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1.
J Biol Chem ; 300(7): 107453, 2024 Jul.
Artículo en Inglés | MEDLINE | ID: mdl-38852886

RESUMEN

Identification of a conserved G-quadruplex in E165R of ASFVAfrican swine fever virus (ASFV) is a double-stranded DNA arbovirus with high transmissibility and mortality rates. It has caused immense economic losses to the global pig industry. Currently, no effective vaccines or medications are to combat ASFV infection. G-quadruplex (G4) structures have attracted increasing interest because of their regulatory role in vital biological processes. In this study, we identified a conserved G-rich sequence within the E165R gene of ASFV. Subsequently, using various methods, we verified that this sequence could fold into a parallel G4. In addition, the G4-stabilizers pyridostatin and 5,10,15,20-tetrakis-(N-methyl-4-pyridyl) porphin (TMPyP4) can bind and stabilize this G4 structure, thereby inhibiting E165R gene expression, and the inhibitory effect is associated with G4 formation. Moreover, the G4 ligand pyridostatin substantially impeded ASFV proliferation in Vero cells by reducing gene copy number and viral protein expression. These compelling findings suggest that G4 structures may represent a promising and novel antiviral target against ASFV.


Asunto(s)
Virus de la Fiebre Porcina Africana , Antivirales , G-Cuádruplex , Virus de la Fiebre Porcina Africana/genética , Virus de la Fiebre Porcina Africana/metabolismo , Animales , Chlorocebus aethiops , Células Vero , Antivirales/farmacología , Antivirales/química , Porcinos , Fiebre Porcina Africana/virología , Fiebre Porcina Africana/metabolismo , Porfirinas/química , Porfirinas/farmacología , Ácidos Picolínicos/química , Ácidos Picolínicos/farmacología , Ácidos Picolínicos/metabolismo , Replicación Viral/efectos de los fármacos , Proteínas Virales/genética , Proteínas Virales/metabolismo , Proteínas Virales/química , Aminoquinolinas
2.
Br J Haematol ; 204(3): 861-870, 2024 Mar.
Artículo en Inglés | MEDLINE | ID: mdl-37939390

RESUMEN

Gilteritinib, a potent FMS-like tyrosine kinase 3 (FLT3) inhibitor, was approved for relapsed/refractory (R/R) FLT3-mutated acute myeloid leukaemia (AML) patients but still showed limited efficacy. Here, we retrospectively analysed the efficacy and safety of different gilteritinib-based combination therapies (gilteritinib plus hypomethylating agent and venetoclax, G + HMA + VEN; gilteritinib plus HMA, G + HMA; gilteritinib plus venetoclax, G + VEN) in 33 R/R FLT3-mutated AML patients. The composite complete response (CRc) and modified CRc (mCRc) rates were 66.7% (12/18) and 88.9% (16/18) in patients received G + HMA + VEN, which was higher compared with that in G + HMA (CRc: 18.2%, 2/11; mCRc: 45.5%, 5/11) or G + VEN (CRc: 50.0%, 2/4; mCRc: 50.0%, 2/4). The median overall survival (OS) for G + HMA + VEN, G + HMA and G + VEN treatment was not reached, 160.0 days and 231.0 days. The median duration of remission (DOR) for G + HMA + VEN, G + HMA and G + VEN treatment was not reached, 82.0 days and 77.0 days. Four patients in the G + HMA + VEN group received alloHSCT after remission exhibited prolonged median DOR. The most common grade 3/4 adverse events were cytopenia, febrile neutropenia and pulmonary infection; there were no differences among the three groups. In conclusion, our data demonstrated promising response of G + HMA + VEN combination therapy in R/R FLT3-mutated AML, and it may be considered an effective therapy bridge to transplantation.


Asunto(s)
Compuestos de Anilina , Compuestos Bicíclicos Heterocíclicos con Puentes , Leucemia Mieloide Aguda , Pirazinas , Sulfonamidas , Tirosina Quinasa 3 Similar a fms , Adulto , Humanos , Estudios Retrospectivos
3.
Biochem Biophys Res Commun ; 704: 149613, 2024 Apr 16.
Artículo en Inglés | MEDLINE | ID: mdl-38387325

RESUMEN

Myocardial dysfunction is a prevalent complication of sepsis (septic cardiomyopathy) with a high mortality rate and limited therapeutic options. Naringenin, a natural flavonoid compound with anti-inflammatory and antioxidant properties, holds promise as a potential treatment for sepsis-induced myocardial dysfunction. This study investigated the pharmacological effects of naringenin on septic cardiomyopathy. In vivo and in vitro experiments demonstrated that naringenin improved cardiomyocyte damage. Network pharmacology and database analysis revealed that HIF-1α is a key target protein of naringenin. Elevated expression of HIF-1α was observed in damaged cardiomyocytes, and the HIF-1α inhibitor effectively protected against LPS-induced cardiomyocyte damage. Molecular docking studies confirmed the direct binding between naringenin and HIF-1α protein. Importantly, our findings demonstrated that naringenin did not provide additional attenuation of cardiomyocyte injury on the biases of HIF-1α inhibitor treatment. In conclusion, this study proves that naringenin protects against septic cardiomyopathy through HIF-1α signaling. Naringenin is a promising therapeutic candidate for treating septic cardiomyopathy.


Asunto(s)
Cardiomiopatías , Flavanonas , Sepsis , Animales , Ratones , Cardiomiopatías/tratamiento farmacológico , Cardiomiopatías/etiología , Cardiomiopatías/prevención & control , Lipopolisacáridos/farmacología , Simulación del Acoplamiento Molecular , Miocitos Cardíacos/metabolismo , Sepsis/complicaciones , Sepsis/tratamiento farmacológico , Sepsis/metabolismo , Subunidad alfa del Factor 1 Inducible por Hipoxia
4.
Mol Carcinog ; 62(10): 1546-1562, 2023 10.
Artículo en Inglés | MEDLINE | ID: mdl-37493101

RESUMEN

Circular RNAs (circRNAs), a type of endogenous noncoding RNA (ncRNA), exert vital roles in leukemia progression and are promising prognostic factors. Here, we report a novel circRNA, circSLC25A13 (hsa_circ_0081188), which was increased in acute myeloid leukemia (AML) patients with poor overall survival (OS) comparing to patients with good prognosis. Knockdown of circSLC25A13 in AML cells inhibited proliferation and increased cell apoptosis in vitro and in vivo. Enhanced circSLC25A13 expression promoted the survival of AML cells. Mechanistically, circSLC25A13 played as a microRNA sponge of miR-616-3p, which inhibited the expression of adenylate cyclase 2 (ADCY2). Downregulation of miR-616-3p and overexpression of ADCY2 partially rescued circSLC25A13 deficient induced cell growth arrest. In summary, through competitive absorption of miR-616-3p and thereby upregulating ADCY2 expression, circSLC25A13 promoted AML progression. Moreover, circSLC25A13 may represent a potential novel biomarker for the prognosis of AML and offer a potential therapeutic target for AML treatment.


Asunto(s)
Leucemia Mieloide Aguda , MicroARNs , Humanos , Apoptosis/genética , Línea Celular Tumoral , Proliferación Celular/genética , Regulación hacia Abajo , Regulación Neoplásica de la Expresión Génica , Leucemia Mieloide Aguda/genética , Leucemia Mieloide Aguda/metabolismo , MicroARNs/genética , MicroARNs/metabolismo , ARN Circular/genética
5.
Ann Hematol ; 102(3): 583-595, 2023 Mar.
Artículo en Inglés | MEDLINE | ID: mdl-36697954

RESUMEN

Acute myeloid leukemia (AML) is a group of hematological malignancies characterized by clonal proliferation of immature myeloid cells. Lipid rafts are highly organized membrane subdomains enriched in cholesterol, sphingolipids, and gangliosides and play roles in regulating apoptosis through subcellular redistribution. Flotillin1 (FLOT1) is a component and also a marker of lipid rafts and had been reported to be involved in the progression of cancers and played important roles in cell death. However, the role of FLOT1 in AML remains to be explored. In this study, we found that increased expression of FLOT1 was correlated with poor clinical outcome in AML patients. Knockdown of FLOT1 in AML cells not only promoted cell death in vitro but also inhibited malignant cells engraftment in vivo. Mechanically, FLOT1 knockdown triggered apoptosis and pyroptosis. FLOT1 overexpression promoted AML cell growth and apoptosis resistance. Our findings indicate that FLOT1 is a prognostic factor of AML and may be a potential target for AML treatment.


Asunto(s)
Leucemia Mieloide Aguda , MicroARNs , Humanos , Apoptosis , Línea Celular Tumoral , Proliferación Celular , Leucemia Mieloide Aguda/patología , Piroptosis
6.
Virol J ; 20(1): 264, 2023 Nov 15.
Artículo en Inglés | MEDLINE | ID: mdl-37968757

RESUMEN

The porcine pseudorabies virus (PRV) is one of the most devastating pathogens and brings great economic losses to the swine industry worldwide. Viruses are intracellular parasites that have evolved numerous strategies to subvert and utilize different host processes for their life cycle. Among the different systems of the host cell, the cytoskeleton is one of the most important which not only facilitate viral invasion and spread into neighboring cells, but also help viruses to evade the host immune system. RhoA is a key regulator of cytoskeleton system that may participate in virus infection. In this study, we characterized the function of RhoA in the PRV replication by chemical drugs treatment, gene knockdown and gene over-expression strategy. Inhibition of RhoA by specific inhibitor and gene knockdown promoted PRV proliferation. On the contrary, overexpression of RhoA or activation of RhoA by chemical drug inhibited PRV infection. Besides, our data demonstrated that PRV infection induced the disruption of actin stress fiber, which was consistent with previous report. In turn, the actin specific inhibitor cytochalasin D markedly disrupted the normal fibrous structure of intracellular actin cytoskeleton and decreased the PRV replication, suggesting that actin cytoskeleton polymerization contributed to PRV replication in vitro. In summary, our data displayed that RhoA was a host restriction factor that inhibited PRV replication, which may deepen our understanding the pathogenesis of PRV and provide further insight into the prevention of PRV infection and the development of anti-viral drugs.


Asunto(s)
Herpesvirus Suido 1 , Seudorrabia , Porcinos , Animales , Herpesvirus Suido 1/fisiología , Actinas , Línea Celular , Replicación Viral
7.
Fish Shellfish Immunol ; 138: 108801, 2023 Jul.
Artículo en Inglés | MEDLINE | ID: mdl-37164122

RESUMEN

The development of sequencing technology has further accelerated the research of noncoding RNA (ncRNA). A large number of studies have shown that long noncoding RNA (lncRNA) in ncRNA can regulate gene expression in various ways and then affect various physiological and biochemical processes of the host. In this study, we found a novel lncRNA in Miichthys miiuy, named LTCONS6801, which is beneficial to TANK-binding kinase 1 (TBK1) and its mediated pathway to promote the host immune function. First, we found that lncRNA LTCONS6801 can enhance cell activity through cell viability detection and cell proliferation detection. Besides, after poly (I: C) stimulation, overexpression of lncRNA LTCONS6801 promoted the expression of antiviral gene and TBK1. We found that lncRNA LTCONS6801 further affects NF-κB and IRF3 signaling pathways by regulating the expression of TBK1. In short, lncRNA LTCONS6801 is an lncRNA that can positively regulate the host innate immune response by regulating the expression of TBK1. Our study enriches the theory and insight of lncRNA regulating antiviral immune pathway and clarifies the important role of lncRNA in antiviral immunity of teleost fish.


Asunto(s)
Perciformes , ARN Largo no Codificante , Animales , ARN Largo no Codificante/genética , Antivirales , Transducción de Señal , Inmunidad Innata/genética , Perciformes/genética
8.
J Immunol ; 207(11): 2770-2784, 2021 12 01.
Artículo en Inglés | MEDLINE | ID: mdl-34697227

RESUMEN

Circular RNAs (circRNAs) are a subgroup of endogenous noncoding RNA that is covalently closed rings and widely expressed. In recent years, there is accumulating evidence indicating that circRNAs are a class of important regulators, which play an important role in various biological processes. However, the biological functions and regulation mechanism of circRNAs in lower vertebrates are little known. In this study, we discovered a circRNA Samd4a (circSamd4a) that is related to the antiviral immune response of teleost fish. It can act as a key regulator of the host's antiviral response and play a key role in inhibiting Sininiperca chuatsi rhabdovirus replication. Further studies have shown that circSamd4a may act as a competing endogenous RNA, which can enhance the STING-mediated NF-κB/IRF3 signaling pathway by adsorbing miR-29a-3p, thereby enhancing the antiviral immune response. Therefore, circSamd4a plays an active regulatory role in the antiviral immune response of bony fish. Our research results provide a strong foundation for circular RNA to play a regulatory role in the antiviral immune response of teleost fish.


Asunto(s)
Interferones/inmunología , MicroARNs/inmunología , ARN Circular/inmunología , Regulación hacia Arriba/inmunología , Animales , Células Cultivadas , Perciformes
9.
Appl Microbiol Biotechnol ; 107(20): 6351-6362, 2023 Oct.
Artículo en Inglés | MEDLINE | ID: mdl-37606789

RESUMEN

The structural integrity and esthetic appeal of concrete can be compromised by concrete cracks. Promise has been shown by microbe-induced calcium carbonate precipitation (MICP) as a solution for concrete cracking, with a focus on urease-producing microorganisms in research. Bacillus cereus was isolated from soil and employed for this purpose in this study due to its high urease activity. The strain exhibited strong tolerance for alkaline media and high salt levels, which grew at a pH of 13 and 4% salt concentration. The repair of concrete cracks with this strain was evaluated by assessing the effects of four different thickeners at varying concentrations. The most effective results were achieved with 10 g/L of sodium carboxymethyl cellulose (CMC-Na). The data showed that over 90% repair of cracks was achieved by this system with an initial water penetration time of 30 s. The study also assessed the quantity and sizes of crystals generated during the bacterial mineralization process over time to improve our understanding of the process. KEY POINTS: • MICP using Bacillus cereus shows potential for repairing concrete cracks. • Strain tolerates alkaline media and high salt levels, growing at pH 13 and 4% salt concentration. • Sodium carboxymethyl cellulose (CMC-Na) at 10 g/L achieved over 90% repair of cracks.


Asunto(s)
Bacillus cereus , Bacillus , Ureasa , Carboximetilcelulosa de Sodio , Carbonato de Calcio/química , Cloruro de Sodio , Sodio , Precipitación Química , Materiales de Construcción/microbiología
10.
BMC Womens Health ; 23(1): 471, 2023 09 02.
Artículo en Inglés | MEDLINE | ID: mdl-37660004

RESUMEN

BACKGROUND: Overweight and obese females demonstrate a significantly increased risk of anovulatory infertility. This study aims to investigate whether depression score could mediate the association between a body shape index (ABSI) and infertility, especially in overweight and obese population. METHODS: We included 5431 adult female Americans from the National Health and Nutrition Examination Survey (NHANES, 2013-2018) database. ABSI manifested the body shape using waist circumference, weight, and height. Infertility or fertility status was defined by interviewing female participants aged ≥ 18 through the reproductive health questionnaires. Depression symptoms were assessed using the Patient Health Questionnaire-9 (PHQ-9) with total scores between 0 and 27. To investigate the association of infertility with ABSI and other individual components, survey-weighted multivariable logistic regression was performed. Mediation analysis of PHQ-9 score was conducted to disentangle the pathways that link ABSI to infertility among the NHANES participants. RESULTS: 596 (10.97%) females were categorized with having infertility among 5431 participants. Participants with infertility showed higher ABSI and PHQ-9 score, appearing greater population proportion with depression symptoms. In the multivariable logistic regression model, ABSI (adjusted odds ratio = 0.14, 95% CI: 0.04 to 0.50) and PHQ-9 (adjusted odds ratio = 1.04, 95% CI: 1.01 to 1.07) were positively associated with infertility. PHQ-9 score was estimated to mediate 0.2% (P = 0.03) of the link between ABSI and infertility in all individuals, but to mediate 13.5% (P < 0.01) of the ABSI-infertility association in overweight and obese adult females. CONCLUSION: The association between ABSI and infertility seems to be mediated by depression symptoms scored by PHQ-9, especially in those adult females with overweigh and obesity. Future studies should be implemented to further explore this mediator in ABSI-infertility link.


Asunto(s)
Infertilidad , Sobrepeso , Adulto , Femenino , Humanos , Masculino , Sobrepeso/complicaciones , Sobrepeso/epidemiología , Encuestas Nutricionales , Índice de Masa Corporal , Depresión/epidemiología , Somatotipos , Obesidad/complicaciones , Obesidad/epidemiología
11.
Plant Dis ; 107(7): 2205-2208, 2023 Jul.
Artículo en Inglés | MEDLINE | ID: mdl-36947835

RESUMEN

Botryosphaeria dothidea is a worldwide pathogenic fungus that causes stem canker, leaf dieback, and fruit rot on a large number of crops and trees. Gummosis caused by B. dothidea is one of the most prevalent and devastating diseases on peach in southern China. This study reported a high-quality and well-annotated genome sequence of B. dothidea strain XNHG241. The findings can be used as a reference for studying fungal biology, pathogenic mechanism of B. dothidea, and the interaction between B. dothidea and host, and eventually facilitate peach gummosis management.


Asunto(s)
Ascomicetos , Enfermedades de las Plantas , Enfermedades de las Plantas/microbiología , Ascomicetos/genética , China
12.
Biochem Biophys Res Commun ; 600: 35-43, 2022 04 16.
Artículo en Inglés | MEDLINE | ID: mdl-35182973

RESUMEN

The excessive inflammatory response mediated by macrophage is one of the key factors for the progress of acute pancreatitis (AP). Paeonol (Pae) was demonstrated to exert multiple anti-inflammatory effects. However, the role of Pae on AP is not clear. In the present study, we aimed to investigate the protective effect and mechanism of Pae on AP in vivo and vitro. In the caerulein-induced mild acute pancreatitis (MAP) model, we found that Pae administration reduced serum levels of amylase, lipase, IL-1ß and IL-6 and alleviated the histopathological manifestations of pancreatic tissue in a dose-dependent manner. And Pae decrease the ROS generated, restore mitochondrial membrane potential (ΔΨm), inhibit M1 macrophage polarization and NLRP3 inflammasome in bone marrow-derived macrophages (BMDMs) in vitro. In addition, specific NLRP3 inhibitor MCC950 eliminated the protective effect of Pae on AP induced by caerulein in mice. Correspondingly, the inhibitory effect of Pae on ROS generated and M1 polarization was not observed in BMDMs with MCC950 in vitro. Taken together, our datas for the first time confirmed the protective effects of Pae on AP via the NLRP3 inflammasomes Pathway.


Asunto(s)
Inflamasomas , Pancreatitis , Acetofenonas , Enfermedad Aguda , Animales , Ceruletida/farmacología , Inflamasomas/metabolismo , Macrófagos/metabolismo , Ratones , Ratones Endogámicos C57BL , Proteína con Dominio Pirina 3 de la Familia NLR/metabolismo , Pancreatitis/inducido químicamente , Pancreatitis/tratamiento farmacológico , Especies Reactivas de Oxígeno/efectos adversos
13.
J Transl Med ; 20(1): 299, 2022 07 06.
Artículo en Inglés | MEDLINE | ID: mdl-35794605

RESUMEN

BACKGROUND: Despite advances in targeted agent development, effective treatment of acute myeloid leukemia (AML) remains a major clinical challenge. The B-cell lymphoma-2 (BCL-2) inhibitor exhibited promising clinical activity in AML, acute lymphoblastic leukemia (ALL) and diffuse large B-cell lymphoma (DLBCL) treatment. APG-2575 is a novel BCL-2 selective inhibitor, which has demonstrated anti-tumor activity in hematologic malignancies. Homoharringtonine (HHT), an alkaloid, exhibited anti-AML activity. METHODS: The synergistic effects of APG-2575 and HHT were studied in AML cell lines and primary samples. MTS was used to measure the cell viability. Annexin V/propidium iodide staining was used to measure the apoptosis rate by flow cytometry. AML cell xenografted mouse models were established to evaluate the anti-leukemic effect of BCL-2 inhibitor, HHT and their combination in vivo. Western blot was used to determine the expression of related proteins. RESULTS: APG-2575 showed comparable anti-leukemic effect to the FDA-approved BCL-2 inhibitor ABT-199 in vitro and in vivo. Combined treatment of HHT with APG-2575 synergistically inhibited AML cell growth and engraftment. Mechanistically, HHT promoted degradation of myeloid cell leukemia-1 (MCL-1), which was reported to induce BCL-2 inhibitor resistant, through the PI3K/AKT/GSK3ß signaling pathway. CONCLUSION: Our results provide an effective AML treatment strategy through combination of APG-2575 and HHT, which is worthy of further clinical research.


Asunto(s)
Protocolos de Quimioterapia Combinada Antineoplásica , Homoharringtonina , Leucemia Mieloide Aguda , Animales , Protocolos de Quimioterapia Combinada Antineoplásica/farmacología , Línea Celular Tumoral , Sinergismo Farmacológico , Homoharringtonina/administración & dosificación , Homoharringtonina/farmacología , Leucemia Mieloide Aguda/tratamiento farmacológico , Leucemia Mieloide Aguda/metabolismo , Leucemia Mieloide Aguda/patología , Ratones , Fosfatidilinositol 3-Quinasas/metabolismo , Proteínas Proto-Oncogénicas c-bcl-2/antagonistas & inhibidores , Proteínas Proto-Oncogénicas c-bcl-2/metabolismo
14.
Appl Environ Microbiol ; 88(18): e0080422, 2022 09 22.
Artículo en Inglés | MEDLINE | ID: mdl-36036598

RESUMEN

Microbial-induced calcite precipitation is a promising technology to solve the problem of cracks in soil concrete. The most intensively investigated microorganisms are urease-producing bacteria. Lysinibacillus that is used as urease-producing bacteria in concrete repair has rarely been reported. In this study, Lysinibacillus boronitolerans with a high urease activity was isolated from soil samples. This strain is salt- and alkali-tolerance, and at pH 13, can grow to ~OD600 2.0 after 24 h. At a salt concentration of 6%, the strain can still grow to ~OD600 1.0 after 24 h. The feasibility of using this strain in self-healing concrete was explored. The data showed that cracks within ~0.6 mm could be repaired naturally with hydration when spores and substrates were added to the concrete in an appropriate proportion. Moreover, the number and morphology of CaCO3 crystals that were produced by bacteria can be influenced by the concrete environment. An efficiency method to elucidate the process of microbial-induced calcium carbonate crystal formation was established with Particle Track G400. This study provides a template for future studies on the theory of mineralization based on microorganisms. IMPORTANCE The formation of calcium carbonate crystals in concrete by urease-producing bacteria is not understood fully. In this study, a Lysinibacillus boronitolerans strain with a high urease activity was isolated and used to analyze the counts and sizes of the crystals and the relationship with time. The data showed that the number of crystal particles increases exponentially in a short period with sufficient substrate, after which the crystals grow, precipitate or break. In concrete, the rate-limiting steps of calcium carbonate crystal accumulation are spore germination and urease production. These results provided data support for the rational design of urease-producing bacteria in concrete repair.


Asunto(s)
Materiales de Construcción , Ureasa , Álcalis , Bacillaceae , Bacterias , Carbonato de Calcio/química , Materiales de Construcción/microbiología , Suelo
15.
Fish Shellfish Immunol ; 126: 263-270, 2022 Jul.
Artículo en Inglés | MEDLINE | ID: mdl-35618171

RESUMEN

With the further study of long noncoding RNAs (lncRNAs), an increasing number of biological studies have demonstrated that lncRNAs are involved in various physiological processes, including cell proliferation, apoptosis, invasion, development and disease states. However, unlike mammals, little is known about the role of lncRNAs in the innate immunity of teleost fish. Here, we identify a lncRNA, named LTCONS5539, as critical role in the antiviral and antibacterial response of miiuy croaker and the results showed that lncRNA LTCONS5539 plays a critical regulatory role on TRAF6. Firstly, we found that LPS and poly(I:C) can up-regulate the expression of lncRNA LTCONS5539. Elevated lncRNA LTCONS5539 is capable of increasing the production of inflammatory factors and antiviral genes. Furthermore, the over-expression of lncRNA LTCONS5539 increases the expression of TRAF6 which was confirmed by qPCR and western blotting. On these foundations, we also proved that lncRNA LTCONS5539 modulates innate immunity through TRAF6-mediated immune responses through dual luciferase reporter assay. These results will help to further understand the immunomodulatory mechanisms of lncRNA in teleost fish.


Asunto(s)
Perciformes , ARN Largo no Codificante , Animales , Antivirales , Proteínas de Peces/genética , Proteínas de Peces/metabolismo , Inmunidad Innata/genética , Mamíferos/genética , Mamíferos/metabolismo , ARN Largo no Codificante/genética , Factor 6 Asociado a Receptor de TNF/genética , Factor 6 Asociado a Receptor de TNF/metabolismo
16.
Palliat Support Care ; : 1-7, 2022 Jun 09.
Artículo en Inglés | MEDLINE | ID: mdl-35678169

RESUMEN

OBJECTIVES: A meta-analysis has explored the effect of psychotherapy on the quality of life (QOL) but has not explored the effect on advanced cancer patients' survival, which is highly debated. Therefore, we consider the survival days and QOL as the primary outcomes in our analysis. METHODS: Eligible studies were collected from four databases (PubMed, Embase, Cochrane Library, and Web of Science) until February 20, 2021. The pooled effect sizes were presented as weighted mean difference (WMD) or relative risk (RR) with 95% confidence intervals (CIs). Publication bias was evaluated by Egger's test, and I2 statistics was used to assess the heterogeneity. RESULTS: Thirty-three studies were finally included, containing 2,159 patients in the psychotherapy group and 2,170 patients in the control group. McGill Quality of Life Questionnaire (MQOL) and European Organization for Research and Treatment of Cancer Quality of Life-C15-Palliative (EORTC-QLQ-C15-Pal) supported that QOL of the psychotherapy group was significantly higher than that of the control group, and WMD value was 0.42 (95% CI: 0.12-0.71) and 17.26 (95% CI: 11.08-23.44), respectively. No significant difference was observed between the two groups regarding to the survival time (WMD: 17.85, 95% CI: -8.79, 44.49, P = 0.189). Moreover, the levels of anxiety, depression, confusion, pain, and suffering were lowered in psychotherapy group (all P < 0.05). SIGNIFICANCE OF RESULTS: Psychotherapy could improve the QOL of advanced cancer patients but not affect the survival time.

17.
Am J Physiol Cell Physiol ; 321(5): C846-C858, 2021 11 01.
Artículo en Inglés | MEDLINE | ID: mdl-34550795

RESUMEN

Glypican-1 (GPC1) is one of the six glypican family members in humans. It is composed of a core protein with three heparan sulfate chains and attached to the cell membrane by a glycosyl-phosphatidylinositol anchor. GPC1 modulates various signaling pathways including fibroblast growth factors (FGF), vascular endothelial growth factor-A (VEGF-A), transforming growth factor-ß (TGF-ß), Wnt, Hedgehog (Hh), and bone morphogenic protein (BMP) through specific interactions with pathway ligands and receptors. The impact of these interactions on signaling pathways, activating or inhibitory, is dependent upon specific GPC1 domain interaction with pathway components, as well as cell surface context. In this review, we summarize the current understanding of the structure of GPC1, as well as its role in regulating multiple signaling pathways. We focus on the functions of GPC1 in cancer cells and how new insights into these signaling processes can inform its translational potential as a therapeutic target in cancer.


Asunto(s)
Glipicanos/metabolismo , Transducción de Señal , Animales , Antineoplásicos Inmunológicos/uso terapéutico , Glipicanos/antagonistas & inhibidores , Glipicanos/química , Humanos , Inmunoconjugados/uso terapéutico , Inmunoterapia Adoptiva , Ligandos , Neoplasias/inmunología , Neoplasias/metabolismo , Neoplasias/terapia , Conformación Proteica , Relación Estructura-Actividad
18.
BMC Med ; 19(1): 28, 2021 02 01.
Artículo en Inglés | MEDLINE | ID: mdl-33517886

RESUMEN

BACKGROUND: Although there are many clinical and molecular biomarkers in acute myeloid leukemia (AML), the novel and reliable biomarkers are still required to predict the overall survival at the time of disease diagnosis. METHODS: In order to identify independent predictors, we firstly selected 60 cytogenetically normal AML (CN-AML) patients using the propensity score analysis to balance the confounders and performed circular RNA (circRNA) sequencing. Next, one outcome related to circRNA was selected and validated in the independent cohort of 218 CN-AML patients. We then constructed circRNA-miRNA-mRNA regulated network and performed cellular metabolomic analysis to decipher the underlying biological insights. RESULTS: We identified 308 circRNAs as independent candidate predictors of overall survival. Hsa_circ_0075451 expression was validated as an independent predictor with a weak predictive ability for overall survival. The regulated network of this circular RNA indicated 84 hub genes that appear to be regulated by 10 miRNAs sponged by hsa_circ_0075451. The regulatory axis of hsa_circ_0075451 -| miR-330-5p/miR-326 -| PRDM16 was validated by the dual luciferase report assay, fluorescence in situ hybridization, and ShRNA interference assay. CONCLUSIONS: Our data demonstrates that hsa_circ_0075451 expression may independently contribute to the poor prognosis of AML and present a novel therapeutic target.


Asunto(s)
Biomarcadores de Tumor/metabolismo , Leucemia Mieloide Aguda/metabolismo , MicroARNs/metabolismo , ARN Circular/metabolismo , ARN Mensajero/genética , Regulación Neoplásica de la Expresión Génica , Humanos , Hibridación Fluorescente in Situ/métodos , Leucemia Mieloide Aguda/genética , Masculino , Pronóstico , ARN/metabolismo , ARN Mensajero/metabolismo , Análisis de Secuencia de ARN
19.
J Transl Med ; 19(1): 181, 2021 04 29.
Artículo en Inglés | MEDLINE | ID: mdl-33926484

RESUMEN

BACKGROUND: Fatty acid oxidation (FAO) provides an important source of energy to promote the growth of leukemia cells. Carnitine palmitoyltransferase 1a(CPT1a), a rate-limiting enzyme of the essential step of FAO, can facilitate cancer metabolic adaptation. Previous reports demonstrated that CPT1a acts as a potential molecular target in solid tumors and hematologic disease. However, no systematic study was conducted to explore the prognostic value of CPT1a expression and possible treatment strategies with CPT1a inhibitor on acute myeloid leukemia (AML). METHODS: The expression of CPT1a in 325 cytogenetically normal AML (CN-AML) patients was evaluated using RT-PCR. The combination effects of ST1326 and ABT199 were studied in AML cells and primary patients. MTS was used to measure the cell proliferation rate. Annexin V/propidium iodide staining and flow cytometry analysis was used to measure the apoptosis rate. Western blot was used to measure the expression of Mcl-1. RNAseq and GC-TOFMS were used for genomic and metabolic analysis. RESULTS: In this study, we found AML patients with high CPT1a expression (n = 245) had a relatively short overall survival (P = 0.01) compared to patients in low expression group (n = 80). In parallel, downregulation of CPT1a inhibits proliferation of AML cells. We also conducted genomic and metabolic interactive analysis in AML patients, and found several essential genes and pathways related to aberrant expression of CPT1a. Moreover, we found downregulation of CPT1a sentitized BCL-2 inhibitor ABT199 and CPT1a-selective inhibitor ST1326 combined with ABT199 had a strong synergistic effect to induce apoptosis in AML cells and primary patient blasts for the first time. The underlying synergistic mechanism might be that ST1326 inhibits pGSK3ß and pERK expression, leading to downregulation of Mcl-1. CONCLUSION: Our study indicates that overexpression of CPT1a predicts poor clinical outcome in AML. CPT1a-selective inhibitor ST1326 combined with Bcl-2 inhibitor ABT199 showed strong synergistic inhibitory effects on AML.


Asunto(s)
Leucemia Mieloide Aguda , Apoptosis , Línea Celular Tumoral , Humanos , Leucemia Mieloide Aguda/tratamiento farmacológico , Leucemia Mieloide Aguda/genética , Pronóstico , Sulfonamidas
20.
J Clin Lab Anal ; 34(7): e23257, 2020 Jul.
Artículo en Inglés | MEDLINE | ID: mdl-32100923

RESUMEN

OBJECTIVE: To investigate the correlation between hTREC and human papillomavirus (HPV) load and cervical intraepithelial neoplasia (CIN) grade II/III lesions and cervical cancer. METHODS: A total of 135 patients with cervical lesions of different degrees admitted to our hospital from January 2016 to February 2017 were selected, including CIN I/III 65 cases, grade III 39 cases, and cervical cancer 31 cases. The expression of hTERC gene was detected by fluorescence in situ hybridization (FISH) in three groups, and the HPV load was detected by second-generation hybridization capture (HC II) method, and its relationship with cervical lesion grade was analyzed. Department. RESULTS: The positive expression rate of hTERC gene amplification was cervical cancer > CIN I/II lesion > CIN III lesion; the positive expression rate of HPV was cervical cancer > CIN I/II lesion > CIN III lesion. After treatment, the positive rate of hTERC gene amplification and HPV expression decreased significantly within 1 year (P < .05). Spearman's analysis showed that the degree of cervical lesion was positively correlated with hTREC and HPV load (P < .05). CONCLUSION: hTREC and HPV are closely related to the occurrence and development of cervical precancerous lesions and cervical cancer. The abnormal amplification of hTERC gene increases with the grade of cervical lesions. Both of them can be used as auxiliary indicators for early screening, treatment, and prognosis of cervical cancer.


Asunto(s)
Infecciones por Papillomavirus/patología , ARN/genética , Telomerasa/genética , Neoplasias del Cuello Uterino/patología , Neoplasias del Cuello Uterino/virología , Carga Viral , Femenino , Regulación Neoplásica de la Expresión Génica , Humanos , Hibridación Fluorescente in Situ , Neoplasias del Cuello Uterino/genética
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