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1.
Clin Transl Radiat Oncol ; 46: 100767, 2024 May.
Artigo em Inglês | MEDLINE | ID: mdl-38576855

RESUMO

Centrally located hepatocellular carcinoma (HCC) is difficult to be radically resected due to its special location close to major hepatic vessels. Thus, we aimed to assess whether stereotactic body radiation therapy (SBRT) can be an effective and safe approach for centrally located HCC. This retrospective study included 172 patients with centrally located HCC who were treated with SBRT. Overall survival (OS) was analyzed as the primary endpoint. Rates of progression-free survival (PFS), local control, intrahepatic relapse, extrahepatic metastasis and toxicities were analyzed as secondary endpoints. The OS rates of 1-, 3-, and 5-year were 97.7%, 86.7%, and 76.3%, respectively. The PFS/local control rates of 1-, 3-, and 5-year were 94.1%/98.2%, 76.8%/94.9%, and 59.3%/92.3%, respectively. The cumulative incidence of intrahepatic relapse/extrahepatic metastases of 1-, 3-, and 5-year were 3.7%/2.9%, 25.0%/7.4%, and 33.3%/9.8%, respectively. Both univariate and multivariate analyses revealed that patients received BED10 at 100 Gy or more had better OS. Radiation-related adverse events were mild to moderate according to Common Terminology Criteria for Adverse Events, and no toxicities over grade 3 were observed. Patients with centrally located HCC in our cohort who received SBRT had similar OS and PFS rates compared to those reported in literatures who received surgery with neoadjuvant or adjuvant intensity-modulated radiation therapy. These results indicate that SBRT is an effective and well-tolerated method for patients with centrally located HCC, suggesting that it may serve as a reasonable alternative treatment for these kind of patients.

2.
J Craniofac Surg ; 35(4): 1253-1257, 2024 Jun 01.
Artigo em Inglês | MEDLINE | ID: mdl-38687045

RESUMO

PURPOSE: To investigate the clinical outcomes of reverse Z-plasty in the reconstruction of epicanthal fold. METHODS: We conducted a retrospective analysis on clinical data from patients who underwent medial canthal skin redundancy reconstruction surgery from September 2019 to January 2023. The surgical procedure involved a preoperative design for the incision line, suborbicularis oculi dissection to create a muscle flap, and the use of a reverse Z-flap for the reconstruction of the lateral canthal fold. Postoperative follow-up assessments focused on the intercanthal distance, positional changes of the medial canthus point, alterations in the medial canthus angle, and patient satisfaction levels. The statistical evaluation was carried out utilizing paired t -tests, with a P -value of less than 0.05 denoting statistical significance. RESULTS: Postsurgery, the lacrimal prominences were less exposed, and inner canthal angles naturally reshaped. Inconspicuous scarring with diminished reverse Z-plasty marks was noted within 3 months. The average ICD has increased by 3 to 6 mm, corresponding to elongation ratios of 9.09% to 28.30%. Preoperatively, the ICD averaged 31.25±2.32 mm, expanding postoperatively to 35.19±2.26 mm. The canthal angle enlarged significantly from 49.031±6.627 to 62.188±6.662. Inner canthal points shifted notably postsurgery, with a decrease in x-value and an increase in y-value, signalling a movement upwards and away from the nose. Patient satisfaction is high. CONCLUSION: The reverse Z-plasty technique has proven to be an effective approach for reconstructing the epicanthal fold. The clarity and precision of the incision design, coupled with the stability of postoperative results, demonstrate that this method can reliably achieve successful epicanthal fold reconstruction.


Assuntos
Satisfação do Paciente , Retalhos Cirúrgicos , Humanos , Estudos Retrospectivos , Feminino , Masculino , Adulto , Pessoa de Meia-Idade , Pálpebras/cirurgia , Procedimentos de Cirurgia Plástica/métodos , Idoso
3.
Pest Manag Sci ; 80(6): 2710-2723, 2024 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-38358029

RESUMO

BACKGROUND: Xanthomonas oryzae pv. oryzae (Xoo) is often considered one of the most destructive bacterial pathogens causing bacterial leaf blight (BLB), resulting in significant yield and cost losses in rice. In this study, a series of novel derivatives containing the isopropanolamine moiety linked to various substituted phenols and piperazines were designed, synthesized and screened. RESULTS: Antibacterial activity results showed that most compounds had good inhibitory effects on Xoo, among which compound W2 (EC50 = 2.74 µg mL-1) exhibited the most excellent inhibitory activity, and W2 also had a certain curative effect (35.89%) on rice compared to thiodiazole copper (TC) (21.57%). Scanning electron microscopy (SEM) results indicated that compound W2 could cause rupture of the Xoo cell membrane. Subsequently, proteomics and quantitative real-time polymerase chain reaction revealed that compound W2 affected the physiological processes of Xoo and may exert antibacterial activity by targeting the two-component system pathway. Interestingly, W2 upregulated Xoo's methyltransferase to impact on its pathogenicity. CONCLUSION: The present study offers a promising phenolic-piperazine-sopropanolamine compound as an innovative antibacterial strategy by specifically targeting the two-component system pathway and inducing upregulation of methyltransferase to effectively impact Xoo's pathogenicity. © 2024 Society of Chemical Industry.


Assuntos
Antibacterianos , Xanthomonas , Xanthomonas/efeitos dos fármacos , Antibacterianos/farmacologia , Antibacterianos/síntese química , Antibacterianos/química , Fenóis/farmacologia , Fenóis/química , Desenho de Fármacos , Piperazinas/farmacologia , Piperazinas/química , Piperazinas/síntese química , Oryza/microbiologia , Doenças das Plantas/microbiologia
4.
Acta Pharmacol Sin ; 45(4): 831-843, 2024 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-38052867

RESUMO

Chronic rhinosinusitis with nasal polyp (CRSwNP) is a refractory inflammatory disease with epithelial-mesenchymal transition (EMT) as one of the key features. Since ubiquitin modification has been shown to regulate the EMT process in other diseases, targeting ubiquitin ligases may be a potential strategy for the treatment of CRSwNP. In this study we investigated whether certain E3 ubiquitin ligases could regulate the EMT process in CRSwNP, and whether these regulations could be the potential drug targets as well as the underlying mechanisms. After screening the potential drug target by bioinformatic analyses, the expression levels of three potential E3 ubiquitin ligases were compared among the control, eosinophilic nasal polyp (ENP) and non-eosinophilic nasal polyp (NENP) group in clinical samples, and the significant decrement of the expression level of NEDD4L was found. Then, IP-MS, bioinformatics and immunohistochemistry studies suggested that low NEDD4L expression may be associated with the EMT process. In human nasal epithelial cells (hNECs) and human nasal epithelial cell line RPMI 2650, knockdown of NEDD4L promoted EMT, while upregulating NEDD4L reversed this effect, suggesting that NEDD4L inhibited EMT in nasal epithelial cells. IP-MS and Co-IP studies revealed that NEDD4L mediated the degradation of DDR1. We demonstrated that NEDD4L inhibited the ß-catenin/HIF-1α positive feedback loop either directly (degrading ß-catenin and HIF-1α) or indirectly (mediating DDR1 degradation). These results were confirmed in a murine NP model in vivo. This study for the first time reveals the regulatory role of ubiquitin in the EMT process of nasal epithelial cells, and identifies a novel drug target NEDD4L, which has promising efficacy against both ENP and NENP by suppressing ß-catenin/HIF-1α positive feedback loop.


Assuntos
Transição Epitelial-Mesenquimal , Terapia de Alvo Molecular , Pólipos Nasais , Ubiquitina-Proteína Ligases Nedd4 , Rinossinusite , Animais , Humanos , Camundongos , beta Catenina/metabolismo , Doença Crônica , Retroalimentação , Pólipos Nasais/tratamento farmacológico , Pólipos Nasais/enzimologia , Rinossinusite/tratamento farmacológico , Rinossinusite/enzimologia , Ubiquitinas/metabolismo , Ubiquitina-Proteína Ligases Nedd4/antagonistas & inibidores , Ubiquitina-Proteína Ligases Nedd4/metabolismo
5.
Eur Arch Otorhinolaryngol ; 280(8): 3707-3720, 2023 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-36939907

RESUMO

OBJECTIVES: To explore associations between inflammatory endotypes and clinical presentations in CRS. To investigate the value of secretions myeloperoxidase (MPO) and eosinophilic cationic protein (ECP) detections in the diagnosis of endotypes of chronic rhinosinusitis (CRS), so as to provide guidance for the clinical application of MPO and ECP detection in secretions. METHODS: We collected clinical symptom scores from patients with CRS and examined the differences between endotypes in clinical features. Patients' nasal secretions and polyps (or middle turbinate for control) were collected and their NEU number, EOS%, MPO and ECP levels were measured. Correlation analysis was performed for these biomarkers in secretions and tissues, respectively. Receiver operating characteristic curves were used to assess the predictive potential of the biomarkers mentioned above in nasal secretions. RESULTS: Patients with Eos+Neu+ and Eos+Neu-CRS scored highest in most clinical symptom scores, while Eos-Neu+ and Eos-Neu-CRS scored lowest. Correlation analysis showed that tissues NEU number was correlated with NEU number and MPO level in nasal secretions (R = 0.4088; 0.6613); tissues EOS % was correlated with EOS% and ECP level in nasal secretions (R = 0.2344; 0.5774). To diagnose Neu+CRS, the highest area under the curve (AUC) (0.8961) was determined for MPO in secretions; the highest AUC (0.7400) was determined for NEU number in secretions. To diagnose Eos+Neu-CRS from Eos-Neu-CRS in Neu-CRS, the highest AUC (0.8801) was determined for ECP in secretions. CONCLUSIONS: Clinical presentations are directly associated with CRS endotypes. Measurement of MPO and ECP in nasal secretions is useful for the endotypes diagnosis of CRS.


Assuntos
Pólipos Nasais , Rinite , Sinusite , Humanos , Rinite/diagnóstico , Rinite/metabolismo , Proteína Catiônica de Eosinófilo/metabolismo , Peroxidase , Doença Crônica , Sinusite/diagnóstico , Sinusite/metabolismo , Biomarcadores , Pólipos Nasais/diagnóstico , Pólipos Nasais/metabolismo
6.
Int J Ophthalmol ; 16(2): 191-200, 2023.
Artigo em Inglês | MEDLINE | ID: mdl-36816211

RESUMO

AIM: To study the effect of palmitoylethanolamide (PEA) on apoptosis of retinal pigment epithelial (RPE) cells induced by all-trans retinal (atRAL) and to explore the possible molecular mechanism. METHODS: CellTiter 96® Aqueous One Solution Cell Proliferation Assay (MTS) was used to detect the effect of PEA on human-derived retinal epithelial cells (ARPE-19) viability induced by atRAL. A Leica DMi8 inverted microscope was used to observe cell morphology. Reactive oxygen species (ROS) production was evaluated with 2',7'-dichlorodihydrof-luorescein diacetate (H2DCFDA) staining and fluorescence microscopy. Expression of c-Jun N-terminal kinase (JNK), phosphorylated JNK (p-JNK), c-Jun, phosphorylated c-Jun (p-c-Jun), Bak, cleaved caspase-3, C/EBP homologous protein (CHOP), and binding (Bip) protein levels were tested by Western blot. Abca4 -/- Rdh8 -/- mice, mouse models of atRAL clearance defects which displays some symbolic characteristics of dry age-related macular degeneration (AMD) and Stargardt disease (STGD1). In the animal models, PEA was injected intraperitoneally. The full-field electroretinogram was used to detect visual function under scotopic conditions traced from mice. Optical coherence tomography showed reconstitution or thickening of the retinal pigment epithelium layer. Effect of PEA on fundus injury induced by light in Abca4-/-Rdh8-/- mice was observed by fundus photography. RESULTS: PEA ameliorated ARPE-19 cells apoptosis and inhibited ROS (including mitochondrial ROS) production induced by atRAL. PEA improved the retinal functional, prohibited both RPE and photoreceptor from death, ameliorates light-induced fundus impairment in Abca4 -/- Rdh8 -/- mice. In vitro and in vivo, PEA inhibited JNK, p-JNK, c-Jun, p-c-Jun, Bak, cleaved caspase-3, CHOP, and Bip protein levels induced by all-trans retinal in ARPE-19 cells. CONCLUSION: PEA has effect on treating RPE cells apoptosis in retinopathy caused by atRAL accumulation. PEA is a potential treatment strategy for dry AMD and STGD1. The molecular mechanism is affecting the ROS-JNK-CHOP signaling pathway partly.

7.
Int J Biol Macromol ; 225: 987-996, 2023 Jan 15.
Artigo em Inglês | MEDLINE | ID: mdl-36403764

RESUMO

The genus Streptomyces comprises the most important chitin decomposers in soil and revealing their chitinolytic machinery is beneficial for the conversion of chitinous wastes. Streptomyces sp. SCUT-3, a chitin-hydrolyzing and a robust feather-degrading bacterium, was isolated previously. The potential chitin-degrading enzymes produced by SCUT-3 were analyzed in the present study. Among these enzymes, three chitinases were successfully expressed in Pichia pastoris at comparatively high yields of 4.8 U/mL (SsExoChi18A), 11.2 U/mL (SsExoChi18B), and 17.8 U/mL (SsEndoChi19). Conserved motifs and constructive 3D structures of these three exo- and endochitinases were also analyzed. These chitinases hydrolyzed colloidal chitin to chitin oligomers. SsExoChi18A showed apparent synergic effects with SsEndoChi19 in colloidal chitin and shrimp shell hydrolysis, with an improvement of 29.3 % and 124.9 %, respectively. Compared with SsExoChi18B and SsEndoChi19, SsExoChi18A exhibited the strongest antifungal effects against four plant pathogens by inhibiting mycelial growth and spore germination. This study provided good candidates for chitinous waste-processing enzymes and antifungal biocontrol agents. These synergic chitin-degrading enzymes of SCUT-3 are good targets for its further genetical modification to construct super chitinous waste-degrading bacteria with strong abilities to hydrolyze both protein and chitin, thereby providing a direction for the future path of the chitinous waste recycling industry.


Assuntos
Quitinases , Streptomyces , Quitina/química , Quitinases/química , Antifúngicos/farmacologia , Fungos/metabolismo
8.
Artigo em Chinês | WPRIM (Pacífico Ocidental) | ID: wpr-970446

RESUMO

Objective To compare the image quality of three high-resolution dynamic MRI methods for evaluating the motion of temporomandibular joint disc and condyle. Methods Twenty-five patients with suspected temporomandibular joint disorders were examined by single-shot fast spin-echo (SSFSE),fast imaging employing steady-state acquisition (FIESTA),and spoiled gradient echo (SPGR) on the oblique sagittal position.Two radiologists performed subjective and objective evaluation on the images with double-blind method.The subjective evaluation included the signal intensity of mandibular condyle,articular disc,soft tissue around articular disc,and lateral pterygoid muscle,the contrast between articular disc and condyle,the contrast between articular disc and surrounding soft tissue,condylar motion,and disc movement.The objective evaluation indexes included image signal intensity,signal-to-noise ratio (SNR),and contrast-to-noise ratio (CNR).The subjective and objective indexes of the image quality were compared between the three sequences. Results The SSFSE sequence had lower signal intensity of articular disc and higher signal intensity of condyle and surrounding soft tissue than FIESTA and SPGR sequences (all P<0.001).The SPGR sequence showed higher signal intensity of lateral pterygoid muscle than the SSFSE and FIESTA sequences (P=0.017,P<0.001).Among the three sequences,SSFSE sequence showed the clearest articular disc structure (χ2=41.952,P<0.001),the strongest contrast between articular disc and condyle (χ2=35.379,P<0.001),the strongest contrast between articular disc and surrounding soft tissue (χ2=27.324,P<0.001),and the clearest movement of articular disc (χ2=44.655,P<0.001).SSFSE and FIESTA sequences showed higher proportion of disc displacement and reduction than SPGR sequence (all P<0.001).The CNR (χ2=21.400,P<0.001),SNR (χ2=34.880,P<0.001),and condyle signal intensity (F=337.151,P<0.001) demonstrated differences among SSFSE,FIESTA,and SPGR sequences.The CNR of SSFSE sequence was higher than that of FIESTA sequence (P<0.001),while it had no significant difference between SSFSE and SPGR sequences (P=0.472).In addition,the SSFSE sequence had higher SNR and signal intensity than FIESTA and SPGR sequences (all P<0.001). Conclusion The best image quality can be observed from SSFSE sequence where both the structure and movement of temporomandibular joint are well displayed.Therefore,SSFSE is preferred for the examination of temporomandibular joint movement.


Assuntos
Humanos , Articulação Temporomandibular/diagnóstico por imagem , Movimento (Física) , Procedimentos de Cirurgia Plástica
9.
Artigo em Chinês | WPRIM (Pacífico Ocidental) | ID: wpr-959055

RESUMO

Objective To analyze the residents' satisfaction with the enforcement of The Regulations of Tianjin Municipality on Smoking Control in Public Places (hereinafter referred to as The Regulations) and its influencing factors. Methods From November to December 2020, 16 districts of Tianjin were selected as the research site, and one street was randomly selected from each district. The accidental sampling was used to conduct a questionnaire survey on 4,160 permanent residents in Tianjin. χ2 test was used in univariate analysis and multivariate logistic regression model was used to analyze and adjust the confounding factors. The public satisfaction and its influencing factors were analyzed. Results A total of 4 022 questionnaires were collected and 2 730 were included in the study. In 2020, 89.3 percent of Tianjin residents were satisfied with the enforcement of the Regulations. Compared with residents aged 15-24, residents in other age groups were less satisfied with the enforcement of the Regulations. Compared with residents with primary school education or below, residents with high school education or bachelor's degree or the same educational level were less satisfied with the enforcement of the Regulations. Residents with chronic diseases (OR=1.885 , P<0.01) and exposure to second-hand smoke in the last 30 days (OR=1.903, P<0.01) were less satisfied with the enforcement of the Regulations, while those who supported the Regulations (OR=0.511, P<0.01) and residents who had been exposed to public service advertisements on tobacco control in the last 30 days (OR=0.043, P<0.01) were more satisfied with the enforcement of the Regulations. Conclusion The residents of Tianjin are highly satisfied with the enforcement of the Regulations. Age, education background, support for the Regulations, chronic disease, exposure to secondhand smoke in the last 30 days and exposure to public service advertisements in the last 30 days are the main influencing factors of satisfaction with the enforcement of tobacco control regulations.

10.
Sci Total Environ ; 848: 157539, 2022 Nov 20.
Artigo em Inglês | MEDLINE | ID: mdl-35908690

RESUMO

Peatlands are vital soil carbon sinks, yet this function is jeopardized by plant carbon which could change the decomposition rate of soil organic carbon, knowing as "priming effect". How the priming effect depends on depth is a critical question in drained peatland given the heterogeneity of soil layers defined by the water table, which include the surface acrotelm, inter-mesotelm and deep catotelm. Here, through incubation, we quantified the response of these three soil layers to addition of 13C-labeled oxalate, glucose, cellulose, or cinnamic acid under anoxic or oxic conditions on the Zoige Plateau in Tibet. Soil carbon in the inter-mesotelm showed the greatest decomposition, with the highest humification index and lowest microbial biomass carbon, while the soil carbon at the surface acrotelm was least decomposed. Under anoxic conditions, exogenous carbon addition reduced CO2 emission by 12.2% at the surface acrotelm but increased by 59.8% in the inter-mesotelm and 23.5% in the deep catotelm. In the inter-mesotelm, oxalate addition significantly increased CO2 emission by 63.9%, while cinnamic acid significantly increased it by 92.9%. In the deep catotelm, cinnamic acid significantly increased CO2 emission by 55.3%. These results suggested that deeper soil organic carbon was more sensitive to plant carbon, particularly complex or recalcitrant carbon, than surface acrotelm soil. Under oxic conditions, carbon addition increased surface soil CO2 emission by 18.9%, and triggered even greater increase at inter-mesotelm and deep catotelm soil, with proportions of 48.3% and 32.0%, respectively. Under both conditions, peat profile CO2 release increased by 17.2-31.4% after exogenous carbon addition, and more than 77.8% of the increase came from the deeper two layers. These findings highlighted the need to take full account of priming effect of deeper soil in order to assess and predict the stability of carbon stocks in drained peatland.


Assuntos
Carbono , Solo , Dióxido de Carbono/análise , Celulose , Cinamatos , Glucose , Oxalatos , Plantas
11.
Front Microbiol ; 13: 867633, 2022.
Artigo em Inglês | MEDLINE | ID: mdl-35572630

RESUMO

Xanthomonas oryzae pv. textitoryzae (Xoo) is a causal agent of rice bacterial leaf blight (BLB), the major rice disease, which is seriously constraining rice production in Asia. The interaction between Xoo and rice is in a dynamic process, essentially the co-evolution. Tracking the occurrence of plant diseases and identifying the epidemic pathogens in time are critical to assessing the epidemic disease status and understanding the pathogen evolution. In 2020, the occurrences of rice BLB were spotted in many places of Guangxi, the major rice growing region in China. Two of the 2020-epidemic Xoo strains, namely, GXO20-01 and GXO20-06, were isolated from low land and high mountain paddies in Guangxi, respectively, and were demonstrated to be race R8 of Chinese Xoo strains, but with significantly different virulence on certain susceptible varieties of rice. The HiFi PacBio sequencing revealed that GXO20-01 and GXO20-06 share the highly syntenic genome structures and the major genome contents, but only differ in <10 genes, including one gene encoding for transcription activator-like effector (TALE). A phylogenomic analysis grouped GXO20-01 and GXO20-06 into the PX-A lineage, stood close to PXO563 and PXO71 strains, but stood away from the other Chinese Xoo strains; for example, the JL25 and YC11. A comparative genomic analysis revealed that the major pathogenicity/virulence genes are conserved in two, newly isolated Xoo strains and the other Xoo strains in PX-A lineage, including the majority genes for the TALomes. The genomic differences between the Xoo strains were pinpointed to a few tal genes, which were variable in both their numbers and sequences, even between GXO20-01 and GXO20-06, the two 2020-epidemic Xoo strains. The study further revealed the instability and variability of tal genes in Xoo and highlighted the utility of HiFi long-read sequencing in TALE analysis and pathogen tracking.

12.
Fish Shellfish Immunol ; 123: 453-459, 2022 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-35339659

RESUMO

CD4-a transmembrane glycoprotein molecule expressed on the surface of helper T (Th) cells-plays a central role in adaptive immune protection. In the current study, we developed a monoclonal antibody (mAb) against the grouper CD4-1. Western blotting and immunohistochemistry results revealed that the CD4-1 mAb could recognize the recombinant and natural protein of grouper CD4-1 as well as the CD4-1+ cells in the various tissues from grouper. Tissue distribution analyses revealed that the grouper CD4-1+ cells were expressed in all tissues tested in the healthy grouper, with greater localization in the thymus, head kidney, and spleen tissues. In addition, we tested the changes in the proportion of CD4-1+ cells in the thymus, head kidney, and the gills of grouper post the infection by C. irritans. Our data suggest that the CD4-1 mAb produced against grouper in the current study can be used as a tool to characterize CD4-1+ cells and to investigate the functions of the grouper CD4-1+ cells in the host response against pathogens infection.


Assuntos
Bass , Infecções por Cilióforos , Cilióforos , Doenças dos Peixes , Animais , Anticorpos Monoclonais/metabolismo , Cilióforos/fisiologia , Proteínas de Peixes/química , Filogenia
15.
Int J Radiat Oncol Biol Phys ; 112(5): 1243-1255, 2022 04 01.
Artigo em Inglês | MEDLINE | ID: mdl-34986380

RESUMO

PURPOSE: Radiation therapy (RT) is one of the main treatments for patients with unresectable hepatocellular carcinoma (HCC). Emerging evidence indicates that the cyclic guanosine monophosphate-adenosine monophosphate synthase (cGAS) stimulator of interferon gene (STING) pathway is crucial in RT-induced antitumor immune responses. Here, we discovered that activation of the cancer cell-intrinsic cGAS-STING pathway mediated immune cloaking after RT-induced DNA damage. METHODS AND MATERIALS: Key regulatory proteins in the cGAS-STING signaling pathway in human and murine HCC cell lines were knocked out or down using CRISPR and CRISPR-associated protein 9 or small interfering RNA. The underlying mechanism of immune cloaking and clinical significance of cGAS-STING-induced programmed cell death ligand 1 (PD-L1) expression were studied with both ex vivo analyses and in vitro experiments. RESULTS: RT upregulated PD-L1 in patients with HCC, which correlated with poor survival. RT activated cGAS-STING, increasing immune-checkpoint PD-L1 expression in human and mouse liver cancer cells. Ionizing radiation activated the STING-TANK-binding kinase 1 (TBK1)-interferon regulatory factor 3 (IRF3) innate immune pathway, leading to PD-L1 upregulation in HCC cells and inhibiting cytotoxic T-lymphocyte activity and protecting tumor cells from immune-mediated eradication. Knockdown of cGAS, STING, TBK1, and IRF3 reversed the antitumor effect of cytotoxic T-lymphocyte-mediated cytotoxicity after ionizing radiation in vitro or in vivo. RT potentiated the antitumor effect of programmed cell death protein 1 and PD-L1 axis blockade and augmented cytotoxic T-cell (CTL) infiltration in HCC tumors in immunocompetent mice. CD8 depletion compromised the synergetic antitumor effect of combined RT and anti-PD-L1 blockade, demonstrating that CD8+ CTLs are required for antitumor immunity induced by combination therapy. CONCLUSIONS: Our results identified an immune-cloaking mechanism for RT-activated, innate immune cGAS-STING and suggested that RT enhances HCC immunotherapy.


Assuntos
Carcinoma Hepatocelular , Neoplasias Hepáticas , Proteínas de Membrana , Nucleotidiltransferases , Animais , Antígeno B7-H1/metabolismo , Linfócitos T CD8-Positivos/imunologia , Carcinoma Hepatocelular/imunologia , Carcinoma Hepatocelular/radioterapia , Humanos , Neoplasias Hepáticas/imunologia , Neoplasias Hepáticas/radioterapia , Proteínas de Membrana/genética , Proteínas de Membrana/metabolismo , Camundongos , Nucleotidiltransferases/genética , Nucleotidiltransferases/metabolismo , Regulação para Cima
17.
Artigo em Chinês | WPRIM (Pacífico Ocidental) | ID: wpr-936232

RESUMO

Objective: To investigate the effects of dopamine on olfactory function and inflammatory injury of olfactory bulb in mice with allergic rhinitis (AR). Methods: AR mouse model was established by using ovalbumin (OVA), and the mice were divided into two groups: olfactory dysfunction (OD) group and without OD group through buried food pellet test (BFPT). The OD mice were randomly divided into 2 groups, and OVA combined with dopamine (3, 6, 9 and 12 days, respectively) or OVA combined with an equal amount of PBS (the same treatment time) was administered nasally. The olfactory function of mice was evaluated by BFPT. The number of eosinophils and goblet cells in the nasal mucosa were detected by HE and PAS staining. Western blotting, immunohistochemistry or immunofluorescence were used to detect the expression of olfactory marker protein (OMP) in olfactory epithelium, the important rate-limiting enzyme tyrosine hydroxylase (TH) of dopamine, and the marker proteins glial fibrillary acidic protein (GFAP) and CD11b of glial cell in the olfactory bulb. TUNEL staining was used to detect the damage of the olfactory bulb. SPSS 26.0 software was used for statistical analysis. Results: AR mice with OD had AR pathological characteristics. Compared with AR mice without OD, the expression of OMP in olfactory epithelium of AR mice with OD was reduced (F=26.09, P<0.05), the expression of GFAP and CD11b in the olfactory bulb was increased (F value was 38.95 and 71.71, respectively, both P<0.05), and the expression of TH in the olfactory bulb was decreased (F=77.00, P<0.05). Nasal administration of dopamine could shorten the time of food globule detection in mice to a certain extent, down-regulate the expression of GFAP and CD11b in the olfactory bulb (F value was 6.55 and 46.11, respectively, both P<0.05), and reduce the number of apoptotic cells in the olfactory bulb (F=25.64, P<0.05). But dopamine had no significant effect on the number of eosinophils and goblet cells in nasal mucosa (F value was 36.26 and 19.38, respectively, both P>0.05), and had no significant effect on the expression of OMP in the olfactory epithelium (F=55.27, P>0.05). Conclusion: Dopamine can improve olfactory function in mice with AR to a certain extent, possibly because of inhibiting the activation of glial cells in olfactory bulb and reducing the apoptotic injury of olfactory bulb cells.


Assuntos
Animais , Humanos , Camundongos , Modelos Animais de Doenças , Dopamina , Camundongos Endogâmicos BALB C , Mucosa Nasal/metabolismo , Bulbo Olfatório/patologia , Ovalbumina , Rinite Alérgica/metabolismo
18.
Artigo em Chinês | WPRIM (Pacífico Ocidental) | ID: wpr-927886

RESUMO

Ewing's sarcoma in the cervix is characterized by extremely rare occurrence,high degree of malignancy,and rapid progression.The diagnosis of this disease is based on pathology and immunohistochemistry. The main image of the case reported in this paper showed the cervical cyst with solid mass,large volume,and uneven density and signal,and the solid part can be strengthened in enhanced scanning.Because of the rapid growth,the lesion is prone to liquefaction necrosis and bleeding.Since the metastasis occurs early,timely diagnosis is essential.


Assuntos
Feminino , Humanos , Colo do Útero/patologia , Imuno-Histoquímica , Tumores Neuroectodérmicos Primitivos Periféricos/patologia , Sarcoma de Ewing/patologia , Neoplasias do Colo do Útero
19.
Artigo em Chinês | WPRIM (Pacífico Ocidental) | ID: wpr-927883

RESUMO

As the detection rate of pancreatic cystic neoplasms (PCN) increases,recommendations or guidelines for the diagnosis and treatment of PCN have been released from professional organizations.From the perspective of radiology,we compared seven guidelines in terms of general introduction,preoperative monitoring methods and strategies,stratification of risk factors,surgical indications,and postoperative follow-ups,aiming to provide references for the evaluation of images and the formulation of individualized approach for the treatment of PCN.


Assuntos
Humanos , Cisto Pancreático/terapia , Neoplasias Pancreáticas/terapia , Carbonitrila de Pregnenolona , Radiografia , Radiologia
20.
Fish Shellfish Immunol ; 119: 67-75, 2021 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-34607009

RESUMO

Hybridization is an artificial breeding strategy for generating potentially desirable offspring. Recently, a novel Hulong grouper hybrid (Epinephelus fuscogutatus × Epinephelus lanceolatus) yielded significant growth superiority over its parent. Improved innate immunity is considered as another desirable feature during hybridization. However, whether this Hulong grouper achieved disease resistance has not yet been revealed. In this study, we first examine the infection intensity of C. irritans in the Hulong grouper, and found that the Hulong grouper is less susceptible to C. irritans primary infection. A higher immobilization titer was found in the infected Hulong grouper at Day 2 when compared with the control grouper. Furthermore, severe hyperplasia was observed in the orange-spotted grouper, but not in the Hulong grouper's skin epidermis. To further understand the innate immune mechanism against C. irritans, we conducted a comparative transcriptome analysis of the Hulong grouper during the infection. There are 6464 differentially expressed genes (DEGs) identified in the skin between the control and infected Hulong grouper. This indicates that the innate immune components, such as the complement system, nicotinamide adenine dinucleotide phosphate (NADPH) oxidase, Interleukin 17 (IL-17) signaling pathway, and Toll-like receptor (TLR) signaling pathway were up-regulated during the infection. These results show that the C. irritans infection can induce a remarkable inflammatory response in the Hulong grouper. Moreover, a total of 75 pairs of orthologs with the ratio of nonsynonymous (Ka) to synonymous (Ks) substitutions >1, considered rapidly evolving genes (REGs), was identified between the Hulong and orange-spotted grouper. More critically, most REGs were enriched in the immune system, suggesting that rapid evolution of the immune system might occur in the Hulong grouper. These results provide a more comprehensive understanding of the innate immunity mechanism of the hybrid Hulong grouper.


Assuntos
Bass , Infecções por Cilióforos , Doenças dos Peixes , Parasitos , Animais , Bass/genética , Infecções por Cilióforos/veterinária , Proteínas de Peixes/genética , Perfilação da Expressão Gênica/veterinária , Imunidade Inata/genética , Transcriptoma
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