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Aim: Groove pancreatitis (GP) is a rare type of chronic pancreatitis characterized by varying degrees of thickening and scarring of the duodenal wall, duodenal lumen stenosis, mucosal hypertrophy with plicae and cyst formation. GP is primarily observed in middle-aged male patients with a history of alcohol consumption. Clinical symptoms are usually non-specific, and there is currently no unified diagnostic standard. However, imaging methods, particularly endoscopic ultrasound (EUS), are useful for diagnosis. EUS-guided biopsy can provide a strong basis for the final diagnosis. This review summarizes the value of EUS and its derivative technologies in the diagnosis, differential diagnosis and treatment of GP.Methods: After searching in PubMed and Web of Science databases using 'groove pancreatitis (GP)' and 'endoscopic ultrasonography (EUS)' as keywords, studies related were compiled and examined.Results: EUS and its derivative technologies are of great significance in the diagnosis, differential diagnosis, and treatment of GP, but there are still limitations that need to be comprehensively applied with other diagnostic methods to obtain the most accurate results.Conclusion: EUS has unique value in both the diagnosis and treatment of GP. Clinicians need to be well-versed in the advantages and limitations of EUS for GP diagnosis to select the most suitable imaging diagnostic method for different cases and to reduce the unnecessary waste of medical resources.
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Endossonografia , Pancreatite Crônica , Pessoa de Meia-Idade , Humanos , Masculino , Pancreatite Crônica/diagnóstico por imagem , BiópsiaRESUMO
BACKGROUND: Predictive biomarkers for oesophageal squamous cell carcinoma (ESCC) immunotherapy are lacking, and immunotherapy resistance remains to be addressed. The role of long noncoding RNA (lncRNA) in ESCC immune escape and immunotherapy resistance remains to be elucidated. METHODS: The tumour-associated macrophage-upregulated lncRNAs and the exosomal lncRNAs highly expressed in ESCC immunotherapy nonresponders were identified by lncRNA sequencing and polymerase chain reaction assays. CRISPR-Cas9 was used to explore the functional roles of the lncRNA. RNA pull-down, MS2-tagged RNA affinity purification (MS2-TRAP) and RNA-binding protein immunoprecipitation (RIP) were performed to identify lncRNA-associated proteins and related mechanisms. In vivo, the humanized PBMC (hu-PBMC) mouse model was established to assess the therapeutic responses of specific lncRNA inhibitors and their combination with programmed cell death protein 1 (PD-1) monoclonal antibody (mAb). Single-cell sequencing, flow cytometry, and multiplex fluorescent immunohistochemistry were used to analyze immune cells infiltrating the tumour microenvironment. RESULTS: We identified a lncRNA that is involved in tumour immune evasion and immunotherapy resistance. High LINC02096 (RIME) expression in plasma exosomes correlates with a reduced response to PD-1 mAb treatment and poor prognosis. Mechanistically, RIME binds to mixed lineage leukaemia protein-1 (MLL1) and prevents ankyrin repeat and SOCS box containing 2 (ASB2)-mediated MLL1 ubiquitination, improving the stability of MLL1. RIME-MLL1 increases H3K4me3 levels in the promoter regions of programmed death-ligand 1 (PD-L1) and indoleamine 2,3-dioxygenase 1 (IDO-1), constitutively increasing the expression of PD-L1/IDO-1 in tumour cells and inhibiting CD8+ T cells infiltration and activation. RIME depletion in huPBMC-NOG mice significantly represses tumour development and improves the effectiveness of PD-1 mAb treatment by activating T-cell-mediated antitumour immunity. CONCLUSIONS: This study reveals that the RIME-MLL1-H3K4me3 axis plays a critical role in tumour immunosuppression. Moreover, RIME appears to be a potential prognostic biomarker for immunotherapy and developing drugs that target RIME may be a new therapeutic strategy that overcomes immunotherapy resistance and benefits patients with ESCC.
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Neoplasias Esofágicas , Carcinoma de Células Escamosas do Esôfago , RNA Longo não Codificante , Animais , Camundongos , Anticorpos Monoclonais , Antígeno B7-H1/genética , Linfócitos T CD8-Positivos , Neoplasias Esofágicas/genética , Carcinoma de Células Escamosas do Esôfago/genética , Leucócitos Mononucleares , Proteína de Leucina Linfoide-Mieloide , Receptor de Morte Celular Programada 1 , RNA Longo não Codificante/genética , Microambiente Tumoral/genéticaRESUMO
Benign and malignant pelvic masses with or without intestinal invasion are common in women of childbearing age. Patients may have nonspecific symptoms and signs or experience no symptoms. Laparoscopic resection of pelvic masses is currently the mainstream treatment; therefore, accurate preoperative evaluation is not only essential for patients suspected of having intestinal invasion, but also extremely important for the selection of follow-up treatment. Procedures, including endoscopic ultrasonography (EUS), pelvic magnetic resonance imaging, abdominal computed tomography, vaginal ultrasonography, barium enema, and colonoscopy, aid in determining the presence, depth, and histology of the disease. In particular, the wide application and continuous developments in EUS techniques have improved the diagnostic accuracy for intestinal subepithelial and peripheral organ lesions. This article reviewed the clinical value of EUS in the diagnosis of benign and malignant pelvic masses with bowel involvement.
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BACKGROUND: Mycobacterium marinum is a nontuberculous mycobacterium and a conditional pathogen to humans, which can be inoculated directly and cause chronic skin granulomas. Dermoscopy has been applied to other granulomatous skin diseases, but not to M. marinum infection. AIM: To explore the dermoscopic features of M. marinum infection, and its correlation with clinical and histopathological features. METHODS: In total, 27 lesions from 27 patients (19 women, 8 men, age range 28-71 years) diagnosed with M. marinum infection were identified by clinical examination, histopathological results, PCR sequencing and mycobacterial culture in the dermatology outpatient department of our hospital from March 2020 to February 2022. The dermoscopy images and pathological characteristics were analysed. RESULTS: Lesions were located on the hands, forearms and upper arms. The following dermoscopic features were observed: yellowish-orange structureless areas (85·2%), white striped structures (59·3%), follicular plugs (29·6%), yellowish oval clods (14·8%) and reddish or pinkish areas (14·8%). Vessel structures were visible in all cases: long hairpin vessels (81·5%), corkscrew vessels (25·9%), comma-shaped vessels (22·2%) and linear vessels (22·2%). CONCLUSION: Yellowish-orange structureless areas, white striped structures and long hairpin vessels are the most common dermoscopic features of M. marinum infection. Thus, dermoscopy could be used as a noninvasive auxiliary diagnostic method to provide a diagnostic basis for this disease.
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Infecções por Mycobacterium não Tuberculosas , Neoplasias Cutâneas , Masculino , Humanos , Feminino , Adulto , Pessoa de Meia-Idade , Idoso , Dermoscopia , Infecções por Mycobacterium não Tuberculosas/diagnóstico por imagem , Neoplasias Cutâneas/patologia , Micobactérias não TuberculosasRESUMO
Circular RNA (circRNA) is a category of non-coding RNAs characterized by the absence of a 5'-cap and 3'-poly(A) tail, and participates in the physiological processes of various human diseases. Nonetheless, the diagnostic and functional significance of circRNAs in active pulmonary tuberculosis (ATB) remains uncertain. Consequently, the purpose of this study is to investigate whether hsa_circ_0007460 can be employed as a potential diagnostic biomarker in ATB patients and explore its function. The result of real-time quantitative fluorescent PCR (RT-qPCR) validated a notable increase in the expression of hsa_circ_0007460 in the peripheral blood of 32 ATB patients, as well as in THP-1 human macrophages infected with Bacillus Calmette Guerin (BCG) which is an attenuated strain of Mycobacterium bovis. Additionally, the receiver operating curve (ROC) illustrated that the area under the ROC curve (AUC), sensitivity and specificity were 0.7474, 76.67%, and 78.13% respectively. RNase R, Actinomycin D and other experiments confirmed that hsa_circ_0007460 was stabler than its linear mRNA, indicating that hsa_circ_0007460 has potential as a diagnostic biomarker of ATB. Furthermore, Western blot (WB), Cell Counting Kit-8 (CCK-8), plate counting, and immunofluorescence experiments revealed that hsa_circ_0007460 could regulate apoptosis and autophagy of macrophages. The downstream miRNAs and mRNAs were subsequently predicted using bioinformatics, and the hsa circ 0007460/hsa-miR-3127-5p/PATZ1 axis was built. These above results suggest that hsa_circ_0007460 is substantially up-regulated in the peripheral blood of patients with ATB and can be utilized as a potential diagnostic biomarker. In addition, hsa_circ_0007460 can promote apoptosis of macrophages and inhibit autophagy of macrophages, thereby promoting the survival of BCG.
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Apoptose , Autofagia , Macrófagos , Mycobacterium tuberculosis , RNA Circular , Humanos , Autofagia/genética , RNA Circular/genética , Macrófagos/microbiologia , Macrófagos/metabolismo , Apoptose/genética , Mycobacterium tuberculosis/genética , Mycobacterium tuberculosis/fisiologia , Feminino , Adulto , Masculino , Tuberculose Pulmonar/genética , Tuberculose Pulmonar/microbiologia , Células THP-1 , Pessoa de Meia-IdadeRESUMO
To date, Cd contamination of cropland and crops is receiving more and more attention around the world. As a plant hormone, abscisic acid (ABA) plays an important role in Cd stress response, but its effect on plant Cd uptake and translocation varies among plant species. In some species, such as Arabidopsis thaliana, Oryza sativa, Brassica chinensis, Populus euphratica, Lactuca sativa, and Solanum lycopersicum, ABA inhibits Cd uptake and translocation, while in other species, such as Solanum photeinocarpum and Boehmeria nivea, ABA severs the opposite effect. Interestingly, differences in the methods and concentrations of ABA addition also triggered the opposite result of Cd uptake and translocation in Sedum alfredii. The regulatory mechanism of ABA involved in Cd uptake and accumulation in plants is still not well-established. Therefore, we summarized the latest studies on the ABA synthesis pathway and comparatively analyzed the physiological and molecular mechanisms related to ABA uptake, translocation, and detoxification of Cd in plants at different ABA concentrations or among different species. We believe that the control of Cd uptake and accumulation in plant tissues can be achieved by the appropriate ABA application methods and concentrations in plants.
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BACKGROUND: Plant diseases caused by viruses and fungi have caused great losses to crop quality and yield. The discovery of novel and efficient antiviral and antiphytopathogenic-fungus agents is urgently needed. It is the most important pesticide innovation strategy to find active compounds from natural products. Here, glyantrypine-family alkaloids were taken as the parent structures and a series of their derivatives were designed through molecular splicing, ring expansion, and ring contraction strategies, and synthesized. The anti-tobacco mosaic virus (TMV) activities and antifungal activities of these alkaloids were systematically investigated for the first time. RESULT: The antiviral activities of compounds 7bb, 7bc, 11c, 18b, 18d, 28d, and 28e are equivalent to or better than that of ribavirin (inhibitory rates 39%, 37%, and 40% at 500 µg mL-1 for inactivation, curative, and protection activity in vivo, respectively). Compounds 18d and 28d with good antiviral activities were selected for antiviral mode of action studies, which indicated that these alkaloids could achieve good antiviral effects by inhibiting TMV particle extension during assembly. These compounds also exhibited broad-spectrum fungicidal activities. CONCLUSION: Glyantrypine-family alkaloids and their derivatives were synthesized and evaluated for anti-TMV and fungicidal activities for the first time. Compounds 18d and 28d with excellent antiviral activities and compound 7bc with remarkable fungicidal activity emerged as novel lead compounds. This study lays a foundation for the application of glyantrypine alkaloids in plant protection.
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Alcaloides , Fungicidas Industriais , Vírus do Mosaico do Tabaco , Alcaloides/farmacologia , Antivirais/farmacologia , Desenho de Fármacos , Fungos , Fungicidas Industriais/farmacologia , Quinazolinas , Relação Estrutura-Atividade , Triptofano/análogos & derivadosRESUMO
PURPOSE: The aim of this study was to determine a better criterion for end-of-treatment PET (EoT-PET) assessment and prognostic evaluation of patients with diffuse large B cell lymphoma (DLBCL). METHOD: EoT-PET scans were assessed using the visual Deauville 5-point scale (5PS) and LLR, the maximum standard uptake value ratio between the lesion and the liver. The cutoff value of LLR was obtained by receiver operator characteristic curve analysis. Patient outcomes were compared using Kaplan-Meier survival analysis. Prognostic indexes of different criteria were compared. Multivariate Cox regression analysis was performed to evaluate the prognostic factors. RESULTS: Four hundred forty-nine newly diagnosed DLBCL patients who received rituximab-based immunochemotherapy were included, and the median follow-up duration was 41.4 months. Patients with Deauville score (DS) 4 displayed significantly longer PFS and OS compared with patients with DS 5 (both p < 0.001), and they had significantly shorter PFS (p < 0.01) but similar OS (p = 0.057) compared with patients with DS 1-3. The differences in PFS and OS between groups were all significant whether positive EoT-PET was defined as DS 4-5 or DS 5 (all p < 0.001). The optimal cutoff of LLR was 1.83, and both PFS and OS were significantly different between EoT-PET-positive and EoT-PET-negative patients as defined by the cutoff (both p < 0.001). LLR-based criterion displayed higher specificity, positive predictive value, and accuracy than 5PS-based criterion in the prediction of disease progression and death events. In the multivariate analysis, positive EoT-PET (as defined by LLR) was related to unfavorable PFS and OS (both p < 0.001). Additional treatment was not correlated with outcomes of EoT-PET-negative patients either defined by LLR or 5PS or EoT-PET-positive patients classified by 5PS, but it was the only beneficial factor for OS (p < 0.05) in EoT-PET-positive patients with LLR ≥ 1.83. CONCLUSION: The optimal cutoff of LLR may be superior to Deauville criteria in identifying low-risk DLBCL patients with negative EoT-PET after the first-line immunochemotherapy and sparing them the cost and toxicity of additional treatment.
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Fluordesoxiglucose F18 , Linfoma Difuso de Grandes Células B , Humanos , Fígado , Linfoma Difuso de Grandes Células B/diagnóstico por imagem , Linfoma Difuso de Grandes Células B/tratamento farmacológico , Tomografia por Emissão de Pósitrons combinada à Tomografia Computadorizada , Tomografia por Emissão de Pósitrons , Prognóstico , Estudos Retrospectivos , Tomografia Computadorizada por Raios XRESUMO
PURPOSE: To investigate the effects of dose reduction on image quality and lesion detectability of oncological 18F-FDG total-body PET/CT in pediatric oncological patients and explore the minimum threshold of administered tracer activity. METHODS: A total of 33 pediatric patients (weight 8.5-58.5 kg; age 0.8-17.6 years) underwent total-body PET/CT using uEXPLORER scanner with an 18F-FDG administered dose of 3.7 MBq/kg and an acquisition time of 600 s were retrospectively enrolled. Low-dose images (0.12-1.85 MBq/kg) were simulated by truncating the list-mode PET data to reducing count density. Subjective image quality was rated on a 5-point scale. Semi-quantitative uptake metrics for low-dose images were assessed using region-of-interest (ROI) analysis of healthy liver and suspected lesions and were compared with full-dose images. The micro-lesion detectability was compared among the dose-dependent PET images. RESULTS: Our analysis shows that sufficient subjective image quality and lesion conspicuity could be maintained down to 1/30th (0.12 MBq/kg) of the administered dose of 18F-FDG, where good image quality scores were given to 1/2- and 1/10- dose groups. The image noise was significantly more deranged than the overall quality and lesion conspicuity in 1/30- to 1/10-dose groups (all p < 0.05). With reduced doses, quantitative analysis of ROIs showed that SUVmax and SD in the liver increased gradually (p < 0.05), but SUVmax in the lesions and lesion-to-background ratio (LBR) showed no significant deviation down to 1/30-dose. One hundred percent of the 18F-FDG-avid micro-lesions identified in full-dose images were localized down to 1/15-dose images, while 97% of the lesion were localized in 1/30-dose images. CONCLUSION: The total-body PET/CT might significantly decrease the administered dose upon maintaining the image quality and diagnostic performance of micro-lesions in pediatric patients. Data suggests that using total-body PET/CT, optimal image quality could be achieved with an administered dose-reduction down to 1/10-dose (0.37 MBq/kg).
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Fluordesoxiglucose F18 , Neoplasias , Adolescente , Criança , Pré-Escolar , Humanos , Lactente , Tomografia por Emissão de Pósitrons combinada à Tomografia Computadorizada , Tomografia por Emissão de Pósitrons , Estudos RetrospectivosRESUMO
PURPOSE: To evaluate the treatment-dependent changes in FDG uptake in the adenoid, palatine tonsils, and thymus in paediatric patients with lymphoma. METHODS: Eight hundred PET/CT scans of 212 paediatric patients between 2007 and 2019 (mean age, 11.9 years; median follow-up, 26.2 months) were retrospectively reviewed for discernible FDG uptake in the adenoid (A+), palatine tonsils (P+), and thymus (T+). The distribution of metabolic activity in the interested lymphoid organs was examined. Statistical analysis was performed using SPSS packages. RESULTS: There were 513 (64 %) Aâ¯+â¯scans, 548 (69 %) Pâ¯+â¯scans, 270 (48 %) Tâ¯+â¯scans identified. The percentage of Aâ¯+â¯was 88 % at baseline, decreased to 48 % at the end of treatment, and then rebounded to 73 % during follow up; Pâ¯+â¯went from 79 % to 45 % then to 82 %; and for Tâ¯+â¯was 75 %, 21 %, 72 %. SUVmax was significantly higher (Pâ¯<â¯0.001) in scans performed during follow-up than that of the baseline (Aâ¯+â¯7.0⯱â¯3.5 vs. 5.8⯱â¯2.5; Pâ¯+â¯9.4⯱â¯3.5 vs. 8.2⯱â¯2.8; Tâ¯+â¯4.0⯱â¯1.4 vs. 3.4⯱â¯1.1). Aâ¯+â¯and Pâ¯+â¯peaked between 6-12 months of follow-up with a SUVmax of 7.6⯱â¯3.2, 10.6⯱â¯3.2, accordingly; Tâ¯+â¯peaked within 3-12 months with a SUVmax of 4.4⯱â¯1.4. Despite that Aâ¯+â¯and Tâ¯+â¯were more commonly seen in younger patients at any given study time, evident uptake rebound persisted in patients aged ≥16. CONCLUSIONS: In paediatric patients with lymphoma, evident and benign rebound adenotonsillar and thymic 18F-FDG uptake commonly occur during post-treatment surveillance.
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Fluordesoxiglucose F18 , Linfoma , Idoso , Criança , Humanos , Linfoma/diagnóstico por imagem , Tomografia por Emissão de Pósitrons combinada à Tomografia Computadorizada , Tomografia por Emissão de Pósitrons , Compostos Radiofarmacêuticos , Estudos RetrospectivosRESUMO
BACKGROUND: Intestinal mucosal barrier dysfunction plays an important role in the pathogenesis of ulcerative colitis (UC). Recent studies have revealed that impaired autophagy is associated with intestinal mucosal dysfunction in the mucosa of colitis mice. Resveratrol exerts anti-inflammatory functions by regulating autophagy. AIM: To investigate the effect and mechanism of resveratrol on protecting the integrity of the intestinal mucosal barrier and anti-inflammation in dextran sulfate sodium (DSS)-induced ulcerative colitis mice. METHODS: Male C57BL/6 mice were divided into four groups: negative control group, DSS model group, DSS + resveratrol group, and DSS + 5-aminosalicylic acid group. The severity of colitis was assessed by the disease activity index, serum inflammatory cytokines were detected by enzyme-linked immunosorbent assay. Colon tissues were stained with haematoxylin and eosin, and mucosal damage was evaluated by mean histological score. The expression of occludin and ZO-1 in colon tissue was evaluated using immunohistochemical analysis. In addition, the expression of autophagy-related genes was determined using reverse transcription-polymerase chain reaction and Western-blot, and morphology of autophagy was observed by transmission electron microscopy. RESULTS: The resveratrol treatment group showed a 1.72-fold decrease in disease activity index scores and 1.42, 3.81, and 1.65-fold decrease in the production of the inflammatory cytokine tumor necrosis factor-α, interleukin-6 and interleukin-1ß, respectively, in DSS-induced colitis mice compared with DSS group (P < 0.05). The expressions of the tight junction proteins occludin and ZO-1 in DSS model group were decreased, and were increased in resveratrol-treated colitis group. Resveratrol also increased the levels of LC3B (by 1.39-fold compared with DSS group) and Beclin-1 (by 1.49-fold compared with DSS group) (P < 0.05), as well as the number of autophagosomes, which implies that the resveratrol may alleviate intestinal mucosal barrier dysfunction in DSS-induced UC mice by enhancing autophagy. CONCLUSION: Resveratrol treatment decreased the expression of inflammatory factors, increased the expression of tight junction proteins and alleviated UC intestinal mucosal barrier dysfunction; this effect may be achieved by enhancing autophagy in intestinal epithelial cells.
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Colite , Animais , Autofagia , Colite/induzido quimicamente , Colite/tratamento farmacológico , Colo , Sulfato de Dextrana/toxicidade , Modelos Animais de Doenças , Mucosa Intestinal , Masculino , Camundongos , Camundongos Endogâmicos C57BL , Resveratrol/farmacologiaRESUMO
BACKGROUND: Conventional Crohn's disease (CD) treatments are supportive rather than curative and have serious side effects. Adipose-derived mesenchymal stem cells (ADSCs) have been gradually applied to treat various diseases. The therapeutic effect and underlying mechanism of ADSCs on CD are still not clear. AIM: To investigate the effect of ADSC administration on CD and explore the potential mechanisms. METHODS: Wistar rats were administered with 2,4,6-trinitrobenzene sulfonic acid (TNBS) to establish a rat model of CD, followed by tail injections of green fluorescent protein (GFP)-modified ADSCs. Flow cytometry, qRT-PCR, and Western blot were used to detect changes in the Wnt signaling pathway, T cell subtypes, and their related cytokines. RESULTS: The isolated cells showed the characteristics of ADSCs, including spindle-shaped morphology, high expression of CD29, CD44, and CD90, low expression of CD34 and CD45, and osteogenic/adipogenic ability. ADSC therapy markedly reduced disease activity index and ameliorated colitis severity in the TNBS-induced rat model of CD. Furthermore, serum anti-sacchromyces cerevisiae antibody and p-anti-neutrophil cytoplasmic antibody levels were significantly reduced in ADSC-treated rats. Mechanistically, the GFP-ADSCs were colocalized with intestinal epithelial cells (IECs) in the CD rat model. GFP-ADSC delivery significantly antagonized TNBS-induced increased canonical Wnt pathway expression, decreased noncanonical Wnt signaling pathway expression, and increased apoptosis rates and protein level of cleaved caspase-3 in rats. In addition, ADSCs attenuated TNBS-induced abnormal inflammatory cytokine production, disturbed T cell subtypes, and their related markers in rats. CONCLUSION: Successfully isolated ADSCs show therapeutic effects in CD by regulating IEC proliferation, the Wnt signaling pathway, and T cell immunity.
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Tecido Adiposo , Colite , Células-Tronco Mesenquimais , Animais , Colite/induzido quimicamente , Colite/terapia , Células Epiteliais , Transplante de Células-Tronco Mesenquimais , Ratos , Ratos Wistar , Regeneração , Linfócitos T , Ácido Trinitrobenzenossulfônico/toxicidade , Via de Sinalização WntRESUMO
BACKGROUND: Gastric cancer (GC) is one of the most common and deadliest types of cancer worldwide due to its delayed diagnosis and high metastatic frequency, but its exact pathogenesis has not been fully elucidated. ETS homologous factor (EHF) is an important member of the ETS family and contributes to the pathogenesis of multiple malignant tumors. To date, whether EHF participates in the development of GC via the c-Met signaling pathway remains unclear. AIM: To investigate the role and mechanism of EHF in the occurrence and development of GC. METHODS: The expression of EHF mRNA in GC tissues and cell lines was measured by quantitative PCR. Western blotting was performed to determine the protein expression of EHF, c-Met, and its downstream signal molecules. The EHF expression in GC tissues was further detected by immunohistochemical staining. To investigate the role of EHF in GC oncogenesis, small interfering RNA (siRNA) against EHF was transfected into GC cells. The cell proliferation of GC cells was determined by Cell Counting Kit-8 and colony formation assays. Flow cytometry was performed following Annexin V/propidium iodide (PI) to identify apoptotic cells and PI staining to analyze the cell cycle. Cell migration and invasion were assessed by transwell assays. RESULTS: The data showed that EHF was upregulated in GC tissues and cell lines in which increased expression of c-Met was also observed. Silencing of EHF by siRNA reduced the proliferation of GC cells. Inhibition of EHF induced significant apoptosis and cell cycle arrest in GC cells. Cell migration and invasion were significantly inhibited. EHF silencing led to c-Met downregulation and further blocked the Ras/c-Raf/extracellular signal-related kinase 1/2 (Erk1/2) pathway. Additionally, phosphatase and tensin homolog was upregulated and glycogen synthase kinase 3 beta was deactivated. Moreover, inactivation of signal transducer and activator of transcription 3 was detected following EHF inhibition, leading to inhibition of the epithelial-to-mesenchymal transition (EMT). CONCLUSION: These results suggest that EHF plays a key role in cell proliferation, invasion, apoptosis, the cell cycle and EMT via the c-Met pathway. Therefore, EHF may serve as an antineoplastic target for the diagnosis and treatment of GC.
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Neoplasias Gástricas , Linhagem Celular Tumoral , Movimento Celular , Proliferação de Células , Transição Epitelial-Mesenquimal , Regulação Neoplásica da Expressão Gênica , Humanos , Invasividade Neoplásica , Neoplasias Gástricas/genéticaRESUMO
BACKGROUND: Sirtuin 1 (SIRT1) is a nicotinamide adenine dinucleotide (NAD+)-dependent protein deacetylase that is involved in various diseases, including cancers, metabolic diseases, and inflammation-associated diseases. However, the role of SIRT1 in ulcerative colitis (UC) is still confusing. AIM: To investigate the role of SIRT1 in intestinal epithelial cells (IECs) in UC and further explore the underlying mechanisms. METHODS: We developed a coculture model using macrophages and Caco-2 cells. After treatment with the SIRT1 activator SRT1720 or inhibitor nicotinamide (NAM), the expression of occludin and zona occludens 1 (ZO-1) was assessed by Western blot analysis. Annexin V-APC/7-AAD assays were performed to evaluate Caco-2 apoptosis. Dextran sodium sulfate (DSS)-induced colitis mice were exposed to SRT1720 or NAM for 7 d. Transferase-mediated dUTP nick-end labeling (TUNEL) assays were conducted to assess apoptosis in colon tissues. The expression levels of glucose-regulated protein 78 (GRP78), CCAAT/enhancer-binding protein homologous protein (CHOP), caspase-12, caspase-9, and caspase-3 in Caco-2 cells and the colon tissues of treated mice were examined by quantitative real-time PCR and Western blot. RESULTS: SRT1720 treatment increased the protein levels of occludin and ZO-1 and inhibited Caco-2 apoptosis, whereas NAM administration caused the opposite effects. DSS-induced colitis mice treated with SRT1720 had a lower disease activity index (P < 0.01), histological score (P < 0.001), inflammatory cytokine levels (P < 0.01), and apoptotic cell rate (P < 0.01), while exposure to NAM caused the opposite effects. Moreover, SIRT1 activation reduced the expression levels of GRP78, CHOP, cleaved caspase-12, cleaved caspase-9, and cleaved caspase-3 in Caco-2 cells and the colon tissues of treated mice. CONCLUSION: SIRT1 activation reduces apoptosis of IECs via the suppression of endoplasmic reticulum stress-mediated apoptosis-associated molecules CHOP and caspase-12. SIRT1 activation may be a potential therapeutic strategy for UC.
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Apoptose , Colite Ulcerativa/patologia , Estresse do Retículo Endoplasmático , Mucosa Intestinal/patologia , Sirtuína 1/metabolismo , Animais , Células CACO-2 , Caspase 12/metabolismo , Técnicas de Cocultura , Colite Ulcerativa/induzido quimicamente , Colite Ulcerativa/tratamento farmacológico , Sulfato de Dextrana/toxicidade , Modelos Animais de Doenças , Chaperona BiP do Retículo Endoplasmático , Células Epiteliais/efeitos dos fármacos , Células Epiteliais/patologia , Feminino , Compostos Heterocíclicos de 4 ou mais Anéis/administração & dosagem , Humanos , Mucosa Intestinal/citologia , Macrófagos , Camundongos , Niacinamida/administração & dosagem , Sirtuína 1/antagonistas & inibidores , Fator de Transcrição CHOP/metabolismoRESUMO
Mesh migration and penetration into abdominal viscera rarely occur after laparoscopic inguinal hernia repair. We present the first case of mesh migration into the sigmoid colon identified as a colonic polyp at initial colonoscopic examination. The patient complained of mild abdominal distention in the lower abdomen over the previous year without changes in bowel habits or stool appearance and without weight loss. By complementary endoscopic ultrasonography, a cavity-like structure beneath the suspected polyp was further confirmed. Enhanced abdominal computed tomography merely revealed local bowel wall thickening and inflammation of the colosigmoid junction. The migrating mesh, which was lodged in the sigmoid colon and caused intra-abdominal adhesion in the lower abdominal cavity, was finally identified via exploratory surgery. The components of inflammatory granulation tissue around the mesh material were diagnosed based on histological examination of the surgical specimen after sigmoidectomy. In this patient, nonspecific endoscopic and imaging outcomes during clinical work-up led to the diagnostic dilemma of mesh migration. Therefore, the clinical, radiological and endoscopic challenges specific to this case as well as the underlying reasons for mesh migration are discussed in detail.
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RATIONALE: Intrauterine contraceptive devices (IUDs) are recommended as a means of contraception. Translocation of IUD is a rare and serious complication. Colonic inflammatory mass caused by translocated IUD initially misdiagnosed as a colonic polyp is extremely rare and has not been reported yet. PATIENT CONCERNS: This report presents a case of sigmoid colon translocation of intrauterine device on a 37-year-old female patient. Colonoscopy was performed due to her complain of repeated blood in stools and subsequently the patient was misdiagnosed as a sigmoid colon polyp. Nonetheless, the "polyp" was not able to be removed endoscopically. DIAGNOSES: Sigmoid colon translocation of an intrauterine device. INTERVENTIONS: To further clarify the diagnosis, computed tomography (CT) scan was performed and the "polyp" was confirmed to be caused by a translocated IUD. OUTCOMES: The translocated IUD was removed easily by surgery, and the patient recovered soon after the operation. LESSONS: The present case indicates that an annual gynaecologic examination is necessary to determine the position of the IUD, and a CT examination may help confirm an ectopic IUD.
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Colite , Colo Sigmoide , Pólipos do Colo/diagnóstico , Colonoscopia/métodos , Erros de Diagnóstico , Migração de Dispositivo Intrauterino/efeitos adversos , Adulto , Colite/diagnóstico , Colite/etiologia , Colite/cirurgia , Colo Sigmoide/patologia , Colo Sigmoide/cirurgia , Remoção de Dispositivo/métodos , Diagnóstico Diferencial , Feminino , Humanos , Dispositivos Intrauterinos/efeitos adversos , Tomografia Computadorizada por Raios X/métodos , Resultado do TratamentoRESUMO
Mesenchymal stem cells (MSCs) and regulatory T cells (Tregs) are both potent immune-modulators. The aberrant proliferation and function of Tregs plays an important role in the development of asthma. Our previous studies have demonstrated the role of MSCs in promoting proliferation and immune-modulating of Tregs, as well as alleviating airway inflammation of asthmatic mice. In the present study, we isolated exosomes secreted by MSCs and investigated their immunomodulation effect on peripheral blood mononuclear cells (PBMCs) of asthmatic patient. We found that MSC exosomes upregulated IL-10 and TGF-ß1 from PBMCs, thus promoting proliferation and immune-suppression capacity of Tregs. Furthermore, antigen presenting cells (APCs) but not CD4+ T cells-dependent pathway was shown to be possible mechanism involved in MSC exosome-mediated regulation. Our data elucidated the key role of exosomes in immune-modulation of MSCs, and suggested the therapeutic potential of MSC exosomes for asthma.
Assuntos
Asma/metabolismo , Exossomos/metabolismo , Terapia de Imunossupressão , Células-Tronco Mesenquimais/metabolismo , Linfócitos T Reguladores/imunologia , Proliferação de Células/fisiologia , Células Cultivadas , Humanos , Tolerância Imunológica/imunologia , Síndromes de Imunodeficiência/metabolismo , Imunomodulação/imunologia , Terapia de Imunossupressão/métodos , Leucócitos Mononucleares/metabolismo , Fator de Crescimento Transformador beta1/metabolismoRESUMO
Aberrant autophagic processes have been found to have fundamental roles in the pathogenesis of different kinds of tumors, including hepatocellular carcinoma (HCC). P300/CBP-associated factor (PCAF), a histone acetyltransferase (HAT), performs its function by acetylating both histone and non-histone proteins. Our previous studies showed that PCAF was downregulated in HCC tissues and its high expression was significantly associated with patient survival after surgery, serving as a prognostic marker. In this study we found that overexpression of PCAF induced autophagy of HCC cells and its knockdown depressed autophagy. As type II programmed cell death, autophagy induced by PCAF-elicited cell death in HCC cells. In vivo experiments confirmed that PCAF-induced autophagy inhibited tumor growth. Subsequent in vitro experiments showed that PCAF promoted autophagy by inhibiting Akt/mTOR signaling pathway. Our findings show that PCAF is a novel modulator of autophagy in HCC, and can serve as an attractive therapeutic strategy of HCC treatment.
Assuntos
Autofagia , Carcinoma Hepatocelular/metabolismo , Carcinoma Hepatocelular/patologia , Neoplasias Hepáticas/metabolismo , Neoplasias Hepáticas/patologia , Fatores de Transcrição de p300-CBP/metabolismo , Adenina/análogos & derivados , Adenina/farmacologia , Animais , Apoptose/efeitos dos fármacos , Autofagia/efeitos dos fármacos , Linhagem Celular Tumoral , Proliferação de Células/efeitos dos fármacos , Feminino , Técnicas de Silenciamento de Genes , Humanos , Macrolídeos/farmacologia , Camundongos Endogâmicos BALB C , Camundongos Nus , Oligopeptídeos/farmacologia , Proteínas Proto-Oncogênicas c-akt/metabolismo , Transdução de Sinais/efeitos dos fármacos , Serina-Treonina Quinases TOR/metabolismo , Ensaios Antitumorais Modelo de XenoenxertoRESUMO
The goal of this work was to characterize how the date of harvest of 'Viking' aronia berry impacts juice pigmentation, sugars, and antioxidant activity. Aronia juice anthocyanins doubled at the fifth week of the harvest, and then decreased. Juice hydroxycinnamic acids decreased 33% from the first week, while proanthocyanidins increased 64%. Juice fructose and glucose plateaued at the fourth week, but sorbitol increased 40% to the seventh harvest week. Aronia juice pigment density increased due to anthocyanin concentration, and polyphenol copigmentation did not significantly affect juice pigmentation. Anthocyanin stability at pH 4.5 was similar between weeks. However, addition of quercetin, sorbitol, and chlorogenic acid to aronia anthocyanins inhibited pH-induced loss of color. Sorbitol and citric acid may be partially responsible for weekly variation in antioxidant activity, as addition of these agents inhibited DPPH scavenging 13-30%. Thus, aronia polyphenol and non-polyphenol components contribute to its colorant and antioxidant functionality.
Assuntos
Antocianinas/química , Antioxidantes/análise , Bebidas/análise , Carboidratos/análise , Photinia/química , Extratos Vegetais/química , Polifenóis/análise , Frutas/química , Frutas/crescimento & desenvolvimento , Photinia/crescimento & desenvolvimento , Proantocianidinas/análiseRESUMO
The hormesis characterized by low-concentration stimulation and high-concentration inhibition has gained significant interest over the past decades. Some organic solvents and ionic liquids (ILs) have hormetic concentration responses (HCR) to bioluminescence such as firefly luciferase and Vibrio qinghaiensis sp.-Q67. In this study, we determine the effects of 1-alkyl-3-methylimidazolium chlorine ILs ([Cnmim]Cl, n=2, 4, 6, 8, 10 and 12) to firefly luciferase in order to verify the mechanism of hormesis. The luminescence inhibition toxicity tests show that the stimulation effects of [C8mim]Cl and [C10mim]Cl are obvious, [C6mim]Cl and [C12mim]Cl are minor, and [C2mim]Cl and [C4mim]Cl are rare. The enzyme kinetics show that [C8mim]Cl and [C10mim]Cl are the competitive inhibitors with ATP while [C2mim]Cl and [C4mim]Cl are the noncompetitive ones. Molecular dynamics simulation results reveal that imidazolium rings of [C8mim] and [C10mim] locate at the entrance of luciferin pocket which is adjacent to AMP pocket, while alkyl-chains insert into the bottom of the luciferin pocket. Combining the results from inhibition test, kinetics assay and molecular simulation, we can deduce that occupying AMP pocket by imidazolium ring is responsible for hormetic stimulation.