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1.
Sci Rep ; 14(1): 12280, 2024 05 29.
Artigo em Inglês | MEDLINE | ID: mdl-38811827

RESUMO

Loss of the tumor suppressor PTEN homolog daf-18 in Caenorhabditis elegans (C. elegans) triggers diapause cell division during L1 arrest. While prior studies have delved into established pathways, our investigation takes an innovative route. Through forward genetic screening in C. elegans, we pinpoint a new player, F12E12.11, regulated by daf-18, impacting cell proliferation independently of PTEN's typical phosphatase activity. F12E12.11 is an ortholog of human estradiol 17-beta-dehydrogenase 8 (HSD17B8), which converts estradiol to estrone through its NAD-dependent 17-beta-hydroxysteroid dehydrogenase activity. We found that PTEN engages in a physical interplay with HSD17B8, introducing a distinctive suppression mechanism. The reduction in estrone levels and accumulation of estradiol may arrest tumor cells in the G2/M phase of the cell cycle through MAPK/ERK. Our study illuminates an unconventional protein interplay, providing insights into how PTEN modulates tumor suppression by restraining cell division through intricate molecular interactions.


Assuntos
Proteínas de Caenorhabditis elegans , Caenorhabditis elegans , Proliferação de Células , PTEN Fosfo-Hidrolase , PTEN Fosfo-Hidrolase/metabolismo , PTEN Fosfo-Hidrolase/genética , Animais , Caenorhabditis elegans/metabolismo , Caenorhabditis elegans/genética , Proteínas de Caenorhabditis elegans/metabolismo , Proteínas de Caenorhabditis elegans/genética , Humanos , 17-Hidroxiesteroide Desidrogenases/metabolismo , 17-Hidroxiesteroide Desidrogenases/genética , Estradiol/metabolismo , Estrona/metabolismo
2.
Xi Bao Yu Fen Zi Mian Yi Xue Za Zhi ; 40(5): 428-434, 2024 May.
Artigo em Chinês | MEDLINE | ID: mdl-38790099

RESUMO

Objective To establish a colloidal gold immunochromatography and develop the corresponding test strip for detecting organophosphorus compounds including omethoate, phoxim, dipterex, and parathion in fruits, vegetables and drinking water. Methods Artificial antigen molecules of organophosphorus compounds were synthesized using N-hydroxysuccinimide esters. Acetylcholinesterase antigen was prepared and purified, and the serum containing the corresponding antibody was prepared, purified, and labeled. The working parameters of the test strip were optimized, and the performance evaluation of it was conducted. Results The titer of the antisera ranged from 1:32 to 1:64, with a protein content of approximately 2 mg/mL. The purified polyclonal antibodies displayed target bands at relative molecular masses (Mr) of 25 000 and 55 000, indicating satisfactory purity. The reaction time of the test strips was between 5 to 10 minutes, with a detection limit for samples at 200 ng/mL. Both specificity and accuracy were satisfactory, and the test strip remained valid for 6 months. Conclusion A simple and rapid colloidal gold immunochromatography is established successfully for detecting several organophosphorus compounds and may be useful for on-site preliminary screening of samples in large quantities.


Assuntos
Cromatografia de Afinidade , Coloide de Ouro , Compostos Organofosforados , Praguicidas , Coloide de Ouro/química , Compostos Organofosforados/análise , Cromatografia de Afinidade/métodos , Praguicidas/análise , Animais , Verduras/química , Frutas/química , Acetilcolinesterase
3.
Bioresour Technol ; 404: 130913, 2024 May 29.
Artigo em Inglês | MEDLINE | ID: mdl-38821426

RESUMO

This work proposes an advanced biochar material (ß-CD@SiBC) for controllable transformation of specific silicon (Si) forms through endogenous Si activation and functional group introduction for efficient cadmium (Cd) immobilization and removal. The maximum adsorption capacity of ß-CD@SiBC for Cd(II) reached 137.6 mg g-1 with a remarkable removal efficiency of 99 % for 200 mg L-1Cd(II). Moreover, the developed ß-CD@SiBC flow column exhibited excellent performance at the environmental Cd concentration, with the final concentration meeting the environmental standard for surface water quality (0.05 mg L-1). The remediation mechanism of ß-CD@SiBC could be mainly attributed to mineral precipitation and ion exchange, which accounted for 42 % and 29 % of the remediation effect, respectively, while functional group introduction enhanced its binding stability with Cd. Overall, this work proposes the role and principle of transformation of Si forms within biochar, providing new strategies for better utilizing endogenous components in biomass.

4.
ACS Cent Sci ; 10(4): 813-822, 2024 Apr 24.
Artigo em Inglês | MEDLINE | ID: mdl-38680567

RESUMO

Innovating the design of chimeric antigen receptors (CARs) beyond conventional structures would be necessary to address the challenges of efficacy, safety, and applicability in T cell-based cancer therapy, whereas excessive genetic modification might complicate CAR design and manufacturing, and increase gene editing risks. In this work, we used aptamers as the antigen-recognition unit to develop a nongenetic CAR engineering strategy for programming the antitumor activity and specificity of CAR T cells. Our results demonstrated that aptamer-functionalized CAR (Apt-CAR) T cells could be directly activated by recognizing target antigens on cancer cells, and then impart a cytotoxic effect for cancer elimination in vitro and in vivo. The designable antigen recognition capability of Apt-CAR T cells allows for easy modulation of their efficacy and specificity. Additionally, multiple features, e.g., tunable antigen-binding avidity and the tumor microenvironment responsiveness, could be readily integrated into Apt-CAR design without T cell re-engineering, offering a new paradigm for developing adaptable immunotherapeutics.

5.
Phytochem Anal ; 35(3): 599-616, 2024 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-38287705

RESUMO

INTRODUCTION: Accurate screening and targeted preparative isolation of active substances from natural medicines have long been technical challenges in natural medicine research. OBJECTIVES: This study outlines a new approach for improving the efficiency of natural product preparation, focusing on the rapid and accurate screening of potential active ingredients in Ganoderma lucidum and efficient preparation of lipoxidase inhibitors, with the aim of providing new ideas for the treatment of Alzheimer's disease with G. lucidum. METHODS: The medicinal plant G. lucidum was selected through ultrafiltration coupled with liquid chromatography and mass spectrometry (UF-LC-MS) and computer-assisted screening for lipoxygenase (LOX) inhibitors. In addition, the inhibitory effect of the active compounds on LOX was studied using enzymatic reaction kinetics, and the underlying mechanism is discussed. Finally, based on the earlier activity screening guidelines, the identified ligands were isolated and purified through complex chromatography (high-speed countercurrent chromatography and semi-preparative high-performance liquid chromatography). RESULTS: Five active ingredients, ganoderic acids A, B, C2, D2, and F, were identified and isolated from G. lucidum. We improved the efficiency and purity of active compound preparation using virtual computer screening and enzyme inhibition assays combined with complex chromatography. CONCLUSION: The innovative methods of UF-LC-MS, computer-aided screening, and complex chromatography provide powerful tools for screening and separating LOX inhibitors from complex matrices and provide a favourable platform for the large-scale production of bioactive substances and nutrients.


Assuntos
Antineoplásicos , Reishi , Inibidores de Lipoxigenase/farmacologia , Cromatografia Líquida de Alta Pressão , Distribuição Contracorrente
6.
Anesth Analg ; 2024 Jan 09.
Artigo em Inglês | MEDLINE | ID: mdl-38195081

RESUMO

BACKGROUND: The effect of intraoperative anesthetic regimen on pulmonary outcome after minimally invasive esophagectomy for esophageal cancer is yet undetermined. The aim of this study was to determine the effect of volatile anesthesia (sevoflurane or desflurane) compared with propofol-based intravenous anesthesia on pulmonary complications after minimally invasive esophagectomy. METHODS: Patients scheduled for minimally invasive esophagectomy were randomly assigned to 1 of 3 general anesthetic regimens (sevoflurane, desflurane, or propofol). The primary outcome was the incidence of pulmonary complications within the 7 days postoperatively, which was a collapsed composite end point, including respiratory infection, pleural effusion, pneumothorax, atelectasis, respiratory failure, bronchospasm, pulmonary embolism, and aspiration pneumonitis. The severity of pulmonary complications, surgery-related complications, and other secondary outcomes were also assessed. RESULTS: Of 647 patients assessed for eligibility, 558 were randomized, and 553 were analyzed. A total of 185 patients were assigned to the sevoflurane group, 185 in the desflurane, and 183 in the propofol group. Patients receiving a volatile anesthetic (sevoflurane or desflurane) had a significantly lower incidence (36.5% vs 47.5%; odds ratio, 0.63; 95% confidence interval, 0.44-0.91; P = .013) and lower severity grade of pulmonary complications (P = .035) compared to the patients receiving propofol. There were no statistically significant differences in other secondary outcomes between the 2 groups. CONCLUSIONS: In patients undergoing minimally invasive esophagectomy, the use of volatile anesthesia (sevoflurane or desflurane) resulted in the reduced risk and severity of pulmonary complications within the first 7 postoperative days as compared to propofol-based intravenous anesthesia.

7.
Mol Neurobiol ; 61(1): 132-147, 2024 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-37592185

RESUMO

Post-stroke depression (PSD) affects approximately one-third of stroke survivors, severely impacting general recovery and quality of life. Despite extensive studies, the exact mechanisms underlying PSD remain elusive. However, emerging evidence implicates proinflammatory cytokines, including interleukin-1ß, interleukin-6, tumor necrosis factor-alpha, and interleukin-18, play critical roles in PSD development. These cytokines contribute to PSD through various mechanisms, including hypothalamic-pituitary-adrenal (HPA) axis dysfunction, neurotransmitter alterations, neurotrophic factor changes, gut microbiota imbalances, and genetic predispositions. This review is aimed at exploring the role of cytokines in stroke and PSD while identifying their potential as specific therapeutic targets for managing PSD. A more profound understanding of the mechanisms regulating inflammatory cytokine expression and anti-inflammatory cytokines like interleukin-10 in PSD may facilitate the development of innovative interventions to improve outcomes for stroke survivors experiencing depression.


Assuntos
Citocinas , Acidente Vascular Cerebral , Humanos , Citocinas/genética , Depressão/etiologia , Qualidade de Vida , Acidente Vascular Cerebral/tratamento farmacológico , Interleucina-6
8.
J Clin Endocrinol Metab ; 109(5): 1263-1274, 2024 Apr 19.
Artigo em Inglês | MEDLINE | ID: mdl-38038628

RESUMO

CONTEXT: Papillary thyroid microcarcinoma (PTMC) is the most common type of thyroid cancer. It has been shown that lymph node metastasis is associated with poor prognosis in patients with PTMC. OBJECTIVE: We aim to characterize the PTMC transcriptome landscape and identify the candidate transcripts that are associated with lateral neck lymph node metastasis of PTMC. METHODS: We performed full-length transcriptome sequencing in 64 PTMC samples. Standard bioinformatic pipelines were applied to characterize and annotate the full-length expression profiles of 2 PTMC subtypes. Functional open reading frame (ORF) annotation of the known and novel transcripts were predicted by HMMER, DeepLoc, and DeepTMHMM tools. Candidate transcripts associated with the pN1b subtype were identified after transcript quantification and differential gene expression analyses. RESULTS: We found that skipping exons accounted for the more than 27.82% of the alternative splicing events. At least 42.56% of the discovered transcripts were novel isoforms of annotated genes. A total of 39 193 ORFs in novel transcripts and 18 596 ORFs in known transcripts were identified. Distribution patterns of the characterized transcripts in functional domain, subcellular localization, and transmembrane structure were predicted. In total, 1033 and 1204 differentially expressed genes were identified in the pN0 and pN1b groups, respectively. Moreover, novel isoforms of FRMD3, NOD1, and SHROOM4 were highlighted for their association with pN1b subtype. CONCLUSION: Our data provided the global transcriptome landscape of PTMC and also revealed the novel isoforms that associated with PTMC aggressiveness.

9.
Phytochem Anal ; 35(1): 116-134, 2024 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-37798938

RESUMO

INTRODUCTION: Studies show that Polyporus umbellatus has some pharmacological effects in enhancing immunity and against gout. OBJECTIVES: We aimed to establish new techniques for extraction, biological activity screening, and preparation of xanthine oxidase inhibitors (XODIs) from P. umbellatus. METHODS: First, the extraction of P. umbellatus was investigated using the back propagation (BP) neural network genetic algorithm mathematical regression model, and the extraction variables were optimised to maximise P. umbellatus yield. Second, XODIs were rapidly screened using ultrafiltration, and the change of XOD activity was tested by enzymatic reaction kinetics experiment to reflect the inhibitory effect of active compounds on XOD. Meanwhile, the potential anti-gout effects of the obtained active substances were verified using molecular docking, molecular dynamics simulations, and network pharmacology analysis. Finally, with activity screening as guide, a high-speed countercurrent chromatography (HSCCC) method combined with consecutive injection and two-phase solvent system preparation using the UNIFAC mathematical model was successfully developed for separation and purification of XODIs, and the XODIs were identified using MS and NMR. RESULTS: The results verified that polyporusterone A, polyporusterone B, ergosta-4,6,8(14),22-tetraen-3-one, and ergosta-7,22-dien-3-one of P. umbellatus exhibited high biological affinity towards XOD. Their structures have been further identified by NMR, indicating that the method is effective and applicable for rapid screening and identification of XODIs. CONCLUSION: This study provides new ideas for the search for natural XODIs active ingredients, and the study provide valuable support for the further development of functional foods with potential therapeutic benefits.


Assuntos
Polyporus , Xantina Oxidase , Simulação de Acoplamento Molecular , Polyporus/química , Inibidores Enzimáticos/farmacologia
11.
ACS Nano ; 18(1): 119-135, 2024 Jan 09.
Artigo em Inglês | MEDLINE | ID: mdl-38117770

RESUMO

T cell-mediated immunity plays a pivotal role in cancer immunotherapy. The anticancer actions of T cells are coordinated by a sequence of biological processes, including the capture and presentation of antigens by antigen-presenting cells (APCs), the activation of T cells by APCs, and the subsequent killing of cancer cells by activated T cells. However, cancer cells have various means to evade immune responses. Meanwhile, these vulnerabilities provide potential targets for cancer treatments. Functional nucleic acids (FNAs) make up a class of synthetic nucleic acids with specific biological functions. With their diverse functionality, good biocompatibility, and high programmability, FNAs have attracted widespread interest in cancer immunotherapy. This Review focuses on recent research progress in employing FNAs as molecular tools for T cell-mediated cancer immunotherapy, including corresponding challenges and prospects.


Assuntos
Imunomodulação , Neoplasias , Humanos , Neoplasias/terapia , Células Apresentadoras de Antígenos , Imunoterapia , Linfócitos T , Apresentação de Antígeno
12.
J Exp Clin Cancer Res ; 42(1): 277, 2023 Oct 23.
Artigo em Inglês | MEDLINE | ID: mdl-37872588

RESUMO

BACKGROUND: Tumor cell-induced platelet aggregation (TCIPA) is not only a recognized mechanism for paraneoplastic thrombocytosis but also a potential breakthrough alternative for a low response to immune checkpoint inhibitors (ICIs) in hematogenous metastasis of malignant melanoma (MM). However, there is no TCIPA-specific model for further investigation of the relationship among TCIPA, the tumor immune microenvironment (TIME), and metastasis. METHODS: We developed a TCIPA metastatic melanoma model with advanced hematogenous metastasis and enhanced TCIPA characteristics. We also investigated the pathway for TCIPA in the TIME. RESULTS: We found that TCIPA triggers the recruitment of tumor-associated macrophages (TAMs) to lung metastases by secreting B16 cell-educated platelet-derived chemokines such as CCL2, SDF-1, and IL-1ß. Larger quantities of TAMs in the TCIPA model were polarized to the M2 type by B16 cell reprocessing, and their surface programmed cell death 1 ligand 1 (PD-L1) expression was upregulated, ultimately assisting B16 cells in escaping host immunity and accelerating MM hematogenous metastasis. CONCLUSIONS: TCIPA accelerates MM lung metastasis via tumor-educated platelets (TEPs), triggering TAM recruitment, promoting TAM polarization (M2), and remodeling the suppressive TIME in lung metastases.


Assuntos
Neoplasias Pulmonares , Melanoma , Humanos , Agregação Plaquetária/fisiologia , Macrófagos , Microambiente Tumoral , Melanoma Maligno Cutâneo
13.
Int J Biol Macromol ; 253(Pt 8): 127605, 2023 Dec 31.
Artigo em Inglês | MEDLINE | ID: mdl-37871715

RESUMO

In this study, Cnidium officinale-derived polysaccharides were isolated and investigated for their immune enhancing and anticancer activities. The isolated crude and its fractions, such as F1 and F2, contain carbohydrates (51.3-63.1%), sulfates (5.4-5.8%), proteins (1.5-7.1%), and uronic acids (2.1-26.9%). The molecular weight (Mw) of the polysaccharides ranged from 59.9 to 429.0 × 103 g/mol. The immunostimulatory activity of the polysaccharides was tested on RAW 264.7 cells, and the results showed that the F2 treatment notably enhanced pro-inflammatory activity in RAW 264.7 cells by increasing NO production and the expression of various cytokines. Furthermore, the influence of polysaccharide treatment on natural killer cells (NK-92) anticancer activities was investigated using a colon cancer cell line (HCT-116). Crude polysaccharide and its fractions showed no direct cytotoxicity to NK-92 and HCT-116 cells. However, the treatment of F2 showed an enhancement of NK-92 cells cytotoxicity against HCT-116 cells by upregulating the mRNA expression of IFN-γ, TNF-α, NKGp44, and granzyme-B. The western blot results showed that the induced RAW 264.7 cells activation and NK-92 cells cytotoxicity occur via NF-κB and MAPK signaling pathways. Overall, C. officinale-derived polysaccharides show potential as immunotherapeutic agents capable of enhancing pro-inflammatory macrophage signaling and activating NK-92 cells; thus, they could be useful for biomedical applications.


Assuntos
Neoplasias do Colo , NF-kappa B , Animais , Camundongos , Humanos , Células RAW 264.7 , NF-kappa B/metabolismo , Cnidium/metabolismo , Polissacarídeos/farmacologia , Transdução de Sinais , Neoplasias do Colo/tratamento farmacológico
14.
Radiology ; 308(2): e223091, 2023 08.
Artigo em Inglês | MEDLINE | ID: mdl-37552092

RESUMO

Background Infectious complications after percutaneous thermal ablation are seldom discussed, but better understanding of risk factors and early prediction is critical. Purpose To estimate the incidence of infectious complications after percutaneous thermal ablation of liver malignancies and to develop prediction models. Materials and Methods This single-center retrospective study reviewed the data of 3167 patients who underwent 7545 percutaneous US-guided thermal ablation procedures of liver malignancies between January 2010 and January 2022. All procedures with infectious complications were included as the case group. For each case, one treatment date-matched control subject without infection was randomly selected following a nested case-control design. Independent factors of overall and hepatobiliary infection were investigated with multivariable logistic regression. Results A total of 80 patients (median age, 59 years; IQR, 51-68 years; 64 men, 16 women) developed infectious complications after 80 ablation procedures; the incidence was 1.1% (80 of 7545 procedures). Of those with infection, 18% (14 of 80 patients) were severe, and 10% (eight of 80 patients) died as a result. Independent risk factors for overall infectious complication included prior biliary intervention (odds ratio [OR], 18.6; 95% CI: 4, 86; P < .001), prior transarterial chemoembolization (TACE) (OR, 2.4; 95% CI: 1.0, 5.8; P = .045), and the largest tumor size (OR, 1.9; 95% CI: 1.3, 2.8; P = .002); on this basis, subcapsular location was an additional risk factor of hepatobiliary infection. Prediction models for overall and hepatobiliary infection had an area under the receiver operating characteristics curve (AUC) of 0.77 and 0.82, respectively, both of which showed better AUC compared with the models, including prior biliary intervention alone (AUC = 0.63 and 0.65, respectively; P = .01 and P = .005, respectively). Conclusion Infectious complications after percutaneous thermal ablation of liver malignancies were uncommon but potentially fatal. Independent predictors were prior biliary intervention, prior transarterial chemoembolization, and the largest tumor size. © RSNA, 2023 Supplemental material is available for this article. See also the editorial by Ben-Arie and Sosna in this issue.


Assuntos
Carcinoma Hepatocelular , Ablação por Cateter , Quimioembolização Terapêutica , Neoplasias Hepáticas , Masculino , Humanos , Feminino , Pessoa de Meia-Idade , Neoplasias Hepáticas/terapia , Carcinoma Hepatocelular/cirurgia , Estudos Retrospectivos , Resultado do Tratamento , Ablação por Cateter/métodos
15.
ACS Nano ; 17(14): 13430-13440, 2023 07 25.
Artigo em Inglês | MEDLINE | ID: mdl-37410377

RESUMO

Although many smart probes for precise tumor recognition have been reported, the challenge of "on-target, off-tumor" remains. Therefore, we herein report the fabrication of a series of allosterically tunable DNA nanosensing-circles (NSCs). The recognition affinity of NSCs is programmed through sensitivity to tumor microenvironment (TME) hallmarks such as small molecules, acidity, or oncoproteins. Because of their special programming conditions and active targeting capabilities, NSCs can overcome the obstacles noted above, thus achieving precise tumor recognition. Results from in vitro analysis demonstrated that NSCs obtain their recognition ability through allosteric regulation after sensing TME hallmarks. Furthermore, in vivo imaging indicated that NSCs enable precise tumor imaging. These results demonstrate that our NSCs will be promising tools for precise tumor imaging and therapy.


Assuntos
Neoplasias , Humanos , Microambiente Tumoral
16.
Angew Chem Int Ed Engl ; 62(39): e202307656, 2023 09 25.
Artigo em Inglês | MEDLINE | ID: mdl-37423897

RESUMO

Nongenetic strategies that enable control over the cell-cell interaction network would be highly desired, particularly in T cell-based cancer immunotherapy. In this work, we developed an aptamer-functionalized DNA circuit to modulate the interaction between T cells and cancer cells. This DNA circuit was composed of recognition-then-triggering and aggregation-then-activation modules. Upon recognizing target cancer cells, the triggering strand was released to induce aggregation of immune receptors on the T cell surface, leading to an enhancement of T cell activity for effective cancer eradication. Our results demonstrated the feasibility of this DNA circuit for promoting target cancer cell-directed stimulation of T cells, which, consequently, enhanced their killing effect on cancer cells. This DNA circuit, as a modular strategy to modulate intercellular interactions, could lead to a new paradigm for the development of nongenetic T cell-based immunotherapy.


Assuntos
Aptâmeros de Nucleotídeos , Neoplasias , Linfócitos T/metabolismo , Aptâmeros de Nucleotídeos/metabolismo , DNA/metabolismo , Membrana Celular/metabolismo , Imunoterapia , Neoplasias/terapia , Neoplasias/metabolismo
17.
Biomed Pharmacother ; 165: 115207, 2023 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-37499455

RESUMO

Tumor metastasis is the main reason for cancer-related death, but there is still a lack of effective therapeutic to inhibit tumor metastasis. Therefore, the discovery and study of new tumor metastasis regulators is a prominent measure for cancer diagnosis and treatment. Long non-coding RNA (lncRNA) is a type of non-coding RNAs over 200 bp in length. It has been shown that the abnormally expressed lncRNAs promote tumor metastasis by participating in the epithelial-to-mesenchymal transition (EMT) process, altering the metastatic tumor microenvironment, or changing the extracellular matrix. It is,thus, critical to explore the regulation of lncRNAs expression in cells and the molecular mechanism of lncRNA-mediated cancer metastasis. Simultaneously, it has been shown that lncRNA is one kind of the main components of exosomes, which protects lncRNAs from being rapidly degraded. Meanwhile, the components of exosomes are parent-specific, making exosomal lncRNAs to be potential tumor metastasis markers and therapeutic targets. In view of this, we also summarized the aberrant enrichment of lncRNAs in exosomes and their role in metastatic cancer. The aberrant lncRNAs and exosomal lncRNAs gradually become biomarkers and therapeutic targets for tumor metastatic, and the potential of lncRNAs in therapeutics are studied here. Besides, the lncRNA-related databases, which could greatly facilitate in the study of lncRNAs and exosomal lncRNAs in metastatic of cancer are included in this review.


Assuntos
Exossomos , Neoplasias , RNA Longo não Codificante , Humanos , RNA Longo não Codificante/genética , RNA Longo não Codificante/metabolismo , Neoplasias/genética , Neoplasias/metabolismo , Exossomos/genética , Exossomos/metabolismo , Biomarcadores Tumorais/genética , Biomarcadores Tumorais/metabolismo , Transição Epitelial-Mesenquimal/genética , Microambiente Tumoral/genética
18.
J Neurooncol ; 164(1): 117-125, 2023 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-37474745

RESUMO

PURPOSE: Chemotherapy is commonly used for treatment in children over three years old with high-risk medulloblastoma(MB). However, little is currently known about the therapeutic benefits and side effects of intrathecal methotrexate(MTX), warranting further research. METHODS: In this retrospective study, patients who received intrathecal MTX during chemotherapy were included in the MTX group (n = 32), and patients that only underwent cerebrospinal fluid (CSF) cytology analysis were assigned to the control group (n = 14). RESULTS: In the MTX group, 27(84.38%) patients had metastatic disease, 3(9.38%) had diffuse anaplasia, and 3(9.38%) had residual disease greater than 1.5 cm2. Molecular subgroup classification was available for 28(87.5%) patients. In the control group, 8(57.14%) patients had metastatic disease, 3(27.27%) had diffuse anaplasia, and 6(42.86%) had residual disease greater than 1.5 cm2. Molecular subgroup classification was available for 6(42.86%) patients. The 5-year progression-free survival was 70.99% and the 5-year overall survival was 72.99% for the MTX group, and the corresponding values were 41.67% and 50% for the control group, respectively. 6 (18.75%) patients in the MTX group with group 4 disease developed MTX-related acute leukoencephalopathy and one of them died. CONCLUSIONS: Our findings support the addition of intrathecal MTX during chemotherapy as the optimal management for children with group 3 and SHH high-risk MB. However, it is not recommended for group 4 MB patients, especially in resource-limited regions. TRIAL REGISTRATION NUMBER: Retrospective registered No.(2020 - 117).


Assuntos
Neoplasias Cerebelares , Meduloblastoma , Criança , Humanos , Pré-Escolar , Metotrexato/efeitos adversos , Meduloblastoma/patologia , Estudos Retrospectivos , Anaplasia/induzido quimicamente , Anaplasia/tratamento farmacológico , Protocolos de Quimioterapia Combinada Antineoplásica/efeitos adversos , Neoplasias Cerebelares/patologia
19.
Mol Cell Proteomics ; 22(7): 100583, 2023 07.
Artigo em Inglês | MEDLINE | ID: mdl-37236439

RESUMO

Single-cell proteomics as an emerging field has exhibited potential in revealing cellular heterogeneity at the functional level. However, accurate interpretation of single-cell proteomics data suffers from challenges such as measurement noise, internal heterogeneity, and the limited sample size of label-free quantitative mass spectrometry. Herein, the author describes peptide-level differential expression analysis for single-cell proteomic (pepDESC), a method for detecting differentially expressed proteins using peptide-level information designed for label-free quantitative mass spectrometry-based single-cell proteomics. While, in this study, the author focuses on the heterogeneity among the limited number of samples, pepDESC is also applicable to regular-size proteomics data. By balancing proteome coverage and quantification accuracy using peptide quantification, pepDESC is demonstrated to be effective in real-world single-cell and spike-in benchmark datasets. By applying pepDESC to published single-mouse macrophage data, the author found a large fraction of differentially expressed proteins among three types of cells, which remarkably revealed distinct dynamics of different cellular functions responding to lipopolysaccharide stimulation.


Assuntos
Peptídeos , Proteômica , Animais , Camundongos , Proteômica/métodos , Peptídeos/análise , Espectrometria de Massas/métodos , Proteoma/metabolismo
20.
Front Endocrinol (Lausanne) ; 14: 1128248, 2023.
Artigo em Inglês | MEDLINE | ID: mdl-36926030

RESUMO

Objectives: To develop and validate a nomogram model for predicting residue of partially cystic thyroid nodules (PCTNs) after ethanol and thermal ablation. Materials and Methods: From July 2015 to August 2022, a total of 97 patients (age 40.78 ± 12.61 years) with 107 treated benign PCTNs receiving ethanol and thermal ablation were enrolled. Pre-ablative laboratory test results and the ultrasound (US) and contrast-enhanced ultrasound (CEUS) features of lesions were collected. They were categorized into non-residue group and residue group according to the CEUS examination assessment after ablation. Univariate and multivariate logistic regression analysis were adopted to build a nomogram. The nomogram was validated by internal stratified fivefold cross-validation. The calibration, discrimination and clinical utility of the nomogram were investigated to assess the performance of the model. Results: Residue was reported in 30 out of 107nodules (28.0%). Multivariate logistic regression analysis revealed initial volume (OR=1.12, 95%CI 1.06-1.19) and presence of septum (OR=3.19, 95%CI 1.09-9.36) were predictors of residue of PCTNs. The nomogram developed by the above factors showed good calibration and discrimination. The area under the curve (AUC), sensitivity and specificity of this model were 0.832, 86.7% and 68.8%, respectively. When applied to internal validation, the model revealed good generalizability with stratified fivefold cross-validation in the cohort (mean AUC = 0.821). Conclusions: The nomogram model has good performance for predicting the residue of PCTNs undergoing ethanol and thermal ablation. This could play a role in the decision of treatment and follow-up in clinical practice.


Assuntos
Nódulo da Glândula Tireoide , Humanos , Adulto , Pessoa de Meia-Idade , Nódulo da Glândula Tireoide/diagnóstico por imagem , Nódulo da Glândula Tireoide/cirurgia , Nomogramas , Etanol , Ultrassonografia/métodos , Ultrassonografia de Intervenção
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