RESUMEN
By integrating magnetic resonance-visible components with scaffold materials, hydrogel microspheres (HMs) become visible under magnetic resonance imaging(MRI), allowing for non-invasive, continuous, and dynamic monitoring of the distribution, degradation, and relationship of the HMs with local tissues. However, when these visualization components are physically blended into the HMs, it reduces their relaxation rate and specificity under MRI, weakening the efficacy of real-time dynamic monitoring. To achieve MRI-guided in vivo monitoring of HMs with tissue repair functionality, we utilized airflow control and photo-crosslinking methods to prepare alginate-gelatin-based dual-network hydrogel microspheres (G-AlgMA HMs) using gadolinium ions (Gd (III)), a paramagnetic MRI contrast agent, as the crosslinker. When the network of G-AlgMA HMs degrades, the cleavage of covalent bonds causes the release of Gd (III), continuously altering the arrangement and movement characteristics of surrounding water molecules. This change in local transverse and longitudinal relaxation times results in variations in MRI signal values, thus enabling MRI-guided in vivo monitoring of the HMs. Additionally, in vivo data show that the degradation and release of polypeptide (K2 (SL)6 K2 (KK)) from G-AlgMA HMs promote local vascular regeneration and soft tissue repair. Overall, G-AlgMA HMs enable non-invasive, dynamic in vivo monitoring of biomaterial degradation and tissue regeneration through MRI, which is significant for understanding material degradation mechanisms, evaluating biocompatibility, and optimizing material design.
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Alginatos , Medios de Contraste , Gadolinio , Hidrogeles , Imagen por Resonancia Magnética , Microesferas , Imagen por Resonancia Magnética/métodos , Gadolinio/química , Animales , Alginatos/química , Hidrogeles/química , Medios de Contraste/química , Cicatrización de Heridas/efectos de los fármacos , Reactivos de Enlaces Cruzados/química , Gelatina/química , Ratones , Andamios del Tejido/químicaRESUMEN
OBJECTIVES: This study aimed to investigate the expression and biological significance of Semenogelin 1 (SEMG1), a member of the cancer-testis antigen family, in oral squamous cell carcinoma (OSCC). Further, we explored its potential association with metabolism-related molecules. METHODS: SEMG1 expression levels in OSCC were determined through immunohistochemistry, flow cytometry, and Western blot analyses. To decipher the biological implications of SEMG1 in OSCC, the CAL27 OSCC cell line was either stably overexpressed with SEMG1 or subjected to SEMG1-shRNA knockdown. The relationship between clinicopathological parameters and SEMG1 expression in OSCC patients was also assessed. RESULTS: SEMG1 was found to be overexpressed in OSCC, though its expression was not influenced by the pathological grade. The fluorescent dihydroethidium assay indicated that SEMG1 augmented reactive oxygen species production. The mitochondrial membrane potential assay suggested a significant upregulation of mitochondrial membrane potential by SEMG1. Cell cycle assessments highlighted that SEMG1 overexpression led to a notable rise in cells entering the S-phase. Additionally, a strong correlation between SEMG1 expression and both ENO1 and PKM2 expression in OSCC was observed. CONCLUSIONS: The findings underscore the elevated expression of SEMG1 in OSCC and its contributory role in the tumorigenesis of OSCC patients.
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Recruitment and accumulation of reactive astrocytes around senile plaques are common pathological features of Alzheimer's disease (AD), with unclear mechanisms. Chemerin, an adipokine implicated in neuroinflammation, acts through its receptor, chemokine-like receptor 1 (CMKLR1), which also functions as a receptor for amyloid ß (Aß). The impact of the chemerin/CMKLR1 axis on astrocyte migration towards Aß plaques is unknown. Here we investigated the effect of CMKLR1 on astrocyte migration around Aß deposition in APP/PS1 mice with Cmklr1 knockout (APP/PS1-Cmklr1-/-). CMKLR1-expressed astrocytes were upregulated in the cortices and hippocampi of 9-month-old APP/PS1 mice. Chemerin mainly co-localized with neurons, and its expression was reduced in the brains of APP/PS1 mice, compared to WT mice. CMKLR1 deficiency decreased astrocyte colocalization with Aß plaques in APP/PS1-Cmklr1-/- mice, compared to APP/PS1 mice. Activation of the chemerin/CMKLR1 axis promoted the migration of primary cultured astrocytes and U251 cells, and reduced astrocyte clustering induced by Aß42. Mechanistic studies revealed that chemerin/CMKLR1 activation induced STING phosphorylation. Deletion of STING attenuated the promotion of the chemerin/CMKLR1 axis relative to astrocyte migration and abolished the inhibitory effect of chemerin on Aß42-induced astrocyte clustering. These findings suggest the involvement of the chemerin/CMKLR1/STING pathway in the regulation of astrocyte migration and recruitment to Aß plaques/Aß42.
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Enfermedad de Alzheimer , Astrocitos , Quimiocinas , Péptidos y Proteínas de Señalización Intercelular , Placa Amiloide , Receptores de Quimiocina , Animales , Astrocitos/metabolismo , Quimiocinas/metabolismo , Péptidos y Proteínas de Señalización Intercelular/metabolismo , Péptidos y Proteínas de Señalización Intercelular/genética , Ratones , Receptores de Quimiocina/metabolismo , Receptores de Quimiocina/genética , Placa Amiloide/metabolismo , Placa Amiloide/patología , Enfermedad de Alzheimer/metabolismo , Enfermedad de Alzheimer/genética , Enfermedad de Alzheimer/patología , Humanos , Péptidos beta-Amiloides/metabolismo , Ratones Noqueados , Movimiento Celular , Transducción de Señal , Ratones Transgénicos , Ratones Endogámicos C57BLRESUMEN
In the past 40 years, the gradually increasing incidence and mortality rates of malignant tumors have severely impacted the quality of life of patients, bringing significant physical and psychological burdens and becoming an increasingly serious social issue. With the development of medical standards, new methods for cancer detection and treatment have been continuously proposed. Although it has been proven that cancer is related to increased psychological burden and suicidal behaviors in patients, current research on the psychological burden caused by cancer is insufficient. Clinicians often overlook the psychological health issues of patients while treating their physical diseases. Considering the high incidence of cancer, this review will outline the psychological burdens of cancer patients worldwide in recent years and its high-risk factors. Moreover, this review will summarize the common methods for evaluating psychological burdens, present current predictive models and treatment methods for the psychological burden of cancer patients, aiming to provide a research basis and future direction for the timely and accurate assessment of the psychological burden in cancer patients.
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Probiotics offer numerous beneficial functions for human bodies, while the low survival rate under gastric acid and short retention time in the intestine are the major obstacles to their utilization. To address these issues, we designed a novel dual-network hydrogel microsphere that combines gastric acid resistance with enhanced mucoadhesion, aiming for the targeted delivery of probiotics. Thiolated oxidized guar gum (SOGG) was disulfide-linked to form the first network, and sodium alginate (SA) was cross-linked with Ca2+ to form the second network. Under the protection of the interpenetrating dual network microspheres, a much higher viability of Lactobacillus rhamnosus (LGG) (8.73 log CFU/mL) was achieved in simulated gastric fluid, compared to the zero-survival rate of free LGG. Mucoadhesion tests showed that the adhesion rate of SOGG/SA microspheres to the intestinal mucosa was 1.75 times higher than that of thiol-free microspheres. In vivo studies revealed that LGG-loaded microspheres significantly enhanced intestinal barrier function, remodeled the gut microbiome, and alleviated DSS-induced colitis in mice. Overall, SOGG/SA microspheres provide an effective strategy to the challenges of probiotic reduction in the stomach and rapid expulsion from the intestines, enhancing their health benefits.
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Alginatos , Galactanos , Ácido Gástrico , Lacticaseibacillus rhamnosus , Mananos , Microesferas , Gomas de Plantas , Probióticos , Alginatos/química , Alginatos/farmacología , Probióticos/administración & dosificación , Mananos/química , Mananos/farmacología , Gomas de Plantas/química , Galactanos/química , Galactanos/farmacología , Animales , Ratones , Ácido Gástrico/metabolismo , Ácido Gástrico/química , Oxidación-Reducción , Mucosa Intestinal/metabolismo , Mucosa Intestinal/efectos de los fármacos , Humanos , Compuestos de Sulfhidrilo/química , Colitis/tratamiento farmacológico , Microbioma Gastrointestinal/efectos de los fármacos , Sistemas de Liberación de MedicamentosRESUMEN
BACKGROUND: Patients with oral cancer usually experience disfigurement and dysfunction which are shared risk factors of suicide. The aim of the study was to comprehensively assess the characteristics of suicide and risk factors for suicide in patients with oral cancer. METHODS: Surveillance, Epidemiology, and End Results database was used to acquire information of patients with common malignant tumors including oral cancer from 1975 to 2020. The aim was to explore the incidence of suicide, and timing of suicide among patients with oral cancer. A Fine-Gray competing risks regression model was employed to analyze risk factors associated with suicide among patients with various demographic and tumor characteristics. RESULTS: Totally, 7685 patients with different malignant tumors committed suicide. Among them, 203 patients with oral cancer died due to suicide, presenting a suicide rate of 54.5/100,000 person-years, which was almost 3.5 times that of the US general population and 1.5 times that of the overall US patients with cancer in our study. Approximately 18â¯%, 40â¯%, and 55â¯% of suicides occurred in first year, first 3 years, and first 5 years after diagnosis. Being male, White race, and having a single primary tumor might be regarded as the risk factors for suicide. CONCLUSION: As oral cavity is closely associated with appearance, pronunciation and ingestion, patients with oral cancer have a significant high risk of suicide. Tremendous attention needs to be paid to patients with oral cancer particularly those exhibiting characteristics associated with a high risk of suicide.
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OBJECTIVES: To determine the imaging details and diagnostic information of the treatment response to neoadjuvant chemoradiotherapy (nCRT) of rectal adenocarcinoma at 9.4T magnetic resonance imaging (MRI) by ex vivo. METHODS: Fifteen cases with locally advanced rectal cancer (LARC) followed by radical surgery after nCRT between September 2022 and February 2023 were recruited. Resected specimens were fixed in a perfluoropolyether-filled test tube and scanned with a 3.0T and 9.4T MRI system ex vivo. The residual tumor depth and MRI-based tumor regression grade (TRG) were subjectively assessed and then compared with the pathological findings. RESULTS: The ex vivo 9.4T T2WI without fat suppression clearly differentiated tumor tissue, fibrosis and normal rectal wall, which clearly corresponded to the pathologic tissues of the rectal specimens. The TRG could be accurately assessed on ex vivo 9.4T images in 13/15 specimens (86.7%), while in 11/15 specimens (73.3%) on ex vivo 3.0T images. CONCLUSION: Ex vivo 9.4T MR imaging clearly displayed the components of rectal wall and proved excellent diagnostic performance for evaluating the treatment response to nCRT, which allow radiologists to understand and then assess more accurately the TRG of LARC after nCRT.
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Adenocarcinoma , Imagen por Resonancia Magnética , Terapia Neoadyuvante , Neoplasias del Recto , Humanos , Neoplasias del Recto/terapia , Neoplasias del Recto/diagnóstico por imagen , Neoplasias del Recto/patología , Terapia Neoadyuvante/métodos , Imagen por Resonancia Magnética/métodos , Masculino , Femenino , Adenocarcinoma/terapia , Adenocarcinoma/diagnóstico por imagen , Adenocarcinoma/patología , Persona de Mediana Edad , Anciano , Adulto , Resultado del Tratamiento , Recto/diagnóstico por imagen , Recto/patología , Recto/cirugía , Quimioradioterapia/métodosRESUMEN
BACKGROUND: Bone or brain metastases may develop in 20-40% of individuals with late-stage non-small-cell lung cancer (NSCLC), resulting in a median overall survival of only 4-6 months. However, the primary lung cancer tissue's distinctions between bone, brain and intrapulmonary metastases of NSCLC at the single-cell level have not been underexplored. METHODS: We conducted a comprehensive analysis of 14 tissue biopsy samples obtained from treatment-naïve advanced NSCLC patients with bone (n = 4), brain (n = 6) or intrapulmonary (n = 4) metastasis using single-cell sequencing originating from the lungs. Following quality control and the removal of doublets, a total of 80 084 cells were successfully captured. RESULTS: The most significant inter-group differences were observed in the fraction and function of fibroblasts. We identified three distinct cancer-associated fibroblast (CAF) subpopulations: myofibroblastic CAF (myCAF), inflammatory CAF (iCAF) and antigen-presenting CAF (apCAF). Notably, apCAF was prevalent in NSCLC with bone metastasis, while iCAF dominated in NSCLC with brain metastasis. Intercellular signalling network analysis revealed that apCAF may play a role in bone metastasis by activating signalling pathways associated with cancer stemness, such as SPP1-CD44 and SPP1-PTGER4. Conversely, iCAF was found to promote brain metastasis by activating invasion and metastasis-related molecules, such as MET hepatocyte growth factor. Furthermore, the interaction between CAFs and tumour cells influenced T-cell exhaustion and signalling pathways within the tumour microenvironment. CONCLUSIONS: This study unveils the direct interplay between tumour cells and CAFs in NSCLC with bone or brain metastasis and identifies potential therapeutic targets for inhibiting metastasis by disrupting these critical cell-cell interactions.