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1.
Arch Gynecol Obstet ; 309(1): 295-304, 2024 01.
Artigo em Inglês | MEDLINE | ID: mdl-37787836

RESUMO

PURPOSE: To investigate developmental competence and neonatal outcomes of nonpronuclear (0PN) zygotes following single vitrified-warmed blastocyst transfers (VBT). METHODS: The clinical, laboratorial and neonatal data of 996 patients with ≤ 38 years who underwent blastocyst culture and single VBT were retrospectively analyzed. The pregnancy and neonatal outcomes of VBT were compared between 0PN and 2PN blastocysts using propensity score matching (PSM). Moreover, Day 3 (D3) embryo development and blastocyst formation were compared between 0PN and 2PN zygotes. RESULTS: There were no significant differences in clinical pregnancy rate (CPR), live birth rate (LBR) and neonatal outcomes of VBT between the 0PN and 2PN blastocysts irrespectively of whether PSM was used. However, early abortion rate (EAR) was higher in blastocysts from 0PN D3 embryos > 10 cells (p < 0.05) before PSM. Moreover, the early developmental competence of 0PN zygotes was different from that of 2PN zygotes presenting higher percentages of D3 embryos ≤ 6 cells (p < 0.01) and > 10 cells (p < 0.01), lower available blastocyst formation rate (ABFR) (p < 0.01) and good-quality blastocyst formation rate (GBFR) (p < 0.01) in D3 embryos with 4-6 cells. ABFR and GBFR increased with cell number when compared among embryos with 4-6 cells, 7-10 cells and > 10 cells, irrespectively of 0PN or 2PN embryos. CONCLUSION: The early developmental competence of 0PN zygotes was different from that of 2PN zygotes, but did not influence pregnancy and neonatal outcomes following VBT. ABFR and GBFR increased with cell number, irrespectively of 0PN or 2PN embryos.


Assuntos
Transferência Embrionária , Zigoto , Gravidez , Feminino , Recém-Nascido , Humanos , Estudos Retrospectivos , Pontuação de Propensão , Taxa de Gravidez , Blastocisto
2.
Anal Chem ; 95(27): 10390-10397, 2023 07 11.
Artigo em Inglês | MEDLINE | ID: mdl-37358224

RESUMO

Oxidation and protein phosphorylation are critical mechanisms involved in regulating various cellular activities. Increasing research has suggested that oxidative stress could affect the activities of specific kinases or phosphatases, leading to alterations in the phosphorylation status of certain proteins. Ultimately, these alterations can affect cellular signaling pathways and gene expression patterns. However, the relationship between oxidation and protein phosphorylation remains complex and not yet fully understood. Therefore, the development of effective sensors capable of detecting both oxidation and protein phosphorylation simultaneously presents an ongoing challenge. To address this need, we introduce a proof-of-concept nanochannel device that is dual-responsive to both H2O2 and phosphorylated peptide (PP). Specifically, we design a peptide GGGCEG(GPGGA)4CEGRRRR, which contains an H2O2-sensitive unit CEG, an elastic peptide fragment (GPGGA)4, and a phosphorylation site recognition fragment RRRR. When the peptides are immobilized on the inner walls of conical nanochannels in a polyethylene terephthalate membrane, this peptide-modified nanochannel device exhibits a sensitive response to both H2O2 and PPs. The peptide chains undergo a random coil-to-α-helix transition in response to H2O2, which leads to a close-to-open transition of the nanochannel, accompanied with a remarkable increase in the transmembrane ionic current. In contrast, binding of the peptides with PPs shields the positive charge of the RRRR fragments, causing a decrease of the transmembrane ionic current. These unique features enable the sensitive detection of reactive oxygen species released by 3T3-L1 cells stimulated by platelet-derived growth factor (PDGF) as well as PDGF-induced change in the PP level. Real-time kinase activity monitoring further confirms the device's potential utility for kinase inhibitor screening.


Assuntos
Peróxido de Hidrogênio , Peptídeos , Peróxido de Hidrogênio/farmacologia , Peptídeos/metabolismo , Fator de Crescimento Derivado de Plaquetas/metabolismo , Fosforilação , Estresse Oxidativo
3.
Small ; 19(29): e2207932, 2023 07.
Artigo em Inglês | MEDLINE | ID: mdl-37052499

RESUMO

Self-assembly of cellulose nanocrystals (CNCs) is invaluable for the development of sustainable optics and photonics. However, the functional failure of CNC-derived materials in humid or liquid environments inevitably impairs their development in biomedicine, membrane separation, environmental monitoring, and wearable devices. Here, a facile and robust method to fabricate insoluble hydrogels in a self-assembled CNC-polyvinyl alcohol (PVA) system is reported. Due to the reconstruction of inter- or intra-molecular hydrogen bond interactions, thermal dehydration makes an optimized CNC/PVA photonic film form a stable hydrogel network in an aqueous solution rather than dissolve. Notably, the resulting hydrogel exhibits superb mechanical performance (stress up to 3.3 Mpa and tough up to 0.73 MJ m-3 ) and reversible conversion between dry and wet states, enabling it convenient for specific functionalization. Sodium alginate (SA) can be adsorbed into the CNC photonic structure by swelling dry CNC/PVA film in a SA solution. The prepared hydrogel showcases the comprehensive properties of freezing resistance (-20°C), strong adhesion, satisfactory biocompatibility, and highly sensitive and selective Ca2+ sensing. The material could act as a portable wearable patch on the skin for the continuous analysis of calcium trends during different physical exercises, facilitating their development in precision nutrition and health monitoring.


Assuntos
Celulose , Nanopartículas , Celulose/química , Cálcio , Suor , Óptica e Fotônica , Nanopartículas/química , Álcool de Polivinil/química , Hidrogéis/química
4.
Int J Mol Sci ; 24(17)2023 Aug 23.
Artigo em Inglês | MEDLINE | ID: mdl-37685916

RESUMO

Alzheimer's disease (AD) urgently needs innovative treatments due to the increasing aging population and lack of effective drugs and therapies. The amyloid fibrosis of AD-associated ß-amyloid (Aß) that could induce a series of cascades, such as oxidative stress and inflammation, is a critical factor in the progression of AD. Recently, peptide-based therapies for AD are expected to be great potential strategies for the high specificity to the targets, low toxicity, fast blood clearance, rapid cell and tissue permeability, and superior biochemical characteristics. Specifically, various chiral amino acids or peptide-modified interfaces draw much attention as effective manners to inhibit Aß fibrillation. On the other hand, peptide-based inhibitors could be obtained through affinity screening such as phage display or by rational design based on the core sequence of Aß fibrosis or by computer aided drug design based on the structure of Aß. These peptide-based therapies can inhibit Aß fibrillation and reduce cytotoxicity induced by Aß aggregation and some have been shown to relieve cognition in AD model mice and reduce Aß plaques in mice brains. This review summarizes the design method and characteristics of peptide inhibitors and their effect on the amyloid fibrosis of Aß. We further describe some analysis methods for evaluating the inhibitory effect and point out the challenges in these areas, and possible directions for the design of AD drugs based on peptides, which lay the foundation for the development of new effective drugs in the future.


Assuntos
Doença de Alzheimer , Animais , Camundongos , Doença de Alzheimer/tratamento farmacológico , Peptídeos beta-Amiloides , Envelhecimento , Aminoácidos , Proteínas Amiloidogênicas
5.
Analyst ; 146(22): 6846-6851, 2021 Nov 08.
Artigo em Inglês | MEDLINE | ID: mdl-34617079

RESUMO

The preparation of ideal sensing materials is of great significance for the realization of high-performance electrochemical analysis. However, in previous methods, most electrode materials are firstly synthesized and dispersed, finally dropped on the electrode surface, which led to complicated operation and poor adhesion between the materials and electrode surface. In this study, a PEDOT-CNT hybrid film has been prepared by combining carboxylated carbon nanotubes as dopants with PEDOT through scalable and easy-to-operate electrochemical deposition. The PEDOT-CNT modified electrode shows excellent performance for the determination of tertiary butylhydroquinone, with a wide linear range of 0.5-820 µM, a low detection limit of 0.12 µM, high stability and reproducibility. In addition, the mechanism of electrodeposition of CNTs and tertiary butylhydroquinone has also been discussed briefly. The PEDOT-CNT hybrid film possesses the preeminent sensing capacity in monitoring tertiary butylhydroquinone, providing research clues for the design and development of new electrode materials in the future.

6.
Analyst ; 146(2): 691-697, 2021 Jan 21.
Artigo em Inglês | MEDLINE | ID: mdl-33210665

RESUMO

A portable electrode with usability, availability, and high-sensitivity is of great significance for effective on-site detection in practical situations. In this paper, a novel flexible, disposable sensor for Cd2+ and Pb2+ with ultrahigh sensitivity and a fast response, based on acid-etched Fe/Fe2O3 encapsulated into a disposable carbon cloth electrode, has been successfully fabricated. Differential pulse anode stripping voltammetry (DPASV) was used to investigate the stripping behavior of Cd2+ and Pb2+, achieving high sensitivity for Cd2+ and Pb2+ (338.7 and 408.0 µA mM-1 cm-2) with limits of detection (LODs) of 0.42 ppb and 0.50 ppb, respectively. Meanwhile, remarkable stability and reproducibility were obtained. Such an electrode can detect Cd2+ and Pb2+ in actual water samples so this is a good candidate to act as a simple and convenient sensor for general applications. More importantly, the novel disposable electrode exhibited the unique advantages of convenience, portability, and reliability compared to a conventional electrode, which may make it an alternative advantageous choice for practical on-site detection.

7.
Anal Chem ; 92(23): 15663-15670, 2020 12 01.
Artigo em Inglês | MEDLINE | ID: mdl-33169968

RESUMO

Protein methylation is one of the most common and important post-translational modifications, and it plays vital roles in epigenetic regulation, signal transduction, and chromatin metabolism. However, due to the diversity of methylation forms, slight difference between methylated sites and nonmodified ones, and ultralow abundance, it is extraordinarily challenging to capture and separate methylated peptides from biological samples. Here, we introduce a simple and highly efficient method to separate methylated and nonmethylated peptides using 18-crown-6 as a mobile phase additive in high-performance liquid chromatography. Selective complexation between lysine and 18-crown-6 remarkably increases the retention of the peptides on a C18 stationary phase, leading to an excellent baseline separation between the lysine methylated and nonmethylated peptides. A possible binding mechanism is verified by nuclear magnetic resonance titration, biolayer interferometry technology, and quantum chemistry calculation. Through establishment of a simple enrichment methodology, a good selectivity is achieved and four methylated peptides with greatly improved signal-to-noise (S/N) ratios are successfully separated from a complex peptide sample containing 10-fold bovine serum albumin tryptic digests. By selecting rLys N as an enzyme to digest histone, methylation information in the histone could be well identified based on our enrichment method. This study will open an avenue and provide a novel insight for selective enrichment of lysine methylated peptides in post-translational modification proteomics.


Assuntos
Éteres de Coroa/química , Lisina/química , Peptídeos/química , Peptídeos/isolamento & purificação , Animais , Bovinos , Metilação , Proteólise , Soroalbumina Bovina/química , Soroalbumina Bovina/metabolismo , Tripsina/metabolismo
8.
Zhonghua Nan Ke Xue ; 23(12): 1059-1062, 2017 Dec.
Artigo em Zh | MEDLINE | ID: mdl-29738173

RESUMO

OBJECTIVE: To investigate the application value of the frozen-thawed round spermatids of the mouse in in vitro fertilization (IVF). METHODS: Haploid spermatids of the mouse obtained in vitro were divided into a frozen-thawed and a fresh group and oocytes were collected from 6-8 weeks old female mice. After diamidino-phenyl-indole (DAPI) staining, the oocytes were subjected to intracytoplasmic round spermatid injection (ROSI), 259 in the frozen-thawed and 238 in the fresh group. Comparisons were made between the two groups in the capacities of fertilization and embryonic development. RESULTS: The survival rate of the frozen-thawed haploid spermatids was (75.9 ± 2.3) %. No statistically significant differences were observed between the frozen-thawed and fresh groups after ROSI in the rates of fertilization (51.9 vs 55.7%, P >0.05), 2-cell embryos (51.0 vs 62.2%, P >0.05), 4-8-cell embryos (41.8 vs 42.9%, P >0.05), or morula-blastocysts (12.2 vs 21.4%, P >0.05). CONCLUSIONS: Frozen-thawed round spermatids of the mouse are similar to fresh ones in their capacities of fertilization and embryonic development.


Assuntos
Criopreservação , Injeções de Esperma Intracitoplásmicas , Espermátides/transplante , Animais , Desenvolvimento Embrionário , Feminino , Fertilização in vitro , Masculino , Camundongos , Oócitos , Gravidez
9.
Zhonghua Nan Ke Xue ; 21(8): 698-701, 2015 Aug.
Artigo em Zh | MEDLINE | ID: mdl-26442295

RESUMO

OBJECTIVE: To search for an optimal protocol and freezing conditions for the cryopreservation of microamount round spermatids of the mouse. METHODS: We compared the survival rates of frozen-thawed microamount round spermatids of the mouse achieved by vitrification or standard slow freezing with different concentrations of glycerol (5, 7, or 9%) and different lengths of equilibrium time (0, 15, 30, 45, or 60 min). RESULTS: Under the conditions of 7% glycerol and 30 min equilibrium, both vitrification and standard slow freezing achieved high survival rates of spermatids, and the former obtained an even higher rate than the latter ([72.9 ± 15.4]% vs [58.2 ± 17.7]%, P < 0.05). CONCLUSION: A high rate of frozen-thawed microamount round spermatids of the mouse can be achieved by vitrification under the conditions of 7% glycerol and 30 min equilibrium.


Assuntos
Criopreservação/métodos , Espermátides , Vitrificação , Animais , Sobrevivência Celular , Crioprotetores/administração & dosagem , Crioprotetores/farmacologia , Glicerol/administração & dosagem , Glicerol/farmacologia , Masculino , Camundongos , Fatores de Tempo , Vitrificação/efeitos dos fármacos
10.
Zhonghua Nan Ke Xue ; 20(8): 679-83, 2014 Aug.
Artigo em Zh | MEDLINE | ID: mdl-25195361

RESUMO

OBJECTIVE: To study the promoting effects of the epidermal growth factor (EGF) and stem cell factor (SCF) on the proliferation and differentiation of spermatogenic cells in mice. METHODS: We cocultured in vitro spermatogenic cells of male mice aged 7 - 8 days in the medium with EGF and/or SCF at the concentrations of 5, 10, 20, 40 and 100 ng/ml, respectively. Then we observed the survival rate and morphological changes of the spermatogenic cells, detected the expressions of the pachytene-specific phosphoprotein gene (P19) and haploid sperm cell-specific transition protein gene (TP1), and analyzed the ploidy of the cells. RESULTS: After cocultured with EGF or SCF for 2 - 4 days, the spermatogenic cells began to proliferate in masses or chains in all concentration groups, most obviously in the 20 ng/ml EGF and 40 ng/ml SCF groups. At 7 days, both the number and survival rate of spermatogenic cells were significantly higher in the 20 ng/ml EGF and 40 ng/ml SCF groups than in the others (P < 0.05), and meanwhile, the P19/TP1 ratio was obviously decreased and the rate of haploid sperm markedly increased in the 40 ng/ml SCF group (P < 0.05). Combination of EGF and SCF remarkably promoted the proliferation of the spermatogenic cells (P < 0.05). CONCLUSION: Both EGF and SCF could increase the number and survival rate of spermatogenic cells. SCF could promote the formation of haploid sperm, and the combination of the two cytokines could enhance the effect on the proliferation of spermatogenic cells.


Assuntos
Fator de Crescimento Epidérmico/farmacologia , Espermatócitos/efeitos dos fármacos , Fator de Células-Tronco/farmacologia , Animais , Diferenciação Celular/efeitos dos fármacos , Proliferação de Células/efeitos dos fármacos , Células Cultivadas , Proteínas Cromossômicas não Histona/metabolismo , Masculino , Camundongos , Espermatócitos/citologia
11.
Zhonghua Nan Ke Xue ; 20(2): 111-6, 2014 Feb.
Artigo em Zh | MEDLINE | ID: mdl-24520660

RESUMO

OBJECTIVE: To search for an optimal activation protocol by comparing the chemical activation effects of single-activator and combined activation protocols on mouse oocytes following injection of round spermatids (ROSI) from spermatogenic cells cultured in vitro. METHODS: Using different concentrations of ethanol, ionomycin (Ion), calcium ionophore A23187 (CIA), strontium chloride (SrCl2), cycloheximide (CHX), and 6-dimethylaminopurine (6-DMAP) , we activated post-ROSI oocytes for different times, and activated them by combined protocols at optimal concentrations and action times according to different activation channels. We compared the activation effects of single-activator and combined activation protocols by comparing the rates of fertilization, cleavages, and morulas and blastocysts. RESULTS: With a single activator, the optimal protocols of different activators were as follows: 7% ethanol for 6 min, 5 micromol/L CIA for 5 min, 5 micromol/L Ion for 5 min, 2 mmol/L 6-DMAP for 2 h, 10 mmol/L SrCl2 for 1.5 h, and 10 microg/ml CHX for 1.5 h, among which 10 mmol/L SrCl2 for 1.5 h achieved the highest rate of morulas and blastocysts, significantly better than CHX (P < 0.05) but with no remarkable difference from other activators. The ethanol + 6-DMAP group showed a significantly higher rate of morulas and blastocysts (29.63%) than all other combined activation groups and single-activator groups except SrCl2 (P < 0.05), and it also exhibited higher rates of normal fertilization, cleavages and morula than the SrCl2 group, but with no significant difference. CONCLUSION: The single-activator 10 mmol/L SrCl2 for 1.5 h and the combined activation of 7% ethanol for 6 min + 2 mmol/L 6-DMAP for 2 h are the optimal protocols for chemical activation of mouse oocytes following ROSI, and the combined activation of ethanol + 6-DMAP is even superior to the single-activator protocol.


Assuntos
Fertilização in vitro , Espermátides/citologia , Espermátides/efeitos dos fármacos , Animais , Cicloeximida/farmacologia , Feminino , Ionomicina/farmacologia , Masculino , Camundongos , Camundongos Endogâmicos , Oócitos/citologia , Oócitos/efeitos dos fármacos
12.
ACS Appl Mater Interfaces ; 16(36): 47110-47123, 2024 Sep 11.
Artigo em Inglês | MEDLINE | ID: mdl-39189050

RESUMO

Sepsis is defined as a life-threatening organ dysfunction caused by a dysregulated host response to infection. Research indicates that circulating histones, as pathogenic factors, may represent a therapeutic target for sepsis. However, effectively clearing circulating histones poses a challenge due to their structural similarity to normal blood proteins, their low abundance in the bloodstream, and serious interference from other blood biomacromolecules. Here we design a dodecapeptide-based functional polymer that can selectively adsorb circulating histones from the blood. The peptide, named P1 (HNHHQLALVESY), was discovered through phage display screening and demonstrated a strong affinity for circulating histones while exhibiting negligible affinities for common proteins in the blood, such as human serum albumin (HSA), immunoglobulin G (IgG), and transferrin (TRF). Furthermore, the P1 peptide was incorporated into a functional polymer design, poly(PEGMA-co-P1), which was immobilized onto a silica gel surface through reversible addition-fragmentation chain transfer polymerization. The resulting material was characterized using solid nuclear magnetic resonance, thermogravimetric analysis, and X-ray photoelectron spectroscopy. This material demonstrated the ability to selectively and efficiently capture circulating histones from both model solutions and whole blood samples while also exhibiting satisfactory blood compatibility, good antifouling properties, and resistance to interference. Satisfactory binding affinity and efficient capture capacity toward histone were also observed for the other screened peptide P2 (QMSMDLFGSNFV)-grafted polymer, validating phage display as a reliable ligand screening strategy. These findings present an approach for the specific clearance of circulating histones and hold promise for future clinical applications in blood purification toward sepsis.


Assuntos
Histonas , Sepse , Sepse/sangue , Humanos , Histonas/química , Histonas/sangue , Peptídeos/química , Adsorção , Polímeros/química , Albumina Sérica Humana/química
13.
J Nat Med ; 78(4): 1029-1043, 2024 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-38926328

RESUMO

Alzheimer's disease (AD) remains a challenging neurodegenerative disorder with limited therapeutic success. Traditional Chinese Medicine (TCM), as a promising new source for AD, still requires further exploration to understand its complex components and mechanisms. Here, focused on addressing Aß (1-40) aggregation, a hallmark of AD pathology, we employed a Thioflavin T fluorescence labeling method for screening the active molecular library of TCM which we established. Among the eight identified, 1,3-di-caffeoylquinic acid emerged as the most promising, exhibiting a robust binding affinity with a KD value of 26.7 nM. This study delves into the molecular intricacies by utilizing advanced techniques, including two-dimensional (2D) 15N-1H heteronuclear single quantum coherence nuclear magnetic resonance (NMR) and molecular docking simulations. These analyses revealed that 1,3-di-caffeoylquinic acid disrupts Aß (1-40) self-aggregation by interacting with specific phenolic hydroxyl and amino acid residues, particularly at Met-35 in Aß (1-40). Furthermore, at the cellular level, the identified compounds, especially 1,3-di-caffeoylquinic acid, demonstrated low toxicity and exhibited therapeutic potential by regulating mitochondrial membrane potential, reducing cell apoptosis, and mitigating Aß (1-40)-induced cellular damage. This study presents a targeted exploration of catechol compounds with implications for effective interventions in AD and sheds light on the intricate molecular mechanisms underlying Aß (1-40) aggregation disruption.


Assuntos
Peptídeos beta-Amiloides , Simulação de Acoplamento Molecular , Ácido Quínico , Peptídeos beta-Amiloides/metabolismo , Peptídeos beta-Amiloides/antagonistas & inibidores , Ácido Quínico/análogos & derivados , Ácido Quínico/farmacologia , Ácido Quínico/química , Humanos , Fragmentos de Peptídeos , Doença de Alzheimer/tratamento farmacológico , Doença de Alzheimer/metabolismo , Agregados Proteicos/efeitos dos fármacos
14.
Chem Commun (Camb) ; 59(29): 4368-4371, 2023 Apr 06.
Artigo em Inglês | MEDLINE | ID: mdl-36946304

RESUMO

We have developed a reactive oxygen species (ROS) sensor based on nanopores modified with GGGCEG(GPGGA)4CEG. The formation of an intramolecular disulfide bond oxidized by ROS leads to conformation changes in GGGCEG(GPGGA)4CEG, which then induces an obvious change in the size of the nanopores and a corresponding ionic current change. This work allows the accurate and dynamic monitoring of ROS through the combination of (GPGGA)4 and nanopores.

15.
Taiwan J Obstet Gynecol ; 62(6): 817-822, 2023 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-38008499

RESUMO

OBJECTIVE: To investigate the relationship between serum progesterone (P) levels on the day of blastocyst transfer and pregnancy outcomes in frozen-thawed embryo transfer (FET) cycles using hormone replacement therapy (HRT) with oral dydrogesterone for strengthened luteal phase support (LPS). MATERIALS AND METHODS: This was a retrospective study including 1176 FET cycles. All patients received 40 mg of intramuscular (IM) P daily for endometrium transformation plus oral dydrogesterone 10 mg BID from transfer day for strengthened LPS. Pregnancy outcomes were compared between serum P levels on the transfer day ≥10 ng/ml and <10 ng/ml. Furthermore, cycles were divided into 10 groups by deciles of P and ongoing pregnancy rate (OPR) was calculated in each group. Analyses using deciles of serum P were completed to see if these could create further prognostic power. RESULTS: No differences were observed in clinical pregnancy rates (CPRs), OPRs and live birth rates (LBRs) between serum P levels ≥10 ng/ml and <10 ng/ml. Patients with serum P levels <5.65 ng/ml (10th percentile) had a significantly lower OPR (48.31% vs. 58.98%, p = 0.03) and LBR (43.22% vs. 57.75%, p = 0.003) than the rest of the patients. Multivariate logistic regression analysis showed serum P levels on the transfer day were not associated with pregnancy outcomes. CONCLUSION: Measuring serum P levels on the day of HRT-FET is of clinical importance. Lower serum P levels impact the success of HRT-FET cycles, suggesting that there may be a threshold below which it is difficult to improve pregnancy outcomes via oral dydrogesterone to strengthen LPS.


Assuntos
Didrogesterona , Resultado da Gravidez , Gravidez , Feminino , Humanos , Progesterona , Estudos Retrospectivos , Fase Luteal , Lipopolissacarídeos , Taxa de Gravidez , Terapia de Reposição Hormonal
16.
Sci Adv ; 9(21): eade0293, 2023 05 26.
Artigo em Inglês | MEDLINE | ID: mdl-37235655

RESUMO

Innovative therapeutic strategies are urgently needed for Alzheimer's disease (AD) due to the increasing size of the aging population and the lack of effective drug treatment. Here, we report the therapeutic effects of extracellular vesicles (EVs) secreted by microglia, including macrosomes and small EVs, on AD-associated pathology. Macrosomes strongly inhibited ß-amyloid (Aß) aggregation and rescued cells from Aß misfolding-induced cytotoxicity. Furthermore, macrosome administration reduced Aß plaques and ameliorated cognitive impairment in mice with AD. In contrast, small EVs slightly promoted Aß aggregation and did not improve AD pathology. Proteomic analysis of small EVs and macrosomes revealed that macrosomes harbor several important neuroprotective proteins that inhibit Aß misfolding. In particular, the small integral membrane protein 10-like protein 2B in macrosomes has been shown to inhibit Aß aggregation. Our observations provide an alternative therapeutic strategy for the treatment of AD over conventional ineffective drug treatments.


Assuntos
Doença de Alzheimer , Disfunção Cognitiva , Camundongos , Animais , Doença de Alzheimer/metabolismo , Proteômica , Peptídeos beta-Amiloides/metabolismo , Microglia/metabolismo , Modelos Animais de Doenças
17.
ACS Appl Mater Interfaces ; 15(27): 32251-32261, 2023 Jul 12.
Artigo em Inglês | MEDLINE | ID: mdl-37377344

RESUMO

Blood infection can release toxic bacterial lipopolysaccharides (LPSs) into bloodstream, trigger a series of inflammatory reactions, and eventually lead to multiple organ dysfunction, irreversible shock, and even death, which seriously threatens human life and health. Herein, a functional block copolymer with excellent hemocompatibility is proposed to enable broad-spectrum clearance of LPSs from whole blood blindly before pathogen identification, facilitating timely rescue from sepsis. A dipeptide ligand of histidine-histidine (HH) was designed as the LPS binding unit, and poly[(trimethylamine N-oxide)-co-(histidine-histidine)], a functional block copolymer combining the LPS ligand of HH and a zwitterionic antifouling unit of trimethylamine N-oxide (TMAO), was then designed by reversible addition-fragmentation chain transfer (RAFT) polymerization. The functional polymer achieved effective clearance of LPSs from solutions and whole blood in a broad-spectrum manner and had good antifouling and anti-interference properties and hemocompatibility. The proposed functional dihistidine polymer provides a novel strategy for achieving broad-spectrum clearance of LPSs, with potential applications in clinical blood purification.


Assuntos
Lipopolissacarídeos , Polímeros , Humanos , Polímeros/química , Histidina , Ligantes
18.
J Agric Food Chem ; 71(31): 12004-12014, 2023 Aug 09.
Artigo em Inglês | MEDLINE | ID: mdl-37523494

RESUMO

Umami peptides are small molecular weight oligopeptides that play a role in umami taste attributes. However, the identification of umami peptides is easily limited by environmental conditions, and the abundant source and high chromatographic separation efficiency remain difficult. Herein, we report a robust strategy based on a phage random linear heptapeptide library that targets the T1R1-Venus flytrap domain (T1R1-VFT). Two candidate peptides (MTLERPW and MNLHLSF) were readily identified with high affinity for T1R1-VFT binding (KD of MW-7 and MF-7 were 790 and 630 nM, respectively). The two peptides exhibited umami taste and significantly enhanced the umami intensity when added to the monosodium glutamate solution. Overall, this strategy shows that umami peptides could be developed via phage display technology for the first time. The phage display platform has a promising application to discover other taste peptides with affinity for taste receptors of interest and has more room for improvement in the future.


Assuntos
Peptídeos , Receptores Acoplados a Proteínas G , Receptores Acoplados a Proteínas G/metabolismo , Peptídeos/química , Glutamato de Sódio , Paladar
19.
Adv Mater ; 35(33): e2302560, 2023 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-37247257

RESUMO

Lipopolysaccharide (LPS) is the primary bacterial toxin that is vital to the pathogenesis and progression of sepsis associated with extremely high morbidity and mortality worldwide. However, specific clearance of LPS from circulating blood is highly challenging because of the structural complexity and its variation between/within bacterial species. Herein, a robust strategy based on phage display screening and hemocompatible peptide bottlebrush polymer design for specific clearance of targeted LPS from circulating blood is proposed. Using LPS extracted from Escherichia coli as an example, a novel peptide (HWKAVNWLKPWT) with high affinity (KD < 1.0 nм), specificity, and neutralization activity (95.9 ± 0.1%) against the targeted LPS is discovered via iterative affinity selection coupled with endotoxin detoxification screening. A hemocompatible bottlebrush polymer bearing the short peptide [poly(PEGMEA-co-PEP-1)] exhibits high LPS selectivity to reduce circulating LPS level from 2.63 ± 0.01 to 0.78 ± 0.05 EU mL-1 in sepsis rabbits via extracorporeal hemoperfusion (LPS clearance ratio > 70%), reversing the LPS-induced leukocytopenia and multiple organ damages significantly. This work provides a universal paradigm for developing a highly selective hemoadsorbent library fully covering the LPS family, which is promising to create a new era of precision medicine in sepsis therapy.


Assuntos
Lipopolissacarídeos , Sepse , Animais , Coelhos , Endotoxinas , Sepse/terapia , Peptídeos , Bactérias
20.
RSC Adv ; 12(46): 29845-29851, 2022 Oct 17.
Artigo em Inglês | MEDLINE | ID: mdl-36321087

RESUMO

TBHQ is a significant synthetic antioxidant, but excessive use of TBHQ is harmful to human health. Therefore, the preparation of a high-efficiency TBHQ electrochemical sensor is of great significance. In this work, a core-shell structured Co3O4@PPy composite is synthesized for TBHQ determination and exhibits remarkable electrochemical properties. The core-shell structure of Co3O4@PPy composite shows the synergistic effects of fast charge transfer, rich active surface area and more active sites. Under optimal conditions, the linear range of the developed sensor is 0.2-600 µM, and the detection limit is 0.05 µM (S/N = 3). In addition, it also has good stability and reproducibility due to the stable protective role of the PPy shell. The proposed sensor can also be applied to practical sample detection.

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