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1.
Mol Immunol ; 140: 267-275, 2021 Nov 19.
Artigo em Inglês | MEDLINE | ID: mdl-34808497

RESUMO

BACKGROUND: Leukemia is a group of hematopoietic malignancies characterized by the accumulation and infiltration of abnormal hematopoietic stem cells or early progenitor cells. T cell acute lymphoblastic leukemia (T-ALL) is a hematologic malignancy occurring in 15 % of pediatric and 25 % of adult ALL cases. Infiltration and metastasis of leukemic cells to specific organs are consequences of disease relapse and dismal prognosis. Long non-coding RNAs (lncRNAs) have been identified to function in the migration, invasion and infiltration of tumors by regulating gene expression. Our previous studies showed that CC chemokine receptor 9 (CCR9), which specifically bind to CC chemokine ligand 25 (CCL25), promotes T-ALL infiltration. METHODS: Bioinformatic methods were used to screen LINC00853 in gene expression omnibus (GEO) datasets. RT-qPCR, western bolt and flow cytometry were applied to detect the expression of LINC00853 and CCR9. Transwell and martrigel-transwell were employed to assess the cells migration and invasion abilities. Fluorescence microscope was applied to observed the green fluorescence protein positive (GFP+) cells. Lentivirus and adenovirus were packed to construct nc-blank, sh-LINC00853-blank and sh-LINC00853-rescue jurkat cell lines. RESULTS: In this study, we found out the negative correlation of LINC00853 and CCR9 expression. LINC00853 was downregulated while CCR9 was upregulated in GEO datasets, T-ALL cell lines and clinical samples. Moreover, LINC00853 suppressed jurkat cells migration and invasion in vitro and restrained infiltration in liver, spleen, kidney, lung, brain, ovary of nonobese diabetic/severe combined immunodeficient (NOD/SCID) mice. CONCLUSIONS: These findings indicate that LINC00853 restrains T-ALL cell invasion and infiltration by regulating CCR9/CCL25.

2.
Front Oncol ; 11: 689843, 2021.
Artigo em Inglês | MEDLINE | ID: mdl-34485125

RESUMO

Primary central nervous system lymphoma (PCNSL) is a rare subtype of extra-nodal lymphoma. The high relapse rate of PCNSL remains a major challenge to the hematologists, even though patients exhibit high sensitivity to the methotrexate-based chemotherapeutic regimens. Recently, the advent of Bruton's tyrosine kinase inhibitor (BTKi) and CAR T treatment has made more treatment options available to a proportion of patients. However, whether BTKi monotherapy should be given alone or in combination with conventional chemotherapy is still a clinical question. The status of CAR T therapy for PCNSLs also needs to be elucidated. In this review, we summarized the latest progress on the epidemiology, pathology, clinical manifestation, diagnosis, and treatment options for PCNSLs.

3.
Medicine (Baltimore) ; 100(28): e26640, 2021 07 16.
Artigo em Inglês | MEDLINE | ID: mdl-34260561

RESUMO

INTRODUCTION: In recent years, with the development of molecular epidemiology, molecular transmission networks based on evolutionary theory and sequence analysis have been widely used in research on human immunodeficiency virus (HIV)-1 transmission dynamics and precise intervention for high-risk populations. The HIV-1 molecular transmission network is a new method to study the population's access to the network, the characteristics of clustering, and the characteristics of interconnection in the network. Here, we analyzed the characteristics of the HIV-1 molecular transmission network of sexually transmitted people in Liaoning Province. METHODS: A study of HIV-infected persons who were sexually transmitted in Liaoning Province from 2003 to 2019. HIV-1 RNA was extracted, amplified and sequenced, and a phylogenetic tree was constructed to determine the subtype using the well matched pol gene region sequence. The gene distance between sequences was calculated, the threshold was determined, and the molecular transmission network was constructed. RESULTS: 109 samples of pol gene region were obtained. The main subtype of HIV-1 was CRF01_AE, followed by B, CRF07_BC, etc. 12.8% of them were resistant to HIV. At the threshold of 0.55 gene distance, 60.6% of them entered the HIV-1 molecular transmission network. Workers, sample source voluntary counseling and testing, other testing, subtype B and drug resistance are the factors influencing the access to HIV-1 molecular transmission network. The subtype of CRF01_AE formed 6 clusters in the molecular transmission network. In the network, the difference of connection degree between different subtypes was statistically significant. DISCUSSION: The three subtypes CRF01_AE, CRF07_BC and B that enter the molecular transmission network do not have interconnections, and they form clusters with each other. It shows that the risk of transmission among the three subtypes is less than the risk of transmission within each subtype. The factors affecting HIV-1 entry into the molecular transmission network were occupation, sample source, genotype and drug resistance. The L33F mutation at the HIV-1 resistance mutation site constitutes the interconnection in the largest transmission cluster in the network. The epidemiological characteristics of HIV-infected persons in each molecular transmission cluster show that 97% of the study subjects come from the same area and have a certain spatial aggregation. CONCLUSION: Constructing a molecular transmission network and conducting long-term monitoring, while taking targeted measures to block the spread of HIV can achieve precise prevention and control.


Assuntos
Infecções por HIV/epidemiologia , Infecções por HIV/genética , HIV-1/genética , Doenças Virais Sexualmente Transmissíveis/epidemiologia , Doenças Virais Sexualmente Transmissíveis/genética , Adulto , China/epidemiologia , Feminino , Genótipo , Infecções por HIV/etnologia , Infecções por HIV/transmissão , Comportamentos Relacionados com a Saúde , Humanos , Masculino , Pessoa de Meia-Idade , Epidemiologia Molecular , RNA Viral , Análise de Sequência de DNA , Doenças Virais Sexualmente Transmissíveis/etnologia , Fatores Socioeconômicos
4.
Neuroreport ; 32(12): 1017-1026, 2021 08 11.
Artigo em Inglês | MEDLINE | ID: mdl-34102644

RESUMO

OBJECTIVES: Secondary spinal cord injury (SCI), a reversible pathological change, involves neural inflammation and apoptosis. This study explored how microRNA (miR)-488, an inflammatory regulator as reported affected secondary SCI. METHODS: In vivo, Wistar rats were clipped on the spinal cord for SCI induction. In vitro, PC-12 cells were treated with lipopolysaccharide (LPS) to induce cell injuries to mimic the environment during the secondary SCI. Cell viability and apoptosis were measured by CCK-8 assay and flow cytometry. The levels of inflammation-related factors (interleukin (IL)-6, IL-1ß and tumor necrosis factor (TNF)-α) in the serum and PC-12 cells were determined by ELISA. The expressions of miR-488, high mobility group box 1 (HMGB1), B-cell lymphoma 2 (Bcl-2), Bcl-2-associated X protein (Bax), cleaved caspase-3, toll-like receptor 4 (TLR4), phosphorylated (p)-p65 and total-p65 in rat spinal cord or PC-12 cells were analyzed by quantitative reverse transcription PCR or western blot. RESULTS: After SCI induction, rats exhibited low Basso-Beattie-Bresnahan scores, promoted the release of inflammation-related factors and downregulated miR-488. LPS treatment decreased cell viability, enhanced apoptosis and downregulated miR-488. Upregulating miR-488 neutralized LPS-induced releases of inflammation-related factors and expressions of Bax and cleaved caspase-3 and counteracted LPS-induced inhibition on Bcl-2 expression. MiR-488 directly targeted HMGB1 and miR-488 mimic decreased LPS-induced HMGB1 expression. Overexpressing HMGB1 counteracted miR-488 mimic-induced decreases in the expressions of TLR4 and p-p65 and the ratio of p-p65 to Total-p65 in LPS-treated PC-12 cells. CONCLUSION: MiR-488 inhibited neural inflammation and apoptosis in SCI via its binding with HMGB1-mediated restraint on the TLR4/NF-κB signaling pathway.

5.
Behav Brain Res ; 412: 113384, 2021 08 27.
Artigo em Inglês | MEDLINE | ID: mdl-34147565

RESUMO

Autophagy is involved in aging-related cognitive impairment. Aerobic exercise training can improve cognitive function in the elderly and this effect may be associated with autophagic mechanisms and mitochondrial respiratory function. High intensity interval training (HIIT) has beneficial effects on heart and skeletal muscles by activating autophagy and/or mitophagy, but the effects of HIIT on autophagy/mitophagy in the aging brain are unknown. This study investigated the effects of HIIT on the mitochondrial respiratory complex and autophagy/mitophagy, and its relation to brain function. Thirteen middle-aged male ICR mice underwent HIIT for 7 weeks. The exercise program reduced the spontaneous behavior and exploration activities of the mice. The phosphorylation level of cAMP response element binding protein (CREB) and the protein expression of brain-derived neurotrophic factor (BDNF) decreased after the 7-week HIIT. Exercise downregulated the protein expression of Complex Ⅰ and upregulated the protein expression of Complex Ⅲ, Complex Ⅳ and Complex Ⅴ. HIIT also decreased the expression of mitophagy-related proteins in the mitochondrial fractions of the hippocampus. However, HIIT did not change the expression of autophagy-related proteins LC3, P62, Atg5, Atg7, Beclin-1 and Lamp2 in the total lysate of the hippocampus. These data indicated that HIIT might have negative effects on the plasticity of the hippocampus in middle-aged mice. The effects may be related to the dysregulation of CREB-BDNF signaling, mitochondrial respiratory complex and mitophagy induced by HIIT.

6.
Front Physiol ; 12: 599892, 2021.
Artigo em Inglês | MEDLINE | ID: mdl-34025444

RESUMO

The cardioprotection of exercise preconditioning (EP) has been well documented. EP can be divided into two phases that are the induction of exercise preconditioning (IEP) and the protection of exercise preconditioning (PEP). PEP is characterized by biphasic protection, including early exercise preconditioning (EEP) and late exercise preconditioning (LEP). LC3 lipidation-mediated autophagy plays a pivotal role in cardioprotection. This study aimed to investigate the alterations of LC3 lipidation-associated proteins during EP-induced cardioprotection against myocardial injury induced by exhaustive exercise (EE) was used in a rat model of EP. These rats were subjected to an intermittent exercise consisting of four periods, with each period including 10 min of running at 30 m/min and 0% grade (approximately 75% VO2max) followed by 10 min of intermittent rest. A model of EE-induced myocardial injury was developed by subjecting rats to a consecutive running (30 m/min, 0% grade) till exhaustion. Following EEP, the colocalization of LC3 with Atg7 was significantly increased, and LC3-I, LC3-II, LC3-II/LC3-I, Atg7, Atg4B, and Atg3 levels were significantly increased. Atg7, Atg4B, and Atg3 mRNAs were all significantly upregulated, and LC3 mRNAs tended to be higher. Following LEP, Atg4B, and Atg3 levels were significantly increased. Atg7, Atg4B, and Atg3 mRNAs were all significantly upregulated, and LC3 mRNAs tended to be higher. A group of rats were subjected to EEP followed by EE, and the co-localization of LC3 with Atg7 was significantly increased, while LC3-I, LC3-II, LC3-II/LC3-I, Atg7, Atg4B, and Atg3 levels were also significantly increased. Moreover, there was a significant increase in the co-localization of LC3 with Atg7, LC3-I, LC3-II, Atg7, and Atg4B levels during LEP followed by EE. The formation of autophagosome during LEP followed by EE may have been weaker than that during EEP followed by EE due to the lower lipidation of LC3. EP may promote autophagy to maintain cell homeostasis and survival, which cooperates for cardioprotection of alleviating exhaustive exercise-induced myocardial injury by increasing LC3 lipidation-associated proteins. There is a difference between EEP and LEP in terms of the mechanisms of cardioprotection afforded by these respective conditions. The positive regulation of transcription and translation level of LC3 lipidation-associated proteins may all be involved in the mechanism of EEP and LEP, while compared with LEP, the regulation of translation level of EEP is more positively to promote autophagy.

7.
Int Heart J ; 62(2): 407-415, 2021 Mar 30.
Artigo em Inglês | MEDLINE | ID: mdl-33678798

RESUMO

Exercise preconditioning (EP) provides protective effects for acute cardiovascular stress; however, its mechanisms need to be further investigated. Autophagy is a degradation pathway essential for myocardium health. Therefore, we investigated whether intermittent myocardial ischemia-hypoxia affected Beclin1 and whether the changes in autophagy levels contribute to EP-induced early myocardial protective effects. Rats were trained on a treadmill using an EP model (four cycles of 10 minutes of running/10 minutes of rest). Exhaustive exercise (EE) was performed to induce myocardial injury. Cardiac troponin I (cTnI) and ischemia-hypoxia staining were used to evaluate myocardial injury and protection. Double-labeled immunofluorescence staining and western blot analysis were employed to examine related markers. EP attenuated the myocardial ischemic-hypoxic injury induced by EE. Compared with the control (C) group, the dissociations of Beclin1/Bcl-2 ratio and Beclin1 expression were both higher in all other groups. Compared with the C group, PI3KC3 and the LC3-II/LC3-I ratio were higher in all other groups, whereas LC3-II was higher in the EE and EEP + EE groups. p62 was higher in the EE group than in the C group but lower in the EEP + EE group than in the EE group. We concluded that EP increases Beclin1 via intermittent myocardial ischemia-hypoxia and induces autophagy, which exerts early myocardial protective effects and reduces the myocardial ischemic-hypoxic injury induced by exhaustive exercise.


Assuntos
Proteína Beclina-1/metabolismo , Isquemia Miocárdica/prevenção & controle , Miocárdio/metabolismo , Condicionamento Físico Animal/métodos , Animais , Autofagia , Western Blotting , Modelos Animais de Doenças , Masculino , Isquemia Miocárdica/fisiopatologia , Miocárdio/patologia , Ratos , Ratos Sprague-Dawley
8.
J Mol Histol ; 52(2): 373-383, 2021 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-33543337

RESUMO

Exercise preconditioning (EP) can alleviate myocardial ischemic/hypoxic injury by inducing endogenous cardioprotection. Hematoxylin-eosin (HE), hematoxylin-basic fuchsin-picric acid (HBFP), and chromotrope-2R brilliant green (C-2R BG) staining have been used to visualize myocardial ischemic/hypoxic changes in previous EP studies, but comprehensive evaluation and comparisons of these methods are lacking. This study evaluated ischemic/hypoxic changes in adjacent myocardial sections by HE, HBFP, and C-2R BG and compared the characteristics of sections stained by these three methods to show changes associated with exercise-induced myocardial ischemic/hypoxic injury. Rats were randomly divided into four groups: control (C), exercise preconditioning (EP), exhaustive exercise (EE), and exercise preconditioning + exhaustive exercise (EP + EE). Adjacent myocardial sections were stained as described above and compared to evaluate the effects of exercise-induced myocardial ischemic/hypoxic injury. The three staining methods revealed consistent localization patterns of myocardial ischemic/hypoxic injury in all groups. Results suggest that EP can alleviate exhaustive exercise-induced myocardial ischemic/hypoxic injury, and the three staining methods are suitable for the histological study of exercise-induced myocardial ischemic/hypoxic injury and protection. HE staining is a simple procedure but is not specific for myocardial ischemic/hypoxic injury. HBFP and C-2R BG staining can be used to specifically visualize myocardial ischemic/hypoxic injury.

9.
Burns ; 47(3): 684-691, 2021 05.
Artigo em Inglês | MEDLINE | ID: mdl-32917474

RESUMO

INTRODUCTION: Even after reconstructive surgery, it is still difficult for patients with severe burns to achieve independent eating activity. In this project, we customized the forearm pronation's assistant tableware to assist in improvement with eating activities. METHODS: From January 2017 to December 2018, 28 patients with severe burns including the hands were recruited. For the patient's independent eating activities, we customized forearm pronation's tableware (forks and spoons). We compared modified Barthel index (MBI) and Visual analogue scale (VAS) of satisfaction under three conditions: no auxiliary tableware, ADL universal cuff, or forearm pronation tableware; to compare the duration and the weight of food spilled during lunch when the patients wore the ADL universal cuff or the forearm pronation's tableware. Differences in MBI (rank data) were tested by the Friedman test, differences in VAS (normal distribution) were tested with One-way ANOVA (Bonferroni), differences in the duration and the weight (normal distribution data) were tested by paired sample t test. RESULTS: After wearing the forearm pronation's assistant tableware, MBI VAS both increased more than when the patients did not wear the auxiliary tableware (all p<0.05). When the subjects wore forearm pronation tableware, the duration of lunch significantly decreased and the quality of eating activity significantly improved compared to the ADL universal cuff in eating activity (all p<0.05). CONCLUSION: After wearing the forearm pronation's assistant tableware, the patients with severe burns completely or almost completely accomplished independent eating, the duration was decreased, and during eating activity the quality and the satisfaction were improved. CLINICAL TRIAL REGISTRATION: Chinese Clinical trial registry, ChiCTR1800019963.

10.
Acta Diabetol ; 58(1): 63-72, 2021 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-32815005

RESUMO

AIM: Autoimmune diabetes mellitus (defined as ADM) comprises classical type 1 diabetes mellitus (T1DM) and latent autoimmune diabetes in adults (LADA). In this study, microRNAs (miRNAs) expression profiles and functions in peripheral blood mononuclear cells (PBMCs) of ADM patients were mapped and used to explore epigenetic regulation of the pathogenesis of ADM. METHODS: PBMCs samples from T1DM patients, LADA patients, and type 2 diabetes mellitus (T2DM) patients, as well as age- and sex-matched healthy controls for T1DM and T2DM, respectively, were collected and were sequenced to screen the miRNAs expression profiles. The target genes were verified by dual-luciferase reporter assay. Silencing or overexpressing of the differentially expressed miRNAs, or simultaneously silencing the miRNAs and it's target gene, and then levels of the mRNAs, protein and cytokines were detected. RESULTS: miR-143-3p expression was upregulated in ADM patients. The target gene of miR-143-3p was identified as Fos-related antigen 2 (FOSL2). Transfection of a miR-143-3p inhibitor into PBMCs upregulated FOSL2 expression, resulting in a downregulated expression of the IL-2, TNF-α, and IFN-γ, and an upregulated expression of IL-6. Transfection of a miR-143-3p mimic into PBMCs downregulated FOSL2 expression, leading to an upregulation of IL-2 and TNF-α expression and a downregulation of IL-6 expression. When silencing FOSL2 while inhibiting miR-143-3p in PBMCs, there was no significant change in expression of the FOSL2 mRNA, protein and cytokines. CONCLUSION: The expression of miR-143-3p in PBMCs from ADM patients is upregulated. miR-143-3p could function in the pathogenesis of ADM by modulating the inflammatory reaction through FOSL2.


Assuntos
Diabetes Mellitus Tipo 1/genética , Antígeno 2 Relacionado a Fos/genética , Leucócitos Mononucleares/metabolismo , MicroRNAs/fisiologia , Adolescente , Adulto , Estudos de Casos e Controles , Células Cultivadas , Criança , Diabetes Mellitus Tipo 1/imunologia , Diabetes Mellitus Tipo 1/metabolismo , Diabetes Mellitus Tipo 1/patologia , Diabetes Mellitus Tipo 2/genética , Diabetes Mellitus Tipo 2/imunologia , Diabetes Mellitus Tipo 2/metabolismo , Diabetes Mellitus Tipo 2/patologia , Epigênese Genética/genética , Feminino , Regulação da Expressão Gênica , Células HEK293 , Humanos , Leucócitos Mononucleares/patologia , Masculino , Pessoa de Meia-Idade , Adulto Jovem
11.
Int J Inf Manage ; 55: 102196, 2020 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-32836647

RESUMO

The recent outbreak of the COVID-19 pandemic has posed a significant threat to the healthy lives and well-being of billions of people worldwide. As the world begins to open up from lockdowns and enters an unprecedented state of vulnerability, or what many have called "the new normal", it makes sense to reflect on what we have learned, revisit our fundamental assumptions, and start charting the way forward to contribute to building a sustainable world. In this essay, we argue that despite its significant damage to human lives and livelihoods, the coronavirus pandemic presents an excellent opportunity for the human family to act in solidarity and turn this crisis into an impetus to achieve the United Nation's (UN) Sustainable Development Goals (SDG). In this article, we will highlight the six relevant themes that have evolved during the pandemic and the corresponding topics that future researchers could focus on. We conclude by issuing a call for more research attention on tackling SDG through developing the concept and practice of digital sustainability.

13.
Cell Metab ; 31(5): 892-908.e11, 2020 05 05.
Artigo em Inglês | MEDLINE | ID: mdl-32375062

RESUMO

Nonalcoholic steatohepatitis (NASH) is becoming one of the leading causes of hepatocellular carcinoma (HCC). Sorafenib is the only first-line therapy for advanced HCC despite its serious adverse effects. Here, we report that at an equivalent of approximately one-tenth the clinical dose for HCC, sorafenib treatment effectively prevents the progression of NASH in both mice and monkeys without any observed significant adverse events. Mechanistically, sorafenib's benefit in NASH is independent of its canonical kinase targets in HCC, but involves the induction of mild mitochondrial uncoupling and subsequent activation of AMP-activated protein kinase (AMPK). Collectively, our findings demonstrate a previously unappreciated therapeutic effect and signaling mechanism of low-dose sorafenib treatment in NASH. We envision that this new therapeutic strategy for NASH has the potential to translate into a beneficial anti-NASH therapy with fewer adverse events than is observed in the drug's current use in HCC.

14.
Int J Inf Manage ; 54: 102143, 2020 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-32394997

RESUMO

The outbreak of the COVID-19 pandemic has created significant challenges for people worldwide. To combat the virus, one of the most dramatic measures was the lockdown of 4 billion people in what is believed to be the largest quasi-quarantine in human history. As a response to the call to study information behavior during a global health crisis, we adopted a resource orchestration perspective to investigate six Chinese families who survived the lockdown. We explored how elderly, young and middle-aged individuals and children resourced information and how they adapted their information behavior to emerging online technologies. Two information resource orchestration practices (information resourcing activities and information behavior adaptation activities) and three mechanisms (online emergence and convergence in community resilience, the overcoming of information flow impediments, and the application of absorptive capacity) were identified in the study.

15.
Endocr J ; 67(7): 793-802, 2020 Jul 28.
Artigo em Inglês | MEDLINE | ID: mdl-32295990

RESUMO

This study aims to investigate the prevalence of islet autoantibodies and other organ-specific autoantibodies in type 1 diabetes mellitus (T1DM) patients and characterize their clinical features. Glutamic acid decarboxylase antibody (GADA), insulinoma antigen 2 antibody (IA-2A), zinc transporter 8 antibody (ZnT8A) and tetraspanin7 antibody (TSPAN7A) were assayed by radioligand or luciferase immunoprecipitation system assays in 205 newly diagnosed acute-onset T1DM patients and 170 healthy controls. Other organ-specific autoantibodies, including thyroid peroxidase antibody (TPOA), thyroglobulin antibody (TGA), tissue transglutaminase antibody (tTGA) and 21-hydroxylase antibody (21-OHA), were also measured. The prevalence of GADA, IA-2A, ZnT8A, TSPAN7A, TPOA, TGA and 21-OHA was higher in T1DM patients than in healthy controls. The combinational assay of various islet autoantibodies could increase the frequency of autoantibody positivity in T1DM to 85.4%. GADA+ IA-2A+ T1DM patients preferentially had TPOA and TGA, while IA-2A+ patients often had tTGA. Patients positive for two or more islet autoantibodies often had TPOA and TGA. BMI of multiple islet autoantibody-positive patients was lower than that of patients with single or no islet autoantibodies, and there were no significant differences in C-peptide and glycated hemoglobin between patients positive for islet autoantibodies combined with other organ-specific antibodies and noncombined patients. Younger female patients who were islet autoantibody positive were more likely to have TPOA and TGA. The frequency of Graves' disease was much higher in T1DM patients than in healthy controls. T1DM usually occurs together with other organ-specific autoantibodies. Measuring of other organ-specific autoantibodies will be beneficial for T1DM patients.


Assuntos
Autoanticorpos/sangue , Diabetes Mellitus Tipo 1/sangue , Adolescente , Adulto , Idoso , Autoanticorpos/análise , Estudos de Casos e Controles , Criança , Pré-Escolar , China/epidemiologia , Diabetes Mellitus Tipo 1/diagnóstico , Diabetes Mellitus Tipo 1/epidemiologia , Diabetes Mellitus Tipo 1/imunologia , Feminino , Proteínas de Ligação ao GTP/imunologia , Glutamato Descarboxilase/imunologia , Humanos , Lactente , Ilhotas Pancreáticas/imunologia , Masculino , Pessoa de Meia-Idade , Proteínas do Tecido Nervoso/imunologia , Especificidade de Órgãos/imunologia , Esteroide 21-Hidroxilase/imunologia , Tetraspaninas/imunologia , Transglutaminases/imunologia , Adulto Jovem , Transportador 8 de Zinco/imunologia
16.
Oncol Rep ; 43(5): 1451-1466, 2020 May.
Artigo em Inglês | MEDLINE | ID: mdl-32323856

RESUMO

Patients with hepatocellular carcinoma (HCC) have different prognoses depending on whether or not they also have fibrosis. Since long non­coding RNAs (lncRNAs) affect tumor formation and progression, the present study aimed to investigate whether their expression might help predict the survival of patients with HCC. Expression profiles downloaded from The Cancer Genome Atlas database were examined to identify lncRNAs differentially expressed (DElncRNAs) between HCC patients with or without fibrosis. These DElncRNAs were then used to develop a risk scoring system to predict overall survival (OS) or recurrence­free survival (RFS). A total of 142 significant DElncRNAs were identified using data from 135 patients with fibrosis and 72 without fibrosis. For HCC patients with fibrosis, a risk scoring system to predict OS was constructed based on five lncRNAs (AL359853.1, Z93930.3, HOXA­AS3, AL772337.1 and AC012640.3), while the risk scoring system to predict RFS was based on 12 lncRNAs (PLCE1­AS1, Z93930.3, LINC02273, TRBV11­2, HHIP­AS1, AC004687.1, LINC01857, AC004585.1, AP000808.1, CU638689.4, AC090152.1 and AL357060.1). For HCC patients without fibrosis, the risk scoring system to predict OS was established based on seven lncRNAs (LINC00239, AC104971.4, AP006285.2, HOXA­AS3, AC079834.2, NRIR and LINC01929), and the system to predict RFS was based on five lncRNAs (AC021744.1, NRIR, LINC00487, AC005858.1 and AC107398.3). Areas under the receiver operating characteristic curves for all risk scoring systems exceeded 0.7. Uni­ and multivariate Cox analyses showed that the risk scoring systems were significant independent predictors of OS for HCC patients with fibrosis, or of OS and RFS for HCC patients without fibrosis, after adjusting for clinical factors. Functional enrichment analysis suggested that, depending on the risk scoring system, highly associated genes were involved in pathways mainly associated with the cell cycle, chemokines, Th17 cell differentiation or thermogenesis. The findings of the present study indicate that risk scoring systems based on lncRNA expression can effectively predict the OS of HCC patients with fibrosis as well as the OS or RFS of HCC patients without fibrosis.


Assuntos
Biomarcadores Tumorais/genética , Carcinoma Hepatocelular/mortalidade , Cirrose Hepática/mortalidade , Neoplasias Hepáticas/mortalidade , RNA Longo não Codificante/genética , Área Sob a Curva , Carcinoma Hepatocelular/complicações , Carcinoma Hepatocelular/genética , Feminino , Regulação Neoplásica da Expressão Gênica , Redes Reguladoras de Genes , Humanos , Cirrose Hepática/genética , Neoplasias Hepáticas/complicações , Neoplasias Hepáticas/genética , Masculino , Prognóstico , Análise de Sobrevida
17.
Cancer Manag Res ; 12: 1523-1534, 2020.
Artigo em Inglês | MEDLINE | ID: mdl-32184657

RESUMO

Background: Gastric cancer (GC) is among the most common forms of cancer affecting the digestive system. This study sought to identify hub genes regulating early GC (EGC) in order to explore their potential for early diagnosis and prognosis of patients. Methods: We utilized a publically available dataset from the Gene Expression Omnibus database (GSE55696). Differences between EGC and LGIN with respect to gene expression were compared using the limma software. Identified differentially expressed genes (DEGs) were subjected to gene ontology (GO) and pathway enrichment analyses with the DAVID application, and the STRING website and Cytoscape software were used to construct a protein-protein interaction (PPI) network incorporating these DEGs. This network was in turn used to identify hub genes among selected DEGs, which were analyzed with the Kaplan-Meier Plotter database. In addition, Western blotting, qRT-PCR, immunohistochemistry, and UALCAN were all employed to validate the relationship between the expression of these genes and GC patient prognosis. Results: A total of 482 DEGs were identified, with GO analyses indicating an increase in the expression of genes linked with the development of cancer. Pathway analyses also indicated that these genes play a role in certain cancer-related pathways. The PPI network highlighted four potential hub genes, of which only ICAM1 was linked to a poor GC patient prognosis. This link between ICAM1 and GC patient outcomes was confirmed via UALCAN, Western blotting, immunohistochemistry, and qRT-PCR. Conclusion: ICAM1 may therefore modulate tumor progression in GC, thus potentially representing a valuable prognostic and diagnostic biomarker of EGC.

18.
J Physiol Sci ; 70(1): 10, 2020 Feb 17.
Artigo em Inglês | MEDLINE | ID: mdl-32066368

RESUMO

Exercise has been reported to induce autophagy. We hypothesized that exercise preconditioning (EP)-related autophagy in cardiomyocytes could be attributed to intermittent ischemia-hypoxia, allowing the heart to be protected for subsequent high-intensity exercise (HE). We applied approaches, chromotrope-2R brilliant green (C-2R BG) staining and plasma cTnI levels measuring, to characterize two periods of cardioprotection after EP: early EP (EEP) and late EP (LEP). Further addressing the relationship between ischemia-hypoxia and autophagy, key proteins, Beclin1, LC3, Cathepsin D, and p62, were determined by immunohistochemical staining, western blotting, and by their adjacent slices with C-2R BG. Results indicated that exercise-induced ischemia-hypoxia is a key factor in Beclin1-dependent autophagy. High-intensity exercise was associated with the impairment of autophagy due to high levels of LC3II and unchanged levels of p62, intermittent ischemia-hypoxia by EP itself plays a key role in autophagy, which resulted in more favorable cellular effects during EEP-cardioprotection compared to LEP.


Assuntos
Autofagia , Traumatismos Cardíacos/metabolismo , Precondicionamento Isquêmico Miocárdico/métodos , Condicionamento Físico Animal/efeitos adversos , Traumatismo por Reperfusão , Troponina I/sangue , Animais , Regulação da Expressão Gênica/fisiologia , Humanos , Isquemia Miocárdica/metabolismo , Miocárdio/metabolismo , Miócitos Cardíacos/metabolismo , Ratos , Ratos Sprague-Dawley , Troponina I/genética , Troponina I/metabolismo
19.
Clin Transl Sci ; 13(2): 400-409, 2020 03.
Artigo em Inglês | MEDLINE | ID: mdl-31995663

RESUMO

Variation in response to biologic therapy for inflammatory diseases, such as psoriasis, is partly driven by variation in drug exposure. Real-world psoriasis data were used to develop a pharmacokinetic/pharmacodynamic (PK/PD) model for the first-line therapeutic antibody ustekinumab. The impact of differing dosing strategies on response was explored. Data were collected from a UK prospective multicenter observational cohort (491 patients on ustekinumab monotherapy, drug levels, and anti-drug antibody measurements on 797 serum samples, 1,590 measurements of Psoriasis Area Severity Index (PASI)). Ustekinumab PKs were described with a linear one-compartment model. A maximum effect (Emax ) model inhibited progression of psoriatic skin lesions in the turnover PD mechanism describing PASI evolution while on treatment. A mixture model on half-maximal effective concentration identified a potential nonresponder group, with simulations suggesting that, in future, the model could be incorporated into a Bayesian therapeutic drug monitoring "dashboard" to individualize dosing and improve treatment outcomes.


Assuntos
Fármacos Dermatológicos/farmacocinética , Modelos Biológicos , Psoríase/tratamento farmacológico , Ustekinumab/farmacocinética , Adolescente , Adulto , Idoso , Teorema de Bayes , Fármacos Dermatológicos/administração & dosagem , Cálculos da Dosagem de Medicamento , Monitoramento de Medicamentos/métodos , Feminino , Humanos , Injeções Subcutâneas , Masculino , Pessoa de Meia-Idade , Estudos Prospectivos , Psoríase/sangue , Psoríase/diagnóstico , Índice de Gravidade de Doença , Resultado do Tratamento , Ustekinumab/administração & dosagem , Adulto Jovem
20.
Transplantation ; 104(3): 467-475, 2020 03.
Artigo em Inglês | MEDLINE | ID: mdl-31596739

RESUMO

Myeloid-derived suppressor cells (MDSCs), a heterogeneous population of myeloid cells, are characterized by their immunosuppressive abilities through the secretion of various cytokines such as inducible nitric oxide synthase, nitric oxide, reactive oxygen species, transforming growth factor-ß, and arginase-1. Accumulating evidence highlights its potential role in maintaining immune tolerance in solid organ and hematopoietic stem cell transplantation. Mechanistically, MDSCs-induced transplant tolerance is mainly dependent on direct suppression of allogeneic reaction or strengthened cross-talk between MDSCs and Treg or NKT cells. Adopted transfer of in vitro- or in vivo-induced MDSCs by special drugs therefore becomes a potential strategy for maintaining transplantation tolerance. In this review, we will summarize the previously published data about the role of MDSCs in the biology of transplantation tolerance and gain insights into the possible molecular mechanism governing this process.


Assuntos
Transferência Adotiva/métodos , Rejeição de Enxerto/prevenção & controle , Sobrevivência de Enxerto/imunologia , Células Supressoras Mieloides/imunologia , Tolerância ao Transplante , Animais , Modelos Animais de Doenças , Rejeição de Enxerto/imunologia , Transplante de Células-Tronco Hematopoéticas/efeitos adversos , Humanos , Células Supressoras Mieloides/transplante , Transplante de Órgãos/efeitos adversos
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