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1.
Insights Imaging ; 15(1): 165, 2024 Jun 28.
Article de Anglais | MEDLINE | ID: mdl-38940988

RÉSUMÉ

OBJECTIVES: We aimed to develop MRI-based radiomic models (RMs) to improve the diagnostic accuracy of radiologists in characterizing intestinal fibrosis in patients with Crohn's disease (CD). METHODS: This retrospective study included patients with refractory CD who underwent MR before surgery from November 2013 to September 2021. Resected bowel segments were histologically classified as none-mild or moderate-severe fibrosis. RMs based on different MR sequence combinations (RM1: T2WI and enhanced-T1WI; RM2: T2WI, enhanced-T1WI, diffusion-weighted imaging [DWI], and apparent diffusion coefficient [ADC]); RM3: T2WI, enhanced-T1WI, DWI, ADC, and magnetization transfer MRI [MTI]), were developed and validated in an independent test cohort. The RMs' diagnostic performance was compared to that of visual interpretation using identical sequences and a clinical model. RESULTS: The final population included 123 patients (81 men, 42 women; mean age: 30.26 ± 7.98 years; training cohort, n = 93; test cohort, n = 30). The area under the receiver operating characteristic curve (AUC) of RM1, RM2, and RM3 was 0.86 (p = 0.001), 0.88 (p = 0.001), and 0.93 (p = 0.02), respectively. The decision curve analysis confirmed a progressive improvement in the diagnostic performance of three RMs with the addition of more specific sequences. All RMs performance surpassed the visual interpretation based on the same MR sequences (visual model 1, AUC = 0.65, p = 0.56; visual model 2, AUC = 0.63, p = 0.04; visual model 3, AUC = 0.77, p = 0.002), as well as the clinical model composed of C-reactive protein and erythrocyte sedimentation rate (AUC = 0.60, p = 0.13). CONCLUSIONS: The RMs, utilizing various combinations of conventional, DWI and MTI sequences, significantly enhance radiologists' ability to accurately characterize intestinal fibrosis in patients with CD. CRITICAL RELEVANCE STATEMENT: The utilization of MRI-based RMs significantly enhances the diagnostic accuracy of radiologists in characterizing intestinal fibrosis. KEY POINTS: MRI-based RMs can characterize CD intestinal fibrosis using conventional, diffusion, and MTI sequences. The RMs achieved AUCs of 0.86-0.93 for assessing fibrosis grade. MRI-radiomics outperformed visual interpretation for grading CD intestinal fibrosis.

2.
J Appl Biomed ; 22(2): 99-106, 2024 Jun.
Article de Anglais | MEDLINE | ID: mdl-38912865

RÉSUMÉ

Resveratrol (RSV) is a polyphenol antioxidant that has been shown to have neuroprotective effects. We sought molecular mechanisms that emphasize the anti-inflammatory activity of RSV in traumatic brain injury (TBI) in mice associated with endoplasmic reticulum stress (ERS). After establishing three experimental groups (sham, TBI, and TBI+RSV), we explored the results of RSV after TBI on ERS and caspase-12 apoptotic pathways. The expression levels of C/EBP homologous protein (CHOP), glucose regulated protein 78kD (GRP78), caspase-3, and caspase-12 in cortical brain tissues were assessed by western blotting. The qPCR analysis was also performed on mRNA expression of tumor necrosis factor (TNF)-α and interleukin (IL)-1ß in cortical brain tissue. In addition, the expression of GRP78 in microglia (ionized calcium binding adaptor molecule 1; Iba-1) and neurons (neuronal nuclei; NeuN) was identified by immunofluorescence staining. The neurological function of mice was assessed by modified neurological severity scores (mNSS). After drug treatment, the expression of CHOP, GRP78, caspase-3 and caspase-12 decreased, and qPCR results showed that TNF-α and IL-1ß were down-regulated. Immunofluorescence staining showed down-regulation of Iba-1+/GRP78+ and NeuN+/GRP78+ cells after RSV treatment. The mNSS analysis confirmed improvement after RSV treatment. RSV improved apoptosis by downregulating the ERS signaling pathway and improved neurological prognosis in mice with TBI.


Sujet(s)
Lésions traumatiques de l'encéphale , Chaperonne BiP du réticulum endoplasmique , Stress du réticulum endoplasmique , Resvératrol , Animaux , Lésions traumatiques de l'encéphale/traitement médicamenteux , Lésions traumatiques de l'encéphale/anatomopathologie , Lésions traumatiques de l'encéphale/métabolisme , Resvératrol/pharmacologie , Resvératrol/usage thérapeutique , Stress du réticulum endoplasmique/effets des médicaments et des substances chimiques , Souris , Mâle , Apoptose/effets des médicaments et des substances chimiques , Pronostic , Neuroprotecteurs/pharmacologie , Neuroprotecteurs/usage thérapeutique , Neurones/effets des médicaments et des substances chimiques , Neurones/anatomopathologie , Neurones/métabolisme , Interleukine-1 bêta/métabolisme , Interleukine-1 bêta/génétique , Caspase-12/métabolisme , Caspase-12/génétique , Protéines du choc thermique/métabolisme , Protéines du choc thermique/génétique , Facteur de nécrose tumorale alpha/métabolisme , Souris de lignée C57BL , Mort cellulaire/effets des médicaments et des substances chimiques , Microglie/effets des médicaments et des substances chimiques , Microglie/métabolisme , Microglie/anatomopathologie , Facteur de transcription CHOP/métabolisme , Facteur de transcription CHOP/génétique
3.
Nat Commun ; 15(1): 3768, 2024 May 04.
Article de Anglais | MEDLINE | ID: mdl-38704409

RÉSUMÉ

Accurate intraoperative differentiation of primary central nervous system lymphoma (PCNSL) remains pivotal in guiding neurosurgical decisions. However, distinguishing PCNSL from other lesions, notably glioma, through frozen sections challenges pathologists. Here we sought to develop and validate a deep learning model capable of precisely distinguishing PCNSL from non-PCNSL lesions, especially glioma, using hematoxylin and eosin (H&E)-stained frozen whole-slide images. Also, we compared its performance against pathologists of varying expertise. Additionally, a human-machine fusion approach integrated both model and pathologic diagnostics. In external cohorts, LGNet achieved AUROCs of 0.965 and 0.972 in distinguishing PCNSL from glioma and AUROCs of 0.981 and 0.993 in differentiating PCNSL from non-PCNSL lesions. Outperforming several pathologists, LGNet significantly improved diagnostic performance, further augmented to some extent by fusion approach. LGNet's proficiency in frozen section analysis and its synergy with pathologists indicate its valuable role in intraoperative diagnosis, particularly in discriminating PCNSL from glioma, alongside other lesions.


Sujet(s)
Tumeurs du système nerveux central , Apprentissage profond , Coupes minces congelées , Gliome , Lymphomes , Humains , Tumeurs du système nerveux central/anatomopathologie , Tumeurs du système nerveux central/chirurgie , Tumeurs du système nerveux central/diagnostic , Lymphomes/anatomopathologie , Lymphomes/diagnostic , Lymphomes/chirurgie , Gliome/chirurgie , Gliome/anatomopathologie , Étude de validation de principe , Mâle , Femelle , Diagnostic différentiel , Adulte d'âge moyen , Sujet âgé , Période peropératoire
4.
BMC Cancer ; 24(1): 580, 2024 May 12.
Article de Anglais | MEDLINE | ID: mdl-38735973

RÉSUMÉ

BACKGROUND: SRSF1, a member of Serine/Arginine-Rich Splicing Factors (SRSFs), has been observed to significantly influence cancer progression. However, the precise role of SRSF1 in osteosarcoma (OS) remains unclear. This study aims to investigate the functions of SRSF1 and its underlying mechanism in OS. METHODS: SRSF1 expression level in OS was evaluated on the TCGA dataset, TAGET-OS database. qRT-PCR and Western blotting were employed to assess SRSF1 expression in human OS cell lines as well as the interfered ectopic expression states. The effect of SRSF1 on cell migration, invasion, proliferation, and apoptosis of OS cells were measured by transwell assay and flow cytometry. RNA sequence and bioinformatic analyses were conducted to elucidate the targeted genes, relevant biological pathways, and alternative splicing (AS) events regulated by SRSF1. RESULTS: SRSF1 expression was consistently upregulated in both OS samples and OS cell lines. Diminishing SRSF1 resulted in reduced proliferation, migration, and invasion and increased apoptosis in OS cells while overexpressing SRSF1 led to enhanced growth, migration, invasion, and decreased apoptosis. Mechanistically, Gene Ontology (GO) analysis, Kyoto Encyclopedia of Genes and Genomes (KEGG) analysis, and Gene Set Enrichment Analysis (GSEA) revealed that the biological functions of SRSF1 were closely associated with the dysregulation of the protein targeting processes, location of the cytosolic ribosome, extracellular matrix (ECM), and proteinaceous extracellular matrix, along with the PI3K-AKT pathway, Wnt pathway, and HIPPO pathway. Transcriptome analysis identified AS events modulated by SRSF1, especially (Skipped Exon) SE events and (Mutually exclusive Exons) MXE events, revealing potential roles of targeted molecules in mRNA surveillance, RNA degradation, and RNA transport during OS development. qRT-PCR confirmed that SRSF1 knockdown resulted in the occurrence of alternative splicing of SRRM2, DMKN, and SCAT1 in OS. CONCLUSIONS: Our results highlight the oncogenic role of high SRSF1 expression in promoting OS progression, and further explore the potential mechanisms of action. The significant involvement of SRSF1 in OS development suggests its potential utility as a therapeutic target in OS.


Sujet(s)
Apoptose , Tumeurs osseuses , Mouvement cellulaire , Prolifération cellulaire , Évolution de la maladie , Régulation de l'expression des gènes tumoraux , Ostéosarcome , Facteurs d'épissage riches en sérine-arginine , Humains , Facteurs d'épissage riches en sérine-arginine/génétique , Facteurs d'épissage riches en sérine-arginine/métabolisme , Ostéosarcome/génétique , Ostéosarcome/anatomopathologie , Ostéosarcome/métabolisme , Tumeurs osseuses/génétique , Tumeurs osseuses/anatomopathologie , Tumeurs osseuses/métabolisme , Prolifération cellulaire/génétique , Lignée cellulaire tumorale , Apoptose/génétique , Mouvement cellulaire/génétique , Régulation positive , Épissage alternatif
5.
Onco Targets Ther ; 17: 339-344, 2024.
Article de Anglais | MEDLINE | ID: mdl-38644954

RÉSUMÉ

Gastric adenocarcinoma (GAS) is a rare subtype of mucinous adenocarcinoma characterized by gastric differentiation and is unrelated to human papillomavirus (HPV) infection. This report discusses a 40-year-old female who presented with abdominal distension accompanied by increased abdominal circumference. CT of the abdomen and pelvis showed a large 21.0*12.7*26.0 cm mass later diagnosed as GAS combined with squamous cell carcinoma on surgical pathology. Immunohistological staining of GAS was positive for CK7, MUC6, PAX-8 CEA, and P53 (wild type) and negative for CDX2, CK20, ER, PR, P16, and WT1. The proliferative index (Ki-67) was 20%. Immunohistochemical staining of squamous cell carcinoma was positive for P16 and P53 (wild type), and the proliferative index (Ki-67) was 90%. However, the pathogenesis and molecular mechanisms of GAS have not been fully elucidated. As more cases are identified and reported, additional targeted therapies can be developed and tested in these patients.

6.
iScience ; 27(3): 109243, 2024 Mar 15.
Article de Anglais | MEDLINE | ID: mdl-38420592

RÉSUMÉ

Accurate tumor diagnosis by pathologists relies on identifying specific morphological characteristics. However, summarizing these unique morphological features in tumor classifications can be challenging. Although deep learning models have been extensively studied for tumor classification, their indirect and subjective interpretation obstructs pathologists from comprehending the model and discerning the morphological features accountable for classifications. In this study, we introduce a new approach utilizing Style Generative Adversarial Networks, which enables a direct interpretation of deep learning models to detect significant morphological characteristics within datasets representing patients with deficient mismatch repair/microsatellite instability-high gastric cancer. Our approach effectively identifies distinct morphological features crucial for tumor classification, offering valuable insights for pathologists to enhance diagnostic accuracy and foster professional growth.

7.
Nanoscale ; 16(4): 1673-1684, 2024 Jan 25.
Article de Anglais | MEDLINE | ID: mdl-38189461

RÉSUMÉ

Addressing the challenges of chemodynamic therapies (CDTs) relying on Fenton reactions in malignant tumors is an active research area. Here, we report a method to develop pH-responsive hybrid nanoparticles for enhanced chemodynamic tumor treatment. Reactive CaO2 nanoparticles (core) are isolated by biocompatible ZIF-8 doped with Fe2+ (shell), and then encapsulated by macrophage membranes (symbolized as CaO2@Fe-ZIF-8@macrophage membrane or CFZM), thus endowed with high stability under normal physiological conditions. Our design features active tumor-homing by the macrophage-membrane coating, tumor microenvironment (TME)-responsive cargo release, and self-supplied hydrogen peroxide for promotion of the Fenton reaction. We demonstrate the improved delivery/tumor cell uptake of CFZM, the efficient production of toxic ˙OH with self-supplied H2O2 in CFZM, and high-efficacy tumor ablation on BALB/c mice bearing CT26 tumor cells. This offers a translational strategy to develop active tumor-targeting and TME-responsive nanotherapeutics with enhanced CDT against malignant tumors.


Sujet(s)
Nanoparticules , Tumeurs , Animaux , Souris , Peroxyde d'hydrogène , Cytoplasme , Macrophages , Souris de lignée BALB C , Microenvironnement tumoral , Lignée cellulaire tumorale
8.
J Transl Med ; 22(1): 88, 2024 01 22.
Article de Anglais | MEDLINE | ID: mdl-38254188

RÉSUMÉ

BACKGROUND: Risk stratification and personalized care are crucial in managing osteosarcoma due to its complexity and heterogeneity. However, current prognostic prediction using clinical variables has limited accuracy. Thus, this study aimed to explore potential molecular biomarkers to improve prognostic assessment. METHODS: High-throughput inhibitor screening of 150 compounds with broad targeting properties was performed and indicated a direction towards super-enhancers (SEs). Bulk RNA-seq, scRNA-seq, and immunohistochemistry (IHC) were used to investigate SE-associated gene expression profiles in osteosarcoma cells and patient tissue specimens. Data of 212 osteosarcoma patients who received standard treatment were collected and randomized into training and validation groups for retrospective analysis. Prognostic signatures and nomograms for overall survival (OS) and lung metastasis-free survival (LMFS) were developed using Cox regression analyses. The discriminatory power, calibration, and clinical value of nomograms were evaluated. RESULTS: High-throughput inhibitor screening showed that SEs significantly contribute to the oncogenic transcriptional output in osteosarcoma. Based on this finding, focus was given to 10 SE-associated genes with distinct characteristics and potential oncogenic function. With multi-omics approaches, the hyperexpression of these genes was observed in tumor cell subclusters of patient specimens, which were consistently correlated with poor outcomes and rapid metastasis, and the majority of these identified SE-associated genes were confirmed as independent risk factors for poor outcomes. Two molecular signatures were then developed to predict survival and occurrence of lung metastasis: the SE-derived OS-signature (comprising LACTB, CEP55, SRSF3, TCF7L2, and FOXP1) and the SE-derived LMFS-signature (comprising SRSF3, TCF7L2, FOXP1, and APOLD1). Both signatures significantly improved prognostic accuracy beyond conventional clinical factors. CONCLUSIONS: Oncogenic transcription driven by SEs exhibit strong associations with osteosarcoma outcomes. The SE-derived signatures developed in this study hold promise as prognostic biomarkers for predicting OS and LMFS in patients undergoing standard treatments. Integrative prognostic models that combine conventional clinical factors with these SE-derived signatures demonstrate substantially improved accuracy, and have the potential to facilitate patient counseling and individualized management.


Sujet(s)
Tumeurs osseuses , Tumeurs du poumon , Ostéosarcome , Humains , Pronostic , Études rétrospectives , Ostéosarcome/génétique , Tumeurs du poumon/génétique , Tumeurs osseuses/génétique , Marqueurs biologiques , bêta-Lactamases , Protéines membranaires , Protéines mitochondriales , Protéines de répression , Facteurs de transcription Forkhead , Facteurs d'épissage riches en sérine-arginine
9.
Fetal Pediatr Pathol ; 43(2): 111-122, 2024.
Article de Anglais | MEDLINE | ID: mdl-38213180

RÉSUMÉ

Background: We evaluated CD30 and CD56 expression in lymphoblastic lymphoma (LBL) and correlated the results with clinicopathological features and prognosis. Methods: Immunohistochemical (IHC) staining was performed on 85 formalin-fixed paraffin-embedded LBL specimens using two CD30 clones and one CD56 antibody clone. Results: Weak and diffuse expression of CD30 was expressed in 4.7% (clone Ber-H2) or 14.1% (clone EPR4102) in LBL, while CD56 was expressed in 24.7%. CD30 and CD56 expression correlated with lactate dehydrogenase levels. CD56-positive expression was closely associated with an unfavorable prognosis. Although CD30 expression exhibited a trend toward poorer overall survival, it did not reach statistical significance. Conclusion: CD56 is a potential negative prognostic marker. These findings suggest that CD30 and CD56 targeted therapies could be potential therapeutic targets for LBL patients.


Sujet(s)
Pertinence clinique , Leucémie-lymphome lymphoblastique à précurseurs B et T , Humains , Immunohistochimie , Inclusion en paraffine , Leucémie-lymphome lymphoblastique à précurseurs B et T/diagnostic , Études rétrospectives , Antigènes CD30
11.
Am J Surg Pathol ; 48(1): 16-26, 2024 Jan 01.
Article de Anglais | MEDLINE | ID: mdl-38117285

RÉSUMÉ

Epstein-Barr virus (EBV)-positive plasma cell neoplasms (PCNs) in immunocompetent patients are a rare entity, the clinicopathological and prognostic features of which have not been well characterized. Fifteen cases of EBV-positive PCN arising in immunocompetent patients from south China were retrospectively analyzed, and an additional 44 cases from the literature were reviewed. The overall EBV-positive rate defined by EBV-encoded small RNAs (EBERs) in-situ hybridization of PCNs was 12.3% (15/122), and it was significantly higher in plasmacytoma (17.1%, 13/76) than in plasma cell myeloma/multiple myeloma (4.3%, 2/46; P=0.031). The age of the patients ranged from 17 to 79 years, with a median age of 56 years. There was a large preponderance of men, with a male-to-female ratio of 4:1. Solitary plasmacytoma of bone (23.8%, 5/21) had comparable EBV-encoded small RNAs-positive rates with extramedullary plasmacytoma arising in the upper respiratory tract (19.5%, 8/41; P=0.949). Anaplastic and classic cytologic appearance was observed in 61.5% (8/13) and 38.5% (5/13) of EBV-positive plasmacytomas, respectively. Cases with an anaplastic cytologic appearance had a significantly higher Ki-67 proliferation index than those with a classic cytologic appearance (median: 55% vs. 10%, P=0.001). In the combined cohorts, anaplastic/plasmablastic cytologic appearance was significantly more common in extramedullary plasmacytoma arising in the upper respiratory tract (72.0%, 18/25) than outside the upper respiratory tract (11.1%, 1/9; P=0.006). Among the 59 cases of EBV-positive PCN, survival data of 34 cases were available for analysis, including 30 cases of plasmacytoma and 4 cases of plasma cell myeloma/multiple myeloma. There was no statistically significant difference in overall survival between patients with EBV-positive plasmacytomas in the combined cohorts and EBV-negative plasmacytomas in the present cohort. The prevalence of EBV in PCN in immunocompetent patients varies according to histologic subtype and tumor location. Compared with EBV-negative cases, EBV-positive plasmacytomas tend to have an anaplastic/plasmablastic cytologic appearance. No significant impact of EBV infection on clinical outcomes is observed in the limited number of reported cases.


Sujet(s)
Infections à virus Epstein-Barr , Myélome multiple , Tumeurs à plasmocytes , Plasmocytome , Humains , Femelle , Mâle , Adulte d'âge moyen , Adolescent , Jeune adulte , Adulte , Sujet âgé , Herpèsvirus humain de type 4/génétique , Infections à virus Epstein-Barr/complications , Études rétrospectives , Chine/épidémiologie
12.
Rev Esp Enferm Dig ; 2023 Oct 26.
Article de Anglais | MEDLINE | ID: mdl-37882154

RÉSUMÉ

A 60-year-old man presented with a 1-month history of lacking in strength. He had a history of hepatitis B. Laboratory evaluation revealed the following: alpha fetoprotein, 7.05 ng/mL (normal level, 0-7.00 ng/mL); neuron-specific enolase, 52.20 ng/mL (normal level, 0-20.00 ng/mL). Other tumor markers were normal, including carcinoembryonic antigen and cancer antigen 199. Abdominal MR demonstrated a 1.5 cm diameter nodule and a 7.0 cm diameter mass, both with inhomogeneous hyperintensities on T2WI, fat-suppressed T2WI and diffusion weighted image. After Gd-EOB-DTPA enhancement, the small nodule showed rapid enhancement at arterial phase and washout at portal venous phase, with decrease in Gd-EOB-DTPA uptake at hepatobiliary phase. The big mass showed rim-like enhancement at arterial phase and portal venous phase, with similar decrease in Gd-EOB-DTPA uptake at hepatobiliary phase. Partial hepatectomy was performed and pathological examination of the tissues indicated that the small nodule was highly differentiated hepatocellular carcinoma. However, a gross examination of the big mass revealed grayish white solid tissue. The mass was finally diagnosed as undiferentiated pleomorphic sarcoma, with immunohistochemical results as follows: CKpn (-), Vimentin (+), Glypican3 (-), HepPar-1 (-), CK19 (-), S-100 (-), SMA (-), Desmin (-), MyoD1 (-), Myogenin (-), caldesmon (+), CD117 (-), D0 g-1 (-), CD34 (-), CD99 (+), CD68 (+), CD56 (-), CD21 (-), CD23 (-), EMA (-), S0X-10 (-), Melan-A (+), Ki67 (60%+). The patient was feeling well at 1 month of follow-up.

13.
Nat Commun ; 14(1): 6276, 2023 Oct 07.
Article de Anglais | MEDLINE | ID: mdl-37805612

RÉSUMÉ

Magnetic liquid metal (LM) soft robots attract considerable attentions because of distinctive immiscibility, deformability and maneuverability. However, conventional LM composites relying on alloying between LM and metallic magnetic powders suffer from diminished magnetism over time and potential safety risk upon leakage of metallic components. Herein, we report a strategy to composite inert and biocompatible iron oxide (Fe3O4) magnetic nanoparticles into eutectic gallium indium LM via reactive wetting mechanism. To address the intrinsic interfacial non-wettability between Fe3O4 and LM, a silver intermediate layer was introduced to fuse with indium component into AgxIny intermetallic compounds, facilitating the anchoring of Fe3O4 nanoparticles inside LM with improved magnetic stability. Subsequently, a miniature soft robot was constructed to perform various controllable deformation and locomotion behaviors under actuation of external magnetic field. Finally, practical feasibility of applying LM soft robot in an ex vivo porcine stomach was validated under in-situ monitoring by endoscope and X-ray imaging.

14.
Micromachines (Basel) ; 14(10)2023 Sep 24.
Article de Anglais | MEDLINE | ID: mdl-37893261

RÉSUMÉ

Hydrogel, a material with outstanding biocompatibility and shape deformation ability, has recently become a hot topic for researchers studying innovative functional materials due to the growth of new biomedicine. Due to their stimulus responsiveness to external environments, hydrogels have progressively evolved into "smart" responsive (such as to pH, light, electricity, magnetism, temperature, and humidity) materials in recent years. The physical and chemical properties of hydrogels have been used to construct hydrogel micro-nano robots which have demonstrated significant promise for biomedical applications. The different responsive deformation mechanisms in hydrogels are initially discussed in this study; after which, a number of preparation techniques and a variety of structural designs are introduced. This study also highlights the most recent developments in hydrogel micro-nano robots' biological applications, such as drug delivery, stem cell treatment, and cargo manipulation. On the basis of the hydrogel micro-nano robots' current state of development, current difficulties and potential future growth paths are identified.

15.
Biomaterials ; 302: 122320, 2023 11.
Article de Anglais | MEDLINE | ID: mdl-37738742

RÉSUMÉ

Treatment of acute bacterial meningitis is difficult due to the impermeability of the blood-brain barrier, greatly limiting the antibiotic concentrations that can be achieved in the brain. Escherichia coli grown in presence of iron-oxide magnetic nanoparticles secrete large amounts of magnetic outer-membrane vesicles (OMVs) in order to remove excess Fe from their cytoplasm. OMVs are fully biomimetic nanocarriers, but can be inflammatory. Here, non-inflammatory magnetic OMVs were prepared from an E. coli strain in which the synthesis of inflammatory lipid A acyltransferase was inhibited using CRISPR/Cas9 mediated gene knockout. OMVs were loaded with ceftriaxone (CRO) and meso-tetra-(4-carboxyphenyl)porphine (TCPP) and magnetically driven across the blood-brain barrier for sonodynamic treatment of bacterial meningitis. ROS-generation upon ultrasound application of CRO- and TCPP-loaded OMVs yielded similar ROS-generation as by TCPP in solution. In vitro, ROS-generation by CRO- and TCPP-loaded OMVs upon ultrasound application operated synergistically with CRO to kill a hard-to-kill, CRO-tolerant E. coli strain. In a mouse model of CRO-tolerant E. coli meningitis, CRO- and TCPP-loaded OMVs improved survival rates and clinical behavioral scores of infected mice after magnetic targeting and ultrasound application. Recurrence did not occur for at least two weeks after arresting treatment.


Sujet(s)
Antibactériens , Méningite bactérienne , Animaux , Souris , Antibactériens/pharmacologie , Antibactériens/usage thérapeutique , Escherichia coli , Espèces réactives de l'oxygène , Ceftriaxone/pharmacologie , Ceftriaxone/usage thérapeutique , Méningite bactérienne/traitement médicamenteux , Protéines de la membrane externe bactérienne
16.
Acta Biomater ; 170: 442-452, 2023 Oct 15.
Article de Anglais | MEDLINE | ID: mdl-37634834

RÉSUMÉ

It is an active research area in the development of engineered bacteria to address the bottleneck issue of hypoxic tumors, which otherwisely possess resistance to chemotherapies, radiotherapies, and photodynamic therapies. Here we report a new method to ablate hypoxic tumors with NIR-nanoantenna sensitized engineered bacteria (NASEB) in a highly effective and dual selective manner. It features engineered E. coli MG1655 (EB) with coatings of lanthanide upconversion nanoparticles (UCNPs) as external antennas on bacterial surface (MG1655/HlyE-sfGFP@UCNP@PEG), enabling NIR laser-switchable generation/secretion of HlyE perforin to kill cancer cells. We have demonstrated that NASEB enrichment on hypoxic tumor sites via their innate chemotactic tendency, in assistance of localized NIR laser irradiation, can suppress tumors with improved efficacy and selectivity, thus minimizing potential side effects in cancer treatment. The NIR-responsive nanoantenna sensitized switching in engineering bacteria is distinct from the previous reports, promising conceptually new development of therapeutics against hypoxic tumors. STATEMENT OF SIGNIFICANCE: Tumor hypoxia exacerbates tumor progression, but also reduces the efficacy of conventional chemotherapies, radiotherapies, or photodynamic therapies. Here we develop near infrared Nano Antenna Sensitized Engineered Bacteria (NASEB) to treat hypoxic tumors. NASEB can accumulate and proliferate on hypoxic tumor sites via their innate chemotactic tendency. After receiving NIR laser signals, the upconversion nanoparticles on NASEB surface as antennas can transduce them to blue light for activation of HlyE perforin in the protein factory of EB. Our method features dual selectivity on the tumor sites, contributed by hypoxic tumor homing of anaerobic bacteria and spatial confinement through selective NIR laser irradiation. The concept of NASEB promises to address the challenges of tumor hypoxia for cancer therapies.

17.
Biomater Sci ; 11(16): 5680-5693, 2023 Aug 08.
Article de Anglais | MEDLINE | ID: mdl-37439322

RÉSUMÉ

As a key pathogen of periodontitis, P. gingivalis requires support of the initial colonizing bacterium (S. gordonii preferably) to form symbiotic biofilms on gingival tissues with enhanced antibiotic resistance. Here, we report a new strategy to treat periodontitis biofilms with S. gordonii membrane-coated H2O2 self-supplied nanocomposites (ZnO2/Fe3O4@MV NPs) in a "Jenga" style. Integration of our special MV coatings enables selectively enhanced internalization of the cargos in S. gordonii, thus inducing severe damage to the foundational bacterial layer and collapse/clearance of symbiotic biofilms consequently. This strategy allows us to clear the symbiotic biofilms of S. gordonii and P. gingivalis with active hydroxyl radicals (˙OH) derived from ZnO2-Fe3O4@MV NPs in a H2O2 self-supplied, nanocatalyst-assisted manner. This "Jenga-style" treatment provides a cutting-edge proof of concept for the removal of otherwise robust symbiotic biofilms of periodontitis where the critical pathogens are difficult to target and have antibiotic resistance.


Sujet(s)
Parodontite , Oxyde de zinc , Humains , Adhérence bactérienne , Peroxyde d'hydrogène , Protéines bactériennes , Streptococcus gordonii , Parodontite/microbiologie , Biofilms
19.
Pol J Pathol ; 74(1): 42-50, 2023.
Article de Anglais | MEDLINE | ID: mdl-37306352

RÉSUMÉ

Obg-like ATPase 1 (OLA1) is a member of the Obg family of P-loop NTPases and has recently been detected in several human cancer cells. However, its expression type and clinical relevance in gastric cancer remains unclear. In the present study, mRNA level of OLA1 in gastric cancer (GC) was detected in 2 datasets downloaded from the open Gene Expression Omnibus database and 30 cancer tissues. Immunohistochemistry was performed on GC and its association with Snail in 334 GC patients. The results showed that OLA1 mRNA and protein were elevated in GC tissues. High expression of OLA1 was significantly associated with aggressive features, such as tumour size, lymph-node-metastasis and tumour-nodus-metastases stage ( p = 0.0146, p = 0.0037, p < 0.001, respectively). Moreover, high levels of OLA1 predicted worse overall survival. Multivariate Cox regression analysis indicated that high expression of OLA1 was an independent prognostic factor for poor overall survival ( p = 0.009). Additionally, OLA1 expression was positively correlated with Snail, and a combination of them revealed improved prognostic accuracy for GC patients. High expression of OLA1 predicts poor prognosis in GC patients and may be serviced as a novel target for GC.


Sujet(s)
Tumeurs de l'estomac , Humains , Adenosine triphosphatases/génétique , Pertinence clinique , Protéines G , Métastase lymphatique , ARN messager , Tumeurs de l'estomac/génétique
20.
Am J Med Sci ; 366(5): e75-e76, 2023 Nov.
Article de Anglais | MEDLINE | ID: mdl-37290743
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