RESUMO
Primary testicular lymphoma (PTL) is a rare lymphoma predominantly occurring in the elderly male population. It is characterized by a limited response to treatment and a heightened tendency towards relapse. Histologically, approximately 90% of PTL cases are classified as diffuse large B-cell lymphomas (DLBCL). Genetic features of PTL were delineated in a limited scope within several independent studies. Some of the articles which analyzed the genetic characterization of DLBCL have incorporated PTL samples, but these have been constrained by small sample sizes. In addition, there have been an absence of independent molecular typing studies of PTL. This report summarizes the common mutational features, copy number variations (CNVs) and molecular typing of PTL patients, based on whole-exome sequencing (WES) conducted on a cohort of 25 PTL patients. Among them, HLA, CDKN2A and MYD88 had a high mutation frequency. In addition, we found two core mutational characteristics in PTL including mutation in genes linked to genomic instability (TP53 and CDKN2A) and mutation in immune-related genes (HLA, MYD88, CD79B). We performed molecular typing of 25 PTL patients into C1 subtype with predominantly TP53 mutations and C2 subtype with predominantly HLA mutations. Notably, mutations in the TP53 gene predicted a poor outcome in most types of lymphomas. However, the C1 subtype, dominated by TP53 mutations, had a better prognosis compared to the C2 subtype in PTL. C2 subtype exhibited a worse prognosis, aligning with our finding that the mechanism of immune escape in PTL was primarily the deletions of HLA rather than PD-L1/PD-L2 alterations, a contrast to other DLBCLs. Moreover, we calculated the tumor mutation burden (TMB) and identified that TMB can predict prognosis and recurrence rate in PTL. Our study underscores the significance of molecular typing in PTL based on mutational characteristics, which plays a crucial role in prognostication and guiding therapeutic strategies for patients.
Assuntos
Variações do Número de Cópias de DNA , Genômica , Mutação , Neoplasias Testiculares , Humanos , Masculino , Neoplasias Testiculares/genética , Neoplasias Testiculares/patologia , Neoplasias Testiculares/classificação , Mutação/genética , Variações do Número de Cópias de DNA/genética , Idoso , Pessoa de Meia-Idade , Linfoma/genética , Linfoma/patologia , Linfoma/classificação , Sequenciamento do Exoma , Idoso de 80 Anos ou mais , Adulto , Linfoma Difuso de Grandes Células B/genética , Linfoma Difuso de Grandes Células B/patologia , Linfoma Difuso de Grandes Células B/classificaçãoRESUMO
Blastoid or pleomorphic mantle cell lymphoma (B/P-MCL) is characterized by high invasiveness and unfavorable outcomes, which is still a challenge for treating MCL. This retrospective study was performed to comprehensively analyze the clinical, genomic characteristics and treatment options of patients with B/PMCL from multicenter in China. Data were obtained from 693 patients with B/PMCL from three centers in China between April 1999 and December 2019. Seventy-four patients with BMCL (n = 43) or PMCL (n = 31) were included in the analysis. The median age of the cohort was 60.0 years with a male-to-female ratio of 2.89:1. The 3-year progression-free survival (PFS) and overall survival (OS) rates were 44.1% and 46.0%, respectively. Mutations of TP53, ATM, NOTCH1, NOTCH2, NSD2, SMARCA4, CREBBP, KMT2D, FAT1, and TRAF2 genes were the most common genetic changes in B/P-MCL. Progression of disease within 12 months (POD12) could independently predict the poor prognosis of patients with blastoid and pleomorphic variants. Patients with POD12 carried a distinct mutation profile (TP53, SMARCA4, NSD2, NOTCH2, KMT2D, PTPRD, CREBBP, and CDKN2A mutations) compared to patients with non-POD12. First-line high-dose cytosine arabinoside exposure obtained survival benefits in these populations, and BTKi combination therapy as the front-line treatment had somewhat improvement in survival with no significant difference in the statistic. In conclusion, B/P-MCL had inferior outcomes and a distinct genomic profile. Patients with POD12 displayed a distinct mutation profile and a poor prognosis. New therapeutic drugs and clinical trials for B/P-MCL need to be further explored.
Assuntos
Linfoma de Célula do Manto , Mutação , Humanos , Linfoma de Célula do Manto/genética , Linfoma de Célula do Manto/mortalidade , Linfoma de Célula do Manto/tratamento farmacológico , Masculino , Feminino , Pessoa de Meia-Idade , China/epidemiologia , Estudos Retrospectivos , Idoso , Adulto , Prognóstico , Taxa de Sobrevida , Idoso de 80 Anos ou maisRESUMO
CONTEXT: The Xihuang pill (XHP) is a traditional Chinese medicine formulation that has been historically used in the prevention and treatment of proliferative breast diseases. However, there is a lack of guidelines that offer recommendations for its clinical use. OBJECTIVE: The task force from the Chinese Guangdong Pharmaceutical Association aims to develop evidence-based guidelines for XHP to prevent and treat proliferative breast diseases. METHODS: We searched six Chinese and English electronic databases, including the China National Knowledge Infrastructure, the Chinese Scientific Journal Database, the Wanfang Medical Database, PubMed, and Embase, up to November 1, 2022. Publications (case reports, clinical observation, clinical trials, reviews) on using XHP to treat proliferative breast diseases were manually searched. The search terms were Xihuang pill, hyperplasia of the mammary gland, breast lump, and mastalgia. The writing team developed recommendations based on the best available evidence. RESULTS: Treatment should be customized based on syndrome identification. We recommend using XHP for the prevention and treatment of breast hyperplasia disease when a patient presents the following syndromes: concurrent blood stasis syndrome, concurrent phlegm-stasis syndrome, and concurrent liver fire syndrome. Safety indicators, including blood analysis and liver and kidney function monitoring, should be performed regularly during treatment. CONCLUSIONS: Current clinical evidence suggests that XHP can be used as a standalone treatment or in conjunction with other medications to prevent and manage breast hyperplasia diseases. More randomized controlled studies are warranted to establish high-quality evidence of its use.
Assuntos
Doenças Mamárias , Medicamentos de Ervas Chinesas , Hiperplasia , Medicina Tradicional Chinesa , Humanos , Feminino , Medicamentos de Ervas Chinesas/uso terapêutico , Medicamentos de Ervas Chinesas/administração & dosagem , Doenças Mamárias/tratamento farmacológico , Medicina Tradicional Chinesa/métodos , ChinaRESUMO
We report a mode-locked high-power all-polarization-maintaining Er/Yb-doped large-mode-area fiber oscillator based on a bias nonlinear amplifying loop mirror (NALM). The oscillator can generate â¼1-nJ femtosecond pulses without dispersion compensation. By inserting a Martinez-type compensator to provide normal dispersion, it can generate >10-nJ picosecond dissipative solitons (DSs). The measured M2 factors are below 1.5, indicating a good beam quality. When the cavity dispersion is tuned to be â¼0.704 ps2, the oscillator can deliver chirped DSs with an average power as high as 690 mW at a repetition rate of 49.86â MHz, corresponding to a pulse energy of â¼13.8 nJ. The pulse after compression has a near Fourier-limited width of â¼2 ps. Successful demonstration of this laser provides a robust scheme for improving the performance of ultrafast fiber lasers in average power and pulse energy.
RESUMO
BACKGROUND: Gut microbiota plays an important role in the development of atopic dermatitis (AD). We aimed to elucidate research trends in gut microbiota and AD in children, to provide evidence and insights to the clinical prevention and treatment of AD in children. METHODS: A scoping literature review on the studies of gut microbiota and AD were conducted. Two authors independently searched Pubmed et al. databases for studies focused on gut microbiota and AD in children up to January 15, 2022. The literatures were screened and analyzed by two reviewers. RESULTS: A total of 44 reports were finally included and analyzed. Current researches have indicated that abnormal human microecology is closely associated with AD, and the disturbance of intestinal microbiota plays an important role in the occurrence and development of AD. Probiotics can correct the microbiota disorder, have the functions of regulating immunity, antioxidant, and help to restore the microecological homeostasis. However, there is still a lack of high-quality research reports on the efficacy and safety of probiotics in the prevention and treatment of AD in children. CONCLUSIONS: The changes of gut microbiota are essential to the development of AD in children, which may be an effective target for the prevention and treatment of AD. Future studies with larger sample size and rigorous design are needed to elucidate the effects and safety of probiotics in AD.
Assuntos
Dermatite Atópica , Microbioma Gastrointestinal , Microbiota , Probióticos , Criança , Dermatite Atópica/terapia , Homeostase , Humanos , Probióticos/uso terapêuticoRESUMO
Anthurium is an important ornamental crop in the world market and its floral scent can enhance its ornamental value. To date, studies of the components and formation mechanism of the floral scent of Anthurium are relatively few. In this study, the scent profiles of two Anthurium varieties were measured by gas chromatograph-mass spectrometer (GC-MS). There were 32 volatile organic compounds (VOCs) identified in Anthurium 'Mystral', and the most abundant compound was eucalyptol (57.5%). Extremely small amounts of VOCs were detected in Anthurium 'Alabama'. Compared with A. 'Alabama', most genes related to floral scent synthesis exhibited a higher expression in A.'Mystral', including AaDXS, AaDXR, AaMDS, AaHDS, AaTPS, AaDAHPS, AaADT2, AaPAL1, and AaPAL2. In order to produce new varieties of Anthurium with fragrance, 454 progenies of two crossbred combinations of A. 'Mystral' and A. 'Alabama' were obtained. Four F1 generation plants with different floral scent intensities were selected for further study. The major components of floral scent in the progenies were similar to that of the parental A.'Mystral' plant. The expression patterns of genes related to floral scent synthesis were consistent with the relative contents of different types of VOCs. This study revealed the profiles of volatile compounds and associated gene expression in two Anthurium cultivars and their F1 hybrids, which provided a basis for the floral scent inheritance of Anthurium andraeanum.
Assuntos
Araceae/genética , Cruzamentos Genéticos , Regulação da Expressão Gênica de Plantas , Hibridização Genética , Compostos Orgânicos Voláteis/análise , Vias Biossintéticas/genética , Segregação de Cromossomos/genética , Flores/química , Inflorescência/genética , Odorantes/análise , FenótipoRESUMO
We studied the global microRNA (miRNA) expression in diffuse large B-cell lymphoma (DLBCL; n = 79), Burkitt lymphoma (BL; n = 36), primary mediastinal B-cell lymphoma (PMBL; n = 12), B-cell lines (n = 11), and normal subsets of naïve B cells, centroblasts (CBs), and peripheral blood B cells along with their corresponding gene expression profiles (GEPs). The normal B-cell subsets have well-defined miRNA signatures. The CB miRNA signature was significantly associated with germinal center B-cell (GCB)-DLBCL compared with activated B-cell (ABC)-DLBCL (P = .002). We identified a 27-miRNA signature that included v-myc avian myelomatosis viral oncogene homolog (MYC) targets and enabled the differentiation of BL from DLBCL, a distinction comparable with the "gold standard" GEP-defined diagnosis. Distinct miRNA signatures were identified for DLBCL subgroups, including GCB-DLBCL, activated B-cell (ABC)-DLBCL, and PMBL. Interestingly, most of the unclassifiable-DLBCL by GEP showed a strong similarity to the ABC-DLBCL by miRNA expression profiling. Consistent results for BL and DLBCL subgroup classification were observed in formalin-fixed, paraffin-embedded tissue, making such tests practical for clinical use. We also identified predictive miRNA biomarker signatures in DLBCL, including high expression of miR-155, which is significantly associated with rituximab plus cyclophosphamide, doxorubicin, vincristine, and prednisone (R-CHOP) treatment failure. This finding was further supported by the observation that high expression of miR-155 sensitizes cells to v-akt murine thymoma viral oncogene homolog-1 inhibitors in vitro, suggesting a novel treatment option for resistant DLBCL.
Assuntos
Biomarcadores Tumorais/metabolismo , Linfoma de Células B/classificação , Linfoma de Células B/patologia , MicroRNAs/metabolismo , Adolescente , Adulto , Idoso , Idoso de 80 Anos ou mais , Biomarcadores Tumorais/genética , Linhagem Celular Tumoral , Criança , Pré-Escolar , Feminino , Perfilação da Expressão Gênica , Regulação Neoplásica da Expressão Gênica , Humanos , Linfoma de Células B/genética , Masculino , MicroRNAs/genética , Pessoa de Meia-Idade , Invasividade Neoplásica , Análise de Sequência com Séries de Oligonucleotídeos , Prognóstico , Transcriptoma , Adulto JovemRESUMO
Cloth fabrics and smartphones have become the two things people are most familiar with. Particularly, smartphones are used as portable personal computers, revolutionizing communication and lifestyle. Here, screen-printing technology is applied to fabricate carbon electrodes and electrochemical chambers on a single hydrophilic cloth, while the cloth-based electrochemiluminescence (ECL) signals are read out by using an inexpensive smartphone. Therefore, the ECL detection is available in both low-cost disposable sensors and a portable format, which may be very suitable to be used as a non-invasive monitoring tool for medical diagnostics. As a proof-of-principle, lactate oxidase is immobilized onto the working electrode for the lactate measurement. Under optimized conditions, the lactate levels can be quantified over the range of 0.05-2.5 mM, with a detection limit of 0.035 mM and the relative standard deviations of 4.7%, 5.2% and 5.0% for 0.05, 0.5 and 2.5 mM lactate (n = 5). In addition, the proposed biosensor has an acceptable stability and selectivity. Finally, the ECL biosensor is successfully applied for the determination of lactate in human saliva. These results show that the presented ECL platform has the potential to be applied to non-invasively detect a variety of analytes of medical interest.
Assuntos
Técnicas Biossensoriais , Ácido Láctico/análise , Medições Luminescentes , Saliva/química , Smartphone , Têxteis , Técnicas Eletroquímicas , Eletrodos , HumanosRESUMO
In order to explore whether NF-κB activation correlates to the prognosis, chemoresistance, and sex hormone receptors status in ovarian serous carcinoma, we analyzed the expression of NF-κB, ER, and PR by immunohistochemistry in 72 cases of ovarian serous carcinoma, investigated the association among these markers, and evaluated their relations to clinicopathologic factors and prognosis. The positive rates were 88.9% for NF-κB cytoplasmic expression, 45.8% for NF-κB nuclear expression, 41.7% for ER, and 29.2% for PR. NF-κB nuclear expression was positively correlated with the 4th edition WHO grade (P=0.045) and tumor stage (P=0.001). NF-κB cytoplasmic expression was associated with preoperative serum CA125 level (P=0.015) and ascites (P=0.042). Neither cytoplasmic nor nuclear staining of NF-κB showed any association with survival. PR expression was correlated with tumor stage (P=0.023) and omental metastasis (P=0.022). Omental metastasis occurred more frequently in ER-/PR- tumors (P=0.009). No correlation between NF-κB expression and ER, PR expression was observed. In conclusion, in ovarian serous carcinoma, NF-κB nuclear expression correlated with the 4th edition WHO grade and PR was a favorable prognostic factor for ovarian serous carcinoma.
Assuntos
Cistadenocarcinoma Seroso/metabolismo , NF-kappa B/metabolismo , Neoplasias Ovarianas/metabolismo , Receptores de Estrogênio/metabolismo , Receptores de Progesterona/metabolismo , Adulto , Idoso , Idoso de 80 Anos ou mais , Cistadenocarcinoma Seroso/diagnóstico , Cistadenocarcinoma Seroso/patologia , Feminino , Humanos , Imuno-Histoquímica , Pessoa de Meia-Idade , Neoplasias Ovarianas/diagnóstico , Neoplasias Ovarianas/patologia , PrognósticoRESUMO
BACKGROUND: Processed Chuanwu (PCW), the mother root of Aconitum carmichaelii Debeauxv, has been widely used as a classic Traditional Chinese Medicine for pain relieve for over two millennia clinically. However, its action on chronic inflammatory pain has not been clarified. Here, we investigated the antinociceptive effect of PCW in complete freund's adjuvant (CFA)-induced mice and its possible mechanisms associated with opioid system and TRPV1 ion channel. METHODS: Male ICR mice were intraplantarly injected with CFA. PCW (0.34, 0.68 and 1.35 g/kg) was orally given to mice once a day for 7 days. Von frey hairs and planter test were assessed to evaluate the antinociceptive effect of PCW. To investigate the participation of dynorphin/opioid system in PCW antinociception, subtype-specific opioid receptor antagonists or anti-dynorphin A antiserum were used. To eliminate other central mechanisms that contribute to PCW antinociception, hot plate (50 °C) test were performed. Further, involvements of TRPV1 in PCW antinociception were evaluated in CFA-induced TRPV1(-/-) and TRPV1(+/+) C57BL/6 male mice, and in capsaicin-induced nociception ICR naive mice pretreated with nor-BNI. Meanwhile, calcium imaging was performed in HEK293T-TRPV1 cells. Finally, rotarod, open-field tests and body temperature measurement were carried out to assess side effects of PCW. RESULTS: PCW dose-dependently attenuated mechanical and heat hypersensitivities with no tolerance, which could be partially attenuated by coadministration of k-opioid receptor antagonist nor-binaltorphimine (nor-BNI) or anti-dynorphin A (1-13) antiserum. And PCW antinociception was totally erased by pretreatment with nor-BNI in the hot plate test. In addition, PCW antinociception was decreased in TRPV1(-/-) mice compared to TRPV1(+/+) group. And PCW still manifested inhibitory effects in capsaicin-induced nociception with nor-BNI pretreatment. PCW significantly inhibited capsaicin-induced calcium influx in HEK293T-TRPV1 cells. Finally, no detectable side effects were found in naive mice treated with PCW. CONCLUSIONS: This study shows PCW's potent antinociceptive effect in inflammatory conditions without obvious side effects. This effect may result from the activation of κ-opioid receptor via dynorpin release and the inhibition of TRPV1. These findings indicate that PCW might be a potential agent for the management of chronic inflammatory pain.
Assuntos
Aconitum/química , Analgésicos/química , Dinorfinas/metabolismo , Extratos Vegetais/química , Receptores Opioides kappa/metabolismo , Canais de Cátion TRPV/metabolismo , Administração Oral , Analgésicos Opioides/química , Animais , Temperatura Corporal , Calibragem , Sobrevivência Celular , Cromatografia Líquida de Alta Pressão , Dinorfinas/antagonistas & inibidores , Dinorfinas/química , Adjuvante de Freund/química , Células HEK293 , Humanos , Inflamação/metabolismo , Masculino , Camundongos , Camundongos Endogâmicos C57BL , Camundongos Endogâmicos ICR , Raízes de Plantas/químicaRESUMO
Anaplastic large-cell lymphomas (ALCLs) encompass at least 2 systemic diseases distinguished by the presence or absence of anaplastic lymphoma kinase (ALK) expression. We performed genome-wide microRNA (miRNA) profiling on 33 ALK-positive (ALK[+]) ALCLs, 25 ALK-negative (ALK[-]) ALCLs, 9 angioimmunoblastic T-cell lymphomas, 11 peripheral T-cell lymphomas not otherwise specified (PTCLNOS), and normal T cells, and demonstrated that ALCLs express many of the miRNAs that are highly expressed in normal T cells with the prominent exception of miR-146a. Unsupervised hierarchical clustering demonstrated distinct clustering of ALCL, PTCL-NOS, and the AITL subtype of PTCL. Cases of ALK(+) ALCL and ALK(-) ALCL were interspersed in unsupervised analysis, suggesting a close relationship at the molecular level. We identified an miRNA signature of 7 miRNAs (5 upregulated: miR-512-3p, miR-886-5p, miR-886-3p, miR-708, miR-135b; 2 downregulated: miR-146a, miR-155) significantly associated with ALK(+) ALCL cases. In addition, we derived an 11-miRNA signature (4 upregulated: miR-210, miR-197, miR-191, miR-512-3p; 7 downregulated: miR-451, miR-146a, miR-22, miR-455-3p, miR-455-5p, miR-143, miR-494) that differentiates ALK(-) ALCL from other PTCLs. Our in vitro studies identified a set of 32 miRNAs associated with ALK expression. Of these, the miR-17â¼92 cluster and its paralogues were also highly expressed in ALK(+) ALCL and may represent important downstream effectors of the ALK oncogenic pathway.
Assuntos
Perfilação da Expressão Gênica , Regulação Neoplásica da Expressão Gênica , Linfoma Anaplásico de Células Grandes/genética , MicroRNAs/genética , Adolescente , Adulto , Idoso , Idoso de 80 Anos ou mais , Quinase do Linfoma Anaplásico , Antígenos de Superfície/metabolismo , Linhagem Celular Tumoral , Criança , Pré-Escolar , Análise por Conglomerados , Feminino , Expressão Gênica , Ordem dos Genes , Humanos , Imunofenotipagem , Linfoma Anaplásico de Células Grandes/metabolismo , Linfoma Anaplásico de Células Grandes/patologia , Masculino , MicroRNAs/metabolismo , Pessoa de Meia-Idade , Estadiamento de Neoplasias , Especificidade de Órgãos/genética , Interferência de RNA , Receptores Proteína Tirosina Quinases/genética , Receptores Proteína Tirosina Quinases/metabolismo , Linfócitos T/metabolismo , Adulto JovemRESUMO
BACKGROUND: Alpha-fetoprotein (AFP)-producing pancreatic neuroendocrine tumors (pNETs) are rare, and the few reported cases usually coexisted with other malignant components such as adenocarcinoma or hepatoid carcinoma. We present here the first case of pure AFP-producing pNET. CASE PRESENTATION: A 56-year-old male patient underwent resection of the pancreatic tail and body because of elevated serum AFP levels and pancreatic mass. Microscopy showed that the tumor tissue consisted of large and small solid nests of polygonal cells. The tumor cells were positive for chromogranin A, synaptophysin, CD99, cytokeratin 19, pan-cytokeratin and ß-catenin, and also showed diffuse immunoreactivity for AFP and human chorionic gonadotrophin. The mitotic rate was nearly 30 per 10 high-power fields and the Ki-67 index was nearly 25%. The histopathologic findings supported the diagnosis of an AFP-producing pNET. Other malignant components were not found. Serum AFP levels decreased to near-normal after operation and gradually increased to >1000 ng/ml at 5 months post-surgery. Recurrence and hepatic metastases were revealed by computed tomography. The patient died 21 months after surgery. CONCLUSION: This was the first case of pure AFP-producing pNET to be reported in the English literature. Serum AFP levels may provide useful information for monitoring the therapeutic effectiveness, early recurrence or metastases.
Assuntos
Carcinoma Neuroendócrino/sangue , Carcinoma Neuroendócrino/secundário , Neoplasias Hepáticas/secundário , Recidiva Local de Neoplasia , Neoplasias Pancreáticas/sangue , alfa-Fetoproteínas/metabolismo , Evolução Fatal , Humanos , Neoplasias Hepáticas/diagnóstico por imagem , Masculino , Pessoa de Meia-Idade , Recidiva Local de Neoplasia/diagnóstico por imagem , Neoplasias Pancreáticas/patologia , RadiografiaRESUMO
BACKGROUND: Insulin enhancer binding protein-1 (ISL-1), a LIM-homeodomain transcription factor, is essential for the heart, motor neuron and pancreas development. Recently, ISL-1 has been found in some types of human cancers. However, how ISL-1 exerts the role in tumor development is not clear. METHODS AND RESULTS: The expression of ISL-1 was assessed in 211 human lymphoma samples and 23 normal lymph node samples. Immunohistochemistry results demonstrated a markedly higher expression of ISL-1 in 75% of non-Hodgkin lymphoma (NHL) samples compared with that in normal lymph nodes or Hodgkin lymphoma (HL) samples. CCK-8 analysis, cell cycle assay and xenograft model were performed to characterize the association between ISL-1 expression level and biological functions in NHL. The results showed that ISL-1 overexpression obviously promoted NHL cells proliferation, changed the cell cycle distribution in vitro and significantly enhanced xenografted lymphoma development in vivo. Real-time PCR, Western blot, luciferase assay and ChIP assay were used to explore the potential regulatory targets of ISL-1 and the results demonstrated that ISL-1 activated the c-Myc expression in NHL by direct binding to a conserved binding site on the c-Myc enhancer. Further results revealed that ISL-1 could be positively regulated by the c-Jun N-terminal kinase (JNK) and the Janus kinase/signal transducer and activator of transcription (JAK/STAT) pathways. Both the JNK and JAK/STAT signaling inhibitors could significantly suppressed the growth of NHL cells through the down-regulation of ISL-1 as demonstrated by CCK-8 and Western blot assays. Bioinformatic analysis and luciferase assay exhibited that ISL-1 was a novel target of p-STAT3 and p-c-jun. ChIP, Co-IP and ChIP-re-IP analysis revealed that ISL-1 could participate with p-STAT3 and p-c-Jun to form a p-STAT3/p-c-Jun/ISL-1 transcriptional complex that binds directly on the ISL-1 promoter, demonstrating a positive feedback regulatory mechanism for ISL-1 expression in NHL. CONCLUSIONS: Our results provide the first evidence that ISL-1 is tightly linked to NHL proliferation and development by promoting c-Myc transcription, and its aberrant expression was regulated by p-STAT3/p-c-Jun/ISL-1 complex activation.
Assuntos
Proteínas com Homeodomínio LIM/metabolismo , Linfoma não Hodgkin/metabolismo , Linfoma não Hodgkin/patologia , Proteínas Proto-Oncogênicas c-jun/metabolismo , Fator de Transcrição STAT3/metabolismo , Fatores de Transcrição/metabolismo , Sequência de Bases , Ciclo Celular , Linhagem Celular Tumoral , Proliferação de Células , Regulação para Baixo , Técnicas de Silenciamento de Genes , Humanos , Imuno-Histoquímica , Proteínas Quinases JNK Ativadas por Mitógeno/metabolismo , Janus Quinases/metabolismo , Proteínas com Homeodomínio LIM/genética , Dados de Sequência Molecular , Fosforilação , Regiões Promotoras Genéticas/genética , Ligação Proteica , Proteínas Proto-Oncogênicas c-myc/metabolismo , Fatores de Transcrição/genética , Transcrição Gênica , Regulação para Cima , Ensaios Antitumorais Modelo de XenoenxertoRESUMO
miRNA deregulation has been implicated in the pathogenesis of mantle cell lymphoma (MCL). Using a high-throughput quantitative real-time PCR platform, we performed miRNA profiling on cyclin D1-positive MCL (n = 30) and cyclin D1-negative MCL (n = 7) and compared them with small lymphocytic leukemia/lymphoma (n = 12), aggressive B-cell lymphomas (n = 138), normal B-cell subsets, and stromal cells. We identified a 19-miRNA classifier that included 6 up-regulated miRNAs and 13 down regulated miRNA that was able to distinguish MCL from other aggressive lymphomas. Some of the up-regulated miRNAs are highly expressed in naive B cells. This miRNA classifier showed consistent results in formalin-fixed paraffin-embedded tissues and was able to distinguish cyclin D1-negative MCL from other lymphomas. A 26-miRNA classifier could distinguish MCL from small lymphocytic leukemia/lymphoma, dominated by 23 up-regulated miRNAs in MCL. Unsupervised hierarchical clustering of MCL patients demonstrated a cluster characterized by high expression of miRNAs from the polycistronic miR17-92 cluster and its paralogs, miR-106a-363 and miR-106b-25, and associated with high proliferation gene signature. The other clusters showed enrichment of stroma-associated miRNAs, and also had higher expression of stroma-associated genes. Our clinical outcome analysis in the present study suggested that miRNAs can serve as prognosticators.
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Regulação Neoplásica da Expressão Gênica , Linfoma de Célula do Manto/diagnóstico , Linfoma de Célula do Manto/genética , MicroRNAs/genética , Adulto , Idoso , Idoso de 80 Anos ou mais , Biomarcadores Tumorais/análise , Biomarcadores Tumorais/genética , Biomarcadores Tumorais/isolamento & purificação , Feminino , Perfilação da Expressão Gênica , Genoma Humano , Ensaios de Triagem em Larga Escala , Humanos , Linfoma de Célula do Manto/classificação , Linfoma de Célula do Manto/mortalidade , Masculino , MicroRNAs/fisiologia , Análise em Microsséries , Pessoa de Meia-Idade , Prognóstico , Estudos de Validação como AssuntoRESUMO
Systemic anaplastic large cell lymphoma is a category of T-cell non-Hodgkin's lymphoma which can be further subdivided into two distinct entities (ALK(+) and ALK(-)) based on the presence or absence of ALK gene rearrangements. Among several pathways triggered by ALK signaling, constitutive activation of STAT3 is strictly required for ALK-mediated transformation and survival. Here we performed genome-wide microRNA profiling and identified 48 microRNA concordantly modulated by the inducible knock-down of ALK and STAT3. To evaluate the functional role of differentially expressed miRNA, we forced their expression in ALK(+) anaplastic large cell lymphoma cells, and monitored their influence after STAT3 depletion. We found that the expression of the microRNA-17~92 cluster partially rescues STAT3 knock-down by sustaining proliferation and survival of ALK(+) cells. Experiments in a xenograft mouse model indicated that forced expression of microRNA-17~92 interferes with STAT3 knock-down in vivo. High expression levels of the microRNA-17~92 cluster resulted in down-regulation of BIM and TGFßRII proteins, suggesting that their targeting might mediate resistance to STAT3 knock-down in anaplastic large cell lymphoma cells. We speculate that the microRNA-17~92 cluster is involved in lymphomagenesis of STAT3(+) ALCL and that its inhibition might represent an alternative avenue to interfere with ALK signaling in anaplastic large cell lymphomas.
Assuntos
Linfoma Anaplásico de Células Grandes/genética , Linfoma Anaplásico de Células Grandes/metabolismo , MicroRNAs/genética , Família Multigênica , Receptores Proteína Tirosina Quinases/metabolismo , Fator de Transcrição STAT3/metabolismo , Ativação Transcricional , Quinase do Linfoma Anaplásico , Ciclo Celular/genética , Linhagem Celular Tumoral , Proliferação de Células , Sobrevivência Celular/genética , Análise por Conglomerados , Perfilação da Expressão Gênica , Regulação Neoplásica da Expressão Gênica , Técnicas de Silenciamento de Genes , Humanos , Linfoma Anaplásico de Células Grandes/mortalidade , Interferência de RNARESUMO
OBJECTIVE: To study the clinicopathologic features, differential diagnosis and prognosis of primary bone anaplastic large cell lymphoma(ALCL). METHODS: Twelve patients diagnosed with primary bone ALCL were retrospectively reviewed. The clinicopathologic features, immunohistochemic findings and results of in situ hybridization for EB virus were analyzed. RESULTS: Of the 12 patients, the male-to-female was 7: 5 with a median age of 17.5 years (range from 9 to 64 years). Bone pain was the presenting symptom in all patients. Radiographic examination demonstrated solitary osteolytic lesion in 8 patients and multiple lesions in the rest 4 patients. Spine (7 cases) was the most common site to be involved, followed by ilium (5 cases), sacrum (2 cases), humerus (1 case) and collarbone (1 case). Ten patients were available with the follow-up data including 5 ALK-positive and 5 ALK-negative patients, and the follow-up time was 2 to 47 months. Interestingly, the 3 dead patients were ALK-negative whereas 5 of 7 ALK-positive patients achieved remission. CONCLUSIONS: Primary bone ALCL is a rare type of non-Hodgkin lymphoma and it more frequently involves the axial skeleton. Boys and young males are more commonly affected. Patients usually present at an early stage and have a relatively favorable prognosis. Expression of ALK protein may be associated with a favorable prognosis in primary bone ALCL.
Assuntos
Neoplasias Ósseas , Linfoma Anaplásico de Células Grandes , Receptores de Ativinas Tipo I , Adolescente , Adulto , Fosfatase Alcalina , Doenças Ósseas/etiologia , Neoplasias Ósseas/diagnóstico por imagem , Neoplasias Ósseas/enzimologia , Neoplasias Ósseas/mortalidade , Criança , Feminino , Humanos , Linfoma Anaplásico de Células Grandes/diagnóstico por imagem , Linfoma Anaplásico de Células Grandes/enzimologia , Linfoma Anaplásico de Células Grandes/mortalidade , Masculino , Pessoa de Meia-Idade , Dor/etiologia , Prognóstico , Radiografia , Receptores Proteína Tirosina Quinases , Estudos Retrospectivos , Adulto JovemRESUMO
Due to the significant price differences among different types of edible oils, expensive oils like olive oil are often blended with cheaper edible oils. This practice of adulteration in edible oils, aimed at increasing profits for producers, poses a major concern for consumers. Furthermore, adulteration in edible oils can lead to various health issues impacting consumer well-being. In order to meet the requirements of fast, non-destructive, universal, accurate, and reliable quality testing for edible oil, the oblique-incidence reflectivity difference (OIRD) method combined with machine learning algorithms was introduced to detect a variety of edible oils. The prediction accuracy of Gradient Boosting, K-Nearest Neighbor, and Random Forest models all exceeded 95%. Moreover, the contribution rates of the OIRD signal, DC signal, and fundamental frequency signal to the classification results were 45.7%, 34.1%, and 20.2%, respectively. In a quality evaluation experiment on olive oil, the feature importance scores of three signals reached 63.4%, 18.9%, and 17.6%. The results suggested that the feature importance score of the OIRD signal was significantly higher than that of the DC and fundamental frequency signals. The experimental results indicate that the OIRD method can serve as a powerful tool for detecting edible oils.
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Schistosomiasis is a parasitic disease that endangers human health and social development. The granulomatous reaction of Schistosoma eggs in the liver is the main cause of hepatosplenomegaly and fibrotic lesions. Anti liver fibrosis therapy is crucial for patients with chronic schistosomiasis. Although Praziquantel is the only clinical drug used, it is limited in insecticide treatment and has a long-term large-scale use, which is forcing the search for cost-effective alternatives. Previous research has demonstrated that plant metabolites and extracts have effective therapeutic effects on liver fibrosis associated with schistosomiasis. This paper summarizes the mechanisms of action of metabolites and some plant extracts in alleviating schistosomiasis-associated liver fibrosis. The analysis was conducted using databases such as PubMed, Google Scholar, and China National Knowledge Infrastructure (CNKI) databases. Some plant metabolites and extracts ameliorate liver fibrosis by targeting multiple signaling pathways, including reducing inflammatory infiltration, oxidative stress, inhibiting alternate macrophage activation, suppressing hepatic stellate cell activation, and reducing worm egg load. Natural products improve liver fibrosis associated with schistosomiasis, but further research is needed to elucidate the effectiveness of natural products in treating liver fibrosis caused by schistosomiasis, as there is no reported data from clinical trials in the literature.
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Background/purpose: Lymphoepithelial sialadenitis (LESA), Sjögren's syndrome (SS), and salivary MALT lymphoma are diseases characterized by lymphoepithelial lesions, and the differential diagnosis between them in the salivary glands is challenging. This study aimed to explore clinicopathological and genetic characteristics of the three diseases. Materials and methods: We retrospectively analyzed the clinical features, the histomorphology, immunohistochemistry, and genetic profiling by polymerase chain reaction (PCR) and next-generation sequencing (NGS). Results: There included 68 LESAs, 25 SSs, and 62 MALT lymphomas. Ten cases relapsed in total, and 3 of MALT lymphomas died due to high-level transformation. Immunohistochemical double staining showed FCRL4 cells co-expressed Pax-5 and Ki-67, suggesting FCRL4 cells were proliferative B-cells. The expression level of the FCRL4 was significantly higher in MALT lymphoma than LESA and SS. The detection rates of clonal IGH, IGK, and IGL gene rearrangements in MALT lymphoma with a sensitivity of 83.33%. Monoclonal immunoglobulin gene rearrangements were confirmed in five suspected patients by NGS (100%). Conclusion: FCRL4 B cells might play an important role in the formation of lymphoepithelial lesions and might be as a diagnostic positive marker of salivary MALT lymphoma. The application of multiple detection methods could significantly improve the diagnostic accuracy for MALT lymphomas from LESA and SS.
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Assessing crop seed phenotypic traits is essential for breeding innovations and germplasm enhancement. However, the tough outer layers of thin-shelled seeds present significant challenges for traditional methods aimed at the rapid assessment of their internal structures and quality attributes. This study explores the potential of combining terahertz (THz) time-domain spectroscopy and imaging with semantic segmentation models for the rapid and non-destructive examination of these traits. A total of 120 watermelon seed samples from three distinct varieties, were curated in this study, facilitating a comprehensive analysis of both their outer layers and inner kernels. Utilizing a transmission imaging modality, THz spectral images were acquired and subsequently reconstructed employing a correlation coefficient method. Deep learning-based SegNet and DeepLab V3+ models were employed for automatic tissue segmentation. Our research revealed that DeepLab V3+ significantly surpassed SegNet in both speed and accuracy. Specifically, DeepLab V3+ achieved a pixel accuracy of 96.69 % and an intersection over the union of 91.3 % for the outer layer, with the inner kernel results closely following. These results underscore the proficiency of DeepLab V3+ in distinguishing between the seed coat and kernel, thereby furnishing precise phenotypic trait analyses for seeds with thin shells. Moreover, this study accentuates the instrumental role of deep learning technologies in advancing agricultural research and practices.