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1.
Leuk Lymphoma ; 65(5): 647-652, 2024 May.
Artigo em Inglês | MEDLINE | ID: mdl-38557285

RESUMO

Acalabrutinib studies have limited Asian participation. This phase 1/2 study (NCT03932331) assessed acalabrutinib in Chinese patients with relapsed/refractory (R/R) mantle cell lymphoma (MCL). Primary endpoint was blinded independent central review (BICR)-assessed overall response rate (ORR). Overall, 34 patients were enrolled. Most patients were men (88%); median age was 63 years and 59% had ≥3 prior treatments. Median treatment duration was 14 months (range, 1-24). Any-grade adverse events (AEs) and grade ≥3 AEs occurred in 85.3% and 44.1% of patients, respectively. AEs causing treatment discontinuation were aplastic anemia, thrombocytopenia, and gastrointestinal infection (n = 1 each). Fatal AEs occurred in 2 patients (aplastic anemia and multiple organ dysfunction syndrome [n = 1 each]). BICR-assessed ORR was 82.4% (95% confidence interval [CI]: 65.5, 93.2); 12 (35.3%) patients achieved complete response. Estimated 12-month OS was 84.5% (95% CI: 66.6, 93.3). Acalabrutinib yielded tolerable safety and high response rates in Chinese patients with R/R MCL.


Assuntos
Benzamidas , Linfoma de Célula do Manto , Pirazinas , Humanos , Masculino , Pessoa de Meia-Idade , Feminino , Pirazinas/efeitos adversos , Pirazinas/administração & dosagem , Pirazinas/uso terapêutico , Linfoma de Célula do Manto/tratamento farmacológico , Linfoma de Célula do Manto/mortalidade , Linfoma de Célula do Manto/patologia , Idoso , Benzamidas/efeitos adversos , Benzamidas/uso terapêutico , Benzamidas/administração & dosagem , Adulto , Resultado do Tratamento , Recidiva Local de Neoplasia/tratamento farmacológico , Recidiva Local de Neoplasia/patologia , Resistencia a Medicamentos Antineoplásicos , Idoso de 80 Anos ou mais , Antineoplásicos/uso terapêutico , Antineoplásicos/efeitos adversos , China/epidemiologia , População do Leste Asiático
2.
Cancer Lett ; 591: 216877, 2024 Apr 13.
Artigo em Inglês | MEDLINE | ID: mdl-38615930

RESUMO

Mantle cell lymphoma (MCL) is an incurable and aggressive subtype of non-Hodgkin B-cell lymphoma. Increased lipid uptake, storage, and lipogenesis occur in a variety of cancers and contribute to rapid tumor growth. However, no data has been explored for the roles of lipid metabolism reprogramming in MCL. Here, we identified aberrant lipid metabolism reprogramming and PRMT5 as a key regulator of cholesterol and fatty acid metabolism reprogramming in MCL patients. High PRMT5 expression predicts adverse outcome prognosis in 105 patients with MCL and GEO database (GSE93291). PRMT5 deficiency resulted in proliferation defects and cell death by CRISPR/Cas9 editing. Moreover, PRMT5 inhibitors including SH3765 and EPZ015666 worked through blocking SREBP1/2 and FASN expression in MCL. Furthermore, PRMT5 was significantly associated with MYC expression in 105 MCL samples and the GEO database (GSE93291). CRISPR MYC knockout indicated PRMT5 can promote MCL outgrowth by inducing SREBP1/2 and FASN expression through the MYC pathway.

3.
Zhonghua Yi Xue Yi Chuan Xue Za Zhi ; 41(4): 404-410, 2024 Apr 10.
Artigo em Chinês | MEDLINE | ID: mdl-38565504

RESUMO

OBJECTIVE: To explore the genetic background for a patient with refractory myelodysplastic/myeloproliferative neoplasm (MDS/MPN) with co-morbid neutrophilia patient. METHODS: A MDS/MPN patient who was admitted to the First Affiliated Hospital of Nanjing Medical University in May 2021 was selected as the study subject. RNA sequencing was carried out to identify fusion genes in his peripheral blood mononuclear cells. Fusion gene sequence was searched through transcriptome-wide analysis with a STAR-fusion procedure. The novel fusion genes were verified by quantitative real-time PCR and Sanger sequencing. RESULTS: The patient, a 67-year-old male, had progressive thrombocytopenia. Based on the morphological and molecular examinations, he was diagnosed as MDS/MPN with co-morbid neutropenia, and was treated with demethylating agents and Bcl-2 inhibitors. Seventeen months after the diagnosis, he had progressed to AML. A novel fusion gene NCOR1::GLYR1 was identified by RNA-sequencing in his peripheral blood sample, which was verified by quantitative real-time PCR and Sanger sequencing. The patient had attained morphological remission after a DCAG regimen (a combinatory chemotherapy of decitabine, cytarabine, aclarubicin and granulocyte colony-stimulating factors) plus Chidamide treatment. A significant decrease in the NCOR1::GLYR1 expression was revealed by quantitative real-time PCR at post-chemotherapy evaluation. CONCLUSION: NCOR1::GLYR1 gene is considered as the pathogenic factor for the MDS/MPN patient with neutropenia.


Assuntos
Leucemia Mieloide Aguda , Síndromes Mielodisplásicas , Neutropenia , Masculino , Humanos , Idoso , Síndromes Mielodisplásicas/genética , Leucócitos Mononucleares , Citarabina/uso terapêutico , Correpressor 1 de Receptor Nuclear
4.
Zhongguo Shi Yan Xue Ye Xue Za Zhi ; 32(2): 639-642, 2024 Apr.
Artigo em Chinês | MEDLINE | ID: mdl-38660879

RESUMO

Berberine, a traditional Chinese medicine, is an isoquinoline alkaloid extracted from the rhizome of Coptis chinensis. It has anti-inflammatory and antidiarrheal effects and is commonly used in the treatment of infections and gastrointestinal diseases. In recent years, studies have found that berberine can play a wide range of anti-cancer effects in the treatment of leukemia, lymphoma, multiple myeloma, etc. In hematologic malignancies, berberine can induce autophagy, promote apoptosis, regulate cell cycle, inhibit inflammatory response, cause oxidative damage to cancer cells and interact with miRNA to inhibit the proliferation, migration and colony formation of cancer cells. This paper will review the role and related mechanisms of berberine in hematological malignancies.


Assuntos
Apoptose , Berberina , Neoplasias Hematológicas , Berberina/farmacologia , Humanos , Neoplasias Hematológicas/tratamento farmacológico , Apoptose/efeitos dos fármacos , Autofagia/efeitos dos fármacos , Proliferação de Células/efeitos dos fármacos , Ciclo Celular/efeitos dos fármacos , MicroRNAs
5.
Ann Hematol ; 2024 Apr 22.
Artigo em Inglês | MEDLINE | ID: mdl-38649594

RESUMO

Elderly patients with lymphoproliferative diseases (LPD) are vulnerable to severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection. Here, we retrospectively described the clinical features and outcomes of the first time infection of Omicron SARS-CoV-2 in 364 elderly patients with lymphoma enrolled in Jiangsu Cooperative Lymphoma Group (JCLG) between November 2022 and April 2023 in China. Median age was 69 years (range 60-92). 54.4% (198/364) of patients were confirmed as severe and critical COVID-19 infection. In univariable analysis, Age > 70 years (OR 1.88, p = 0.003), with multiple comorbidities (OR 1.41, p = 0.005), aggressive lymphoma (OR 2.33, p < 0.001), active disease (progressive or relapsed/refractory, OR 2.02, p < 0.001), and active anti-lymphoma therapy (OR 1.90, p < 0.001) were associated with severe COVID-19. Multiple (three or more) lines of previous anti-lymphoma therapy (OR 3.84, p = 0.021) remained an adverse factor for severe COVID-19 in multivariable analysis. Moreover, CD20 antibody (Rituximab or Obinutuzumab)-based treatments within the last 6 months was associated with severe COVID-19 in the entire cohort (OR 3.42, p < 0.001). Continuous BTK inhibitors might be protective effect on the outcome of COVID-19 infection (OR 0.44, p = 0.043) in the indolent lymphoma cohort. Overall, 7.7% (28/364) of the patients ceased, multiple lines of previous anti-lymphoma therapy (OR 3.46, p = 0.016) remained an adverse factor for mortality.

6.
Int J Biol Macromol ; 267(Pt 2): 131563, 2024 Apr 16.
Artigo em Inglês | MEDLINE | ID: mdl-38626837

RESUMO

Excessive exudation from the wound site and the difficulty of determining the state of wound healing can make medical management more difficult and, in extreme cases, lead to wound deterioration. In this study, we fabricated a pH-sensitive colorimetric chronic wound dressing with self-pumping function using electrostatic spinning technology. It consisted of three layers: a polylactic acid-curcumin (PCPLLA) hydrophobic layer, a hydrolyzed polyacrylonitrile (HPAN) transfer layer, and a polyacrylonitrile-purple kale anthocyanin (PAN-PCA) hydrophilic layer. The results showed that the preparation of porous PLLA fiber membrane loaded with 0.2 % Cur was achieved by adjusting the spinning-related parameters, which could ensure that the composite dressing had sufficient anti-inflammatory, antibacterial and antioxidant properties. The HPAN membrane treated with alkali for 30 min had significantly enhanced liquid wetting ability, and the unidirectional transport of liquid could be achieved by simple combination with the 20 um PCPLLA fiber membrane. In addition, the 4 % loaded PCA showed more obvious color difference than the colorimetric membrane. In vivo and ex vivo experiments have demonstrated the potential of multifunctional dressings for the treatment of chronic wounds.

7.
Pest Manag Sci ; 2024 Apr 02.
Artigo em Inglês | MEDLINE | ID: mdl-38563512

RESUMO

BACKGROUND: The tomato leafminer, Phthorimaea absoluta (Meyrick) (Lepidoptera: Gelechiidae), is a destructive invasive pest that originated in South America and has spread within China since 2017. A rapid method for on-site identification of P. absoluta is urgently needed for interception of this pest across China. RESULTS: We developed a loop-mediated isothermal amplification (LAMP) technique to differentiate P. absoluta from Liriomyza sativae, Chromatomyia horticola, and Phthorimaea operculella using extracted genomic DNA, which was then refined to create an on-site LAMP diagnostic method that can be performed under field conditions without the need for laboratory equipment. CONCLUSION: In the present research, we developed an on-site diagnostic method for rapid differentiation of P. absoluta from other insects with similar morphology or damage characteristics in China. © 2024 Society of Chemical Industry.

8.
Sensors (Basel) ; 24(5)2024 Feb 26.
Artigo em Inglês | MEDLINE | ID: mdl-38475056

RESUMO

In this paper, an improved APF-GFARRT* (artificial potential field-guided fuzzy adaptive rapidly exploring random trees) algorithm based on APF (artificial potential field) guided sampling and fuzzy adaptive expansion is proposed to solve the problems of weak orientation and low search success rate when randomly expanding nodes using the RRT (rapidly exploring random trees) algorithm for disinfecting robots in the dense environment of disinfection operation. Considering the inherent randomness of tree growth in the RRT* algorithm, a combination of APF with RRT* is introduced to enhance the purposefulness of the sampling process. In addition, in the context of RRT* facing dense and restricted environments such as narrow passages, adaptive step-size adjustment is implemented using fuzzy control. It accelerates the algorithm's convergence and improves search efficiency in a specific area. The proposed algorithm is validated and analyzed in a specialized environment designed in MATLAB, and comparisons are made with existing path planning algorithms, including RRT, RRT*, and APF-RRT*. Experimental results show the excellent exploration speed of the improved algorithm, reducing the average initial path search time by about 46.52% compared to the other three algorithms. In addition, the improved algorithm exhibits faster convergence, significantly reducing the average iteration count and the average final path cost by about 10.01%. The algorithm's enhanced adaptability in unique environments is particularly noteworthy, increasing the chances of successfully finding paths and generating more rational and smoother paths than other algorithms. Experimental results validate the proposed algorithm as a practical and feasible solution for similar problems.

9.
ACS Appl Mater Interfaces ; 16(14): 17145-17162, 2024 Apr 10.
Artigo em Inglês | MEDLINE | ID: mdl-38534071

RESUMO

The fabrication of antifouling zwitterionic polymer brushes represents a leading approach to mitigate nonspecific adhesion on the surfaces of medical devices. This investigation seeks to elucidate the correlation between the material composition and structural attributes of these polymer brushes in preventing protein adhesion. To achieve this goal, we modeled three different zwitterionic brushes, namely, carboxybetaine methacrylate (CBMA), sulfobetaine methacrylate (SBMA), and (2-(methacryloyloxy)ethyl)-phosphorylcholine (MPC). The simulations revealed that elevating the grafting density enhances the structural stability, hydration strength, and resistance to protein adhesion exhibited by the polymer brushes. PCBMA manifests a more robust hydration layer, while PMPC demonstrates the slightest interaction with proteins. In a comprehensive evaluation, PSBMA polymer brushes emerged as the best choice with superior stability, enhanced protein repulsion, and minimally induced protein deformation, resulting in effective resistance to nonspecific adhesion. The high-density SBMA polymer brushes significantly reduce the level of protein adhesion in AFM testing. In addition, we have pioneered the quantitative characterization of hydration repulsion in polymer brushes by analyzing the hydration repulsion characteristics at different materials and graft densities. In summary, our study provides a nuanced understanding of the material and structural determinants influencing the capacity of zwitterionic polymer brushes to thwart protein adhesion. Additionally, it presents a quantitative elucidation of hydration repulsion, contributing to the advancement and application of antifouling polymer brushes.


Assuntos
Polímeros , Proteínas , Polímeros/química , Fenômenos Físicos , Adsorção , Metacrilatos/química
11.
Comput Biol Med ; 172: 108315, 2024 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-38503093

RESUMO

The incidence of blinding eye diseases is highly correlated with changes in retinal morphology, and is clinically detected by segmenting retinal structures in fundus images. However, some existing methods have limitations in accurately segmenting thin vessels. In recent years, deep learning has made a splash in the medical image segmentation, but the lack of edge information representation due to repetitive convolution and pooling, limits the final segmentation accuracy. To this end, this paper proposes a pixel-level retinal vessel segmentation network with multiple-dimension attention and adaptive feature fusion. Here, a multiple dimension attention enhancement (MDAE) block is proposed to acquire more local edge information. Meanwhile, a deep guidance fusion (DGF) block and a cross-pooling semantic enhancement (CPSE) block are proposed simultaneously to acquire more global contexts. Further, the predictions of different decoding stages are learned and aggregated by an adaptive weight learner (AWL) unit to obtain the best weights for effective feature fusion. The experimental results on three public fundus image datasets show that proposed network could effectively enhance the segmentation performance on retinal blood vessels. In particular, the proposed method achieves AUC of 98.30%, 98.75%, and 98.71% on the DRIVE, CHASE_DB1, and STARE datasets, respectively, while the F1 score on all three datasets exceeded 83%. The source code of the proposed model is available at https://github.com/gegao310/VesselSeg-Pytorch-master.


Assuntos
Algoritmos , Retina , Retina/diagnóstico por imagem , Vasos Retinianos/diagnóstico por imagem , Fundo de Olho , Software , Processamento de Imagem Assistida por Computador/métodos
12.
Biomed Pharmacother ; 173: 116400, 2024 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-38484560

RESUMO

Hyperlipidemia caused by abnormal lipid metabolism has reached epidemic proportions. This phenomenon is also common in companion animals. Previous studies showed that AEE significantly improves abnormal blood lipids in hyperlipidemia rats and mice, but its mechanism is still not clear enough. In this study, the mechanism and potential key pathways of AEE on improving hyperlipidemia in mice were investigated through the transcriptome and proteome study of ApoE-/- mice liver and the verification study on high-fat HepG2 cells. The results showed that AEE significantly decreased the serum TC and LDL-C levels of hyperlipidemia ApoE-/- mice, and significantly increased the enzyme activity of CYP7A1. After AEE intervention, the results of mice liver transcriptome and proteome showed that differential genes and proteins were enriched in lipid metabolism-related pathways. The results of RT-qPCR showed that AEE significantly regulated the expression of genes related to lipid metabolism in mice liver tissue. AEE significantly upregulated the protein expression of CYP7A1 in hyperlipidemia ApoE-/- mice liver tissue. The results in vitro showed that AEE significantly decreased the levels of TC and TG, and improved lipid deposition in high-fat HepG2 cells. AEE significantly increased the expression of CYP7A1 protein in high-fat HepG2 cells. AEE regulates the expression of genes related to lipid metabolism in high-fat HepG2 cells, mainly by FXR-SHP-CYP7A1 and FGF19-TFEB-CYP7A1 pathways. To sum up, AEE can significantly improve the hyperlipidemia status of ApoE-/- mice and the lipid deposition of high-fat HepG2 cells, and its main pathway is probably the bile acid metabolism-related pathway centered on CYP7A1.


Assuntos
Hiperlipidemias , Camundongos , Ratos , Animais , Hiperlipidemias/tratamento farmacológico , Hiperlipidemias/genética , Hiperlipidemias/metabolismo , Proteômica , Proteoma/metabolismo , Dieta Hiperlipídica/efeitos adversos , Lipídeos , Metabolismo dos Lipídeos/genética , Perfilação da Expressão Gênica , Apolipoproteínas E/genética , Apolipoproteínas E/metabolismo , Fígado/metabolismo
13.
Clin. transl. oncol. (Print) ; 26(3): 613-622, mar. 2024.
Artigo em Inglês | IBECS | ID: ibc-230791

RESUMO

Purpose The purpose of the study was to evaluate the prognostic value of low T3 syndrome in peripheral T-cell lymphomas (PTCLs). Methods One hundred and seventy-four patients of newly diagnosed PTCLs were enrolled in the study. We performed statistical analysis based on the clinical data collected. Results Thirty-Six (20.69%) patients had low T3 syndrome at first admission. Results suggested that the patients with higher score of ECOG PS, International Prognostic Index (IPI) and Prognostic Index for T-cell lymphoma (PIT), bone marrow involvement and lower level of albumin tended to develop low T3 syndrome. The median progression-free survival (PFS) and overall survival (OS) were 10 months and 36 months, respectively, for all patients. Pre-existing low T3 syndrome was in correlation with worse PFS and OS. Patients with low T3 syndrome showed worse PFS (4 months vs 13 months, P = 0.0001) and OS (7 months vs 83 months, P < 0.0001) than patients without low T3 syndrome. IPI and PIT, respectively, combined with low T3 syndrome improved the ability to predict OS and PFS of PTCLs. Conclusions The study indicated that low T3 syndrome may be a good candidate for predicting prognosis of peripheral T-cell lymphomas (AU)


Assuntos
Humanos , Linfoma de Células T Periférico/patologia , Síndromes do Eutireóideo Doente , Intervalo Livre de Progressão , Estudos Retrospectivos , Prognóstico
14.
Clin. transl. oncol. (Print) ; 26(3): 720-731, mar. 2024.
Artigo em Inglês | IBECS | ID: ibc-230801

RESUMO

Purpose The International Extranodal Lymphoma Study Group (IELSG) score is widely used in clinical practice to stratify the risk of primary central nervous system lymphoma (PCNSL) patients. Our study aims to confirm and improve the IELSG score in PCNSL patients based on Chinese populations. Materials and methods A total of 79 PCNSL patients were retrospectively analyzed. All patients treated with high-dose methotrexate (HD-MTX)-based therapy collected clinical data. The receiver-operating characteristic (ROC) curve was used to determine the optimal cut-off values for the factors in IELSG score. Progression of disease (POD) at the most landmark time point was determine by Epanechnikov kernel and the area under the ROC curve (AUROC). Kaplan–Meier and multivariable regression methods were used to analyze survival data. Nomogram was generated for calculating the weight of each selected factor. Results The traditional IELSG score had no significant difference on OS and PFS except ECOG ≥ 2 and could not stratify the risk groups in PCNSL. The improved IELSG scoring system was established, which incorporated age ≥ 54 years, ECOG ≥ 2, deep brain structure, elevated CSF protein, and LDH/ULN > 0.75. On the other hand, POD18 was identified as a new powerful prognostic factor for PCNSL. In multivariate analysis, POD18 and the improved IELSG scoring system were independent prognostic factors for OS. Nomogram including the two significant variables showed the best performance (C-index = 0.828). Conclusions In this study, the IELSG score was improved and a new prognostic indicator POD18 was incorporated to construct a nomogram prognostic model, thereby further improving the predictive ability of the model (AU)


Assuntos
Humanos , Pessoa de Meia-Idade , Linfoma Composto/tratamento farmacológico , Linfoma Composto/metabolismo , Metotrexato/uso terapêutico , Estudos Retrospectivos , Resultado do Tratamento , Encéfalo/metabolismo , Prognóstico
15.
Artigo em Inglês | MEDLINE | ID: mdl-38535092

RESUMO

BACKGROUND: Measurable residual disease (MRD) is an important prognostic indicator of chronic lymphocytic leukemia (CLL). Different flow cytometric panels have been developed for the MRD assessment of CLL in Western countries; however, the application of these panels in China remains largely unexplored. METHODS: Owing to the requirements for high accuracy, reproducibility, and comparability of MRD assessment in China, we investigated the performance of a flow cytometric approach (CD45-ROR1 panel) to assess MRD in patients with CLL. The European Research Initiative on CLL (ERIC) eight-color panel was used as the "gold standard." RESULTS: The sensitivity, specificity, and concordance rate of the CD45-ROR1 panel in the MRD assessment of CLL were 100% (87/87), 88.5% (23/26), and 97.3% (110/113), respectively. Two of the three inconsistent samples were further verified using next-generation sequencing. In addition, the MRD results obtained from the CD45-ROR1 panel were positively associated with the ERIC eight-color panel results for MRD assessment (R = 0.98, p < 0.0001). MRD detection at low levels (≤1.0%) demonstrated a smaller difference between the two methods (bias, -0.11; 95% CI, -0.90 to 0.68) than that at high levels (>1%). In the reproducibility assessment, the bias was smaller at three data points (within 24, 48, and 72 h) in the CD45-ROR1 panel than in the ERIC eight-color panel. Moreover, MRD levels detected using the CD45-ROR1 panel for the same samples from different laboratories showed a strong statistical correlation (R = 0.99, p < 0.0001) with trivial interlaboratory variation (bias, 0.135; 95% CI, -0.439 to 0.709). In addition, the positivity rate of MRD in the bone marrow samples was higher than that in the peripheral blood samples. CONCLUSIONS: Collectively, this study demonstrated that the CD45-ROR1 panel is a reliable method for MRD assessment of CLL with high sensitivity, reproducibility, and reliability.

16.
Acta Biomater ; 178: 111-123, 2024 Apr 01.
Artigo em Inglês | MEDLINE | ID: mdl-38423351

RESUMO

High-performance catheters are essential for interventional surgeries, requiring reliable anti-adhesive and lubricated surfaces. This article develops a strategy for constructing high-density sulfobetaine zwitterionic polymer brushes on the surface of catheters, utilizing dopamine and sodium alginate as the primary intermediate layers, where dopamine provides mussel-protein-like adhesion to anchor the polymer brushes to the catheter surface. Hydroxyl-rich sodium alginate increases the number of grafting sites and improves the grafting mass by more than 4 times. The developed high-density zwitterionic polymer brushes achieve long-lasting and effective lubricity (µ<0.0078) and are implanted in rabbits for four hours without bio-adhesion and thrombosis in the absence of anticoagulants such as heparin. Experiments and molecular dynamics simulations demonstrate that graft mass plays a decisive role in the lubricity and anti-adhesion of polymer brushes, and it is proposed to predict the anti-adhesion of polymer brushes by their lubricity to avoid costly and time-consuming bioassays during the development of amphoteric polymer brushes. A quantitative influence of hydration in the anti-adhesion properties of amphiphilic polymer brushes is also revealed. Thus, this study provides a new approach to safe, long-lasting lubrication and anticoagulant surface modification for medical devices in contact with blood. STATEMENT OF SIGNIFICANCE: High friction and bioadhesion on medical device surfaces can pose a significant risk to patients. In response, we have developed a safer, simpler, and more application-specific surface modification strategy that addresses both the lubrication and anti-bioadhesion needs of medical device surfaces. We used dopamine and sodium alginate as intermediate layers to drastically increase the grafting density of the zwitterionic brushes and enabled the modified surfaces to have an extremely low coefficient of friction (µ = 0.0078) and to remain non-bioadhesive for 4 hours in vivo. Furthermore, we used molecular dynamics simulations to gain insight into the mechanisms behind the superior anti-adhesion properties of the high-density polymer brushes. Our work contributes to the development and application of surface-modified coatings.


Assuntos
Fibrinolíticos , Polímeros , Animais , Humanos , Coelhos , Polímeros/farmacologia , Dopamina , Lubrificação , Propriedades de Superfície , Alginatos/farmacologia
17.
Int J Mol Sci ; 25(3)2024 Jan 23.
Artigo em Inglês | MEDLINE | ID: mdl-38338675

RESUMO

Klebsiella pneumoniae (K. pneumoniae) exhibits the ability to form biofilms as a means of adapting to its adverse surroundings. K. pneumoniae in this biofilm state demonstrates remarkable resistance, evades immune system attacks, and poses challenges for complete eradication, thereby complicating clinical anti-infection efforts. Moreover, the precise mechanisms governing biofilm formation and disruption remain elusive. Recent studies have discovered that fingolimod (FLD) exhibits biofilm properties against Gram-positive bacteria. Therefore, the antibiofilm properties of FLD were evaluated against multidrug-resistant (MDR) K. pneumoniae in this study. The antibiofilm activity of FLD against K. pneumoniae was assessed utilizing the Alamar Blue assay along with confocal laser scanning microscopy (CLSM), scanning electron microscopy (SEM), and crystal violet (CV) staining. The results showed that FLD effectively reduced biofilm formation, exopolysaccharide (EPS), motility, and bacterial abundance within K. pneumoniae biofilms without impeding its growth and metabolic activity. Furthermore, the inhibitory impact of FLD on the production of autoinducer-2 (AI-2) signaling molecules was identified, thereby demonstrating its notable anti-quorum sensing (QS) properties. The results of qRT-PCR analysis demonstrated that FLD significantly decreased the expression of genes associated with the efflux pump gene (AcrB, kexD, ketM, kdeA, and kpnE), outer membrane (OM) porin proteins (OmpK35, OmpK36), the quorum-sensing (QS) system (luxS), lipopolysaccharide (LPS) production (wzm), and EPS production (pgaA). Simultaneously, FLD exhibited evident antibacterial synergism, leading to an increased survival rate of G. mellonella infected with MDR K. pneumoniae. These findings suggested that FLD has substantial antibiofilm properties and synergistic antibacterial potential for colistin in treating K. pneumoniae infections.


Assuntos
Cloridrato de Fingolimode , Klebsiella pneumoniae , Cloridrato de Fingolimode/farmacologia , Biofilmes , Percepção de Quorum , Antibacterianos/farmacologia , Antibacterianos/química
19.
Braz. j. med. biol. res ; 57: e13284, fev.2024. tab, graf
Artigo em Inglês | LILACS-Express | LILACS | ID: biblio-1534074

RESUMO

This study aimed to analyze the safety and applicability of a 90-min duration of infusion (SDI) of obinutuzumab in patients with B-cell non-Hodgkin's lymphoma (NHL) in a tertiary hospital in China. This exploratory clinical trial was performed at Jiangsu Province Hospital. All patients were treated with the standard infusion regimen for the first infusion. If no grade ≥3 infusion-related reactions (IRRs) occurred, the subsequent infusions were given as SDI. The primary endpoint was the incidence of IRR during the standard infusion (3-4 h) and 90-min SDI regimens. This study enrolled 208 patients and all completed cycle 1. Forty-one patients (19.71%) had IRRs: five (2.40%) with grade 1, twenty-eight (13.46%) with grade 2, and eight (3.85%) with grade 3. The 41 patients had 71 IRRs, mainly fever (40.85%), chest pain/tightness (12.68%), and dyspnea (9.86%). The occurrence of IRRs in the first infusion was significantly lower in patients who received oral acetaminophen prophylaxis than those who did not (10.72% vs 30.21%, P<0.001). For the subsequent cycles with 90-min SDI, only two (0.25%) IRRs occurred among 814 infusions (one grade 1 hand numbness and one grade 2 chill/fever). The 90-min obinutuzumab SDI might be safe and feasible in patients with B-cell NHL in China.

20.
Immun Inflamm Dis ; 12(2): e1202, 2024 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-38411294

RESUMO

BACKGROUND: Histiocytic necrotizing lymphadenitis (HNL) is a self-limited inflammatory disease of unknown pathogenesis. A very small fraction of patients with HNL could develop hemophagocytic lymphohistiocytosis (HLH), a hyperinflammatory disorder. These patients are diagnosed as HNL with HLH (HNL-HLH). HNL-HLH in the pediatric population has been systemically studied, however, the clinical, laboratory, and radiological features and outcomes of adult patients with HNL-HLH remain to be explored. We aimed to explore the clinical, laboratory, and radiological features and outcomes of adult patients with HNL-HLH. METHODS: We collected the clinical data of patients with HNL-HLH admitted to the First Affiliated Hospital of Nanjing Medical University from October 2010 to June 2015. All the patients underwent lymph node biopsy and have a pathological diagnosis of HNL. The age, gender, clinical presentation, lymph node signs, laboratory findings and imaging data, and pathological findings of the patients were collected. RESULTS: In this study, we reported five adult patients with HNL-HLH. All five patients showed enlarged lymph nodes and prolonged fever. Laboratory findings were consistent with the diagnosis of HLH. 18F-fluorodeoxyglucose positron emission tomography/computed tomography (18F-FDG PET/CT) showed enlarged lymph nodes with increased FDG uptake and splenic hypermetabolism could be present. All the patients responded well to corticosteroids and had a good prognosis. Two of the five patients were diagnosed with systemic lupus erythematosus during the follow-up. CONCLUSIONS: Our study demonstrated that adult patients with HNL-HLH showed distinct clinical, laboratory, and radiological features. And the prognosis is good and patients could be managed with steroids and supportive care.


Assuntos
Linfadenite Histiocítica Necrosante , Linfo-Histiocitose Hemofagocítica , Adulto , Humanos , Criança , Linfadenite Histiocítica Necrosante/complicações , Linfadenite Histiocítica Necrosante/diagnóstico , Linfadenite Histiocítica Necrosante/tratamento farmacológico , Linfo-Histiocitose Hemofagocítica/complicações , Linfo-Histiocitose Hemofagocítica/diagnóstico , Linfo-Histiocitose Hemofagocítica/tratamento farmacológico , Tomografia por Emissão de Pósitrons combinada à Tomografia Computadorizada/efeitos adversos , Linfonodos , Biópsia/efeitos adversos
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