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1.
Microbiol Res ; 284: 127727, 2024 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-38636241

RESUMO

Heme oxygenase HO-1 (HMOX) regulates cellular inflammation and apoptosis, but its role in regulation of autophagy in Mycoplasma bovis infection is unknown. The objective was to determine how the HO-1/CO- Protein kinase RNA-like endoplasmic reticulum kinase (PERK)-Ca2+- transcription factor EB (TFEB) signaling axis induces autophagy and regulates clearance of M. bovis by bovine mammary epithelial cells (bMECs). M. bovis inhibited autophagy and lysosomal biogenesis in bMECs and suppressed HO-1 protein and expression of related proteins, namely nuclear factor erythroid 2-related factor 2 (Nrf2) and Kelch-like ECH-associated protein 1 (keap1). Activation of HO-1 and its production of carbon monoxide (CO) were required for induction of autophagy and clearance of intracellular M. bovis. Furthermore, when HO-1 was deficient, CO sustained cellular autophagy. HO-1 activation increased intracellular calcium (Ca2+) and cytosolic localization activity of TFEB via PERK. Knockdown of PERK or chelation of intracellular Ca2+ inhibited HO-1-induced M. bovis autophagy and clearance. M. bovis infection affected nuclear localization of lysosomal TFEB in the MiT/TFE transcription factor subfamily, whereas activation of HO-1 mediated dephosphorylation and intranuclear localization of TFEB, promoting autophagy, lysosomal biogenesis and autophagic clearance of M. bovis. Nuclear translocation of TFEB in HO-1 was critical to induce M. bovis transport and survival of infected bMECs. Furthermore, the HO-1/CO-PERK-Ca2+-TFEB signaling axis induced autophagy and M. bovis clearance, providing a viable approach to treat persistent M. bovis infections.


Assuntos
Autofagia , Fatores de Transcrição de Zíper de Leucina e Hélice-Alça-Hélix Básicos , Cálcio , Núcleo Celular , Retículo Endoplasmático , Células Epiteliais , Glândulas Mamárias Animais , Mycoplasma bovis , Animais , Bovinos , Células Epiteliais/microbiologia , Células Epiteliais/metabolismo , Cálcio/metabolismo , Fatores de Transcrição de Zíper de Leucina e Hélice-Alça-Hélix Básicos/metabolismo , Fatores de Transcrição de Zíper de Leucina e Hélice-Alça-Hélix Básicos/genética , Retículo Endoplasmático/metabolismo , Glândulas Mamárias Animais/microbiologia , Glândulas Mamárias Animais/metabolismo , Núcleo Celular/metabolismo , Feminino , eIF-2 Quinase/metabolismo , eIF-2 Quinase/genética , Infecções por Mycoplasma/microbiologia , Infecções por Mycoplasma/veterinária , Infecções por Mycoplasma/metabolismo , Lisossomos/metabolismo , Heme Oxigenase-1/metabolismo , Heme Oxigenase-1/genética , Monóxido de Carbono/metabolismo , Transdução de Sinais , Fator 2 Relacionado a NF-E2/metabolismo , Fator 2 Relacionado a NF-E2/genética
2.
Antioxidants (Basel) ; 13(2)2024 Jan 29.
Artigo em Inglês | MEDLINE | ID: mdl-38397769

RESUMO

Streptococcus uberis mastitis in cattle infects mammary epithelial cells. Although oxidative responses often remove intracellular microbes, S. uberis survives, but the mechanisms are not well understood. Herein, we aimed to elucidate antioxidative mechanisms during pathogenesis of S. uberis after isolation from clinical bovine mastitis milk samples. S. uberis's in vitro pathomorphology, oxidative stress biological activities, transcription of antioxidative factors, inflammatory response cytokines, autophagosome and autophagy functions were evaluated, and in vivo S. uberis was injected into the fourth mammary gland nipple of each mouse to assess the infectiousness of S. uberis potential molecular mechanisms. The results showed that infection with S. uberis induced early oxidative stress and increased reactive oxygen species (ROS). However, over time, ROS concentrations decreased due to increased antioxidative activity, including total superoxide dismutase (T-SOD) and malondialdehyde (MDA) enzymes, plus transcription of antioxidative factors (Sirt1, Keap1, Nrf2, HO-1). Treatment with a ROS scavenger (N-acetyl cysteine, NAC) before infection with S. uberis reduced antioxidative responses and the inflammatory response, including the cytokines IL-6 and TNF-α, and the formation of the Atg5-LC3II/LC3I autophagosome. Synthesis of antioxidants determined autophagy functions, with Sirt1/Nrf2 activating autophagy in the presence of S. uberis. This study demonstrated the evasive mechanisms of S. uberis in mastitis, including suppressing inflammatory and ROS defenses by stimulating antioxidative pathways.

3.
Sensors (Basel) ; 24(2)2024 Jan 10.
Artigo em Inglês | MEDLINE | ID: mdl-38257518

RESUMO

To investigate the impact of underground water seepage and soil stress fields on the deformation of excavation and support structures, this study initially identified the key influencing factors on excavation deformation. Subsequently, through a finite element simulation analysis using Plaxis, this study explored the effects of critical factors, such as the excavation support form, groundwater lowering depth, permeability coefficient, excavation layer, and sequence on excavation deformation. Furthermore, a comprehensive consideration of various adverse factors was integrated to establish excavation support early warning thresholds, and optimal dewatering strategies. Finally, this study validated the simulation analysis through an on-site in situ testing with wireless sensors in the context of a physical construction site. The research results indicate that the internal support system within the excavation piles exhibited better stability compared to the external anchor support system, resulting in a 34.5% reduction in the overall deformation. Within the internal support system, the factors influencing the excavation deformation were ranked in the following order: water level (35.5%) > permeability coefficient (17.62%) > excavation layer (11.4%). High water levels, high permeability coefficients, and multi-layered soils were identified as the most unfavorable factors for excavation deformation. The maximum deformation under the coupled effect of these factors was established as the excavation support early warning threshold, and the optimal dewatering strategy involved lowering the water level at the excavation to 0.5 m below the excavation face. The on-site in situ monitoring data obtained through wireless sensors exhibited low discrepancies compared to the finite element simulation data, indicating the high precision of the finite element model for considering the fluid-structure interaction.

4.
Radiol Med ; 129(1): 29-37, 2024 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-37919521

RESUMO

PURPOSE: This study aimed to develop a radiomics nomogram based on grayscale ultrasound (US) to distinguish triple-negative breast cancer (TNBC) from non-triple-negative breast cancer (NTNBC) prior to surgery. METHODS: A retrospective analysis of 454 breast carcinoma patients confirmed by pathology was conducted, with 317 patients in the training dataset (59 with TNBC) and 137 patients in the validation dataset (27 with TNBC). Clinical information, conventional US features, and radiomics features were collected, and the Radscore model was constructed after feature selection. Independent risk factors were identified using univariate and multivariate logistic regression analysis. The nomogram model was assessed using the receiver operating characteristic (ROC) curve analysis, calibration curve, decision curve analysis (DCA), net reclassification improvement (NRI) and integrated discrimination improvement (IDI). RESULTS: Tumor shape, margin, and calcification were independent risk factors in the clinical prediction model. Additionally, 16 radiomics features were selected to construct the Radscore model out of a total of 474 extracted features. The radiomics nomogram model, which incorporated tumor shape, margin, calcification, and Radscore, achieved an AUC value of 0.837 in the training dataset and 0.813 in the validation dataset, outperforming both the Radscore and clinical models in terms of predictive performance. The significant improvement of NRI and IDI indicated that the Radscore may be useful biomarkers for TNBC. CONCLUSION: The US-based radiomics nomogram showed satisfactory preoperative prediction of TNBC.


Assuntos
Calcinose , Neoplasias de Mama Triplo Negativas , Humanos , Modelos Estatísticos , Nomogramas , Radiômica , Estudos Retrospectivos , Prognóstico
5.
Acad Radiol ; 31(5): 1748-1761, 2024 05.
Artigo em Inglês | MEDLINE | ID: mdl-38097466

RESUMO

RATIONALE AND OBJECTIVES: This study aimed to create a nomogram model that combines clinical factors with radiomics analysis of both intra- and peritumoral regions extracted from preoperative digital breast tomosynthesis (DBT) images, in order to develop a reliable method for predicting the lymphovascular invasion (LVI) status in invasive breast cancer (IBC) patients. MATERIALS AND METHODS: A total of 178 patients were randomly split into a training dataset (N = 124) and a validation dataset (N = 54). Comprehensive clinical data, encompassing DBT features, were gathered for all cases. Radiomics features were extracted and selected from intra- and peritumoral region to establish radiomics signature (Radscore). To construct the clinical model and nomogram model, univariate and multivariate logistic regression analyses were utilized to identify independent risk factors. To assess and validate these models, various analytical methods were employed, including receiver operating characteristic (ROC) curve analysis, calibration curve analysis, decision curve analysis (DCA), net reclassification improvement (NRI), and integrated discriminatory improvement (IDI). RESULTS: The clinical model is constructed based on two independent risk factors: tumor margin and the DBT-reported lymph node metastasis (DBT_reported_LNM). Incorporating Radscore_Combine (utilizing both intra- and peritumoral radiomics features), tumor margin, and DBT_reported_LNM into the nomogram achieved a reliable predictive performance, with area under the curve (AUC) values of 0.906 and 0.905 in both datasets, respectively. The significant improvement demonstrated by the NRI and IDI indicates that the Radscore_Combine could be a valuable biomarker for effectively predicting the status of LVI. CONCLUSION: The nomogram demonstrated a reliable ability to predict LVI in IBC patients.


Assuntos
Neoplasias da Mama , Metástase Linfática , Mamografia , Invasividade Neoplásica , Nomogramas , Humanos , Neoplasias da Mama/diagnóstico por imagem , Neoplasias da Mama/patologia , Feminino , Pessoa de Meia-Idade , Invasividade Neoplásica/diagnóstico por imagem , Mamografia/métodos , Metástase Linfática/diagnóstico por imagem , Adulto , Idoso , Estudos Retrospectivos , Reprodutibilidade dos Testes , Cuidados Pré-Operatórios/métodos , Radiômica
6.
Microb Pathog ; 183: 106270, 2023 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-37499842

RESUMO

Autophagy is a highly conserved cellular defensive mechanism that can eliminate bacterial pathogens such as Streptococcus uberis, that causes mastitis in cows. However, S. uberis induced autophagy is still unclear. In this study, we tested if certain inflammatory cytokines such as IL-6, TNF-α, and IFN-γ, critical in mastitis due to S. uberis infection, regulate autophagy activation in bovine mammary epithelial cells (bMECs). Using Western blot and laser scanning confocal microscope in bMECs challenged by S. uberis, showed that the expression of IL-6, TNF-α, IFN-γ oscillated with the expressions of autophagic Atg5, ULK1, PTEN, P62, and LC3ӀӀ/LC3Ӏ. S. uberis infection induced autophagosomes and LC3 puncta in bMECs with upregulation of Atg5, ULK1, PTEN, LC3ӀӀ/LC3Ӏ, and downregulation of P62. The levels of IL-6, TNF-α, and IFN-γ increased during autophagy flux formation to decrease during autophagy induction. Autophagy inhibition increased the expression of IL-6, TNF-α, and IFN-γ and increased S. uberis burden. This study indicates autophagy is induced during S. uberis infection and IL-6, TNF-α, and IFN-γ contribute to autophagy and autophagy flux formation.


Assuntos
Mastite Bovina , Infecções Estreptocócicas , Feminino , Bovinos , Animais , Humanos , Fator de Necrose Tumoral alfa/metabolismo , Infecções Estreptocócicas/microbiologia , Interleucina-6/metabolismo , Glândulas Mamárias Animais/microbiologia , Interferon gama/metabolismo , Células Epiteliais/microbiologia , Autofagia , Mastite Bovina/microbiologia
7.
BMC Cancer ; 23(1): 604, 2023 Jun 30.
Artigo em Inglês | MEDLINE | ID: mdl-37391709

RESUMO

BACKGROUND: Aspartoacylase (ASPA) is a gene that plays an important role in the metabolic reprogramming of cancer. However, the clinical relevance of ASPA in gastric cancer (GC) has not been demonstrated. METHODS: The link between ASPA and the clinical features of GC was determined using two public genomic databases. The multivariate Cox proportional hazard model and generalised linear regression model were applied to examine whether the ASPA level is associated with the prognosis and other pathological factors. In addition, the role of specific genes in the infiltration of immune cells in the setting of GC was investigated using a further immunological database. The expression level of various proteins was detected using a western blotting assay. Transwell and methyl thiazolyl tetrazolium tests were applied for the detection of cellular invasion and proliferation, with small hairpin ribonucleic acid used to knockdown ASPA. RESULTS: According to the multivariate Cox regression results, the down-regulated ASPA expression is a distinct prognostic factor. Furthermore, ASPA has significant positive correlations with the infiltration of immune cells in GC lesions. Compared to the non-cancer tissues, the GC tissues had a significantly lower level of ASPA expression (p < 0.05). Using knockdown and overexpression techniques, it was demonstrated that ASPA affects the capacity of cell lines for GC to both proliferate and invade. CONCLUSION: Overall, ASPA could promote the occurrence and development of GC and presents a promising predictive biomarker for the disease since it is favourably connected with immune infiltrates and negatively correlated with prognosis.


Assuntos
Neoplasias Gástricas , Humanos , Neoplasias Gástricas/genética , Amidoidrolases/genética , Western Blotting , Linhagem Celular
8.
J Cancer Res Clin Oncol ; 149(11): 9317-9328, 2023 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-37208454

RESUMO

PURPOSE: This study aimed to establish a radiomics nomogram model based on digital breast tomosynthesis (DBT) images, to predict the status of axillary lymph nodes (ALN) in patients with breast carcinoma. METHODS: The data of 120 patients with confirmed breast carcinoma, including 49 cases with axillary lymph node metastasis (ALNM), were retrospectively analyzed in this study. The dataset was randomly divided into a training group consisting of 84 patients (37 with ALNM) and a validation group comprising 36 patients (12 with ALNM). Clinical information was collected for all cases, and radiomics features were extracted from DBT images. Feature selection was performed to develop the Radscore model. Univariate and multivariate logistic regression analysis were employed to identify independent risk factors for constructing both the clinical model and nomogram model. To evaluate the performance of these models, receiver operating characteristic (ROC) curve analysis, calibration curve, decision curve analysis (DCA), net reclassification improvement (NRI), and integrated discriminatory improvement (IDI) were conducted. RESULTS: The clinical model identified tumor margin and DBT_reported_LNM as independent risk factors, while the Radscore model was constructed using 9 selected radiomics features. Incorporating tumor margin, DBT_reported_LNM, and Radscore, the radiomics nomogram model exhibited superior performance with AUC values of 0.933 and 0.920 in both datasets, respectively. The NRI and IDI showed a significant improvement, suggesting that the Radscore may serve as a useful biomarker for predicting ALN status. CONCLUSION: The radiomics nomogram based on DBT demonstrated effective preoperative prediction performance for ALNM in patients with breast cancer.


Assuntos
Neoplasias da Mama , Nomogramas , Humanos , Feminino , Metástase Linfática , Estudos Retrospectivos , Neoplasias da Mama/diagnóstico por imagem , Neoplasias da Mama/cirurgia , Linfonodos/diagnóstico por imagem , Linfonodos/cirurgia
9.
Front Oncol ; 12: 1071677, 2022.
Artigo em Inglês | MEDLINE | ID: mdl-36568215

RESUMO

Purpose: The aim of this study was to develop a radiomics nomogram based on grayscale ultrasound (US) for preoperatively predicting Lymphovascular invasion (LVI) in patients with pathologically confirmed T1 (pT1) breast invasive ductal carcinoma (IDC). Methods: One hundred and ninety-two patients with pT1 IDC between September 2020 and August 2022 were analyzed retrospectively. Study population was randomly divided in a 7: 3 ratio into a training dataset of 134 patients (37 patients with LVI-positive) and a validation dataset of 58 patients (19 patients with LVI-positive). Clinical information and conventional US (CUS) features (called clinic_CUS features) were recorded and evaluated to predict LVI. In the training dataset, independent predictors of clinic_CUS features were obtained by univariate and multivariate logistic regression analyses and incorporated into a clinic_CUS prediction model. In addition, radiomics features were extracted from the grayscale US images, and the radiomics score (Radscore) was constructed after radiomics feature selection. Subsequent multivariate logistic regression analysis was also performed for Radscore and the independent predictors of clinic_CUS features, and a radiomics nomogram was developed. The performance of the nomogram model was evaluated via its discrimination, calibration, and clinical usefulness. Results: The US reported axillary lymph node metastasis (LNM) (US_LNM) status and tumor margin were determined as independent risk factors, which were combined for the construction of clinic_CUS prediction model for LVI in pT1 IDC. Moreover, tumor margin, US_LNM status and Radscore were independent predictors, incorporated as the radiomics nomogram model, which achieved a superior discrimination to the clinic_CUS model in the training dataset (AUC: 0.849 vs. 0.747; P < 0.001) and validation dataset (AUC: 0.854 vs. 0.713; P = 0.001). Calibration curve for the radiomic nomogram showed good concordance between predicted and actual probability. Furthermore, decision curve analysis (DCA) confirmed that the radiomics nomogram had higher clinical net benefit than the clinic_CUS model. Conclusion: The US-based radiomics nomogram, incorporating tumor margin, US_LNM status and Radscore, showed a satisfactory preoperative prediction of LVI in pT1 IDC patients.

10.
Front Immunol ; 13: 934819, 2022.
Artigo em Inglês | MEDLINE | ID: mdl-36148236

RESUMO

Prototheca bovis, a highly contagious pathogen, causes bovine mastitis, resulting in premature culling of affected cows and severe economic losses. Infection with P. bovis caused oxidative stress and apoptosis in bovine mammary epithelial cells (bMECs); however, mechanisms underlying P. bovis-induced autophagy remain unclear. Therefore, the autophagy flux induced by P. bovis in bMECs was analyzed by Western blot and laser scanning confocal microscopy. Expression levels of proteins in the HIF-1α and AMPKα/ULK1 pathway, including HIF-1α, AMPKα, p-AMPKα, ULK1, p-ULK1, mTOR, and p-mTOR, plus expression of autophagy-related genes including SQSTM1/p62, Atg5, Beclin1, and LC3II/LC3I, were quantified with Western blot. Infection with P. bovis induced autophagosomes and LC3 puncta in bMECs that were detected using transmission electron microscopy and laser scanning confocal microscopy, respectively. In addition, lysosome-associated proteins Rab7 and LAMP2a, and lysosomal activity were measured with Western blot and laser scanning confocal microscopy. Infection with P. bovis induced an unobstructed autophagic flux, increased protein expression of LC3II/LC3I, and decreased SQSTM1/p62 protein expression at 6 hpi. Furthermore, P. bovis upregulated protein expression in the HIF-1α and AMPKα/ULK1 pathway and increased the ratio of LC3II/LC3I, implying autophagy was activated in bMECs. However, deletion of AMPKα or ULK1 decreased LC3II/LC3I expression levels and LC3 puncta numbers, suggesting that autophagy was inhibited in bMECs. Additionally, deficiency of HIF-1α decreased protein expression of AMPKα and ULK1 as well as LC3 puncta numbers, and autophagy induced by P. bovis was also inhibited in bMECs. At 6 hpi, lysosome-associated protein Rab7 was decreased and LAMP2a was increased, indicating normal autophagy. In contrast, at 12 hpi, expression of Rab7 and LAMP2a proteins indicated that autophagy was inhibited in bMECs at that time. Therefore, we confirmed that P. bovis infection induced autophagy in bMECs via the HIF-1α and AMPKα/ULK1 pathway, with involvement of lysosome-associated protein Rab7 and LAMP2a.


Assuntos
Prototheca , Proteínas Quinases Ativadas por AMP/metabolismo , Animais , Autofagia , Proteína Beclina-1/genética , Proteína Beclina-1/metabolismo , Bovinos , Células Epiteliais/metabolismo , Feminino , Prototheca/metabolismo , Proteína Sequestossoma-1/metabolismo , Serina-Treonina Quinases TOR/metabolismo
11.
Front Microbiol ; 13: 935547, 2022.
Artigo em Inglês | MEDLINE | ID: mdl-35958147

RESUMO

Although autophagy can eliminate some intracellular pathogens, others, e.g., Staphylococcus aureus, Salmonella, Mycoplasma bovis, can evade it. The phosphoinositide 3-kinase (PI3K)/protein kinase B (Akt)/mammalian target of rapamycin (mTOR) pathway, a key regulator of autophagy, is involved in initiation and promotion of a range of pathological diseases. As the effects of M. bovis on the autophagic pathway are not well documented, our objective was to elucidate the effects of M. bovis infection on the PI3K-Akt-mTOR cellular autophagic pathway in bovine mammary epithelial cells (bMECs). Ultrastructure of bMECs infected with M. bovis was assessed with transmission electron microscopy, co-localization of LC3 puncta with M. bovis was confirmed by laser confocal microscopy, and autophagy-related indicators were quantified with Western blotting and RT-PCR. In M. bovis-infected bMECs, intracellular M. bovis was encapsulated by membrane-like structures, the expression level of LC3-II and Beclin1 protein decreased at the middle stage of infection, degradation of SQSTM1/P62 was blocked, autophagy of bMECs was inhibited, and PI3K-Akt-mTOR protein was activated by phosphorylation. Furthermore, the tumor suppressor PTEN can inhibit the PI3K-Akt signaling pathway through dephosphorylation of phosphatidylinositol 3,4,5-trisphosphate and may be important for cellular resistance to infection. In the present study, the number of intracellular M. bovis was inversely related to the change in the level of autophagy markers (e.g., LC3-II, SQSTM1/P62) within host cells induced by the low knockdown of Akt or PTEN. We concluded that M. bovis-infected bMECs alleviated cellular autophagy through a PI3K-Akt-mTOR pathway, and that PTEN acted as a protective gene regulating autophagy, a key step in controlling infection.

12.
Cancer Manag Res ; 14: 1515-1524, 2022.
Artigo em Inglês | MEDLINE | ID: mdl-35478712

RESUMO

Objective: To investigate the value of gray-scale ultrasound (US) image histogram in the differential diagnosis between small (≤2.00 cm), oval, or round triple negative breast invasive ductal carcinoma (TN-IDC) and fibroadenoma (FA). Methods: Fifty-five cases of triple negative breast invasive ductal carcinoma (TN-IDC group) and 57 cases of breast fibroadenoma (FA group) confirmed by pathology in Hubei cancer hospital from September 2017 to September 2021 were analyzed retrospectively. The gray-scale US images were analyzed by histogram analysis method, from which some parameters (including mean, variance, skewness, kurtosis and 1st, 10th, 50th, 90th and 99th percentile) can be obtained. Intraclass correlation coefficient (ICC) was used to evaluate the inter observer reliability of histogram parameters. Histogram parameters between the TN-IDC and FA groups were compared using independent Student's t-test or Mann-Whitney U-test, respectively. In addition, the receiver operating characteristic (ROC) curve analysis was used for the significant parameters to calculate the differential diagnosis efficiency. Results: All the histogram parameters showed excellent inter-reader consistency, with the ICC values ranged from 0.883 to 0.999. The mean value, 1st, 10th, 50th, 90th and 99th percentiles of TN-IDC group were significantly lower than those of FA group (P < 0.05). The area under ROC curve (AUC) values of mean and n percentiles were from 0.807 to 0.848. However, there were no significant differences in variance, skewness and kurtosis between the two groups (P > 0.05). Conclusion: Histogram analysis of gray-scale US images can well distinguish small, oval, or round TN-IDC from FA.

13.
Free Radic Biol Med ; 184: 148-157, 2022 05 01.
Artigo em Inglês | MEDLINE | ID: mdl-35417750

RESUMO

Prototheca bovis is a serious pathogen for animals, but pathogenesis of P. bovis mastitis is unclear. The objective was to characterize how P. bovis induces inflammatory responses in mouse mammary gland tissue and mammary epithelial cells (mMECs). Prototheca bovis damaged mammary gland tissue and mitochondrial structure, and induced oxidative stress, as evident by significant increases in mtROS and MDA concentrations and significant decreases in T-SOD activity in both mammary gland tissue and mMECs. Expression of Nrf2, HO-1 and Keap1 proteins was significantly changed in mammary gland tissue and mMECs after P. bovis infection. Additionally, cytokines (IL-1ß, IL-6 and IL-18) and protein expressions in NF-κB and in the NLRP3 inflammasome pathway were significantly increased in mammary gland tissue and mMECs. In the P. bovis group, treatment with N-acetyl-l-cysteine (NAC) significantly decreased protein expression in NF-κB and the NLRP3 inflammasome pathway, as well as IL-1ß, IL-6 and IL-18, whereas protein expression in the Nrf2 pathway was significantly changed. Inhibition of NF-κB or NLRP3 significantly decreased expression of IL-1ß and IL-18 proteins in mMECs infected with P. bovis. Additionally, activating Nrf2 inhibited expression of NLRP3 and IL-1ß. In conclusion, P. bovis induced an inflammatory response via the NF-κB/NLRP3 inflammasome pathway; however, scavenging ROS or activating Nrf2 mitigated the inflammatory response in infected mMECs.


Assuntos
Infecções , Inflamassomos , Glândulas Mamárias Animais , Prototheca , Animais , Feminino , Camundongos , Células Epiteliais/metabolismo , Inflamassomos/genética , Inflamassomos/metabolismo , Interleucina-18/genética , Interleucina-18/metabolismo , Interleucina-6/genética , Interleucina-6/metabolismo , Proteína 1 Associada a ECH Semelhante a Kelch/metabolismo , Fator 2 Relacionado a NF-E2/genética , Fator 2 Relacionado a NF-E2/metabolismo , NF-kappa B/metabolismo , Proteína 3 que Contém Domínio de Pirina da Família NLR/metabolismo , Prototheca/metabolismo , Espécies Reativas de Oxigênio/metabolismo , Transdução de Sinais/fisiologia , Glândulas Mamárias Animais/patologia
14.
Int J Gen Med ; 14: 8293-8299, 2021.
Artigo em Inglês | MEDLINE | ID: mdl-34815701

RESUMO

BACKGROUND: Immunotherapy is considered as a powerful and promising clinical approach for the treatment of gastric cancer (GC). However, it is still challenging to precisely screen patients who potentially benefit from immune checkpoint therapy (ICT). Identification of potential biomarkers for selecting patients sensitive to immunotherapy was urgently needed. METHODS: Public sequence data and corresponding clinical data were used to explore the potential biomarkers for immunotherapy. RESULTS: We found that CSMD1 is the most frequently mutated gene and its mutation is highly correlated with prognosis in gastric cancer patients. Interestingly, patients with mutated CSMD1 exhibit a high mutation burden and upregulated PDL1 expression. The ratio of microsatellite instability (MSI) in the CSMD1 mutation cohort was higher than that in the cohort without CSMD1 mutation. Furthermore, patients with CSMD1 mutation have been found to possess a higher number of activated CD4+ T cells and neoantigens. CONCLUSION: CSMD1 mutation may act as a novel biomarker for assessing the survival and immune therapy response in patients with gastric cancer.

15.
Quant Imaging Med Surg ; 11(4): 1518-1531, 2021 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-33816188

RESUMO

BACKGROUND: To investigate the value of apparent diffusion coefficient (ADC) histograms in differentiating Ki-67 expression in T1 stage invasive ductal breast carcinoma (IDC). METHODS: The records of 111 patients with pathologically confirmed T1 stage IDC who underwent magnetic resonance imaging prior to surgery were retrospectively reviewed. The expression of Ki-67 in tumor tissue samples from the patients was assessed using immunohistochemical (IHC) staining, with a cut-off value of 25% for high Ki-67 labeling index (LI). ADC images of the maximum lay of tumors were selected, and the region of interest (ROI) of each lay was delineated using the MaZda software and analyzed by histogram. The correlations between the histogram characteristic parameters and the Ki-67 LI were investigated. Additionally, the histogram characteristic parameters of the high Ki-67 group (n=54) and the low Ki-67 group (n=57) were statistically analyzed to determine the characteristic parameters with significant difference. Receiver operator characteristic (ROC) analyses were further performed for the significant parameters. RESULTS: The mean value, and the 1st, 10th, 50th, 90th, and 99th percentiles were found to be negatively correlated with the expression of Ki-67 (all P values <0.001), with a correlation coefficient of -0.624, -0.749, -0.717, -0.621, -0.500, and -0.410, respectively. In the high Ki-67 group, the mean value, and the 1st, 10th, 50th, 90th, and 99th percentiles extracted by the histogram were significantly lower (all P values <0.05) than that of the low Ki-67 group, with areas under the ROC curves ranging from 0.717-0.856. However, the variance, skewness, and kurtosis did not differ between the two groups (all P values >0.05). CONCLUSIONS: Histogram-derived parameters for ADC images can serve as a reliable tool in the prediction of Ki-67 proliferation status in patients with T1 stage IDC. Among the significant ADC histogram values, the 1st and 10th percentiles showed the best predictive values.

16.
Updates Surg ; 73(3): 1049-1056, 2021 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-33394355

RESUMO

The objective of this study is to evaluate the perioperative and long-term outcomes of robot-assisted hemicolectomy (RAH) versus laparoscopy-assisted hemicolectomy (LAH) for left-sided colon cancers. Patients who underwent RAH and LAH from January 2012 to December 2018 were reviewed retrospectively. Patient characteristics and perioperative outcomes were compared between the two groups. Follow-up consultations were conducted to evaluate the long-term outcomes of these procedures. A total of 460 patients were included (RAH, n = 205; LAH, n = 255). There was no difference in patient characteristics between the two groups. Compared with the LAH group, the RAH group showed longer operative time (150.23 ± 43.77 min vs. 125.85 ± 38.67 min, p < 0.001) and higher surgery cost (6.33 ± 1.50 vs. 2.88 ± 0.72 thousand $, p < 0.001) and total hospital cost (14.97 ± 3.05 vs. 9.05 ± 2.31 thousand $, p < 0.001). No significant differences in tumor pathology, TNM staging, and perioperative outcomes were observed. There were no obvious differences in the 3-year and 5-year overall survival (OS) or 3-year and 5-year disease-free survival. Cox multivariate analyses showed that age, body mass index, and intravascular cancer embolus were independent risk factors for OS. Moreover, the robotic approach was not an independent risk factor for prognosis of left-sided colon cancers. RAH is an appropriate operation method for left-sided colon cancer, with perioperative and long-term outcomes comparable to those of laparoscopy. Meanwhile, RHA has longer operative time and higher cost.


Assuntos
Colectomia , Neoplasias do Colo , Laparoscopia , Procedimentos Cirúrgicos Robóticos , Robótica , Colectomia/métodos , Neoplasias do Colo/cirurgia , Humanos , Estudos Retrospectivos , Resultado do Tratamento
17.
Updates Surg ; 73(3): 1037-1048, 2021 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-33481214

RESUMO

Surgery is developing in the direction of minimal invasiveness, and robotic surgery is becoming increasingly adopted in colonic resection procedures. The ergonomic improvements of robot promote surgical performance, reduce workload for surgeons and benefit patients. Compared with laparoscopy-assisted colon surgery, the robotic approach has the advantages of shorter length of hospital stay, lower rate of conversion to open surgery, and lower rate of intraoperative complications for short-term outcomes. Synchronous robotic liver resection with colon cancer is feasible. The introduction of the da Vinci Xi System (Intuitive Surgical, Inc., Sunnyvale, CA, USA) has introduced more flexibility to colonic operations. Optimization of the suprapubic surgical approach may shorten the length of hospital stay for patients who undergo robotic colonic resection. Single-port robotic colectomy reduces the number of robotic ports for better looking and faster recovery. Intestinal anastomosis methods using totally robotic surgery result in shorter time to bowel function recovery and tolerance to a solid diet, although the operative time is longer. Indocyanine green is used as a tracer to assess blood supplementation in the anastomosis and marks lymph nodes during operation. The introduction of new surgical robots from multiple manufacturers is bound to change the landscape of robotic surgery and yield high-quality surgical outcomes. The present article reviews recent advances in robotic colonic resection over the past five years.


Assuntos
Colo , Neoplasias do Colo , Laparoscopia , Procedimentos Cirúrgicos Robóticos , Robótica , Colectomia , Colo/cirurgia , Neoplasias do Colo/cirurgia , Humanos , Duração da Cirurgia
18.
Int J Clin Exp Pathol ; 13(8): 2153-2157, 2020.
Artigo em Inglês | MEDLINE | ID: mdl-32922613

RESUMO

Pilomatrix carcinoma (PC) is a rare skin adnexal neoplasm derived from piliferous follicles, usually occurring in the head and neck region. An optimal treatment for PC has not yet been established, while surgery with wide margins is recommended, with radiation therapy (RT) and chemotherapy improving the curative effect. Location of this tumor in the breast is exceedingly rare, especially for a male. We now report an unusual case of a 53-year-old male who presented with 2 palpable masses in the right breast, which had been removed surgically about 4 and a half years prior, but recurred after 7 months. Ultrasonography revealed 2 irregular low-echo masses with a well-defined boundary, and computed tomography (CT) showed 2 soft tissue masses in subcutaneous tissue of the right breast. The tumors were completely removed without RT and chemotherapy. After about 4 years' follow-up, the patient remains free of local recurrence and metastasis. To the best of our knowledge, only 2 cases of PC in the breast region have been reported, but were female.

19.
Medicine (Baltimore) ; 99(27): e20859, 2020 Jul 02.
Artigo em Inglês | MEDLINE | ID: mdl-32629673

RESUMO

RATIONALE: Extra osseous Ewing sarcoma (ES), an uncommon malignant neoplasm, accounts for about 15% of Ewing sarcoma, which mainly affects paravertebral region, lower extremity, chest wall, retroperitoneum, pelvis, and hip. Here is a 54-year-old woman of primary vaginal Ewing sarcoma with uterine fibroid, which has been fewly known or reported. PATIENT CONCERNS: The patient was admitted to our hospital because of vaginal pain. Her uterus showed as parallel position and enlarged as about 3 months of pregnancy size. DIAGNOSIS: Magnetic resonance imaging (MRI) and ultrasonography (US) demonstrated 2 heterogeneous masses in the vagina and uterus, respectively. Ultrasound-guided puncture biopsy revealed a malignant tumor in the right lateral vaginal wall. INTERVENTIONS: The patient was treated by hysterectomy, bilateral salpingo-oophorectomy, and tumors excision, with the subsequent treatment of chemotherapy. OUTCOMES: The patient recovered well without local recurrence for >1 year. LESSONS: Primary vaginal Ewing sarcoma is extremely rare. The treatments of uterine fibroid include uterine artery embolization and surgical options, While wide local excision followed by adjuvant chemotherapy and/or radiotherapy should be recommended for the vaginal ES.


Assuntos
Leiomioma/complicações , Sarcoma de Ewing/complicações , Sarcoma de Ewing/diagnóstico , Neoplasias Vaginais/complicações , Neoplasias Vaginais/diagnóstico , Feminino , Humanos , Leiomioma/diagnóstico , Pessoa de Meia-Idade , Sarcoma de Ewing/patologia , Neoplasias Vaginais/patologia
20.
Front Genet ; 11: 301, 2020.
Artigo em Inglês | MEDLINE | ID: mdl-32373154

RESUMO

BACKGROUND: Aberrant DNA methylation is a crucial epigenetic regulator that is closely related to the occurrence and development of various cancers, including breast cancer (BC). The present study aimed to identify a novel methylation-based prognosis biomarker panel by integrally analyzing gene expression and methylation patterns in BC patients. METHODS: DNA methylation and gene expression data of breast cancer (BRCA) were downloaded from The Cancer Genome Atlas (TCGA). R packages, including ChAMP, SVA, and MethylMix, were applied to identify the unique methylation-driven genes. Subsequently, these genes were subjected to Metascape for GO analysis. Univariant Cox regression was used to identify survival-related genes among the methylation-driven genes. Robust likelihood-based survival modeling was applied to define the prognosis markers. An independent data set (GSE72308) was used for further validation of our risk score system. RESULTS: A total of 879 DNA methylation-driven genes were identified from 765 BC patients. In the discovery cohort, we identified 50 survival-related methylation-driven genes. Finally, we built an eight-methylation-driven gene panel that serves as prognostic predictors. CONCLUSIONS: Our analysis of transcriptome and methylome variations associated with the survival status of BC patients provides a further understanding of basic biological processes and a basis for the genetic etiology in BC.

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