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Sulphated glycosaminoglycans (GAGs) such as heparin are a major component of mast cell granules and form the matrix within which biogenic mediators are stored. Since GAGs released from mast cells also play an important role in helminth expulsion, understanding GAG storage can offer new insights into mast cell function. Sodium butyrate (NaBu), a short-chain fatty acid, causes ultrastructural changes within the granules of human mast cells (HMC-1) and increases their histamine content. Therefore, we hypothesized that NaBu treatment would also modify the storage of polysaccharides such as GAGs. NaBu (1 mM) significantly increased GAG content and granularity in a time- and concentration-dependent manner without affecting cell viability and metabolic activity. NaBu increased the expression of enzymes associated with heparin biosynthesis (GLCE, NDST1, NDST2, HS6ST1, and GALT1) in a time-dependent manner. A cholesteryl butyrate emulsion (CholButE) increased heparin content after 24 and 48 h and modestly altered the expression of genes involved in heparin biosynthesis. Similar to NaBu, CholButE reduced cell proliferation without significantly altering viability or metabolic activity. These data show that butyrate increases the synthesis and storage of heparin in human mast cells, perhaps by altering their metabolic pathways.
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Heparina , Mastócitos , Humanos , Mastócitos/metabolismo , Mastócitos/efeitos dos fármacos , Heparina/farmacologia , Heparina/metabolismo , Sobrevivência Celular/efeitos dos fármacos , Butiratos/farmacologia , Butiratos/metabolismo , Proliferação de Células/efeitos dos fármacos , Ácido Butírico/farmacologia , Linhagem Celular , Ésteres do Colesterol/metabolismoRESUMO
PURPOSE: This study explored the relationship between central sensitization symptoms, assessed using the Central Sensitization Inventory (CSI), and psychophysical factors in patients with chronic masticatory myofascial pain (MMP) transitioning from the acute to chronic stages. METHODS: In this study, 23 patients with MMP and 22 healthy volunteers were assessed using psychophysical tests, including measurements of pressure pain threshold (PPT) and temporal summation of pain (TSP). Additionally, CSI scores were recorded to evaluate central sensitization symptoms. RESULTS: Patients with chronic MMP showed significantly lower PPT in all masticatory muscles and extratrigeminal areas compared with controls. However, there was no significant correlation between CSI scores and psychophysical test results in patients with MMP. CONCLUSION: The significant enhancement of TSP in patients with subchronic MMP suggests a potential role in the onset of myofascial pain. The main finding suggests that sub-chronic symptom patients show higher CSI scores despite no sensory testing changes, indicating that central sensitization possibly precedes observable symptoms.
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Sensibilização do Sistema Nervoso Central , Limiar da Dor , Humanos , Feminino , Masculino , Adulto , Sensibilização do Sistema Nervoso Central/fisiologia , Pessoa de Meia-Idade , Estudos de Casos e Controles , Medição da Dor , Síndromes da Dor Miofascial/fisiopatologia , Músculos da Mastigação/fisiopatologia , Psicofísica , Adulto Jovem , Síndrome da Disfunção da Articulação Temporomandibular/fisiopatologiaRESUMO
Diffuse large B-cell lymphoma (DLBCL) stands out as the most common type of malignant cancer, representing the majority of cases of non-Hodgkin's lymphoma. Ethyl pyruvate (EP) is a derivative of pyruvic acid and found to have potent anti-tumor properties. Despite its potential benefits, the impact of EP on DLBCL remains ambiguous. Our objective is to elucidate the role of EP in modulating the development of DLBCL. Analysis of cholecystokinin-8 (CCK-8) revealed that treatment with EP significantly diminished the viability of DLBCL cells. Furthermore, EP administration suppressed colony formation and hindered cell adhesion and invasion in DLBCL cells. Examination of cell cycle progression showed that EP treatment induced arrest at the G1 phase and subsequently reduced the S phase population in DLBCL cells. EP treatment consistently exhibited apoptosis-inducing properties in Annexin-V assays, and notably downregulated the expression of Bcl-2 while increasing levels of proapoptotic cleaved caspase 3 and BAX in DLBCL cells. Additionally, EP treatment decreased the overexpression of c-Jun in c-Jun-transfected DLBCL cells. Further, EP demonstrated DNA-damaging effects in TUNEL assays. In vivo, xenograft animal models revealed that EP treatment significantly mitigated DLBCL tumor growth and suppressed DLBCL cell adhesion to bone marrow stromal cells. In summary, these findings suggest that EP mitigates DLBCL progression by inducing apoptosis, inducing cell cycle arrest, and promoting DNA damage.
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Adesão Celular , Proliferação de Células , Linfoma Difuso de Grandes Células B , Piruvatos , Piruvatos/farmacologia , Piruvatos/uso terapêutico , Linfoma Difuso de Grandes Células B/tratamento farmacológico , Linfoma Difuso de Grandes Células B/patologia , Humanos , Animais , Adesão Celular/efeitos dos fármacos , Proliferação de Células/efeitos dos fármacos , Linhagem Celular Tumoral , Camundongos , Apoptose/efeitos dos fármacos , Proteínas Proto-Oncogênicas c-jun/metabolismo , Proteínas Proto-Oncogênicas c-jun/genética , Ensaios Antitumorais Modelo de XenoenxertoRESUMO
OBJECTIVES: Burning mouth syndrome (BMS) is a chronic orofacial pain disorder with unclear etiology, in which the tongue is most commonly affected. This study aims to provide implication of the possible relationship between oral microbiota and the pathogenesis of BMS. MATERIALS AND METHODS: Saliva and tongue swabs of 15 primary BMS patients and 10 healthy controls were collected and assessed by 16S rRNA gene amplicon sequencing. The microbiota compositions were compared and bioinformatic analysis was conducted. RESULTS: Differences in microbiota compositions between BMS patients and healthy controls were revealed in both saliva and tongue samples. In saliva, Streptococcus, Rothia, and Neisseria were the predominant genus at the taxonomic level in BMS patients. In tongue samples, Prevotella, Streptococcus, and Neisseria were the dominant genus at the taxonomic level in BMS patients. LEfSe analysis and linear discriminant analysis score showed that Actinobacteria were the predominant phylum in saliva, and Selenomonas were enriched in the dorsum of the tongue of BMS patients. CONCLUSIONS: This study for the first-time reported saliva and tongue microbiota profiles were distinguished from that of healthy controls, indicating a necessity for further research on the possible relationship between oral microbes and the pathogenesis of BMS.
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Candida albicans is one of the most common opportunistic fungi in cancer patients. This study explored the influence of C. albicans on gut microbiota in oral tumour-bearing mice by means of 16S rRNA sequencing and ITS sequencing. It was found that C. albicans infection induced the decrease of alpha diversity of bacteria and fungi in the gut microbiome. For the bacteria, C. albicans caused the reduction of Ralstonia, Alistipes, Clostridia UCG-014, Ruminococcus, and Lachnospiraceae NK4A136 group. For the fungi, C. albicans inhibited the growth of other fungi including Aspergillus, Cladosporium, and Bipolaris. The neutralisation of γδT cells partly alleviated the out-of-balance of Firmicutes/Bacteroidota (F/B) ratio in the gut caused by C. albicans infection. However, γδT cell neutralisation boosted the overgrowth of C. albicans. Additionally, IL-17A neutralisation aggravated the microbial dysbiosis of bacteria and fungi caused by C. albicans infection. Further analysis indicated that C. albicans overgrowth might influence the correlations between fungal and bacterial kingdoms. In conclusion, C. albicans infection disturbed the gut microbiota of both bacteria and fungi in oral tumour-bearing mice, which may be associated with the intestinal immune components including γδT cells and IL-17A.
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Background: The prevalence of community-onset infections of extended spectrum ß-lactamase (ESBL)-producing strains has increased globally, yet surveillance and resistance in patients with oral and maxillofacial surgery site infections is less investigated. Patients and Methods: A retrospective cohort study was performed to investigate risk factors and resistance of ESBL-producing Escherichia coli (ESBL-EC) and ESBL-producing Klebsiella pneumonia (ESBL-KP) among community-onset patients with oral and maxillofacial surgery during January 2010 to December 2016. Demographic features, predisposing factors, clinical outcomes, and antibiotic agent costs were analyzed. Antimicrobial susceptibility testing of nine antimicrobial agents against ESBL-KP and ESBL-EC were measured. Results: Among 2,183 cultures from infection sites in patients with oral and maxillofacial surgery site (45 cases [2.06%]) were confirmed with community-onset ESBL-KP (24; 1.10%) or ESBL-EC (21; 0.96%) infection. Multivariable analysis showed the independent risk factors for ESBL-producing bacterial infection were prior history of hospitalization (adjusted odds ratio [aOR], 10.984; 95% confidence interval [CI], 5.965-59.879; p = 0.025) and malignant condition (aOR, 3.373; 95% CI 2.947-7.634; p = 0.024). Based on antimicrobial susceptibility testing, 57.8% ESBL-KP and ESBL-EC were found receiving inappropriate antimicrobial therapy, and antibiotic agent costs were higher than non-ESBL-producing bacterial infections ($493.8 ± $367.3 vs. $304.1 ± $334.7; p = 0.031). Conclusions: Infections caused by ESBL-KP and ESBL-EC among patients in sites with oral and maxillofacial surgery are associated with prior history of hospitalization and malignant conditions. Prompt detection and appropriate antibiotic administration for community-onset infections of ESBLs are necessary for such populations.
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Infecções por Escherichia coli , Infecções por Klebsiella , Pneumonia , Humanos , Infecções por Escherichia coli/tratamento farmacológico , Infecções por Escherichia coli/epidemiologia , Infecções por Escherichia coli/microbiologia , Estudos Retrospectivos , beta-Lactamases , Escherichia coli , Infecções por Klebsiella/tratamento farmacológico , Infecções por Klebsiella/epidemiologia , Klebsiella pneumoniae , Antibacterianos/farmacologia , Antibacterianos/uso terapêutico , Fatores de Risco , Klebsiella , Infecção da Ferida Cirúrgica/tratamento farmacológico , Infecção da Ferida Cirúrgica/epidemiologiaRESUMO
OBJECTIVE: To analyze the clinical features, diagnosis and treatment and prognosis of the rare hairy cell leukemia (HCL), in order to provide new references for the clinical and basic research of HCL. METHODS: The clinical data of 17 patients with HCL admitted to Fujian Medical University Union Hospital, the Affiliated Hospital of Putian University and the First Affiliated Hospital of Gannan Medical University from January 1, 2016 to July 1, 2023 were collected and retrospectively studied, and the clinical features, diagnosis and treatment effects and prognosis of patients with HCL were analyzed. The Kaplan-Meier method was used for survival analysis. Meanwhile, the latest literature from PubMed was retrieved to systematically discuss the research progress in the diagnosis and treatment of HCL. RESULTS: In this study, there were 11 males and 6 females, the median age at diagnosis was 59.5 (30-81) years old, and the median time from the onset of clinical symptoms or signs to diagnosis was 4.5 (0.5-28.5) months. There were 9 cases (52.94%) with lymphoma B symptoms (fever, night sweating, and weight loss), 15 cases (88.24%) were accompanied by splenomegaly (3 cases of mild splenomegaly, 4 cases of moderate splenomegaly, and 8 cases of megasplenomegaly), the positive rate of BRAFV600E mutation is 76.47% (13/17). All patients in this study were treated, of which 11 were treated with Cladribine, 3 with Interferon, 2 with FC regimen, and 1 with R-CVP regimen + Cladribine. The median follow-up time was 39 (range, 2-83) months, 3 patients died, all due to failure of chemotherapy due to disease progression. The prognosis of HCL-v patients was significantly worse than that of cHCL patients (P=0.01), and there was no significant difference in the impact of different treatment regiments on the OS of HCL patients (P=0.328). CONCLUSION: HCL is a rare clinically indolent hematological tumor, which is sensitive to Cladribine, with the emergence of precision treatments such as the novel molecular-targeted drugs and immunotherapy also plays an indispensable role in clinical practice of HCL.
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Candida albicans (C. albicans) is associated with the development of oral cancer. Here, we report the altered tumor microenvironment in oral tumor-bearing mice caused by C. albicans infection. Single-cell RNA sequencing showed that C. albicans infection influenced the tumor microenvironment significantly. Specifically, C. albicans infection reduced the CD8+ T cells but increased the IL-17A+ CD4+ T cells and IL-17A+ γδ T cells in oral tumor. The neutralization of IL-17A or TCR γ/δ alleviated the tumor progression caused by C. albicans infection. Additionally, C. albicans infection promoted the infiltration of myeloid-derived suppressor cells (MDSCs) into tumor, especially polymorphonuclear (PMN)-MDSCs, which infiltration was reduced after the neutralization of CCL2. Thus, our findings reveal the myeloid cells-T lymphocytes axis in oral tumor microenvironment with C. albicans infection, which helps to understand the mechanisms for C. albicans promoting oral cancer from the perspective of immune microenvironment.
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Neoplasias Bucais , Células Supressoras Mieloides , Camundongos , Animais , Candida albicans , Linfócitos T CD8-Positivos , Interleucina-17/genética , Microambiente Tumoral , Células MieloidesRESUMO
Over the past three decades, considerable efforts have been expended on understanding the Janus kinase/signal transducer and activator of transcription (JAK/STAT) signaling pathway in leukemia, following the identification of the JAK2V617F mutation in myeloproliferative neoplasms (MPNs). The aim of this review is to summarize the latest progress in our understanding of the involvement of the JAK/STAT signaling pathway in the development of leukemia. We also attempt to provide insights into the current use of JAK/STAT inhibitors in leukemia therapy and explore pertinent clinical trials in this field.
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Leucemia , Transtornos Mieloproliferativos , Humanos , Janus Quinases/genética , Janus Quinases/metabolismo , Fatores de Transcrição STAT/genética , Fatores de Transcrição STAT/metabolismo , Transtornos Mieloproliferativos/tratamento farmacológico , Transtornos Mieloproliferativos/genética , Transdução de SinaisRESUMO
OBJECTIVES: To develop and validate MRI-based scoring models for predicting placenta accreta spectrum (PAS) invasiveness. MATERIALS AND METHODS: This retrospective study comprised a derivation cohort and a validation cohort. The derivation cohort came from a systematic review of published studies evaluating the diagnostic performance of MRI signs for PAS and/or placenta percreta in high-risk women. The significant signs were identified and used to develop prediction models for PAS and placenta percreta. Between 2016 and 2021, consecutive high-risk pregnant women for PAS who underwent placental MRI constituted the validation cohort. Two radiologists independently evaluated the MRI signs. The reference standard was intraoperative and pathologic findings. The predictive ability of MRI-based models was evaluated using the area under the curve (AUC). RESULTS: The derivation cohort included 26 studies involving 2568 women and the validation cohort consisted of 294 women with PAS diagnosed in 258 women (88%). Quantitative meta-analysis revealed that T2-dark bands, placental/uterine bulge, loss of T2 hypointense interface, bladder wall interruption, placental heterogeneity, and abnormal intraplacental vascularity were associated with both PAS and placenta percreta, and myometrial thinning and focal exophytic mass were exclusively associated with PAS. The PAS model was validated with an AUC of 0.90 (95% CI: 0.86, 0.93) for predicting PAS and 0.85 (95% CI: 0.79, 0.90) for adverse peripartum outcome; the placenta percreta model showed an AUC of 0.92 (95% CI: 0.86, 0.98) for predicting placenta percreta. CONCLUSION: MRI-based scoring models established based on quantitative meta-analysis can accurately predict PAS, placenta percreta, and adverse peripartum outcome. CLINICAL RELEVANCE STATEMENT: These proposed MRI-based scoring models could help accurately predict PAS invasiveness and provide evidence-based risk stratification in the management of high-risk pregnant women for PAS. KEY POINTS: ⢠Accurately identifying placenta accreta spectrum (PAS) and assessing its invasiveness depending solely on individual MRI signs remained challenging. ⢠MRI-based scoring models, established through quantitative meta-analysis of multiple MRI signs, offered the potential to predict PAS invasiveness in high-risk pregnant women. ⢠These MRI-based models allowed for evidence-based risk stratification in the management of pregnancies suspected of having PAS.
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Placenta Acreta , Doenças Placentárias , Placenta Prévia , Humanos , Feminino , Gravidez , Placenta/diagnóstico por imagem , Placenta/patologia , Placenta Acreta/diagnóstico por imagem , Estudos Retrospectivos , Imageamento por Ressonância MagnéticaRESUMO
OBJECTIVE: This study aims to provide a scoping review and attempts to uncover the possible association between burning mouth disorder and gastroesophageal reflux disease. METHODS: PubMed, EMBASE, Web of Science, the Cochrane Library, Ovid, Scopus, and a search platform (EBSCOhost) were searched from their inception to August 22, 2023. RESULTS: After screening 2795 records, 18 articles were included in the final review, comprising cross-sectional studies (n = 9), case-control studies (n = 5), case reports (n = 2), case series (n = 1), and experimental study (n = 1). The prevalence of gastroesophageal reflux disease and its extraesophageal manifestations of laryngopharyngeal reflux in burning mouth patients was reported 3.39%-23.4% and 50%-93.8%, respectively, while oral burning was reported in 9%-45% of patients with gastroesophageal reflux disease. In case-control studies, gastroesophageal reflux disease was more prevalent in patients with burning mouth disorder compared with controls. Burning mouth would be resolved after antireflux therapy in laryngopharyngeal reflux patients in case series. PH value and saliva alternation might be the possible mechanisms. CONCLUSION: The possibility of the correlation between burning mouth disorder and gastroesophageal reflux disease still needs to be clearly demonstrated through better-conducted studies. The link between them is worth to be explored in future research.
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As one of the worst complications after solid organ transplantation (SOT) or hematopoietic stem cell transplantation (HSCT), post-transplant lymphoproliferative disorder (PTLD) usually progresses rapidly and accompanies with a high mortality rate, which is the most notorious adverse event threatening long-term survival of organ transplant recipients. PTLD is generally characterized by malignant clonal proliferation of lymphocytes, so the location of the disease is uncertain, the clinical symptoms and signs are very complex, lack of specificity, and it is easy to miss diagnosis and misdiagnosis in clinical practice, which will lead to low survival of patients after transplantation. To this end, the clinical data of two patients with PTLD were retrospectively studied, and characteristics of medical history, clinical manifestations, treatment process, curative effect and prognosis of the patients with PTLD were systematically analyzed and discussed, with a view to improving the novel understanding of PTLD in the field of hematology and oncology.
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OBJECTIVE: To discuss and analyze the clinical and prognostic characteristics of rare prolymphocytic leukemia (PLL), in order to provide new references for the clinical diagnosis and treatment and basic research of PLL. METHODS: The clinical data of 8 patients with PLL admitted to the Department of Hematology in Fujian Medical University Union Hospital from January 1, 2011 to May 31, 2023 were collected and retrospectively studied, and the clinical treatment and prognosis were analyzed. Meanwhile, the latest literature from PubMed was retrieved to systematically discuss the research progress in the diagnosis and treatment of PLL. RESULTS: In this study, of the 8 patients with PLL, 6 were males and 2 were females; the ages ranged from 52 to 80 years, with a median age of 70.5 years. The immunophenotypes were divided into B-PLL (7 cases) and T-PLL (1 case). Morphological, flow cytometric, cytogenetic and molecular biological tests of bone marrow cells were performed in all patients. Among them, 1 case refused chemotherapy after diagnosis and died in a short time, the other 7 cases received standard chemotherapy. Among the 7 patients, one patient died of severe infection caused by myelosuppression after chemotherapy, one patient died within 3 months after chemotherapy; two patients died of progression at 4 and 7 months after chemotherapy. A total of 3 patients achieved complete remission (CR) after chemotherapy, and 1 patient underwent allogeneic hematopoietic stem cell transplantation without disease progression or recurrence. CONCLUSION: PLL is a rare lymphoid malignancy with an extremely poor prognosis, which tends to occur in the elderly, and the clinical manifestations of PLL lack specificity. Chemotherapy combined with targeted drugs or epigenetic drugs may benefit PLL patients. Hematopoietic stem cell transplantation should be performed after CR is obtained to improve the prognosis to the greatest extent.
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OBJECTIVE: To analyze the effects of mangiferin combined with bortezomib on the proliferation, invasion, apoptosis and autophagy of human Burkitt lymphoma Raji cells, as well as the expression of CXC chemokine receptors (CXCRs) family, and explore the molecular mechanism between them to provide scientific basis for basic research and clinical work of Burkitt lymphoma. METHODS: Raji cells were intervened with different concentrations of mangiferin and bortezomib alone or in combination, then cell proliferation was detected by CCK-8 assay, cell invasion ability was detected by Transwell chamber method, cell apoptosis was detected by Annexin V/PI double-staining flow cytometry, apoptosis, autophagy and Akt/mTOR pathway protein expression were detected by Western blot, and the expression changes of CXCR family was detected by real-time quantitative PCR (RT-qPCR). RESULTS: Different concentrations of mangiferin intervened Raji cells for different time could inhibit cell viability in a concentration- and time-dependent manner (r =-0.682, r =-0.836). When Raji cells were intervened by combination of mangiferin and bortezomib, compared with single drug group, the proliferation and invasion abilities were significantly decreased, while the apoptosis level was significantly increased (P <0.01). Mangiferin combined with bortezomib could significantly up-regulate the expression of pro-apoptotic protein Bax and down-regulate the expression of anti-apoptotic protein Bcl-2 after intervention in Raji cells. Caspase-3 was also hydrolyzed and activated, and then induced the apoptosis of Raji cells. Mangiferin combined with bortezomib could up-regulate the expression of LC3â ¡ protein in Raji cells, and the ratio of LC3â ¡/LC3â in cells was significantly up-regulated compared with single drug or control group (P <0.01). Mangiferin combined with bortezomib could significantly inhibit the phosphorylation levels of Akt and mTOR, inhibit the proliferation and invasion of Raji cells by inhibiting Akt/mTOR pathway, and induce cell autophagy and apoptosis. Mangiferin and bortezomib could down-regulate the expressions of CXCR4 and CXCR7 mRNA after single-agent intervention in Raji cells, and the down-regulations of CXCR4 and CXCR7 mRNA expression were more significant when the two drugs were combined (P <0.01). Mangiferin alone or combined with bortezomib had no significant effect on CXCR5 mRNA expression in Raji cells (P >0.05), while the combination of the two drugs could down-regulate the expression of CXCR3 (P <0.05). CONCLUSION: Mangiferin combined with bortezomib can synergistically inhibit the proliferation and invasion of Raji cells, and induce autophagy and apoptosis. The mechanism may be related to the inhibition of Akt/mTOR signaling pathway, down-regulation of anti-apoptotic protein Bcl-2 and up-regulation of pro-apoptotic protein Bax, and the inhibition of the expression of CXCR family.
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Antineoplásicos , Bortezomib , Linfoma de Burkitt , Receptores CXCR , Xantonas , Humanos , Antineoplásicos/imunologia , Antineoplásicos/farmacologia , Antineoplásicos/uso terapêutico , Apoptose/efeitos dos fármacos , Proteínas Reguladoras de Apoptose/biossíntese , Proteínas Reguladoras de Apoptose/imunologia , Autofagia/efeitos dos fármacos , Autofagia/imunologia , Proteína X Associada a bcl-2/biossíntese , Proteína X Associada a bcl-2/imunologia , Bortezomib/imunologia , Bortezomib/farmacologia , Bortezomib/uso terapêutico , Linfoma de Burkitt/tratamento farmacológico , Linfoma de Burkitt/imunologia , Linhagem Celular Tumoral , Proliferação de Células/efeitos dos fármacos , Quimioterapia Combinada , Proteínas Proto-Oncogênicas c-akt , Proteínas Proto-Oncogênicas c-bcl-2 , Receptores CXCR/biossíntese , Receptores CXCR/imunologia , RNA Mensageiro , Serina-Treonina Quinases TOR , Xantonas/imunologia , Xantonas/farmacologia , Xantonas/uso terapêuticoRESUMO
In this report, we present a photocatalytic ring-opening fluorosulfonylation of strained cycloalkanols with sulfur dioxide and NFSI under mild conditions for the synthesis of carbonyl-containing aliphatic sulfonyl fluorides. The synthetic potential of the carbonyl-containing aliphatic sulfonyl fluoride products has been examined by diverse transformations, including SuFEx reactions and Baeyer-Villiger oxidation reactions. Mechanistic studies demonstrate that the reaction operates through a radical C-C bond cleavage/SO2 insertion/fluorination cascade process.
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Ticlopidine exerts its anti-platelet effects mainly by antagonizing platelet p2y12 receptors. Previously, a few studies have shown that ticlopidine can induce liver injury, but the exact mechanism of hepatotoxicity remains unclear. Oxidative stress, metabolic disorders, hepatocyte apoptosis, lipid peroxidation, and inflammatory responses can all lead to hepatic liver damage, which can cause hepatotoxicity. In this study, in order to deeply explore the potential molecular mechanisms of ticlopidine -induced hepatotoxicity, we used zebrafish as a model organism to comprehensively evaluate the hepatotoxicity of ticlopidine and its associated mechanism. Three days post-fertilization, zebrafish larvae were exposed to varying concentrations (1.5, 1.75 and 2 µg/mL) of ticlopidine for 72 h, in contrast, adult zebrafish were exposed exposure to 4 µg/mL of ticlopidine for 28 days. Ticlopidine-exposed zebrafish larvae showed changes in liver morphology, shortened body length, and delayed development of the swim bladder development. Liver tissues of ticlopidine-exposed zebrafish larvae and adults stained with Hematoxylin & Eosin revealed vacuolization and increased cellular interstitial spaces in liver tissues. Furthermore, using Oil Red O and periodic acid-Schiff staining methods and evaluating different metabolic enzymes of ticlopidine-exposed zebrafish larvae and adults suggested abnormal liver metabolism and liver injury in both ticlopidine-exposed zebrafish larvae and adults. Ticlopidine also significantly elevated inflammation and oxidative stress and reduced hepatocyte proliferation. During the rescue intervention using N-acetylcysteine, we observed significant improvement in ticlopidine-induced morphological changes in the liver, shortened body length, delayed swim bladder development, and proliferation of liver tissues showed significant improvement. In conclusion, ticlopidine might inhibit normal development and liver proliferation in zebrafish by upregulation of oxidative stress levels, thus leading to embryonic developmental toxicity and hepatotoxicity. In this study, we used zebrafish as a model organism to elucidate the developmental toxicity and hepatotoxicity induced by ticlopidine upregulation of oxidative stress signaling pathway in zebrafish, providing a theoretical basis for clinical application.
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The pathogenesis of hematological tumors has not been fully elucidated. The academic community believes that genetic mutation abnormalities play a crucial role in the occurrence and development of hematological malignancies. Chronic neutrophilic leukemia (CNL) is a rare hematological tumor in the world. It is characterized by a Philadelphia chromosome BCR-ABL1-negative myeloproliferative tumor. It can be accompanied by mutations in various genes. Colony-stimulating factor 3 receptor (CSF3R) is a classic mutation in CNL and is included in the diagnostic criteria for CNL. This article described a 46-year-old male patient who came to the hospital with non-specific clinical manifestations such as unrelieved abdominal distension and edema of both lower extremities as the primary symptoms. The middle-aged male patient was provided with a peripheral a routine blood test. The biochemical tests revealed abnormalities. A bone marrow biopsy was performed to complete various tests such as bone marrow morphology, immunology, molecular biology, cytogenetics, and imaging. He was diagnosed with a rare chronic neutrophilic leukemia. After the diagnosis, the patient took ruxolitinib orally targeted therapy as prescribed by the doctor. Doctors regularly reviewed the peripheral blood examination and bone marrow status. The current condition is well controlled. CNL is extremely rare. The disease usually has non-specific clinical features and manifestations as the primary symptoms. These symptoms can easily be missed or lead to misdiagnosed ailments by clinicians. It is necessary to increase the awareness and vigilance of CNL.
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Recent interest in mushrooms and their components as potential therapies for mental health, along with recent government and health authority approvals, has necessitated a more comprehensive understanding of their effects on the cellular microenvironment of the brain. Amanita muscaria has been ingested as a treatment for a variety of ailments for centuries, most notably those affecting the central nervous system and conditions associated with neuroinflammation. However, the effects of these extracts on neuroinflammatory cells, such as microglia, are unknown. The effect of commercially-sourced A. muscaria extract (AME-1) on human microglial cell line (HMC3) expression of surface receptors such as CD86, CXCR4, CD45, CD125 and TLR4 was determined by flow cytometry. AME-1 upregulated expression of all of these receptors. The effect of AME-1 on HMC3 production of IL-8 and IL-6 was determined and compared to tumor necrosis factor (TNF), polyinosinic-polycytidylic acid [poly(I:C)], substance P and lipopolysaccharide (LPS), all known activators of HMC-3 and primary microglia. HMC3 produced both IL-8 and IL-6 when activated with LPS, TNF and poly(I:C) but not when they were activated with substance P. Although AME-1 at higher concentrations increased IL-8 production of HMC3 on its own, AME-1 notably potentiated HMC3 production of IL-8 in response to poly(I:C). AME-1 altered expression of toll-like receptor 3 (TLR3) mRNA but not surface protein by HMC3. AME-1 also did not significantly alter expression of retinoic acid-inducible gene I (RIG-I) or melanoma differentiation-associated protein 5 (MDA5), both cytosolic sensors of dsRNA. Metabolomics analysis showed that AME-1 contained several metabolites, including the autophagy inducer, trehalose. Like AME-1, trehalose also potentiated HMC3 poly(I:C) mediated production of IL-8. This study suggests that A. muscaria extracts can modify HMC3 inflammatory responses, possibly due to their trehalose content.