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1.
Pediatr Rheumatol Online J ; 20(1): 77, 2022 Sep 05.
Artigo em Inglês | MEDLINE | ID: mdl-36064564

RESUMO

BACKGROUND: Peripheral gangrene is rarely documented as a possible complication of Kawasaki disease (KD). There are many causes of peripheral gangrene, and the common cause is in situ thrombosis or embolism. Most cases are reported to have regrettable outcomes (amputation or necrotic shedding). Herein, we report the successful management of KD complicated by peripheral artery thrombosis in an older Chinese boy, and a review of all cases of peripheral gangrene in KD in the literature. CASE PRESENTATION: We found that most of the children with this complication were under 1 year old, had a heavy inflammatory response combined with the use of cortisol and immunoglobulin, and most children had coronary artery lesions. In addition, Peripheral gangrene mainly occurred in the subacute or chronic stage, and the prognosis is poor. CONCLUSIONS: In the presence of high risk factors, we consider it is necessary to monitor coagulation function and administer prophylactic anticoagulation therapy. When peripheral artery thrombosis or embolism occur, heparin and prostaglandins can be used for treatment.


Assuntos
Embolia , Síndrome de Linfonodos Mucocutâneos , Trombose , Criança , Vasos Coronários , Embolia/complicações , Gangrena/complicações , Humanos , Lactente , Masculino , Síndrome de Linfonodos Mucocutâneos/complicações , Síndrome de Linfonodos Mucocutâneos/terapia , Trombose/etiologia
2.
Sci Rep ; 12(1): 14973, 2022 Sep 02.
Artigo em Inglês | MEDLINE | ID: mdl-36056058

RESUMO

There is a gap in knowledge how maternal exposure to environmental tobacco smoke (ETS) is associated with offspring congenital heart defects (CHDs). In this case-control study, we collected data on 749 fetuses with CHDs and 880 fetuses without any congenital anomalies to examine the association of maternal ETS with fetal CHDs and the potentially moderating effect by maternal hazardous and noxious substances (HNS), periconceptional folate intake and paternal smoking. Maternal exposure to ETS in first trimester was associated with increased risk of CHDs in a dose-response gradient, with the AORs (95% CI) were1.38 (1.00-1.92), 1.60 (1.07-2.41), and 4.94 (2.43-10.05) for ETS < 1 h/day, 1-2 h/day, and ≥ 2 h/day, respectively. With the doubly unexposed group as reference categories, AORs for maternal ETS exposure ≥ 2 h/day in the absence of folate intake, in the presence of HNS exposure or paternal smoking, were 7.21, 11.43, and 8.83, respectively. Significant additive interaction between ETS exposure and maternal folate intake on CHDs was detected. Maternal ETS exposure during first trimester may increase the risk of offspring CHDs in a dose-response shape, and such effect may be modified by maternal folate intake or other potential factors.


Assuntos
Cardiopatias Congênitas , Poluição por Fumaça de Tabaco , Estudos de Casos e Controles , China/epidemiologia , Feminino , Ácido Fólico , Cardiopatias Congênitas/induzido quimicamente , Cardiopatias Congênitas/etiologia , Humanos , Masculino , Exposição Materna/efeitos adversos , Fatores de Risco , Fumaça , Tabaco , Poluição por Fumaça de Tabaco/efeitos adversos
3.
Front Oncol ; 12: 911906, 2022.
Artigo em Inglês | MEDLINE | ID: mdl-36052257

RESUMO

Immune checkpoint inhibitors (ICIs) have shown definite therapeutic effects in various types of cancers, especially non-small cell lung cancer (NSCLC). However, ICIs have unique side effects, called immune-related adverse events (irAEs), which can occur in various systems throughout the body. Among such irAEs, immune checkpoint inhibitor-related pneumonitis (ICI-P) is a fatal adverse reaction. In this review, we discussed the risk factors, pathogenesis, clinical characteristics, radiological manifestations, pathological features, diagnosis, grading, and management of ICI-P in NSCLC and the relationship between ICI-P and the efficacy of ICI therapy. In addition, we discussed the predictive factors for ICI-P. This review will play a crucial role in the prediction, evaluation, and management of ICI-P for widespread application of immunotherapy.

4.
Leuk Lymphoma ; : 1-10, 2022 Sep 07.
Artigo em Inglês | MEDLINE | ID: mdl-36074798

RESUMO

As a rare lymphoproliferative disorder, many patients with HHV-8/HIV-negative Castleman disease (CD) have hypoalbuminemia. However, data is limited on whether hypoalbuminemia is an independent predictor of CD. We retrospectively collected data from 230 patients diagnosed at 12 medical centers in China and the U.S. Different classifications included 147 patients with unicentric CD (UCD) and 83 with idiopathic multicentric CD (iMCD). Adjusted smooth curve fitting showed that the relationship between albumin and all-cause death of patients with CD and iMCD was linear. Cox proportional hazards regression modeling showed a negative association between the risk of death and albumin level (hazard ratio [HR]: 0.84; 95% CI, 0.76, 0.93). Using the Kaplan-Meier method, we determined that hypoproteinemia was a risk factor for poorer prognosis in patients with CD, UCD, and iMCD. Albumin was independently and negatively associated with the risk of death in CD patients, especially those with iMCD.

5.
HLA ; 2022 Sep 17.
Artigo em Inglês | MEDLINE | ID: mdl-36114742

RESUMO

One nucleotide replacement at nucleotide 397 of HLA-C*07:02:01:01 results in a new allele, HLA-C*07:1024. This article is protected by copyright. All rights reserved.

6.
Preprint em Inglês | medRxiv | ID: ppmedrxiv-22279589

RESUMO

BACKGROUNDThe rising breakthrough infections caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) variants, especially Omicron and its sub-lineages, have raised an urgent need to develop broad-spectrum vaccines against coronavirus disease 2019 (COVID-19). We have developed a mosaic-type recombinant vaccine candidate, named NVSI-06-09, having immune potentials against a broad range of SARS-CoV-2 variants. METHODSAn ongoing randomized, double-blind, controlled phase 2 trial was conducted to evaluate the safety and immunogenicity of NVSI-06-09 as a booster dose in subjects aged 18 years and older from the United Arab Emirates (UAE), who had completed two or three doses of BBIBP-CorV vaccinations at least 6 months prior to the enrollment. The participants were randomly assigned with 1:1 to receive a booster dose of NVSI-06-09 or BBIBP-CorV. The primary outcomes were immunogenicity and safety against SARS-CoV-2 Omicron variant, and the exploratory outcome was cross-immunogenicity against other circulating strains. RESULTSA total of 516 participants received booster vaccination. Interim results showed a similar safety profile between NVSI-06-09 and BBIBP-CorV booster groups, with low incidence of adverse reactions of grade 1 or 2. For immunogenicity, by day 14 after the booster vaccination, the fold rises in neutralizing antibody geometric mean titers (GMTs) from baseline level elicited by NVSI-06-09 were remarkably higher than those by BBIBP-CorV against the prototype strain (19.67 vs 4.47-fold), Omicron BA.1.1 (42.35 vs 3.78-fold), BA.2 (25.09 vs 2.91-fold), BA.4 (22.42 vs 2.69-fold), and BA.5 variants (27.06 vs 4.73-fold). Similarly, the neutralizing GMTs boosted by NVSI-06-09 against Beta and Delta variants were also 6.60-fold and 7.17-fold higher than those boosted by BBIBP-CorV. CONCLUSIONSA booster dose of NVSI-06-09 was well-tolerated and elicited broad-spectrum neutralizing responses against SARS-CoV-2 prototype strain and immune-evasive variants, including Omicron and its sub-lineages. The immunogenicity of NVSI-06-09 as a booster vaccine was superior to that of BBIBP-CorV. (Funded by LIBP and BIBP of Sinopharm; ClinicalTrials.gov number, NCT05293548).

7.
J Musculoskelet Neuronal Interact ; 22(3): 401-410, 2022 Sep 01.
Artigo em Inglês | MEDLINE | ID: mdl-36046997

RESUMO

OBJECTIVE: To explore the regulation of LncRNA TUG /miRNA-204/SIRT1 pathway on osteogenic differentiation of bone marrow mesenchymal stem cells (BMSCs), so as to provide a new theoretical basis for the clinical treatment of osteoporosis. METHODS: Detect changes of LncRNA and miRNA expression predicted in post-differentiation BMSCs with Western blot and qPCR tests. Verify the regulatory relationship between LncRNA and miRNA, miRNA and SIRT1 through the luciferase reporter assay. Transfect recombinant plasmids with LncRNA and their shRNA or transfected miRNA mimics and inhibitors. RESULTS: According to the bioinformatic prediction, LncRNA TUG/miR-204 affected the regulation of SIRT1 on osteogenic differentiation of BMSCs, which were consistent with the results of luciferase reporter assay, namely, there are direct regulation targets between LncRNA TUG and miR-204, miR-204 and SIRT1. Overexpression and knockdown experiments revealed that LncRNA TUG overexpression/knockdown down/up-regulated miR-204 expression, which otherwise increased/decreased SIRT1 levels, and was positively correlated with osteogenic differentiation of BMSCs. Conversely, miR-204 was negatively correlated with LncRNA TUG and SIRT1, and negatively regulated osteogenic differentiation. CONCLUSION: This study found the direct regulatory relationship of LncRNA TUG/miR-204/SIRT1 during the osteogenic differentiation of BMSCs, and revealed that SIRT1 positively regulates the osteogenic differentiation of BMSCs, which provides a theoretical basis and potential therapeutic targets for a series of osteogenic differentiation-related diseases including osteoporosis.


Assuntos
Células-Tronco Mesenquimais , MicroRNAs , Osteoporose , RNA Longo não Codificante , Diferenciação Celular/genética , Células Cultivadas , Humanos , Células-Tronco Mesenquimais/metabolismo , MicroRNAs/genética , MicroRNAs/metabolismo , Osteogênese/genética , Osteoporose/genética , Osteoporose/metabolismo , RNA Longo não Codificante/genética , RNA Longo não Codificante/metabolismo , Sirtuína 1/genética , Sirtuína 1/metabolismo
8.
J Med Syst ; 46(10): 67, 2022 Sep 13.
Artigo em Inglês | MEDLINE | ID: mdl-36097228

RESUMO

Resource coordination in surgical scheduling remains challenging in health care delivery systems. This is especially the case in highly-specialized settings such as coordinating Intraoperative Neurophysiologic Monitoring (IONM) resources. Inefficient coordination yields higher costs, limited access to care, and creates constraints to surgical quality and outcomes. To maximize utilization of IONM resources, optimization-based algorithms are proposed to effectively schedule IONM surgical cases and technologists and evaluate staffing needs. Data with 10 days of case volumes, their surgery durations, and technologist staffing was used to demonstrate method effectiveness. An iterative optimization-based model that determines both optimal surgery and technologist start time (operational scenario 4) was built in an Excel spreadsheet along with Excel's Solver settings. It was compared with current practice (operational scenario 1) and optimization solution on only surgery start time (operational scenario 2) or technologist start time (operational scenario 3). Comparisons are made with respect to technologist overtime and under-utilization time. The results conclude that scenario 4 significantly reduces overtime by 74% and under-utilization time by 86% as well as technologist needs by 10%. For practices that do not have flexibility to alter surgeon preference on surgery start time or IONM technologist staffing levels, both scenarios 2 and 3 also result in substantial reductions in technologist overtime and under-utilization. Moreover, IONM technologist staffing options are discussed to accommodate technologist preferences and set constraints for surgical case scheduling. All optimization-based approaches presented in this paper are able to improve utilization of IONM resources and ultimately improve the coordination and efficiency of highly-specialized resources.


Assuntos
Monitorização Neurofisiológica Intraoperatória , Cirurgiões , Custos e Análise de Custo , Humanos
9.
Oncogene ; 2022 Sep 12.
Artigo em Inglês | MEDLINE | ID: mdl-36097193

RESUMO

NY-ESO-1 is a well-known cancer-testis antigen (CTA) with re-expression in numerous cancer types, but its expression is suppressed in myeloid leukemia cells. Patients with acute myeloid leukemia (AML) receiving decitabine (DAC) exhibit induced expression of NY-ESO-1 in blasts; thus, we investigated the effects of NY-ESO-1-specific TCR-engineered T (TCR-T) cells combined with DAC against AML. NY-ESO-1-specific TCR-T cells could efficiently eliminate AML cell lines (including U937, HL60, and Kasumi-1cells) and primary AML blasts in vitro by targeting the DAC-induced NY-ESO-1 expression. Moreover, the incubation of T cells with DAC during TCR transduction (designated as dTCR-T cells) could further enhance the anti-leukemia efficacy of TCR-T cells and increase the generation of memory-like phenotype. The combination of DAC with NY-ESO-1-specific dTCR-T cells showed a superior anti-tumor efficacy in vivo and prolonged the survival of an AML xenograft mouse model, with three out of five mice showing complete elimination of AML cells over 90 days. This outcome was correlated with enhanced expressions of IFN-γ and TNF-α, and an increased proportion of central memory T cells (CD45RO+CD62L+ and CD45RO+CCR7+). Taken together, these data provide preclinical evidence for the combined use of DAC and NY-ESO-1-specific dTCR-T cells for the treatment of AML.

10.
Dev Psychopathol ; : 1-14, 2022 Sep 13.
Artigo em Inglês | MEDLINE | ID: mdl-36097811

RESUMO

The present study examined the intergenerational transmission of internalizing and externalizing symptom severity, which indexes comorbidity, and symptom directionality, which indicates differentiation toward externalizing versus internalizing problems. Data are from 854 male and female, same-sex adult twin pairs born between 1926 and 1971 (32-60 years old, M = 44.9 years, SD = 4.9 years) from the Twin and Offspring Study in Sweden and their adolescent offspring (11-22 years old, M = 15.7 years, SD = 2.4 years, 52% female). Children-of-twins models revealed additive (9%) and dominant (45%) genetic and nonshared environmental (47%) influences on twins' symptom severity, and additive genetic (39%) and nonshared environmental (61%) influences on twins' symptom directionality. Both comorbid problems and preponderance of symptoms of a particular - internalizing versus externalizing - spectrum were correlated across parent and child generations, although associations were modest especially for directionality (i.e., transmission of specific symptom type). By interpreting findings alongside a recent study of adolescent twins, we demonstrate that the intergenerational transmission of symptom severity and symptom directionality are both unlikely to be attributable to genetic transmission, are both likely to be influenced by direct phenotypic transmission and/or nonpassive rGE, and the intergenerational transmission of symptom severity is also likely to be influenced by passive rGE.

11.
Circ Res ; : 101161CIRCRESAHA122320916, 2022 Sep 13.
Artigo em Inglês | MEDLINE | ID: mdl-36098045

RESUMO

BACKGROUND: Chronic heart failure (CHF) is associated with redox imbalance. Downregulation of Nrf2 (nuclear factor [erythroid-derived 2]-like 2) plays important roles in disrupting myocardial redox hemostasis and mediating sympathetic nerve activity in the setting of CHF. However, it is unclear if circulating extracellular vesicles (EVs) elicit sympathetic excitation in CHF by disrupting central redox homeostasis. We tested the hypothesis that cardiac-derived EVs circulate to the presympathetic rostral ventrolateral medulla and contribute to oxidative stress and sympathetic excitation via EV-enriched microRNA-mediated Nrf2 downregulation. METHODS: Data were collected on rats with CHF post-myocardial infarction (MI) and on human subjects with ischemic CHF. EVs were isolated from tissue and plasma, and we determined the miRNAs cargo that related to targeting Nrf2 translation. We tracked the distribution of cardiac-derived EVs using in vitro labeled circulating EVs and cardiac-specific membrane GFP+ transgenic mice. Finally, we tested the impact of exogenously loading of antagomirs to specific Nrf2-related miRNAs on CHF-EV-induced pathophysiological phenotypes in normal rats (eg, sympathetic and cardiac function). RESULTS: Nrf2 downregulation in CHF rats was associated with an upregulation of Nrf2-targeting miRNAs, which were abundant in cardiac-derived and circulating EVs from rats and humans. EVs isolated from the brain of CHF rats were also enriched with Nrf2-targeting miRNAs and cardiac-specific miRNAs. Cardiac-derived EVs were taken up by neurons in the rostral ventrolateral medulla. The administration of cardiac-derived and circulating EVs from CHF rats into the rostral ventrolateral medulla of normal rats evoked an increase in renal sympathetic nerve activity and plasma norepinephrine compared with Sham-operated rats, which were attenuated by exogenously preloading CHF-EVs with antagomirs to Nrf2-targeting miRNAs. CONCLUSIONS: Cardiac microRNA-enriched EVs from animals with CHF can mediate crosstalk between the heart and the brain in the regulation of sympathetic outflow by targeting the Nrf2/antioxidant signaling pathway. This new endocrine signaling pathway regulating sympathetic outflow in CHF may be exploited for novel therapeutics.

12.
Neuroreport ; 33(15): 656-662, 2022 Oct 12.
Artigo em Inglês | MEDLINE | ID: mdl-36126263

RESUMO

OBJECTIVES: To determine the effects of astragaloside IV on cerebral ischemic-reperfusion injury in rats and to explore underlying mechanisms of brain protection. METHODS: Sixty Sprague-Dawley rats were randomized into four groups: Sham, cerebral ischemia-reperfusion (I/R group), I/R+astragaloside IV (I/R+AST-IV group) and I/R+astragaloside IV+PKA kinase inhibitor H-89 (I/R+AST-IV+H-89 group). All I/R rats were subjected to 2 h cerebral ischemia, followed by 24 h reperfusion and scored for neurobehavior. Cerebral infarct volume, pathomorphological changes and brain apoptosis, in addition to changes in expression of Cx36, PKA, Bax and Bcl-2 proteins, were assessed. RESULTS: Astragaloside IV treatment reduced neurobehavioral score and percentage volume of cerebral infarct, reducing pathomorphological injury and brain apoptosis. Expressions of Cx36 and PKA protein were increased and the Bax/Bcl-2 ratio decreased. All astragaloside IV effects were reversed by the PKA inhibitor and H-89. CONCLUSIONS: Astragaloside IV attenuated cerebral I/R injury in rats by increasing Cx36 and PKA protein expression and reducing the Bax/Bcl-2 ratio.

13.
J Immunother ; 2022 Sep 20.
Artigo em Inglês | MEDLINE | ID: mdl-36121316

RESUMO

Immune checkpoint inhibitors (ICIs) are widely used for first-line cisplatin-ineligible patients with metastatic urothelial carcinoma (mUC). However, whether to use ICIs as monotherapy or in combination with chemotherapy is still uncertain. We retrospectively analyzed cisplatin-ineligible patients with mUC who underwent first-line ICI monotherapy or ICI plus chemotherapy at 2 medical centers in Taiwan from 2016 to 2021. We calculated the objective response rate, progression-free survival, and overall survival (OS) using the Kaplan-Meier method and Cox regression model for multivariable analysis. In total, 130 patients were enrolled and categorized into 2 groups: an ICI monotherapy group [immunotherapy (IO), n=101] and an ICI plus noncisplatin chemotherapy group [immunotherapy and chemotherapy (IC), n=29]. The median OS of patients in the IO and IC groups was 19.5 and 9.7 months (P=0.33). Among patients with high programmed cell death ligand-1-expressing tumors, the median OS was significantly prolonged in the IO group compared with the IC group (not reached vs. 6.3 mo, P=0.02). First-line ICI monotherapy demonstrated robust antitumor activity in cisplatin-ineligible patients with mUC. Combining noncisplatin chemotherapy with ICI did not improve clinical outcomes.

14.
J Hazard Mater ; 441: 129853, 2022 Sep 01.
Artigo em Inglês | MEDLINE | ID: mdl-36084459

RESUMO

Sensitive, on-site and multiple detection of mycotoxins is a vital early-warning tool to minimize food losses and protect human health and the environment. Although paper-based lateral flow immunoassay (LFIA) has been extensively applied in mycotoxins monitoring, low-cost, portable, ultrasensitive and quantitative detection is still a formidable challenge. Herein, a series of Fe-N-C single-atom nanozymes (SAzymes) were synthesized and systematic characterized. The optimal Fe-N-C SAzyme with highly efficient catalytic performance was successfully used as both label and catalyst in lateral flow immunoassays for mycotoxin detection. By taking advantage of the catalytic amplified system, the qualitative and quantitative detection can be easily and flexibly done via observing the test lines by naked eyes or a smartphone, with the limit of detections (LODs) of 2.8 and 13.9 pg mL-1 for AFB1 and FB1, which were respectively over 700- and 71,000-fold lower than the maximum limit set by the European Union. Besides, underlying catalytic mechanisms and the active sites of the Fe-N-C SAzyme are also investigated by DFT simulation. This work not only provides a promising detection strategy for the application of advanced SAzymes but also offers experimental and theoretical guidelines to understand the active centers of Fe-N-C SAzymes and the catalytic process.

15.
Anal Chem ; 94(37): 12781-12787, 2022 Sep 20.
Artigo em Inglês | MEDLINE | ID: mdl-36054869

RESUMO

Liquid crystal (LC)-based sensors have been extensively applied in the detection of chemical and biological events. However, the calculation of the optical images of the LC-based sensors is usually time-consuming and also might bring some errors due to the use of different judgment criteria by different users. In the present study, an automated calculation method for LC sensing images based on deep learning is provided. A convolutional network is trained with the prepared LC sensing images and their corresponding segmentation annotations to predict the positive responses. The ratio is calculated from the area of positive response to the total area selected by our image processing method. The robustness of the proposed algorithm is validated on both the test set and the label-free Cd2+ detection. The results show that the method based on deep learning can detect the positive response area in real time and the speed is much faster than the manual processing method. In addition, deep learning method can be directly applied to other label-free molecular detection assays.

16.
Int J Mol Sci ; 23(17)2022 Sep 04.
Artigo em Inglês | MEDLINE | ID: mdl-36077537

RESUMO

Celery seed is known to be difficult to germinate due to its morphological dormancy. Light is the key signal to release morphological dormancy and promote seed germination. However, this mechanism has rarely been studied. We performed physiological, transcriptome analyses on celery seed exposed to light and dark to decipher the mechanism by which light promotes germination of celery seed. The results showed that light significantly enhanced the expression of gibberellin synthesis genes and abscisic acid degradation genes and inhibited the expression of abscisic acid synthesis genes and gibberellin degradation genes. Moreover, gibberellin synthesis inhibitor could completely inhibit the germination capacity of celery seed, indicating that gibberellin is indispensable in the process of celery seed germination. Compared with dark, light also increased the activity of α-amylase and ß-amylase and the expression of related coding genes and promoted the degradation of starch and the increase of soluble sugar content, suggesting that light enhanced the sugar metabolism of celery seed. In addition, transcriptome analysis revealed that many genes related to endosperm weakening (cell wall remodeling enzymes, extension proteins) were up-regulated under light. It was also found that light promoted the accumulation of hydrogen peroxide in the radicle, which promoted the endosperm weakening process of celery seed. Our results thus indicated that light signal may promote the release of morphological dormancy through the simultaneous action of multiple factors.


Assuntos
Apium , Reguladores de Crescimento de Plantas , Ácido Abscísico/metabolismo , Ácido Abscísico/farmacologia , Apium/genética , Apium/metabolismo , Endosperma/genética , Endosperma/metabolismo , Perfilação da Expressão Gênica , Regulação da Expressão Gênica de Plantas , Germinação , Giberelinas/metabolismo , Giberelinas/farmacologia , Dormência de Plantas/genética , Reguladores de Crescimento de Plantas/metabolismo , Sementes/metabolismo , Açúcares/metabolismo
17.
Acta Biomater ; 2022 Sep 14.
Artigo em Inglês | MEDLINE | ID: mdl-36115656

RESUMO

Prospective tumor pH-responsive and charge-convertible nanoparticles have been utilized to reduce side effects and improve the active tumor-targeting ability and nuclear/cytoplasmic localization of chemo- and gene therapeutics for the treatment of head and neck cancer (HNC). Oxaliplatin (Oxa) is a third-generation platinum compound that prevents DNA replication. miR-320 may regulate cancer cell apoptosis, resistance, and progression. Innovative nanoparticles incorporating miR-320 and Oxa were modified with a ligand, cell-penetrating peptide, and nucleus-targeted peptide. The nanoparticles were coated with a charge/size-tunable shield to prevent peptide degradation and decoated at acidic tumor sites to expose peptides for active targeting. Results indicated that the designed nanoparticles exhibited a uniform size and satisfactory drug encapsulation efficiency. The nanoparticles displayed the pH-responsive release and uptake of Oxa and miR-320 into human tongue squamous carcinoma SAS cells. The nanoparticles successfully delivered Oxa and miR-320 to the nucleus and cytoplasm, respectively. This work is the first to demonstrate the concurrent intracellular modulation of the NRP1/Rac1, PI3K/Akt/mTOR, GSK-3ß/FOXM1/ß-catenin, P-gp/MRPs,KRAS/Erk/Oct4/Yap1, and N-cadherin/Vimentin/Slug pathways to inhibit the growth, progression, and multidrug resistance of cancer cells. In SAS-bearing mice, co-treatment with Oxa- and miR-320-loaded nanoparticles exhibited superior antitumor efficacy and remarkably decreased Oxa-associated toxicities. The nucleus/cytoplasm-localized nanoparticles with a tumor pH-sensitive and size/charge-adjustable coating may be a useful combinatorial spatiotemporal nanoplatform for nucleic acids and chemotherapeutics to achieve maximum therapeutic safety and efficacy against HNC. STATEMENT OF SIGNIFICANCE: : Innovative nanoparticles incorporating miR-320 and oxaliplatin were modified with a ligand, cell-penetrating peptide, and nucleus-targeted peptide. The tumor pH-sensitive and charge/size-adjustable shield of polyglutamic acid-PEG protected against peptide degradation during systemic circulation. This work represents the first example of the concurrent intracellular modulation of the NRP1/Rac1, PI3K/Akt/mTOR,GSK-3ß/FOXM1/ß-catenin, P-gp/MRPs, KRAS/Erk/Oct4/Yap1, and N-cadherin/Vimentin/Slug pathways to inhibit cancer cell growth, cancer cell progression, and multidrug resistance simultaneously. The versatile nanoparticles with a tumor pH-functionalized coating could deliver chemotherapeutics and miRNA to the nucleus/cytoplasm. The nanoparticles successfully reduced chemotherapy-associated toxicities and maximized the antitumor efficacy of combinatorial therapy against head and neck cancer.

18.
Mol Biotechnol ; 2022 Sep 15.
Artigo em Inglês | MEDLINE | ID: mdl-36109428

RESUMO

Advanced proliferative diabetic retinopathy (PDR) characterized by aberrant retinal angiogenesis is a leading cause of retinal detachment and blindness. Krüppel-like factor 9 (KLF9), a member of the zinc-finger family of transcription factors, participates in the development of diabetic nephropathy and the promotion of angiogenesis of human umbilical vein endothelial cells. Therefore, we speculate that KLF9 may exert a crucial role in PDR. The current study revealed that KLF9 was highly expressed in the high glucose (HG)-treated human retinal microvascular endothelial cells (HRMECs) and the retinas of oxygen-induced retinopathy (OIR) rats. Knockdown of KLF9 inhibited the proliferation, migratory capability, invasiveness and tube formation of HG-treated HRMECs. Besides, knockdown of KLF9 decreased the expression of yes-associated protein 1 (YAP1) in HG-treated HRMECs. Dual-luciferase reporter assays confirmed that KLF9 transcriptionally upregulated YAP1 expression. Overexpression of YAP1 reversed the KLF9 silencing-induced repression of HRMEC proliferation and tube formation. Further in vivo evidence demonstrated that knockdown of KLF9 reduced the expression of Ki67, CD31 and vascular endothelial growth factor A (VEGFA) in the retinas of OIR rats. Collectively, KLF9 silencing might mitigate the progression of PDR by inhibiting angiogenesis via blocking YAP1 transcription.

19.
Medicina (Kaunas) ; 58(8)2022 Aug 19.
Artigo em Inglês | MEDLINE | ID: mdl-36013593

RESUMO

Background and Objectives: Supplementary motor area (SMA) syndrome is a common post-operation complication in intra-axial brain tumors, such as glioma. Direct damage to parenchyma or scarification of the major vessels during an operation are the main causes. However, it is rarely reported as a postoperative complication in extra-axial tumors. Materials and Methods: We reviewed 11 reported cases of supplementary motor area syndrome after removal of extra-axial meningiomas in the English literature from the PubMed database. We also added our case, which presented as an unusual huge meningioma, to analyze the clinical parameters and outcomes of these 12 reported cases. Results: Recovery time of supplementary motor area syndrome in extra-axial tumors could be within 1-7 weeks, shorter than intra-axial tumors (2-9 weeks). Epilepsy and progressive limb weakness are the most common presentations in 50% of cases. Different degrees of postoperative muscle power deterioration were noted in the first 48 h (from 0-4). Lower limbs (66.6%, 8/12) were slightly predominant compared to upper limbs (58.3%, 7/12). Mutism aphasia was also observed in 41.6% (5/12, including our case), and occurred in tumors which were involved in the dominant side; this recovered faster than limb weakness. Discussion and Conclusions: Our work indicated that SMA syndrome could occur in extra-axial brain tumors presenting as mutism aphasia and limb weakness without any direct brain parenchyma damage. In our analysis, we found that recovery time of postoperative motor function deficit could be within 1-7 weeks. Our study also provides a further insight of SMA syndrome in extra-axial brain tumors.


Assuntos
Neoplasias Encefálicas , Neoplasias Meníngeas , Meningioma , Córtex Motor , Mutismo , Neoplasias Encefálicas/cirurgia , Humanos , Neoplasias Meníngeas/complicações , Neoplasias Meníngeas/cirurgia , Meningioma/complicações , Meningioma/cirurgia , Córtex Motor/patologia , Córtex Motor/cirurgia , Mutismo/etiologia , Síndrome
20.
Metabolomics ; 18(9): 70, 2022 Aug 27.
Artigo em Inglês | MEDLINE | ID: mdl-36029375

RESUMO

BACKGROUND: Demonstrating that the data produced in metabolic phenotyping investigations (metabolomics/metabonomics) is of good quality is increasingly seen as a key factor in gaining acceptance for the results of such studies. The use of established quality control (QC) protocols, including appropriate QC samples, is an important and evolving aspect of this process. However, inadequate or incorrect reporting of the QA/QC procedures followed in the study may lead to misinterpretation or overemphasis of the findings and prevent future metanalysis of the body of work. OBJECTIVE: The aim of this guidance is to provide researchers with a framework that encourages them to describe quality assessment and quality control procedures and outcomes in mass spectrometry and nuclear magnetic resonance spectroscopy-based methods in untargeted metabolomics, with a focus on reporting on QC samples in sufficient detail for them to be understood, trusted and replicated. There is no intent to be proscriptive with regard to analytical best practices; rather, guidance for reporting QA/QC procedures is suggested. A template that can be completed as studies progress to ensure that relevant data is collected, and further documents, are provided as on-line resources. KEY REPORTING PRACTICES: Multiple topics should be considered when reporting QA/QC protocols and outcomes for metabolic phenotyping data. Coverage should include the role(s), sources, types, preparation and uses of the QC materials and samples generally employed in the generation of metabolomic data. Details such as sample matrices and sample preparation, the use of test mixtures and system suitability tests, blanks and technique-specific factors are considered and methods for reporting are discussed, including the importance of reporting the acceptance criteria for the QCs. To this end, the reporting of the QC samples and results are considered at two levels of detail: "minimal" and "best reporting practice" levels.


Assuntos
Metabolômica , Espectroscopia de Ressonância Magnética , Espectrometria de Massas , Controle de Qualidade
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