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Emulsions have been applied in a number of industries such as pharmaceutics, cosmetics, and food, which are also of great scientific interest. Although aqueous emulsions are commonly used in our daily life, oil-in-oil (o/o) emulsions also play an irreplaceable role in view of their unique physics and complementary applications. In this paper, we investigate typical behaviors of organic droplets surrounded by organic medium (o/o emulsions) with different functional groups controlled by the AC electric field. Droplet behaviors can be catalogued into five types: namely, "no effect", "movement", "deformation", "interface rupture", and "disorder". We identify the key dimensionless number Wee·Ca, combined with the channel geometry, for characterizing the typical behaviors in silicon oil/1,6-hexanediol diacrylate and mineral oil/1,6-hexanediol diacrylate emulsions. Unlike aqueous emulsion, the Maxwell-Wagner relaxation inhibits the electric effect and leads to an effective frequency, ranging from 0.5 to 3 kHz. The increasing viscosity of the droplet facilitates the escalation by promoting the shearing effect under the same flow conditions. Ethylene glycol droplets primarily show the efficient coalescence even at a low Wee·Ca, which is attributed to the attraction of free charges induced by the increasing conductivity. In 1,6-hexanediol diacrylate/silicon oil emulsion, the droplet tends to form a liquid film that expands into the entire channel due to the affinity of the droplet to the channel wall. A variety of elongated columns are observed to oscillate between the electrodes at high voltages. These findings can contribute to understanding the electrohydrodynamic physics in o/o emulsion and controlling droplet behaviors in a fast response, programmable, and high-throughput way. We expect that this droplet manipulation technology can be widely adopted in a broad range of chemical synthesis and biological and material science.
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Enol silyl ethers are versatile, robust, and readily accessible substrates widely used in chemical synthesis. However, the conventional reactivity of these motifs has been limited to classical two electron (2-e) enolate-type chemistry with electrophilic partners or as radical acceptors in one electron (1-e) reactivity leading, in both cases, to exclusive α-monofunctionalization of carbonyls. Herein we describe a mild, fast, and operationally simple one-step protocol that combines readily available fluoroalkyl halides, silyl enol ethers, and, for the first time, hetero(aryl) Grignard reagents to promote selective dicarbofunctionalization of enol silyl ethers. From a broader perspective, this work expands the synthetic utility of enol silyl ethers and establishes bisphosphine-iron catalysis as enabling technology capable of orchestrating selective C-C bond formations with short-lived α-silyloxy radicals with practical implications towards sustainable chemical synthesis.
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BACKGROUND: Acupuncture has been used to relieve chronic pain in patients with knee osteoarthritis (KOA), but the evidence is contradictory. Therefore, we carefully designed a double-dummy randomized controlled trial (RCT) to explore the therapeutic effect of acupuncture for KOA. METHODS/DESIGN: A total of 138 eligible participants with KOA who consent to participate will be randomly divided into Groups A, B, and C in a ratio of 1:1:1. Participants in Group A will receive verum acupuncture and placebo gel, while those in Groups B and C will be treated with diclofenac diethylammon gel and sham acupuncture, sham acupuncture and placebo gel, respectively. The patients will receive 4 weeks of treatment, five times a week, including acupuncture treatment once a day for 30 min and gel treatment three times a day. The primary outcome will be the change of Western Ontario and McMaster Universities Osteoarthritis Index (WOMAC) at week 4. The secondary outcomes will include visual analog scale (VAS), Arthritis Quality of Life Measurement Scale Simplified Scale (AIMS2-SF), Beck Anxiety Inventory (BAI), Beck Depression Inventory (BDI) and Credibility/Expectancy Questionnaire. The evaluation will be performed at baseline, week 4, 8, and 12 after randomization. DISCUSSION: This double-dummy RCT used diclofenac diethylammon gel as a positive control, and the completion of this trial will provide detailed and accurate evidence of the efficacy and safety of acupuncture for KOA. TRIAL REGISTRATION: China Clinical Trials Registry No.ChiCTR2100043947. Registered on September 24, 2020. https://www.chictr.org.cn/showproj.html?proj=122536 .
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Terapia por Acupuntura , Osteoartrite do Joelho , Humanos , Osteoartrite do Joelho/terapia , Osteoartrite do Joelho/complicações , Diclofenaco , Terapia por Acupuntura/métodos , Projetos de Pesquisa , China , Resultado do Tratamento , Ensaios Clínicos Controlados Aleatórios como AssuntoRESUMO
RNA-binding proteins (RBPs) play essential roles in regulating gene expression. However, the RNA ligands of RBPs are poorly understood in plants, not least due to the lack of efficient tools for genome-wide identification of RBP-bound RNAs. An RBP-fused adenosine deaminase acting on RNA (ADAR) can edit RBP-bound RNAs, which allows efficient identification of RNA ligands of RBPs in vivo. Here, we report the RNA editing activities of the ADAR deaminase domain (ADARdd) in plants. Protoplast experiments indicated that RBP-ADARdd fusions efficiently edited adenosines within 41 nucleotides (nt) of their binding sites. We then engineered ADARdd to profile the RNA ligands of rice (Oryza sativa) Double-stranded RNA-Binding Protein 1 (OsDRB1). Overexpressing the OsDRB1-ADARdd fusion protein in rice introduced thousands of A-to-G and T-to-C RNAâDNA variants (RDVs). We developed a stringent bioinformatic approach to identify A-to-I RNA edits from RDVs, which removed 99.7% to 100% of background single-nucleotide variants in RNA-seq data. This pipeline identified a total of 1,798 high-confidence RNA editing (HiCE) sites, which marked 799 transcripts as OsDRB1-binding RNAs, from the leaf and root samples of OsDRB1-ADARdd-overexpressing plants. These HiCE sites were predominantly located in repetitive elements, 3'-UTRs, and introns. Small RNA sequencing also identified 191 A-to-I RNA edits in miRNAs and other sRNAs, confirming that OsDRB1 is involved in sRNA biogenesis or function. Our study presents a valuable tool for genome-wide profiling of RNA ligands of RBPs in plants and provides a global view of OsDRB1-binding RNAs.
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MicroRNAs , Oryza , Oryza/genética , Oryza/metabolismo , Edição de RNA/genética , MicroRNAs/genética , Adenosina/metabolismo , Adenosina Desaminase/genética , Adenosina Desaminase/química , Adenosina Desaminase/metabolismo , Proteínas de Ligação a RNA/genética , Proteínas de Ligação a RNA/metabolismoRESUMO
OBJECTIVE: To improve the diagnostic yield of prostate biopsy, which we can achieve by puncture more sites and number of cores, another way to obtain more tissue is to take longer tissue strips. In this study, we evaluated the effect of strip length on cancer diagnosis by needle biopsy and derived a cutoff value of strip length to improve cancer detection. METHODS: The pathological reports of 754 patients with suspected prostate cancer who underwent transperineal prostate biopsy were retrospectively analyzed. The age, serum prostate specific antigen (PSA), prostate volume, Gleason score and tissue strip length were analyzed. The length of the tissue strip was compared between the biopsy positive patients and the biopsy negative patients, and the patients were divided into group Aï¼biopsy positive groupï¼and group Bï¼biopsy negative groupï¼, respectively. Statistical analysis of tissue strip lengths was performed to determine cutoff values for biopsy length quality. RESULTS: A total of 10 556 tissue strips were obtained from 754 patients, and 45.1 % of the patients were pathologically diagnosed as prostate cancer. The median length of the tissue strip was 10.5 (9.5, 12.5) mm, the median age was 69 (64,75) years, the median PSA was 12.4 (8.6, 20.8) µg/L, and the median prostate volume was 44.8 (30.5, 64.4) ml. The median length of tissue strips in group A and group B was 11 (10,13) mm and 10 (9,12) mm, respectively. Receiver operating characteristic (ROC) curve analysis was performed on the length of tissue strips in all cases, and the cutoff value of quality assurance was 11.8mm, the area under curve (AUC) was 0.82, and the cut-off value of quality assurance was 11.8mm. Sensitivity 71.4%, specificity 73.8%(P<0.001). CONCLUSIONS: In transperineal prostate biopsy, the cancer detection rate of tissue strips may increase with length. The results of ROC analysis showed that 11.8 mm was used as the cut-off value for quality assurance.
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Próstata , Neoplasias da Próstata , Masculino , Humanos , Idoso , Próstata/patologia , Antígeno Prostático Específico , Estudos Retrospectivos , Biópsia , Neoplasias da Próstata/patologia , Curva ROCRESUMO
BACKGROUND: Osteoarthritis (OA) is a common articular disorder. Epidemiologic surveys show a higher prevalence of OA in women than men and that morbidity is higher during menopause. We aimed to explore whether menopause influences the clinical recovery of a knee joint following OA and injury, and identify associated mechanisms by analyzing the proteomic profile of synovial tissue (ST) samples. METHODS: Routine blood examination and hormone level tests were conducted before surgery. ST samples from eight participants were collected intraoperatively for proteomic analysis. One day before and one month after the surgery, we assessed various aspects of function in the affected knee including the with Visual Analog Score (VAS), Lysholm, The Western Ontario, and McMaster Universities Osteoarthritis Index (WOMAC) scores. The relationships between proteomic data, estrogen levels, and affected knee function were compared and analyzed. This was a retrospective study. RESULT: Menopause was associated with the clinical outcomes of knee OA and knee injuries. ST proteomic data identified that 80 proteins in premenopausal OA females were significantly different from menopausal OA females. In addition, 100 proteins were significantly different between premenopausal OA females and premenopausal injured females. CONCLUSIONS: Age and menopause showed a positive correlation with the protein profile of ST from OA or knee injury female patients, indicating that the protein components might be affected by menopause. Postoperative clinical outcomes were affected by menopause. We conclude that menopause may, in part, regulate knee joint function by altering ST protein expression.
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Phototheranostics that concurrently integrates accurate diagnosis (e.g., fluorescence and photoacoustic (PA) imaging) and in situ therapy (e.g., photodynamic therapy (PDT) and photothermal therapy (PTT)) into one platform represents an attractive approach for accelerating personalized and precision medicine. The second near-infrared window (NIR-II, 1000-1700 nm) has attracted considerable attention from both the scientific community and clinical doctors for improved penetration depth and excellent spatial resolution. NIR-II agents with a PDT property as well as other functions are recently emerging as a powerful tool for boosting the phototheranostic outcome. In this minireview, we summarize the recent advances of photodynamic NIR-II aggregation-induced emission luminogens (AIEgens) for biomedical applications. The molecular design strategies for tuning the electronic bandgaps and photophysical energy transformation processes are discussed. We also highlight the biomedical applications, such as image-guided therapy of both subcutaneous and orthotopic tumors, and multifunctional theranostics in combination with other treatment methods, including chemotherapy and immunotherapy; and the precise treatment of both tumor and bacterial infection. This review aims to provide guidance for PDT agents with long-wavelength emissions to improve the imaging precision and treatment efficacy. We hope it will provide a comprehensive understanding about the chemical structure-photophysical property-biomedical application relationship of NIR-II luminogens.
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Nanopartículas , Neoplasias , Fotoquimioterapia , Fluorescência , Humanos , Nanopartículas/química , Neoplasias/diagnóstico por imagem , Neoplasias/tratamento farmacológico , Fotoquimioterapia/métodos , Medicina de Precisão , Nanomedicina Teranóstica/métodosRESUMO
Precision medicine requires highly sensitive and specific diagnostic strategies with high spatiotemporal resolution. Accurate detection and monitoring of endogenously generated biomarkers at the very early disease stage is of extensive importance for precise diagnosis and treatment. Aggregation-induced emission luminogens (AIEgens) have emerged as a new type of excellent optical agents, which show great promise for numerous biomedical applications. In this review, we highlight the recent advances of AIE-based probes for detecting reactive species (including reactive oxygen species (ROS), reactive nitrogen species (RNS), reactive sulfur species (RSS), and reactive carbonyl species (RCS)) and related biomedical applications. The molecular design strategies for increasing the sensitivity, tuning the response wavelength, and realizing afterglow imaging are summarized, and theranostic applications in reactive species-related major diseases such as cancer, inflammation, and vascular diseases are reviewed. The challenges and outlooks for the reactive species-activatable AIE systems for disease diagnostics and therapeutics are also discussed. This review aims to offer guidance for designing AIE-based specifically activatable optical agents for biomedical applications, as well as providing a comprehensive understanding about the structure-property application relationships. We hope it will inspire more interesting researches about reactive species-activatable probes and advance clinical translations.
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Neoplasias , Nanomedicina Teranóstica , Corantes Fluorescentes , Humanos , Espécies Reativas de Oxigênio , Nanomedicina Teranóstica/métodosRESUMO
Long noncoding RNAs (lncRNAs) have been shown to be involved in the development of osteoarthritis. However, the expression, function, and mechanism of DLEU1 in OA development remain largely unclear. The present reference demonstrates that DLEU1 is overexpressed in OA specimens compared to control cartilages. Inflammatory cytokines IL-1ß, TNF-α, and IL-6 induce DLEU1 expression in chondrocytes. Ectopic expression of DLEU1 induces chondrocyte proliferation, degradation of ECM, and inflammation mediators such as IL-6, IL-8, and TNF-α secretion. Moreover, we demonstrated that DLEU1 targets miR-671-5p expression in chondrocytes. Overexpression of DLEU1 suppresses miR-671-5p expression in chondrocytes. The expression of miR-671-5p is decreased in OA specimens compared to control cartilages. There is a negative correlation between the expression of miR-671-5p and DLEU1 in OA specimens. Inflammatory mediators IL-1ß, TNF-α, and IL-6 suppress miR-671-5p expression in OA specimens. Elevated expression of miR-671-5p suppresses chondrocyte proliferation, degradation of ECM, and secretion of inflammation mediators. DLEU1 overexpression promotes chondrocytes proliferation, degradation of ECM, and secretion of inflammation mediators via regulating miR-671-5p. These results suggested that DLEU1 acts as one destructive role in OA development via regulating miR-671-5p.
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MicroRNAs , Osteoartrite , RNA Longo não Codificante , Proliferação de Células/genética , Condrócitos/metabolismo , Matriz Extracelular/metabolismo , Humanos , Inflamação/metabolismo , Mediadores da Inflamação/metabolismo , Interleucina-6/metabolismo , MicroRNAs/genética , MicroRNAs/metabolismo , Osteoartrite/genética , Osteoartrite/metabolismo , RNA Longo não Codificante/genética , RNA Longo não Codificante/metabolismo , Fator de Necrose Tumoral alfa/metabolismoRESUMO
Renal fibrosis (RF) predisposes patients to an increased risk of progressive chronic kidney disease, and effective treatments remain elusive. Mesenchymal stem cell (MSC)-derived exosomes are considered a new treatment for tissue damage. Our study aimed to investigate the in vitro effects of bone marrow MSC-derived exosomes (BM-MSC-Exs) on transforming growth factor-ß1 (TGF-ß1)-induced fibrosis in renal tubular epithelial cells (HK-2 cells) and the associated mechanisms. Herein, we found BM-MSC-Exs could inhibit TGF-ß1-induced epithelial-mesenchymal transition (EMT) in HK-2 cells, and may involve autophagy activation of BM-MSC-Exs. Moreover, we first reported that after ceria nanoparticles (CeNPs) treatment, the improvements induced by BM-MSC-Ex on EMT were significantly enhanced by upregulating the expression of Nedd4Lof MSCs and promoting the secretion of exosomes, which contained Nedd4L. In addition, Nedd4L could activate autophagy in HK-2 cells. In conclusion, BM-MSC-Ex prevents the TGF-ß1-induced EMT of renal tubular epithelial cells by transporting Nedd4L, which activates autophagy. The results of this in vitro experiment may extend to RF, whereby BM-MSC-Ex may also be used as a novel treatment for improving RF. Impact statement Renal fibrosis (RF) is an important pathological change in chronic kidney disease that ultimately leads to end-stage renal failure, and effective treatments remain elusive. In this study, there are two contributions. First, our results suggest that bone marrow mesenchymal stem cell-derived exosomes (BM-MSC-Exs) can prevent transforming growth factor-ß1 (TGF-ß1)-induced epithelial-mesenchymal transition (EMT) of renal tubular epithelial cells through Nedd4L trafficking, which activates autophagy. Second, the improvement effects of BM-MSC-Ex on TGF-ß1-induced HK-2 EMT can be enhanced by ceria nanoparticles (CeNPs). The findings in this study may be extended to RF: BM-MSC-Exs may be used as a novel treatment to improve RF.
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Exossomos , Células-Tronco Mesenquimais , Insuficiência Renal Crônica , Transição Epitelial-Mesenquimal , Exossomos/metabolismo , Fibrose , Humanos , Fator de Crescimento Transformador beta1/farmacologiaRESUMO
Bladder cancer (BC) is one of the most common malignant tumors in the urinary system. Our research aimed to explore the function and underlying mechanisms of long noncoding RNA (lncRNA) PSMA3-AS1 in BC. RT-qPCR was utilized to detect the levels of PSMA3-AS1, miR-214-5p, and PD-L1. ChIP assay was employed to confirm the transcription factor of PSMA3-AS1. Luciferase reporter assay was carried out to demonstrate the relationships between miR-214-5p and PSMA3-AS1 or PD-L1. The diagnostic value of PSMA3-AS1 was evaluated by the ROC curve. CCK-8, wound healing, transwell, and flow cytometry assays were applied to analyze cell viability, migration, invasion, and apoptosis. Western blotting was used to confirm the expression of cleaved caspase-3. The present study revealed that BC tissues and cells exhibited an increased expression in PSMA3-AS1. High expression of PSMA3-AS1 was related to poor prognosis in BC patients. Then, the area under the ROC curve for PSMA3-AS1 was up to 0.8954. Moreover, ChIP assay elaborated that YY1 could bind to the PSMA3-AS1 promoter region. Furthermore, it was found that that PSMA3-AS1 knockdown repressed BC cell viability and metastasis, and promoted apoptosis. In addition, miR-214-5p was inversely correlated with PSMA3-AS1 or PD-L1 levels. MiR-214-5p deletion reversed the impacts of PSMA3-AS1 deletion on BC progression, and PD-L1 inhibition also abrogated the influence of miR-214-5p deletion in BC development. In conclusion, YY1-induced PSMA3-AS1 exerted an oncogenic function in BC cells via targeting miR-214-5p and enhancing PD-L1, providing potential biomarkers for BC therapy.
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Apoptose/genética , Antígeno B7-H1/genética , Regulação Neoplásica da Expressão Gênica , MicroRNAs/metabolismo , RNA Longo não Codificante/metabolismo , Neoplasias da Bexiga Urinária/genética , Neoplasias da Bexiga Urinária/patologia , Fator de Transcrição YY1/metabolismo , Sequência de Bases , Carcinogênese/genética , Carcinogênese/patologia , Linhagem Celular Tumoral , Sobrevivência Celular/genética , Progressão da Doença , Deleção de Genes , Humanos , MicroRNAs/genética , Metástase Neoplásica , Ligação Proteica , RNA Longo não Codificante/genéticaRESUMO
AIM: The main objective of this article was to evaluate the association of voltage-dependent anion channel 1 (VDAC1) with Cytochrome C (Cytc) expression, various clinicopathological features, and prognosis in breast cancer (BC) patients. Meanwhile, the correlation of Cytc expression with various clinical features and 5-year disease-free survival (5-DFS) of BC was also investigated. METHODS: In vivo, expression of VDAC1 and Cytc was examined in 219 BC tissues and 100 benign breast lesions by immunohistochemical (IHC) analysis. In vitro, MTT and wound healing migration assay were performed to detect the effect of VDAC1 on BC cells. RESULTS: Expression of VDAC1 is conversely associated with Cytc in BC (P = 0.011), especially in triple-negative breast cancer (TNBC) (P = 0.004). Knockdown of VDAC1 inhibited proliferation (P < 0.001) and migration (P < 0.05) of MCF-7 cells. High expression of VDAC1 and low expression of Cytc had a significant association with multiple clinicopathological parameters (P < 0.05) and poor 5-DFS (P < 0.001) in BC. CONCLUSION: VDAC1 was elevated in BC tissues and conversely associated with Cytc. Detection of VDAC1 may provide guidance for the poor prognosis of BC, especially TNBC.
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Neoplasias da Mama/metabolismo , Citocromos c/metabolismo , Canal de Ânion 1 Dependente de Voltagem/metabolismo , Neoplasias da Mama/patologia , Movimento Celular , Proliferação de Células , Intervalo Livre de Doença , Feminino , Técnicas de Silenciamento de Genes , Humanos , Estimativa de Kaplan-Meier , Células MCF-7 , Pessoa de Meia-Idade , Análise Multivariada , Prognóstico , Receptor ErbB-2/metabolismo , Neoplasias de Mama Triplo Negativas/metabolismo , Neoplasias de Mama Triplo Negativas/patologiaRESUMO
The fruit trichomes of Cucurbitaceae are widely desired in many Asian countries and have been a key determinant of cucumber (Cucumis sativus L.) cultivar selection for commercial production and breeding. However, our understanding of the initiation and development of cucumber trichomes is still limited. Here, we found that the cucumber TINY BRANCHED HAIR (TBH) gene is preferentially expressed in multicellular trichomes. Overexpression of CsTBH in tbh mutants restored the trichome phenotype and increased the percentage of female flowers, whereas silencing of CsTBH in wild-type plants resulted in stunted trichomes with a lower rate of female flowers. Furthermore, we provide evidence that CsTBH can directly bind to the promoters of cucumber 1-Aminocyclopropane-1-Carboxylate Synthase (CsACS) genes and regulate their expression, which affects multicellular trichome development, ethylene accumulation, and sex expression. Two cucumber acs mutants with different trichome morphology and sex morphs compared with their near-isogenic line further support our findings. Collectively, our study provides new information on the molecular mechanism of CsTBH in regulating multicellular trichome development and sex expression through an ethylene pathway.
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Cucumis sativus/metabolismo , Etilenos/metabolismo , Genes de Plantas/genética , Redes e Vias Metabólicas , Fatores de Transcrição/genética , Tricomas/crescimento & desenvolvimento , Cucumis sativus/crescimento & desenvolvimento , Genes de Plantas/fisiologia , Regiões Promotoras Genéticas , Fatores de Transcrição/fisiologia , Tricomas/metabolismoRESUMO
This case report describes a 43-year-old female initially diagnosed with gestational trophoblastic neoplasia that then experienced metastasis to the liver and then subsequently to the pancreas nearly 4 years after the primary diagnosis. After resection of the body and tail of the pancreas, the postoperative histopathological examination confirmed a placental site trophoblastic tumour that had developed after several cycles of chemotherapy for the original primary tumour and the liver metastases. This type of sequential recurrence of gestational trophoblastic neoplasia in the primary site or metastatic sites, such as the liver or pancreas, can be cured by a comprehensive treatment strategy involving surgery and/or salvage chemotherapy and continuous follow-up over a long period, especially for patients with a high-risk status.
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Doença Trofoblástica Gestacional , Neoplasias Uterinas , Adulto , Protocolos de Quimioterapia Combinada Antineoplásica/uso terapêutico , Feminino , Doença Trofoblástica Gestacional/diagnóstico por imagem , Doença Trofoblástica Gestacional/tratamento farmacológico , Doença Trofoblástica Gestacional/cirurgia , Humanos , Fígado , Recidiva Local de Neoplasia , Pâncreas , Gravidez , Estudos RetrospectivosRESUMO
Mucinous tubular and spindle cell carcinoma (MTSCC) of the kidney is a rare and polymorphic tumor, which has been previously considered to be a low-grade malignancy, predominantly occurring in women. To the best of our knowledge, MTSCC with bladder metastasis has never been reported. The current study presents five adult cases of MTSCC that included three male and two female patients. Among the male cases, two were of advanced stage, one with MTSCC and renal chromophobe cell carcinoma with bladder metastasis and the other with MTSCC with invasion of the renal vein. The other three cases with small masses were at an early stage. All five cases had a good prognosis and were without recurrence after several years of follow-up. A 70-year-old male with intermittent gross hematuria, intermittent renal colic, and groin radiation pain for a year (case 1), was incidentally detected to have a left renal density mass by total abdominal enhanced computed tomography scans. In the other four cases, renal masses were found by B-ultrasound. The patient in case 1 underwent a retroperitoneal laparoscopic radical nephroureterectomy with bladder cuff resection and transurethral resection of the bladder tumor, and received gemcitabine hydrochloride via intravesical instillation therapy plus cisplatin chemotherapy every 3 months. The patient in case 2 underwent an open left radical nephrectomy and renal pedicle lymph node dissection. The other three patients underwent a laparoscopic radical nephrectomy. All five patients had no recurrence or new metastasis in other organs after follow-up. In conclusion, the incidence of MTSCC in men and women is not as disparate as reported in previous publications. The characteristics of the images of the five adult cases in the present study showed a considerable consistency, with only minor differences. The malignancy and prognosis of MTSCC are still controversial, and thus inclusion and review of more cases is required to reach a definite final conclusion. Sunitinib and gemcitabine chemotherapy in combination with cisplatin may be effective for the therapy of MTSCC patients with metastasis, but a larger range of treatments needs to be identified.
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In Brassicaceae, the requirement for vernalization is conferred by high expression of FLOWERING LOCUS C (FLC). The expression of FLC is known to be repressed by prolonged exposure to cold. Rapeseed (Brassica napus L.) cultivars can be classified into spring, winter, and semi-winter crop types, depending on their respective vernalization requirements. In addition to two known distinct transposon insertion events, here we identified a 4.422 kb hAT and a 5.625 kb long interspersed nuclear element transposon insertion within BnaFLC.A10, and a 810 bp miniature inverted-repeat transposable element (MITE) in BnaFLC.A2. Quantitative PCR demonstrated that these insertions lead to distinct gene expression patterns and contribute differentially to the vernalization response. Transgenic and haplotype analysis indicated that the known 621 bp MITE in the promoter region of BnaFLC.A10 is a transcriptional enhancer that appears to be the main determinant of rapeseed vernalization, and has contributed to the adaptation of rapeseed in winter cultivation environments. In the absence of this transposon insertion, the functional allele of BnaFLC.A2 is a major determinant of vernalization demand. Thus, the combination of BnaFLC.A10 carrying the 621 bp MITE insertion and a functional BnaFLC.A2 appears necessary to establish the winter rapeseed crop phenotype.
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Brassica napus , Alelos , Benzenoacetamidas , Brassica napus/genética , Flores , Regulação da Expressão Gênica de Plantas , Piperidonas , Estações do AnoRESUMO
A large number of literature has shown that high expression of X inactive-specific transcript (XIST) is associated with poor prognosis and metastasis of cancer in patients. However, most of this literature is limited by the small sample sizes and discrete outcomes. Therefore, a meta-analysis was performed to investigate the relation between XIST expression and tumor node metastasis (TNM) stage, lymph node metastasis, distant metastasis, and overall survival of cancer patients. We searched for literature in PubMed, Embase, and Web of Science. The pooled hazard ratios (HRs) or odds ratios (ORs) with 95% confidence intervals (CIs) were calculated to evaluate the association of XIST expression with prognosis and clinicopathological characteristics of cancer patients. Finally, a total of 14 articles involving 1123 patients were included in this meta-analysis. The results suggested that high expression of XIST has a significant relationship with a relatively poor overall survival for patients with malignant tumors (HR 1.82; 95% CI 1.32, 2.52; P = 0.0003). Moreover, high expression of XIST was significantly associated with poor TNM stage (OR 3.64; 95% CI 2.62, 5.07; P < 0.0001), lymph node metastasis (OR 2.39; 95% CI 1.65, 3.46; P < 0.0001) and distant metastasis (OR 2.84; 95% CI 1.90, 4.23; P < 0.0001). In conclusion, high expression of lncRNA XIST may be a predictive factor of poor prognosis in human cancers.
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Neoplasias/genética , RNA Longo não Codificante/genética , Humanos , Neoplasias/patologia , PrognósticoRESUMO
AIM: The aim of this study was to explore the correlation of chemokine receptor CXCR3 with M2 macrophage infiltration, various clinicopathological features, and prognosis in patients diagnosed with gastric cancer (GC). METHODS: Expression of CXCR3 protein and M2 macrophage was evaluated in 156 GC patients and corresponding paracancerous tissues by immunohistochemical (IHC) analysis. RESULTS: In our study, 59 (37.82%) showed high expression of CXCR3 protein in 156 GC tissues. Expression of CXCR3 protein was significantly increased in tumor tissues compared with corresponding paracancerous tissues (P < 0.001). Overexpression of CXCR3 protein correlated with decreased M2 macrophage infiltration (P = 0.001). By analyzing the association between expression of CXCR3 protein and clinicopathological factors of GC patients, we found that high level of CXCR3 protein was significantly correlated with better differentiation (P =0.017), I/II TNM stage (P = 0.02), and smaller invasion depth (P = 0.003). Moreover, we found through Kaplan-Meier analysis and log-rank test that GC patients with high expression of CXCR3 protein and low M2 macrophage infiltration had better overall survival (OS) and low mortality rate (P < 0.001 and P = 0.024, respectively). The multivariate survival analysis showed that high expression of CXCR3 protein could serve as a favorable independent biomarker for prognosis in GC patients [hazard ratio (HR): 0.342 (0.204-0.571); P < 0.001]. CONCLUSION: Our study indicates that overexpression of CXCR3 protein in GC is associated with decreased M2 macrophage infiltration and improved OS and thus can be further exploited as a biomarker in GC.
Assuntos
Quimiocinas/metabolismo , Macrófagos/metabolismo , Receptores CXCR3/metabolismo , Neoplasias Gástricas/metabolismo , Adulto , Idoso , Idoso de 80 Anos ou mais , Biomarcadores Tumorais , Feminino , Humanos , Imuno-Histoquímica , Estimativa de Kaplan-Meier , Masculino , Pessoa de Meia-Idade , Mortalidade , Análise Multivariada , Prognóstico , Modelos de Riscos Proporcionais , Neoplasias Gástricas/mortalidade , Neoplasias Gástricas/patologia , Análise de Sobrevida , Adulto JovemRESUMO
This study explored the effect of LncRNA Lnc-LIF-AS on cell proliferation, migration and invasion in the human cervical cancer (HCC) cell line SiHa. SiHa cells had the lowest expression of Lnc-LIF-AS in the 4 human cervical cancer cell lines (SiHa, ME-180, C-33A and HeLa) and were transfected and divided into the SiHa/con (transfected with pMIGRI) cell group, SiHa/Lnc-LIF-AS (transfected with pMIGRI-Lnc-LIF-AS) cell group, and SiHa/Lnc-LIF-AS-DN (transfected with pMIGRI-Lnc-LIF-AS-DN, in which the sequences overlapping with LIF mRNA was deleted) cell group. Overexpression of Lnc-LIF-AS could promote the proliferation, colony formation, invasion and migration in SiHa and ME-180 cells. And the low expression of Lnc-LIF-AS suppress the proliferation, colony formation invasion and migration in HeLa cells when the Lnc-LIF-AS expression has been suppressed. In the SiHa/Lnc-LIF-AS cells group, the cell cycle was mainly halted in the S phase and overexpression of Lnc-LIF-AS had no effect on the apoptosis of SiHa cells. Overexpression of Lnc-LIF-AS could promote the secretion of LIF in SiHa cells, and the supernatant from SiHa/Lnc-LIF-AS cells could promote cell proliferation in the SiHa/con cells. The STAT3 inhibitor could inhibit cell proliferation in the SiHa/Lnc-LIF-AS cells. The expression level of Lnc-LIF-AS in cervical cancer tissues was higher than that in normal tissues and the expression level of Lnc-LIF-AS was positively correlated with the level of LIF. In the SiHa/con and SiHa/Lnc-LIF-AS-DN cell groups, there were no significant differences in cell proliferation, cell migration and cell invasion. The overexpression of Lnc-LIF-AS can promote cell proliferation, migration and invasion in cervical cancer cells, and the core function domain of this lncRNA was located in the overlapping a 3'-UTR base sequence of LIF mRNA.
Assuntos
Movimento Celular/genética , RNA Longo não Codificante/metabolismo , Neoplasias do Colo do Útero/genética , Neoplasias do Colo do Útero/patologia , Regiões 3' não Traduzidas/genética , Animais , Sequência de Bases , Linhagem Celular Tumoral , Proliferação de Células/genética , Feminino , Regulação Neoplásica da Expressão Gênica , Humanos , Camundongos Nus , MicroRNAs/genética , MicroRNAs/metabolismo , Invasividade Neoplásica , RNA Longo não Codificante/genética , RNA Mensageiro/genética , RNA Mensageiro/metabolismoRESUMO
PURPOSE: In the present study, we aimed to evaluate the prognostic significance of the systemic inflammation response index (SIRI), which was defined based on peripheral blood counts of neutrophils, lymphocytes, and monocytes, in patients with localized or locally advanced clear cell renal cell carcinoma (CCRCC). PATIENTS AND METHODS: The prognostic value of SIRI was evaluated in a primary cohort consisting of 414 patients with localized or locally advanced CCRCC and then further validated in an independent cohort composed of 168 patients. RESULTS: Kaplan-Meier survival analyses of both cohorts revealed that CCRCC patients with high SIRI levels exhibited poorer overall survival (OS) and cancer-specific survival (CSS) compared with those with low SIRI levels. Furthermore, univariate and multivariate analyses identified SIRI as a significant independent predictor for both OS (HR: 4.853; 95% CI: 2.362-9.972; P<0.001) and CSS (HR: 5.913; 95% CI: 2.681-13.040; P<0.001). Following propensity score matching analysis, SIRI remained an excellent predictor for both OS and CSS. The area under the curve for SIRI was larger than that of the platelet-to-lymphocyte ratio (PLR), neutrophil-to-lymphocyte ratio (NLR), monocyte-to-lymphocyte ratio (MLR), and Memorial Sloan Kettering Cancer Center (MSKCC) prognostic score in both cohorts. CONCLUSION: SIRI might be a better prognostic predictor than PLR, NLR, MLR, and MSKCC score in patients with localized or locally advanced CCRCC. INSTITUTIONAL REVIEW BOARD APPROVAL NUMBER: (2010) Scientific Research Project No. 39.