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The relationship among polycystic ovary syndrome (PCOS), endometrial cancer (EC), and glycometabolism remains unclear. We explored shared genes between PCOS and EC, using bioinformatics to unveil their pathogenic connection and influence on EC prognosis. Gene Expression Omnibus datasets GSE226146 (PCOS) and GSE196033 (EC) were used. A protein-protein interaction (PPI) network was constructed to identify the central genes. Candidate markers were screened using dataset GSE54250. Differences in marker expression were confirmed in mouse PCOS and human EC tissues using RT-PCR and immunohistochemistry. The effect of PGD on EC proliferation and migration was explored using Ki-67 and Transwell assays. PGD's impact on the glycometabolic pathway within carbon metabolism was assessed by quantifying glucose content and lactic acid production. R software identified 31 common genes in GSE226146 and GSE196033. Gene Ontology functional classification revealed enrichment in the "purine nucleoside triphosphate metabolism process," with key Kyoto Encyclopedia of Genes and Genomes pathways related to "carbon metabolism." The PPI network identified 15 hub genes. HK2, NDUFS8, PHGDH, PGD, and SMAD3 were confirmed as candidate markers. The RT-PCR analysis validated distinct HK2 and PGD expression patterns in mouse PCOS ovarian tissue and human EC tissue, as well as in normal and EC cells. Transfection experiments with Ishikawa cells further confirmed PGD's influence on cell proliferation and migration. Suppression of PGD expression impeded glycometabolism within the carbon metabolism of EC cells, suggesting PGD as a significant PCOS risk factor impacting EC proliferation and migration through modulation of single carbon metabolism. These findings highlight PGD's pivotal role in EC onset and prognosis.
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Surface ligands play crucial roles in modifying the properties of metal nanoclusters and stabilizing atomically precise structures, and also serve as vital linkers for constructing cluster-based coordination polymers. In this study, we present the results of the solvothermal synthesis of eight novel copper alkynyl clusters incorporating pyridine ligands using a one-pot method. The resulting compounds underwent characterization through elemental analysis, Fourier transform infrared (FT-IR) spectroscopy, powder X-ray diffraction (PXRD), and single-crystal X-ray diffraction (SCXRD). Our observations revealed that distinct pyridine ligands with varying lengths and coordination sites exert significant influence on the structure and dimensionality of the clusters. The structural diversity of these clusters led to the formation of one-dimensional (1D), two-dimensional (2D), or dimer arrangements linked by seven pyridine bridging ligands. Remarkably, these complexes exhibited unique UV-vis absorption and photoluminescence properties, which were influenced by the specific bridging ligand and structural framework. Furthermore, density functional theory (DFT) calculations demonstrated the capability of the conjugated system in the pyridine ligand to impact the band gap of clusters. This study not only unveils the inherent structural diversity in coordination polymers based on copper alkynyl clusters but also offers valuable insights into harnessing ligand engineering for structural and property modulation.
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BACKGROUND: Nonalcoholic fatty liver disease (NAFLD) is strongly associated with type 2 diabetes mellitus (T2DM). Lifestyle intervention remains a preferred treatment modality for NAFLD. The glucagon-like peptide (GLP-1) receptor agonists and sodium-glucose cotransporter-2 (SGLT-2) inhibitors have been developed as new glucose-lowering drugs, which can improve fatty liver via an insulin-independent glucose-lowering effect. However, studies exploring the efficacy of GLP-1 receptor agonists combined with SGLT-2 inhibitors in patients with NAFLD and T2DM are scanty. Thus, the present randomised controlled trial aims at comparing the efficacy and safety of semaglutide plus empagliflozin with each treatment alone in patients with NAFLD and T2DM. METHODS: This 52-week double-blinded, randomised, parallel-group, active-controlled trial evaluates the effects of semaglutide, empagliflozin and semaglutide + empagliflozin in 105 eligible overweight/obese subjects with NAFLD and T2DM. The primary outcome will be a change from baseline to week 52 in the controlled attenuation parameter, free fatty acid and glucagon. Secondary endpoints include changes in liver stiffness measurement, liver enzymes, blood glucose, lipid levels, renal function, electrolyte balances, minerals and bone metabolism, cytokines, high-sensitivity C-reactive protein, ferritin, anthropometric indicators, nonalcoholic fatty liver fibrosis score, fibrosis 4 score and homeostatic model assessment for insulin resistance. In addition, intention-to-treat, interim analysis and safety analysis will be performed. DISCUSSION: This double-blinded, randomised, clinical trial involves a multi-disciplinary approach and aims to explore the synergistic effects of the combination of semaglutide and empagliflozin. The results can provide important insights into mechanisms of GLP-1 receptor agonists and/or SGLT-2 inhibitors in patients with NAFLD and T2DM. TRIAL REGISTRATION: This study has been registered with Chinese Clinical Trial Registry (ChiCTR2300070674).
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Compostos Benzidrílicos , Diabetes Mellitus Tipo 2 , Peptídeos Semelhantes ao Glucagon , Glucosídeos , Hepatopatia Gordurosa não Alcoólica , Humanos , Hepatopatia Gordurosa não Alcoólica/tratamento farmacológico , Hepatopatia Gordurosa não Alcoólica/complicações , Glucosídeos/uso terapêutico , Glucosídeos/efeitos adversos , Diabetes Mellitus Tipo 2/tratamento farmacológico , Diabetes Mellitus Tipo 2/complicações , Peptídeos Semelhantes ao Glucagon/uso terapêutico , Compostos Benzidrílicos/uso terapêutico , Compostos Benzidrílicos/efeitos adversos , Pessoa de Meia-Idade , Masculino , Método Duplo-Cego , Feminino , Hipoglicemiantes/uso terapêutico , Hipoglicemiantes/efeitos adversos , Adulto , Inibidores do Transportador 2 de Sódio-Glicose/uso terapêutico , Quimioterapia Combinada , Glicemia/metabolismo , Idoso , Resultado do TratamentoRESUMO
Alloying nanoclusters (NCs) has emerged as a widely explored and versatile strategy for tailoring tunable properties, facilitating in-depth atomic-level investigations of structure-property correlations. In this study, we have successfully synthesized six atomically precise copper NCs alloyed with Group 10 metals (Pd or Pt). Notably, the Pd0 or Pt0 atom situated at the center of the distorted hexagonal antiprism Pd0/Pt0@Cu12 cage, coordinated with twelve Cu+ and two tBuC≡C- ligands. Moreover, ligand exchange strategies demonstrated the potential for Cl- and Br- to replace one or two alkynyl ligands positioned at the top or side of the NCs. The chirality exhibited by these racemic NCs is primarily attributed to the involvement of halogens and a chiral (Pd/Pt)@Cu18 skeleton. Furthermore, all the NCs exhibit near-infrared (NIR) luminescence, characterized by emission peaks at 705-755â nm, lifetimes ranging from 6.630 to 9.662â µs, and absolute photoluminescence quantum yields (PLQYs) of 1.75 %-2.52 % in their crystalline state. The experimental optical properties of these NCs are found to be in excellent agreement with the results of theoretical calculations. These alloy NCs not only offer valuable insights into the synthesis of Pd0/Pt0-Cu alloy NCs, but also bridge the gap in understanding the structure-luminescence relationships of Pd0/Pt0-Cu molecules.
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A photocatalytic radical cascade with an unusual endo-trig cyclization was developed, which enables the efficient assembly of divergent tricyclic diterpenoid frameworks. The first total synthesis of abietane 10-epi-epoxyhinoliol was thus achieved in six steps by a subsequent reductive coupling of i-PrBr under photoredox/nickel dual catalysis. Inhibitory tests of chiral 10-epi-epoxyhinoliol and its analogues in 4T1 cancer cells demonstrated the critical role of the C12 hydroxyl group, leading to a discovery of the simplified analogue with better activity.
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Antineoplásicos , Ciclização , Catálise , Estrutura Molecular , Antineoplásicos/síntese química , Antineoplásicos/farmacologia , Antineoplásicos/química , Ensaios de Seleção de Medicamentos Antitumorais , Abietanos/química , Abietanos/farmacologia , Abietanos/síntese química , Humanos , Estereoisomerismo , Linhagem Celular Tumoral , Proliferação de Células/efeitos dos fármacosRESUMO
MicroRNAs (miRNAs) are small non-coding RNAs that play pivotal roles in the host response to invading pathogens. Among these pathogens, Bombyx mori nucleopolyhedrovirus (BmNPV) is one of the main causes of substantial economic losses in sericulture, and there are relatively few studies on the specific functions of miRNAs in the B. mori-BmNPV interaction. Therefore, we conducted transcriptome sequencing to identify differentially expressed (DE) messenger RNAs (mRNAs) and miRNAs in the midgut of 2 B. mori strains (BmNPV-susceptible strain P50 and BmNPV-resistant strain A35) after BmNPV infection. Through correlation analysis of the miRNA and mRNA data, we identified a comprehensive set of 21 miRNAs and 37 predicted target mRNAs. Notably, miR-3351, which has high expression in A35, exhibited remarkable efficacy in suppressing BmNPV proliferation. Additionally, we confirmed that miR-3351 binds to the 3' untranslated region (3' UTR) of B. mori glutathione S-transferase epsilon 6 (BmGSTe6), resulting in its downregulation. Conversely, BmGSTe6 displayed an opposite expression pattern to miR-3351, effectively promoting BmNPV proliferation. Notably, BmGSTe6 levels were positively correlated with glutathione S-transferase activity, consequently influencing intracellular glutathione content in the infected samples. Furthermore, our investigation revealed the protective role of glutathione against BmNPV infection in BmN cells. In summary, miR-3351 modulates glutathione content by downregulating BmGSTe6 to inhibit BmNPV proliferation in B. mori. Our findings enriched the research on the role of B. mori miRNAs in the defense against BmNPV infection, and suggests that the antiviral molecule, glutathione, offers a novel perspective on preventing viral infection in sericulture.
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Background: Research into disordered eating (DE), shame and self-compassion (SC) has poorly represented men, general populations and non-Western communities. Aim: To explore associations between these variables in an international community sample of men and women. Methods: An online exploratory sequential mixed methods cross-sectional survey assessed levels of (quantitative Phase 1) and perceptions of (qualitative Phase 2) eating behaviours, external shame and body image shame (BIS) and SC. Results: Phase 1: Nearly 60% of our 142 survey participants were male (82/142) and about one-third were from India (43/142). About one-third of people (41/142) had a high-level concern regarding dieting, body weight, or eating (based on Eating Attitudes Test scores), and they had significantly higher levels of external shame, BIS and (SC-related) self-judgement and overidentification - compared to the 101/142 participants with low concern. Men had healthier levels of study outcomes than women. Phase 2: Four key themes were identified using inductive thematic analysis of the responses of 55 survey participants: (T1) DE as a Psychological Issue, (T2) DE as a Social Issue, (T3) The Vicious Cycle of Shame and (T4) Seeking Help. Conclusion: In participants in Phase 1 of our study - who were mostly male - DE behaviours were related to more external shame and body image-specific shame, and to less SC. Men had healthier levels of study variables than women. In Phase 2, participants talked about a vicious cycle of pathological eating and shame.
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Polycystic ovary syndrome (PCOS) is a complex endocrine disease that can cause female infertility and bring economic burden to families and to society. The clinical and/or biochemical manifestations include hyperandrogenism, persistent anovulation, and polycystic ovarian changes, often accompanied by insulin resistance and obesity. Although its pathogenesis is unclear, PCOS involves the abnormal regulation of the hypothalamic-pituitary-ovarian axis and the abnormal activation of GnRH neurons. Neuropeptide Y (NPY) is widely distributed in the arcuate nucleus of the hypothalamus and functions as the physiological integrator of two neuroendocrine systems, one governing feeding and the other controlling reproduction. In recent years, an increasing number of studies have focused on the improvement of the reproductive and metabolic status of PCOS through the therapeutic application of NPY and its receptors. In this review, we summarize the central and peripheral regulation of NPY and its receptors in the development of PCOS and discuss the potential for NPY receptor-related therapies for PCOS.
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Hiperandrogenismo , Síndrome do Ovário Policístico , Feminino , Humanos , Síndrome do Ovário Policístico/terapia , Síndrome do Ovário Policístico/metabolismo , Receptores de Neuropeptídeo Y , Hormônio Liberador de GonadotropinaRESUMO
Polycystic ovary syndrome (PCOS) is a reproductive dysfunction associated with endocrine disorders and is most common in women of reproductive age. Clinical and/or biochemical manifestations include hyperandrogenism, persistent anovulation, polycystic ovary, insulin resistance, and obesity. Presently, the aetiology and pathogenesis of PCOS remain unclear. In recent years, the role of circadian rhythm changes in PCOS has garnered considerable attention. Changes in circadian rhythm can trigger PCOS through mechanisms such as oxidative stress and inflammation; however, the specific mechanisms are unclear. Exosomes are vesicles with sizes ranging from 30-120nm that mediate intercellular communication by transporting microRNAs (miRNAs), proteins, mRNAs, DNA, or lipids to target cells and are widely involved in the regulation of various physiological and pathological processes. Circadian rhythm can alter circulating exosomes, leading to a series of related changes and physiological dysfunctions. Therefore, we speculate that circadian rhythm-induced changes in circulating exosomes may be involved in PCOS pathogenesis. In this review, we summarize the possible roles of exosomes and their derived microRNAs in the occurrence and development of PCOS and discuss their possible mechanisms, providing insights into the potential role of exosomes for PCOS treatment.
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Exossomos , MicroRNAs , Síndrome do Ovário Policístico , Humanos , Feminino , MicroRNAs/genética , Síndrome do Ovário Policístico/etiologia , Síndrome do Ovário Policístico/terapia , Ritmo Circadiano , RNA MensageiroRESUMO
Vacuoles are the most conspicuous organelles in plants for their indispensable functions in cell expansion, solute storage, water balance, etc. Extensive studies on angiosperms have revealed that a set of conserved core molecular machineries orchestrate the formation of vacuoles from multiple pathways. Usually, vacuoles in seed plants are classified into protein storage vacuoles and lytic vacuoles for their distinctive morphology and physiology function. Bryophytes represent early diverged non-vascular land plants, and are of great value for a better understanding of plant science. However, knowledge about vacuole morphology and biogenesis is far less characterized in bryophytes. In this review, first we summarize known knowledge about the morphological and metabolic constitution properties of bryophytes' vacuoles. Then based on known genome information of representative bryophytes, we compared the conserved molecular machinery for vacuole biogenesis among different species including yeast, mammals, Arabidopsis and bryophytes and listed out significant changes in terms of the presence/absence of key machinery genes which participate in vacuole biogenesis. Finally, we propose the possible conserved and diverged mechanism for the biogenesis of vacuoles in bryophytes compared with seed plants.
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Enhancer of Zeste Homologue 2 (EZH2) as a histone methyltransferase epigenetically regulates laryngeal carcinoma (LGC) progression. The present study sought to explore the role and mechanism of EZH2 in the epithelial-mesenchymal transition (EMT) of LGC cells. Expressions of EZH2, secreted frizzled-related protein 1 (SFRP1), and trimethylation of lysine 27 on histone H3 (H3K27me3) in LGC tissues or cells were detected via reverse transcription quantitative polymerase chain reaction (qRT-PCR) and western blotting. Upon transfection of si-EZH2, si-SFRP1, oe-SFRP1, or H3K27me3 upregulation, cell viability was assessed via cell counting kit-8, protein levels of E-cadherin, N-cadherin, ß-catenin, c-Myc, and Cyclin D1 were determined via western blotting, and Vimentin expression was determined via immunofluorescence. The enrichment level of H3K27me3 in the SFRP1 promoter was measured via chromatin immunoprecipitation-PCR. EZH2 was highly expressed in LGC tissues and cells. Silencing EZH2 repelled the EMT of LGC cells. Mechanically, EZH2 upregulated H3K27me3 in the SFRP1 promotor to inhibit SFRP1 expression, and SFRP1 overexpression inactivated the Wnt pathway. H3K27me3 upregulation or SFRP1 downregulation reversed the inhibition of silencing EZH2 in the EMT of LGC cells. Overall, EZH2 upregulated H3K27me3 in the SFRP1 promoter to inhibit SFRP1 expression and activate the Wnt pathway, thereby facilitating the EMT of LGC cells.
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Carcinoma , Neoplasias Laríngeas , Linhagem Celular Tumoral , Proteína Potenciadora do Homólogo 2 de Zeste/genética , Epigênese Genética , Transição Epitelial-Mesenquimal/genética , Regulação Neoplásica da Expressão Gênica , Histonas , Humanos , Peptídeos e Proteínas de Sinalização Intercelular/metabolismo , Peptídeos e Proteínas de Sinalização Intracelular , Neoplasias Laríngeas/genética , Proteínas de Membrana/genética , Proteínas de Membrana/metabolismoRESUMO
OBJECTIVE: To investigate the effects of visual feedback training on knee function and balance ability in postoperative patients with knee fracture. METHODS: A clinical randomized controlled trial with 104 participants, randomly assigned (1:1) to a visual feedback training group or a control group. Eligible participants were evaluated using Lysholm scores, the Tinetti scale, and the evaluation module of TecnoBody® to demonstrate dynamic balance function in a standing position before treatment and after 4 and 8 weeks of treatment. RESULTS: Both visual feedback training and control groups improved significantly in the Lysholm and Tinetti scores after 8 weeks. Compared with the control group, the TecnoBody® tests included centre of pressure path length, and the area over centre of pressure movement, both of which significantly improved in the visual feedback training group at 8 weeks after treatment. There was no difference between the 2 groups in terms of their Lysholm scores and Tinetti gait before the intervention and 4 weeks after treatment. CONCLUSION: Applying visual feedback training in conjunction with traditional rehabilitation strategies may improve knee function and motor control in postoperative patients with knee fracture. Although visual feedback training does not have a short-term effect on knee function and gait, this method could be a useful addition for rehabilitation of knee fracture patients.
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Retroalimentação Sensorial , Equilíbrio Postural , Terapia por Exercício/métodos , Marcha , Humanos , Joelho , Articulação do JoelhoRESUMO
Notoginsenoside R1 (NG-R1), the extract and the main ingredient of Panax notoginseng, has anti-inflammatory effects and can be used in treating acute lung injury (ALI). In this study, we explored the pulmonary protective effect and the underlying mechanism of the NG-R1 on rats with ALI induced by severe acute pancreatitis (SAP). MiR-128-2-5p, ERK1, Tollip, HMGB1, TLR4, IκB, and NF-κB mRNA expression levels were measured using real-time qPCR, and TLR4, Tollip, HMGB1, IRAK1, MyD88, ERK1, NF-κB65, and P-IκB-α protein expression levels using Western blot. The NF-κB and the TLR4 activities were determined using immunohistochemistry, and TNF-α, IL-6, IL-1ß, and ICAM-1 levels in the bronchoalveolar lavage fluid (BALF) using ELISA. Lung histopathological changes were observed in each group. NG-R1 treatment reduced miR-128-2-5p expression in the lung tissue, increased Tollip expression, inhibited HMGB1, TLR4, TRAF6, IRAK1, MyD88, NF-κB65, and p-IκB-α expression levels, suppressed NF-κB65 and the TLR4 expression levels, reduced MPO activity, reduced TNF-α, IL-1ß, IL-6, and ICAM-1 levels in BALF, and alleviated SAP-induced ALI. NG-R1 can attenuate SAP-induced ALI. The mechanism of action may be due to a decreased expression of miR-128-2-5p, increased activity of the Tollip signaling pathway, decreased activity of HMGB1/TLR4 and ERK1 signaling pathways, and decreased inflammatory response to SAP-induced ALI. Tollip was the regulatory target of miR-128-2-5p.
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Lesão Pulmonar Aguda , Proteína HMGB1 , MicroRNAs , Pancreatite , Doença Aguda , Lesão Pulmonar Aguda/tratamento farmacológico , Lesão Pulmonar Aguda/metabolismo , Animais , Ginsenosídeos , Proteína HMGB1/metabolismo , Molécula 1 de Adesão Intercelular/metabolismo , Interleucina-6/metabolismo , Peptídeos e Proteínas de Sinalização Intracelular , MicroRNAs/genética , MicroRNAs/metabolismo , Fator 88 de Diferenciação Mieloide/metabolismo , Inibidor de NF-kappaB alfa/metabolismo , NF-kappa B/metabolismo , Pancreatite/tratamento farmacológico , Ratos , Transdução de Sinais , Receptor 4 Toll-Like/metabolismo , Fator de Necrose Tumoral alfa/metabolismoRESUMO
BACKGROUND: Pulmonary fibrosis is a respiratory disease caused by the proliferation of fibroblasts and accumulation of the extracellular matrix (ECM). It is known that the lung ECM is mainly composed of a three-dimensional fiber mesh filled with various high-molecular-weight proteins. However, the small-molecular-weight proteins in the lung ECM and their differences between normal and fibrotic lung ECM are largely unknown. METHODS: Healthy adult male Sprague-Dawley rats (Rattus norvegicus) weighing about 150 to 200 g were randomly divided into three groups using random number table: A, B, and C and each group contained five rats. The rats in Group A were administered a single intragastric (i.g.) dose of 500 µL of saline as control, and those in Groups B and C were administered a single i.g. dose of paraquat (PQ) dissolved in 500 µL of saline (20 mg/kg). After 2 weeks, the lungs of rats in Group B were harvested for histological observation, preparation of de-cellularized lung scaffolds, and proteomic analysis for small-molecular-weight proteins, and similar procedures were performed on Group C and A after 4 weeks. The differentially expressed small-molecular-weight proteins (DESMPs) between different groups and the subcellular locations were analyzed. RESULTS: Of the 1626 small-molecular-weight proteins identified, 1047 were quantifiable. There were 97 up-regulated and 45 down-regulated proteins in B vs. A, 274 up-regulated and 31 down-regulated proteins in C vs. A, and 237 up-regulated and 28 down-regulated proteins identified in C vs. B. Both the up-regulated and down-regulated proteins in the three comparisons were mainly distributed in single-organism processes and cellular processes within biological process, cell and organelle within cellular component, and binding within molecular function. Further, more up-regulated than down-regulated proteins were identified in most sub-cellular locations. The interactions of DESMPs identified in extracellular location in all comparisons showed that serum albumin (Alb) harbored the highest degree of node (25), followed by prolyl 4-hydroxylase beta polypeptide (12), integrin ß1 (10), apolipoprotein A1 (9), and fibrinogen gamma chain (9). CONCLUSIONS: Numerous PQ-induced DESMPs were identified in de-cellularized lungs of rats by high throughput proteomics analysis. The DESMPs between the control and treatment groups showed diversity in molecular functions, biological processes, and pathways. In addition, the interactions of extracellular DESMPs suggested that the extracellular proteins Alb, Itgb1, Apoa1, P4hb, and Fgg in ECM could be potentially used as biomarker candidates for pulmonary fibrosis. These results provided useful information and new insights regarding pulmonary fibrosis.
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Proteômica , Fibrose Pulmonar , Animais , Matriz Extracelular , Pulmão , Masculino , Fibrose Pulmonar/induzido quimicamente , Ratos , Ratos Sprague-DawleyRESUMO
Reprogrammed glucose metabolism is essential for tumor initiation and development, especially for pancreatic ductal adenocarcinoma (PDAC). Most cancer cells rely on aerobic glycolysis, a phenomenon termed "the Warburg effect", to support uncontrolled proliferation and evade apoptosis. However, the direct regulators of the Warburg effect remain areas of active investigation. In this study, we found that the highly conserved transcription factor, TWIST1, is a crucial regulator of aerobic glycolysis in PDAC. Genetic silencing of TWIST1 significantly inhibited the glycolytic phenotypes of PDAC cells as revealed by reduced glucose uptake, lactate production, and extracellular acidification rate, which can be restored by re-expression of siRNA-resistant TWIST1. Moreover, tamoxifen-inducible expression of TWIST1 promoted the Warburg metabolism of PDAC cells. Mechanistically, by luciferase reporter assay and chromatin immunoprecipitation experiment, we showed that TWIST1 can directly increase the expression of several glycolytic genes, including SLC2A1, HK2, ENO1, and PKM2. Of note, the transcriptional regulation by TWIST1 was not dependent on HIF1α or c-Myc. In The Cancer Genome Atlas and Gene Expression Omnibus accession GSE15471, we confirmed that TWIST1 was closely associated with the glycolysis pathway. Collectively, our findings indicate that TWIST1 is likely to act as important regulator of the Warburg effect in PDAC.
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Adenocarcinoma/metabolismo , Regulação Neoplásica da Expressão Gênica , Glicólise , Proteínas Nucleares/genética , Neoplasias Pancreáticas/metabolismo , Proteína 1 Relacionada a Twist/genética , Adenocarcinoma/genética , Adenocarcinoma/patologia , Biomarcadores Tumorais/genética , Biomarcadores Tumorais/metabolismo , Proteínas de Transporte/genética , Proteínas de Transporte/metabolismo , Linhagem Celular Tumoral , Proteínas de Ligação a DNA/genética , Proteínas de Ligação a DNA/metabolismo , Transportador de Glucose Tipo 1/genética , Transportador de Glucose Tipo 1/metabolismo , Hexoquinase/genética , Hexoquinase/metabolismo , Humanos , Proteínas de Membrana/genética , Proteínas de Membrana/metabolismo , Neoplasias Pancreáticas/genética , Neoplasias Pancreáticas/patologia , Fosfopiruvato Hidratase/genética , Fosfopiruvato Hidratase/metabolismo , Hormônios Tireóideos/genética , Hormônios Tireóideos/metabolismo , Proteínas Supressoras de Tumor/genética , Proteínas Supressoras de Tumor/metabolismo , Proteínas de Ligação a Hormônio da TireoideRESUMO
LncRNA TP73 antisense RNA 1T (TP73-AS1) plays an important role in human malignancies. However, the levels of TP73-AS1 and its functional mechanisms in pancreatic cancer metastasis remain unknown, and the clinical significance of TP73-AS1 in human pancreatic cancer is also unclear. In the present study, the levels of TP73-AS1 and its candidate target miR-141 in pancreatic cancer and adjacent normal tissue were detected using qRT-PCR. The association between TP73-AS1 levels and the clinicopathologic characteristics of pancreatic cancer patients were analyzed. The relationship between TP73-AS1 and miR-141, and miR-141 and its candidate target 3-hydroxybutyrate dehydrogenase type 2 (BDH2) was confirmed using dual-luciferase reporter assays. TP73-AS1 and/or miR-141 were knocked down using siRNA or an inhibitor in pancreatic cancer cells and cell migration and invasion then examined. The results showed that TP73-AS1 was up-regulated in pancreatic cancer tissue and cell lines. High levels of TP73-AS1 were correlated with poor clinicopathological characteristics and shorter overall survival. MiR-141 was a direct target for TP73-AS1, while BDH2 was a direct target for miR-141. The knockdown of TP73-AS1 significantly inhibited the migration and invasion of pancreatic cancer cells, while the miR-141 inhibitor significantly restored the migration and invasion. Therefore, TP73-AS1 positively regulated BDH2 expression by sponging miR-141. These findings suggest that TP73-AS1 serves as an oncogene and promotes the metastasis of pancreatic cancer. Moreover, TP73-AS1 could serve as a predictor and a potential drug biotarget for pancreatic cancer.
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Movimento Celular/genética , Regulação Neoplásica da Expressão Gênica , Hidroxibutirato Desidrogenase/genética , MicroRNAs/genética , Neoplasias Pancreáticas/genética , RNA Longo não Codificante/genética , Linhagem Celular Tumoral , Feminino , Humanos , Hidroxibutirato Desidrogenase/metabolismo , Estimativa de Kaplan-Meier , Masculino , Pessoa de Meia-Idade , Invasividade Neoplásica , Neoplasias Pancreáticas/metabolismo , Neoplasias Pancreáticas/patologia , Interferência de RNA , Regulação para CimaRESUMO
BACKGROUND: Total laryngectomy is preserved for those the most advanced larynx cancer and nonsurgical cases. However, stomal recurrence is frequently occurred and leads to high mortality. Herein, we aimed to determine the risk factors for the stomal recurrence after total laryngectomy (SRAL). METHODS: Databases such as PubMed and EMBASE were comprehensively searched using the keywords "stomal recurrence" and "total laryngectomy." Based on the inclusion and exclusion criteria, qualified studies would be incorporated in this meta-analysis, followed by quality evaluation and data extraction. Risk ratios (RRs) were used. RESULTS: A total of six studies were included in the meta-analysis, and the pooled RRs showed that subglottic location increased the incidence of stomal recurrence most among the four primary locations. Expectedly, advanced tumor stage before the laryngectomy was the risk factor for stomal recurrence, while lymph node metastases showed no difference in this meta-analysis. Further, preoperative tracheostomy increased two times more risk in the stomal recurrence compared with nonpreoperative surgery. CONCLUSIONS: In this study, we proved that subglottic location, advanced tumor stage, especially T4 stage, and preoperative tracheostomy were risk factors for SRAL for larynx cancer. However, many other potential risk factors, such as surgical margins, could not be determined for inadequate records. Hence, more prospective trials should be designed to determine the risk factors for SRAL for larynx cancer.
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Carcinoma de Células Escamosas/cirurgia , Neoplasias Laríngeas/cirurgia , Laringectomia/efeitos adversos , Recidiva Local de Neoplasia/epidemiologia , Complicações Pós-Operatórias/epidemiologia , Carcinoma de Células Escamosas/patologia , Humanos , Incidência , Neoplasias Laríngeas/patologia , Laringectomia/métodos , Metástase Linfática , Margens de Excisão , Recidiva Local de Neoplasia/etiologia , Recidiva Local de Neoplasia/patologia , Estadiamento de Neoplasias , Complicações Pós-Operatórias/etiologia , Complicações Pós-Operatórias/patologia , Cuidados Pré-Operatórios/efeitos adversos , Cuidados Pré-Operatórios/métodos , Fatores de Risco , Traqueostomia/efeitos adversos , Traqueostomia/métodosRESUMO
In this study, we analyze and discuss the treatments of postoperative nasal complications after endonasal transsphenoidal resection of pituitary neoplasms (PNs). We performed 129 endonasal transsphenoidal resections of PNs and analyzed and treated cases with nasal complications. After endonasal transsphenoidal resection of PNs, there were 26 cases of postoperative nasal complications (20.1%), including nasal hemorrhage (4.8%), cerebrospinal fluid rhinorrhea (6.9%), sphenoid sinusitis (2.3%), atrophic rhinitis (1.6%), olfactory disorder (1.6%), perforation of nasal septum (0.8%), and nasal adhesion (2.3%). All patients clinically recovered after therapy, which included treatment of the cavity through nasal endoscopy, intranasal corticosteroids, and nasal irrigation. We propose that regular nasal endoscopic review, specific nasal medications, and regular nasal irrigation can effectively clear nasal mucosal hyperemia-induced edema and nasal/nasoantral secretions, as well as promote regeneration of nasal mucosa, prevent nasal adhesion, maintain the sinus cavity drainage, and accelerate the recovery of the physiological function of the paranasal sinus. Timely treatment of patients with nasal complications after endonasal transsphenoidal resections of PNs could greatly relieve the clinical symptoms. Nasal cleaning is very beneficial to patients after surgery recovery.
Assuntos
Lavagem Nasal/métodos , Cirurgia Endoscópica por Orifício Natural/efeitos adversos , Doenças Nasais/terapia , Neoplasias Hipofisárias/cirurgia , Complicações Pós-Operatórias/terapia , Adolescente , Adulto , Assistência ao Convalescente/métodos , Idoso , Rinorreia de Líquido Cefalorraquidiano/etiologia , Rinorreia de Líquido Cefalorraquidiano/terapia , Criança , Epistaxe/etiologia , Epistaxe/terapia , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Mucosa Nasal/patologia , Perfuração do Septo Nasal/etiologia , Perfuração do Septo Nasal/terapia , Procedimentos Cirúrgicos Nasais/métodos , Cirurgia Endoscópica por Orifício Natural/métodos , Nariz/lesões , Nariz/cirurgia , Doenças Nasais/etiologia , Doenças do Nervo Olfatório/etiologia , Doenças do Nervo Olfatório/terapia , Seios Paranasais/fisiopatologia , Complicações Pós-Operatórias/etiologia , Recuperação de Função Fisiológica , Estudos Retrospectivos , Rinite Atrófica/etiologia , Rinite Atrófica/terapia , Seio Esfenoidal/cirurgia , Sinusite Esfenoidal/etiologia , Sinusite Esfenoidal/terapia , Aderências Teciduais/etiologia , Aderências Teciduais/terapia , Adulto JovemRESUMO
AIM: To investigate the mechanisms and effects of sphincter of Oddi (SO) motility on cholesterol gallbladder stone formation in guinea pigs. METHODS: Thirty-four adult male Hartley guinea pigs were divided randomly into two groups, the control group (n = 10) and the cholesterol gallstone group (n = 24), which was sequentially divided into four subgroups with six guinea pigs each according to time of sacrifice. The guinea pigs in the cholesterol gallstone group were fed a cholesterol lithogenic diet and sacrificed after 3, 6, 9, and 12 wk. SO manometry and recording of myoelectric activity were obtained by a multifunctional physiograph at each stage. Cholecystokinin-A receptor (CCKAR) expression levels in SO smooth muscle were detected by quantitative real-time PCR (qRT-PCR) and serum vasoactive intestinal peptide (VIP), gastrin, and cholecystokinin octapeptide (CCK-8) were detected by enzyme-linked immunosorbent assay at each stage in the process of cholesterol gallstone formation. RESULTS: The gallstone formation rate was 0%, 0%, 16.7%, and 83.3% in the 3, 6, 9, and 12 wk groups, respectively. The frequency of myoelectric activity in the 9 wk group, the amplitude of myoelectric activity in the 9 and 12 wk groups, and the amplitude and the frequency of SO in the 9 wk group were all significantly decreased compared to the control group. The SO basal pressure and common bile duct pressure increased markedly in the 12 wk group, and the CCKAR expression levels increased in the 6 and 12 wk groups compared to the control group. Serum VIP was elevated significantly in the 9 and 12 wk groups and gastrin decreased significantly in the 3 and 9 wk groups. There was no difference in serum CCK-8 between the groups. CONCLUSION: A cholesterol gallstone-causing diet can induce SO dysfunction. The increasing tension of the SO along with its decreasing activity may play an important role in cholesterol gallstone formation. Expression changes of CCKAR in SO smooth muscle and serum VIP and CCK-8 may be important causes of SO dysfunction.
Assuntos
Cálculos Biliares/fisiopatologia , Disfunção do Esfíncter da Ampola Hepatopancreática/fisiopatologia , Esfíncter da Ampola Hepatopancreática/fisiopatologia , Animais , Colesterol , Modelos Animais de Doenças , Eletromiografia , Ensaio de Imunoadsorção Enzimática , Cálculos Biliares/genética , Cálculos Biliares/metabolismo , Gastrinas/genética , Gastrinas/metabolismo , Cobaias , Manometria , Músculo Liso/metabolismo , Reação em Cadeia da Polimerase em Tempo Real , Receptor de Colecistocinina A/genética , Receptor de Colecistocinina A/metabolismo , Sincalida/genética , Sincalida/metabolismo , Esfíncter da Ampola Hepatopancreática/metabolismo , Disfunção do Esfíncter da Ampola Hepatopancreática/genética , Disfunção do Esfíncter da Ampola Hepatopancreática/metabolismo , Peptídeo Intestinal Vasoativo/genética , Peptídeo Intestinal Vasoativo/metabolismoRESUMO
The study aims to investigate nasal and lower airway inflammation in patients with non-allergic rhinitis (NAR), and to discuss a method of NAR classification based on inflammatory characteristics and its clinical significance. A total of 117 NAR patients admitted to our hospital from June 2010 to June 2011 were enrolled in this study, 162 healthy participants were employed as healthy controls. Nasal and lower airway inflammation were evaluated using the skin prick test, nasal and pulmonary visual analogue scale scoring, cell blood count, nasal douche, induced sputum assay, nasal provocation test, and bronchial provocation test. Compared to the healthy controls, NAR patients have significant higher levels of nasal douche eosinophils, more induced sputum eosinophils as well as blood eosinophils, and higher rates of nasal and bronchial provocation. Patient with high level of eosinophil in nasal douch tended to be with higher concentrations of eosinophils in induced sputum. Scores on the nasal and bronchial provocation tests are also correlated to each other. Among all NAR patients, 28 cases (23.9%) were with no abnormality detectable by eosinophil measurement or a provocation test, 39 cases (33.3%) were with elevated levels of eosinophils, and 50 cases (42.7%) exhibited a nasal provocation response. Based on this, all studied NAR cases were classified into 3 groups: non-specific type (group A, 28/117), increased eosinophil type (group B, 39/117), and hyper-reactive type (group C, 50/117). Some NAR cases may be considered as systemic inflammatory disease characterized by increased nasal eosinophil and nasal hyperreactivity.