order to get a deeper understanding of the relationship between nucleolus structure and its function, the dynamic change and derivation of FC (fibrillar center) and DFC (dense fibrillar component) through interphase were investigated in HeLa cells synchronized at the ultrastructural level. The results showed that there was a process of FC and DFC derivation in the nucleolus of HeLa cells during interphase. In G1 phase there were a few big FCs in the nucleolus of the HeLa cell. In S phase DFC around the FC got thickened and the configuration of the DFC changed. A lot of tiny FCs were derived from parts of the thickened DFC. We called the FC and DFC formed in G1 phase as primary FC (pri-FC) and primary DFC (pri-DFC) and the FC and DFC derived from the thickened pri-DFC as secondary FC (sec-FC) and secondary DFC (sec-DFC). In G2 phase sec-FC and sec-DFC were gradually separated from pri-DFC and scattered evenly in the nucleolus. Few large pri-FCs coexisted with numerous tiny sec-FCs in the nucleolus of HeLa cells in G2 phase. Based on the results of our observation, we suggest here a model of the dynamic change and the process of derivation of FC and DFC through interphase.


Asunto(s)
Ciclo Celular/fisiología , Núcleo Celular/ultraestructura , Cromatina/ultraestructura , Fase G1/fisiología , Fase G2/fisiología , Células HeLa , Humanos , Interfase , Modelos Biológicos , Región Organizadora del Nucléolo , Fase S/fisiología
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