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Our previous study demonstrated that combined transplantation of bone marrow-derived mesenchymal stem cells and retinal progenitor cells in rats has therapeutic effects on retinal degeneration that are superior to transplantation of retinal progenitor cells alone. Bone marrow- derived mesenchymal stem cells regulate and interact with various cells in the retinal microenvironment by secreting neurotrophic factors and extracellular vesicles. Small extracellular vesicles derived from bone marrow-derived mesenchymal stem cells, which offer low immunogenicity, minimal tumorigenic risk, and ease of transportation, have been utilized in the treatment of various neurological diseases. These vesicles exhibit various activities, including anti-inflammatory actions, promotion of tissue repair, and immune regulation. Therefore, novel strategies using human retinal progenitor cells combined with BMSC-derived small extracellular vesicles may represent an innovation in stem cell therapy for retinal degeneration. In this study, we developed such an approach utilizing retinal progenitor cells combined with bone marrow-derived mesenchymal stem cell-derived small extracellular vesicles to treat retinal degeneration in Royal College of Surgeons rats, a genetic model of retinal degeneration. Our findings revealed that the combination of bone marrow-derived mesenchymal stem cell-derived small extracellular vesicles and retinal progenitor cells significantly improved visual function in these rats. The addition of bone marrow-derived mesenchymal stem cell-derived small extracellular vesicles as adjuvants to stem cell transplantation with retinal progenitor cells enhanced the survival, migration, and differentiation of the exogenous retinal progenitor cells. Concurrently, these small extracellular vesicles inhibited the activation of regional microglia, promoted the migration of transplanted retinal progenitor cells to the inner nuclear layer of the retina, and facilitated their differentiation into photoreceptors and bipolar cells. These findings suggest that bone marrow-derived mesenchymal stem cell-derived small extracellular vesicles potentiate the therapeutic efficacy of retinal progenitor cells in retinal degeneration by promoting their survival and differentiation.
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Background: The major facilitator superfamily glucose transporters (GLUTs), encoded by solute carrier 2A (SLC2A) genes, mediate the transmembrane movement and uptake of glucose. To satisfy the improved energy demands, glycolysis flux is increased in cancers compared with healthy tissues. Multiple diseases, including cancer, have been associated with GLUTs. Nevertheless, not much research has been done on the functions of SLC2As in pan-cancer prognosis or their clinical treatment potential. Methods: The SLC2A family genes' level of expression and prognostic values were analyzed in relation to pan-cancer. We then examined the association among SLC2As expression and TME, Stemness score, clinical characteristics, immune subtypes, and drug sensitivity. We merged bioinformatics analysis techniques with up-to-date public databases. Additionally, SLC2As from the KOBAS database were subjected to enrichment analysis. Results: We discovered that SLC2As' gene expression differed significantly between normal tissues and many malignancies. A number of tumors from various databases demonstrate a relationship between prognosis and SLC2A family gene expression. For instance, SLC2A2 and SLC2A5 were associated with the overall survival (OS) of hepatocellular carcinoma. SLC2A1 was associated with the OS of lung adenocarcinoma and pancreatic adenocarcinoma. Moreover, the SLC2A family gene expression is significantly correlated with the pan-cancer stromal and immune scores, and the RNA and DNA stemness scores. Furthermore, we found that the majority of SLC2As had a strong correlation with the tumor stages in KIRC. The immunological subtypes and all members of the SLC2A gene family exhibited a substantial correlation. Moreover, pathways containing insulin resistance and adipocytokine signaling pathway may influence the progression of some cancers. Finally, there is a significant positive or negative connection between drug sensitivity and SLC2A1 expression. Conclusion: Our research highlights the significant promise of SLC2As as prognostic indicators and offers insightful approaches for upcoming exploration of SLC2As as putative therapeutic targets in malignancies.
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Sonic hedgehog (SHH) and heat shock protein 90ß (HSP90ß) have been implicated in nonalcoholic steatohepatitis (NASH) but their molecular mechanisms of action remain elusive. We find that HSP90ß is a key SHH downstream molecule for promoting NASH process. In hepatocytes, SHH reduces HSP90ß ubiquitylation through deubiquitylase USP31, thus preventing HSP90ß degradation and promoting hepatic lipid synthesis. HSP90ß significantly increases in NASH mouse model, leading to secretion of exosomes enriched with miR-28-5p. miR-28-5p directly targetes and decreases Rap1b levels, which in turn promotes NF-κB transcriptional activity in macrophages and stimulates the expression of inflammatory factors. Genetic deletion, pharmacological inhibition of the SHH-HSP90ß axis, or delivery of miR-28-5p to macrophages in the male mice liver, impairs NASH symptomatic development. Importantly, there is a markedly higher abundance of miR-28-5p in NASH patient sera. Taken together, the SHH-HSP90ß-miR-28-5p axis offers promising therapeutic targets against NASH, and serum miR-28-5p may serve as a NASH diagnostic biomarker.
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MicroRNAs , Hepatopatia Gordurosa não Alcoólica , Humanos , Masculino , Camundongos , Animais , Hepatopatia Gordurosa não Alcoólica/metabolismo , Proteínas Hedgehog/genética , Proteínas Hedgehog/metabolismo , Proteínas de Choque Térmico/metabolismo , Fígado/metabolismo , MicroRNAs/metabolismo , Camundongos Endogâmicos C57BLRESUMO
Tooth development is regulated by numerous genes and signaling pathways. Some studies suggest that mutations in these genes may be associated with several cancer types. However, the tooth agenesis mutated genes role in the prognosis and their clinical therapeutic potentials in pan-cancer have not been elaborately explored. Moreover, the intrinsic correlation between tooth agenesis and cancers also needs to be further verified. We preliminarily analyzed expression levels and prognostic values of causative genes of tooth agenesis, and explored the correlation between the expression of tooth agenesis mutated genes and TME, Stemness score, clinical characteristic, immune subtype, and drug sensitivity in pan-cancer, which based on updated public databases and integrated some bioinformatics analysis methods. In addition, we conducted the enrichment analysis of tooth agenesis mutant genes from KOBAS database. We observed that TA mutant genes had significant gene expression differences in multiple cancer types compared with normal tissues. The expression of causative genes of TA is associated with the prognosis in several cancers from different databases. For example, AXIN2 and MSX1 were correlated to the overall survival (OS) of uterine corpus endometrial carcinoma. PAX9 and TP63 were related to OS of lung squamous cell carcinoma. And TP63 was associated with OS in breast invasive carcinoma and pancreatic adenocarcinoma. Furthermore, the expression of TA mutant genes also has a significant correlation with stromal and immune scores, and RNA stemness score and DNA stemness score in pan-cancer. Besides, we observed that all causative genes of TA were significantly correlated with immune subtypes. Moreover, KEGG pathway analysis showed that causative genes of TA were associated with the development and progression of breast cancer, basal cell carcinoma, gastric cancer, and hepatocellular carcinoma. Finally, AXIN2 expression has a significantly positive or negative correlation with drug sensitivity. Our study indicates the great potential of TA mutant genes as biomarkers for prognosis and provides valuable strategies for further investigation of TA mutant genes as potential therapeutic targets in cancers. Our study can further verify that there may be an intrinsic correlation between tooth agenesis and the occurrence of multiple cancers.
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Adenocarcinoma , Neoplasias Pancreáticas , Humanos , MutaçãoRESUMO
It is discovered that activated caspase-3 tends to induce apoptosis in gasdermin E (GSDME)-deficient cells, but pyroptosis in GSDME-sufficient cells. The high GSDME expression and apoptosis resistance of pancreatic ductal adenocarcinoma (PDAC) cells shed light on another attractive strategy for PDAC treatment by promoting pyroptosis. Here we report a hGLuc-hGSDME-PCA system for high-throughput screening of potential GSDME activators against PDAC. This screening system neatly quantifies the oligomerization of GSDME-N to characterize whether pyroptosis occurs under the stimulation of chemotherapy drugs. Based on this system, ponatinib and perifosine are screened out from the FDA-approved anti-cancer drug library containing 106 compounds. Concretely, they exhibit the most potent luminescent activity and cause drastic pyroptosis in PDAC cells. Further, we demonstrate that perifosine suppresses pancreatic cancer by promoting pyroptosis via caspase-3/GSDME pathway both in vitro and in vivo. Collectively, this study reveals the great significance of hGLuc-hGSDME-PCA in identifying compounds triggering GSDME-dependent pyroptosis and developing promising therapeutic agents for PDAC.
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To investigate the inhibitory mechanism of the KIF3A gene on nasopharyngeal carcinoma (NPC) tumor stem cells. Set up a blank control group (BCG), NPC group, and KIF3A silence (si-KIF3A) group. The BCG cells were nasopharyngeal normal epithelial cell line NP69, without any treatment, and were cultured routinely; The NPC group cells are human NPC cell line CNE2 cells, which are not subjected to any treatment and are cultured routinely; si-KIF3A group cells were cultured in the offspring of human NPC cell line CNE2 infected with Lentivirus knockdown KIF3A gene. CCK8 was used to detect the cell proliferation ability, Western blot and qPCR were used to detect protein and related mRNA expression, while cell migration and invasion were detected using Transwell. The KIF3A protein and mRNA in the NPC group were higher than those in the BCG (P<0.05), while those in the si-KIF3A group cells were lower compared to BCG cells (P<0.05). The cell proliferation, migration and invasion activity in the si-KIF3A group were reduced than those in BCG (P<0.05). Si-KIF3A group cells HIF-1, NF-κB was reduced than that of BCG (P<0.05). The expression level of HIF-1, NF-κB protein in si-KIF3A group cells was reduced compared to BCG cells (P<0.05). Knocking down the KIF3A gene can reduce the vitality of NPC stem cells, and inhibit the malignant phenotype of NPC stem cells, via inhibiting HIF-1 and NF-κB expression.
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NF-kappa B , Neoplasias Nasofaríngeas , Humanos , Cinesinas/genética , Carcinoma Nasofaríngeo/genética , Neoplasias Nasofaríngeas/genética , Células-Tronco Neoplásicas , NF-kappa B/genética , RNA Mensageiro/genéticaRESUMO
In real world industrial applications, the working environment of a bearing varies with time, and some unexpected vibration noises from other equipment are inevitable. In order to improve the anti-noise performance of neural networks, a new prediction model and a multi-channel sample generation method are proposed to address the above problem. First, we proposed a multi-channel sample representation method based on the envelope time-frequency spectrum of a different channel and subsequent three-dimensional filtering to extract the fault features of samples. Second, we proposed a multi-channel data fusion neural network (MCFNN) for bearing fault discrimination, where the dropout technique is used in the training process based on a dataset with a wide rotation speed and various loads. In a noise-free environment, our experimental results demonstrated that the proposed method can reach a higher fault classification of 99.00%. In a noisy environment, the experimental results show that for the signal-to-noise ratio (SNR) of 0 dB, the fault classification averaged 11.80% higher than other methods and 32.89% higher under a SNR of -4 dB.
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The establishment of mathematical models to predict the diffusion coefficients of gas and liquid systems have important theoretical significance and practical value. In this work, based on the previously proposed diffusion coefficient model DLV, the distribution and influencing factors of the model parameters characteristic length (L) and diffusion velocity (V) were further investigated using molecular dynamics simulations. The statistical analysis of L and V for 10 gas systems and 10 liquid systems was presented in the paper. New distribution functions were established to describe the probability distributions of molecular motion L and V. The mean values of the correlation coefficients were 0.98 and 0.99, respectively. Meanwhile, the effects of molecular molar mass and system temperature on the molecular diffusion coefficients were discussed. The results show that the effect of molecular molar mass on the diffusion coefficient mainly affects the molecular motion L, and the effect of system temperature on the diffusion coefficient mainly affects V. For the gas system, the average relative deviation of DLV and DMSD is 10.73% and that of DLV and experimental value is 12.63%; for the solution system, the average relative deviation of DLV and DMSD is 12.93% and that of DLV and experimental value is 18.86%, which indicates the accuracy of the new model results. The new model reveals the potential mechanism of molecular motion and provides a theoretical basis for further study of the diffusion process.
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Pancreatic cancer is highly aggressive and lethal, and treatment options for it are limited. Gasdermin E (GSDME) is highly expressed in pancreatic cancer and can induce pyroptosis. In this type of programmed cell death, cells swell and emit large gas bubbles through their plasma membranes. Hence, GSDME induction is potentially an efficacious therapeutic approach against pancreatic cancer. In the present study, we found that the steroidal saponins polyphyllin I (PPI), collettiside III (CCRIS), and paris saponin V (PSV) significantly inhibited PANC-1, AsPC-1, and BxPC-3 cell proliferation. PPI/CCRIS/PSV altered the morphology of PANC-1 cells and induced the release of lactate dehydrogenase (LDH) from them. Therefore, these three constituents caused PANC-1 cells to undergo pyroptosis. This conclusion was confirmed by propidium iodide (PI) staining and flow cytometry assays. The present work also revealed that PPI/CCRIS/PSV induced pyroptosis via GSDME rather than gasdermin D (GSDMD). Whereas PPI/CCRIS/PSV induced caspase-3 to cleave GSDME, it had no such effect on GSDMD. We also established a PANC-1 xenograft tumor model in BALB/c nude mice and administered CCRIS to them as this compound demonstrated the most substantial pyroptotic effect in the in vitro experiments. This treatment significantly inhibited tumor growth in the mice by activating GSDME-dependent pyroptosis. This research demonstrates demonstrate that pyroptosis induction by PPI/CCRIS/PSV has important implications in basic science and clinical medicine. Future investigations should endeavor to determine the benefits and risks associated with the administration of these steroidal saponins as anti-PDAC therapy.
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Neoplasias Pancreáticas , Piroptose , Humanos , Animais , Camundongos , Camundongos Nus , Gasderminas , Morte Celular , Modelos Animais de Doenças , Neoplasias Pancreáticas/tratamento farmacológico , Caspase 3/metabolismo , Neoplasias PancreáticasRESUMO
ETHNOPHARMACOLOGICAL RELEVANCE: Qing-Zhi-Tiao-Gan-Tang or Qing-Zhi-Tiao-Gan Decoction (QZTGT) is based on the compatibility theory of traditional Chinese medicine (TCM), that is a combination of three classical formulae for the treatment of nonalcoholic fatty liver disease (NAFLD). Its pharmacodynamic material basis is made up of quinones, flavanones, and terpenoids. AIM OF THE STUDY: This study aimed to look for a promising recipe for treating nonalcoholic steatohepatitis (NASH), a more advanced form of NAFLD, and to use a transcriptome-based multi-scale network pharmacological platform (TMNP) to find its therapy targets. MATERIALS AND METHODS: A classical dietary model of NASH was established using MCD (Methionine- and choline-deficient) diet-fed mice. Liver coefficients like ALT, AST, serum TC, and TG levels were tested following QZTGT administration. A transcriptome-based multi-scale network pharmacological platform (TMNP) was used to further analyze the liver gene expression profile. RESULTS: The composition of QZTGT was analyzed by HPLC-Q-TOF/MS, a total of 89 compounds were separated and detected and 31 of them were found in rat plasma. QZTGT improved liver morphology, inflammation and fibrosis in a classical NASH model. Transcriptomic analysis of liver samples from NASH animal model revealed that QZTGT was able to correct gene expression. We used transcriptome-based multi-scale network pharmacological platform (TMNP) to predicted molecular pathways regulated by QZTGT to improve NASH. Further validation indicated that "fatty acid degradation", "bile secretion" and "steroid biosynthesis" pathways were involved in the improvement of NASH phenotype by QZTGT. CONCLUSIONS: Using HPLC-Q-TOF/MS, the compound composition of QZTGT, a Traditional Chinese prescription, was separated, analyzed and identified systematically. QZTGT mitigated NASH symptoms in a classical dietary model of NASH. Transcriptomic and network pharmacology analysis predicted the potential QZTGT regulated pathways. These pathways could be used as therapeutic targets for NASH.
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Hepatopatia Gordurosa não Alcoólica , Ratos , Camundongos , Animais , Hepatopatia Gordurosa não Alcoólica/tratamento farmacológico , Hepatopatia Gordurosa não Alcoólica/genética , Hepatopatia Gordurosa não Alcoólica/metabolismo , Fígado/metabolismo , Cirrose Hepática/tratamento farmacológico , Colina , Dieta , Camundongos Endogâmicos C57BL , Modelos Animais de DoençasRESUMO
In order to prepare nano-TbF3 coating with high quality on the surface of Nd-Fe-B magnets by electrophoretic deposition (EPD) more efficiently, Mg2+ and Cu2+ charging agents are introduced into the electrophoretic suspension and the influence on the electrophoretic deposition is systematically investigated. The results show that the addition of Mg2+ and Cu2+ charging agents can improve the electrophoretic deposition efficiency and coating adhesion of nano-TbF3 powders on sintered Nd-Fe-B magnets. The EPD efficiency increases by 116% with a relative content of Mg2+ as 3%, while it increases by 109% with a relative content of Cu2+ as 5%. Combining the Hamaker equation and diffusion electric double layer theory, the addition of Mg2+ and Cu2+ can change the zeta potential of charged particles, resulting in the improvement of EPD efficiency. The relative content of Mg2+ below 3% and Cu2+ below 5% can increase the thickness of the diffusion electric double layer, the excessive addition of a charging agent will compress the diffusion electric double layer, and thicker diffusion layer represents higher zeta potential. Furthermore, the addition of Mg2+ and Cu2+ charging agents greatly improves the coating adhesion, and the critical load for the cracking of the coating increases to 146.4 mN and 40.2 mN from 17.9 mN, respectively.
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Farrerol, a natural flavanone, promotes homologous recombination (HR) repair to improve genome-editing efficiency, but the specific protein that farrerol directly targets to regulate HR repair and the underlying molecular mechanisms have not been determined. Here, we find that the deubiquitinase UCHL3 is the direct target of farrerol. Mechanistically, farrerol enhanced the deubiquitinase activity of UCHL3 to promote RAD51 deubiquitination, thereby improving HR repair. Importantly, we find that embryos of somatic cell nuclear transfer (SCNT) exhibited defective HR repair, increased genomic instability and aneuploidy, and that the farrerol treatment post nuclear transfer enhances HR repair, restores transcriptional and epigenetic network, and promotes SCNT embryo development. Ablating UCHL3 significantly attenuates farrerol-mediated stimulation in HR and SCNT embryo development. In summary, we identify farrerol as an activator of the deubiquitinase UCHL3, highlighted the importance of HR and epigenetic changes in SCNT reprogramming and provide a feasible method to promote SCNT efficiency.
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Reparo do DNA , Técnicas de Transferência Nuclear , Reprogramação Celular/genética , Enzimas Desubiquitinantes/genética , Embrião de Mamíferos , Desenvolvimento Embrionário/genética , Epigênese Genética , AnimaisRESUMO
Accurate prediction of infinite dilution activity coefficient (γ∞) is essential for the calculation of phase equilibria, solubility, and related properties in molecular thermodynamics. Here, we propose a new model to accurately predict the value of γ∞. It is applicable to calculate γ∞ for compounds in aqueous solution at different temperatures. The model is based on the relationship of (∂p/∂x) T,xâ0 with γ∞ and temperature at low pressure. First, we introduce the new idea of using the group contribution method to estimate (∂p/∂x) T,xâ0 and then obtain the activity coefficient of a solute at infinite dilution in water based on the relationship between (∂p/∂x) T,xâ0 and γ∞. The accuracy of this model is verified using experimental data from 46 systems and more than 450 data points. The result shows that the total average relative deviation of the predicted values from the experimental values for training data is 4.73%. Besides, we test the applicability of the model using solutes that are not part of the training data set. The result shows that the model is satisfactory for the prediction of testing data. Compared with other models, the results prove that the developed model outperforms the UNIFAC model, the modified UNIFAC model, and previous predictive models for aqueous systems. The final equation with only simple arithmetic is more easily applied in engineering practices.
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Livestock manure with high moisture content is a challenge for management and further disposal. In this study, the organic chelating acid(EDTA)-assisted hydrothermal (EAHT) process was used to achieve dewatering, dry mass minimization, and volume reduction of dairy manure (DM). The hydrophobic modification of DM resulted in a 55% reduction in dry mass, and the specific resistance to filtration (SRF) showed a shift in dewatering performance from unfilterable to highly filterable. An investigation of the reaction mechanisms suggests that proteins and polysaccharides were released from the damaged extracellular polymeric substances (EPS) of the DM into effluent. The surface functional groups of the hydrochar were changed from hydrophilic to hydrophobic, which promotes the transformation of bound water to free water in the DM with enhanced dewatering performance. The obtained hydrochar at 17.5 mg/g EDTA dosage exhibited the highest calorific value (HHVdaf = 29.25 MJ/kg). The HHVdry of samples have little difference and approach that of anthracite coal (19.2-21.1 MJ/kg)After EAHT, the combustion safety of the hydrochar was improved, which is highly significant for its use as biofuel. The by-product effluent showed lower biological toxicity after EAHT than after HT. The findings of this study demonstrated that EAHT can be efficient in achieving DM reduction and energy recovery, which provides widespread agricultural and environmental application prospects.
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Esgotos , Eliminação de Resíduos Líquidos , Esgotos/química , Eliminação de Resíduos Líquidos/métodos , Esterco , Ácido Edético , Compostos Orgânicos , Água/químicaRESUMO
We propose a two-dimensional model of biochemical activation process, whereby self-propelling particles of finite correlation times are injected at the center of a circular cavity with constant rate equal to the inverse of their lifetime; activation is triggered when one such particle hits a receptor on the cavity boundary, modeled as a narrow pore. We numerically investigated this process by computing the particle mean-first exit times through the cavity pore as a function of the correlation and injection time constants. Due to the breach of the circular symmetry associated with the positioning of the receptor, the exit times may depend on the orientation of the self-propelling velocity at injection. Stochastic resetting appears to favor activation for large particle correlation times, where most of the underlying diffusion process occurs at the cavity boundary.
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Directed differentiation of human pluripotent stem cells (hPSCs) into functional ureteric and collecting duct (CD) epithelia is essential to kidney regenerative medicine. Here we describe highly efficient, serum-free differentiation of hPSCs into ureteric bud (UB) organoids and functional CD cells. The hPSCs are first induced into pronephric progenitor cells at 90% efficiency and then aggregated into spheres with a molecular signature similar to the nephric duct. In a three-dimensional matrix, the spheres form UB organoids that exhibit branching morphogenesis similar to the fetal UB and correct distal tip localization of RET expression. Organoid-derived cells incorporate into the UB tips of the progenitor niche in chimeric fetal kidney explant culture. At later stages, the UB organoids differentiate into CD organoids, which contain >95% CD cell types as estimated by single-cell RNA sequencing. The CD epithelia demonstrate renal electrophysiologic functions, with ENaC-mediated vectorial sodium transport by principal cells and V-type ATPase proton pump activity by FOXI1-induced intercalated cells.
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Células-Tronco Pluripotentes , Ureter , Humanos , Rim , Ureter/metabolismo , Diferenciação Celular , Organoides , Morfogênese , Fatores de Transcrição Forkhead/metabolismoRESUMO
Heat shock protein 90ß (Hsp90ß, encoded by Hsp90ab1 gene) is the most abundant proteins in the cells and contributes to variety of biological processes including metabolism, cell growth and neural functions. However, genetic evidences showing Hsp90ß in vivo functions using tissue specific knockout mice are still lacking. Here, we showed that Hsp90ß exerted paralogue-specific role in osteoclastogenesis. Using myeloid-specific Hsp90ab1 knockout mice, we provided the first genetic evidence showing the in vivo function of Hsp90ß. Hsp90ß binds to Ikkß and reduces its ubiquitylation and proteasomal degradation, thus leading to activated NF-κB signaling. Meanwhile, Hsp90ß increases cholesterol biosynthesis by activating Srebp2. Both pathways promote osteoclastogenic genes expression. Genetic deletion of Hsp90ab1 in osteoclast or pharmacological inhibition of Hsp90ß alleviates bone loss in ovariectomy-induced mice. Therefore, Hsp90ß is a promising druggable target for the treatment of osteoporosis.
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NF-kappa B , Osteogênese , Animais , Feminino , Camundongos , Colesterol/metabolismo , Camundongos Endogâmicos C57BL , NF-kappa B/metabolismo , Osteoclastos/metabolismo , Osteogênese/genética , Ligante RANK/metabolismo , Transdução de SinaisRESUMO
Background: Serine protease inhibitor E (SERPINE) family genes participate in the tumor growth, cancer cell survival and metastasis. However, the SERPINE family members role in the prognosis and their clinical therapeutic potentials in various human cancer types have not been elaborately explored. Methods: We preliminarily analyzed expression levels and prognostic values of SERPINE family genes, and investigated the correlation between SERPINEs expression and tumor microenvironment (TME), Stemness score, clinical characteristic, immune infiltration, tumor mutational burden (TMB), immune subtype, and drug sensitivity in pan-cancer, which based on updated public databases and integrated some bioinformatics analysis methods. In addition, we conducted the enrichment analysis of SERPINEs from DAVID and KOBAS databases. Results: SERPINE1, SERPINE2, and SERPINE3 expression were upregulated in nine cancers, twelve cancers, and six cancers, respectively. The expression of SERPINE family genes was associated with the prognosis in several cancers from The Cancer Genome Atlas (TCGA). Furthermore, SERPINE family genes expression also had a significant relation to stromal and immune scores, and RNA stemness score and DNA stemness score in pan-cancer. SERPINE1 and SERPINE2 expression significantly increased in tumor advanced stage in colon adenocarcinoma (COAD). Results showed that SERPINE1 and SERPINE2 expression were negatively related with B cells and Monocytes, respectively. SERPINE2 expression had a significantly positive relation with B cells and Macrophages. In terms of TMB, SERPINE1, SERPINE2, and SERPINE3 were found to associated with TMB in seven cancers, fourteen cancers, and four cancers, respectively. Moreover, all SERPINE gene family members were significantly correlated with immune subtypes. SERPINE1 expression had a significantly positive or negative correlation with drug sensitivity. Conclusion: The study indicated the great potential of SERPINE family genes as biomarkers for prognosis and provided valuable strategies for further investigation of SERPINE family genes as potential targets in cancer.
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The functional tight junctions' integrity plays an important role in liver physiology. A variety of liver diseases have been associated with the perturbation of tight junctions. Herein, we showed that the lower expression of α5 integrin in hepatocytes in patients with liver cirrhosis is associated with matrix deposition in the space of Disse. Selective silencing of α5 integrin in hepatocytes compromised the ultrastructure of tight junctions by downregulating claudin 1 in an SRC (proto-oncogene, non-receptor tyrosine kinase) signaling-dependent manner. α5 integrin signaling induced SRC-TET-mediated changes in 5-hydroxymethylcytosine and 5-methylcytosine levels in hepatocytes in vitro and in vivo. hMeDIP sequencing showed intergenic hypohydroxymethylation of the claudin 1 gene in hepatocytes after α5 integrin silencing in mice. Therefore, understanding the mechanisms regulating hepatic tight junction integrity in which α5 integrin-SRC signaling and epigenetic modifications cooperate might help advance the development of useful diagnostics and therapeutic approaches for liver disease.
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Pulp and paper mill effluent is rich in recalcitrant and toxic pollutants compounds and causes pollution. To find an efficient biocatalyst for the treatment of effluent, a dye-decolorizing peroxidase from Bacillus amyloliquefaciens MN-13, which is capable of degrading lignin, was used for the bioremediation of paper and pulp mill effluent. The dye-decolorizing peroxidase from Bacillus amyloliquefaciens (BaDyP) exhibited high-redox potential to 2, 2'-azinobis (3-ethylbenzothiazoline- 6-sulfonic acid) ammonium salt (ABTS), veratryl alcohol, Mn2+, reactive blue 19, reactive black 5 and lignin dimer guaiacylglycerol-beta-guaiacyl ether (GGE). When GGE was used as substrate, BaDyP broke ß-O-4 bond of GGE and then oxidize Cα to generate vanillin. The Km values for ABTS and veratryl alcohol were 2.19 mm and 0.07 mm, respectively. The Vmax for ABTS and veratryl alcohol were 1.8 mm/min and 14.12 mm/min, respectively. The BaDyP-mediated treatment of pulp and paper mill effluent led to significant reduction of chemical oxygen demand (COD) and color. When 5% (v/v) of effluent was treated with BaDyP for 12 h at 30°C and pH 2, the removal of COD, color, and lignin was achieved at 82.7, 80.2, and 78.20%, respectively. In detoxification assay, the seeds of Vigna unguiculata grown in treated effluent showed a significant increase in germination rate from 66.7% (untreated effluent) to 90%, and in radicle length from 0.68 cm (untreated effluent) to 1.26 cm, respectively. In the meanwhile, the inhibition of Escherichia coli and Bacillus subtilis by the treated effluent reduced significantly as compared to untreated effluent, indicating high detoxification performance of BaDyP for the treatment of pulp and paper mill effluent. The findings suggest that BaDyP is a potential catalyst for bioremediation of pulp and paper mill effluent, as it is effective in substantial lowering of pollutants load as well as reduces COD, color, and toxicity of effluent.