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OBJECTIVE: To explore the clinical characteristics and prognosis of patients with diffuse large B-cell lymphoma (DLBCL) of the breast. METHODS: The clinical data of 28 DLBCL patients admitted to Shanxi Provincial Cancer Hospital from January 2013 to January 2023 were retrospectively analysed, including 13 cases of primary breast DLBCL (PB-DLBCL) and 15 cases of secondary breast DLBCL (SB-DLBCL), and the data of their clinical manifestations, laboratory tests, pathological examinations, treatment protocols, and follow-up were statistically analyzed. RESULTS: There were significant differences in IPI score, LDH level and ß2- microglobulin between PB-DLBCL and SB-DLBCL patients (P < 0.05). Among the 23 patients with breast DLBCL who received regular treatment, 13 patients achieved complete remission (9 patients with PB-DLBCL and 4 patients with SB-DLBCL) after initial treatment. By the end of follow-up, 11 patients relapsed or progressed (5 patients with PB-DLBCL and 6 patients with SB-DLBCL) and 9 patients died (3 patients with PB-DLBCL and 6 patients with SB-DLBCL). The 5-year OS rate was (75.0±15.3)% in PB-DLBCL group and (32.3±17.1)% in SB-DLBCL group. The 5-year PFS rate was ï¼59.1±19.8ï¼% in PB-DLBCL and 0% in SB-DLBCL group. The 5-year OS rate and PFS rate of PB-DLBCL patients were higher than those of SB-DLBCL patients (P < 0.05); the 5-year OS rate of the combined central preventive treatment group was higher than that of the chemotherapy group (P < 0.05). CONCLUSION: Breast DLBCL is divided into two categories: PB-DLBCL and SB-DLBCL. Compared with SB-DLBCL, PB-DLBCL has the characteristics of lower IPI score, LDH, and ß2-microglobulin levels. PB-DLBCL patients have a longer survival period. In addition, the prognosis of patients receiving central preventive treatment is more optimistic.
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Neoplasias da Mama , Linfoma Difuso de Grandes Células B , Humanos , Estudos Retrospectivos , Prognóstico , Neoplasias da Mama/terapia , Feminino , Taxa de Sobrevida , Microglobulina beta-2 , Pessoa de Meia-IdadeRESUMO
OBJECTIVES: To observe the effect of electroacupuncture (EA) preconditioning at "Quchi" (LI11) and "Xuehai" (SP10) in prevention of urticaria. METHODS: Twenty-four male SD rats were randomly divided into control, model and preconditioning of EA (Pre-EA) groups (8 rats/group). The urticaria model was established by intradermal injection of dilute allogeneic antioalbumin serum at the spots of the bilateral symmetry of the spine on the back, and followed by tail venous injection of mixture solution of egg albumin diluent, plus 0.5% Evans blue and normal saline. Ten days before the end of modeling, rats of the pre-EA group received EA stimulation of LI11 and SP10 for 20 min, once a day for 10 consecutive days. The times of rat's scratching the sensitized skin were recorded. HE staining method was used to observe the pathological changes of skin tissue, and toluidine blue staining method was used to observe the morphology of mast cells (MCs) in the skin, blood, mesentery, and peritoneal fluid, and calculate the degranulation rate. Immunohistochemical stainning was used to detect immunoglobulin E (IgE), histamine (HIS), and 5-hydroxytryptamine (5-HT) expressions in subcutaneous tissue. NOD like receptor thermal domain associated protein 3 (NLRP3) inflammasome, apoptosis related granule protein (ASC), and cysteine aspartate aminotransferase 1 (Caspase-1) protein expression levels in skin tissue were detected by Western blot. The contents of serum interleukin(IL)-1ß and IL-18 were detected using ELISA method. RESULTS: Compared with the control group, the scratching times, amount of Evans blue exudation of the sensitized blue spots, degranulation rate of MCs in skin, blood, mesentery and peritoneal fluid, the expression levels of IgE, HIS, 5-HT in subcutaneous tissue, protein expression levels of NLRP3, ASC, Caspase-1 in skin tissue, and the contents of serum IL-1ß and IL-18 were significantly increased (P<0.01, P<0.05) in the model group. In comparison with the model group, the scratching times, amount of Evans blue exudation of the sensitized blue spots, degranulation rate of MCs, the expression levels of IgE, HIS, 5-HT in subcutaneous tissue, protein expression levels of NLRP3, ASC, Caspase-1 in skin tissue, and the contents of serum IL-1ß and IL-18 in EA group were significantly decreased (P<0.01, P<0.05). CONCLUSIONS: EA preconditioning at LI11 and SP10 can prevent and treat UR by inhibiting inflammatory response, which is related to the regulation of pyroptosis.
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Pontos de Acupuntura , Eletroacupuntura , Interleucina-1beta , Proteína 3 que Contém Domínio de Pirina da Família NLR , Ratos Sprague-Dawley , Urticária , Animais , Masculino , Ratos , Proteína 3 que Contém Domínio de Pirina da Família NLR/metabolismo , Proteína 3 que Contém Domínio de Pirina da Família NLR/genética , Humanos , Interleucina-1beta/metabolismo , Interleucina-1beta/genética , Urticária/terapia , Urticária/metabolismo , Imunoglobulina E/sangue , Mastócitos/metabolismo , Interleucina-18/genética , Interleucina-18/metabolismo , Caspase 1/metabolismo , Caspase 1/genética , Histamina/metabolismo , Inflamação/terapia , Inflamação/prevenção & controle , Inflamação/metabolismo , Inflamação/genéticaRESUMO
BACKGROUND: Infant hepatitis syndrome (IHS) is a clinical syndrome in infants less than one year of age with generalized skin jaundice, abnormal liver function, and hepatomegaly due to various etiologies such as infection. AIM: To investigate the effect of IHS patients, after treatment with arsphenamine-based peptides, on patients' liver function damage and immune function. METHODS: Of 110 patients with IHS treated in our hospital from January 2019 to January 2021 were grouped according to the randomized residual grouping method, with 5 cases in each group shed due to transfer, etc. Ultimately, 50 cases remained in each group. The control group was treated with reduced glutathione, and the treatment group was treated with sesquiterpene peptide based on the control group. Observe and compare the differences in indicators after treatment. RESULTS: The comparison of serum total bilirubin, direct bilirubin, and serum alanine transferase after treatment was significantly different and lower in the treatment group than in the control group (P < 0.05). The comparison of CD4+, CD3+, CD4+/CD8+ after treatment was significantly different and higher in the treatment group than in the control group, and the comparison was statistically significant (P < 0.05). The complication of the two groups showed that the rash, cough and sputum, elevated platelets, and gastrointestinal reactions in the treatment group were significantly lower than those in the control group, and the differences were statistically significant by test (P < 0.05). CONCLUSION: The comparative study of IHS treated with arsphenamine combined with reduced glutathione is more effective.
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Regulatory T (Treg) cells play a critical regulatory role in the immune system by suppressing excessive immune responses and maintaining immune balance. The effective migration of Treg cells is crucial for controlling the development and progression of inflammatory diseases. However, the mechanisms responsible for directing Treg cells into the inflammatory tissue remain incompletely elucidated. In this study, we identified BAF60b, a subunit of switch/sucrose nonfermentable (SWI/SNF) chromatin remodeling complexes, as a positive regulator of Treg cell migration that inhibits the progression of inflammation in experimental autoimmune encephalomyelitis (EAE) and colitis animal models. Mechanistically, transcriptome and genome-wide chromatin-landscaped analyses demonstrated that BAF60b interacts with the transcription factor RUNX1 to promote the expression of CCR9 on Treg cells, which in turn affects their ability to migrate to inflammatory tissues. Our work provides insights into the essential role of BAF60b in regulating Treg cell migration and its impact on inflammatory diseases.
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Movimento Celular , Inflamação , Camundongos Endogâmicos C57BL , Linfócitos T Reguladores , Linfócitos T Reguladores/imunologia , Linfócitos T Reguladores/metabolismo , Animais , Camundongos , Inflamação/patologia , Inflamação/metabolismo , Montagem e Desmontagem da Cromatina , Proteínas Cromossômicas não Histona/metabolismo , Encefalomielite Autoimune Experimental/imunologia , Encefalomielite Autoimune Experimental/patologia , Encefalomielite Autoimune Experimental/metabolismo , Encefalomielite Autoimune Experimental/genética , Humanos , Fatores de Transcrição/metabolismo , Subunidade alfa 2 de Fator de Ligação ao Core/metabolismo , Subunidade alfa 2 de Fator de Ligação ao Core/genética , Colite/metabolismo , Colite/patologia , Colite/imunologia , Colite/genéticaRESUMO
Following the publication of this paper, it was drawn to the Editors' attention by a concerned reader that certain of the JC1 staining images in Fig. 2C were strikingly similar to data appearing in different form in other articles written by different authors at different research institutes that had either already been published elsewhere prior to the submission of this paper to Molecular Medicine Reports, or were under consideration for publication at around the same time (a small number of which have been retracted). In addition, the Snail western blot data in Fig. 3E bore a close similarity to certain of the Mfn2 data shown in Fig. 4A. In view of the fact that certain of the contentious data had already apparently been published previously, and owing to a lack of confidence in the presentation of certain of the data in this paper, the Editor of Molecular Medicine Reports has decided that this paper should be retracted from the Journal. The authors were asked for an explanation to account for these concerns, but the Editorial Office did not receive a reply. The Editor apologizes to the readership for any inconvenience caused. [Molecular Medicine Reports 22: 398404, 2020; DOI: 10.3892/mmr.2020.11098].
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Introduction: The present study aimed to investigate the effect of resilience on sleep quality and explore the role of social support between resilience and sleep quality in cancer patients. Methods: A multicenter and cross-sectional study was conducted in China from May to November 2021. A total of 202 cancer patients were recruited to complete the questionnaires composed of demographic information, Pittsburg Sleep Quality Index (PSQI), Resilience Scale-14 (RS-14), and Multidimensions Scale of Perceived Social Support (MSPSS). The associations between resilience, social support, and sleep quality were explored through hierarchical regression analysis. Results: The prevalence of poor sleep quality was 50% among cancer patients. Resilience, social support, and the interaction between resilience and social support were all found to be significantly associated with sleep quality. Results of simple slope analysis indicated that the association between resilience and sleep quality were gradually decreased with the increasing social support levels (1 SD below the mean, B=-0.225, ß=-0.551, P<0.001), mean social support (B=-0.147, ß=-0.353, P<0.001) and high social support (1 SD above the mean, B=-0.065, ß=-0.156, P<0.001). Additionally, social support mediated the effect of resilience on sleep quality among cancer patients. Discussion: Poor sleep quality has been common in cancer patients. Social support could mediate and alleviate the relationship between resilience and sleep quality among cancer patients. Besides providing sufficient social support, interventions based on resilience should be applied to address sleep problems in cancer patients.
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Hepatocellular carcinoma (HCC) is a serious neoplastic disease with increasing incidence and mortality, accounting for 90% of all liver cancers. Hepatitis viruses are the major causative agents in the development of HCC. Hepatitis A virus (HAV) primarily causes acute infections, which is associated with HCC to a certain extent, as shown by clinicopathological studies. Chronic hepatitis B virus (HBV) or hepatitis C virus (HCV) infections lead to persistent liver inflammation and cirrhosis, disrupt multiple pathways associated with cellular apoptosis and proliferation, and are the most common viral precursors of HCC. Mutations in the HBV X protein (HBx) gene are closely associated with the incidence of HCC, while the expression of HCV core proteins contributes to hepatocellular lipid accumulation, thereby promoting tumorigenesis. In the clinical setting, hepatitis D virus (HDV) frequently co-infects with HBV, increasing the risk of chronic hepatitis. Hepatitis E virus (HEV) usually causes acute infections. However, chronic infections of HEV have been increasing recently, particularly in immuno-compromised patients and organ transplant recipients, which may increase the risk of progression to cirrhosis and the occurrence of HCC. Early detection, effective intervention and vaccination against these viruses may significantly reduce the incidence of liver cancer, while mechanistic insights into the interplay between hepatitis viruses and HCC may facilitate the development of more effective intervention strategies. This article provides a comprehensive overview of hepatitis viruses and reviews recent advances in research on aberrant hepatic immune responses and the pathogenesis of HCC due to viral infection.
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Carcinoma Hepatocelular , Hepatite B Crônica , Hepatite B , Hepatite C , Hepatite Viral Humana , Neoplasias Hepáticas , Humanos , Neoplasias Hepáticas/genética , Hepatite B Crônica/complicações , Hepatite B/complicações , Hepatite Viral Humana/complicações , Hepatite C/complicações , Cirrose Hepática/complicaçõesRESUMO
BACKGROUND: The paucity of reliable biomarkers for predicting immunotherapy efficacy in patients with advanced hepatocellular carcinoma (HCC) has emerged as a burgeoning concern with the expanding use of immunotherapy. This study endeavors to delve into the potential peripheral biomarkers capable of prognosticating efficacy in HCC patients who are poised to receive anti-PD-1 monotherapy within the phase III clinical trial, KEYNOTE394. Additionally, we sought to elucidate the underlying molecular mechanisms for resistance to immune checkpoint blockade (ICB) and propose innovative combination immunotherapy strategies for future clinical application. METHODS: Patient blood samples were collected for single-cell RNA sequencing to evaluate the immune cell signature before receiving ICB therapy. Subsequently, in vitro assays and in vivo murine model experiments were conducted to validate the mechanism that S100A9+CD14+ monocytes play a role in ICB resistance. RESULTS: Our study demonstrates a notable enrichment of S100A9+CD14+ monocytes in the peripheral blood of patients exhibiting suboptimal responses to anti-PD-1 therapy. Moreover, we identified the Mono_S100A9 signature as a predictive biomarker, indicative of reduced efficacy in immunotherapy and decreased survival benefits across various tumor types. Mechanistically, S100A9 activates PD-L1 transcription by directly binding to the CD274 (PD-L1) gene promoter, thereby suppressing T-cell proliferation and cytotoxicity via the PD-1/PD-L1 axis, consequently diminishing the therapeutic effectiveness of subsequent anti-PD-1 treatments. Furthermore, our in vivo studies revealed that inhibiting S100A9 can synergistically enhance the efficacy of anti-PD-1 drugs in the eradication of hepatocellular carcinoma. CONCLUSIONS: Our study underscores the significance of S100A9+CD14+ monocytes in predicting inadequate response to ICB treatment and provides insights into the monocyte cell-intrinsic mechanisms of resistance to ICB therapy. We also propose a combined therapeutic approach to enhance ICB efficacy by targeting S100A9.
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Carcinoma Hepatocelular , Neoplasias Hepáticas , Humanos , Animais , Camundongos , Carcinoma Hepatocelular/tratamento farmacológico , Carcinoma Hepatocelular/genética , Monócitos/metabolismo , Neoplasias Hepáticas/tratamento farmacológico , Neoplasias Hepáticas/metabolismo , Antígeno B7-H1/metabolismo , Linfócitos T/metabolismo , Imunoterapia , Microambiente Tumoral , Calgranulina B/metabolismoRESUMO
BACKGROUND: Cancer-related fatigue (CRF) is considered one of the most prevalent and distressing symptoms among cancer patients and may vary among patients with different cancer types. However, few studies have explored the influence of physical and psychological symptoms on CRF among esophageal cancer (EC) patients without esophagectomy. Therefore, this study aimed to examine the effects of physical and psychological symptoms on CRF among EC patients without esophagectomy. METHODS: In the present study, a cross-sectional study was conducted from February 2021 to March 2022 in Liaoning Province, China. Among the 112 included participants, 97 completed our investigation. The questionnaires used consisted of the Brief Fatigue Inventory (BFI), the MD Anderson Symptom Inventory Gastrointestinal Cancer Module (MDASI-GI), the Patient Health Questionnaire-9 (PHQ-9), the Generalized Anxiety Disorder-7 (GAD-7), and demographic and clinical information. Multivariate linear regression was conducted to test the relationships between physical and psychological symptoms and CRF. RESULTS: Of the 97 EC patients, 60.8% reported CRF (BFI ≥ 4). The mean age of the participants was 64.92 years (SD = 8.67). According to the regression model, all the variables explained 74.5% of the variance in CRF. Regression analysis indicated that physical symptoms, including constipation, diarrhoea, and difficulty swallowing, contributed to CRF. On the other hand, depressive symptoms increased the level of CRF among EC patients without esophagectomy. CONCLUSIONS: Given the high prevalence of CRF among EC patients without esophagectomy, it is urgent to emphasize the importance of fatigue management interventions based on physical and psychological symptoms to alleviate CRF in EC patients.
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Neoplasias Esofágicas , Neoplasias , Humanos , Pessoa de Meia-Idade , Idoso , Estudos Transversais , Neoplasias Esofágicas/complicações , Neoplasias Esofágicas/epidemiologia , Inquéritos e Questionários , Análise de Regressão , Fadiga/epidemiologia , Fadiga/etiologia , Fadiga/diagnóstico , Qualidade de VidaRESUMO
The increase in the styrene content in styrene-butadiene rubber (SBR) can improve the abrasion performance and cutting resistance of rubber, which has received attention in the tire industry. The fatigue performance is the main evaluation index of rubber materials applied to tires. In this study, the effect of the styrene content and its interaction with carbon black (CB) on the dynamic fatigue performance and mechanism of SBR were investigated. The results indicated that the dynamic fatigue life of the rubber composite materials was prolonged with increasing styrene content; furthermore, it showed a trend of increasing and then decreasing with increasing CB content. At a certain CB content, styrene and CB displayed a synergistic effect on improving the dynamic fatigue life of the composite materials. The dynamic fatigue performance of SBR40/CB20 was the best. The expansion of the fatigue cracks followed the secondary cracking mechanism, which consumed a large amount of strain energy and slowed the development of the main crack. However, when the CB content exceeded 40 phr, the mechanism transformed to main crack self-propagation and the fatigue life decreased.
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BACKGROUND: Previous epidemiological studies have shown inconsistent results regarding the relation between the risk of asthma in offspring and parental occupational exposure. Therefore, we conducted a comprehensive and systematic collection of currently available epidemiological data to quantify the correlation between the 2. METHODS: Related studies published before March 2023 were identified through searches of the Cochrane Library, Embase, PubMed, and Web of Science databases. The quality of included studies was assessed using the Newcastle-Ottawa Scale, while pooled odds ratios (ORs) with 95% confidence intervals (CIs) were computed using fixed-effect or random-effects models. RESULTS: This systematic review included 10 cohort studies, with a total of 89,571 parent-child pairs included in the quantitative analysis. The results exhibited a substantial association between parental occupational exposure to allergens (ORâ =â 1.11; 95% CI: 1.00, 1.23; Pâ =â .051) and irritants (ORâ =â 1.19; 95% CI: 1.07, 1.32; Pâ =â .001) and an increased risk of asthma in offspring. This association was also observed in the analysis of wheezing (ORâ =â 1.22; 95% CI: 1.11, 1.35; Pâ <â .001 and ORâ =â 1.19; 95% CI: 1.08, 1.32; Pâ =â .001). Subgroup analysis demonstrated that maternal occupational exposure to allergens (ORâ =â 1.07; 95% CI: 1.02, 1.12; Pâ =â .008) and irritants (ORâ =â 1.13; 95% CI: 1.05, 1.21; Pâ =â .001) significantly increased the risk of childhood asthma. Furthermore, parental postnatal occupational exposure to allergens (ORâ =â 1.26; 95% CI: 1.10, 1.46; Pâ =â .001) and irritants (ORâ =â 1.26; 95% CI: 1.06, 1.49; Pâ =â .009) had a more pronounced impact on childhood asthma. Higher levels of exposure (ORâ =â 1.26; 95% CI: 1.10, 1.46; Pâ =â .001 and ORâ =â 1.30; 95% CI: 1.16, 1.47; Pâ <â .001) were recognized as significant risk factors for childhood asthma. CONCLUSION: Parental occupational exposure to allergens and irritants increases the risk of asthma and wheezing in offspring, with maternal exposure, postnatal exposure, and high-dose exposure being the primary risk factors for childhood asthma.
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Asma , Exposição Ocupacional , Feminino , Humanos , Sons Respiratórios/etiologia , Irritantes , Exposição Ocupacional/efeitos adversos , Asma/etiologia , Asma/complicações , Pais , Alérgenos/efeitos adversosRESUMO
Six transmembrane epithelial antigen of the prostate (STEAP) 1-4 are membrane-embedded hemoproteins that chelate a heme prosthetic group in a transmembrane domain (TMD). STEAP2-4, but not STEAP1, have an intracellular oxidoreductase domain (OxRD) and can mediate cross-membrane electron transfer from NADPH via FAD and heme. However, it is unknown whether STEAP1 can establish a physiologically relevant electron transfer chain. Here, we show that STEAP1 can be reduced by reduced FAD or soluble cytochrome b5 reductase that serves as a surrogate OxRD, providing the first evidence that STEAP1 can support a cross-membrane electron transfer chain. It is not clear whether FAD, which relays electrons from NADPH in OxRD to heme in TMD, remains constantly bound to the STEAPs. We found that FAD reduced by STEAP2 can be utilized by STEAP1, suggesting that FAD is diffusible rather than staying bound to STEAP2. We determined the structure of human STEAP2 in complex with NADP+ and FAD to an overall resolution of 3.2 Å by cryo-electron microscopy and found that the two cofactors bind STEAP2 similarly as in STEAP4, suggesting that a diffusible FAD is a general feature of the electron transfer mechanism in the STEAPs. We also demonstrated that STEAP2 reduces ferric nitrilotriacetic acid (Fe3+-NTA) significantly slower than STEAP1 and proposed that the slower reduction is due to the poor Fe3+-NTA binding to the highly flexible extracellular region in STEAP2. These results establish a solid foundation for understanding the function and mechanisms of the STEAPs.
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Elétrons , Próstata , Masculino , Humanos , NADP/metabolismo , Microscopia Crioeletrônica , Próstata/metabolismo , Oxirredutases/metabolismo , Heme/metabolismo , Antígenos de NeoplasiasRESUMO
OBJECTIVE: To investigate the clinical characteristics of diffuse large B-cell lymphoma(DLBCL) patients with bone marrow involvement and chromosome abnormalities, and further analyze the correlation between the degree of chromosome abnormality and prognosis. METHODS: The clinical data of 88 patients diagnosed with DLBCL with bone marrow involvement and complete chromosomal findings in Shanxi Province Cancer Hospital were retrospectively analyzed. The χ2 test was used to analyze their clinical characteristics, and the Kaplan-Meier method was used in PFS and OS, and log-rank method in comparison. RESULTS: Chromosome abnormalities were detected in 31 of the 88 patients(35.2%), 15 of whom had complex karyotype(17.0%). The positive rate of BCL-2, BCL-6, C-MYC and Ki-67≥80% was high in patients with complex karyotype, and most of them are double expressor lymphoma. Survival analysis showed that patients with complex karyotype of DLBCL had poorer PFS and OS compared to those with normal karyotype and 1-2 chromosomal abnormalities. CONCLUSION: In DLBCL patients with bone marrow involvement and chromosome abnormalities, patients with complex karyotype have a shorter survival time.
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Melanoma is a highly aggressive form of skin cancer with limited therapeutic options. Chemo-photothermal combination therapy has demonstrated potential for effectively treating melanoma, and transdermal administration is considered the optimal route for treating skin diseases due to its ability to bypass first-pass metabolism and enhance drug concentration. However, the stratum corneum presents a formidable challenge as a significant barrier to drug penetration in transdermal drug delivery. Lipid-nanocarriers, particularly cubosomes, have been demonstrated to possess significant potential in augmenting drug permeation across the stratum corneum. Herein, cubosomes co-loaded with doxorubicin (DOX, a chemotherapeutic drug) and indocyanine green (ICG, a photothermal agent) (DOX-ICG-cubo) transdermal drug delivery system was developed to enhance the therapeutic efficiency of melanoma by improving drug permeation. The DOX-ICG-cubo showed high encapsulation efficiency of both DOX and ICG, and exhibited good stability under physiological conditions. In addition, the unique cubic structure of the DOX-ICG-cubo was confirmed through transmission electron microscopy (TEM) images, polarizing microscopy, and small angle X-ray scattering (SAXS). The DOX-ICG-cubo presented high photothermal conversion efficiency, as well as pH and thermo-responsive DOX release. Notably, the DOX-ICG-cubo exhibited enhanced drug permeation efficiency, good biocompatibility, and improved in vivo anti-melanoma efficacy through the synergistic effects of chemo-photothermal therapy. In conclusion, DOX-ICG-cubo presented a promising strategy for melanoma treatment.
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Hipertermia Induzida , Melanoma , Nanopartículas , Humanos , Verde de Indocianina , Fototerapia/métodos , Terapia Fototérmica , Administração Cutânea , Espalhamento a Baixo Ângulo , Difração de Raios X , Doxorrubicina/farmacologia , Melanoma/tratamento farmacológico , Nanopartículas/química , Linhagem Celular TumoralRESUMO
BACKGROUND: Propranolol is the first choice for treating infantile hemangioma (IH). How propranolol works in IH remains unclear. Infantile hemangioma endothelial cells (HemECs) express Notch1, Jagged, Hey1, and other molecules in the Notch pathway, suggesting that Notch pathway-related molecules play an important role in affecting vascular endothelial cell proliferation. Whether propranolol can affect the Notch signaling pathway in IH treatment is unclear. METHODS: We performed this study to observe the effect of propranolol on the expression of Notch signaling pathway molecules in human umbilical vein endothelial cells (HUVECs) and to explore the therapeutic mechanism of propranolol on IH. HUVECs cultured in vitro were exposed to 60, 120, 240, 360, or 480 µM propranolol. The morphological changes of the HUVECs were observed under an inverted microscope. HUVECs proliferation was detected with Cell Counting Kit-8 (CCK-8). The effects of propranolol on HUVECs apoptosis were detected by flow cytometry. The role of Notch in propranolol inhibition of HUVEC proliferation was analyzed with real-time polymerase chain reaction (PCR) and western blotting. RESULTS: Propranolol reduced HUVECs numbers and altered their morphology. The inhibitory effect of propranolol on cell proliferation was dependent on the reaction time and drug concentration. Propranolol upregulated Jagged1, Notch1, and Hey1 expression and downregulated delta-like ligand4 (DLL4) expression. CONCLUSIONS: Propranolol may play a role in IH treatment by increasing Jagged1 expression in endothelial cells, activating the Notch pathway and inducing the upregulation of the downstream target gene HEY1.
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Hemangioma , Propranolol , Humanos , Células Endoteliais da Veia Umbilical Humana , Propranolol/farmacologia , Propranolol/uso terapêutico , Transdução de Sinais/genética , Hemangioma/tratamento farmacológico , Hemangioma/genética , Biologia , Proliferação de CélulasRESUMO
BACKGROUND: Complicated Periumbilical abscess in late pregnancy is rare in clinical practice. Pubmed searches for articles published from January 1980 to September 2021. Such related reports did not retrieve article about "pregnancy" and "periumbilical abscess." CASE PRESENTATION: We reported on a 34-year-old female patient who was admitted to the hospital with periumbilical pain for 3 days at 34â +â 1 weeks of pregnancy. The result of imaging examination showed that there was an inflammatory mass in the middle and lower abdominal wall in the third trimester of pregnancy. The periumbilical abscess was punctured and drained first, and then the pregnant woman was assisted to give birth to a baby girl through vagina after the condition was stable.Subsequently, laparotomyâ +â abdominal abscess resection and drainageâ +â partial small bowel resectionâ +â ileostomy were performed. Pathology showed inflammatory mass. CONCLUSIONS: Periumbilical abscess in the third trimester of pregnancy is rare clinically. For some pregnant women with previous trauma and surgical history, obstetric examination should not be restricted. For example, pregnant women with a history of abdominal surgery should expand the range of abdominal color Doppler ultrasound during the prenatal examination. When necessary, combine with computed tomography for diagnosis and treatment, avoid missed diagnosis, which will make the treatment more difficult and increase the risk. If the pregnant women has corresponding symptoms in the third trimester, vaginal delivery can be performed to terminate the pregnancy, and then the periumbilical abscess can be removed. At the same time, closely monitor the vital signs of newborn and mothers.
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Abscesso , Complicações na Gravidez , Recém-Nascido , Gravidez , Humanos , Feminino , Adulto , Abscesso/diagnóstico , Abscesso/cirurgia , Terceiro Trimestre da Gravidez , Complicações na Gravidez/diagnóstico , Complicações na Gravidez/cirurgiaRESUMO
OBJECTIVE: To observe the effect of electroacupuncture (EA) pretreatment at "Quchi "(LI11) and "Xuehai "(SP10) on expression of interleukin (IL)-33, suppression of tumorigenicity 2 (ST2) and mast cell degranulation in sensitive area of skin tissue in rats with urticaria, so as to explore its mechanisms underlying prevention of urticaria. METHODS: A total of 32 male SD rats were randomly divided into blank control, model, EA preconditioning and medication groups, with 8 rats in each group. The urticaria model was established by topical injection of the prepared anti-ovalbumin serum (foreign serum, 0.1 mL/spot) along the bilateral sides of the spinal column on the back, followed by injection of mixture solution of ovalbumin, 0.5% evans blue and normal saline via the tail vein 48 h later. EA intervention (2 Hz/15 Hz, 1 mA) was applied to bilateral LI11 and SP10 for 20 min, once daily for 7 d before modeling.Back sensitization was started from the 5th day on. Rats of the medication group received gavage of loratadine, and those of the model group received gavage of the same volume of normal saline. The diameter of evans blue spots at the back skin tissue was measured; the histopathological changes of the blue spot tissues were observed by light microscope after H.E. staining. The state of degranulation of mast cells in the subcutaneous loose connective tissue was observed by using toluidine blue staining. Serum IgE and histamine contents were detected by ELISA, and the immunoactivity of IL-33 and ST2 in the skin and subcutaneous tissues of the sensitized spots (evans blue exudation spots) was observed by immunohistochemistry. RESULTS: Compared with the blank control group, the diameter of evans blue spot, degranulation rate of mast cells, serum IgE and histamine contents, and the immunoactivity of IL-33 and ST2 in the evans blue exudation spot tissues were significantly increased in the model group (P<0.01). In comparison with the model group, the increase of the above-mentioned indexes was reversed in both EA and medication groups (P<0.01ï¼P<0.05). No significant differences were found between the EA and medication groups in down-regulating the levels of the 6 indexes. H.E. staining of the blue spot tissues of rats in the model group showed incomplete structure of the epidermal layer of the skin, unclear interface of tissues, incomplete keratinization, chaotic epidermal cells, disorderly arrangement of fibers in the dermis, and infiltration of inflammatory cells and edema, which was relatively milder in the EA and medication groups. CONCLUSION: EA preconditioning can prevent urticaria (reduce size and sensitive reactions) in rats, which may be associated with its functions in lowering the level of IgE through inhibiting IL-33 and ST2.
Assuntos
Terapia por Acupuntura , Eletroacupuntura , Urticária , Ratos , Masculino , Animais , Ratos Sprague-Dawley , Mastócitos , Proteína 1 Semelhante a Receptor de Interleucina-1 , Histamina , Azul Evans , Interleucina-33/genética , Solução Salina , Urticária/genética , Urticária/terapia , Imunoglobulina E , Pontos de Acupuntura , Receptores de Interleucina-1RESUMO
Drug resistance is a huge hurdle in tumor therapy. Tumor hypoxia contributes to chemotherapy resistance by inducing the hypoxia-inducible factor-1α (HIF-1α) pathway. To reduce tumor hypoxia, novel approaches have been devised, providing significant importance to reverse therapeutic resistance and improve the effectiveness of antitumor therapies. Herein, the nanosystem of bovine serum albumin (BSA)-templated manganese dioxide (MnO2) nanoparticles (BSA/MnO2 NPs) loaded with doxorubicin (DOX) (DOX-BSA/MnO2 NPs) developed in our previous report was further explored for their physicochemical properties and capacity to reverse DOX resistance because of their excellent photothermal and tumor microenvironment (TME) response effects. The DOX-BSA/MnO2 NPs showed good biocompatibility and hemocompatibility. Meanwhile, DOX-BSA/MnO2 NPs could greatly affect DOX pharmacokinetic properties, with prolonged circulation time and reduced cardiotoxicity, besides enhancing accumulation at tumor sites. DOX-BSA/MnO2 NPs can interact with H2O2 and H+ in TME to form oxygen and exhibit excellent photothermal effect to further alleviate hypoxia due to MnO2, reversing DOX resistance by down-regulating HIF-1α expression and significantly improving the antitumor efficiency in DOX-resistant human breast carcinoma cell line (MCF-7/ADR) tumor model. The hypoxia-ameliorated photothermal MnO2 platform is a promising strategy for revering DOX resistance.
RESUMO
BACKGROUND & AIMS: Gastric cancer (GC) is a major cancer type characterized by high heterogeneity in both tumor cells and the tumor immune microenvironment (TIME). One intractable GC subtype is gastric signet-ring cell carcinoma (GSRCC), which is associated with poor prognosis. However, it remains unclear what the GSRCC TIME characteristics are and how these characteristics may contribute to clinical outcomes. METHODS: We enrolled 32 patients with advanced GC of diverse subtypes and profiled their TIME using an immune-targeted single-cell profiling strategy, including (1) immune-targeted single-cell RNA sequencing (n = 20 patients) and (2) protein expression profiling by a targeted antibody panel for mass cytometry (n = 12 patients). We also generated matched V(D)J (variable, diversity, and joining gene segments) sequencing of T and B cells along CD45+ immunocytes. RESULTS: We found that compared to non-GSRCC, the GSRCC TIME appears to be quiescent, where both CD4+ and CD8+ T cells are difficult to be mobilized, which further impairs the proper functions of B cells. CXCL13, mainly produced by follicular helper T cells, T helper type 17, and exhausted CD8+ T cells, is a central coordinator of this transformation. We show that CXCL13 expression can predict the response to immune checkpoint blockade in GC patients, which may be related to its effects on tertiary lymphoid structures. CONCLUSIONS: Our study provides a comprehensive molecular portrait of immune cell compositions and cell states in advanced GC patients, highlighting adaptive immune irresponsiveness in GSRCC and a mediator role of CXCL13 in TIME. Our targeted single-cell transcriptomic and proteomic profiling represents a powerful approach for TIME-oriented translational research.