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1.
Blood Rev ; 65: 101170, 2024 May.
Artigo em Inglês | MEDLINE | ID: mdl-38290895

RESUMO

Hodgkin lymphoma is a rare, but highly curative form of cancer, primarily afflicting adolescents and young adults. Despite multiple seminal trials over the past twenty years, there is no single consensus-based treatment approach beyond use of multi-agency chemotherapy with curative intent. The use of radiation continues to be debated in early-stage disease, as part of combined modality treatment, as well as in salvage, as an important form of consolidation. While short-term disease outcomes have varied little across these different approaches across both early and advanced stage disease, the potential risk of severe, longer-term risk has varied considerably. Over the past decade novel therapeutics have been employed in the retrieval setting in preparation to and as consolidation after autologous stem cell transplant. More recently, these novel therapeutics have moved to the frontline setting, initially compared to standard-of-care treatment and later in a direct head-to-head comparison combined with multi-agent chemotherapy. In 2018, we established the HoLISTIC Consortium, bringing together disease and methods experts to develop clinical decision models based on individual patient data to guide providers, patients, and caregivers in decision-making. In this review, we detail the steps we followed to create the master database of individual patient data from patients treated over the past 20 years, using principles of data science. We then describe different methodological approaches we are taking to clinical decision making, beginning with clinical prediction tools at the time of diagnosis, to multi-state models, incorporating treatments and their response. Finally, we describe how simulation modeling can be used to estimate risks of late effects, based on cumulative exposure from frontline and salvage treatment. The resultant database and tools employed are dynamic with the expectation that they will be updated as better and more complete information becomes available.


Assuntos
Doença de Hodgkin , Adolescente , Adulto Jovem , Humanos , Doença de Hodgkin/diagnóstico , Doença de Hodgkin/terapia , Recidiva Local de Neoplasia/tratamento farmacológico , Terapia Combinada , Transplante de Células-Tronco/métodos , Progressão da Doença , Protocolos de Quimioterapia Combinada Antineoplásica/efeitos adversos
2.
Sci Rep ; 13(1): 19107, 2023 11 04.
Artigo em Inglês | MEDLINE | ID: mdl-37925591

RESUMO

TGFB1, which encodes TGF-ß1, a potent cytokine regulating varies cellular processes including immune responses. TGF-ß1 plays context-dependent roles in cancers and is increasingly recognized as a therapeutic target to enhance immunotherapy responses. We comprehensively evaluated expression of TGFB1 and its clinical and biological effects across hematological malignancies. TGFB1 expression was first explored using data from the GTEx, CCLE, and TCGA databases. The expression and clinical significances of TGFB1 in hematological malignancies were analyzed using Hemap and our In Silico curated datasets. We also analyzed the relationship between TGFB1 with immune scores and immune cell infiltrations in Hemap. We further assessed the value of TGFB1 in predicting immunotherapy response using TIDE and real-world immunotherapy datasets. TGFB1 showed a hematologic-tissue-specific expression pattern both across normal tissues and cancer types. TGFB1 expression were broadly dysregulated in blood cancers and generally associated with adverse prognosis. TGFB1 expression were associated with distinct TME properties among different blood cancer types. In addition, TGFB1 expression was found to be a useful marker in predicting immunotherapy responses. Our results suggest that TGFB1 is broadly dysregulated in hematological malignancies. TGFB1 might regulate the immune microenvironment in a cancer-type-specific manner, which could be applied in the development of new targeted drugs for immunotherapy.


Assuntos
Neoplasias Hematológicas , Fator de Crescimento Transformador beta1 , Humanos , Fator de Crescimento Transformador beta1/genética , Fator de Crescimento Transformador beta1/metabolismo , Citocinas , Prognóstico , Neoplasias Hematológicas/genética , Microambiente Tumoral/genética , Imunoterapia
3.
Materials (Basel) ; 16(14)2023 Jul 18.
Artigo em Inglês | MEDLINE | ID: mdl-37512338

RESUMO

Low-alkali borosilicate glass was used as the immobilization substrate, and Ce was used to replicate the trivalent and tetravalent actinides, in order to create simulated waste glass through melt heat treatment. The valence of Ce and solubility of CeO2 in waste glass were studied as well as its network structure and thermal and chemical stability. The solubility of Ce in waste glass was examined by XRD and SEM. The network structure was examined by Raman spectroscopy. The valence of Ce was determined by X-ray photoelectron spectroscopy. Thermal analysis and product consistency (PCT) were employed to determine the thermal and chemical stability of waste glasses. The results show that the solubility of cerium in low-alkali borosilicate glasses is at least 25.wt.% and precipitates a spherical CeO2 crystalline phase when it exceeds the solid solution limit; Ce is immobilized in the glass by entering the interstices of the glass network. Depolymerization and the transition from [BO3] to [BO4] occurs when CeO2 doping levels rise. About 60 percent of Ce4+ is converted to Ce3+, and the thermal stability of glass rises then falls with the increase of CeO2. All samples exhibit strong leaching resistance, with the average mass loss of Ce at 28 days being less than 10-4 gm-2d-1.

4.
J Clin Med ; 12(7)2023 Mar 30.
Artigo em Inglês | MEDLINE | ID: mdl-37048679

RESUMO

Patients with multiple myeloma (MM) are at a high risk for developing cardiovascular complications. Global longitudinal strain (GLS) can detect early functional impairment before structural abnormalities develop. It remains unknown if reduced GLS is associated with reduced survival in patients with MM. We conducted a retrospective cohort analysis of patients diagnosed with MM between 1 January 2000 and 31 December 2017 at our institution. Patients with a 2D transthoracic echocardiogram completed within 1 year of MM diagnosis, left ventricular ejection fraction (LVEF) greater than 40%, and no history of myocardial infarction prior to MM diagnosis were included. GLS was measured using an artificial-intelligence-powered software (EchoGo Core), with reduced GLS defined as an absolute value of <18%. The primary outcome of interest was overall survival since myeloma diagnosis. Our cohort included 242 patients with a median follow up of 4.28 years. Fifty-two (21.5%) patients had reduced average GLS. Patients with reduced GLS were more likely to have an IVSd ≥ 1.2cm, E/E' > 9.6, LVEF/GLS > 4.1, higher LV mass index, and low-voltage ECG. A Total of 126 (52.1%) deaths occurred during follow-up. Overall survival was lower among patients with reduced GLS (adjusted HR: 1.81, CI: 1.07-3.05).

5.
Cell Death Discov ; 9(1): 15, 2023 Jan 21.
Artigo em Inglês | MEDLINE | ID: mdl-36681681

RESUMO

As a small molecule flavonoid, astragalin (AST) has anti-inflammatory, anti-cancer, and anti-oxidation effects. However, the impact and molecular mechanism of AST in Alzheimer's disease (AD) are still not clear. This study aims to investigate the neuroprotective effect and mechanism of AST on APP/PS1 mice and Aß25-35-injured HT22 cells. In this study, we found that AST ameliorated cognitive dysfunction, reduced hippocampal neuronal damage and loss, and Aß pathology in APP/PS1 mice. Subsequently, AST activated autophagy and up-regulated the levels of autophagic flux-related protein in APP/PS1 mice and Aß25-35-induced injury in HT22 cells. Interestingly, AST down-regulated the phosphorylation level of PI3K/Akt-mTOR pathway-related proteins, which was reversed by autophagy inhibitors 3-Methyladenine (3-MA) or Bafilomycin A1 (Baf A1). At the same time, consistent with the impacts of Akt inhibitor MK2206 and mTOR inhibitor rapamycin, inhibited levels of autophagy in Aß25-35-injured HT22 cells were activated by the administration of AST. Taken together, these results suggested that AST played key neuroprotective roles on AD via stimulating PI3K/Akt-mTOR pathway-mediated autophagy and autophagic flux. This study revealed a new mechanism of autophagy regulation behind the neuroprotection impact of AST for AD treatment.

6.
Acta Anatomica Sinica ; (6): 23-29, 2023.
Artigo em Chinês | WPRIM (Pacífico Ocidental) | ID: wpr-1015252

RESUMO

Objective To investigate the influence of volatile oil from Acori graminei Rhizoma (VOA) on expressions of glial fibrillary acidic protein (GFAP), c-Jun N-terminal protein kainse (JNK) and tumour necrosis factor-α (TNF-α) in the spinal cord dorsal horn of imflammatory pain rats. Methods Totally 36 male SD rats were randomly divided into control group (control), sham-operated group (sham), complete Freund' s adjuvant group (CFA), 5 g/(kg·d) low dose VOA+CFA group (VOA-L+CFA), 10 g/(kg·d) medium dose VOA + CFA group (VOA-M+CFA) and 20 g/(kg·d) high dose VOA + CFA group (VOA-H+CFA). All animals were sacrificed immediately after continuous gavage administration for 22 days. The expressions of GFAP, JNK and TNF-α in the spinal cord dorsal horn of rats in each group were detected by immunofluorescence and Western blotting methods. Results The present results showed that the positive expressions of GFAP, JNK and TNF-α in the spinal cord dorsal horn of rats increased significantly in the CFA group, when compared to the control and sham groups (P < 0. 01). The expressions of GFAP, JNK and TNF-α in the spinal cord dorsal horn of rats with VOA treatment reduced in the dose-dependent manner, when compared to the CFA group, the positive expressions of GFAP, JNK and TNF-α reduced significantly in the dorsal horn of the spinal cord of the VOA-H+CFA group (P<0. 05, P<0. 01). Conclusion VOA reduces the expressions of GFAP, JNK and TNF-α in the spinal cord dorsal horn of rats of CFA-induced inflammatory pain.

7.
Artigo em Chinês | WPRIM (Pacífico Ocidental) | ID: wpr-998990

RESUMO

ObjectiveTo investigate the effect of Astragalin (AST) on apoptosis of cerebral cortex neurons in APP/PS1 transgenic mice. MethodsEighteen six-month-old male APP/PS1 transgenic mice were randomly divided into APP/PS1 group, APP/PS1+ 40 mg/kg AST group and APP/PS1+ 20 mg/kg Donepezil (DNP) group, with six mice in each group. At the same time, six male C57BL/6 mice were selected as the normal control group. After intraperitoneal injection of AST once a day and continuous administration for one month, we used Tunel staining to detect the apoptosis of neurons in the cerebral cortex of APP/PS1 mice; immunofluorescent staining to examine the expression of apoptosis-related proteins Bax, Bcl-2, Caspase9 and Cleaved-Caspase3 in the cerebral cortex neurons of APP/PS1 mice; Western blot method to evaluate the changes of the expression of Bax, Bcl-2, Caspase9 and Caspase3. ResultsTunel staining showed that 40 mg/kg AST and 20 mg/kg DNP both reduced the apoptosis of neurons in the cerebral cortex of APP/PS1 mice, AST with more significant inhibition effect. Immunofluorescent staining revealed that 40 mg/kg AST and 20 mg/kg DNP both inhibited the expression of Bax, Caspase9, and Cleaved-Caspase3, and icreased the expression of Bcl-2 in the cerebral cortex neurons of APP/PS1 mice. Western blot results further confirmed that 40 mg/kg AST and 20 mg/kg DNP both down-regulated the expression of Bax (P < 0.05, P < 0.05), Caspase9 (P < 0.005, P < 0.05) and Caspase3 (P < 0.0001, P < 0.0001) , and up-regulated the expresstion of Bcl-2 (P < 0.05, P < 0.05) in the cerebral cortex neurons of APP/PS1 mice. ConclusionsAST can inhibit the apoptosis of cerebral cortex neurons in APP/PS1 mice.

8.
Materials (Basel) ; 15(15)2022 Aug 08.
Artigo em Inglês | MEDLINE | ID: mdl-35955394

RESUMO

In this paper, the effect of doping phosphorus in a borosilicate glass matrix to improve the solubility of Mo was investigated by X-ray diffraction (XRD), Raman, and solid-state nuclear magnetic resonance (NMR) spectroscopy, and the effectiveness of Na content on P species inhibiting the growth of the crystallization of Mo was assessed. The results indicate that phosphate-doped borosilicate glass can host 4 mol% of Mo, and that such a borosilicate glass matrix could only accommodate 1 mol% of Mo without phosphate doping. The effectiveness of phosphorus may be correlated with the Na content in borosilicate glass, and a high Na content borosilicate glass matrix requires more P doping to accommodate Mo. In addition, incorporating large amounts of P can compromise the aqueous durability of the glass matrix.

9.
Int J Mol Sci ; 23(16)2022 Aug 09.
Artigo em Inglês | MEDLINE | ID: mdl-36012100

RESUMO

RAV transcription factors (TFs) are unique to higher plants and contain both B3 and APETALA2 (AP2) DNA binding domains. Although sets of RAV genes have been identified from several species, little is known about this family in wheat. In this study, 26 RAV genes were identified in the wheat genome. These wheat RAV TFs were phylogenetically clustered into three classes based on their amino acid sequences. A TaRAV gene located on chromosome 1D was cloned and named TaRAV1. TaRAV1 was expressed in roots, stems, leaves, and inflorescences, and its expression was up-regulated by heat while down-regulated by salt, ABA, and GA. Subcellular localization analysis revealed that the TaRAV1 protein was localized in the nucleus. The TaRAV1 protein showed DNA binding activity in the EMSA assay and transcriptional activation activity in yeast cells. Overexpressing TaRAV1 enhanced the salt tolerance of Arabidopsis and upregulated the expression of SOS genes and other stress response genes. Collectively, our data suggest that TaRAV1 functions as a transcription factor and is involved in the salt stress response by regulating gene expression in the SOS pathway.


Assuntos
Arabidopsis , Triticum , Arabidopsis/metabolismo , DNA , Regulação da Expressão Gênica de Plantas , Filogenia , Proteínas de Plantas/genética , Proteínas de Plantas/metabolismo , Plantas Geneticamente Modificadas/genética , Tolerância ao Sal/genética , Estresse Fisiológico/genética , Fatores de Transcrição/genética , Fatores de Transcrição/metabolismo , Triticum/metabolismo
10.
J Glob Antimicrob Resist ; 30: 1-9, 2022 09.
Artigo em Inglês | MEDLINE | ID: mdl-35643393

RESUMO

OBJECTIVES: This network meta-analysis aimed to compare the efficacy and safety of fluoroquinolone (FQ) monotherapy, ß-lactam (BL) monotherapy and ß-lactam/macrolide (BL-M) combination therapy in hospitalized patients with community-acquired pneumonia (CAP). METHODS: Pubmed, Embase and the Cochrane Library were searched for randomized controlled trials (RCTs) comparing FQ monotherapy, BL monotherapy and BL-M combination therapy up to July 2021. The outcomes of interest included all-cause mortality, clinical success, microbiological success and drug-related adverse events. The summary relative risks (RRs) were estimated using pairwise and Bayesian network meta-analysis. RESULTS: A total of 12 RCTs involving 5009 patients were included. In pairwise meta-analysis, no significant differences were found among FQ monotherapy, BL monotherapy and BL-M dual therapy for all-cause mortality, clinical success or microbiological success. FQ monotherapy was associated with fewer adverse events compared with BL-M therapy (RR 0.80, 95% confidence interval [CI] 0.66-0.98). The network meta-analysis showed that there was no significant difference observed among FQ monotherapy, BL monotherapy and BL-M dual therapy regarding all the outcomes. CONCLUSION: FQ monotherapy, BL monotherapy and BL-M combination therapy demonstrated similar efficacy and safety for hospitalized patients with CAP in this network meta-analysis. Due to the limitations of quality and quantity of the included studies, it is difficult to make a definitive recommendation before more large-scale and high-quality RCTs are conducted.


Assuntos
Infecções Comunitárias Adquiridas , Pneumonia , Antibacterianos/efeitos adversos , Infecções Comunitárias Adquiridas/microbiologia , Quimioterapia Combinada , Fluoroquinolonas/efeitos adversos , Humanos , Metanálise em Rede , Pneumonia/tratamento farmacológico , Pneumonia/microbiologia , beta-Lactamas/efeitos adversos
11.
Biosci Rep ; 42(5)2022 05 27.
Artigo em Inglês | MEDLINE | ID: mdl-35506368

RESUMO

The objective of our study was to measure DLEU7-AS1 expression in de novo acute myeloid leukemia (AML) whilst also analyzing its clinical relevance. We used gene expression data from The Cancer Genome Atlas (TCGA), Gene Expression Omnibus (GEO), Cancer Cell Line Encyclopedia (CCLE) and Genotype-Tissue Expression project (GTEx) to assess the expression profile of DLEU7-AS1 in pan-cancers, cancer cell lines and normal tissues. Reverse transcription-quantitative PCR was used to measure DLEU7-AS1 expression in bone marrow from 30 normal individuals and 110 patients with de novo AML. DLEU7-AS1 expression was found to be markedly reduced in the AML samples of the TCGA pan-cancer datasets. In our PCR validation, DLEU7-AS1 expression was significantly decreased in the AML samples compared with that in controls (P<0.001). Low DLEU7-AS1 expression (DLEU7-AS1low) correlated positively with lower blood platelet counts (P=0.029). In addition, low DLEU7-AS1 expression was more frequently observed in the intermediate (58%; 44/76) and favorable karyotypes (65%; 15/23) compared with that in the poor karyotype (10%; 1/10; P=0.005). In particular, patients with high expression levels of DLEU7-AS1 (DLEU7-AS1high) showed lower complete remission rates (P=0.002) than patients with DLEU7-AS1low. Survival analysis revealed that patients with DLEU7-AS1low had longer overall survival (OS) than patients with DLEU7-AS1high (P<0.05). Multivariate Cox analysis demonstrated that in patients with non-acute promyelocytic leukemia (non-M3) who were ≤60 years old, DLEU7-AS1 expression was an independent prognostic factor for OS. Furthermore, we found distinct correlations among the expression of DLEU7-AS1, infiltration by immune cells and immune checkpoint genes in AML.


Assuntos
Leucemia Mieloide Aguda , RNA Longo não Codificante , Humanos , Cariótipo , Pessoa de Meia-Idade , Prognóstico , RNA Longo não Codificante/genética , RNA Longo não Codificante/metabolismo , Indução de Remissão
12.
Z Naturforsch C J Biosci ; 77(5-6): 197-206, 2022 May 25.
Artigo em Inglês | MEDLINE | ID: mdl-35286786

RESUMO

The aim is to establish a model of nonalcoholic fatty liver disease (NAFLD) caused by feeding with high-fat, high-fructose, and high-cholesterol diet (HFFCD) in golden hamsters, and to investigate the characteristics of the NAFLD model and metabolite changes of liver tissue. Golden hamsters were fed HFFCD or control diets for six weeks. Body weight, abdominal fat index, and liver index was assessed, serum parameters, hepatic histology, and liver metabolites were examined. The results showed that body weight, abdominal fat, and liver index of hamsters were significantly increased in the model group, the level of serum total cholesterol (TC), triglyceride (TG), and low density lipoprotein-cholesterol (LDL-C) were significantly increased in model group as well, and high density lipoprotein-cholesterol (HDL-C) was significantly decreased. In addition, lipid deposition in liver tissue formed fat vacuoles of different sizes. Metabonomics analysis of the liver showed that the metabolic pathways of sphingolipid, glycerophospholipids, and arginine biosynthesis were disordered in the NAFLD model. The modeling method is simple, short time, and uniform. It can simulate the early fatty liver caused by common dietary factors, and provides an ideal model for the study of the initial pathogenesis and therapeutic drugs for NAFLD.


Assuntos
Hepatopatia Gordurosa não Alcoólica , Animais , Peso Corporal , Colesterol , Cricetinae , Dieta Hiperlipídica , Fígado/metabolismo , Mesocricetus , Metabolômica , Hepatopatia Gordurosa não Alcoólica/metabolismo
13.
Data Brief ; 40: 107773, 2022 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-35028346

RESUMO

Nonalcoholic Fatty Liver Disease (NAFLD) is a serious problem endangering human health in the world. The pathogenesis of this disease is often accompanied by lipid metabolism disorder and can cause liver lipid accumulation. Highland barley Monascus purpureus Went extract (HBMPWE) can inhibit the liver lipid accumulation caused by a high-fat, high-fructose, high-cholesterol diet. However, it is not clear what changes have taken place in the process of liver lipid metabolism after HBMPWE administration. To fill this knowledge gap and to support the findings published in the companion research article entitled "Highland Barley Monascus purpureus Went Extract Ameliorates High-Fat, High-Fructose, High-Cholesterol Diet Induced Nonalcoholic Fatty Liver Disease by Regulating Lipid Metabolism in Golden Hamsters" [1], we provided important information related to the liver differential metabolites and identified twenty-one differential metabolites of liver metabolism. In the model group, the levels of lactate, linoleic acid, and malic acid increased significantly. After HBMPWE treatment, the expressions of these metabolites reduced significantly. Therefore, these liver differential metabolites could be used as biological signatures reflecting the severity of NAFLD and HBMPWE treatment outcomes.

14.
J Ethnopharmacol ; 286: 114922, 2022 Mar 25.
Artigo em Inglês | MEDLINE | ID: mdl-34923087

RESUMO

ETHNOPHARMACOLOGICAL RELEVANCE: Hepatocyte lipid accumulation is the main feature in the early stage of nonalcoholic fatty liver disease (NAFLD). Highland barley Monascus purpureus Went (HBMPW), a fermentation product of Hordeum vulgare Linn. var. nudum Hook. f. has traditionally been used as fermented foods in Tibet with the effect of reducing blood lipid in folk medicine. AIM OF THE STUDY: This study investigated the protective effects and molecular mechanism of highland barley Monascus purpureus Went extract (HBMPWE) on NAFLD in syrian golden hamster fed with high-fat, high-fructose, high-cholesterol diet (HFFCD). MATERIALS AND METHODS: HFFCD-induced NAFLD golden hamster model was established and treated with HBMPWE. Liver index, biochemical index, and hematoxylin and eosin (HE) staining were observed. Liver metabolomics and western blot analysis were employed. RESULTS: Our study found that HBMPWE ameliorated HFFCD induced dyslipidemia, weight gain and elevated the liver index. In addition, HBMPWE treatment significantly attenuated lipid accumulation in the liver and modulated lipid metabolism (sphingolipid, glycerophospholipid). Our data demonstrated that HBMPWE not only regulated the expression of proteins related to fatty acid synthesis and decomposition (SREBP-1/ACC/FAS/AceS1, PPARα/ACSL/CPT1/ACOX1), but also regulated the expression of proteins related to cholesterol synthesis and clearance (HMGCR, LDLR, CYP7A1). CONCLUSIONS: HBMPWE improved NAFLD through multiple pathways and multiple targets in body metabolism and could be used as a functional food to treat NAFLD and other lipid metabolic disorders.


Assuntos
Alimentos Fermentados , Metabolismo dos Lipídeos/efeitos dos fármacos , Monascus/metabolismo , Hepatopatia Gordurosa não Alcoólica/prevenção & controle , Animais , Dieta Hiperlipídica , Modelos Animais de Doenças , Ácidos Graxos/biossíntese , Frutose , Hordeum/metabolismo , Masculino , Medicina Tradicional Tibetana , Mesocricetus , Tibet
15.
Chinese Journal of Neurology ; (12): 1442-1446, 2022.
Artigo em Chinês | WPRIM (Pacífico Ocidental) | ID: wpr-958051

RESUMO

Epilepsy is one of the most common and disabling chronic neurological diseases. About 70% of patients with epilepsy can be fully controlled by available anti-seizure medications, while the remaining 20%-30% are drug-resistant. Drug-resistant epilepsy is also known as refractory epilepsy, and refractory epilepsy usually requires a combination of anti-seizure medications. A reasonable combination of anti-seizure medications can reduce the frequency or even the freedom of seizures. To this end, this article summarized the general principles of anti-seizure medications combination therapy, tolerance and drug interaction, combination and synergism in human studies, and the application of non-ionic anti-seizure medications in combination therapy of refractory epilepsy by reviewing the literature, to improve clinicians′ understanding of combination therapy with anti-seizure medications for refractory epilepsy.

16.
Stem Cell Investig ; 8: 18, 2021.
Artigo em Inglês | MEDLINE | ID: mdl-34631871

RESUMO

BACKGROUND: Adoptive immunotherapy using CD19-targeted Chimeric antigen receptor T cells (CAR-T) has revolutionized the treatment of relapsed/refractory diffuse large B-cell lymphoma (DLBCL). Data is limited on the propensity of infections and lymphohematopoietic reconstitution after Day 30 (D30) following CAR-T cell therapy. In this study, we evaluated the prevalence and nature of infectious complications in an expanded cohort of DLBCL patients treated with CD19 CAR-T therapy and its association with the dynamics of leukocyte subpopulation reconstitution post-CAR-T cell therapy. METHODS: We conducted a retrospective study including 19 patients who received axicabtagene ciloleucel and investigated associations between cytopenia and infectious complications after D30. RESULTS: Nineteen patients were included, consisting of 42% Hispanic, 32% Caucasian, 21% African-American, and 5% Asian subjects. Post-D30 of CAR-T infusion, 47% patients (n=9) developed an infection and 53% (n=10) remained infection-free. The most common infection type observed was viral (7 patients) followed by bacterial (5 patients) and fungal (3 patients). Of 25 total infectious events, 56% were grade 1 or 2 and 44% were grade 3 with 10 being viral in etiology. To determine the kinetics of lymphohematopoietic reconstitution and its association with infection risk, we evaluated the relationship between cytopenias and rates of infection after D30. Notably, compared to non-infection group, infection group had a higher median absolute lymphocyte count (ALC) (1,000/µL vs. 600/µL, P<0.05), a lower median absolute neutrophil count (ANC)/ALC ratio (1.6 vs. 3.1, P<0.05) and a lower median AMC/ALC at D30 (0.37 vs. 1.67, P<0.05). In addition, we observed that only 22% of patients had recovered ANC >1,500/µL in the infection group as opposed to 70% in the non-infection group at D90 (P<0.05). Fifty-eight percent of the patients (11/19) with relapsed refractory DLBCL achieved a complete response with a median follow-up of 233 days (7.7 months). CONCLUSIONS: Although CAR-T cell therapy is highly effective, infectious complications remain an important cause of morbidity and mortality. Low ANC/ALC and AMC/ALC ratios at D30 are potential novel predictors of infection and can be considered in future prophylactic strategies.

17.
Brain Res ; 1773: 147672, 2021 12 15.
Artigo em Inglês | MEDLINE | ID: mdl-34606748

RESUMO

Wheat embryo globulin nutrient (WEGN), with wheat embryo globulin (WEG) as the main functional component, is a nutritional combination that specifically targets memory impairment. In this study, we explored the protective role of WEGN on Alzheimer's disease (AD)-triggered cognitive impairment, neuronal injury, oxidative stress, and acetylcholine system disorder. Specifically, we established an AD model via administration of d-galactose (d-gal) and Aluminum chloride (AlCl3) for 70 days, then on the 36th day, administered animals in the donepezil and WEGN (300, 600, and 900 mg/kg) groups with drugs by gavage for 35 days. Learning and memory ability of the treated rats was tested using the Morris water maze (MWM) and novel object recognition (NOR) test, while pathological changes and neuronal death in their hippocampus CA1 were detected via HE staining and Nissl staining. Moreover, we determined antioxidant enzymes by measuring levels of superoxide dismutase (SOD), malondialdehyde (MDA), and glutathione peroxidase (GSH-Px) in serum, cortex, and hippocampus, whereas changes in the acetylcholine system were determined by evaluating choline acetyltransferase (ChAT), and acetylcholinesterase (AChE) activities, as well as choline acetylcholine (Ach) content. Results revealed that rats in the WEGN group exhibited significantly lower escape latency, as well as a significantly higher number of targeted crossings and longer residence times in the target quadrant, relative to those in the model group. Notably, rats in the WEGN group spent more time exploring new objects and exhibited lower damage to their hippocampus neuron, had improved learning and memory activity, as well as reversed histological alterations, relative to those in the model group. Meanwhile, biochemical examinations revealed that rats in the WEGN group had significantly lower MDA levels and AChE activities, but significantly higher GSH, SOD, and ChAT activities, as well as Ach content, relative to those in the model group. Overall, these findings indicate that WEGN exerts protective effects on cognitive impairment, neuronal damage, oxidative stress, and choline function in AD rats treated by d-gal/AlCl3.


Assuntos
Disfunção Cognitiva/tratamento farmacológico , Hipocampo/efeitos dos fármacos , Aprendizagem em Labirinto/efeitos dos fármacos , Extratos Vegetais/uso terapêutico , Triticum , Cloreto de Alumínio , Animais , Disfunção Cognitiva/induzido quimicamente , Disfunção Cognitiva/metabolismo , Modelos Animais de Doenças , Donepezila/farmacologia , Donepezila/uso terapêutico , Galactose , Glutationa Peroxidase/metabolismo , Hipocampo/metabolismo , Masculino , Malondialdeído/metabolismo , Neurônios/efeitos dos fármacos , Neurônios/metabolismo , Estresse Oxidativo/efeitos dos fármacos , Extratos Vegetais/farmacologia , Ratos , Ratos Sprague-Dawley , Superóxido Dismutase/metabolismo
18.
Nat Cancer ; 2(4): 392-399, 2021 04.
Artigo em Inglês | MEDLINE | ID: mdl-34661163

RESUMO

Patients with cancer have been identified in several studies to be at high risk of developing severe COVID-19; however, rates of SARS-CoV-2 IgG seroconversion and its association with cancer types and anti-cancer therapy remain obscure. We conducted a retrospective cohort study in patients with cancer that underwent SARS-CoV-2 IgG testing. Two hundred and sixty-one patients with a cancer diagnosis underwent SARS-CoV-2 IgG testing and demonstrated a high rate of seroconversion (92%). However, significantly lower seroconversion was observed in patients with hematologic malignancies (82%), patients that received anti-CD-20 antibody therapy (59%) and stem cell transplant (60%). Interestingly, all 17 patients that received immunotherapy, including 16 that received anti-PD-1/PD-L1 monoclonal antibodies, developed SARS-Cov-2 IgG antibodies (100% seroconversion). These data show differential rates of seroconversion in specific patient groups and bear importance for clinical monitoring and vaccination strategies that are being developed to mitigate the COVID-19 pandemic.


Assuntos
Anticorpos Antivirais/sangue , Imunoglobulina G/sangue , Neoplasias/imunologia , SARS-CoV-2/imunologia , Soroconversão , Adulto , Idoso , Idoso de 80 Anos ou mais , Teste de Ácido Nucleico para COVID-19 , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Neoplasias/tratamento farmacológico , Estudos Retrospectivos , Adulto Jovem
19.
Phys Rev Lett ; 127(9): 092001, 2021 Aug 27.
Artigo em Inglês | MEDLINE | ID: mdl-34506174

RESUMO

We present a novel method for extracting the proton radius from elastic electron-proton (ep) scattering data. The approach is based on interpolation via continued fractions augmented by statistical sampling and avoids any assumptions on the form of function used for the representation of data and subsequent extrapolation onto Q^{2}≃0. Applying the method to extant modern ep datasets, we find that all results are mutually consistent and, combining them, we arrive at r_{p}=0.847(8) fm. This result compares favorably with values obtained from contemporary measurements of the Lamb shift in muonic hydrogen, transitions in electronic hydrogen, and muonic deuterium spectroscopy.

20.
Materials (Basel) ; 14(16)2021 Aug 20.
Artigo em Inglês | MEDLINE | ID: mdl-34443229

RESUMO

The La2O3-doped basaltic glass simulated high-level waste form (HLW) was prepared by the solid-state melt method. The simulated waste La2O3 maximum loading and the doping effect on structure, thermal stability, leaching behavior, density, and hardness of basaltic glasses were studied. XRD and SEM results show that the simulated waste loading of La2O3 in basaltic glass can be up to ~46 wt.%, and apatite (CaLa4(SiO4)3O) precipitates when the content of La2O3 reaches 56 wt.%. Raman results indicate that the addition of La2O3 breaks the Si-O-Si bond of large-membered and four-membered, but the number of A13+ involved in the formation of the network increase. Low content of La2O3 can help to repair the glass network, but it destroys the network as above 26 wt.%. DSC results show the thermal stability of simulated waste forms first increases and then decreases with the increase of La2O3 content. With the increase of La2O3 content, the density of the simulated waste form increases, and the hardness decreases. The leaching chemical stability of samples was evaluated by the ASTM Product Consistency Test (PCT) Method, which show that all the samples have good chemical stability. The leaching rates of La and Fe are three orders of magnitude lower than those of the other elements. Among them, L36 has the best comprehensive leaching performance.

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