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1.
Oncoimmunology ; 13(1): 2373526, 2024.
Artigo em Inglês | MEDLINE | ID: mdl-38948931

RESUMO

Prostate cancer (PCa) is characterized as a "cold tumor" with limited immune responses, rendering the tumor resistant to immune checkpoint inhibitors (ICI). Therapeutic messenger RNA (mRNA) vaccines have emerged as a promising strategy to overcome this challenge by enhancing immune reactivity and significantly boosting anti-tumor efficacy. In our study, we synthesized Tetra, an mRNA vaccine mixed with multiple tumor-associated antigens, and ImmunER, an immune-enhancing adjuvant, aiming to induce potent anti-tumor immunity. ImmunER exhibited the capacity to promote dendritic cells (DCs) maturation, enhance DCs migration, and improve antigen presentation at both cellular and animal levels. Moreover, Tetra, in combination with ImmunER, induced a transformation of bone marrow-derived dendritic cells (BMDCs) to cDC1-CCL22 and up-regulated the JAK-STAT1 pathway, promoting the release of IL-12, TNF-α, and other cytokines. This cascade led to enhanced proliferation and activation of T cells, resulting in effective killing of tumor cells. In vivo experiments further revealed that Tetra + ImmunER increased CD8+T cell infiltration and activation in RM-1-PSMA tumor tissues. In summary, our findings underscore the promising potential of the integrated Tetra and ImmunER mRNA-LNP therapy for robust anti-tumor immunity in PCa.


Assuntos
Adjuvantes Imunológicos , Antígenos de Neoplasias , Vacinas Anticâncer , Células Dendríticas , Neoplasias da Próstata , RNA Mensageiro , Animais , Masculino , Neoplasias da Próstata/imunologia , Neoplasias da Próstata/terapia , Neoplasias da Próstata/patologia , Neoplasias da Próstata/genética , Neoplasias da Próstata/tratamento farmacológico , Antígenos de Neoplasias/imunologia , Camundongos , Células Dendríticas/imunologia , Adjuvantes Imunológicos/farmacologia , Adjuvantes Imunológicos/administração & dosagem , RNA Mensageiro/genética , RNA Mensageiro/metabolismo , RNA Mensageiro/administração & dosagem , Vacinas Anticâncer/administração & dosagem , Vacinas Anticâncer/imunologia , Humanos , Camundongos Endogâmicos C57BL , Linhagem Celular Tumoral , Vacinas de mRNA , Linfócitos T CD8-Positivos/imunologia , Linfócitos T/imunologia , Linfócitos T/metabolismo , Imunoterapia/métodos , Ativação Linfocitária/efeitos dos fármacos
2.
J Agric Food Chem ; 72(26): 14620-14629, 2024 Jul 03.
Artigo em Inglês | MEDLINE | ID: mdl-38885170

RESUMO

Milk fat content is a critical indicator of milk quality. Exploring the key regulatory genes involved in milk fat synthesis is essential for enhancing milk fat content. STF-62247 (STF), a thiazolamide compound, has the potential to bind with ALG5 and upregulate lipid droplets in fat synthesis. However, the effect of STF on the process of milk fat synthesis and whether it acts through ALG5 remains unknown. In this study, the impact of ALG5 on milk fat synthesis and its underlying mechanism were investigated using bovine mammary epithelial cells (BMECs) and mouse models through real-time PCR, western blotting, Oil Red O staining, and triglyceride analysis. Experimental findings revealed a positive correlation between STF and ALG5 with the ability to synthesize milk fat. Silencing ALG5 led to decreased expression of FASN, SREBP1, and PPARγ in BMECs, as well as reduced phosphorylation levels in the PI3K/AKT/mTOR signaling pathway. Moreover, the phosphorylation levels of the PI3K/AKT/mTOR signaling pathway were restored when ALG5 silencing was followed by the addition of STF. These results suggest that STF regulates fatty acid synthesis in BMECs by affecting the PI3K/AKT/mTOR signaling pathway through ALG5. ALG5 is possibly a new factor in milk fat synthesis.


Assuntos
Células Epiteliais , Glândulas Mamárias Animais , Leite , Transdução de Sinais , Proteína de Ligação a Elemento Regulador de Esterol 1 , Serina-Treonina Quinases TOR , Animais , Serina-Treonina Quinases TOR/metabolismo , Serina-Treonina Quinases TOR/genética , Leite/química , Leite/metabolismo , Camundongos , Bovinos , Feminino , Células Epiteliais/metabolismo , Glândulas Mamárias Animais/metabolismo , Proteína de Ligação a Elemento Regulador de Esterol 1/genética , Proteína de Ligação a Elemento Regulador de Esterol 1/metabolismo , Gorduras/metabolismo , PPAR gama/metabolismo , PPAR gama/genética , Fosfatidilinositol 3-Quinases/metabolismo , Fosfatidilinositol 3-Quinases/genética , Ácidos Graxos/metabolismo , Ácido Graxo Sintase Tipo I/genética , Ácido Graxo Sintase Tipo I/metabolismo , Triglicerídeos/metabolismo
3.
ACS Appl Mater Interfaces ; 16(26): 33205-33222, 2024 Jul 03.
Artigo em Inglês | MEDLINE | ID: mdl-38915205

RESUMO

In diabetic patients with skin injuries, bacterial proliferation, accumulation of reactive oxygen species (ROS) in the tissues, and impaired angiogenesis make wound healing difficult. Therefore, eliminating bacteria, removing ROS, and promoting angiogenesis are necessary for treating acute diabetic wounds. In this study, benefiting from the ability of polyphenols to form a metal-phenolic network (MPN) with metal ions, TA-Eu MPN nanoparticles (TM NPs) were synthesized. The prepared photothermal agent CuS NPs and TM NPs were then loaded onto the supporting base and needle tips of PVA/HA (PH) microneedles, respectively, to obtain PH/CuS/TM microneedles. Antibacterial experiments showed that microneedles loaded with CuS NPs could remove bacteria by the photothermal effect. In vitro experiments showed that the microneedles could effectively scavenge ROS, inhibit macrophage polarization to the M1 type, and induce polarization to the M2 type as well as have the ability to promote vascular endothelial cell migration and angiogenesis. Furthermore, in vivo experiments showed that PH/CuS/TM microneedles accelerated wound healing by inhibiting pro-inflammatory cytokines and promoting angiogenesis in a diabetic rat wound model. Therefore, PH/CuS/TM microneedles have efficient antibacterial, ROS scavenging, anti-inflammatory, immunomodulatory, and angiogenic abilities and hold promise as wound dressings for treating acute diabetic wounds.


Assuntos
Antibacterianos , Diabetes Mellitus Experimental , Espécies Reativas de Oxigênio , Cicatrização , Cicatrização/efeitos dos fármacos , Animais , Espécies Reativas de Oxigênio/metabolismo , Ratos , Antibacterianos/farmacologia , Antibacterianos/química , Diabetes Mellitus Experimental/tratamento farmacológico , Camundongos , Neovascularização Fisiológica/efeitos dos fármacos , Agulhas , Ratos Sprague-Dawley , Humanos , Masculino , Células Endoteliais da Veia Umbilical Humana , Sequestradores de Radicais Livres/química , Sequestradores de Radicais Livres/farmacologia , Células RAW 264.7 , Angiogênese
4.
Heliyon ; 10(11): e31816, 2024 Jun 15.
Artigo em Inglês | MEDLINE | ID: mdl-38841440

RESUMO

Objective: This study aimed to delineate the clear cell renal cell carcinoma (ccRCC) intrinsic subtypes through unsupervised clustering of radiomics and transcriptomics data and to evaluate their associations with clinicopathological features, prognosis, and molecular characteristics. Methods: Using a retrospective dual-center approach, we gathered transcriptomic and clinical data from ccRCC patients registered in The Cancer Genome Atlas and contrast-enhanced computed tomography images from The Cancer Imaging Archive and local databases. Following the segmentation of images, radiomics feature extraction, and feature preprocessing, we performed unsupervised clustering based on the "CancerSubtypes" package to identify distinct radiotranscriptomic subtypes, which were then correlated with clinical-pathological, prognostic, immune, and molecular characteristics. Results: Clustering identified three subtypes, C1, C2, and C3, each of which displayed unique clinicopathological, prognostic, immune, and molecular distinctions. Notably, subtypes C1 and C3 were associated with poorer survival outcomes than subtype C2. Pathway analysis highlighted immune pathway activation in C1 and metabolic pathway prominence in C2. Gene mutation analysis identified VHL and PBRM1 as the most commonly mutated genes, with more mutated genes observed in the C3 subtype. Despite similar tumor mutation burdens, microsatellite instability, and RNA interference across subtypes, C1 and C3 demonstrated greater tumor immune dysfunction and rejection. In the validation cohort, the various subtypes showed comparable results in terms of clinicopathological features and prognosis to those observed in the training cohort, thus confirming the efficacy of our algorithm. Conclusion: Unsupervised clustering based on radiotranscriptomics can identify the intrinsic subtypes of ccRCC, and radiotranscriptomic subtypes can characterize the prognosis and molecular features of tumors, enabling noninvasive tumor risk stratification.

5.
Eur J Haematol ; 2024 Jun 07.
Artigo em Inglês | MEDLINE | ID: mdl-38847134

RESUMO

BACKGROUND: IKZF1 deletion (IKZF1del) is associated with poor prognosis in B-cell precursor acute lymphoblastic leukemia (BCP-ALL). But the prognosis of IKZF1del combined with other prognostic stratification factors remains unclear. Whether intensified treatment improves BCP-ALL prognosis has not been determined. METHODS: A retrospective analysis was performed on 1291 pediatric patients diagnosed with BCP-ALL and treated with the South China Children's Leukemia 2016 protocol. Patients were stratified based on IKZF1 status for comparison of characteristics and outcome. Additionally, IKZF1del patients were further divided based on chemotherapy intensity for outcome assessments. RESULTS: The BCP-ALL pediatric patients with IKZF1del in south China showed poorer early response. Notably, the DFS and OS for IKZF1del patients were markedly lower than IKZF1wt group (3-year DFS: 88.7% [95% CI: 83.4%-94.0%] vs. 93.5% [95% CI: 92.0%-94.9%], P = .021; 3-year OS: 90.7% [95% CI: 85.8% to 95.6%] vs. 96.1% [95% CI: 95% to 97.2%, P = .003]), with a concurrent increase in 3-year TRM (6.4% [95% CI: 2.3%-10.5%] vs. 2.9% [95% CI: 1.9%-3.8%], P = .025). However, the 3-year CIR was comparable between the two groups (5.7% [95% CI: 1.8%-9.5%] vs. 3.7% [95% CI: 2.6%-4.7%], P = .138). Subgroup analyses reveal no factor significantly influenced the prognosis of the IKZF1del cohort. Noteworthy, intensive chemotherapy improved DFS from 85.7% ± 4.1% to 94.1% ± 0.7% in IKZF1del group (P = .084). Particularly in BCR::ABL positive subgroup, the 3-year DFS was remarkably improved from 53.6% ± 20.1% with non-intensive chemotherapy to 100% with intensive chemotherapy (P = .026). CONCLUSIONS: Pediatric BCP-ALL patients with IKZF1del in South China manifest poor outcomes without independent prognostic significance. While no factor substantially alters the prognosis in the IKZF1del group. Intensified chemotherapy may reduce relapse rates and improve DFS in patients with IKZF1del subset, particularly in IKZFdel patients with BCR::ABL positive.

6.
Front Neurol ; 15: 1344324, 2024.
Artigo em Inglês | MEDLINE | ID: mdl-38872826

RESUMO

Objective: To construct radiomics models based on MRI at different time points for the early prediction of cystic brain radionecrosis (CBRN) for nasopharyngeal carcinoma (NPC). Methods: A total of 202 injured temporal lobes from 155 NPC patients with radiotherapy-induced temporal lobe injury (RTLI) after intensity modulated radiotherapy (IMRT) were included in the study. All the injured lobes were randomly divided into the training (n = 143) and validation (n = 59) sets. Radiomics models were constructed by using features extracted from T2WI at two different time points: at the end of IMRT (post-IMRT) and the first-detected RTLI (first-RTLI). A delta-radiomics feature was defined as the percentage change in a radiomics feature from post-IMRT to first-RTLI. The radiomics nomogram was constructed by combining clinical risk factors and radiomics signatures using multivariate logistic regression analysis. Predictive performance was evaluated using area under the curve (AUC) from receiver operating characteristic analysis and decision curve analysis (DCA). Results: The post-IMRT, first-RTLI, and delta-radiomics models yielded AUC values of 0.84 (95% CI: 0.76-0.92), 0.86 (95% CI: 0.78-0.94), and 0.77 (95% CI: 0.67-0.87), respectively. The nomogram exhibited the highest AUC of 0.91 (95% CI: 0.85-0.97) and sensitivity of 0.82 compared to any single radiomics model. From the DCA, the nomogram model provided more clinical benefit than the radiomics models or clinical model. Conclusion: The radiomics nomogram model combining clinical factors and radiomics signatures based on MRI at different time points after radiotherapy showed excellent prediction potential for CBRN in patients with NPC.

7.
Front Microbiol ; 15: 1349305, 2024.
Artigo em Inglês | MEDLINE | ID: mdl-38887707

RESUMO

Intercropping systems can improve soil fertility and health, however, soil microbial communities and functional genes related to carbon, nitrogen and phosphorus cycling under the intercropping system of mesquite and perilla have not been studied. Therefore, in the present study, different planting densities and varieties of Perilla frutescens (L.) Britt and kiwifruit were used for intercropping, and changes in soil microbial communities and carbon, nitrogen, and phosphorus cycling genes in kiwifruit inter-roots under inter-cropping conditions were investigated by macro-genome sequencing technology. The results showed that intercropping with Perill caused a decrease in most soil nutrients, soil enzyme activities, and had a significant impact on the microbial (bacteria and fungi) diversity. Inter-cropping increased the relative abundance of the dominant bacterial phylum "Proteobacteria" and "Actinobacteria" by 47 and 57%, respectively, but decreased the relative abundance of the dominant fungal phylum "Chordata" and "Streptophyta" by 11 and 20%, respectively, in the inter-root soil of kiwifruit, and had a significant impact on the microbial (bacteria and fungi) diversity. In addition, inter-cropping could greatly increase the inter-root soil carbon sequestration (PccA, korA/B/C/D, fhs, and rbcl/s), carbon degradation (abfD), organic nitrogen mineralization (GDH2), denitrification (napA/B, nirB, norB), organic phosphorus mineralization (phop, phn), and inorganic phosphorus solubilization (gcd, ppk) gene abundance. The gene co-occurrence network indicated that soil korB, nirB, and gnd key functional genes for carbon, nitrogen, and phosphorus cycling in kiwifruit inter-root soils and their expression was up-regulated in the inter-cropping group. Structural equation (SEM) further showed that soil total nitrogen, organic matter, total carbon and acid phosphatase had significant effects on microbial diversity (p < 0.05) and soil carbon cycling gene korB and phosphorus cycling gene purH (p < 0.001), while korB and purH had positive effects on kiwifruit quality. In conclusion, intercropping perilla in kiwifruit orchards changed the structure of bacterial and fungal communities in the inter-root soil of kiwifruit, but I believe that intercropping perilla stimulates carbon degradation, leading to carbon emission and serious loss of soil nutrients, and that prolonged intercropping may adversely affect the quality of kiwifruit, and thus its limitations should be noted in future studies.

8.
J Ultrasound ; 2024 Jun 21.
Artigo em Inglês | MEDLINE | ID: mdl-38904735

RESUMO

PURPOSE: This is an extremely rare case of complicated fetal esophageal atresia (EA) with tracheoesophageal fistula (TEF) and interrupted inferior vena cava (IVC) diagnosed by prenatal ultrsonography and successfully treated with surgical repair. METHODS: A 35-year-old pregnant woman was referred to our center for prenatal ultrasound, and the fetus was found to have a series of abnormalities, such as an interrupted IVC associated with a dilated azygos vein, an upper neck pouch sign of the thorax, and polyhydramnios. With suspicion of EA with TEF and interrupted IVC, the infant was born at 39 weeks of gestation, and successfully underwent the surgical operation. RESULTS: The baby was doing well after 21 months of follow-up. CONCLUSION: It is beneficial for the prenatal ultrasonic diagnosis of EA with TEF in optimizing labor care, postpartum treatment, and prompting neonatal management.

9.
Sci Rep ; 14(1): 12826, 2024 06 04.
Artigo em Inglês | MEDLINE | ID: mdl-38834813

RESUMO

Lamin A/C gene (LMNA) mutations contribute to severe striated muscle laminopathies, affecting cardiac and skeletal muscles, with limited treatment options. In this study, we delve into the investigations of five distinct LMNA mutations, including three novel variants and two pathogenic variants identified in patients with muscular laminopathy. Our approach employs zebrafish models to comprehensively study these variants. Transgenic zebrafish expressing wild-type LMNA and each mutation undergo extensive morphological profiling, swimming behavior assessments, muscle endurance evaluations, heartbeat measurement, and histopathological analysis of skeletal muscles. Additionally, these models serve as platform for focused drug screening. We explore the transcriptomic landscape through qPCR and RNAseq to unveil altered gene expression profiles in muscle tissues. Larvae of LMNA(L35P), LMNA(E358K), and LMNA(R453W) transgenic fish exhibit reduced swim speed compared to LMNA(WT) measured by DanioVision. All LMNA transgenic adult fish exhibit reduced swim speed compared to LMNA(WT) in T-maze. Moreover, all LMNA transgenic adult fish, except LMNA(E358K), display weaker muscle endurance than LMNA(WT) measured by swimming tunnel. Histochemical staining reveals decreased fiber size in all LMNA mutations transgenic fish, excluding LMNA(WT) fish. Interestingly, LMNA(A539V) and LMNA(E358K) exhibited elevated heartbeats. We recognize potential limitations with transgene overexpression and conducted association calculations to explore its effects on zebrafish phenotypes. Our results suggest lamin A/C overexpression may not directly impact mutant phenotypes, such as impaired swim speed, increased heart rates, or decreased muscle fiber diameter. Utilizing LMNA zebrafish models for drug screening, we identify L-carnitine treatment rescuing muscle endurance in LMNA(L35P) and creatine treatment reversing muscle endurance in LMNA(R453W) zebrafish models. Creatine activates AMPK and mTOR pathways, improving muscle endurance and swim speed in LMNA(R453W) fish. Transcriptomic profiling reveals upstream regulators and affected genes contributing to motor dysfunction, cardiac anomalies, and ion flux dysregulation in LMNA mutant transgenic fish. These findings faithfully mimic clinical manifestations of muscular laminopathies, including dysmorphism, early mortality, decreased fiber size, and muscle dysfunction in zebrafish. Furthermore, our drug screening results suggest L-carnitine and creatine treatments as potential rescuers of muscle endurance in LMNA(L35P) and LMNA(R453W) zebrafish models. Our study offers valuable insights into the future development of potential treatments for LMNA-related muscular laminopathy.


Assuntos
Animais Geneticamente Modificados , Carnitina , Creatina , Lamina Tipo A , Músculo Esquelético , Mutação , Peixe-Zebra , Animais , Lamina Tipo A/genética , Lamina Tipo A/metabolismo , Músculo Esquelético/metabolismo , Músculo Esquelético/patologia , Músculo Esquelético/efeitos dos fármacos , Creatina/metabolismo , Carnitina/metabolismo , Modelos Animais de Doenças , Laminopatias/genética , Laminopatias/metabolismo , Natação , Transcriptoma , Humanos
10.
PhytoKeys ; 243: 9-14, 2024.
Artigo em Inglês | MEDLINE | ID: mdl-38912087

RESUMO

Based on a critical examination of type specimens, images of living plants, and the literature has shown Rhododendronoligocarpum to be conspecific with R.leishanicum. Although slight variations in corolla colour exist amongst different populations of R.oligocarpum, it does not serve as a key distinguishing trait. Therefore, we reduced R.oligocarpum to a synonym of R.leishanicum, and recommend placing it in Subsection Maculifera.

11.
Int Immunopharmacol ; 137: 112428, 2024 Jun 21.
Artigo em Inglês | MEDLINE | ID: mdl-38908077

RESUMO

Herpes simplex keratitis (HSK) is a blinding disease caused by herpes simplex virus type 1 (HSV-1) infection, and rapid eradication of the virus from the affected cornea is imperative. Nod-like receptors (NLRs) are intracellular innate immune sensors closely associated with cell death, inflammation and immune responses. In this study, we investigated the role of NLRP12 in the antiviral immunology in HSK and the underlying mechanisms. We found that NLRP12 expression was significantly decreased in HSV-1-infected human corneal epithelial cells (HCE-Ts) and HSK mouse corneas. Overexpression of NLRP12 significantly reduced viral replication in infected HCE-Ts and functioned through inflammasome-mediated pyroptosis and downstream IL-18-IFN-γ axis. In HSK mouse models, overexpression of NLRP12 reduced viral replication in the cornea and alleviated HSK symptoms. This resulted from enhanced antiviral immune responses including the activation of specific immune cells in both the cornea and the draining lymph nodes. Specifically, the NLRP12-IL-18-IFN-γ axis regulated the interaction between infected corneal epithelial cells and macrophages. In conclusion, our study identified a role of NLRP12 in mediating pyroptosis and regulating antiviral immune responses. This novel finding opens the possibilities of NLRP12 as a viable target in the therapeutic strategies for HSV-1 infection.

12.
Emerg Microbes Infect ; 13(1): 2366359, 2024 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-38855910

RESUMO

Tuberculosis (TB) remains a leading cause of mortality among individuals coinfected with HIV, characterized by progressive pulmonary inflammation. Despite TB's hallmark being focal granulomatous lung lesions, our understanding of the histopathological features and regulation of inflammation in HIV & TB coinfection remains incomplete. In this study, we aimed to elucidate these histopathological features through an immunohistochemistry analysis of HIV & TB co-infected and TB patients, revealing marked differences. Notably, HIV & TB granulomas exhibited aggregation of CD68 + macrophage (Mφ), while TB lesions predominantly featured aggregation of CD20+ B cells, highlighting distinct immune responses in coinfection. Spatial transcriptome profiling further elucidated CD68+ Mφ aggregation in HIV & TB, accompanied by activation of IL6 pathway, potentially exacerbating inflammation. Through multiplex immunostaining, we validated two granuloma types in HIV & TB versus three in TB, distinguished by cell architecture. Remarkably, in the two types of HIV & TB granulomas, CD68 + Mφ highly co-expressed IL6R/pSTAT3, contrasting TB granulomas' high IFNGRA/SOCS3 expression, indicating different signaling pathways at play. Thus, activation of IL6 pathway may intensify inflammation in HIV & TB-lungs, while SOCS3-enriched immune microenvironment suppresses IL6-induced over-inflammation in TB. These findings provide crucial insights into HIV & TB granuloma formation, shedding light on potential therapeutic targets, particularly for granulomatous pulmonary under HIV & TB co-infection. Our study emphasizes the importance of a comprehensive understanding of the immunopathogenesis of HIV & TB coinfection and suggests potential avenues for targeting IL6 signaling with SOCS3 activators or anti-IL6R agents to mitigate lung inflammation in HIV & TB coinfected individuals.


Assuntos
Coinfecção , Granuloma , Infecções por HIV , Pulmão , Macrófagos , Receptores de Interleucina-6 , Fator de Transcrição STAT3 , Humanos , Coinfecção/virologia , Coinfecção/imunologia , Coinfecção/microbiologia , Infecções por HIV/complicações , Infecções por HIV/imunologia , Macrófagos/imunologia , Fator de Transcrição STAT3/metabolismo , Fator de Transcrição STAT3/genética , Granuloma/imunologia , Pulmão/patologia , Pulmão/imunologia , Receptores de Interleucina-6/metabolismo , Receptores de Interleucina-6/genética , Proteína 3 Supressora da Sinalização de Citocinas/metabolismo , Proteína 3 Supressora da Sinalização de Citocinas/genética , Antígenos de Diferenciação Mielomonocítica/metabolismo , Antígenos de Diferenciação Mielomonocítica/genética , Antígenos CD/metabolismo , Antígenos CD/genética , Transdução de Sinais , Tuberculose Pulmonar/imunologia , Tuberculose Pulmonar/complicações , Masculino , Tuberculose/imunologia , Tuberculose/microbiologia , Tuberculose/complicações , Feminino , Adulto , Interleucina-6/metabolismo , Interleucina-6/genética , Molécula CD68
13.
Aging Cell ; : e14244, 2024 Jun 14.
Artigo em Inglês | MEDLINE | ID: mdl-38874013

RESUMO

Moderate physical training has been shown to hinder age-related memory decline. While the benefits of physical training on hippocampal memory function are well-documented, little is known about its impact on working memory, which is linked to the prelimbic cortex (PrL), one major subdivision of the prefrontal cortex. Here, we examined the effects of physical training on spatial working memory in a well-established animal model of physical training, starting at 16 months of age and continuing for 5 months (running wheel 1 h/day and 5 days/week). This training strategy improved spatial working memory in aged mice (22-month-old), which was accompanied by an increased spine density and a lower TAF15 expression in the PrL. Specifically, physical training affected both thin and mushroom-type spines on PrL pyramidal cells, and prevented age-related loss of spines on selective segments of apical dendritic branches. Correlation analysis revealed that increased TAF15-expression was detrimental to the dendritic spines. However, physical training downregulated TAF15 expression in the PrL, preserving the dendritic spines on PrL pyramidal cells and improving working memory in trained aged mice. When TAF15 was overexpressed in the PrL via a viral approach, the benefits of physical training on the dendritic spines and working memory were abolished. These data suggest that physical training at a moderate pace might downregulate TAF15 expression in the PrL, which favors the dendritic spines on PrL pyramidal cells, thereby improving spatial working memory.

14.
Biomed Eng Online ; 23(1): 56, 2024 Jun 18.
Artigo em Inglês | MEDLINE | ID: mdl-38890695

RESUMO

OBJECTIVES: This study was designed to explore and validate the value of different machine learning models based on ultrasound image-omics features in the preoperative diagnosis of lymph node metastasis in pancreatic cancer (PC). METHODS: This research involved 189 individuals diagnosed with PC confirmed by surgical pathology (training cohort: n = 151; test cohort: n = 38), including 50 cases of lymph node metastasis. Image-omics features were extracted from ultrasound images. After dimensionality reduction and screening, eight machine learning algorithms, including logistic regression (LR), support vector machine (SVM), K-nearest neighbors (KNN), random forest (RF), extra trees (ET), extreme gradient boosting (XGBoost), light gradient boosting machine (LightGBM), and multilayer perceptron (MLP), were used to establish image-omics models to predict lymph node metastasis in PC. The best omics prediction model was selected through ROC curve analysis. Machine learning models were used to analyze clinical features and determine variables to establish a clinical model. A combined model was constructed by combining ultrasound image-omics and clinical features. Decision curve analysis (DCA) and a nomogram were used to evaluate the clinical application value of the model. RESULTS: A total of 1561 image-omics features were extracted from ultrasound images. 15 valuable image-omics features were determined by regularization, dimension reduction, and algorithm selection. In the image-omics model, the LR model showed higher prediction efficiency and robustness, with an area under the ROC curve (AUC) of 0.773 in the training set and an AUC of 0.850 in the test set. The clinical model constructed by the boundary of lesions in ultrasound images and the clinical feature CA199 (AUC = 0.875). The combined model had the best prediction performance, with an AUC of 0.872 in the training set and 0.918 in the test set. The combined model showed better clinical benefit according to DCA, and the nomogram score provided clinical prediction solutions. CONCLUSION: The combined model established with clinical features has good diagnostic ability and can be used to predict lymph node metastasis in patients with PC. It is expected to provide an effective noninvasive method for clinical decision-making, thereby improving the diagnosis and treatment of PC.


Assuntos
Metástase Linfática , Aprendizado de Máquina , Neoplasias Pancreáticas , Ultrassonografia , Humanos , Neoplasias Pancreáticas/diagnóstico por imagem , Neoplasias Pancreáticas/patologia , Metástase Linfática/diagnóstico por imagem , Masculino , Pessoa de Meia-Idade , Feminino , Idoso , Processamento de Imagem Assistida por Computador/métodos , Adulto
15.
Br J Haematol ; 2024 Jun 24.
Artigo em Inglês | MEDLINE | ID: mdl-38924065

RESUMO

The global pandemic has resulted in the common occurrence of SARS-CoV-2 infection in the population. In the post-pandemic era, it is imperative to understand the influence of donor SARS-CoV-2 infection on outcomes after allogeneic haematopoietic stem cell transplantation (allo-HSCT). We retrospectively analysed allo-HSCTs from donors with mild SARS-CoV-2 infection or early recovery stage (ERS) (group 1, n = 65) and late recovery stage (group 2, n = 120). Additionally, we included allo-HSCT from donors without prior SARS-CoV-2 infection as group 0 (n = 194). Transplants from donors with different SARS-CoV-2 infection status had comparable primary engraftment and survival rates. However, group 1 had higher incidences of acute graft-versus-host disease (aGvHD), grade II-IV (41.5% vs. 28.1% in group 0 [p = 0.014] and 30.6% in group 2 [p = 0.067]) and grade III-IV (22.2% vs. 9.6% [p = 0.004] in group 0 and 12.2% in group 2 [p = 0.049]). Conversely, the risk of aGvHD in group 2 was similar to that in group 0 (p > 0.5). Multivariable analysis identified group 1 associated with grade II-IV (hazard ratio [HR] 2.307, p = 0.010) and grade III-IV (HR 2.962, p = 0.001) aGvHD, which yielded no significant risk factors for survival. In conclusion, we preliminarily demonstrated donors in the active infection state or ERS of mild SARS-CoV-2 infection were associated with higher incidences of aGvHD in transplants from related donors.

16.
Molecules ; 29(10)2024 May 11.
Artigo em Inglês | MEDLINE | ID: mdl-38792130

RESUMO

Lycium ruthenicum Murray possesses significant applications in both food and medicine, including antioxidative, anti-tumor, anti-fatigue, anti-inflammatory, and various other effects. Consequently, there has been a surge in research endeavors dedicated to exploring its potential benefits, necessitating the organization and synthesis of these findings. This article systematically reviews the extraction and content determination methods of active substances such as polysaccharides, anthocyanins, flavonoids, and polyphenols in LRM in the past five years, as well as some active ingredient composition determination methods, biological activities, and product development. This review is divided into three main parts: extraction and determination methods, their bioactivity, and product development. Building upon prior research, we also delve into the economic and medicinal value of Lycium ruthenicum Murray, thereby contributing significantly to its further exploration and development. It is anticipated that this comprehensive review will serve as a valuable resource for advancing research on Lycium ruthenicum Murray.


Assuntos
Lycium , Extratos Vegetais , Lycium/química , Extratos Vegetais/química , Antocianinas/química , Humanos , Flavonoides/química , Antioxidantes/química , Antioxidantes/farmacologia , Polifenóis/química , Compostos Fitoquímicos/química , Compostos Fitoquímicos/farmacologia , Polissacarídeos/química
17.
Cell Rep Med ; 5(5): 101551, 2024 May 21.
Artigo em Inglês | MEDLINE | ID: mdl-38697104

RESUMO

Accurate diagnosis and prognosis prediction are conducive to early intervention and improvement of medical care for natural killer/T cell lymphoma (NKTCL). Artificial intelligence (AI)-based systems are developed based on nasopharynx magnetic resonance imaging. The diagnostic systems achieve areas under the curve of 0.905-0.960 in detecting malignant nasopharyngeal lesions and distinguishing NKTCL from nasopharyngeal carcinoma in independent validation datasets. In comparison to human radiologists, the diagnostic systems show higher accuracies than resident radiologists and comparable ones to senior radiologists. The prognostic system shows promising performance in predicting survival outcomes of NKTCL and outperforms several clinical models. For patients with early-stage NKTCL, only the high-risk group benefits from early radiotherapy (hazard ratio = 0.414 vs. late radiotherapy; 95% confidence interval, 0.190-0.900, p = 0.022), while progression-free survival does not differ in the low-risk group. In conclusion, AI-based systems show potential in assisting accurate diagnosis and prognosis prediction and may contribute to therapeutic optimization for NKTCL.


Assuntos
Inteligência Artificial , Imageamento por Ressonância Magnética , Humanos , Prognóstico , Imageamento por Ressonância Magnética/métodos , Masculino , Feminino , Pessoa de Meia-Idade , Adulto , Linfoma Extranodal de Células T-NK/diagnóstico por imagem , Linfoma Extranodal de Células T-NK/patologia , Linfoma Extranodal de Células T-NK/mortalidade , Linfoma Extranodal de Células T-NK/diagnóstico , Idoso
18.
Materials (Basel) ; 17(9)2024 May 02.
Artigo em Inglês | MEDLINE | ID: mdl-38730945

RESUMO

Environmental pollution and energy crises have garnered global attention. The substantial discharge of organic waste into water bodies has led to profound environmental contamination. Photocatalytic fuel cells (PFCs) enabling the simultaneous removal of refractory contaminants and recovery of the chemical energy contained in organic pollutants provides a potential strategy to solve environmental issues and the energy crisis. This review will discuss the fundamentals, working principle, and configuration development of PFCs and photocatalytic microbial fuel cells (PMFCs). We particularly focus on the strategies for improving the wastewater treatment performance of PFCs/PMFCs in terms of coupled advanced oxidation processes, the rational design of high-efficiency electrodes, and the strengthening of the mass transfer process. The significant potential of PFCs/PMFCs in various fields is further discussed in detail. This review is intended to provide some guidance for the better implementation and widespread adoption of PFC wastewater treatment technologies.

19.
Int J Hyperthermia ; 41(1): 2353309, 2024.
Artigo em Inglês | MEDLINE | ID: mdl-38749506

RESUMO

OBJECTIVE: Incomplete thermal ablation (ITA) fosters the malignancy of residual cells in Hepatocellular carcinoma (HCC) with unclear mechanisms now. This study aims to investigate the expression changes of NDST2 following ITA of HCC and its impact on residual cancer cells. METHODS: An in vitro model of heat stress-induced liver cancer was constructed to measure the expression of NDST2 using Quantitative Real-Time PCR and Western blotting experiments. The sequencing data from nude mice were used for validation. The clinical significance of NDST2 in HCC was evaluated by integrating datasets. Gene ontology and pathway analysis were conducted to explore the potential signaling pathways regulated by NDST2. Additionally, NDST2 was knocked down in heat stress-induced HCC cells, and the effects of NDST2 on these cells were verified using Cell Counting Kit-8 assays, scratch assays, and Transwell assays. RESULTS: NDST2 expression levels are elevated in HCC, leading to a decrease in overall survival rates of HCC patients. Upregulation of immune checkpoint levels in high NDST2-expressing HCC may contribute to immune evasion by liver cancer cells. Additionally, the low mutation rate of NDST2 in HCC suggests a relatively stable expression of NDST2 in this disease. Importantly, animal and cell models treated with ITA demonstrate upregulated expression of NDST2. Knockdown of NDST2 in heat stress-induced liver cancer cells results in growth inhibition associated with gene downregulation. CONCLUSION: The upregulation of NDST2 can accelerate the progression of residual HCC after ITA, suggesting a potential role for NDST2 in the therapeutic efficacy and prognosis of residual HCC.


Assuntos
Carcinoma Hepatocelular , Neoplasias Hepáticas , Carcinoma Hepatocelular/patologia , Carcinoma Hepatocelular/genética , Carcinoma Hepatocelular/metabolismo , Neoplasias Hepáticas/patologia , Neoplasias Hepáticas/genética , Neoplasias Hepáticas/metabolismo , Humanos , Camundongos , Animais , Camundongos Nus , Linhagem Celular Tumoral
20.
Odontology ; 2024 May 08.
Artigo em Inglês | MEDLINE | ID: mdl-38717525

RESUMO

The purpose of this study was to analyze the biomechanical properties of implants made of different materials to replace missing teeth by using three-dimensional finite element analysis and provide a theoretic basis for clinical application. CBCT data was imported into the Mimics and 3-Matic to construct the three-dimensional finite element model of a missing tooth restored by an implant. Then, the model was imported into the Marc Mentat. Based on the variations of the implant materials (titanium, titanium-zirconia, zirconia and poly (ether-ether-ketone) (PEEK)) and bone densities (high and low), a total of eight models were created. An axial load of 150 N was applied to the crown of the implant to simulate the actual occlusal situation. Both the maximum values of stresses in the cortical bone and implant were observed in the Zr-low model. The maximum displacements of the implants were also within the normal range except for the PEEK models. The cancellous bone strains were mainly distributed in the apical area of the implant, and the maximum value (3225 µstrain) was found in PEEK-low model. Under the premise of the same implant material, the relevant data from various indices in low-density bone models were larger than that in high-density bone models. From the biomechanical point of view, zirconia, titanium and titanium-zirconia were all acceptable implant materials for replacing missing teeth and possessed excellent mechanical properties, while the application of PEEK material needs to be further optimized and modified.

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