Your browser doesn't support javascript.
loading
Mostrar: 20 | 50 | 100
Resultados 1 - 20 de 2.795
Filtrar
1.
FASEB J ; 36 Suppl 12022 May.
Artigo em Inglês | MEDLINE | ID: mdl-35556653

RESUMO

Hepatocellular Carcinoma (HCC) is the most common form of liver cancer and is the leading cause of cancer-related mortality globally. Despite the substantial progress that has been made in current treatments, HCC remains malignancy with a high recurrence rate due to a poor prognosis. Therefore, developing novel immunotherapy approaches to treat HCC is crucial to solving this global public health problem. Anti-tumor vaccines are promising strategies to elicit immune responses for anti-tumor immunity. In this study, we designed and cloned an alphavirus-vesiculovirus hybrid vaccine vector VLV-GPC3 that can generate virus-like vesicles (VLVs) as self-amplifying RNA replicons to additionally express GPC3, a cell-surface heparan sulfate proteoglycan is highly expressed in HCC. The potency of the VLV-GPC3 as tumor vaccine was assessed in vivo by immunization of C57BL/6 mice with 108 PFU of VLV-GPC3, followed by subcutaneous implantation of Hepa1-6 HCC cell line cells into C57BL/6 mice. The results showed that VLV-GPC3 immunization could elicit robust GPC3-specific antibody responses and effective protection by increasing CD8+ T cells and minimizing the tumor size. Further, the immunized mouse splenocytes co-cultured with GPC3 could significantly promote IFN-r production and CD4+ T cell proliferation. Our data indicate that VLV-GPC3 could be developed as a novel vaccine candidate and offer a new treatment strategy against HCC.

2.
Front Aging Neurosci ; 14: 838173, 2022.
Artigo em Inglês | MEDLINE | ID: mdl-35557834

RESUMO

Metformin, one of the first-line of hypoglycemic drugs, has cardioprotective, anti-inflammatory and anticancer activities, in addition to its proven hypoglycemic effects. Furthermore, the preventive and therapeutic potential of metformin for neurodegenerative diseases has become a topic of concern. Increasing research suggests that metformin can prevent the progression of neurodegenerative diseases. In recent years, many studies have investigated the neuroprotective effect of metformin in the treatment of neurodegenerative diseases. It has been revealed that metformin can play a neuroprotective role by regulating energy metabolism, oxidative stress, inflammatory response and protein deposition of cells, and avoiding neuronal dysfunction and neuronal death. On the contrary, some have hypothesized that metformin has a two-sided effect which may accelerate the progression of neurodegenerative diseases. In this review, the results of animal experiments and clinical studies are reviewed to discuss the application prospects of metformin in neurodegenerative diseases.

3.
Front Bioeng Biotechnol ; 10: 865787, 2022.
Artigo em Inglês | MEDLINE | ID: mdl-35557867

RESUMO

Poly (ethylene terephthalate) (PET) plastic is chemically inert and persistent. Massive quantities of PET waste end up in landfill sites and oceans, posing major global pollution concerns. PET degrading enzymes with high efficiency provide plastic recycling and bioremediation possibilities. Here, we report a novel cutinase, MtCut with distinct catalytic behaviors, derived from the deep sea Nocardiopsaceae family strain. Biochemical analyses showed MtCut efficiently hydrolyzed PET at ambient temperatures and in an exo-type manner. The activity and stability of MtCut were enhanced by the addition of calcium ions. Notably, no hydrolysis products inhibition was observed during PET depolymerization, suggesting MtCut is a better biocatalyst when compared to other PET hydrolases. In addition, structural components associated with thermal adaptation were investigated using molecular dynamic (MD) simulations, and key regions regulating MtCut thermostability were identified. Our biochemical and structural analyses of MtCut deepen the understanding of PET hydrolysis by cutinases, and provide invaluable insights on improvement and performance engineering strategies for PET-degrading biocatalysts.

4.
Angiology ; : 33197221087778, 2022 May 04.
Artigo em Inglês | MEDLINE | ID: mdl-35506476

RESUMO

The present study explored the predictive value of culprit high-risk plaque (HRP) detected by optical coherence tomography (OCT) for predicting major adverse cardiovascular events (MACEs) in patients with ST-segment elevation myocardial infarction (STEMI). HRP was defined as the simultaneous presence of four criteria: minimum lumen area <3.5 mm2, fibrous cap thickness <75 µm, lipid plaque with lipid arc extension >180°, and presence of macrophages. Patients (n = 274) were divided into non-HRP group (n = 206) and HRP group (n = 68). MACEs were defined as a composite of all-cause death, myocardial infarction, stroke, and revascularization. During a mean follow-up of 2.2 years, 47 (17.5%) MACEs were observed: 28 (13.6%) in the non-HRP group and 19 (27.9%) in the HRP group (log-rank P = .005). Patients with HRP were 2.05 times more likely to suffer from a MACE than those without HRP (hazards ratio: 2.05, 95% confidence interval: 1.04-4.02, P = .038); MACE risk was comparable between plaque rupture and plaque erosion. In conclusion, HRP was present in 24.8% of STEMI patients and associated with higher cardiovascular risk independent of plaque rupture, suggesting that HRP detected by OCT may help identify patients at high risk of future cardiac events.

5.
Exp Biol Med (Maywood) ; : 15353702221088781, 2022 May 04.
Artigo em Inglês | MEDLINE | ID: mdl-35507096

RESUMO

Due to the lack of an assessment approach, the image of in vivo nasal ciliary motion of allergic rhinitis (AR) has never been captured and analyzed to date. Here, we have used an optimized approach to analyze the nasal ciliary function in vivo in AR rats. The digital microscopy system, a method for direct observation of ciliary motion in a living AR rat model, was applied to visualize and measure ciliary motion in vivo, including ciliary beat frequency (CBF) and ciliary beat distance (CBD). The AR rat model was established by ovalbumin sensitization. Comparisons of nasal ciliary motion in vivo between the experimental group (ovalbumin sensitization, allergen, or histamine) and the control group were analyzed. In the living rat model of allergic rhinitis, CBF and CBD decreased to 57.8 and 73.1% of the control group, respectively, but were restored after administration of chlorpheniramine maleate. Ovalbumin (OVA) significantly inhibited the ciliary motion of normal mucosa in vivo. However, responding to the OVA challenge, the ciliary motion of OVA-sensitized mucosa would not decrease further and stay at a stable level. Histamine stimulated in vivo ciliary motion quickly within 30 min, but afterward, the ciliary motion gradually decreased below the baseline. These results have clarified that in vivo ciliary motion was impaired by nasal mucosal sensitization, and this impairment was most likely related to allergen challenge and histamine. In addition, the short-term stimulation and long-term inhibition effects of histamine on in vivo ciliary motion were first reported in this study.

6.
Artigo em Inglês | MEDLINE | ID: mdl-35507679

RESUMO

In the face of the increasingly serious rapid depletion of fossil fuels, exploring alternative energy conversion technologies may be a promising choice to alleviate this crisis. Transition metal carbides (TMCs)/carbon composites are considered as prospective electrocatalysts due to their high catalytic activities and structural stability. In this work, we report the simple synthesis of TMCs/N-doping carbon aerogels (TMCs/NCAs, including Fe3C/NCA, Mo3C2/NCA, and Fe3C-Mo2C/NCA) for the oxygen reduction reaction (ORR) using protonated chitosan/metal complex anion-chelated aerogels. Among them, the Fe3C/NCA composite possesses efficient ORR activity (similar to Pt/C), and the Fe3C/NCA-assembled Zn-air battery exhibits high power densities of about 250 mW cm-2. The density functional theory calculation reveals that the presence of graphite-N, pyridine-N, and carbon defects in the carbon framework effectively reduces the free energy of ORR occurring in Fe3C. This work provides a simple and extensible strategy for the preparation of TMCs from chitosan, which is expected to be extended to other metal carbides.

7.
J Phys Chem A ; 2022 May 05.
Artigo em Inglês | MEDLINE | ID: mdl-35511037

RESUMO

While examining the heterogeneous reaction of chlorine atoms with alkenes, in the presence of Cl2, we have observed an unexpectedly large enhancement of reactivity and the predominance of chlorinated reaction products even under high O2 conditions, where Cl atom recycling is expected to be minimal. These observations cannot be explained by known free radical oxidation or cycling mechanisms, but rather we find evidence for the multiphase catalytic coupling of free radical oxidation with electrophilic Cl2 addition. The mechanism entails the production of oxygenated reaction intermediates, which act as gas-liquid phase-transfer catalysts (gl-PTCs) by promoting the accommodation of gas-phase Cl2 by the aerosol, thereby enhancing electrophilic addition. Although the majority of PTCs typically couple chemistry between two immiscible liquid phases (aqueous/organic), there are few examples of PTCs that couple gas-liquid reactions. This work shows how multiphase reaction schemes of aerosols can be reimagined for understanding catalytic reaction mechanisms.

8.
Commun Biol ; 5(1): 439, 2022 May 11.
Artigo em Inglês | MEDLINE | ID: mdl-35545661

RESUMO

SARS-CoV-2 variants shaped the second year of the COVID-19 pandemic and the discourse around effective control measures. Evaluating the threat posed by a new variant is essential for adapting response efforts when community transmission is detected. In this study, we compare the dynamics of two variants, Alpha and Iota, by integrating genomic surveillance data to estimate the effective reproduction number (Rt) of the variants. We use Connecticut, United States, in which Alpha and Iota co-circulated in 2021. We find that the Rt of these variants were up to 50% larger than that of other variants. We then use phylogeography to show that while both variants were introduced into Connecticut at comparable frequencies, clades that resulted from introductions of Alpha were larger than those resulting from Iota introductions. By monitoring the dynamics of individual variants throughout our study period, we demonstrate the importance of routine surveillance in the response to COVID-19.

9.
J Hepatocell Carcinoma ; 9: 379-387, 2022.
Artigo em Inglês | MEDLINE | ID: mdl-35547829

RESUMO

Hepatocellular carcinoma is one of the most common malignancies globally. Recently, a newly identified histological subtype, designated as "macrotrabecular-massive hepatocellular carcinoma" (MTM-HCC), has been associated with an aggressive phenotype and has received extensive attention. MTM-HCC was a strong independent prognostic predictor of early and overall recurrence because it is closely related to tumor molecular subclass, gene mutation, carcinogenesis pathways, and immunohistochemical markers. In addition, preoperative imaging examination can potentially provide an essential clue for diagnosing MTM-HCC, intratumor necrosis or ischemia is an independent predictor for MTM-HCC on Gd-EOB-DTPA enhanced MRI or CT. Early diagnosis and appropriate treatment of MTM-HCC could prove beneficial for preventing early recurrence and could improve outcomes.

10.
Org Lett ; 2022 May 16.
Artigo em Inglês | MEDLINE | ID: mdl-35575309

RESUMO

The Rh(III)-catalyzed highly enantioselective C2-arylation of indole derivatives with 1-diazonaphthoquinones is reported. In the presence of 2.5 mol % SCpRh complex and 20 mol % AgNO3, the C2-arylation reactions of indoles proceeded smoothly, affording a wide range of C2-arylated indole atropisomers in good yields and enantioselectivity (≤96% yield, ≤97% ee) under mild conditions. The method displays a broad substrate scope and good functional group tolerance.

11.
Ying Yong Sheng Tai Xue Bao ; 33(4): 1125-1130, 2022 Apr.
Artigo em Chinês | MEDLINE | ID: mdl-35543068

RESUMO

We examined the barrier effects against Bemisia tabaci and the potential to control the tomato yellow leaf curl virus (TYLCV) of different tomato-maize intercropping modes. Tomatoes (variety Jinshan 511) were planted at a fixed row distance either as a monoculture or together with maize (variety Xianyu 335) at the distances of 10, 20, and 30 cm. We investigated the viral index for TYLCV and the population density of B. tabaci. Compared with tomato monoculture, the natural barrier established by the maize stabilized the growth environment for tomato. When the maize spacing was 10, 20, and 30 cm, the average temperature of tomato plants from 6:00 to 20:00 decreased by 3.01, 2.26, and 1.45 ℃, the average relative humidity increased by 13.0%, 8.8%, and 6.0%, and the mean light intensity reduced by 26.1%, 20.4%, and 14.5%, respectively. The changes of those factors alleviated the adverse environmental conditions (i.e., intense light, high temperature, and lack of moisture) that promote the spread of virus-related diseases during the high-temperature period of the day, with the most effective planting distance for the maize being 10 cm. Our results suggested that the intercropping of tomato and maize had a barrier effect against B. tabaci and was able to control the TYLCV in tomato. When the planting distance for the maize was 10, 20, and 30 cm, the number of B. tabaci was 88.7%, 82.0%, and 73.9% lower than tomato monoculture, respectively. The TYLCV was inhibited, with the viral disease index being decreased by 67.3%, 59.4%, and 44.5%, respectively. Tomato-maize intercropping was also beneficial for tomato plant growth and fruit set, which could enhance tomato yield. Such effect was strengthened under higher maize density.


Assuntos
Hemípteros , Lycopersicon esculentum , Animais , Begomovirus , Insetos Vetores , Doenças das Plantas/prevenção & controle , Zea mays
12.
ACS Nano ; 2022 May 13.
Artigo em Inglês | MEDLINE | ID: mdl-35549072

RESUMO

Insulating compensated ferrimagnets, especially hosting room-temperature compensation points, are considered promising candidates for developing ultra-high-density and ultrafast magnonic devices owing to combining the characteristics of both ferromagnets and antiferromagnets. These intriguing features become outstanding close to their compensation points. However, their spin-orbit torque (SOT)-induced magnetization switching, particularly in the vicinity of the compensation points, remains unclear. Herein, we systematically investigated the SOT in insulating compensated ferrimagnetic Gd3Fe5O12/Pt heterostructures with perpendicular magnetic anisotropy. A nearly room-temperature compensation point (Tcomp ∼ 297 K) was consistently identified by the magnetization curves, spin Hall-induced anomalous Hall effect, and spin Hall magnetoresistance measurements. Moreover, using 100 ns duration pulsed current, deterministic current-induced magnetization switching below and above Tcomp, even at 294 and 301 K, was achieved with opposite switching polarity. It is found that a large current is required to switch the magnetization in the vicinity of Tcomp, although the effective SOT field increases close to Tcomp. Our finding provides alternative opportunities for exploring ultrafast room-temperature magnon-based devices.

13.
Schizophr Bull ; 2022 May 15.
Artigo em Inglês | MEDLINE | ID: mdl-35569004

RESUMO

BACKGROUND AND HYPOTHESIS: Antipsychotics remain the main treatment for schizophrenia, but their effectiveness is challenging to compare. We aimed to assess the comparative real-world effectiveness of antipsychotics in preventing readmission among patients in Asia with early-stage schizophrenia to inform clinical decision making. STUDY DESIGN: We did a retrospective cohort study of first-admission schizophrenia patients (ICD-9-CM: 295; ICD-10-CM: F20 and F25) from January 1, 2001, to December 31, 2017. The cohort was identified from the National Health Insurance Research Database NHIRD for Psychiatric Inpatients. The exposure was any antipsychotics prescribed post-discharge. The primary outcome was the readmission risk due to psychotic disorders, which was measured by adjusted hazard ratios (aHRs). Within-individual extended Cox models were applied for analyses, where the periods of oral risperidone use served as his or her own control. STUDY RESULTS: We selected 75 986 patients (men, 53.4%; mean [SD] age, 37.6 [12.0] years; mean [SD] duration of follow-up, 8.9 [5.0]) who were first admitted to psychiatric wards with schizophrenia in Taiwan. Among them, 47 150 patients (62.05%) had at least one readmission within 4 years. Compared to the period under treatment with oral risperidone, that under monotherapy with long-acting injectable antipsychotics (LAIs) had the lowest risk for psychotic readmission, with a risk reduction of 15-20%. However, the prevalence of person-prescription prevalence of LAIs remained low (< 10%) during the follow-up period. CONCLUSIONS: The use of LAIs after the first admission for schizophrenia has notable advantages in preventing readmission. Such formulations should be offered earlier in the course of illness.

14.
Artigo em Inglês | MEDLINE | ID: mdl-35561839

RESUMO

BACKGROUND: The mitochondrial fission protein, dynamin related protein 1 (Drp1), has been suggested to regulate mast cell (MC) activation by certain stimuli in vitro but its functions in MCs activated by various stimuli in vivo has not been examined. OBJECTIVE: Analyze Drp1 function in both mouse and human MCs. METHODS: We used human peripheral blood-derived cultured MCs (PBCMCs) and two genetic mouse models in which MCs were depleted of Drp1: Drp1fl/flMcpt5cre+/- mice and Drp1fl/flCpa3cre+/- mice. RESULTS: In mice, Drp1 depletion enhanced FcεRI-induced MC activation while suppressing substance P (SP)-stimulated MC activation in vitro and in vivo. This was also true in human PBCMCs in vitro after pharmacological inhibition of Drp1. CONCLUSION: Our work shows that Drp1 differentially regulates MC activation by various stimuli. These findings suggest that promoting Drp1 activation might represent a novel therapy for suppressing IgE-dependent MC activation while inhibiting Drp1 activation might mitigate other MC-dependent responses, such as those induced by substance P.

15.
Front Pharmacol ; 13: 803331, 2022.
Artigo em Inglês | MEDLINE | ID: mdl-35529434

RESUMO

Acutely, non-selective cannabinoid (CB) agonists have been shown to increase morphine antinociceptive effects, and we and others have also demonstrated that non-selective CB agonists attenuate morphine antinociceptive tolerance. Activation of cannabinoid CB2 receptors reverses allodynia and hyperalgesia in models of chronic pain, and co-administration of morphine with CB2 receptor selective agonists has been shown to be synergistic. CB2 receptor activation has also been shown to reduce morphine-induced hyperalgesia in rodents, an effect attributed to CB2 receptor modulation of inflammation. In the present set of experiments, we tested both the acute and chronic interactions between morphine and the CB2 receptor selective agonist O-1966 treatments on antinociception and antinociceptive tolerance in C57Bl6 mice. Co-administration of morphine and O-1966 was tested under three dosing regimens: simultaneous administration, morphine pre-treated with O-1966, and O-1966 pre-treated with morphine. The effects of O-1966 on mu-opioid receptor binding were determined using [3H]DAMGO and [35S]GTPγS binding assays, and these interactions were further examined by FRET analysis linked to flow cytometry. Results yielded surprising evidence of interactions between the CB2 receptor selective agonist O-1966 and morphine that were dependent upon the order of administration. When O-1966 was administered prior to or simultaneous with morphine, morphine antinociception was attenuated and antinociceptive tolerance was exacerbated. When O-1966 was administered following morphine, morphine antinociception was not affected and antinociceptive tolerance was attenuated. The [35S]GTPγS results suggest that O-1966 interrupts functional activity of morphine at the mu-opioid receptor, leading to decreased potency of morphine to produce acute thermal antinociceptive effects and potentiation of morphine antinociceptive tolerance. However, O-1966 administered after morphine blocked morphine hyperalgesia and led to an attenuation of morphine tolerance, perhaps due to well-documented anti-inflammatory effects of CB2 receptor agonism.

16.
Proc Natl Acad Sci U S A ; 119(21): e2202016119, 2022 May 24.
Artigo em Inglês | MEDLINE | ID: mdl-35537042

RESUMO

SignificanceAutophagy defects are a risk factor for inflammatory bowel diseases (IBDs), but the mechanism remains unknown. We show here that conditional whole-body deletion of Atg5 or Fip200, but not Atg7, is lethal due to loss of ileum stem cells and barrier function likely caused by different kinetics of autophagy loss, which was rescued by slow deletion. Specific autophagy loss in PDGFRα+ mesenchymal cells (PMCs) resulted in loss of Wnt signaling responsible for failed stem cell renewal. We also observed depletion of aspartate and nucleotides throughout the ileum. Our results illustrate that autophagy is required for PMC metabolism and survival necessary to sustain intestinal stem cells and mouse survival, and failure to maintain PMCs through autophagy contributes to IBD.


Assuntos
Autofagia , Intestinos , Receptor alfa de Fator de Crescimento Derivado de Plaquetas , Células-Tronco , Animais , Autofagia/genética , Proteína 5 Relacionada à Autofagia , Proteína 7 Relacionada à Autofagia , Proteínas Relacionadas à Autofagia , Sobrevivência Celular , Camundongos , Receptor alfa de Fator de Crescimento Derivado de Plaquetas/genética , Receptor alfa de Fator de Crescimento Derivado de Plaquetas/metabolismo , Células-Tronco/metabolismo
17.
Acta Biochim Biophys Sin (Shanghai) ; 54(3): 361-369, 2022 Mar 25.
Artigo em Inglês | MEDLINE | ID: mdl-35538031

RESUMO

Pancreatic cancer is highly lethal due to its aggressive invasive properties and capacity for metastatic dissemination. Additional therapeutic targets and effective treatment options for patients with tumours of high invasive capacity are required. Ras-related protein-2a (RAP2) is a member of the GTP-binding proteins. RAP2 has been reported to be widely upregulated in many types of cancers via regulating cytoskeleton reorganization, cell proliferation, migration, and adhesion, as well as inflammation. As a member of the RAS oncogene family, which has been demonstrated to drive pancreatic cancer oncogenesis and many other malignancies, the physiological roles of RAP2 in pancreatic cancer have seldom been discussed. In the present study, we explored the correlation between RAP2 expression and the prediction of overall survival of pancreatic cancer patients. Mechanistic studies were carried out to shed light on the role of RAP2 in pancreatic cancer invasion and how RAP2 is regulated in the invasive process. Our results demonstrated that patients with higher RAP2 expression showed unfavourable prognoses. studies demonstrated that silencing of inhibited the invasion of pancreatic cancer cells. Moreover, our results demonstrated that transforming growth factor-ß1 (TGF-ß1), an inducer of the metastatic potential of pancreatic cancer cells, regulates the expression of RAP2 via the transcription factor c-Myc. In conclusion, the present study uncovered RAP2 as a novel predictive marker and therapeutic target for pancreatic cancer.


Assuntos
Neoplasias Pancreáticas , Fator de Crescimento Transformador beta1 , Linhagem Celular Tumoral , Movimento Celular/genética , Proliferação de Células/genética , Humanos , Invasividade Neoplásica , Neoplasias Pancreáticas/metabolismo , Neoplasias Pancreáticas/patologia , Fator de Crescimento Transformador beta1/genética , Fator de Crescimento Transformador beta1/metabolismo , Regulação para Cima , Proteínas rap de Ligação ao GTP/genética , Proteínas rap de Ligação ao GTP/metabolismo
18.
Cardiovasc Diabetol ; 21(1): 80, 2022 May 20.
Artigo em Inglês | MEDLINE | ID: mdl-35596184

RESUMO

BACKGROUND: Proprotein convertase subtilisin/kexin type 9 (PCSK9) has been shown to be predictive of cardiovascular outcomes in stable coronary artery disease with diabetes. We aimed to assess the relationship between PCSK9 and major adverse cardiovascular events (MACEs) in ST-segment elevation myocardial infarction (STEMI) patients with or without diabetes, as well as the relationships between PCSK9 and metabolism, inflammation and platelet activation markers. METHODS: A total of 1027 patients with STEMI undergoing primary percutaneous coronary intervention (PCI) and without prior lipid-lowering therapy were consecutively enrolled and the baseline plasma PCSK9 levels were determined by ELISA. Patients were divided into high and low PCSK9 groups according to PCSK9 median. All patients were followed up for the occurrence of MACEs. The associations of PCSK9 with metabolism, inflammation and platelet activation markers and MACEs were evaluated. RESULTS: PCSK9 levels were positively correlated with triglycerides, high-sensitivity C reactive protein, soluble CD40 ligand and soluble P-selectin levels, and the correlations were stronger in diabetic patients than in non-diabetic patients. In diabetic patients receiving ticagrelor, PCSK9 levels were positively correlated with maximal platelet aggregation measured by light transmittance aggregometry and maximum amplitude of adenosine diphosphate-induced platelet-fibrin clots measured by thrombelastography in the maintenance phase of treatment, whereas no correlations were found in non-diabetic patients. During a median follow-up of 2.0 years, 155 (15.1%) MACEs occurred. The Kaplan-Meier analysis displayed that the patients with high PCSK9 levels had lower event-free survival rate than those with low PCSK9 levels (P = 0.030). When participants were categorized into 4 subgroups according to PCSK9 levels and diabetes status, high PCSK9 levels plus diabetes subgroup had the lowest cumulative event-free survival rate (P = 0.043). Multivariable Cox regression analysis revealed that high PCSK9 levels were independently associated with MACEs in diabetic patients (hazard ratio 2.283, 95% confidence interval: 1.094-4.764, P = 0.028), but not in the whole cohort or non-diabetic patients. CONCLUSIONS: The study showed that high PCSK9 levels were independently associated with MACEs in STEMI patients with diabetes undergoing primary PCI, and the association may be due to stronger correlations of PCSK9 with inflammation and platelet activation markers in diabetic patients.


Assuntos
Doenças Cardiovasculares , Diabetes Mellitus , Intervenção Coronária Percutânea , Infarto do Miocárdio com Supradesnível do Segmento ST , Biomarcadores , Fatores de Risco de Doenças Cardíacas , Humanos , Inflamação/diagnóstico , Intervenção Coronária Percutânea/efeitos adversos , Ativação Plaquetária/fisiologia , Pró-Proteína Convertase 9 , Fatores de Risco , Infarto do Miocárdio com Supradesnível do Segmento ST/diagnóstico , Infarto do Miocárdio com Supradesnível do Segmento ST/terapia
19.
Acta Biochim Biophys Sin (Shanghai) ; 54(4): 494-503, 2022 Apr 25.
Artigo em Inglês | MEDLINE | ID: mdl-35607957

RESUMO

Adipose tissue formation and moderate fat deposition are important for the production performance and eating quality of livestock meats. The self-renewal and adipogenic differentiation of adipose-derived stem cells are responsible for the formation and development of adipose tissue. In addition, estrogen targeting G protein-coupled estrogen receptor 1 (GPER1) has been reported to modulate cell proliferation and differentiation during tissue and organ development. However, the potential correlation among estrogen, GPER1, proliferation, and adipogenic differentiation in goat adipose-derived stem cells (gADSCs) is still unclear. Herein, we demonstrated that 17ß-estradiol enhances the proliferative ability of gADSCs, indicated by the increased cell number and cell viability, accompanied by up-regulated expressions of cyclin D1 and PCNA. Meanwhile, the adipogenic differentiation is promoted by 17ß-estradiol, supported by higher ccumulation of intracellular lipids and increased expressions of PPARγ, ACC, and FABP4. Notably, these activities are all obviously reduced by administration with GPER1 antagonist G15, but GPER1 agonist G1 enhances cell proliferation and adipogenic differentiation. Moreover, GPER1 silencing diminishes cell proliferation and adipogenic differentiation. In parallel, 17ß-estradiol elevates the protein level of nuclear p-p65. Furthermore, the phosphorylation of p65 is enhanced by G1 but inhibited by G15 and GPER1 silencing. In addition, the phosphorylation of p65 is mediated by ERK1/2, suggesting that estrogen targeting GPER1 regulates cell proliferation and adipogenic differentiation of gADSCs through the ERK1/2-NF-κB signaling pathway. This study may provide a strong theoretical basis for improving meat quality, flavor, and cold resistance of livestock.

20.
J Clin Invest ; 2022 May 24.
Artigo em Inglês | MEDLINE | ID: mdl-35608905

RESUMO

DNA methyltransferase 3a (DNMT3a) is an important part of the epigenetic machinery that stabilizes patterns of activated T-cell responses. We hypothesized that donor T-cell DNMT3a regulates alloreactivity after allogeneic blood and marrow transplantation (allo-BMT). T-cell conditional Dnmt3a knock-out (KO) animals were used as donors in murine allo-BMT models. Mice receiving allo-BMT from KO donors developed severe acute graft-versus-host disease (aGVHD), with increases in inflammatory cytokine levels and organ histopathology. KO T-cells migrated and proliferated in secondary lymphoid organs earlier and demonstrated a trafficking advantage to the small intestine. Donor T-cell subsets were purified post-BMT for whole genome bisulfite sequencing (WGBS) and RNA sequencing. KO T-cells had similar global methylation to wild-type (WT), with distinct, localized areas of hypomethylation. Using a highly sensitive computational method, we produced a comprehensive profile of the altered epigenome landscape. Hypomethylation corresponded with changes in gene expression in several pathways of T-cell signaling and differentiation. Additionally, Dnmt3a KO T-cells conveyed superior graft-versus-tumor activity. Our findings demonstrate a critical role for DNMT3a in regulating T-cell alloreactivity and illuminate pathways that control T-cell tolerance. These results also provide a platform to decipher clinical data that associate donor DNMT3a mutations with increased GVHD, decreased relapse, and improved survival.

SELEÇÃO DE REFERÊNCIAS
DETALHE DA PESQUISA
...