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While 19S proteasome regulatory particle (RP) inhibition is a promising new avenue for treating bortezomib-resistant myeloma, the anti-tumor impact of inhibiting 19S RP component PSMD14 could not be explained by a selective inhibition of proteasomal activity. Here, we report that PSMD14 interacts with NSD2 on chromatin, independent of 19S RP. Functionally, PSMD14 acts as a histone H2AK119 deubiquitinase, facilitating NSD2-directed H3K36 dimethylation. Integrative genomic and epigenomic analyses revealed the functional coordination of PSMD14 and NSD2 in transcriptional activation of target genes (e.g., RELA) linked to myelomagenesis. Reciprocally, RELA transactivates PSMD14, forming a PSMD14/NSD2-RELA positive feedback loop. Remarkably, PSMD14 inhibitors enhance bortezomib sensitivity and fosters anti-myeloma synergy. PSMD14 expression is elevated in myeloma and inversely correlated with overall survival. Our study uncovers an unappreciated function of PSMD14 as an epigenetic regulator and a myeloma driver, supporting the pursuit of PSMD14 as a therapeutic target to overcome the treatment limitation of myeloma.
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Histonas , Mieloma Múltiplo , Humanos , Histonas/genética , Complexo de Endopeptidases do Proteassoma/genética , Complexo de Endopeptidases do Proteassoma/metabolismo , Bortezomib/farmacologia , Bortezomib/metabolismo , Mieloma Múltiplo/tratamento farmacológico , Mieloma Múltiplo/genética , Mieloma Múltiplo/patologia , Linhagem Celular Tumoral , Enzimas Desubiquitinantes/metabolismo , Inibidores de Proteassoma/farmacologia , Transativadores/metabolismoRESUMO
Single immobilization theory cannot fully account for the extensive bone loss observed after spinal cord injury (SCI). Bone marrow mesenchymal stem cells (BMSCs) are crucial in bone homeostasis because they possess self-renewal capabilities and various types of differentiation potential. This study aimed to explore the molecular mechanism of long non-coding RNA H19 in osteoporosis after SCI and provide new research directions for existing prevention strategies. We used small interfering RNA to knockdown H19 expression and regulated miR-29b-2p expression using miR-29b-3p mimetics and inhibitors. Western blotting, real-time fluorescence quantitative PCR, Alizarin red staining, alkaline phosphatase staining and double-luciferase reporter gene assays were used to assess gene expression, osteogenic ability and binding sites. lncRNA H19 was upregulated in BMSCs from the osteoporosis group, whereas miR-29b-3p was downregulated. We identified the binding sites between miR-29b-3p and lncRNAs H19 and DKK1. H19 knockdown promoted BMSCs' osteogenic differentiation, whereas miR-29b-3p inhibition attenuated this effect. We discovered potential binding sites for miR-29b-3p in lncRNAs H19 and DKK1. Our findings suggest that long non-coding RNA H19 mediates BMSCs' osteogenic differentiation in osteoporosis after SCI through the miR-29b-3p/DKK1 axis and by directly inhibiting the ß-catenin signalling pathway.
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Peptídeos e Proteínas de Sinalização Intercelular , Células-Tronco Mesenquimais , Osteogênese , RNA Longo não Codificante , Animais , Humanos , Masculino , Ratos , Diferenciação Celular , Regulação da Expressão Gênica , Peptídeos e Proteínas de Sinalização Intercelular/metabolismo , Peptídeos e Proteínas de Sinalização Intercelular/genética , Células-Tronco Mesenquimais/metabolismo , Células-Tronco Mesenquimais/citologia , MicroRNAs/genética , MicroRNAs/metabolismo , Osteoporose/genética , Osteoporose/patologia , Osteoporose/metabolismo , RNA Longo não Codificante/genética , RNA Longo não Codificante/metabolismo , Traumatismos da Medula Espinal/genética , Traumatismos da Medula Espinal/metabolismo , Traumatismos da Medula Espinal/patologiaRESUMO
Bisphenol A (BPA), a typical environmental endocrine disruptor, has raised concerns among researchers due to its toxicological effects. Whether neohesperidin (NEO) can intervene in the toxic effects of BPA remains unknown. This study aims to investigate the effects and mechanisms of NEO on the myogenic differentiation of umbilical cord-derived mesenchymal stem cells (UC-MSCs) exposed to BPA. Sheep UC-MSCs were isolated, characterized, and induced to myogenic differentiation. BPA decreased cell viability, cell migration, and the expressions of myogenic marker genes, leading to myogenic differentiation inhibition, which were reversed by NEO. Network pharmacology suggested the IGF1R/AKT1/RHOA pathway as potential targets of BPA and NEO regulating muscle development. Western blot results showed that NEO could reverse the down-regulation of the pathway proteins induced by BPA, and counteract the effects of picropodophyllin (PPP) or MK-2206 dihydrochloride (MK-2206) in the myogenic differentiation of sheep UC-MSCs. Additionally, the expression levels of (p-) IGF1R, AKT1, and RHOA were positively correlated. Taken together, the mechanisms of NEO resistance to BPA involved the IGF1R/AKT1/RHOA signaling pathway. These findings provide a scientific basis for alleviating BPA toxicity, preventing and treating muscular dysplasia, and promoting muscle damage repair.
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Ubiquitin-like with plant homeodomain and ring finger domains 1 (UHRF1) can mediate DNA methylation and histone modifications in the epigenetic regulation of gene expression, stem cell differentiation and tumorigenesis. Here, we analyzed the differentially expressed mRNAs (DEmRNAs) in osteogenesis differentiation of MSCs and osteosarcoma. We identified UHRF1 as the co-DEmRNA to regulate the osteogenesis differentiation of MSCs and osteosarcoma. Moreover, we determined that the functions and pathways of UHRF1 in osteosarcoma. This finding indicates that UHRF1 is closely associated with metastasis and recurrence in osteosarcoma. Based on this finding, we derived a risk signature using UHRF1. In conclusion, UHRF1 is a crucial role in the malignant progression of osteosarcoma and are potentially useful for osteosarcoma progression treatment strategy development.
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Neoplasias Ósseas , Osteossarcoma , Neoplasias Ósseas/genética , Proteínas Estimuladoras de Ligação a CCAAT/genética , Proteínas Estimuladoras de Ligação a CCAAT/metabolismo , Diferenciação Celular/genética , Metilação de DNA , Epigênese Genética , Humanos , Osteogênese/genética , Osteossarcoma/genética , Prognóstico , Ubiquitina-Proteína Ligases/genéticaRESUMO
BACKGROUND: Osteoporosis is a widespread and serious metabolic bone disease. At present, revealing the molecular mechanisms of osteoporosis and developing effective prevention and treatment methods are of great significance to health worldwide. LncRNA is a non-coding RNA peptide chain with more than 200 nucleotides. Researchers have identified many lncRNAs implicated in the development of diseases and lncRNA H19 is an example. RESULTS: A large amount of evidence supports the fact that long non-coding RNA (lncRNA) genes, such as H19, have multiple, far-reaching effects on various biological functions. It has been found that lncRNA H19 has a role in the regulation of different types of cells in the body including the osteoblasts, osteocytes, and osteoclasts found in bones. Therefore, it can be postulated that lncRNA H19 affects the incidence and development of osteoporosis. CONCLUSION: The prospect of targeting lncRNA H19 in the treatment of osteoporosis is promising because of the effects that lncRNA H19 has on the process of osteogenic differentiation. In this review, we summarize the molecular pathways and mechanisms of lncRNA H19 in the pathogenesis of osteoporosis and summarize the research progress of targeting H19 as a treatment option. Research is emerging that explores more effective treatment possibilities for bone metabolism diseases using molecular targets.
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Diferenciação Celular/genética , Proliferação de Células/genética , Regulação da Expressão Gênica , Osteogênese/genética , Osteoporose/genética , RNA Longo não Codificante/genética , Osso e Ossos/citologia , Osso e Ossos/metabolismo , Humanos , Osteoblastos/citologia , Osteoblastos/metabolismo , Osteoclastos/citologia , Osteoclastos/metabolismo , Osteócitos/citologia , Osteócitos/metabolismo , Transdução de Sinais/genéticaRESUMO
Producing high-quality graphene and polymer/graphene nanocomposite is facing the problems of complex procedure, low efficiency, and serious resource waste. To explore a new fabrication approach with high efficiency and low cost is crucial for solving these technical issues, which becomes a current research hotspot and also a great challenge. Herein, a one-step melt mixing strategy based on the synergy of steam explosion and alternating convergent-divergent flow, is innovatively developed to fabricate high-density polyethylene (HDPE)/graphene nanocomposites using industrial-grade expanded graphite (EG) without chemical agents and complex procedures. The co-action of the external force derived from elongational melts and the internal force generated by steam explosion make EG ultrafastly exfoliate into few-layer graphene nanosheets (GNS) and simultaneously disperse in melts within 4 min. The as-produced GNS have a lateral size of over 5 µm and a minimum thickness of 1.4 nm, can introduce super heterogeneous nucleation to HDPE macromolecules and greatly increases nanocomposite crystallinity up to 86.5%. Moreover, plentiful HDPE crystallites and well-dispersed GNS jointly form an improved thermally-conductive network, making nanocomposites with a rapid-respond ability in solar-to-thermal conversion and heat dissipation. This facile strategy will facilitate the development of scalable production and wide application of high-performance graphene and highly-filled nanocomposites.
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Clear cell renal cell carcinoma (ccRCC) is the most common solid renal tumor. Therefore, it is necessary to explore the related tumor markers. LGALS3BP (galectin 3 binding protein) is a multifunctional glycoprotein implicated in immunity and cancer. Some studies have shown that LGALS3BP promotes the occurrence and development of tumors. However, their exact role in renal tumorigenesis remains unclear. Our study used a webserver to explore the mRNA expression and clinical features of LGALS3BP in ccRCC. Survival analysis showed that patients with high LGALS3BP expression had significantly worse OS and DFS than those with low LGALS3BP expression. LGALS3BP expression is significantly related to B cells, CD4+ T cells, macrophages, neutrophils, and dendritic cells. Furthermore, we determined that LGALS3BP is significantly associated with angiogenesis, stemness and proliferation in renal cancer. Three phenotypes may be associated with a poor prognosis. Genes related to proliferation, angiogenesis and stemness were derived from a Venn diagram of FGF2. FGF2 is negatively correlated with proliferation and positively correlated with angiogenesis. Finally, we screened for drugs that may have potential therapeutic value for ccRCC. The PCR results showed that the expression of LGALS3BP in the normal cell line was lower than that in the tumor cell lines. After LGALS3BP knockdown, the proliferation of 769-P and 786-O cells decreased. The present findings show that LGALS3BP is critical for ccRCC cell proliferation and may be a potential target and biomarker for ccRCC.
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Carcinoma de Células Renais , Carcinoma , Neoplasias Renais , Humanos , Carcinoma de Células Renais/patologia , Fator 2 de Crescimento de Fibroblastos/metabolismo , Neoplasias Renais/patologia , Rim/patologia , Biomarcadores Tumorais/genética , Biomarcadores Tumorais/metabolismo , Linhagem Celular Tumoral , Carcinoma/genética , Prognóstico , Regulação Neoplásica da Expressão Gênica , Antígenos de Neoplasias/genética , Antígenos de Neoplasias/metabolismoRESUMO
Pheochromocytomas (PCCs) are rare neuroendocrine tumors that originate from chromaffin cells in the adrenal gland. However, the cellular molecular characteristics and immune microenvironment of PCCs are incompletely understood. Here, we performed single-cell RNA sequencing (scRNA-seq) on 16 tissues from 4 sporadic unclassified PCC patients and 1 hereditary PCC patient with Von Hippel-Lindau (VHL) syndrome. We found that intra-tumoral heterogeneity was less extensive than the inter-individual heterogeneity of PCCs. Further, the unclassified PCC patients were divided into two types, metabolism-type (marked by NDUFA4L2 and COX4I2) and kinase-type (marked by RET and PNMT), validated by immunohistochemical staining. Trajectory analysis of tumor evolution revealed that metabolism-type PCC cells display phenotype of consistently active metabolism and increased metastasis potential, while kinase-type PCC cells showed decreased epinephrine synthesis and neuron-like phenotypes. Cell-cell communication analysis showed activation of the annexin pathway and a strong inflammation reaction in metabolism-type PCCs and activation of FGF signaling in the kinase-type PCC. Although multispectral immunofluorescence staining showed a lack of CD8+ T cell infiltration in both metabolism-type and kinase-type PCCs, only the kinase-type PCC exhibited downregulation of HLA-I molecules that possibly regulated by RET, suggesting the potential of combined therapy with kinase inhibitors and immunotherapy for kinase-type PCCs; in contrast, the application of immunotherapy to metabolism-type PCCs (with antigen presentation ability) is likely unsuitable. Our study presents a single-cell transcriptomics-based molecular classification and microenvironment characterization of PCCs, providing clues for potential therapeutic strategies to treat PCCs.
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Neoplasias das Glândulas Suprarrenais , Feocromocitoma , Humanos , Feocromocitoma/genética , Microambiente Tumoral , Neoplasias das Glândulas Suprarrenais/genética , Apresentação de Antígeno , Linfócitos T CD8-PositivosRESUMO
Marek's disease (MD), caused by the Marek's disease virus (MDV), is a common infectious tumor disease in chickens and was the first neoplastic disease preventable by vaccination. However, the vaccine cannot completely prevent virulent MDV infections, allowing both the vaccine and virulent MDV to coexist in the same chicken for extended periods. This study aims to investigate the changes in viral load of the very virulent strain Md5 and the rHVT-IBD vaccine in different chicken tissues using a real-time PCR assay. The results showed that the rHVT-IBD vaccine significantly reduced the viral load of MDV-Md5 in different organs, while the load of rHVT-IBD was significantly increased when co-infected with Md5. Additionally, co-infection with Md5 and rHVT-IBD in chickens not only changed the original viral load of both viruses but also affected the positive rate of Md5 at 14 days post-vaccination. The positive rate decreased from 100% to 14.29% (feather tips), 0% (skin), 33.33% (liver), 16.67% (spleen), 28.57% (thymus), 33.33% (bursa), and 66.67% (PBL), respectively. This study enhances our understanding of the interactions between HVT vector vaccines and very virulent MDV in chickens and provides valuable insights for the future development of MD vaccines.
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Galinhas , Coinfecção , Vacinas contra Doença de Marek , Doença de Marek , Doenças das Aves Domésticas , Carga Viral , Animais , Doença de Marek/virologia , Doença de Marek/prevenção & controle , Doença de Marek/imunologia , Galinhas/virologia , Coinfecção/virologia , Coinfecção/veterinária , Doenças das Aves Domésticas/virologia , Doenças das Aves Domésticas/prevenção & controle , Vacinas contra Doença de Marek/imunologia , Vacinas contra Doença de Marek/genética , Virulência , Herpesvirus Meleagrídeo 1/imunologia , Herpesvirus Meleagrídeo 1/genética , Vacinas Sintéticas/imunologia , Vacinas Sintéticas/genética , Herpesvirus Galináceo 2/genética , Herpesvirus Galináceo 2/imunologia , Herpesvirus Galináceo 2/patogenicidade , Vacinação , Vetores Genéticos/genéticaRESUMO
PURPOSE: To investigate the remodeling of multiple myeloma (MM) microenvironment after BCMA-targeted chimeric antigen receptor T cell (CAR-T) therapy. EXPERIMENTAL DESIGN: We performed single-cell RNA sequencing (scRNA-seq) on paired bone marrow specimens (n = 14) from 7 MM patients before (i.e., baseline, 'day -4') and after (i.e., 'day 28') post-lymphodepleted BCMA CAR-T therapy. RESULTS: Our analysis revealed heterogeneity in gene expression profiles among MM cells, even those harboring the same cytogenetic abnormalities. The best overall responses (BORs) of patients over the 15-month follow-up are positively correlated with the abundance and targeted cytotoxic activity of CD8+ effector CAR-T cells on day 28 after CAR-T cell infusion. Additionally, favorable responses are associated with attenuated immunosuppression mediated by regulatory T cells (Tregs), enhanced CD8+ effector T cell cytotoxic activity, and elevated type 1 conventional dendritic cell (cDC1) antigen presentation ability. DC re-clustering inferred intramedullary-originated cDC3s with extramedullary migration. Cell-cell communication network analysis indicated BCMA CAR-T therapy mitigates BAFF/GALECTIN/MK pathway-mediated immunosuppression and activates MIF pathway-mediated anti-MM immunity. CONCLUSIONS: Our study sheds light on MM microenvironment dynamics after BCMA CAR-T therapy, offering clues for predicting treatment responsivity.
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Osteosarcoma is the most prevalent malignant bone tumor. In this study, we identified metastasis-related genes (MRG) that are differentially expressed between primary and metastatic osteosarcoma and employed them to create metastasis-related risk tags (MRSs) for the overall survival of osteosarcoma patients. Using consistent cluster analysis, patients with osteosarcoma in the TARGET database were divided into subgroups with different metastatic scoring patterns. The clinicopathological traits, survival rates, tumor microenvironment traits, immune-related scores, and therapeutic responses of these patients varied. Additionally, we constructed MRS-based risk characteristics and nomographs and developed an MRG Score to improve patient characteristics. Thorough evaluations demonstrated that prognostic models and metastasis scores can distinguish high-risk patients from low-risk individuals, offering excellent predictive value. Finally, western blotting was used to confirm the expression of five identified MRG markers, which are crucial for osteosarcoma invasion and migration in terms of mechanism. Our findings represent a novel and practical predictive biomarker for osteosarcoma.
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Neoplasias Ósseas , Osteossarcoma , Humanos , Prognóstico , Genes Neoplásicos , Osteossarcoma/genética , Western Blotting , Neoplasias Ósseas/genética , Microambiente TumoralRESUMO
Osteoporosis is a clinical disease characterized by decreased bone density due to a disrupted balance between bone formation and resorption, which increases fracture risk and negatively affects the quality of life of a patient. LncRNAs are RNA molecules over 200 nucleotides in length with non-coding potential. Many studies have demonstrated that numerous biological processes involved in bone metabolism are affected. However, the complex mechanisms of action of lncRNAs and their clinical applications in osteoporosis have not yet been fully elucidated. LncRNAs, as epigenetic regulators, are widely involved in the regulation of gene expression during osteogenic and osteoclast differentiation. LncRNAs affect bone homeostasis and osteoporosis development through different signaling pathways and regulatory networks. Additionally, researchers have found that lncRNAs have great potential for clinical application in the treatment of osteoporosis. In this review, we summarize the research results on lncRNAs for clinical prevention, rehabilitation treatment, drug development, and targeted therapy for osteoporosis. Moreover, we summarize the regulatory modes of various signaling pathways through which lncRNAs affect the development of osteoporosis. Overall, these studies suggest that lncRNAs can be used as novel targeted molecular drugs for the clinical treatment of osteoporosis to improve symptoms.
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Osteoporose , RNA Longo não Codificante , Humanos , RNA Longo não Codificante/genética , RNA Longo não Codificante/metabolismo , Qualidade de Vida , Osteoporose/tratamento farmacológico , Osteoporose/genética , Osteogênese/genética , Osso e Ossos/metabolismo , Diferenciação CelularRESUMO
Osteoarthritis (OA) is a common joint disease, and studies have reported that the endoplasmic reticulum stress (ERS) in chondrocytes caused by the cartilage tissue damage could mediate the activation of Nod-like receptor protein 3 (NLRP3) inflammasomes through inositol-requiring enzyme 1 alpha (IRE1α) and thioredoxin interacting protein (TXNIP). Ginsenoside compound K (CK) has an inhibitory effect on IRE1α activation. However, the role of IRE1α-TXNIP and its interaction with CK are still unclear. In this study, we examined the role and mechanism of action of CK in OA. We found that CK ameliorated OA and ERS in IL-1ß-treated chondrocytes and a monoiodoacetate-induced rat OA model. The effect of CK on inflammation, pyroptosis, and ERS was blocked by the ERS inducer tunicamycin. In conclusion, CK hindered OA progression by inhibiting the ERS-IRE1α-TXNIP-NLRP3 axis. Overall, our data indicate that CK could be useful in the treatment of OA and other chronic inflammatory diseases.
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Osteoartrite , Proteínas Serina-Treonina Quinases , Ratos , Animais , Proteínas Serina-Treonina Quinases/genética , Proteínas Serina-Treonina Quinases/metabolismo , Piroptose , Proteína 3 que Contém Domínio de Pirina da Família NLR/genética , Proteína 3 que Contém Domínio de Pirina da Família NLR/metabolismo , Proteínas NLR/metabolismo , Endorribonucleases/genética , Endorribonucleases/metabolismo , Endorribonucleases/farmacologia , Condrócitos , Apoptose , Estresse do Retículo Endoplasmático , Inflamassomos , Osteoartrite/tratamento farmacológico , Osteoartrite/genética , Osteoartrite/metabolismo , Proteínas de Ciclo Celular/metabolismo , Proteínas de Ciclo Celular/farmacologiaRESUMO
Enhancing hepatic gluconeogenesis is one of the main modes of meeting the glucose requirement of dairy cows. This study attempted to determine whether the gluconeogenesis precursor propionate had an effect on the expression of the main genes involved in gluconeogenesis in calf hepatocytes and elucidate the associated mechanisms. Calf hepatocytes were obtained from 5 healthy calves (1 d old; 30 to 40 kg) and exposed to 0-, 1-, 2.5-, or 5-mM sodium propionate (NaP), which is known to promote the expression of genes involved in the gluconeogenesis pathway, including fructose 1,6-bisphosphatase, phosphoenolpyruvate carboxykinase, and glucose-6-phosphatase. With regard to the underlying mechanism, propionate promoted the expression of peroxisome proliferator-activated receptor gamma coactivator 1-alpha, hepatocyte nuclear factor 4, and forkhead box O1 (transcription factors that regulate the expression of hepatic gluconeogenic genes) by promoting mammalian target of rapamycin complex 1 (mTORC1), but inhibiting mTORC2 activity (P < 0.01). We also established a model of palmitic acid (PA)-induced hepatic injury in calf hepatocytes and found that PA could inhibit the gluconeogenic capacity of calf hepatocytes by suppressing the expression of gluconeogenic genes, inhibiting mTORC1, and promoting the activity of mTORC2 (P < 0.01). In contrast, NaP provided protection to calf hepatocytes by counteracting the inhibitory effect of PA on the gluconeogenic capacity of calf hepatocytes (P < 0.05). Collectively, these findings indicate that NaP enhances the gluconeogenic capacity of calf hepatocytes by regulating the mTOR pathway activity. Thus, in addition to improving the glucose production potential, propionate may have therapeutic potential for the treatment of hepatic injury in dairy cows.
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Rare-earth orthovanadate REVO4 (RE = La, Pr, Nd, Sm, Eu, Gd, Tb, Dy, Ho, and Y) films were directly synthesized within 2 hours by sacrificial conversion from electrodeposited layered rare-earth hydroxide (RE2(OH)5NO3·nH2O) films at pH â¼ 10, without subsequent heat treatment. Detailed characterization of the products was achieved by combined X-ray diffraction, Fourier-transform infrared spectroscopy, field emission scanning electron microscopy, transmission electron microscopy, X-ray photoelectron spectroscopy, and photoluminescence excitation and photoluminescence. The mechanisms of phase and morphology evolution from Y2(OH)5NO3·nH2O to YVO4 were unveiled through systematic investigations into the influences of the concentration of the anion sources (Na3VO4) and the reaction temperature. The effects of lanthanide contraction on the phase structure and particle morphology of the REVO4 films were also clarified. Additionally, the photoluminescence of RE3+ activators (RE = Eu, Dy, and Eu and Dy) was elaborated with YVO4 as a representative host lattice, and the color-tunable emission and energy transfer from Dy3+ to Eu3+ were also investigated. Electrodeposition combined with a hydrothermal anion exchange technique established in this study led to the rapid synthesis of REVO4 films, and it might have wide implications for the generation of other types of inorganic functional films.
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BACKGROUND: Lung adenocarcinoma (LUAD), the most common type of lung cancer associated with poor prognosis, has become a major health problem. IGF2BPs are types of N6-methyladenosine reader proteins, comprising IGF2BP1, IGF2BP2, and IGF2BP3, that promote LUAD progression. However, the expression profiles and prognostic value of IGF2BPs in LUAD remain unclear. OBJECTIVE: This study aimed to analyze the expression profiles and prognostic significance of the IGF2BP family in lung adenocarcinoma. METHODS: In this study, we included tissue data of LUAD patients and normal or para-carcinoma from the TCGA database and the GTEx project. Using survival analysis, Kaplan-Meier curves, and Cox proportional hazards model, we analyzed the expression profiles and prognostic significance of the IGF2BP family. RESULTS: Patients with high expression levels of IGF2BPs showed a significant association with poor overall survival (p < 0.05). Moreover, the somatic mutation rates of IGF2BP1, IGF2BP2, and IGF2BP3 were determined as 2.65, 1.59, and 1.76%, respectively, by investigating the genetic mutation. In addition, there were significant associations between TMB and IGF2BP family expression profiles, which positively correlated with the expression of PD-1 (p < 0.05). Cox proportional hazard model for LUAD showed the risk score for IGF2BP1, p-TNM stage, and so forth, all independent prognostic indicators for LUAD patients. Finally, the co-expression genes were obtained to build a PPI network and analyze the hub genes of the IGF2BP family. CONCLUSION: Our study provides further insights into the role of the IGF2BP family in LUAD and identifies 10 genes that may be associated with IGF2BPs in LUAD patients.
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Adenocarcinoma de Pulmão , Neoplasias Pulmonares , Proteínas de Ligação a RNA , Adenocarcinoma de Pulmão/genética , Adenocarcinoma de Pulmão/patologia , Biomarcadores Tumorais/genética , Regulação Neoplásica da Expressão Gênica , Humanos , Neoplasias Pulmonares/genética , Neoplasias Pulmonares/patologia , Família Multigênica , Prognóstico , Proteínas de Ligação a RNA/genéticaRESUMO
Long noncoding RNAs (lncRNAs), as an important type of RNA encoded in the human transcriptome, have shown to regulate different genomic processes in human cells, altering cell type and function. These factors are associated with carcinogenesis, cancer metastasis, bone diseases, and immune system diseases, among other pathologies. Although many lncRNAs are involved in various diseases, the molecular mechanisms through which lncRNAs contribute to regulation of disease are still unclear. The lncRNA growth arrest-specific 5 (GAS5) is a key player that we initially found to be associated with regulating cell growth, differentiation, and development. Further work has shown that GAS5 is involved in the occurrence and prognosis of bone diseases, such as osteoporosis, osteosarcoma, and postosteoporotic fracture. In this review, we discuss recent progress on the roles of GAS5 in bone diseases to establish novel targets for the treatment of bone diseases.
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Many carcinomas feature hypoxia, a condition has long been associated with tumor progression and poor prognosis, as well as resistance to chemoradiotherapy. Here, we report that the F-box protein JFK promotes mammary tumor initiation and progression in MMTV-PyMT murine model of spontaneous breast cancer. We find that JFK is inducible under hypoxic conditions, in which hypoxia-inducible factor HIF-1α binds to and transcriptionally activates JFK in breast cancer cells. Consistently, analysis of public clinical datasets reveals that the mRNA level of JFK is positively correlated with that of HIF-1α in breast cancer. We show that JFK deficiency leads to a decrease in HIF-1α-induced glycolysis in breast cancer and sensitizes hypoxic breast cancer cells to ionizing radiation and chemotherapeutic treatment. These results indicate that JFK is an important player in hypoxic response, supporting the pursuit of JFK as a potential therapeutic target for breast cancer intervention.
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BACKGROUND AND AIMS: The value of hepatocyte regeneration in predicting the outcomes of hepatitis B-related acute-on-chronic liver failure (HBV-ACLF) is not fully assessed. The present study was aimed at establishing a novel scoring system to predict patients' outcomes within 3 months by applying serological indicators of hepatic regeneration and liver injury. METHODS: Patients with chronic hepatitis B who had a rapid deterioration were investigated. Patients were observed for 90 days, and the endpoint of follow-up was death or liver transplantation. Serum parameters were estimated on the diagnosis of acute-on-chronic liver failure (ACLF). Cox proportional hazard regression was used to identify independent prognostic factors and create a novel prognostic scoring system, and a receiver operating characteristic (ROC) curve was used to analyze the performance of the model. RESULTS: A total of 308 patients with HBV-ACLF were incorporated and divided into the training cohort (n = 206) and testing cohort (n = 102) randomly. Creatine (Cre), age, total bilirubin (TBil), alpha-fetoprotein (AFP), and international normalized ratio (INR) were found to be independent prognostic factors. According to the results of Cox regression analysis, a new prognostic model (we named it the TACIA score) was calculated. The areas under ROC (AUROC) for the new model were 0.861 and 0.763 in the training and testing cohorts, respectively, and patients with lower TACIA scores (<4.34) would survive longer (P < 0.001). CONCLUSIONS: A pertinent prognostic scoring system for patients with HBV-ACLF was established in our study, and the novel model could predict patients' short-term survival effectively.
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Insuficiência Hepática Crônica Agudizada/sangue , Insuficiência Hepática Crônica Agudizada/diagnóstico , Vírus da Hepatite B/metabolismo , Hepatite B Crônica/sangue , Hepatite B Crônica/diagnóstico , Regeneração Hepática , Insuficiência Hepática Crônica Agudizada/cirurgia , Adolescente , Adulto , Idoso , Idoso de 80 Anos ou mais , Biomarcadores/sangue , Feminino , Hepatite B Crônica/cirurgia , Humanos , Masculino , Pessoa de Meia-Idade , Prognóstico , Estudos RetrospectivosRESUMO
Background and Aims: The value of alpha-fetoprotein (AFP) in hepatitis B-related acute-on-chronic liver failure (HBACLF) is not fully understood. The present study aimed to evaluate the prognostic effect of AFP on the prediction of HBACLF outcomes. Methods: We investigated a cohort of patients with HBACLF admitted from January 2013 to May 2017. The endpoint of followup was 180 days, death, or liver transplantation. AFP concentrations were estimated on admission. To make statistical comparisons, we used chi-squared test, receiver operating characteristic (ROC) curve analysis, survivorship curve analysis, and Cox proportional-hazards model. Results: A total of 92 patients (81.5% male, median age of 46 years) were included. Overall survival rate within 180 days was 43.48%, and the value of log10AFPâ¡â ≥ 2.04 indicated a better prognosis with 76.9% specificity and 62.5% sensitivity for patients with HBACLF. Age (HR 1.041), total bilirubin (HR 1.004), log10AFPâ¡â (HR 2.155), and INR (HR 1.446) were found to be risk factors of survival. Conclusion: AFP could be a useful marker to predict outcomes of acute-on-chronic liver failure.