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In a 55-year-old woman with sigmoid colon cancer, a subcutaneous mass in the left lower abdomen was incidentally found and gradually enlarged. For further diagnosis and staging, an 18F-fluorodeoxyglucose (FDG) positron emission tomography/computed tomography scan was performed, which revealed a subcutaneous mass in the left lower abdomen with mild uptake of 18F-FDG, suggesting the possibility of metastasis. However, post-surgery and pathological confirmation, this mass was diagnosed as a drain-site hernia containing fallopian tube fimbria, which is extremely rare but should be considered in the differential diagnosis of subcutaneous mass in the lower abdomen.
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The dental follicle (DF) plays an indispensable role in tooth eruption by regulating bone remodeling through their influence on osteoblast and osteoclast activity. The process of tooth eruption involves a series of intricate regulatory mechanisms and signaling pathways. Disruption of the parathyroid hormonerelated protein (PTHrP) in the PTHrPPTHrP receptor signaling pathway inhibits osteoclast differentiation by DF cells (DFCs), thus resulting in obstructed tooth eruption. Furthermore, parathyroid hormone receptor1 mutations are linked to primary tooth eruption failure. Additionally, the Wnt/ßcatenin, TGFß, bone morphogenetic protein and Hedgehog signaling pathways have crucial roles in DFC involvement in tooth eruption. DFC signal loss or alteration inhibits osteoclast differentiation, affects osteoblast and cementoblast differentiation, and suppresses DFC proliferation, thus resulting in failed tooth eruptions. Abnormal tooth eruption is also associated with a range of systemic syndromes and genetic diseases, predominantly resulting from pathogenic gene mutations. Among these conditions, the following disorders arise due to genetic mutations that disrupt DFCs and impede proper tooth eruption: Cleidocranial dysplasia associated with Runtrelated gene 2 gene mutations; osteosclerosis caused by CLCN7 gene mutations; mucopolysaccharidosis type VI resulting from arylsulfatase B gene mutations; enamel renal syndrome due to FAM20A gene mutations; and dentin dysplasia caused by mutations in the VPS4B gene. In addition, regional odontodysplasia and multiple calcific hyperplastic DFs are involved in tooth eruption failure; however, they are not related to gene mutations. The specific mechanism for this effect requires further investigation. To the best of our knowledge, previous reviews have not comprehensively summarized the syndromes associated with DF abnormalities manifesting as abnormal tooth eruption. Therefore, the present review aims to consolidate the current knowledge on DFC signaling pathways implicated in abnormal tooth eruption, and their association with disorders of tooth eruption in genetic diseases and syndromes, thereby providing a valuable reference for future related research.
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Saco Dental , Erupción Dental , Humanos , Saco Dental/metabolismo , Mutación , Transducción de Señal , Animales , Osteoclastos/metabolismo , Osteoclastos/patología , Receptor de Hormona Paratiroídea Tipo 1/metabolismo , Receptor de Hormona Paratiroídea Tipo 1/genética , Diferenciación Celular , Proteína Relacionada con la Hormona Paratiroidea/metabolismo , Proteína Relacionada con la Hormona Paratiroidea/genéticaRESUMEN
BACKGROUND: Hypoxic pulmonary hypertension (HPH) is a challenging lung arterial disorder with remarkably high incidence and mortality rates, and the efficiency of current HPH treatment strategies is unsatisfactory. Endothelial-to-mesenchymal transition (EndMT) in the pulmonary artery plays a crucial role in HPH. Previous studies have shown that lncRNA-H19 (H19) is involved in many cardiovascular diseases by regulating cell proliferation and differentiation but the role of H19 in EndMT in HPH has not been defined. METHODS: In this research, the expression of H19 was investigated in PAH human patients and rat models. Then, we established a hypoxia-induced HPH rat model to evaluate H19 function in HPH by Echocardiography and hemodynamic measurements. Moreover, luciferase reporter gene detection, and western blotting were used to explore the mechanism of H19. RESULTS: Here, we first found that the expression of H19 was significantly increased in the endodermis of pulmonary arteries and that H19 deficiency obviously ameliorated pulmonary vascular remodelling and right heart failure in HPH rats, and these effects were associated with inhibition of EndMT. Moreover, an analysis of luciferase activity indicated that microRNA-let-7 g (let-7 g) was a direct target of H19. H19 deficiency or let-7 g overexpression can markedly downregulate the expression of TGFßR1, a novel target gene of let-7 g. Furthermore, inhibition of TGFßR1 induced similar effects to H19 deficiency. CONCLUSIONS: In summary, our findings demonstrate that the H19/let-7 g/TGFßR1 axis is crucial in the pathogenesis of HPH by stimulating EndMT. Our study may provide new ideas for further research on HPH therapy in the near future.
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Transición Epitelial-Mesenquimal , Hipertensión Pulmonar , MicroARNs , ARN Endógeno Competitivo , ARN Largo no Codificante , Transducción de Señal , Factor de Crecimiento Transformador beta , Animales , Femenino , Humanos , Masculino , Ratas , Modelos Animales de Enfermedad , Transición Epitelial-Mesenquimal/fisiología , Transición Epitelial-Mesenquimal/genética , Hipertensión Pulmonar/metabolismo , Hipertensión Pulmonar/genética , Hipertensión Pulmonar/patología , Hipoxia/metabolismo , Hipoxia/genética , MicroARNs/metabolismo , MicroARNs/genética , Arteria Pulmonar/metabolismo , Arteria Pulmonar/patología , Ratas Sprague-Dawley , Receptor Tipo I de Factor de Crecimiento Transformador beta/metabolismo , Receptor Tipo I de Factor de Crecimiento Transformador beta/genética , ARN Endógeno Competitivo/genética , ARN Endógeno Competitivo/metabolismo , ARN Largo no Codificante/genética , ARN Largo no Codificante/metabolismo , Transducción de Señal/fisiología , Factor de Crecimiento Transformador beta/metabolismoRESUMEN
The presence of "viable but nonculturable" (VBNC) state and bacterial antibiotic resistance (BAR) both pose significant threats to the safety of drinking water. However, limited data was available that explicitly addressed the contribution of bacterial VBNC state in the maintenance and propagation of BAR. Here, the VBNC state induction and resuscitation of two antibiotic-resistant Escherichia coli K12 strains, one carrying multidrug-resistant plasmid (RP4 E. coli) and the other with chromosomal mutation (RIF E. coli) were characterized by subjecting them to different doses of UV/chlorine. The results illustrated that the induction, resuscitation, and associated mechanisms of VBNC ARB exhibit variations based on resistance determinants. RP4 E. coli exhibited a higher susceptibility to enter VBNC state compared to the RIF E. coli., and most VBNC state and resuscitated RP4 E. coli retained original antibiotic resistance. While, reverse mutation in the rpoB gene was observed in VBNC state and recovered RIF E. coli strains induced by high doses of UV/chlorine treatment, leading to the loss of rifampicin resistance. According to RT-qPCR results, ARGs conferring efflux pumps appeared to play a more significant role in the VBNC state formation of RP4 E. coli and the down-regulation of rpoS gene enhanced the speed at which this plasmid-carrying ARB entered into the dormant state. As to RIF E. coli, the induction of VBNC state was supposed to be regulated by the combination of general stress response, SOS response, stringent response, and TA system. Above all, this study highlights that ARB could become VBNC state during UV/chlorine treatments and retain, in some cases, their ability to spread ARGs. Importantly, compared with chromosomal mutation-mediated ARB, both VBNC and resuscitated state ARB that carries multidrug-resistant plasmids poses more serious health risks. Our study provides insights into the relationship between the VBNC state and the propagation of BAR in drinking water systems.
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Cloro , Escherichia coli , Rayos Ultravioleta , Escherichia coli/efectos de los fármacos , Escherichia coli/genética , Cloro/farmacología , Antibacterianos/farmacología , Farmacorresistencia Bacteriana/genética , Plásmidos , Proteínas de Escherichia coli/genética , Mutación , Viabilidad MicrobianaRESUMEN
Remote ischemic preconditioning (RIPC) exerts a protective role on myocardial ischemia/reperfusion (I/R) injury by the release of various humoral factors. Lactate is a common metabolite in ischemic tissues. Nevertheless, little is known about the role lactate plays in myocardial I/R injury and its underlying mechanism. This investigation revealed that RIPC elevated the level of lactate in blood and myocardium. Furthermore, AZD3965, a selective monocarboxylate transporter 1 inhibitor, and 2-deoxy-d-glucose, a glycolysis inhibitor, mitigated the effects of RIPC-induced elevated lactate in the myocardium and prevented RIPC against myocardial I/R injury. In an in vitro hypoxia/reoxygenation model, lactate markedly mitigated hypoxia/reoxygenation-induced cell damage in H9c2 cells. Meanwhile, further studies suggested that lactate contributed to RIPC, rescuing I/R-induced autophagy deficiency by promoting transcription factor EB (TFEB) translocation to the nucleus through activating the AMPK-mammalian target of rapamycin (mTOR) pathway without influencing the phosphatidylinositol 3-kinase-Akt pathway, thus reducing cardiomyocyte damage. Interestingly, we also found that lactate up-regulated the mRNA and protein expression of connexin 43 (CX43) by facilitating the binding of TFEB to CX43 promoter in the myocardium. Functionally, silencing of TFEB attenuated the protective effect of lactate on cell damage, which was reversed by overexpression of CX43. Further mechanistic studies suggested lactate facilitated CX43-regulated autophagy via the AMPK-mTOR-TFEB signaling pathway. Collectively, our research demonstrates that RIPC protects against myocardial I/R injury through lactate-mediated myocardial autophagy via the AMPK-mTOR-TFEB-CX43 axis.
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Natural organisms have evolved multi-scale wet gas sensing interfaces with optimized mass transport pathways in biological fluid environments, which sheds light on developing artificial counterparts with improved wet gas sensing abilities and practical applications. Herein, we highlighted current advances in wet gas sensing taking advantage of optimized mass transport pathways endowed by multi-scale interface design. Common moisture resistance (e.g., employing moisture resistant sensing materials, post-modifying moisture resistant coatings, physical heating for moisture resistance, and self-removing hydroxyl groups) and moisture absorption (e.g., employing moisture absorption sensing materials and post-modifying moisture absorption coatings) strategies for wet gas sensing were discussed. Then, the design principles of bioinspired multi-scale wet gas sensing interfaces were provided, including macro-level condensation mediation, micro/nano-level transport pathway adjustment and molecular level moisture-proof design. Finally, perspectives on constructing bioinspired multi-scale wet gas sensing interfaces were presented, which will not only deepen our understanding of the underlying principles, but also promote practical applications.
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Purpose: This study aimed to explore the expression of CX3CL1 induced by lipopolysaccharide (LPS) in oral squamous cell carcinoma (OSCC) and its impact on biological characteristics such as invasion and migration, taking the foundation for new targets for the treatment and prognosis of OSCC. Methods: This study utilized a variety of techniques, including bioinformatics, molecular biology, and cell experiments, to investigate the expression of CX3CL1 and its receptor CX3CR1 in OSCC patients' cancer tissues or OSCC cell lines. Extracting, organizing, and analyzing the TCGA database on the expression of CX3CL1 and its receptor CX3CR1 in cancer tissues and corresponding paracancerous normal tissues of OSCC patients by bioinformatics methods. The expression of CX3CL1 in cancerous and normal tissues of OSCC patients was verified by IHC, and the changes in mRNA and protein expression of CX3CL1 and its receptor CX3CR1 in OSCC cell lines were detected before and after lipopolysaccharide LPS stimulation by RT-PCR, ELISA, and WB. Changes in cell biological behavior by overexpression of CX3CL1 in OSCC cell lines were detected by CCK-8, Transwell, scratch healing assay, and cloning assay. The effects of overexpressing cell lines on the AKT pathway and Epithelial-mesenchymal Transition (EMT)-related protein expression before and after LPS stimulation were detected by Western Blot. Results: (1) CX3CL1 and its receptor CX3CR1 were found to be downregulated in OSCC tissues of patients or OSCC cell lines. (2) After LPS stimulation, CX3CL1 gene expression increased in both OSCC cell lines, while CX3CR1 expression remained unchanged. (3) OSCC cell lines overexpressing CX3CL1 showed changes in cell biological characteristics, including decreased proliferation, invasion, migration, and stemness, which were more pronounced after LPS stimulation. (4) Overexpression of CX3CL1 in OSCC cell lines decreased EMT-related protein expression and AKT phosphorylation. On the contrary were promoted by LPS stimulation. Conclusion: CX3CL1 and CX3CR1 are downregulated in OSCC cancer tissues and cell lines compared to adjacent normal tissues and cells. LPS stimulation increases CX3CL1 expression in OSCC cell lines, suggesting that inflammation may induce CX3CL1 expression and that the CX3CL1 gene may play an important role in OSCC progression. Overexpression of CX3CL1 inhibits OSCC cell proliferation, migration, invasion, and stemness, suggesting that CX3CL1 plays a critical role in suppressing OSCC development. CX3CL1 suppresses OSCC invasion and migration by affecting EMT progression and AKT phosphorylation, and partially reverse the process that LPS causes and affects the development of OSCC.
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PURPOSE: Immunohistochemical staining of programmed death-ligand 1 (PD-L1) in tumor biopsies acquired through invasive procedures is routinely employed in clinical practice to identify patients who are most likely to benefit from anti-programmed cell death protein 1 (PD-1) therapy. Nevertheless, PD-L1 expression is observed in various cellular subsets within tumors and their microenvironments, including tumor cells, dendritic cells, and macrophages. The impact of PD-L1 expression across these different cell types on the responsiveness to anti-PD-1 treatment is yet to be fully understood. METHODS: We synthesized polymer-based lysosome-targeting chimeras (LYTACs) that incorporate both PD-L1-targeting motifs and liver cell-specific asialoglycoprotein receptor (ASGPR) recognition elements. Small-animal positron emission tomography (PET) imaging of PD-L1 expression was also conducted using a PD-L1-specific radiotracer 89Zr-αPD-L1/Fab. RESULTS: The PD-L1 LYTAC platform was capable of specifically degrading PD-L1 expressed on liver cancer cells through the lysosomal degradation pathway via ASGPR without impacting the PD-L1 expression on host cells. When coupled with whole-body PD-L1 PET imaging, our studies revealed that host cell PD-L1, rather than tumor cell PD-L1, is pivotal in the antitumor response to anti-PD-1 therapy in a mouse model of liver cancer. CONCLUSION: The LYTAC strategy, enhanced by PET imaging, has the potential to surmount the limitations of knockout mouse models and to provide a versatile approach for the selective degradation of target proteins in vivo. This could significantly aid in the investigation of the roles and mechanisms of protein functions associated with specific cell subsets in living subjects.
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Cone beam computed tomography (CBCT) is widely employed in modern dentistry, and tooth segmentation constitutes an integral part of the digital workflow based on these imaging data. Previous methodologies rely heavily on manual segmentation and are time-consuming and labor-intensive in clinical practice. Recently, with advancements in computer vision technology, scholars have conducted in-depth research, proposing various fast and accurate tooth segmentation methods. In this review, we review 55 articles in this field and discuss the effectiveness, advantages, and disadvantages of each approach. In addition to simple classification and discussion, this review aims to reveal how tooth segmentation methods can be improved by the application and refinement of existing image segmentation algorithms to solve problems such as irregular morphology and fuzzy boundaries of teeth. It is assumed that with the optimization of these methods, manual operation will be reduced, and greater accuracy and robustness in tooth segmentation will be achieved. Finally, we highlight the challenges that still exist in this field and provide prospects for future directions.
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In this paper, the damage monitoring investigation based on the remote bonding fiber Bragg grating sensing is performed on the aerospace aluminum alloy thin-walled structure with prefabricated damage. Firstly, an ultrasonic excitation-fiber Bragg gratings (UE-FBGs) sensing experimental platform is established for the simulation of defects monitoring, in which the sensors are placed at a certain distance from the bonding area. Secondly, different arrangements of exciters and receivers are utilized for the original signals and the damage signals. Subsequently, the raw signals are processed by filter and feature extraction in order to denoise the signals and acquire the parameters sensitive to the damage. Finally, an improved Reconstruction for Image Defects (RAPID) algorithm is used to locate and reconstruct the pre-existing damage. The results show that the proposed system improves the sensitivity of the FBG receiver signal and the accuracy of the damage imaging.
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OBJECTIVES: Orthodontic tooth movement is a mechanobiological reaction induced by appropriate forces, including bone remodeling. The mechanosensitive Piezo channels have been shown to contribute to bone remodeling. However, information about the pathways through which Piezo channels affects osteoblasts remains limited. Thus, we aimed to investigate the influence of Piezo1 on the osteogenic and osteoclast factors in osteoblasts under mechanical load. MATERIALS AND METHODS: Cyclic stretch (CS) experiments on MC3T3-E1 were conducted using a BioDynamic mechanical stretching device. The Piezo1 channel blocker GsMTx4 and the Piezo1 channel agonist Yoda1 were used 12 h before the application of CS. MC3T3-E1 cells were then subjected to 15% CS, and the expression of Piezo1, Piezo2, BMP-2, OCN, Runx2, RANKL, p-p65/p65, and ALP was measured using quantitative real-time polymerase chain reaction, western blot, alkaline phosphatase staining, and immunofluorescence staining. RESULTS: CS of 15% induced the highest expression of Piezo channel and osteoblast factors. Yoda1 significantly increased the CS-upregulated expression of Piezo1 and ALP activity but not Piezo2 and RANKL. GsMTx4 downregulated the CS-upregulated expression of Piezo1, Piezo2, Runx2, OCN, p-65/65, and ALP activity but could not completely reduce CS-upregulated BMP-2. CONCLUSIONS: The appropriate force is more suitable for promoting osteogenic differentiation in MC3T3-E1. The Piezo1 channel participates in osteogenic differentiation of osteoblasts through its influence on the expression of osteogenic factors like BMP-2, Runx2, and OCN and is involved in regulating osteoclasts by influencing phosphorylated p65. These results provide a foundation for further exploration of osteoblast function in orthodontic tooth movement.
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Proteína Morfogenética Ósea 2 , Subunidad alfa 1 del Factor de Unión al Sitio Principal , Canales Iónicos , Osteoblastos , Osteogénesis , Osteoblastos/metabolismo , Canales Iónicos/metabolismo , Animales , Ratones , Proteína Morfogenética Ósea 2/metabolismo , Osteogénesis/fisiología , Subunidad alfa 1 del Factor de Unión al Sitio Principal/metabolismo , Osteoclastos/metabolismo , Reacción en Cadena en Tiempo Real de la Polimerasa , Ligando RANK/metabolismo , Western Blotting , Estrés Mecánico , Diferenciación Celular , Osteocalcina/metabolismo , Fosfatasa Alcalina/metabolismo , Oligopéptidos/farmacología , Técnicas de Movimiento Dental , Mecanotransducción Celular/fisiología , Línea Celular , Remodelación Ósea/fisiología , Pirazinas , Venenos de Araña , Tiadiazoles , Péptidos y Proteínas de Señalización IntercelularRESUMEN
ABSTRACT: An Al 18F-prostate-specific membrane antigen (PSMA) Q PET/CT scan was performed in a 67-year-old man to identify any potential recurrent prostate cancer lesions, which revealed no recurrent or metastatic lesions. However, a large gallbladder stone with increased PSMA uptake was incidentally detected, which could be a potential pitfall in the interpretation of PSMA PET imaging.
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Cálculos Biliares , Neoplasias de la Próstata , Masculino , Humanos , Anciano , Tomografía Computarizada por Tomografía de Emisión de Positrones/métodos , Próstata/patología , Recurrencia Local de Neoplasia , Neoplasias de la Próstata/diagnóstico por imagen , Neoplasias de la Próstata/patología , Radioisótopos de Galio , Antígeno Prostático EspecíficoRESUMEN
Biofilters are the important source and sink of antibiotic resistance genes (ARGs) and antibiotic resistance bacteria (ARB) in the drinking water. Current studies generally ascribed the prevalence of BAR in biofilter from the perspective of gene behavior, i.e. horizontal gene transfer (HGT), little attentions have been paid on the ARGs carrier- ARB. In this study, we proposed the hypothesis that ARB participating in pollutant metabolism processes and becoming dominant is an important way for the enrichment of ARGs. To verify this, the antibiotic resistome and bacterial functional metabolic pathways of a sand filter was profiled using heterotrophic bacterial plate counting method (HPC), high-throughput qPCR, Illumina Hiseq sequencing and PICRUSt2 functional prediction. The results illustrated a significant leakage of ARB in the effluent of the sand filter with an average absolute abundance of approximately 102-103 CFU/mL. Further contribution analysis revealed that the dominant genera, such as Acinetobacter spp., Aeromonas spp., Elizabethkingia spp., and Bacillus spp., were primary ARGs hosts, conferring resistance to multiple antibiotics including sulfamethoxazole, tetracycline and ß-lactams. Notably, these ARGs hosts were involved in nitrogen metabolism, including extracellular nitrate/nitrite transport and nitrite reduction, which are crucial in nitrification and denitrification in biofilters. For example, Acinetobacter spp., the dominant bacteria in the filter (relative abundance 69.97 %), contributed the majority of ARGs and 53.79 % of nitrite reduction function. That is, ARB can predominate by participating in the nitrogen metabolism pathways, facilitating the enrichment of ARGs. These findings provide insights into the stable presence of ARGs in biofilters from a functional metabolism perspective, offering a significant supplementary to the mechanisms of the emergence, maintenance, and transmission of BARin drinking water.
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Antibacterianos , Agua Potable , Antibacterianos/farmacología , Antibacterianos/análisis , Genes Bacterianos , Antagonistas de Receptores de Angiotensina/análisis , Nitritos/análisis , Farmacorresistencia Microbiana/genética , Inhibidores de la Enzima Convertidora de Angiotensina/análisis , Nitrógeno/análisisRESUMEN
STING-mediated DNA sensing pathway plays a crucial role in the innate antiviral immune responses. Clarifying its regulatory mechanism and searching STING agonists has potential clinical implications. Although multiple STING agonists have been developed to target cancer, there are few for the treatment of infectious diseases. Astaxanthin, a natural and powerful antioxidant, serves many biological functions and as a potential candidate drug for many diseases. However, how astaxanthin combats viruses and whether astaxanthin regulates the cyclic GMP-AMP synthase-STING pathway remains unclear. In this study, we showed that astaxanthin markedly inhibited HSV-1-induced lipid peroxidation and inflammatory responses and enhanced the induction of type I IFN in C57BL/6J mice and mouse primary peritoneal macrophages. Mechanistically, astaxanthin inhibited HSV-1 infection and oxidative stress-induced STING carbonylation and consequently promoted STING translocation to the Golgi apparatus and oligomerization, which activated STING-dependent host defenses. Thus, our study reveals that astaxanthin displays a strong antiviral activity by targeting STING, suggesting that astaxanthin might be a promising STING agonist and a therapeutic target for viral infectious diseases.
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Virosis , Xantófilas , Animales , Ratones , Herpes Simple/tratamiento farmacológico , Inmunidad Innata , Proteínas de la Membrana/metabolismo , Ratones Endogámicos C57BL , Nucleotidiltransferasas/metabolismo , Xantófilas/farmacología , Xantófilas/uso terapéutico , Virosis/tratamiento farmacológicoRESUMEN
Pulmonary arterial hypertension (PAH) is a complex and fatal cardio-pulmonary vascular disease. Decompensated right ventricular hypertrophy (RVH) caused by cardiomyocyte hypertrophy often leads to fatal heart failure, the leading cause of mortality among patients. Sodium butyrate (SB), a compound known to reduce cardiac hypertrophy, was examined for its potential effect and the underlying mechanism of SB on PAH-RVH. The in vivo study showed that SB alleviated RVH and cardiac dysfunction, as well as improved life span and survival rate in MCT-PAH rats. The in vivo and in vitro experiments showed that SB could attenuate cardiomyocyte hypertrophy by reversing the expressions of H19, let-7g-5p, insulin-like growth factor 1 receptor (IGF1 receptor), and pERK. H19 inhibition restored the level of let-7g-5p and prevented the overexpression of IGF1 receptor and pERK in hypertrophic cardiomyocytes. In addition, dual luciferase assay revealed that H19 demonstrated significant binding with let-7g-5p, acting as its endogenous RNA. Briefly, SB attenuated PAH-RVH by inhibiting the H19 overexpression, restoring the level of let-7g-5p, and hindering IGF1 receptor/ERK activation.
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Hipertensión Pulmonar , MicroARNs , Hipertensión Arterial Pulmonar , Humanos , Ratas , Animales , Hipertrofia Ventricular Derecha , Hipertensión Arterial Pulmonar/complicaciones , Ácido Butírico/farmacología , Ácido Butírico/uso terapéutico , Hipertensión Pulmonar/metabolismo , Hipertensión Pulmonar Primaria Familiar , MicroARNs/genética , MicroARNs/metabolismo , Factor I del Crecimiento Similar a la InsulinaRESUMEN
ABSTRACT: A 66-year-old man with gastric signet-ring cell carcinoma underwent both 18 F-FDG and 18 FAl-NOTA-FAPI PET/CT imaging. There was no abnormal FDG activity in the stomach, but there was diffuse intense 18 FAl-NOTA-FAPI uptake in the known lesion and an adjacent metastasis.
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Carcinoma de Células en Anillo de Sello , Neoplasias Gástricas , Masculino , Humanos , Anciano , Fluorodesoxiglucosa F18 , Tomografía Computarizada por Tomografía de Emisión de Positrones , Neoplasias Gástricas/diagnóstico por imagen , Carcinoma de Células en Anillo de Sello/diagnóstico por imagen , Radioisótopos de GalioRESUMEN
Background: Radiotherapy (RT) may trigger systemic antitumor immunity, manifesting as regression of non-irradiated lesions (abscopal effect). Intracellular adhesion molecule-1 (ICAM-1) is a key molecule involved in the abscopal effect of RT. However, the specific function of ICAM-1 in CD8+ T cells during antitumor immune responses remains unclear. Herein, we investigated whether noninvasive imaging of ICAM-1 can be used to annotate CD8+ T-cell function, thereby better selecting combinational therapy to enhance the antitumor immunity induced by RT. Methods: Using knockout mouse models, we investigated the role of ICAM-1 expressed on CD8+ T cells in the antitumor immunity of RT and conducted drug screening guided by ICAM-1-targeted noninvasive imaging. Results: The systemic antitumor effect of RT relies on the expression of ICAM-1 on CD8+ T cells. ICAM-1 expression is essential for CD8+ T-cell activation, proliferation, and effector function. Noninvasive annotation of the proliferation and effector function of CD8+ T cells by ICAM-1-targeted imaging identified VS-6063, a focal adhesion kinase inhibitor, as a new adjuvant to augment systemic antitumor immunity of RT in an immunologically "cold" tumor model. Mechanistically, VS-6063 overcomes the physical barriers in tumors and promotes the migration and infiltration of CD8+ T cells primed by RT into distant tumors. Conclusion: Our findings highlight that molecular imaging of ICAM-1 levels provides a dynamic readout of the proliferation and effector function of tumor-infiltrating CD8+ T cells, which facilitates the high-throughput exploitation of new combinational drugs to maximize the systemic antitumor effect of RT.
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Linfocitos T CD8-positivos , Neoplasias , Ratones , Animales , Molécula 1 de Adhesión Intercelular/metabolismo , Neoplasias/radioterapia , Neoplasias/metabolismo , Adyuvantes Inmunológicos/farmacología , Ratones NoqueadosRESUMEN
In this research, the degradation behavior and failure mechanism of silicone rubber seal rings under the synergistic effects of multiple factors in the marine atmosphere are fully investigated. Firstly, four aging factors of air, temperature, compressive stress, and chemical medium were determined by analyzing the service environment profile of silicone rubber seal under a marine atmosphere environment. Secondly, to better simulate the actual service environment of silicone rubber and shorten the test period, an artificially accelerated aging test was designed and carried out in the laboratory. In this paper, temperature is utilized as the accelerating stress. According to the results of the pre-test, the accelerating stress level is finally determined to be 110-150 ∘C. In addition, the compression set applied is consistent with the constant compression permanent deformation value of 28% of the silicone rubber in the actual service process. Finally, through the macroscopic physical properties and microstructure analysis of the samples before and after aging, the corresponding test results are given, and the failure mechanism is analyzed and discussed in detail. Through the above test results and discussion, it can be concluded that the aging process of multi-factor coupling on the lower silicone rubber seal ring is uneven, and its aging process is not a simple superposition of multiple environmental factors. More importantly, the above test data and results are of great significance for evaluating the service life of silicone rubber seals, which can be utilized in the future to improve the reliability and durability of related equipment in the marine environment.
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INTRODUCTION: Raising the price of cigarettes via taxation has been promoted by the World Health Organization as an important tobacco control strategy. Price elasticity of cigarettes is not uniform and is dependent upon individual and environmental determinants. Many studies have examined the determinants of price-induced smoking, taking into account sociodemographic characteristics and consumption patterns. Little research has been conducted on the association between anti-smoking environments and price-induced smoking behavior. This study addresses the deficit within the Chinese context. METHODS: Participants were 2852 male smokers identified through a multi-stage survey sampling process encompassing 6 cities in China between July and December 2016. A standardized questionnaire tapped price-induced smoking reduction and related information. Both unadjusted and adjusted logistic regression methods were applied in the analyses. RESULTS: In all, 25.5% (95% CI: 22.5-27.9) of smokers in this study decreased their smoking expenditures following the 2015 excise tax increase. The adjusted logistic regression analysis showed that increased exposures to an anti-smoking information environment (AOR=1.39; 95% CI: 1.10-1.79), restricted smoking in their home (AOR=1.67; 95% CI: 1.32-2.08) and workplace (AOR=1.43; 95% CI: 1.09-1.85) were more likely to report diminished cigarette smoking following the tax increases. CONCLUSIONS: This study adds to understanding price-induced smoking behavior among urban male Chinese smokers. Strengthening of excise tax policies needs to intensify environmental smoking restrictions and public education campaigns to increase the sensitivity of cigarette price changes among smokers.
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Persistent infection of high-risk human papillomavirus (HPV) and the expression of E6 and E7 oncoproteins are the main causes of cervical cancer. Several prophylactic HPV vaccines are used in the clinic, but these vaccines have limited efficacy in patients already infected with HPV. Since HPV E7 is vital for tumor-specific immunity, developing a vaccine against HPV E7 is an attractive strategy for cervical cancer treatment. Here, we constructed an HPV16 E7 mutant that loses the ability to bind pRb while still eliciting a robust immune response. In order to build a therapeutic DNA vaccine, the E7 mutant was packaged in an adenovirus vector (Ad-E7) for efficient expression and enhanced immunogenicity of the vaccine. Our results showed that the Ad-E7 vaccine effectively inhibited tumor growth and increased the proportion of interferon-gamma (IFN-γ)-secreting CD8+ T cells in the spleen, and tumor-infiltrating lymphocytes in a mouse cervical cancer model was achieved by injecting with HPV16-E6/E7-expressing TC-1 cells subcutaneously. Combining the Ad-E7 vaccine with the PD-1/PD-L1 antibody blockade significantly improved the control of TC-1 tumors. Combination therapy elicited stronger cytotoxic T lymphocyte (CTL) responses, and IFN-γ secretion downregulated the proportion of Tregs and MDSCs significantly. The expressions of cancer-promoting factors, such as TNF-α, were also significantly down-regulated in the case of combination therapy. In addition, combination therapy inhibited the number of capillaries in tumor tissues and increased the thickness of the tumor capsule. Thus, Ad-E7 vaccination, in combination with an immune checkpoint blockade, may benefit patients with HPV16-associated cervical cancer.