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1.
J Biol Chem ; 299(4): 103052, 2023 04.
Artículo en Inglés | MEDLINE | ID: mdl-36813236

RESUMEN

Phytoplasmas are insect-borne bacterial pathogens capable of secreting effectors into host cells and interfering with host plant defense response processes. Previous studies have found that the Candidatus Phytoplasma tritici effector SWP12 binds to and destabilizes the wheat transcription factor TaWRKY74, increasing wheat susceptibility to phytoplasmas. Here, we used a Nicotiana benthamiana transient expression system to identify two key functional sites of SWP12 and screened a series of truncated mutants and amino acid substitution mutants to determine whether they inhibit Bax-induced cell death. Using a subcellular localization assay and online structure analysis websites, we found that structure rather than intracellular localization probably affects the function of SWP12. D33A and P85H are two inactive substitution mutants, neither of which interacts with TaWRKY74, and P85H does not inhibit Bax-induced cell death, suppress flg22-triggered reactive oxygen species (ROS) bursts, degrade TaWRKY74, or promote phytoplasma accumulation. D33A can weakly suppress Bax-induced cell death and flg22-triggered ROS bursts and degrade a portion of TaWRKY74 and weakly promote phytoplasma accumulation. S53L, CPP, and EPWB are three SWP12 homolog proteins from other phytoplasmas. Sequence analysis revealed that D33 was conserved in these proteins, and they exhibited the same polarity at P85. Transient expression in N. benthamiana showed that these proteins could inhibit Bax-induced cell death and suppress ROS bursts. Our findings clarified that P85 and D33 of SWP12 play critical and minor roles, respectively, in suppressing the plant defense response and that they play a preliminary role in determining the functions of homologous proteins.


Asunto(s)
Phytoplasma , Phytoplasma/química , Phytoplasma/metabolismo , Proteínas Bacterianas/metabolismo , Aminoácidos/metabolismo , Especies Reactivas de Oxígeno/metabolismo , Proteína X Asociada a bcl-2/metabolismo , Plantas/metabolismo , Enfermedades de las Plantas/microbiología
2.
Cardiovasc Diabetol ; 23(1): 337, 2024 Sep 11.
Artículo en Inglés | MEDLINE | ID: mdl-39261816

RESUMEN

BACKGROUND: Triglyceride-glucose (TyG) index, a dependable indicator of insulin resistance, has been identified as a valid marker regarding multiple cardiovascular diseases. Nevertheless, the correlation of TyG index with acute myocardial infarction complicated by cardiogenic shock (AMICS) remains uncertain. Our study aims for elucidating this relationship by comprehensively analyzing two large-scale cohorts. METHODS: Utilizing records from the eICU Collaborative Research Database and the Medical Information Mart for Intensive Care IV, the link between TyG and the incidence and prognosis of AMICS was assessed multicentrally and retrospectively by logistic and correlation models, as well as restricted cubic spline (RCS). Propensity score matching (PSM), inverse probability of treatment weighting (IPTW), and overlap weighting (OW) were employed to balance the potential confounders. Subgroup analyses were performed according to potential modifiers. RESULTS: Overall, 5208 AMI patients, consisting of 375 developing CS were finally included. The TyG index exhibited an apparently higher level in AMI populations developing CS than in those who did not experienced CS [9.2 (8.8-9.7) vs. 9.0 (8.5-9.5)], with a moderate discrimination ability to recognize AMICS from the general AMI (AUC: 0.604). Logistic analyses showed that the TyG index was significantly correlated with in-hospital and ICU mortality. RCS analysis demonstrated a linear link between elevated TyG and increased risks regarding in-hospital and ICU mortality in the AMICS population. An increased mortality risk remains evident in PSM-, OW- and IPTW-adjusted populations with higher TyG index who have undergone CS. Correlation analyses demonstrated an apparent link between TyG index and APS score. Subgroup analyses presented a stable link between elevated TyG and mortality particularly in older age, females, those who are overweight or hypertensive, as well as those without diabetes. CONCLUSIONS: Elevated TyG index was related to the incidence of CS following AMI and higher mortality risks in the population with AMICS. Our findings pointed a previously undisclosed role of TyG index in regard to AMICS that still requires further validation.


Asunto(s)
Biomarcadores , Glucemia , Bases de Datos Factuales , Infarto del Miocardio , Valor Predictivo de las Pruebas , Choque Cardiogénico , Triglicéridos , Humanos , Choque Cardiogénico/diagnóstico , Choque Cardiogénico/mortalidad , Choque Cardiogénico/sangre , Choque Cardiogénico/epidemiología , Femenino , Masculino , Infarto del Miocardio/sangre , Infarto del Miocardio/diagnóstico , Infarto del Miocardio/mortalidad , Infarto del Miocardio/epidemiología , Persona de Mediana Edad , Anciano , Estudios Retrospectivos , Glucemia/metabolismo , Pronóstico , Biomarcadores/sangre , Medición de Riesgo , Triglicéridos/sangre , Incidencia , Factores de Riesgo , China/epidemiología , Factores de Tiempo , Mortalidad Hospitalaria , Anciano de 80 o más Años
3.
Artículo en Inglés | MEDLINE | ID: mdl-39231880

RESUMEN

INTRODUCTION: Accurate diagnosis of liver fibrosis is crucial for preventing cirrhosis and liver tumors. Liver fibrosis is driven by activated hepatic stellate cells (HSCs) with elevated CD44 expression. We developed hyaluronic acid (HA)-coated gadolinium-based nanoprobes to specifically target CD44 for diagnosing liver fibrosis using T1-weighted magnetic resonance imaging (MRI). MATERIALS AND METHODS: NaGdF4 nanoparticles (NPs) were synthesized via thermal decomposition and modified with polyethylene glycol (PEG) to obtain non-targeting NaGdF4@PEG NPs. These were subsequently coated with HA to target HSCs, resulting in liver fibrosis-targeting NaGdF4@PEG@HA nanoprobes. Characterization includedd transmission electron microscopy and X-ray diffraction. Cell viability was assessed using the Cell Counting Kit-8 (CCK-8). Internalization of NaGdF4@PEG@HA nanoprobes by mouse HSCs JS1 cells via ligand-receptor interaction was observed using flow cytometry and confocal laser scanning microscopy (CLSM). Liver fibrosis was induced in C57BL/6 mice using a methionine-choline deficient (MCD) diet. MRI performance and nanoprobe distribution in fibrotic and normal livers were analyzed using a GE Discovery 3.0T MR 750 scanner. RESULTS: NaGdF4@PEG@HA nanoprobes exhibited homogeneous morphology, low toxicity, and a high T1 relaxation rate (7.645 mM⁻¹s⁻¹). CLSM and flow cytometry demonstrated effective phagocytosis of NaGdF4@PEG@HA nanoprobes by JS1 cells compared to NaGdF4@PEG. MRI scans revealed higher T1 signals in fibrotic livers compared to normal livers after injection of NaGdF4@PEG@HA. NaGdF4@PEG@HA demonstrated higher targeting ability in fibrotic mice. CONCLUSIONS: NaGdF4@PEG@HA nanoprobes effectively target HSCs with high T1 relaxation rate, facilitating efficient MRI diagnosis of liver fibrosis.

4.
J Craniofac Surg ; 34(2): 755-756, 2023.
Artículo en Inglés | MEDLINE | ID: mdl-36217232

RESUMEN

Surgery-related salivary fistula is the result of intraoperative or postoperative parotid gland damage and extravasation of fluid secreted by acinar into the interstitial space. Most are treated conservatively. Local injection of botulinum toxin is an effective method, but it is relatively expensive and not available in some hospitals. In clinical practice, the authors observed that packing iodoform gauze from the fistula toward the parotid gland can quickly stop postoperative salivary fistula in several patients. This method is simple and easy to implement, and the effect is quick. The disappearance of the salivary fistula was observed on the next day after packing the iodoform gauze. Iodoform gauze packing is an alternative therapy for postoperative parotid fistula. It can be used in areas where botulinum toxin is not available.


Asunto(s)
Toxinas Botulínicas Tipo A , Fístula , Enfermedades de las Parótidas , Humanos , Glándula Parótida/cirugía , Fístula de las Glándulas Salivales/tratamiento farmacológico , Toxinas Botulínicas Tipo A/uso terapéutico , Enfermedades de las Parótidas/tratamiento farmacológico , Fístula/tratamiento farmacológico , Complicaciones Posoperatorias
5.
J Craniofac Surg ; 34(2): 757-758, 2023.
Artículo en Inglés | MEDLINE | ID: mdl-36138547

RESUMEN

BACKGROUND: Mandibular subcondylar fractures can be fixed with 2 titanium plates or 2 resorbable plates. However, when a wider resorbable plate is used, there might be insufficient space on subcondylar region. The authors have tested the back of the condyle as an alternative location for the wide resorbable plate. METHODS: The fractured condyle was accessed through the preauricular approach. The first resorbable plate (4 hole plate, extended; 2 mm Inion OTPSTM) was contoured around the posterior edge of the mandibular ramus. The upper and lower parts of the very resorbable plate were twisted into 2 different planes. The upper part was adapted and then fixed on the back of the condylar neck. And the lower part was fixed on the lateral surface of the posterior edge of the mandibular ramus. The second plate (4 hole plate; 2 mm Inion OTPSTM) was put below the mandibular notch as usual. RESULTS AND DISCUSSION: Postoperative computed tomography confirmed a stable anatomical reduction of condyle. One-year follow-up showed good fracture healing. The authors believe that the back of the condyle is particularly suitable for wider resorbable plate. And this alternative site on the back of the condyle is also feasible in cases where the conventional site is not available.


Asunto(s)
Fijación Interna de Fracturas , Fracturas Mandibulares , Humanos , Fijación Interna de Fracturas/métodos , Cóndilo Mandibular/cirugía , Fracturas Mandibulares/cirugía , Mandíbula , Curación de Fractura , Placas Óseas
6.
Perfusion ; : 2676591231193987, 2023 Aug 02.
Artículo en Inglés | MEDLINE | ID: mdl-37531577

RESUMEN

BACKGROUND: Venoarterial extracorporeal membrane oxygenation (VA-ECMO) is used as a rescue strategy for patients with refractory post-cardiotomy cardiogenic shock (PCS). These patients often have varying degrees of reduced hemoglobin levels, and there are few detailed investigations about the impact of hemoglobin level on their mortality. The objective of this study was to evaluate whether hemoglobin levels at day 1 from VA-ECMO initiation were associated with in-hospital mortality. METHODS: We performed a retrospective analysis of adult VA-ECMO patients over approximately a 2-year period. We divided patients into survival and death groups based on their clinical outcomes and compared the differences in parameters between the two groups. Multivariate logistic regression analyses were performed to estimate whether hemoglobin level was related to the mortality. RESULTS: One hundred and sixteen patients were included in final analysis. There were 52 patients in the survival group and 64 in the death group. The patients were younger in the survival group than the death group (58 vs 63, p = .023). The median (IQR) hemoglobin level at day 1 was 80 (73-89) × g/L, and the median (IQR) RelΔ hemoglobin was 41% (32-48%). Survival patients had a higher hemoglobin level at day 1 and a lower RelΔ hemoglobin than the death patients (91 vs 76 g/L, p < .001; 35% vs 45%, p < .001). The multivariable logistic regression analyses showed that the low hemoglobin levels at day 1 were independently associated with in-hospital mortality (OR 0.808; 95% CI, 0.747-0.874; p < .001). The AUROC for hemoglobin level was 0.89 (95% CI, 0.83-0.95) which was better than that of RelΔ hemoglobin (0.77, 95% CI, 0.68-0.86). CONCLUSIONS: In patients receiving VA-ECMO for PCS, the low hemoglobin levels at day 1 were independently associated with in-hospital mortality.

7.
Perfusion ; : 2676591231194759, 2023 Sep 13.
Artículo en Inglés | MEDLINE | ID: mdl-37703429

RESUMEN

BACKGROUND: Burnout has gained increasing attention worldwide as a phenomenon that affects health care professionals. However, there is a lack of relevant research about its impact on practitioners in the field of cardiovascular perfusion in China. This study investigated the prevalence of and the factors associated with the burnout affecting perfusionists in mainland China. METHODS: This national cross-sectional study included perfusionists from 31 provinces in mainland China. Participants were asked to complete a self-administered questionnaire, which included three parts: (1) demographic information, (2) work-related information, and (3) dissatisfaction with work and sources of pressure. The levels of burnout were calculated, and logistic regression was used to analyze the factors associated with burnout. RESULTS: The questionnaire, created by the survey program "Questionnaire Star", was sent to 2211 perfusionists in mainland China. A final sample of 1813 perfusionists participated in the survey, with a participation rate of 82.0% (1813/2211). The prevalence of burnout and severe burnout was 86.0% (1559/1813, 95%CI: 84.3%-87.5%) and 13.3% (241/1813, 95%CI: 11.8%-15.0%), respectively. The logistic regression analysis revealed that age [20-29 years, odds ratio (OR) = 1; 30-39 years, OR = 2.009; 40-49 years, OR = 2.220], educational background (bachelor and below, OR = 1; postgraduate, OR = 1.472), and professional background (others, OR = 1; surgery, OR = 1.283; anesthesiology, OR = 2.004) were associated with burnout. We also found that age (20-29 years, OR = 1; 30-39 years, OR = 1.928), professional background (others, OR = 1; surgery, OR = 1.734; anesthesiology, OR = 2.257), annual cardiopulmonary bypass (CPB) case load in the most recent 3 years (< 50, OR = 1; 50-100, OR = 1.613; 100-300, OR = 1.702; ≥300, OR = 2.637), and income level [< 5000 (RMB/month), OR = 1; 5000-10,000, OR = 0.587; 10,000-20,000, OR = 0.366] were associated with severe burnout among perfusionists. CONCLUSIONS: Cardiovascular perfusionists in mainland China experience high rates of burnout. Age, the professional background, annual CPB caseload in the most recent 3 years, and income level are independently associated with the burnout rates experienced by these health care professionals.

8.
Perfusion ; : 2676591231169410, 2023 Apr 13.
Artículo en Inglés | MEDLINE | ID: mdl-37051884

RESUMEN

OBJECTIVE: This study aimed to evaluate the relationship between plasma soluble ST2 (sST2) levels 24 h after extracorporeal membrane oxygenation (ECMO) initiation and continuous renal replacement therapy (CRRT) in patients receiving venoarterial ECMO (V-A ECMO) support. METHODS AND RESULTS: Data of patients who received ECMO support for postcardiotomy cardiogenic shock between January 2017 and July 2019 were retrospectively collected from Beijing Anzhen Hospital, Capital Medical University. Ultimately, 116 patients were included in the present study for analysis. The concentration of sST2 was determined by enzyme-linked immunosorbent assay (ELISA). The log10 sST2 levels were higher in patients undergoing CRRT than those who did not (6.06 vs. 6.22, p = 0.019). Patients undergoing CRRT had a lower survival rate than those who did not (32.8% vs. 67.3%, p < 0.001). In the univariate logistic regression analysis, sST2, HCO3-, lactate, and creatinine levels 24 h after ECMO initiation were related to CRRT (p < 0.05). In the multivariate logistic regression analysis, HCO3- and sST2 were identified as independent risk factors for CRRT use in patients undergoing ECMO (p < 0.05). The area under receiver operator characteristic curve (AUC) for sST2 and HCO3- together was 0.72 (95% confidence interval (CI), 0.79-0.91), which was better than those of sST2 or HCO3- alone (0.63 vs. 0.67). CONCLUSIONS: sST2 and HCO3-levels at 24 h after ECMO initiation were associated with CRRT and could predict CRRT use in postcardiotomy cardiogenic shock patients undergoing ECMO.

9.
Small ; 18(23): e2201643, 2022 06.
Artículo en Inglés | MEDLINE | ID: mdl-35532205

RESUMEN

Recent years have witnessed the rapid development of sustainable materials. Along this line, developing biodegradable or recyclable soft electronics is challenging yet important due to their versatile applications in biomedical devices, soft robots, and wearables. Although some degradable bulk hydrogels are directly used as the soft electronics, the sensing performances are usually limited due to the absence of distributed conducting circuits. Here, sustainable hydrogel-based soft electronics (HSE) are reported that integrate sensing elements and patterned liquid metal (LM) in the gelatin-alginate hybrid hydrogel. The biopolymer hydrogel is transparent, robust, resilient, and recyclable. The HSE is multifunctional; it can sense strain, temperature, heart rate (electrocardiogram), and pH. The strain sensing is sufficiently sensitive to detect a human pulse. In addition, the device serves as a model system for iontophoretic drug delivery by using patterned LM as the soft conductor and electrode. Noncontact detection of nearby objects is also achieved based on electrostatic-field-induced voltage. The LM and biopolymer hydrogel are healable, recyclable, and degradable, favoring sustainable applications and reconstruction of the device with new functions. Such HSE with multiple functions and favorable attributes should open opportunities in next-generation electronic skins and hydrogel machines.


Asunto(s)
Hidrogeles , Dispositivos Electrónicos Vestibles , Alginatos , Biopolímeros , Electrónica , Humanos
10.
Soft Matter ; 18(11): 2149-2156, 2022 Mar 16.
Artículo en Inglés | MEDLINE | ID: mdl-35212340

RESUMEN

Fluorescent hydrogels have attracted tremendous attention recently in the field of information security due to the booming development of information technology. Along this line, it is highly desired to improve the security level of concealed information by the advancements of materials and encryption technologies. Here we report multi-level encryption of information in a bilayer hydrogel with shape-morphing ability and patterned fluorescence. This hydrogel is composed of a fluorescence layer containing chromophore units in the poly(acrylic acid) network and an active layer with UV-absorption agents in the poly(N-isopropylacrylamide-co-acrylic acid) network. The former layer exhibits tunable fluorescence tailored by UV light irradiation to induce unimer-to-dimer transformation of the chromophores, facilitating the write-in of information through photolithography. The latter layer is responsive to temperature, enabling morphing of the bilayer hydrogel. Therefore, the bilayer hydrogel encoded with patterned fluorescent patterns can deform into three-dimensional configurations at room temperature to conceal the information, which is readable only after successive procedures of shape recovery at an appropriate temperature and under UV light irradiation from the right direction. The combination of morphing materials and patterned fluorescence as a new avenue to improve the encryption level of information should merit the design of other smart materials with integrated functions for specific applications.

11.
Immun Ageing ; 19(1): 63, 2022 Dec 13.
Artículo en Inglés | MEDLINE | ID: mdl-36514074

RESUMEN

BACKGROUND: It has been widely accepted that monocytes are one of the central mediators contributing to inflammaging. However, it remains unclear whether aged monocytes, similar to aged T cells, have characteristics of hyperactivation and increased expression of co-inhibitory molecules. METHODS: Peripheral blood mononuclear cells (PBMCs) were isolated from young (21-40 years old), middle-aged (41-60 years old), and older human subjects (> 60 years old). Flow cytometry was used to monitor changes in the expression of surface molecules of monocyte subsets and cytokine-producing capacity. RESULTS: We observed increased tumor necrosis factor-α: TNF-α and decreased interleukin-6 (IL-6) production in monocytes from older adults compared with young and middle-aged adults. Older adults had a greater percentage of intermediate and non-classical monocyte subsets, along with increased levels of the immune activation markers human leukocyte antigen-DR (HLA-DR), and adhesion molecules cluster of differentiation molecule 11b (CD11b) and L-selectin (CD62L). Furthermore, we observed increased C-C motif chemokine receptor 2 (CCR2) expression on classical monocytes and decreased C-X3-C motif chemokine receptor 1 (CX3CR1) expression on non-classical monocytes in older adult subjects. The expression of co-inhibitory receptors was reduced on monocyte subsets in older adults. CONCLUSIONS: Circulating monocytes in older adults exhibit increased expression of activation, adhesion, and migration markers, but decreased expression of co-inhibitory molecules.

12.
Perfusion ; : 2676591221130484, 2022 Sep 29.
Artículo en Inglés | MEDLINE | ID: mdl-36172882

RESUMEN

INTRODUCTION: After cardiac surgery, patients on venoarterial extracorporeal membrane oxygenation (VA-ECMO) have a higher risk of nosocomial infection in the intensive care unit (ICU). We aimed to establish an intuitive nomogram to predict the probability of nosocomial infection in patients on VA-ECMO after cardiac surgery. METHODS: We included patients on VA-ECMO after cardiac surgery between January 2011 and December 2020 at a single center. We developed a nomogram based on independent predictors identified using univariate and multivariate logistic regression analyses. We selected the optimal model and assessed its performance through internal validation and decision-curve analyses. RESULTS: Overall, 503 patients were included; 363 and 140 patients were randomly divided into development and validation sets, respectively. Independent predictors derived from the development set to predict nosocomial infection included older age, white blood cell (WBC) count abnormality, ECMO environment in the ICU, and mechanical ventilation (MV) duration, which were entered into the model to create the nomogram. The model showed good discrimination, with areas under the curve (95% confidence interval) of 0.743 (0.692-0.794) in the development set and 0.732 (0.643-0.820) in the validation set. The optimal cutoff probability of the model was 0.457 in the development set (sensitivity, 0.683; specificity, 0.719). The model showed qualified calibration in both the development and validation sets (Hosmer-Lemeshow test, p > .05). The threshold probabilities ranged from 0.20 to 0.70. CONCLUSIONS: For adult patients receiving VA-ECMO treatment after cardiac surgery, a nomogram-monitoring tool could be used in clinical practice to identify patients with high-risk nosocomial infections and provide an early warning.

13.
Small ; 17(41): e2103836, 2021 10.
Artículo en Inglés | MEDLINE | ID: mdl-34514699

RESUMEN

A simple and effective approach is demonstrated to fabricate tough metallosupramolecular hydrogel films of poly(acrylic acid) by one-pot photopolymerization of the precursor solution in the presence of Zr4+ ions that form coordination complexes with the carboxyl groups and serve as the physical crosslinks of the matrix. Both as-prepared and equilibrated hydrogel films are transparent, tough, and stable over a wide range of temperature, ionic strength, and pH. The thickness of the films can be easily tailored with minimum value of ≈7 µm. Owing to the fast polymerization and gelation process, kirigami structures can be facilely encoded to the gel films by photolithographic polymerization, affording versatile functions such as additional stretchability and better compliance of the planar films to encapsulate objects with sophisticated geometries that are important for the design of soft electronics. By stencil printing of liquid metal on the hydrogel film with a kirigami structure, the integrated soft electronics shows good compliance to cover curved surfaces and high sensitivity to monitor human motions. Furthermore, this strategy is applied to diverse natural and synthetic macromolecules containing carboxyl groups to develop tough hydrogel films, which will open opportunities for the applications of hydrogel films in biomedical and engineering fields.


Asunto(s)
Hidrogeles , Metilgalactósidos , Electrónica , Humanos , Impresión Tridimensional
14.
Bioorg Chem ; 109: 104706, 2021 04.
Artículo en Inglés | MEDLINE | ID: mdl-33607360

RESUMEN

Five new meroterpenoids, gancochlearols E - I (1, 3-6), and one compound ganomycin K (2) were isolated from the fruiting bodies of G. cochlear. Their structures were assigned by 1D and 2D NMR, MS, and CD analysis. Rh2(OCOCF3)4-induced ECD method was used to clarify the absolute configuration of secondary alcohol in 1 and 2. Biochemical evaluation showed that all the isolates significantly inhibit COX-2 enzyme in vitro with the IC50 values range from 1.03 µM to 2.71 µM. Further cellular assay revealed that (+)-3 and (-)-6 could suppress metastatic phenotype of triple-negative breast cancer (TNBC) cells via impeding the epithelial-mesenchymal transition (EMT).


Asunto(s)
Ciclooxigenasa 2/metabolismo , Ganoderma/química , Terpenos/química , Terpenos/farmacología , Neoplasias de la Mama , Línea Celular Tumoral , Femenino , Cuerpos Fructíferos de los Hongos/química , Humanos , Estructura Molecular
15.
PLoS Pathog ; 14(7): e1007130, 2018 07.
Artículo en Inglés | MEDLINE | ID: mdl-30001436

RESUMEN

Human gammaherpesviruses are associated with malignancies in HIV infected individuals; in macaques used in non-human primate models of HIV infection, gammaherpesvirus infections also occur. Limited data on prevalence and tumorigenicity of macaque gammaherpesviruses, mostly cross-sectional analyses of small series, are available. We comprehensively examine all three-rhesus macaque gammaherpesviruses -Rhesus rhadinovirus (RRV), Rhesus Lymphocryptovirus (RLCV) and Retroperitoneal Fibromatosis Herpesvirus (RFHV) in macaques experimentally infected with Simian Immunodeficiency Virus or Simian Human Immunodeficiency Virus (SIV/SHIV) in studies spanning 15 years at the AIDS and Cancer Virus Program of the Frederick National Laboratory for Cancer Research. We evaluated 18 animals with malignancies (16 lymphomas, one fibrosarcoma and one carcinoma) and 32 controls. We developed real time quantitative PCR assays for each gammaherpesvirus DNA viral load (VL) in malignant and non-tumor tissues; we also characterized the tumors using immunohistochemistry and in situ hybridization. Furthermore, we retrospectively quantified gammaherpesvirus DNA VL and SIV/SHIV RNA VL in longitudinally-collected PBMCs and plasma, respectively. One or more gammaherpesviruses were detected in 17 tumors; generally, one was predominant, and the relevant DNA VL in the tumor was very high compared to surrounding tissues. RLCV was predominant in tumors resembling diffuse large B cell lymphomas; in a Burkitt-like lymphoma, RRV was predominant; and in the fibrosarcoma, RFHV was predominant. Median RRV and RLCV PBMC DNA VL were significantly higher in cases than controls; SIV/SHIV VL and RLCV VL were independently associated with cancer. Local regressions showed that longitudinal VL patterns in cases and controls, from SIV infection to necropsy, differed for each gammaherpesvirus: while RFHV VL increased only slightly in all animals, RLCV and RRV VL increased significantly and continued to increase steeply in cases; in controls, VL flattened. In conclusion, the data suggest that gammaherpesviruses may play a significant role in tumorogenesis in macaques infected with immunodeficiency viruses.


Asunto(s)
Coinfección/complicaciones , Infecciones por Herpesviridae/complicaciones , Neoplasias/virología , Síndrome de Inmunodeficiencia Adquirida del Simio/complicaciones , Infecciones Tumorales por Virus/complicaciones , Animales , Gammaherpesvirinae , Macaca mulatta , Virus de la Inmunodeficiencia de los Simios
16.
Invest New Drugs ; 38(3): 610-620, 2020 06.
Artículo en Inglés | MEDLINE | ID: mdl-31227936

RESUMEN

The majority of patients with Philadelphia-negative myeloproliferative neoplasms (MPNs) harbor a gain of function mutation V617F in Janus kinase (JAK) 2. Although JAK2 inhibitors such as ruxolitinib have been shown to be clinically efficacious, the hematological toxicity and eventual drug resistance limit its use as monotherapy. Other gene mutations or dysregulation correlated with the disease phenotype and prognosis have been found to contribute to the complexity and heterogeneity of MPNs, giving rise to an increasing demand for combination therapies. Here, we combine ruxolitinib and the histone deacetylase inhibitor vorinostat as a rational combination strategy for MPNs. We tested the combination of ruxolitinib and vorinostat in cells with the JAK2V617F mutation, such as HEL cells, c-Kit+ cells from JAK2V617F transgenic mice and bone marrow mononuclear cells (BMMNCs) from patients with MPN. Our results showed significant synergistic effects of this combination strategy. Cotreatment with ruxolitinib and vorinostat synergistically induced apoptosis, cell cycle arrest and inhibition of the colony-forming capacity of HEL cells by attenuating the JAK/signal transducer and activator of transcription (STAT) and protein kinase-B (AKT) signaling pathways. In particular, cotreatment with ruxolitinib and vorinostat prevented the formation of large colonies of colony-forming unit-granulocyte/erythroid/macrophage/megakaryocytes (CFU-GEMMs) and colony-forming unit-granulocyte/macrophages (CFU-GMs) derived from the BMMNCs of patients with MPN. Taken together, these data provided preclinical evidence that the combination of ruxolitinib and vorinostat is a potential dual-target therapy for patients with MPN.


Asunto(s)
Histona Desacetilasas/metabolismo , Janus Quinasa 2/metabolismo , Trastornos Mieloproliferativos/tratamiento farmacológico , Neoplasias/tratamiento farmacológico , Pirazoles/farmacología , Factores de Transcripción STAT/metabolismo , Transducción de Señal/efectos de los fármacos , Vorinostat/farmacología , Animales , Apoptosis/efectos de los fármacos , Puntos de Control del Ciclo Celular/efectos de los fármacos , Proliferación Celular/efectos de los fármacos , Sinergismo Farmacológico , Humanos , Macrófagos/efectos de los fármacos , Macrófagos/metabolismo , Ratones Transgénicos , Mutación/genética , Células Progenitoras Mieloides/efectos de los fármacos , Células Progenitoras Mieloides/metabolismo , Trastornos Mieloproliferativos/metabolismo , Neoplasias/metabolismo , Nitrilos , Pirimidinas
17.
Perfusion ; 35(2): 145-153, 2020 03.
Artículo en Inglés | MEDLINE | ID: mdl-31387455

RESUMEN

OBJECTIVES: The benefit of preoperative intra-aortic balloon pump implantation in high-risk cardiac surgery patients is still debated. The role of preoperative intra-aortic balloon pump insertion in acute myocardial infarction patients without cardiogenic shock undergoing off-pump coronary artery bypass grafting remains unknown. This study aimed to determine the efficacy and safety of the preoperative intra-aortic balloon pump insertion in those patients undergoing off-pump coronary artery bypass grafting. METHODS: A total of 421 consecutive acute myocardial infarction patients without cardiogenic shock who underwent isolated off-pump coronary artery bypass grafting were enrolled in this retrospective observational propensity score-matched analysis study. Patients who received intra-aortic balloon pump before off-pump coronary artery bypass grafting (the intra-aortic balloon pump group, n = 157) were compared with those who had not (control group, n = 264). The 30-day postoperative survival, postoperative complications, and postoperative hospital length of stay were compared between the two groups. RESULTS: A total of 99 pairs of patients were matched. The preoperative intra-aortic balloon pump did not show a 30-day postoperative survival benefit compared with the control group (hazard ratio, 0.9; 95% confidence interval, 0.2-4.2; p = 0.92). Patients with preoperative intra-aortic balloon pump were more likely to have shorter postoperative lengths of stay (8 (6-11) days vs. 10 (6-15) days, p = 0.02) and decreased total days in the hospital (median days: 18.2 vs. 21.8, p = 0.02) compared to patients without balloon pumps. CONCLUSION: Preoperative intra-aortic balloon pump insertion in acute myocardial infarction patients without cardiogenic shock undergoing off-pump coronary artery bypass grafting improved convalescence as shown by significantly shorter postoperative lengths of hospital stay.


Asunto(s)
Puente de Arteria Coronaria/métodos , Corazón Auxiliar/normas , Contrapulsador Intraaórtico/métodos , Infarto del Miocardio/cirugía , Cuidados Preoperatorios/métodos , Enfermedad Aguda , Femenino , Humanos , Masculino , Persona de Mediana Edad , Infarto del Miocardio/mortalidad , Estudios Retrospectivos , Análisis de Supervivencia
18.
BMC Cancer ; 19(1): 1164, 2019 11 29.
Artículo en Inglés | MEDLINE | ID: mdl-31783810

RESUMEN

Following publication of the original article [1], the authors reported the following error is the article.

20.
Perfusion ; 34(5): 364-374, 2019 07.
Artículo en Inglés | MEDLINE | ID: mdl-30624149

RESUMEN

BACKGROUND: Cardiopulmonary bypass (CPB) during open-heart surgery triggers an inflammatory response that can cause significant morbidity and mortality. Human monocytes and regulatory T (Treg) cells are phenotypically and functionally heterogeneous and have been shown to play a significant role in the inflammatory dysfunction triggered by CPB. Glucocorticoids (GCs) have been widely administered for decades in patients undergoing CPB to reduce this inflammatory response. However, it has not been clearly established how routine prophylactic administration of glucocorticoids (GCs) affects monocyte and Treg subsets. METHODS: Thirty-six patient who underwent heart surgery with CPB were randomly assigned to a methylprednisolone group (MG, N = 18; 500 mg in the CPB priming) and a non-methylprednisolone group (NMG, N = 18). The circulating monocyte and Treg subsets were analyzed by flow cytometry. RESULTS: The MG and NMG groups had comparable percentages of monocyte subsets and similar expression levels of HLA-DR, CD86, CD64 and toll-like receptor 4 (TLR4). Remarkably, methylprednisolone increased the percentage of CD4+CD25+ Treg cells among CD4+ T cells in patients undergoing CPB, but did not increase the proportion of suppressive Treg cells, either resting or activated, in these patients undergoing CPB. CONCLUSIONS: Our results showed that prophylactic administration of methylprednisolone neither decreased the percentages and counts of inflammatory monocyte subsets nor did it induce the expansion of suppressive Treg cells in patients undergoing CPB. These results clarified the effects of GCs on cell-mediated immune responses and provided additional evidence in practice. TRIAL REGISTRATION: Clinicaltrials.gov : NCT01296074. Registered 14 February 2011.


Asunto(s)
Puente Cardiopulmonar/métodos , Metilprednisolona/uso terapéutico , Monocitos/efectos de los fármacos , Linfocitos T Reguladores/metabolismo , Puente Cardiopulmonar/mortalidad , Femenino , Humanos , Masculino , Metilprednisolona/farmacología , Tasa de Supervivencia
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