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1.
Microb Physiol ; 34(1): 170-181, 2024.
Artigo em Inglês | MEDLINE | ID: mdl-38955164

RESUMO

INTRODUCTION: The global poultry industry produces millions of tons of waste feathers every year, which can be bio-degraded to make feed, fertilizer, and daily chemicals. However, feather bio-degradation is a complex process that is not yet fully understood. This results in low degradation efficiency and difficulty in industrial applications. Omics-driven system biology research offers an effective solution to quickly and comprehensively understand the molecularmechanisms involved in a metabolic pathway. METHODS: In the early stage of this process, feathers are hydrolyzed into water-soluble keratin monomers. In this study, we used high-throughput RNA-seq technology to analyze the genes involved in the internalization and degradation of keratin monomers in Stenotrophomonas maltophilia DHHJ strain cells. Moreover, we used Co-IP with LC-MS/MS technology to search for proteins that interact with recombinant keratin monomers. RESULTS: We discovered TonB transports and molecular chaperones associating with the keratin monomer, which may play a crucial role in the transmembrane transport of keratin. Meanwhile, multiple proteases belonging to distinct families were identified as binding partners of keratin monomers, among which ATPases associated with diverse cellular activity (AAA+) family proteases are overrepresented. Four genes, including JJL50_15620, JJL50_17955 (TonB-dependent receptors), JJL50_03260 (ABC transporter ATP-binding protein), and JJL50_20035 (ABC transporter substrate-binding protein), were selected as representatives for determining their expressions under different culture conditions using qRT-PCR, and they were found to be upregulated in response to keratin degradation consistent with the data from RNA-seq and Co-IP. CONCLUSION: This study highlights the complexity of keratin biodegradation in S. maltophilia DHHJ, in which multiple pathways are involved such as protein folding, protein transport, and several protease systems. Our findings provide new insights into the mechanism of feather degradation.


Assuntos
Proteínas de Bactérias , Biodegradação Ambiental , Queratinas , Stenotrophomonas maltophilia , Stenotrophomonas maltophilia/metabolismo , Stenotrophomonas maltophilia/genética , Queratinas/metabolismo , Queratinas/genética , Animais , Proteínas de Bactérias/metabolismo , Proteínas de Bactérias/genética , Plumas/metabolismo , Plumas/microbiologia , Espectrometria de Massas em Tandem , Regulação Bacteriana da Expressão Gênica , Peptídeo Hidrolases/metabolismo , Peptídeo Hidrolases/genética
2.
Artigo em Inglês | MEDLINE | ID: mdl-38896367

RESUMO

Biodegradation effectiveness of S. maltophilia DHHJ is determined by its ability to attach to the hydrolyzed feather keratin monomers. This binding capacity can be influenced by many components in the culture medium. Keratin monomers from feathers or those produced by gene overexpression can induce keratinase production in S. maltophilia DHHJ, and several proteases lack the ability to degrade keratin fragments and cysteines. In this study, we co-incubated FITC-labelled keratin monomers with S. maltophilia DHHJ cells in the presence of BSA, DNA, ATP, and several metal ions, and measured fluorescence values and keratinase activity. BSA was found to compete with keratins for cell binding sites, resulting in less keratinase production. DNA did not interfere with cellular binding to keratins revealing unchanged keratinase level. ATP, along with metal ions, enhanced the cellular binding capacity to keratins and increased the production of keratinase by S. maltophilia DHHJ. Fragments of keratin monomers degraded by proteases reduced the ability of cells to bind to keratin and affected enzyme production. Cysteine, a characteristic amino acid of feather keratin, did not have an effect on cellular binding to keratin monomer or on keratinase production. This study will facilitate the tweaking of catalytic parameters to improve feather biodegradation by S. maltophilia DHHJ.

3.
N Biotechnol ; 76: 72-81, 2023 Sep 25.
Artigo em Inglês | MEDLINE | ID: mdl-37182820

RESUMO

The development of bacterial cellulose (BC) industrialization has been seriously affected by its production. Mannose/mannan is an essential component in many biomass resources, but Komagataeibacter xylinus uses mannose in an ineffective way, resulting in waste. The aim of this study was to construct recombinant bacteria to use mannose-rich biomass efficiently as an alternative and inexpensive carbon source in place of the more commonly used glucose. This strategy aimed at modification of the mannose catabolic pathway via genetic engineering of K. xylinus ATCC 23770 strain through expression of mannose kinase and phosphomannose isomerase genes from the Escherichia coli K-12 strain. Recombinant and wild-type strains were cultured under conditions of glucose and mannose respectively as sole carbon sources. The fermentation process and physicochemical properties of BC were investigated in detail in the strains cultured in mannose media. The comparison showed that with mannose as the sole carbon source, the BC yield from the recombinant strain increased by 84%, and its tensile strength and elongation were increased 1.7 fold, while Young's modulus was increased 1.3 fold. The results demonstrated a successful improvement in BC yield and properties on mannose-based medium compared with the wild-type strain. Thus, the strategy of modifying the mannose catabolic pathway of K. xylinus is feasible and has significant potential in reducing the production costs for industrial production of BC from mannose-rich biomass.


Assuntos
Escherichia coli K12 , Gluconacetobacter xylinus , Manose/metabolismo , Celulose/química , Escherichia coli K12/metabolismo , Gluconacetobacter xylinus/genética , Gluconacetobacter xylinus/metabolismo , Glucose/metabolismo , Carbono/metabolismo
4.
Discov Med ; 33(169): 55-67, 2022.
Artigo em Inglês | MEDLINE | ID: mdl-36482736

RESUMO

Glycogen synthase kinase 3 beta (GSK3ß) has emerged as a therapeutic target for breast cancer. As inhibitors of GSK-3ß, 1,2,4-thiadiazole-3,5-dione (TDZD) family members have been reported as potential candidates for cancer treatment. In this study, the anticancer effects of ethiadin (ETD-174), one of the chemical synthesis compounds of TDZD, were investigated in MCF-7 human breast cancer cells. MCF-7 cells incubated with different doses of ETD-174 for different time periods. CCK-8 assays were carried out to test the effect of ETD-174 on the proliferation of MCF-7 cells. The occurrence of apoptosis was detected by Hoechst 33258 staining and flow cytometry. ETD-174 on cell migration and colony formation were examined by wound healing experiments and soft agar assays. Relative protein expressions were conducted with immunoblot assay. ETD-174 demonstrated a higher degree of cytotoxicity in MCF-7 cells. Topical morphological changes of apoptotic body formation after ETD-174 treatment were observed. Meanwhile, apoptosis was elicited by ETD-174. Also, ETD-174 could inhibit the migration and clonality of MCF-7 cells. After the treatment with ETD-174, the level of phosphorylation of GSK3ßSer9 in MCF-7 cells increased significantly, and the enzymatic activity of GSK3ß decreased. ETD-174 is likely to have an effective suppressor role in breast cancer, suggesting that pharmacological inhibition of GSK3ß as a novel treatment modality for breast cancer should warrant further investigation.


Assuntos
Neoplasias da Mama , Humanos , Feminino , Células MCF-7 , Glicogênio Sintase Quinase 3 beta , Neoplasias da Mama/tratamento farmacológico , Apoptose
5.
Front Oncol ; 12: 963483, 2022.
Artigo em Inglês | MEDLINE | ID: mdl-36313709

RESUMO

Renal cell carcinoma (RCC), as one of the most common urological malignancies, has many histologic and molecular subtypes, among which clear cell renal cell carcinoma (ccRCC) is one of the most common causes of tumor-related deaths. However, the molecular mechanism of ccRCC remains unclear. In order to identify the candidate genes that may exist in the occurrence and development of ccRCC, microarray datasets GSE6344, GSE16441, GSE36895, GSE53757 and GSE76351 had been downloaded from Gene Expression Omnibus (GEO) database. Apart from that, the differentially expressed genes (DEGs) were screened through Bioinformatics & Evolutionary Genomics. In addition, the protein-protein interaction network (PPI) was constructed, and the module analysis was performed using STRING and Cytoscape. By virtue of DAVID online database, GO/KEGG enrichment analysis of DEGs was performed. Consequently, a total of 118 DEGs were screened, including 24 up-regulated genes and 94 down-regulated genes. The plug-in MCODE of Cytoscape was adopted to analyze the most significant modules of DEGs. What's more, the genes with degree greater than 10 in DEGs were selected as the hub genes. The overall survival (OS) and disease progression free survival (DFS) of 9 hub genes were analyzed through GEPIA2 online platform. As shown by the survival analysis, SLC34A1, SLC12A3, SLC12A1, PLG, and ENO2 were closely related to the OS of ccRCC, whereas SLC34A1 and LOX were closely related to DFS. Among 11 SLC members, 6 SLC members were highly expressed in non-cancerous tissues (SLC5A2, SLC12A1, SLC12A3, SLC34A1, SLC34A2, SLC34A3). Besides, SLC12A5 and SLC12A7 were highly expressed in ccRCC. Furthermore, SLC12A1-A7, SLC34A1 and SLC34A3 were closely related to OS, whereas SLC12A2/A4/A6/A7 and SLC34A1/A3 were closely related to DFS. In addition, 5 algorithms were used to analyze hub genes, the overlapping genes were AQP2 and KCNJ1. To sum up, hub gene can help us understand the molecular mechanism of the occurrence and development of ccRCC, thereby providing a theoretical basis for the diagnosis and targeted therapy of ccRCC.

6.
Biomacromolecules ; 22(12): 4988-4999, 2021 12 13.
Artigo em Inglês | MEDLINE | ID: mdl-34724615

RESUMO

Autograft is currently the gold standard in the clinical treatment of peripheral nerve injury (PNI), which, however, is limited by the availability of a donor nerve and secondary injuries. Nerve guidance conduits (NGC) provide a suitable microenvironment to promote the regeneration of injured nerves, which could be the substitutes for autografts. In this study, nerve growth factor (NGF) encapsulated chitosan nanoparticles (CSNPs) were first constructed in situ in an oxidized bacterial cellulose (OBC) conduit using the ion gel method after the introduction of a CS/NGF solution under pressure to enable a sustainable release of NGF. A novel NGF@CSNPs/OBC nanocomposite with antibacterial activity, biodegradability, and porous microstructure was successfully developed. In vitro experiments showed that the nanocomposite promoted the adhesion and proliferation of Schwann cells. When the nanocomposite was applied as NGC to repair the sciatic nerve defect of rats, a successful repair of the 10 mm nerve defect was observed after 4 weeks. At week 9, the diameter, morphology, histology, and functional recovery of the regenerated nerve was comparable to the autografts, indicating that the NGC effectively promoted the regeneration and function recovery of the nerve. In summary, the NGF@CSNPs/OBC as a novel NGC provides great potential in the treatment of PNI.


Assuntos
Quitosana , Nanopartículas , Fator de Crescimento Neural , Regeneração Nervosa , Animais , Quitosana/química , Nanopartículas/química , Fator de Crescimento Neural/farmacologia , Ratos , Nervo Isquiático/lesões , Nervo Isquiático/fisiologia
7.
ACS Biomater Sci Eng ; 7(8): 3933-3946, 2021 08 09.
Artigo em Inglês | MEDLINE | ID: mdl-34296596

RESUMO

High moisture permeability, excellent mechanical properties in a wet state, high water-holding capability, and high exudate absorption make bacterial nanocellulose (BNC) a favorable candidate for biomedical device production, especially wound dressings. The lack of antibacterial activity and healing-promoting ability are the main drawbacks that limit its wide application. Pullulan (Pul) is a nontoxic polymer that can promote wound healing. Zinc oxide nanoparticles (ZnO-NPs) are well-known as a safe antibacterial agent. In this study, aminoalkylsilane was chemically grafted on a BNC membrane (A-g-BNC) and used as a bridge to combine BNC with Pul-ZnO-NPs hybrid electrospun nanofibers. FTIR results confirmed the successful production of A-g-BNC/Pul-ZnO. The obtained dressing demonstrated blood clotting performance better than that of BNC. The dressing showed an ability to release ZnO, and its antibacterial activity was up to 5 log values higher than that of BNC. The cytotoxicity of the dressing toward L929 fibroblast cells clearly showed safety due to the proliferation of fibroblast cells. The animal test in a rat model indicated faster healing and re-epithelialization, small blood vessel formation, and collagen synthesis in the wounds covered by A-g-BNC/Pul-ZnO. The new functional dressing, fabricated with a cost-effective and easy method, not only showed excellent antibacterial activity but could also accelerate wound healing.


Assuntos
Nanofibras , Nanopartículas , Óxido de Zinco , Animais , Bandagens , Glucanos , Ratos
8.
Biomater Sci ; 9(11): 4169-4177, 2021 Jun 04.
Artigo em Inglês | MEDLINE | ID: mdl-33977985

RESUMO

Injectable hydrogels hold promise in biomedical applications due to their noninvasive administration procedure and capacity enabling the filling of irregularly shaped defects. Protein-based hydrogels provide features including good biocompatibility and inherent biofunction. However, challenges still remain to develop a protein-based injectable hydrogel in a convenient way due to the limited active groups in proteins. Keratins are a group of cysteine-rich structural proteins found abundantly in skin and skin appendages. In this work, we utilized keratin and the Au(iii) salt to develop an injectable hydrogel based on the dynamic exchange between disulfide bonds (S-S) and gold(i)-thiolates (Au-S). Such a hydrogel could be prepared at the physiological pH and applied as an injectable hydrogel for biomedical applications including hemostatic and wound dressing materials. Our findings demonstrated that this keratin injectable hydrogel showed a good hemostatic effect in both tail amputation and liver injury models. Moreover, it was proved efficient as a drug loading carrier, and the deferoxamine-loaded hydrogel showed a desirable wound healing effect in a full-thickness excision wound model.


Assuntos
Hemostáticos , Hidrogéis , Bandagens , Queratinas , Cicatrização
9.
Carbohydr Polym ; 264: 118002, 2021 Jul 15.
Artigo em Inglês | MEDLINE | ID: mdl-33910735

RESUMO

Incorporation of chitosan (CS) into Bacterial nanocellulose (BNC) matrix is of great interests in biomedical field due to the advantageous properties of each material. However, the conventional strategies result in poor composite effect with low efficiency. In this study, the three-dimensional fibrillar network of BNC was utilized as a template for the first time to homogeneously disperse CS to form nanoparticles (CSNPs) in BNC matrix via ionic gelation method, to develop chitosan nanoparticles-embedded bacterial nanocellulose (CSNPs-BNC) composites. This composite method is simple and efficient, without introducing dispersants and crosslinking agents, while retaining the mechanical properties and native 3D network structure of BNC. The CSNPs-BNC composites had excellent antibacterial activity to support potential clinical application. The CSNPs-BNC composites could promote the adhesion and proliferation of Schwann cells, and demonstrate good biocompatibility both in vitro and in vivo. The results indicated that CSNPs-BNC can provide a promising candidate for biomedical applications.


Assuntos
Bactérias/química , Celulose/química , Quitosana/química , Nanopartículas/química , Animais , Antibacterianos/química , Antibacterianos/farmacologia , Adesão Celular/efeitos dos fármacos , Proliferação de Células/efeitos dos fármacos , Celulose/farmacologia , Quitosana/farmacologia , Módulo de Elasticidade , Nanocompostos/química , Tamanho da Partícula , Próteses e Implantes , Ratos , Células de Schwann , Resistência à Tração
10.
Oncol Rep ; 45(6)2021 06.
Artigo em Inglês | MEDLINE | ID: mdl-33907836

RESUMO

Renal cell carcinoma (RCC) is a lethal urologic tumor commonly seen in men that best responds to partial nephrectomy. An enhanced understanding of the molecular pathogenesis of RCC can broaden treatment options and tumor prevention strategies. Sirtuin 1 (SIRT1) is a NAD+­dependent deacetylase that regulates several bioactive substances, and the present study aimed to identify the role of SIRT1/AMP­activated protein kinase (AMPK) signaling in RCC progression. SIRT1 expression was detected in 100 patients with RCC using tissue microarray immunohistochemistry. SIRT1­knockdown and overexpression were performed via RNA interference and plasmid transfection. Inhibition of AMPK was used for the phenotypic rescue assays to verify whether AMPK was a downstream target of SIRT1. Reverse transcription­quantitative PCR was performed to verify transfection efficiency. Transwell, MTT and flow cytometry apoptosis assays were performed to evaluate the migration, invasion, proliferation and early apoptosis level of RCC cells. SIRT1 and AMPK protein expression in human RCC tissues and cell lines (786­O and ACHN) was detected using western blotting and immunofluorescence staining. The current results, combined with data from The Cancer Genome Atlas database, revealed that SIRT1 expression in RCC tissues was downregulated compared with in adjacent normal tissues. Additionally, high SIRT1 expression was associated with an improved prognosis in patients with RCC. Overexpression of SIRT1 inhibited the proliferation, migration and invasion of RCC cell lines and induced apoptosis, while inhibition of SIRT1 expression had the opposite effects. Further experiments indicated that SIRT1 may serve an anticancer role by upregulating the expression levels of downstream AMPK, thus revealing a potential therapeutic target for RCC.


Assuntos
Proteínas Quinases Ativadas por AMP/metabolismo , Carcinoma de Células Renais/genética , Regulação Neoplásica da Expressão Gênica , Neoplasias Renais/genética , Sirtuína 1/metabolismo , Adulto , Idoso , Idoso de 80 Anos ou mais , Carcinoma de Células Renais/mortalidade , Carcinoma de Células Renais/patologia , Linhagem Celular Tumoral , Movimento Celular/genética , Proliferação de Células/genética , Feminino , Técnicas de Silenciamento de Genes , Humanos , Rim/patologia , Rim/cirurgia , Neoplasias Renais/mortalidade , Neoplasias Renais/patologia , Masculino , Pessoa de Meia-Idade , Invasividade Neoplásica/genética , Nefrectomia , Prognóstico , Transdução de Sinais/genética , Sirtuína 1/genética , Regulação para Cima
11.
Acta Biomater ; 125: 208-218, 2021 04 15.
Artigo em Inglês | MEDLINE | ID: mdl-33662598

RESUMO

The development of protein-based in situ forming hydrogel remains a big challenge due to the limited chemical groups in proteins. Keratins are a group of cysteine-rich structural protein found abundant in skin and skin appendant. Recently, our lab has established a disulfide shuffling strategy to prepare keratin hydrogels via oxygen (O2) oxidation. However, such hydrogel still needed to be molded in advance. In this work, inspired by the fact that glucose commonly exists in body fluids, a glucose-triggered in situ forming keratin hydrogel was developed based on the disulfide shuffling strategy via a higher oxidation force of hydrogen peroxide (H2O2). The hydrogel precursor solution consisted of keratin, cysteine and glucose oxidase (GOD), which could generate H2O2 in an indirect and mild way via GOD-catalyzed oxidation of glucose in body fluids. Our findings demonstrated that the GOD-catalyzed oxidation method not only shortened the gelation time but improved the mechanical strength of the hydrogel by comparison with O2 oxidation and direct addition of H2O2 solution methods, and realized in situ gelation within 3 min on a full-thickness wound bed in normal mice. Moreover, the in situ forming keratin hydrogel was applied as a drug depot for wound repair, and the deferoxamine-loaded one accelerated healing in the full-thickness wounds of streptozotocin-induced diabetic rats, notably by promoting angiogenesis and neovascularization in wounds. STATEMENT OF SIGNIFICANCE: Studies show that keratin hydrogels possess tissue regeneration capacity, especially in skin wound repair. However, most of the reported keratin hydrogels needed to be molded in advance and cannot fit irregular wound shape. This work describes a glucose-triggered in situ forming keratin hydrogel via a disulfide shuffling strategy under the oxidation of hydrogen peroxide. Of note, the hydrogen peroxide was supplied indirectly by glucose oxidase-catalyzed oxidation of glucose in wound fluids, and this method needed no additional crosslinking agents or chemical modifications on keratins. Our findings showed that this hydrogel realized in situ gelation within 3 min on a full-thickness wound bed and enabled an injectable mode with good filling ability toward irregular wounds. Moreover, this hydrogel could be applied as a drug depot for the treatment of diabetic wounds.


Assuntos
Diabetes Mellitus Experimental , Hidrogéis , Queratinas/uso terapêutico , Cicatrização , Animais , Diabetes Mellitus Experimental/tratamento farmacológico , Glucose , Peróxido de Hidrogênio , Camundongos , Ratos
12.
Andrologia ; 52(3): e13533, 2020 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-32027043

RESUMO

There have been some conflicting claims whether larger prostate weight (PW) reduces the risk of positive surgical margins (PSMs). This study aims to examine the associations between PW and PSMs. PubMed, Web of Science and Cochrane library were systematically retrieved. Relative risks (RRs) and the corresponding 95% confidence intervals (CIs) were synthesised utilising random-effect models. Ultimately, 22 cohort studies met criteria were enrolled in this meta-analysis, of which 18 studies reporting the RR of the highest VS lowest category of PW yielded the combined RR of PSMs of 0.61 (95% CI 0.50-0.74). Subgroup analysis showed that geographic region and surgical modalities were considered as potential confounders of influence of PW on PSMs. The nonlinear dose-response relationship demonstrated that PSM risk decreased by 1% (RR = 0.99, 95% CI, 0.98-0.99) for every one gram increment in PW. This study suggests PW has a negative association with risk of PSMs, and having a appropriate PW is very important.


Assuntos
Margens de Excisão , Próstata/patologia , Prostatectomia , Neoplasias da Próstata/cirurgia , Humanos , Masculino , Tamanho do Órgão , Próstata/cirurgia , Neoplasias da Próstata/patologia
13.
Mol Med Rep ; 21(1): 329-337, 2020 01.
Artigo em Inglês | MEDLINE | ID: mdl-31939627

RESUMO

Previous studies have demonstrated that the expression of CARD10 is closely associated with the occurrence of tumors, and its role is mainly to promote tumor progression by activating the transcription factor NF­κB. However, the signaling pathway in renal cancer remains unclear. The objective of the present study was to investigate the ability of caspase recruitment domain 10 (CARD10) to regulate the NF­κB signaling pathway and promote the progression of renal cell carcinoma (RCC). Expression of CARD10 in ACHN, 786­O and HK­2 cells was evaluated via western blot analysis, as was the epidermal growth factor (EGF)­induced activation of NF­κB signaling pathway­related proteins in cells. The expression of CARD10 was inhibited by CARD10 short hairpin RNA transfection. Cell cycle analysis and MTT assays were used to evaluate cell proliferation. Cell apoptosis was analyzed via flow cytometry. The invasion of renal cell lines was detected via Transwell cell migration and invasion assays in vitro. The results showed that CARD10 expression was significantly higher in RCC cells than in normal renal tubular epithelial cells. CARD10 silencing inhibited the proliferation, invasion and migration of RCC cells. EGF stimulation upregulated the activation of the NF­κB pathway in RCC cells. Inhibition of CARD10 expression inhibited NF­κB activation in RCC cells. Taken together, these data suggested that CARD10 promotes the progression of renal cell carcinoma by regulating the NF­κB signaling pathway. Thus, this indicated that CARD10 may be a novel therapeutic target in RCC.


Assuntos
Proteínas Adaptadoras de Sinalização CARD/metabolismo , Carcinoma de Células Renais/metabolismo , Neoplasias Renais/metabolismo , NF-kappa B/metabolismo , Transdução de Sinais/genética , Apoptose/efeitos dos fármacos , Apoptose/genética , Proteínas Adaptadoras de Sinalização CARD/genética , Carcinoma de Células Renais/genética , Carcinoma de Células Renais/patologia , Ciclo Celular/efeitos dos fármacos , Ciclo Celular/genética , Linhagem Celular Tumoral , Movimento Celular/efeitos dos fármacos , Movimento Celular/genética , Proliferação de Células/efeitos dos fármacos , Proliferação de Células/genética , Fator de Crescimento Epidérmico/farmacologia , Regulação Neoplásica da Expressão Gênica , Inativação Gênica , Humanos , Neoplasias Renais/genética , Neoplasias Renais/patologia , RNA Interferente Pequeno , Transdução de Sinais/efeitos dos fármacos , Regulação para Cima
14.
Cell Chem Biol ; 26(10): 1417-1426.e5, 2019 Oct 17.
Artigo em Inglês | MEDLINE | ID: mdl-31402318

RESUMO

DEAD-box ATP-dependent helicases (DEAH/D) are a family of conserved genes predominantly involved in gene expression regulation and RNA processing. As its prototype, eIF4AI is an essential component of the protein translation initiation complex. Utilizing a screening system based on wild-type eIF4AI and its L243G mutant with a changed linker domain, we discovered an eIF4AI inhibitor, sanguinarine (SAN) and used it to study the catalytic mechanism of eIF4AI. Herein, we describe the crystal structure of the eIF4AI-inhibitor complex and demonstrate that the binding site displays certain specificity, which can provide the basis for drug design to target eIF4AI. We report that except for competitive inhibition SAN's possible mechanism of action involves interference with eIF4AI catalytic cycling process by hindering the formation of the closed conformation of eIF4AI. In addition, our results highlight a new targetable site on eIF4AI and confirm eIF4AI as a viable pharmacological target.


Assuntos
Benzofenantridinas/farmacologia , Fator de Iniciação 4A em Eucariotos/antagonistas & inibidores , Isoquinolinas/farmacologia , Animais , Benzofenantridinas/química , Biocatálise , Linhagem Celular , Relação Dose-Resposta a Droga , Fator de Iniciação 4A em Eucariotos/metabolismo , Feminino , Humanos , Isoquinolinas/química , Masculino , Camundongos , Modelos Moleculares , Conformação Molecular , Relação Estrutura-Atividade
15.
Expert Rev Anticancer Ther ; 19(7): 645-653, 2019 07.
Artigo em Inglês | MEDLINE | ID: mdl-31177855

RESUMO

Background: Qualitative and quantitative analysis of circulating cell-free DNA (cfDNA) is a potential detection method for bladder cancer. Many studies have focused on the reliability of these results, but the conclusions have not been consistent. Methods: We performed a diagnostic meta-analysis to investigate the diagnostic significance of serum and urine cfDNAs with tumor tissues as the standard control. We searched the MEDLINE, EMABASE, and Cochrane Central Controlled Trials Register (CCTR) databases until January 2019. Results: A total of 11 studies involving early and/or advanced bladder cancer were finally included. The overall diagnostic accuracy was measured as follows: pooled sensitivity and specifcity were 0.69 (95%CI: 0.67, 0.71) and 0.72 (95%CI: 0.70, 0.74). Pooled positive likelihood ratio and negative likelihood ratio were 3.10 (95%CI: 2.35, 4.07) and 0.41 (95%CI: 0.34, 0.49). Combined diagnostic odds ratio was 8.26 (95%CI: 5.64, 12.11). A high diagnostic accuracy was demonstrated by the summary receiver operating characteristic curve, with area under the curve of 0.80 (95%CI: 0.77, 0.83). Conclusions: CfDNA assay has high diagnostic value for the detection of bladder cancer. Larger sample studies are needed to further confirm our conclusions and to make this approach more sensitive and specific.


Assuntos
DNA Tumoral Circulante/análise , Neoplasias da Bexiga Urinária/diagnóstico , DNA Tumoral Circulante/sangue , DNA Tumoral Circulante/urina , Humanos , Reprodutibilidade dos Testes , Sensibilidade e Especificidade , Neoplasias da Bexiga Urinária/patologia
16.
J Colloid Interface Sci ; 544: 121-129, 2019 May 15.
Artigo em Inglês | MEDLINE | ID: mdl-30826530

RESUMO

Protein-based hydrogels that possess tunable properties have long been a challenge in tissue engineering. Keratin is a group of natural proteins derived from skin and skin appendant, and features a rich content of cysteine residue which exists in the form of disulfide bonds. Inspired by this, in this work, a simple disulfide shuffling strategy was utilized to develop keratin hydrogels by converting the intramolecular disulfide bonds into the intermolecular disulfide bonds. To achieve this, the intramolecular disulfide bonds were first cleaved by the reductive reagent such as cysteine, to liberate free thiol group, which formed intermolecular disulfide bonds through thiol oxidation. It was demonstrated that control of the cysteine level led to a tunable disulfide crosslinking density, and thus an altered network structure, gel degradation, and drug release rate. Also, this strategy enables good biocompatibility of the material owing to avoiding extra chemical crosslinkers in the preparation procedure. Moreover, this keratin hydrogel had redox-responsive capacity in both gel degradation and drug release due to the disulfide-bond based network structure, providing extensive applicability in tissue engineering and drug release.


Assuntos
Dissulfetos/química , Portadores de Fármacos/química , Hidrogéis/química , Queratinas/química , Alicerces Teciduais/química , Animais , Materiais Biocompatíveis/química , Linhagem Celular , Sobrevivência Celular/efeitos dos fármacos , Reagentes de Ligações Cruzadas/química , Cisteína/química , Liberação Controlada de Fármacos , Teste de Materiais/métodos , Camundongos , Camundongos Endogâmicos ICR , Estrutura Molecular , Oxirredução , Ratos , Reologia , Relação Estrutura-Atividade , Engenharia Tecidual/métodos
17.
Carbohydr Polym ; 115: 636-42, 2015 Jan 22.
Artigo em Inglês | MEDLINE | ID: mdl-25439942

RESUMO

In this work, a bacterial cellulose/polyacrylamide (BC/PAM) double network composite was prepared to act as the template for in situ synthesis of silver nanoparticles (AgNPs). Effects of reaction conditions of the BC/PAM composite were investigated on its microstructure, mechanical properties and thermal stabilities. Both the BC/PAM composite and pure BC were utilized to prepare the corresponding silver impregnated nanocomposites, i.e., BC/PAM-AgNPs and BC-AgNPs, by an environmental friendly method, UV irradiation. The influences of the templates were investigated on the AgNPs formation and the antibacterial activities of the nanocomposites by both the zone of inhibition and dynamic shake flask methods. It was shown that the BC/PAM composite displayed a denser microstructure and higher thermal stabilities than pure BC. The BC/PAM-AgNPs nanocomposite exhibited a bigger particle size and lower mass content of AgNPs than the BC-AgNPs one. For the antibacterial test, two nanocomposites exhibited a close antibacterial effect, with a high log reduction above 3 and killing ratio above 99.9%, respectively.


Assuntos
Resinas Acrílicas/química , Antibacterianos , Celulose/química , Gluconacetobacter xylinus/química , Nanocompostos , Antibacterianos/química , Antibacterianos/farmacologia , Contagem de Colônia Microbiana , Nanocompostos/química , Staphylococcus aureus/efeitos dos fármacos , Staphylococcus aureus/crescimento & desenvolvimento
18.
Environ Sci Pollut Res Int ; 21(8): 5730-6, 2014 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-24442963

RESUMO

In this work, pigeon feathers, a kind of totally waste by-product from the poultry industry, were utilized to fabricate a highly porous keratin sponge in a very simple way by freeze-drying treatment of the dissolved keratin solution, and applied for the first time as an oil adsorbent. An improved method was proposed to dissolve the feather keratin using the inexpensive sodium disulfite as the reducing reagent for sulfitolysis reaction, with a much lower concentration of all involving reaction regents. Moreover, the regenerated keratin sponges obtained a high oil adsorption capacity of above 30 g/g for both liquid paraffin and soybean oil, as well as a good oil holding ability, suggesting that this keratin sponge might be a potential for use as oil adsorbent.


Assuntos
Recuperação e Remediação Ambiental/métodos , Plumas/química , Queratinas/química , Parafina/química , Óleo de Soja/química , Adsorção , Criação de Animais Domésticos , Animais , Resíduos Industriais , Poríferos , Porosidade , Aves Domésticas , Reciclagem , Eliminação de Resíduos
19.
Mater Sci Eng C Mater Biol Appl ; 33(8): 4732-8, 2013 Dec 01.
Artigo em Inglês | MEDLINE | ID: mdl-24094181

RESUMO

Feather wastes generated from poultry farms will pose a problem for disposal, but they are sustainable resources of keratin. Reduction is one of the commonly used methods to obtain soluble keratin from feather. However, the residues generated during feather reduction reaction were rarely investigated. In this study, the residues were transformed into a porous and flexible sponge film by freeze-drying without pretreatment or addition of cross-linking agents. Glycerol was used to alter the physical and chemical characteristics of the sponge film. The film was characterized with a fiber strong stretch instrument, a Fourier transform infrared spectrophotometer, scanning electron microscopy, an elemental analyzer, a differential scanning calorimeter and an automatic air permeability apparatus. Tensile strength and melting point of the sponge film with the optimum glycerol content were 6.2 MPa and 170°C respectively. Due to air permeability of 368 mm/s, the film can potentially be used in medicine, biology, textile, environmental technology, and so on. It is ecologically friendly and will produce additional benefits from the renewable materials. The film was utilized as adsorbents to remove Cr(VI) from aqueous solutions and as a filtering material for air pollution. Its maximum Cr(VI) uptake capacity was about 148.8 mg/g and the removal rate of PM10 was 98.3%.


Assuntos
Plumas/química , Adsorção , Animais , Galinhas , Cromo/química , Glicerol/química , Queratinas/química , Material Particulado/química , Transição de Fase , Porosidade , Resistência à Tração
20.
Carbohydr Polym ; 87(1): 839-845, 2012 Jan 04.
Artigo em Inglês | MEDLINE | ID: mdl-34663043

RESUMO

Bacterial cellulose (BC), a natural nanoporous matrix, was utilized as the template to in situ synthesize silver nanoparticles (AgNPs) by chemical reduction. Effects of the microstructure of the BC template, produced by different fermentation carbon sources were investigated on the formation of AgNPs. A detailed characterization, e.g. SEM, XRD and nitrogen physisorption for pure BC, and EDX, UV-vis spectroscopy, TEM and inductively coupled plasma for the AgNPs impregnated BC composites (BC/AgNPs) were done, and the antimicrobial activity of every composite was evaluated by both zone of inhibition and log reduction methods. It was revealed that the particle size of AgNPs, and the silver content and antimicrobial activity of the BC/AgNPs composites varied depending on the different BC templates used, mainly due to the differences in the microstructure of the BC template, especially the crystallinity and porous properties. As far as we know, little studies have been done on this issue.

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