Your browser doesn't support javascript.
loading
Mostrar: 20 | 50 | 100
Resultados 1 - 20 de 178
Filtrar
1.
Chembiochem ; : e202400459, 2024 Jun 25.
Artigo em Inglês | MEDLINE | ID: mdl-38924281

RESUMO

Supramolecular hydrogels can be obtained via self-assembly of small molecules in aqueous environments. In this study, we describe the development of oxidation-responsive supramolecular hydrogels comprising glucosamine derivatives with an aryl sulfide group. We demonstrate that hydrogen peroxide can induce a gel-sol transition through the oxidation of the sulfide group to the corresponding sulfoxide. Furthermore, we show that this oxidation responsiveness can be extended to photo-responsiveness with the aid of a photosensitizer.

2.
Clin Exp Nephrol ; 28(6): 547-556, 2024 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-38340245

RESUMO

BACKGROUND: Upward-directed exit-site has been believed to be the worst for frequent ESI by an old retrospective study using straight catheters. No comparison study of 3 exit-site directions using swan-neck catheter has been performed regarding which direction is the best for our endpoints, Easy-to-see the backside area of exit-site: ESBE, Easy-to-disinfect the backside area of exit-site: EDBE, reduction of both exit-site infection (ESI), symptomatic catheter dislocation and peritonitis. METHODS: We assessed the relationship of exit-site direction with our endpoints in a quantitative cross-sectional, multicentered questionnaire survey. Patients who received either non-surgical catheter implantation or exit-site surgery were excluded. RESULTS: The numbers (percentage) of exit-site directions in included 291 patients were upward 79 (26.0), lateralward 108 (37.5) and downward 105 (36.5). Cochran-Armitage analysis showed a significant step-ladder increase in the prevalence of ESI as the direction changed from upward to lateralward to downward (0.15 ± 0.41, 0.25 ± 0.54, 0.38 ± 0.69 episodes/patient-year, p = 0.03). Multivariable regression analysis revealed the upward exit-site independently associates with both higher frequency of ESBE (OR 5.55, 95% CI 2.23-16.45, p < 0.01) and reduction of prevalence of ESI (OR 0.55, 95%CI 0.27-0.98, p = 0.04). Positive association between the prevalence of symptomatic catheter dislocation and ESI (OR 2.84, 95% CI 1.27-7.82, p = 0.01), and inverse association between EDBE and either prevalence of symptomatic catheter dislocation (OR 0.27, 95% CI 0.11-0.72) or peritonitis (OR 0.48, 95% CI 0.23-0.99) observed. CONCLUSION: Upward-directed swan-neck catheter exit-site may be the best for both ESBE and prevention of ESI. EDBE may reduce catheter dislocation and peritonitis. Symptomatic catheter dislocation may predict ESI.


Assuntos
Infecções Relacionadas a Cateter , Cateteres de Demora , Diálise Peritoneal , Peritonite , Humanos , Masculino , Feminino , Estudos Transversais , Pessoa de Meia-Idade , Cateteres de Demora/efeitos adversos , Idoso , Infecções Relacionadas a Cateter/prevenção & controle , Infecções Relacionadas a Cateter/epidemiologia , Infecções Relacionadas a Cateter/etiologia , Peritonite/prevenção & controle , Peritonite/etiologia , Peritonite/epidemiologia , Diálise Peritoneal/instrumentação , Diálise Peritoneal/efeitos adversos , Inquéritos e Questionários , Fatores de Risco
3.
Metab Eng ; 78: 148-158, 2023 07.
Artigo em Inglês | MEDLINE | ID: mdl-37286071

RESUMO

Focusing on the differences in the catalytic properties of two type I fatty acid synthases FasA and FasB, the fasA gene was disrupted in an oleic acid-producing Corynebacterium glutamicum strain. The resulting oleic acid-requiring strain whose fatty acid synthesis depends only on FasB exhibited almost exclusive production (217 mg/L) of palmitic acid (C16:0) from 1% glucose under the conditions supplemented with the minimum concentration of sodium oleate for growth. Plasmid-mediated amplification of fasB led to a 1.47-fold increase in palmitic acid production (320 mg/L), while fasB disruption resulted in no fatty acid production, with excretion of malonic acid (30 mg/L). Next, aiming at conversion of the palmitic acid producer to a producer of palmitoleic acid (POA, C16:1Δ9), we introduced the Pseudomonas nitroreducens Δ9-desaturase genes desBC into the palmitic acid producer. Although this resulted in failure, we noticed the emergence of suppressor mutants that exhibited the oleic acid-non-requiring phenotype. Production experiments revealed that one such mutant M-1 undoubtedly produced POA (17 mg/L) together with palmitic acid (173 mg/L). Whole genomic analysis and subsequent genetic analysis identified the suppressor mutation of strain M-1 as a loss-of-function mutation for the DtxR protein, a global regulator of iron metabolism. Considering that DesBC are both iron-containing enzymes, we investigated the conditions for increased iron availability to improve the DesBC-dependent conversion ratio of palmitic acid to POA. Eventually, supplementation of both hemin and the iron chelator protocatechuic acid in the engineered strain dramatically enhanced POA production to 161 mg/L with a conversion ratio of 80.1%. Cellular fatty acid analysis revealed that the POA-producing cells were really equipped with unnatural membrane lipids comprised predominantly of palmitic acid (85.1% of total cellular fatty acids), followed by non-native POA (12.4%).


Assuntos
Corynebacterium glutamicum , Ácido Palmítico , Ácido Palmítico/metabolismo , Corynebacterium glutamicum/metabolismo , Engenharia Metabólica/métodos , Ácidos Graxos , Ferro/metabolismo
4.
Proc Natl Acad Sci U S A ; 117(42): 26318-26327, 2020 10 20.
Artigo em Inglês | MEDLINE | ID: mdl-33020271

RESUMO

Epstein-Barr virus (EBV) infects human B cells and reprograms them to allow virus replication and persistence. One key viral factor in this process is latent membrane protein 2A (LMP2A), which has been described as a B cell receptor (BCR) mimic promoting malignant transformation. However, how LMP2A signaling contributes to tumorigenesis remains elusive. By comparing LMP2A and BCR signaling in primary human B cells using phosphoproteomics and transcriptome profiling, we identified molecular mechanisms through which LMP2A affects B cell biology. Consistent with the literature, we found that LMP2A mimics a subset of BCR signaling events, including tyrosine phosphorylation of the kinase SYK, the calcium initiation complex consisting of BLNK, BTK, and PLCγ2, and its downstream transcription factor NFAT. However, the majority of LMP2A-induced signaling events markedly differed from those induced by BCR stimulation. These included differential phosphorylation of kinases, phosphatases, adaptor proteins, transcription factors such as nuclear factor κB (NF-κB) and TCF3, as well as widespread changes in the transcriptional output of LMP2A-expressing B cells. LMP2A affected apoptosis and cell-cycle checkpoints by dysregulating the expression of apoptosis regulators such as BCl-xL and the tumor suppressor retinoblastoma-associated protein 1 (RB1). LMP2A cooperated with MYC and mutant cyclin D3, two oncogenic drivers of Burkitt lymphoma, to promote proliferation and survival of primary human B cells by counteracting MYC-induced apoptosis and by inhibiting RB1 function, thereby promoting cell-cycle progression. Our results indicate that LMP2A is not a pure BCR mimic but rather rewires intracellular signaling in EBV-infected B cells that optimizes cell survival and proliferation, setting the stage for oncogenic transformation.


Assuntos
Herpesvirus Humano 4/metabolismo , Receptores de Antígenos de Linfócitos B/metabolismo , Proteínas da Matriz Viral/metabolismo , Proteínas Adaptadoras de Transdução de Sinal/metabolismo , Apoptose/fisiologia , Linfócitos B/metabolismo , Humanos , Proteínas de Membrana/metabolismo , NF-kappa B/metabolismo , Fatores de Transcrição NFATC/metabolismo , Fosforilação , Transdução de Sinais , Quinase Syk/metabolismo
5.
Chemistry ; 28(48): e202201103, 2022 Aug 26.
Artigo em Inglês | MEDLINE | ID: mdl-35561038

RESUMO

Artificially synthesized stimuli-responsive biomolecules are attractive as molecular tools for monitoring and modulating biological systems. In biological systems, redox stimuli are common, and their dysregulation is typically linked to various abnormal or disease states. In this Concept article, the molecular design of reduction-responsive biomolecules, such as peptides, nucleic acids, and saccharides, which are produced by introducing nitroaryl groups into them, is reviewed with a special emphasis on simple 4-nitrobenzene-based motifs.


Assuntos
Ácidos Nucleicos , Oxirredução , Peptídeos
6.
Chemistry ; 28(8): e202104421, 2022 Feb 07.
Artigo em Inglês | MEDLINE | ID: mdl-34984747

RESUMO

Aqueous self-assembly of short peptides has attracted growing attention for the construction of supramolecular materials for various bioapplications. Herein, we describe how the thermolysin-assisted biocatalytic construction of a dipeptide hydrazide from an N-protected amino acid and an amino acid hydrazide leads to the formation of thermally stable supramolecular hydrogels. In addition, we demonstrate the post-assembly modification of the supramolecular architectures constructed in situ tethering hydrazide groups as a chemical handle by means of fluorescence imaging.


Assuntos
Dipeptídeos , Nanoestruturas , Hidrazinas , Hidrogéis , Peptídeos
7.
Clin Exp Nephrol ; 26(5): 435-444, 2022 May.
Artigo em Inglês | MEDLINE | ID: mdl-35132512

RESUMO

BACKGROUND: Tubulointerstitial nephritis (TIN) is an important cause of acute kidney injury (AKI) and advanced CKD. Only a limited number of studies have reported etiology-based differences in the clinical and/or histopathological properties and kidney outcomes of the biopsy-proven TIN. METHODS: Patients with biopsy-proven TIN identified from 2005 to 2016 in five hospitals were categorized based on the etiologies and were retrospectively analyzed in relation to the clinicopathological findings and kidney outcomes. RESULTS: Among 4815 biopsy cases screened, 153 Japanese TIN patients were identified, of whom 139 patients with ≥ 6 months of follow-up data (median 58 years old, 45.3% female, median 31.5 months follow-up) were further analyzed. TIN was drug-induced in 32.4%, autoimmune-related in 24.5%, of unknown etiology in 27.3% and other disease-related in 15.8%. Non-steroidal anti-inflammatory drugs and antibiotics were major causative drugs in drug-induced TIN, and IgG4-related disease, Sjögren's syndrome and sarcoidosis were common in autoimmune-related TIN. Among etiology groups, drug-induced TIN showed advanced AKI with elevated serum creatinine (sCr) and increased C-reactive protein levels at the diagnosis. TIN patients with autoimmune diseases showed less-severe AKI, but were more frequently treated with corticosteroids than others. Tubulointerstitial injury expansion in biopsy specimens was comparable among the groups. Complete or partial kidney function recovery at 6 months was more frequent in drug-induced and autoimmune-related TIN than in others. sCr levels at 6 months were similar among the groups. CONCLUSIONS: This largest case series study of the biopsy-proven TIN in Japan provides detailed information regarding both etiology-based clinicopathological properties and kidney outcomes.


Assuntos
Injúria Renal Aguda , Efeitos Colaterais e Reações Adversas Relacionados a Medicamentos , Nefrite Intersticial , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Injúria Renal Aguda/patologia , Biópsia , Japão/epidemiologia , Rim , Nefrite Intersticial/induzido quimicamente , Nefrite Intersticial/diagnóstico , Nefrite Intersticial/patologia , Estudos Retrospectivos
8.
Appl Environ Microbiol ; 87(5)2021 03 01.
Artigo em Inglês | MEDLINE | ID: mdl-33310719

RESUMO

Fatty acyl-CoA thioesterase (Tes) and acyl-CoA synthetase (FadD) catalyze opposing reactions between acyl-CoAs and free fatty acids. Within the genome of Corynebacterium glutamicum, several candidate genes for each enzyme are present, although their functions remain unknown. Modified expressions of the candidate genes in the fatty acid producer WTΔfasR led to identification of one tes gene (tesA) and two fadD genes (fadD5 and fadD15), which functioned positively and negatively in fatty acid production, respectively. Genetic analysis showed that fadD5 and fadD15 are responsible for utilization of exogenous fatty acids and that tesA plays a role in supplying fatty acids for synthesis of the outer layer components mycolic acids. Enzyme assays and expression analysis revealed that tesA, fadD5, and fadD15 were co-expressed to create a cyclic route between acyl-CoAs and fatty acids. When fadD5 or fadD15 was disrupted in wild-type C. glutamicum, both disruptants excreted fatty acids during growth. Double disruptions of them resulted in a synergistic increase in production. Additional disruption of tesA revealed a canceling effect on production. These results indicate that the FadDs normally shunt the surplus of TesA-generated fatty acids back to acyl-CoAs for lipid biosynthesis and that interception of this shunt provokes cells to overproduce fatty acids. When this strategy was applied to a fatty acid high-producer, the resulting fadDs-disrupted and tesA-amplified strain exhibited a 72% yield increase relative to its parent and produced fatty acids, which consisted mainly of oleic acid, palmitic acid, and stearic acid, on the gram scale per liter from 1% glucose.IMPORTANCE The industrial amino acid producer Corynebacterium glutamicum has currently evolved into a potential workhorse for fatty acid production. In this organism, we obtained evidence showing the presence of a unique mechanism of lipid homeostasis, namely, a formation of a futile cycle of acyl-CoA hydrolysis and resynthesis mediated by acyl-CoA thioesterase (Tes) and acyl-CoA synthetase (FadD), respectively. The biological role of the coupling of Tes and FadD would be to supply free fatty acids for synthesis of the outer layer components mycolic acids and to recycle their surplusage to acyl-CoAs for membrane lipid synthesis. We further demonstrated that engineering of the cycle in a fatty acid high-producer led to dramatically improved production, which provides a useful engineering strategy for fatty acid production in this industrially important microorganism.

9.
Int J Mol Sci ; 22(4)2021 Feb 13.
Artigo em Inglês | MEDLINE | ID: mdl-33668410

RESUMO

Supramolecular hydrogels formed by self-assembly of low-molecular-weight amphiphiles (hydrogelators) have attracted significant attention, as smart and soft materials. However, most of the observed stimuli-responsive behaviour of these supramolecular hydrogels are limited to gel-sol transitions. In this study, we present bola-amphiphilic glycosylated lipopeptide-type supramolecular hydrogelators that exhibit reversible thermochromism along with a gel-sol transition. The bola-amphiphiles have mono-, di-, tri- or tetra-phenylalanine (F) as a short peptide moiety. We investigate and discuss the effects of the number of F residues on the gelation ability and the morphology of the self-assembled nanostructures.


Assuntos
Hidrogéis , Lipopeptídeos , Cor , Hidrogéis/síntese química , Hidrogéis/química , Lipopeptídeos/síntese química , Lipopeptídeos/química , Transição de Fase
10.
Soft Matter ; 16(31): 7274-7278, 2020 Aug 12.
Artigo em Inglês | MEDLINE | ID: mdl-32658225

RESUMO

We diversified the structures of bola-amphiphilic glycolipid-type supramolecular hydrogelators that exhibited reversible thermochromism along with a gel-sol transition. The hydrogelators were designed and synthesized to have homo- or hetero-saccharides on each end of their molecules. Herein, the effects of the saccharides' structure on the gelation ability are discussed.

11.
Soft Matter ; 16(4): 899-906, 2020 Jan 28.
Artigo em Inglês | MEDLINE | ID: mdl-31829395

RESUMO

Artificial supramolecular nanostructures showing transient properties have attracted significant attention in recent years. New discoveries in this area may provide insights into a better understanding of the sophisticated organization of complex biomolecular systems. Nevertheless, research concerning such materials is still limited. Better knowledge of the chemical reactivity and corresponding molecular transformations of self-assembling molecules, which guide their assembly/disassembly, may provide an opportunity to construct transient supramolecular nanostructures capable of showing chemical stimulus responsiveness. Herein, we report a short peptide derivative containing a hydrazone bond, which shows transient hydrogel formation (no only sol-to-gel but also gel-to-shrunken gel phase transition) accompanied by continuous transformation and growth of supramolecular nanostructures triggered by hydrazone-oxime exchange reaction in response to hydroxylamine. Such controlled shrinkage behavior of supramolecular hydrogels in response to specific chemical stimuli has rarely been explored compared with conventional polymer hydrogel systems.


Assuntos
Hidrazonas/química , Hidrogéis/química , Nanoestruturas/química , Peptídeos/química , Fenômenos Biofísicos , Fenômenos Químicos , Hidrogéis/síntese química , Hidroxilamina/química , Estrutura Molecular , Peptídeos/síntese química , Transição de Fase , Polímeros/síntese química , Polímeros/química
12.
Bioorg Med Chem Lett ; 30(24): 127637, 2020 12 15.
Artigo em Inglês | MEDLINE | ID: mdl-33132114

RESUMO

We found that sulfisomidine, a sulfonamide antibiotic, potently binds to the Piwi/Argonaute/Zwille (PAZ) domain of human Argonaute protein 2 and inhibits RNA interference (RNAi). To elucidate the effect on RNAi of strong affinity of the 3'-ends in small interfering RNA (siRNA) to the PAZ domain, chemically modified siRNAs bearing sulfisomidine at the 3'-end were synthesized.


Assuntos
Antibacterianos/farmacologia , Proteínas Argonautas/metabolismo , Interferência de RNA/efeitos dos fármacos , Sulfisomidina/farmacologia , Proteínas Argonautas/química , Humanos , Domínios Proteicos/efeitos dos fármacos , RNA Interferente Pequeno/antagonistas & inibidores , Sulfonamidas/farmacologia
13.
BMC Nephrol ; 21(1): 370, 2020 08 26.
Artigo em Inglês | MEDLINE | ID: mdl-32847525

RESUMO

BACKGROUND: Chronic kidney disease-mineral and bone disorder (CKD-MBD) management in patients with end-stage renal disease is important owing to the risk of cardiovascular diseases. In clinical practice, we manage patients not by monitoring the levels of biologically active ionized calcium (iCa) but by monitoring total serum calcium or corrected calcium (cCa). We previously reported that iCa/cCa ratio was different between patients with hemodialysis and those with peritoneal dialysis (PD). In PD patients, several factors are expected to affect iCa/cCa ratio. Therefore, modifying the strategy to achieve better CKD-MBD management might be necessary; however, no reports have studied this to date. Therefore, we investigated the factors influencing iCa/cCa ratio in PD patients. METHODS: This retrospective cross-sectional study examined background and laboratory data, including iCa, collected at routine outpatient visits. The patients were divided into the first, second, and third tertile of iCa/cCa ratio groups to compare patient background and laboratory data. Multiple regression analysis was used to investigate the factors influencing iCa/cCa ratio. We used multiple imputation to deal with missing covariate data. RESULTS: In total, 169 PD patients were enrolled. In PD patients with lower iCa/cCa ratio, PD duration was longer and pH was higher. Urine volume and weekly renal Kt/V were lower in the patients with lower iCa/cCa ratio than in those with higher iCa/cCa ratio. iCa/cCa ratio and weekly renal Kt/V were directly correlated (r = 0.41, p < 0.01), and weekly renal Kt/V and pH were independent factors affecting iCa/cCa ratio (t = 2.86, p < 0.01 and t = - 5.42, p < 0.01, respectively). CONCLUSIONS: iCa levels were lower in PD patients with lower residual renal function (RRF) even though their cCa levels were equal to those with maintained RRF, warranting caution in the assessment and management of CKD-MBD in PD patients.


Assuntos
Cálcio/sangue , Distúrbio Mineral e Ósseo na Doença Renal Crônica/sangue , Falência Renal Crônica/sangue , Diálise Peritoneal , Idoso , Conservadores da Densidade Óssea/uso terapêutico , Hormônios e Agentes Reguladores de Cálcio/uso terapêutico , Quelantes/uso terapêutico , Distúrbio Mineral e Ósseo na Doença Renal Crônica/tratamento farmacológico , Cinacalcete/uso terapêutico , Estudos Transversais , Feminino , Humanos , Falência Renal Crônica/terapia , Masculino , Pessoa de Meia-Idade , Estudos Retrospectivos , Vitamina D/uso terapêutico
14.
Int J Mol Sci ; 21(24)2020 Dec 12.
Artigo em Inglês | MEDLINE | ID: mdl-33322664

RESUMO

Supramolecular architectures that are built artificially from biomolecules, such as nucleic acids or peptides, with structural hierarchical orders ranging from the molecular to nano-scales have attracted increased attention in molecular science research fields. The engineering of nanostructures with such biomolecule-based supramolecular architectures could offer an opportunity for the development of biocompatible supramolecular (nano)materials. In this review, we highlighted a variety of supramolecular architectures that were assembled from both nucleic acids and peptides through the non-covalent interactions between them or the covalently conjugated molecular hybrids between them.


Assuntos
Nanoestruturas/química , Nanotecnologia/métodos , Ácidos Nucleicos/química , Ácidos Nucleicos Peptídicos/química , Peptídeos/química , Interações Hidrofóbicas e Hidrofílicas , Microscopia Eletrônica de Transmissão , Nanoestruturas/ultraestrutura , Ácidos Nucleicos/ultraestrutura , Ácidos Nucleicos Peptídicos/ultraestrutura , Estrutura Secundária de Proteína , Estrutura Terciária de Proteína
15.
Blood ; 130(23): 2516-2526, 2017 12 07.
Artigo em Inglês | MEDLINE | ID: mdl-29074502

RESUMO

Epstein-Barr virus (EBV) establishes lifelong infection in B lymphocytes of most human hosts and is associated with several B lymphomas. During latent infection, EBV encodes latent membrane protein 2A (LMP2A) to promote the survival of B cells by mimicking host B-cell receptor signaling. By studying the roles of LMP2A during lymphoma development in vivo, we found that LMP2A mediates rapid MYC-driven lymphoma onset by allowing B cells to bypass MYC-induced apoptosis mediated by the p53 pathway in our transgenic mouse model. However, the mechanisms used by LMP2A to facilitate transformation remain elusive. In this study, we demonstrate a key role of LMP2A in promoting hyperproliferation of B cells by enhancing MYC expression and MYC-dependent degradation of the p27kip1 tumor suppressor. Loss of the adaptor protein cyclin-dependent kinase regulatory subunit 1 (Cks1), a cofactor of the SCFSkp2 ubiquitin ligase complex and a downstream target of MYC, increases p27kip1 expression during a premalignant stage. In mice that express LMP2A, Cks1 deficiency reduces spleen weights, restores B-cell follicle formation, impedes cell cycle progression of pretumor B cells, and eventually prolongs MYC-driven tumor onset. This study demonstrates that LMP2A uses the role of MYC in the cell cycle, particularly in the p27kip1 degradation process, to accelerate lymphomagenesis in vivo. Thus, our results reveal a novel mechanism of EBV in diverting the functions of MYC in malignant transformation and provide a rationale for targeting EBV's roles in cell cycle modulation.


Assuntos
Quinases relacionadas a CDC2 e CDC28/metabolismo , Inibidor de Quinase Dependente de Ciclina p27/metabolismo , Linfoma/etiologia , Linfoma/metabolismo , Proteínas Proto-Oncogênicas c-myc/genética , Proteínas da Matriz Viral/metabolismo , Animais , Quinases relacionadas a CDC2 e CDC28/genética , Ciclo Celular/genética , Transformação Celular Neoplásica , Transformação Celular Viral , Inibidor de Quinase Dependente de Ciclina p27/genética , Regulação da Expressão Gênica , Estimativa de Kaplan-Meier , Linfoma/mortalidade , Linfoma/patologia , Camundongos , Camundongos Knockout , Camundongos Transgênicos , Complexo de Endopeptidases do Proteassoma/metabolismo , Proteólise , Proteínas Proto-Oncogênicas c-myc/metabolismo
16.
Chemistry ; 25(51): 11955-11962, 2019 Sep 12.
Artigo em Inglês | MEDLINE | ID: mdl-31268200

RESUMO

Aqueous hybrid soft nanomaterials consisting of plural supramolecular architectures with a high degree of segregation (orthogonal coexistence) and precise hierarchy at the nano- and microscales, which are reminiscent of complex biomolecular systems, have attracted increasing attention. Remarkable progress has been witnessed in the construction of DNA nanostructures obtained by rational sequence design and supramolecular nanostructures of peptide derivatives through self-assembly under aqueous conditions. However, orthogonal self-assembly of DNA nanostructures and supramolecular nanostructures of peptide derivatives in a single medium has not yet been explored in detail. In this study, DNA microspheres, which can be obtained from three single-stranded DNAs, and three different supramolecular nanostructures (helical nanofibers, straight nanoribbons, and flowerlike microaggregates) of semi-artificial glycopeptides were simultaneously constructed in a single medium by a simple thermal annealing process, which gives rise to hybrid soft nanomaterials. Fluorescence imaging with selective staining of each supramolecular nanostructure uncovered the orthogonal coexistence of these structures with only marginal impact on their morphology. Additionally, the biostimuli-responsive degradation propensity of each supramolecular architecture is retained, and this may allow the construction of active soft nanomaterials exhibiting intelligent biofunctions.


Assuntos
DNA/química , Glicopeptídeos/química , Nanoestruturas/química , Peptídeos/química , Microesferas , Nanofibras/química , Água
17.
Clin Exp Nephrol ; 23(3): 409-414, 2019 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-30255261

RESUMO

BACKGROUND: Although peritoneal dialysis (PD) is becoming more widespread, PD among diabetic patients carries some concerns, such as worsened glycemic control due to constant exposure to glucose and operational errors due to diabetic complications. However, several technical advances could overcome these disadvantages. We, therefore, aimed to compare technical and patient survival between diabetic and non-diabetic PD patients. METHODS: We conducted a historical cohort study of 103 patients (mean age, 57 ± 16 years; 75 males, 32 diabetic patients) who started PD between January 2011 and January 2016. Kaplan-Meier survival analysis was used to compare technical and patient survivals between diabetic and non-diabetic patients. Multivariate Cox regression analysis was used to estimate the effects of the presence of diabetes on these outcomes. RESULTS: Technical and patient survivals did not differ significantly between groups (P = 0.62, P = 0.34, respectively). In addition, presence of diabetes affected neither technical nor patient survival in multivariate analysis (hazard ratio [HR], 1.31; 95% confidence interval [CI], 0.58-2.82 and HR 0.80; 95% CI 0.22-2.68, respectively). CONCLUSIONS: Technical and patient survivals of diabetic PD patients were not inferior to those of non-diabetic PD patients. These results suggest that no hesitation is warranted in initiating PD for diabetic patients with end-stage renal disease.


Assuntos
Nefropatias Diabéticas/mortalidade , Diálise Peritoneal/mortalidade , Adulto , Idoso , Nefropatias Diabéticas/terapia , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Modelos de Riscos Proporcionais , Estudos Retrospectivos
18.
Clin Exp Nephrol ; 23(7): 928-938, 2019 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-30879162

RESUMO

BACKGROUND: A decrease in absolute numbers (abs.) of circulating dendritic cells (DCs) and recruitment into target organs has been reported, but whether the level of proteinuria associates with circulating DC abs. has not been clarified. METHODS: We conducted a cross-sectional study of 210 patients with kidney disease aged 21-96 years who were admitted to our hospital for kidney biopsy in 2007-2010. For accuracy, the level of proteinuria was thoroughly measured by 24-h urine collection from patients in their admitted condition. The abs. of total DCs (tDCs), myeloid DCs (mDCs) and plasmacytoid DCs (pDCs) was measured by three-color fluorescence-activated cell sorting (FACS). Patients were divided into four groups based upon the quartile of each DC abs. and one-way ANOVA, and multivariable-adjusted regression analyses were performed. RESULTS: Quantile analysis showed that the level of daily proteinuria decreased with increasing blood mDC abs., with mean proteinuria levels (g/day) of 2.45, 1.68, 1.68, 1.10 for those in mDC abs. quartiles ≤ 445, < 686, < 907, ≥ 907 cells/102 µL (p = 0.0277), respectively. Multivariate-adjusted regression analysis revealed that the mDC abs. was negatively associated with proteinuria (95% CI - 57.0 to - 8.5) and positively associated with male gender (95% CI 66.2-250.5). Independent associations were also shown between pDCs abs. and estimated glomerular filtration rate (eGFR) (95% CI 0.14-2.67) and C-reactive protein (95% CI - 49.4 to - 9.9) and between tDCs abs. and male gender (95% CI 54.5-253.6) and C-reactive protein (95% CI - 80.5 to - 13.4). CONCLUSION: We first reported that circulating mDC abs. has a negative association with the level of proteinuria.


Assuntos
Células Dendríticas/patologia , Nefropatias/patologia , Células Mieloides/patologia , Proteinúria/patologia , Adulto , Idoso , Idoso de 80 Anos ou mais , Contagem de Células , Estudos Transversais , Feminino , Taxa de Filtração Glomerular , Humanos , Rim/fisiopatologia , Nefropatias/sangue , Nefropatias/fisiopatologia , Nefropatias/urina , Masculino , Pessoa de Meia-Idade , Valor Preditivo dos Testes , Prognóstico , Proteinúria/sangue , Proteinúria/fisiopatologia , Proteinúria/urina , Índice de Gravidade de Doença , Fatores Sexuais , Adulto Jovem
19.
J Ren Nutr ; 29(1): 39-47, 2019 01.
Artigo em Inglês | MEDLINE | ID: mdl-30097326

RESUMO

OBJECTIVES: High prevalence of iron deficiency (ID) and cardiomyopathy have been observed in patients with end-stage kidney disease (ESKD). Our objective was to clarify associations between ID and cardiac remodeling in patients with ESKD. DESIGN AND METHODS: A cross-sectional study was conducted using 1974 Japanese patients with ESKD at the initiation of maintenance dialysis. Levels of hemoglobin (Hb), iron status, and cardiac enlargement as assessed by the cardiothoracic ratio (CTR) were determined immediately before the first hemodialysis session. Circulatory ID was defined as transferrin saturation (TSAT) < 20%, and stored ID was defined as ferritin level <100 ng/dL. RESULTS: The mean age was 67 years. Median CTR was 54.0%. The prevalence of circulatory and stored ID was found to be 38% and 34%, respectively. CTR was higher in patients with circulatory ID than in those without. Even in ESKD patients without overhydration, significant negative association was observed between TSAT and CTR. Higher odds ratios in parallel with higher CTR categories compared with the reference category of CTR <45% were found in patients with TSAT <20% on multinomial analysis, but ferritin did not show any significant associations. The odds ratio for CTR >54% showed an upward trend in patients with TSAT <20% (odds ratio: 1.3) and <10% (odds ratio: 1.6) compared with the reference, even after adjusting for confounding variables such as Hb and ferritin. However, that phenomenon was eliminated by adding usage of an iron agent. CONCLUSIONS: Circulatory ID is closely associated with an enlarged heart independent of ferritin and Hb. Iron supplementation in the predialysis phase of chronic kidney disease may prevent cardiac remodeling independent of Hb level in patients chronic kidney disease.


Assuntos
Anemia Ferropriva/epidemiologia , Cardiomegalia/epidemiologia , Falência Renal Crônica/epidemiologia , Idoso , Comorbidade , Estudos Transversais , Bases de Dados Factuais , Feminino , Humanos , Japão , Masculino , Prevalência
20.
Bioconjug Chem ; 29(6): 2058-2067, 2018 06 20.
Artigo em Inglês | MEDLINE | ID: mdl-29742348

RESUMO

Multicomponent self-assembly is a fascinating strategy for the construction of smart soft materials. Among them, supramolecular hydrogels comprising self-sorting nanofibers have recently attracted significant attention owing to their rationally incorporated stimulus responsiveness. However, there have been limited investigations of the crucial factors that control the self-sorting phenomena. Here, we describe an imaging-based approach to evaluate the factors that control the formation of self-sorting nanofibers from peptide- and lipid-type hydrogelators. We screened a small library of hydrogelators with distinct chemical properties by direct visualization of their self-assembly behavior by using confocal laser scanning microscopy. Our systematic research identified two important factors that influence the self-sorting behavior of nanofibers: (i) the surface charge of the hydrogelators; and (ii) the hydrophobicity of the side chain on the peptide-type hydrogelators. We determined that the same net/surface charge on the hydrogelators and side chains with a lower hydrophobicity on the peptide-type hydrogelators were preferred. These findings, in combination with the previously reported kinetic factors, were used to design and successfully prepare a three-component orthogonal self-assembly composed of supramolecular nanofibers from peptide- and lipid-type hydrogelators and a cationic organorhodium complex. Our findings would be beneficial for the design of intelligent soft materials based on self-sorting phenomena.


Assuntos
Hidrogéis/química , Lipídeos/química , Nanofibras/química , Nanofibras/ultraestrutura , Peptídeos/química , Ânions/química , Cinética , Imagem Óptica , Biblioteca de Peptídeos
SELEÇÃO DE REFERÊNCIAS
DETALHE DA PESQUISA