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1.
J Pharm Anal ; 14(4): 100899, 2024 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-38634061

RESUMO

Tyrosine kinase inhibitors (TKIs) have emerged as the first-line small molecule drugs in many cancer therapies, exerting their effects by impeding aberrant cell growth and proliferation through the modulation of tyrosine kinase-mediated signaling pathways. However, there exists a substantial inter-individual variability in the concentrations of certain TKIs and their metabolites, which may render patients with compromised immune function susceptible to diverse infections despite receiving theoretically efficacious anticancer treatments, alongside other potential side effects or adverse reactions. Therefore, an urgent need exists for an up-to-date review concerning the biological matrices relevant to bioanalysis and the sampling methods, clinical pharmacokinetics, and therapeutic drug monitoring of different TKIs. This paper provides a comprehensive overview of the advancements in pretreatment methods, such as protein precipitation (PPT), liquid-liquid extraction (LLE), solid-phase extraction (SPE), micro-SPE (µ-SPE), magnetic SPE (MSPE), and vortex-assisted dispersive SPE (VA-DSPE) achieved since 2017. It also highlights the latest analysis techniques such as newly developed high performance liquid chromatography (HPLC) and high-resolution mass spectrometry (HRMS) methods, capillary electrophoresis (CE), gas chromatography (GC), supercritical fluid chromatography (SFC) procedures, surface plasmon resonance (SPR) assays as well as novel nanoprobes-based biosensing techniques. In addition, a comparison is made between the advantages and disadvantages of different approaches while presenting critical challenges and prospects in pharmacokinetic studies and therapeutic drug monitoring.

2.
CNS Neurosci Ther ; 30(4): e14711, 2024 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-38644551

RESUMO

OBJECTIVE: To elucidate the relationship between USP19 and O(6)-methylguanine-DNA methyltransferase (MGMT) after temozolomide treatment in glioblastoma (GBM) patients with chemotherapy resistance. METHODS: Screening the deubiquitinase pannel and identifying the deubiquitinase directly interacts with and deubiquitination MGMT. Deubiquitination assay to confirm USP19 deubiquitinates MGMT. The colony formation and tumor growth study in xenograft assess USP19 affects the GBM sensitive to TMZ was performed by T98G, LN18, U251, and U87 cell lines. Immunohistochemistry staining and survival analysis were performed to explore how USP19 is correlated to MGMT in GBM clinical management. RESULTS: USP19 removes the ubiquitination of MGMT to facilitate the DNA methylation damage repair. Depletion of USP19 results in the glioblastoma cell sensitivity to temozolomide, which can be rescued by overexpressing MGMT. USP19 is overexpressed in glioblastoma patient samples, which positively correlates with the level of MGMT protein and poor prognosis in these patients. CONCLUSION: The regulation of MGMT ubiquitination by USP19 plays a critical role in DNA methylation damage repair and GBM patients' temozolomide chemotherapy response.


Assuntos
Antineoplásicos Alquilantes , Metilação de DNA , Metilases de Modificação do DNA , Enzimas Reparadoras do DNA , Resistencia a Medicamentos Antineoplásicos , Temozolomida , Proteínas Supressoras de Tumor , Humanos , Temozolomida/farmacologia , Temozolomida/uso terapêutico , Enzimas Reparadoras do DNA/metabolismo , Enzimas Reparadoras do DNA/genética , Metilases de Modificação do DNA/metabolismo , Antineoplásicos Alquilantes/farmacologia , Antineoplásicos Alquilantes/uso terapêutico , Animais , Linhagem Celular Tumoral , Resistencia a Medicamentos Antineoplásicos/efeitos dos fármacos , Resistencia a Medicamentos Antineoplásicos/genética , Proteínas Supressoras de Tumor/metabolismo , Proteínas Supressoras de Tumor/genética , Metilação de DNA/efeitos dos fármacos , Camundongos Nus , Neoplasias Encefálicas/tratamento farmacológico , Neoplasias Encefálicas/genética , Neoplasias Encefálicas/metabolismo , Glioblastoma/tratamento farmacológico , Glioblastoma/genética , Glioblastoma/metabolismo , Camundongos , Masculino , Feminino , Dacarbazina/análogos & derivados , Dacarbazina/farmacologia , Dacarbazina/uso terapêutico , Reparo do DNA/efeitos dos fármacos , Endopeptidases/metabolismo , Endopeptidases/genética , Ensaios Antitumorais Modelo de Xenoenxerto , Ubiquitinação/efeitos dos fármacos
3.
Planta ; 259(5): 119, 2024 Apr 09.
Artigo em Inglês | MEDLINE | ID: mdl-38594473

RESUMO

MAIN CONCLUSION: S. plumbizincicola genetic transformation was optimized using a self-excision molecular-assisted transformation system by integrating the SpGRF4/SpGIF1 gene with XVE and Cre/loxP. Sedum plumbizincicola, despite being an excellent hyperaccumulator of cadmium and zinc with significant potential for soil pollution phytoremediation on farmland, has nonetheless trailed behind other major model plants in genetic transformation technology. In this study, different explants and SpGRF4-SpGIF1 genes were used to optimize the genetic transformation of S. plumbizincicola. We found that petiole and stem segments had higher genetic transformation efficiency than cluster buds. Overexpression of SpGRF4-SpGIF1 could significantly improve the genetic transformation efficiency and shorten the period of obtaining regenerated buds. However, molecular assistance with overexpression of SpGRF4-SpGIF1 leads to abnormal morphology, resulting in plant tissue enlargement and abnormal growth. Therefore, we combined SpGRF4-SpGIF1 with XVE and Cre/loxP to obtain DNA autocleavage transgenic plants induced by estradiol, thereby ensuring normal growth in transgenic plants. This study optimized the S. plumbizincicola genetic transformation system, improved the efficiency of genetic transformation, and established a self-excision molecular-assisted transformation system. This work also established the basis for studying S. plumbizincicola gene function, and for S. plumbizincicola breeding and germplasm innovation.


Assuntos
Sedum , Poluentes do Solo , Melhoramento Vegetal , Cádmio , Biodegradação Ambiental , Transformação Genética , Solo
4.
Neurology ; 102(9): e209305, 2024 May.
Artigo em Inglês | MEDLINE | ID: mdl-38630960

RESUMO

BACKGROUND AND OBJECTIVES: Structural imaging can offer insights into the cortical morphometry of migraine, which might reflect adaptations to recurring nociceptive messaging. This study compares cortical morphometry between a large sample of people with migraine and healthy controls, as well as across migraine subtypes. METHODS: Adult participants with migraine and age-matched and sex-matched healthy controls attended a single MRI session with magnetization-prepared rapid acquisition gradient echo and fluid-attenuated inversion recovery sequences at 3T. Cortical surface area, thickness, and volume were compared between participants with migraine (including subgroups) and healthy controls across the whole cortex within FreeSurfer and reported according to the Desikan-Killiany atlas. The analysis used cluster-determining thresholds of p < 0.0001 and cluster-wise thresholds of p < 0.05, adjusted for age, sex, and total intracranial volume. RESULTS: A total of 296 participants with migraine (mean age 41.6 years ± 12.4 SD, 261 women) and 155 healthy controls (mean age 41.1 years ± 11.7 SD, 133 women) were included. Among the participants with migraine, 180 (63.5%) had chronic migraine, 103 (34.8%) had migraine with aura, and 88 (29.7%) experienced a migraine headache during the scan. The total cohort of participants with migraine had reduced cortical surface area in the left insula, compared with controls (p < 0.0001). Furthermore, participants with chronic migraine (n = 180) exhibited reduced surface area in the left insula (p < 0.0001) and increased surface area in the right caudal anterior cingulate cortex (p < 0.0001), compared with controls. We found no differences specific to participants with aura or ongoing migraine headache. Post hoc tests revealed a positive correlation between monthly headache days and surface area within the identified anterior cingulate cluster (p = 0.014). DISCUSSION: The identified cortical changes in migraine were limited to specific pain processing regions, including the insula and caudal anterior cingulate gyrus, and were most notable in participants with chronic migraine. These findings suggest persistent cortical changes associated with migraine. TRIAL REGISTRATION INFORMATION: The REFORM study (clinicaltrials.gov identifier: NCT04674020).


Assuntos
Transtornos de Enxaqueca , Adulto , Humanos , Feminino , Cefaleia , Imageamento por Ressonância Magnética/métodos , Giro do Cíngulo , Sistema de Registros
5.
Burns Trauma ; 12: tkad060, 2024.
Artigo em Inglês | MEDLINE | ID: mdl-38585341

RESUMO

Acne is a common chronic inflammatory dermatosis that can lead to pathological scars (PSs, divided into hypertrophic scars and keloids). These kinds of abnormal scars seriously reduce the quality of life of patients. However, their mechanism is still unclear, resulting in difficult clinical prevention, unstable treatment effects and a high risk of recurrence. Available evidence supports inflammatory changes caused by infection as one of the keys to abnormal proliferation of skin fibroblasts. In acne-induced PSs, increasing knowledge of the immunopathology indicates that inflammatory cells directly secrete growth factors to activate fibroblasts and release pro-inflammatory factors to promote the formation of PSs. T helper cells contribute to PSs via the secretion of interleukin (IL)-4 and IL-13, the pro-inflammatory factors; while regulatory T cells have anti-inflammatory effects, secrete IL-10 and prostaglandin E2, and suppress fibrosis production. Several treatments are available, but there is a lack of combination regimens to target different aspects of acne-induced PSs. Overall, this review indicates that the joint involvement of inflammatory response and fibrosis plays a crucial role in acne-induced PSs, and also analyzes the interaction of current treatments for acne and PS.

6.
Artigo em Inglês | MEDLINE | ID: mdl-38598173

RESUMO

Motivated by the surging demand for low-temperature waste heat harvesting, materials with both prominent thermoelectric and good mechanical properties are preferred in practical applications. In this present work, the composite exploration of Te-doped Mg3.2Bi1.5Sb0.5-x vol % nanosized SiC (x = 0, 0.05, 0.1, 0.2, and 0.5) was carried out, where nanosized SiC is physically dispersed in the matrix in the form of a second phase. SiC second phase compositing further optimized the matrix carrier concentration, resulting in a higher power factor in the service temperature range (the highest value from 28.9 to 31.7 µW cm-1 K-2), and the (ZT)ave from 0.91 to 0.96 compared with the matrix sample. In addition, the SiC second phase effectively enhanced the mechanical properties of composite materials, including flexural strength, microhardness, and modulus. Because of the simultaneous optimization of thermoelectric and mechanical properties, the overall performance of Te-doped Mg3.2Bi1.5Sb0.5-0.05 vol % SiC composite is leveraged to meet special requirements of power generation. It is expected that the addition of SiC should be broadly applicable to address the physical performance in other thermoelectric systems.

7.
Org Biomol Chem ; 2024 Apr 12.
Artigo em Inglês | MEDLINE | ID: mdl-38606462

RESUMO

A method for generation of SVI sulfones from ß-sulfinyl esters (SIV) under transition-metal-free non-oxidative mild conditions is presented. Various sulfones have been achieved with moderate to excellent yields. The advantage of using ß-sulfinyl esters as masked aryl sulfinates has also been exemplified using brominated substrates. Oxygen isotope-labeling experiments indicated that the oxygen atoms incorporated into the sulfone product come from the sulfoxide of the ß-sulfinyl ester. Successive ß-elimination/O-addition/sulfinate esterification/ß-elimination processes are proposed for the mechanism of generating SVI from SIV.

8.
Bioact Mater ; 36: 48-61, 2024 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-38434148

RESUMO

Photosynthetic bacteria (PSB) has shown significant potential as a drug or drug delivery system owing to their photothermal capabilities and antioxidant properties. Nevertheless, the actualization of their potential is impeded by inherent constraints, including their considerable size, heightened immunogenicity and compromised biosafety. Conquering these obstacles and pursuing more effective solutions remains a top priority. Similar to extracellular vesicles, bacterial outer membrane vesicles (OMVs) have demonstrated a great potential in biomedical applications. OMVs from PSB encapsulate a rich array of bioactive constituents, including proteins, nucleic acids, and lipids inherited from their parent cells. Consequently, they emerge as a promising and practical alternative. Unfortunately, OMVs have suffered from low yield and inconsistent particle sizes. In response, bacteria-derived nanovesicles (BNVs), created through controlled extrusion, adeptly overcome the challenges associated with OMVs. However, the differences, both in composition and subsequent biological effects, between OMVs and BNVs remain enigmatic. In a groundbreaking endeavor, our study meticulously cultivates PSB-derived OMVs and BNVs, dissecting their nuances. Despite minimal differences in morphology and size between PSB-derived OMVs and BNVs, the latter contains a higher concentration of active ingredients and metabolites. Particularly noteworthy is the elevated levels of lysophosphatidylcholine (LPC) found in BNVs, known for its ability to enhance cell proliferation and initiate downstream signaling pathways that promote angiogenesis and epithelialization. Importantly, our results indicate that BNVs can accelerate wound closure more effectively by orchestrating a harmonious balance of cell proliferation and migration within NIH-3T3 cells, while also activating the EGFR/AKT/PI3K pathway. In contrast, OMVs have a pronounced aptitude in anti-cancer efforts, driving macrophages toward the M1 phenotype and promoting the release of inflammatory cytokines. Thus, our findings not only provide a promising methodological framework but also establish a definitive criterion for discerning the optimal application of OMVs and BNVs in addressing a wide range of medical conditions.

9.
PLoS One ; 19(3): e0294758, 2024.
Artigo em Inglês | MEDLINE | ID: mdl-38427701

RESUMO

The multiple global environments have triggered changes in the international environment, leading to a sharp decline of foreign direct investment (FDI) compared to pre-pandemic level. To evaluate the investment risk of FDI and make optimal investment decision becomes the most important issue for investors. This paper focuses on the evaluation of investment risk for FDI. First, an index system for risk evaluation of FDI is constructed. Then, we introduce the probabilistic linguistic entropy and cross entropy measures, based on which, a programming model is developed to identify the objective attribute weights. A composite weight derivation method, which takes both the objective attribute weights and the subjective attribute weights into account, is further introduced. In view of attributes' uncertainty and fuzziness and the conflicting characteristics of some attributes, the VIKOR (the Serbian name: VlseKriterijumska Optimizacija I Kompromisno Resenje, means multi-criteria optimization and compromise solution) method is used to evaluate the risk of FDI under the probabilistic linguistic environment. Furthermore, a case study is presented to illustrate the proposed method. The comparative analysis and some further discussions verify the validity of the proposed method for the FDI risk evaluation.


Assuntos
Linguística , Incerteza , Entropia
10.
Proteomics Clin Appl ; : e2300032, 2024 Mar 08.
Artigo em Inglês | MEDLINE | ID: mdl-38456388

RESUMO

PURPOSE: Diabetic retinopathy (DR), as one of the microvascular complications of diabetes, is a leading cause of acquired vision loss. Most DR cases are detected in the advanced stage through fundoscopy, making molecular biomarkers urgently needed for early diagnosis of DR. EXPERIMENTAL DESIGN: Serum disease-specific haptoglobin-ß (Hp-ß) chains of 100 patients with type 2 diabetes mellitus (T2DM) and 156 T2DM patients with non-proliferative diabetic retinopathy (NPDR) were separated using polyacrylamide gel electrophoresis. After in-gel digestion and enrichment, the intact N-glycopeptides were detected by mass spectrometry. RESULTS: Fucosylation of Hp-ß was significantly increased and sialylation of Hp-ß was significantly decreased in background DR (BDR, an early-stage DR) patients compared with non-diabetic retinopathy patients (p < 0.05) and yielded area under curves (AUCs) of 0.801 and 0.829 in training and validation groups, respectively, which had an advantage over glycated hemoglobin A1c (AUC ≤ 0.691). Moreover, a significant increase in sialylated Hp-ß was found in severe NPDR patients compared with BDR patients and yielded an AUC of 0.828 to distinguish severe NPDR from BDR. CONCLUSION: Changes in Hp-ß glycosylation are closely related to DR, and may be used for early diagnosis and screening of DR.

11.
Int Wound J ; 21(3): e14815, 2024 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-38468410

RESUMO

Diabetic foot ulcers (DFUs) are a serious chronic complication of diabetes mellitus and a leading cause of disability and death in diabetic patients. However, current treatments remain unsatisfactory. Although macrophages are associated with DFU, their exact role in this disease remains uncertain. This study sought to detect macrophage-related genes in DFU and identify possible therapeutic targets. Single-cell datasets (GSE223964) and RNA-seq datasets (GSM68183, GSE80178, GSE134431 and GSE147890) associated with DFU were retrieved from the gene expression omnibus (GEO) database for this study. Analysis of the provided single-cell data revealed the distribution of macrophage subpopulations in the DFU. Four independent RNA-seq datasets were merged into a single DFU cohort and further analysed using bioinformatics. This included differential expression (DEG) analysis, multiple machine learning algorithms to identify biomarkers and enrichment analysis. Finally, key results were validated using reverse transcription-quantitative polymerase chain reaction (RT-qPCR) and Western bolt. Finally, the findings were validated using RT-qPCR and western blot. We obtained 802 macrophage-related genes in single-cell analysis. Differential expression analysis yielded 743 DEGs. Thirty-seven macrophage-associated DEGs were identified by cross-analysis of marker genes with macrophage-associated DEGs. Thirty-seven intersections were screened and cross-analysed using four machine learning algorithms. Finally, HMOX1 was identified as a potentially valuable biomarker. HMOX1 was significantly associated with biological pathways such as the insulin signalling pathway. The results showed that HMOX1 was significantly overexpressed in DFU samples. In conclusion, the analytical results of this study identified HMOX1 as a potentially valuable biomarker associated with macrophages in DFU. The results of our analysis improve our understanding of the mechanism of macrophage action in this disease and may be useful in developing targeted therapies for DFU.


Assuntos
Diabetes Mellitus , Pé Diabético , Humanos , Pé Diabético/genética , Pé Diabético/terapia , Macrófagos/metabolismo , Biomarcadores , Análise de Célula Única , Heme Oxigenase-1/genética
12.
Nanomaterials (Basel) ; 14(6)2024 Mar 07.
Artigo em Inglês | MEDLINE | ID: mdl-38535633

RESUMO

CeO2 is an outstanding support commonly used for the CuO-based CO oxidation catalysts due to its excellent redox property and oxygen storage-release property. However, the inherently small specific surface area of CeO2 support restricts the further enhancement of its catalytic performance. In this work, the novel mesoporous CeO2 nanosphere with a large specific surface area (~190.4 m2/g) was facilely synthesized by the improved hydrothermal method. The large specific surface area of mesoporous CeO2 nanosphere could be successfully maintained even at high temperatures up to 500 °C, exhibiting excellent thermal stability. Then, a series of CuO-based CO oxidation catalysts were prepared with the mesoporous CeO2 nanosphere as the support. The large surface area of the mesoporous CeO2 nanosphere support could greatly promote the dispersion of CuO active sites. The effects of the CuO loading amount, the calcination temperature, mesostructure, and redox property on the performances of CO oxidation were systematically investigated. It was found that high Cu+ concentration and lattice oxygen content in mesoporous CuO/CeO2 nanosphere catalysts greatly contributed to enhancing the performances of CO oxidation. Therefore, the present mesoporous CeO2 nanosphere with its large specific surface area was considered a promising support for advanced CO oxidation and even other industrial catalysts.

13.
J Environ Manage ; 357: 120663, 2024 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-38552509

RESUMO

Wetlands, as core habitats for supporting waterbird diversity, provide a variety of ecosystem services through diverse ecosystem functioning. Wetland degradation and wetland-habitat loss undermine the relationship between biodiversity-ecosystem functioning (BEF), affecting the diversity of habitats and waterbirds. The conservation of waterbird diversity is closely linked to the proper functioning of wetland ecosystems (nutrient cycling, energy storage, and productivity). Waterbirds have complex habitat preferences and sensitivities, which affect biotic interactions. By highlighting the importance of temporal and spatial scales guided by BEF, a habitat-waterbird conservation framework is presented (BEF relationships are described at three levels: habitat, primary producers, and waterbird diversity). We present a novel perspective on habitat conservation for waterbirds by incorporating research on the effects of biodiversity and ecosystem functioning to address the crucial challenges in global waterbird diversity loss, ecosystem degradation, and habitat conservation. Last, it is imperative to prioritize strategies of habitat protection with the incorporation of BEF for future waterbird conservation.


Assuntos
Ecossistema , Áreas Alagadas , Conservação dos Recursos Naturais , Biodiversidade , Ciclismo
14.
Environ Res ; 251(Pt 1): 118643, 2024 Mar 06.
Artigo em Inglês | MEDLINE | ID: mdl-38458590

RESUMO

Coal gasification fine slag (CGFS), as a difficult-to-dispose solid waste in the coal chemical industry, consists of minerals and residual carbon. Due to the aggregate structure of minerals blocking pores and encapsulating active substances, the high-value utilization of CGFS still remains a challenge. Based on the intrinsic characteristics of CGFS, this study synthesized Fe-N doped porous carbon/silicate composites (Fe-NC) by alkali activation and pyrolysis for electrocatalytic degradation of phenolic wastewater. Meanwhile, minerals were utilized to regulate the surface chemical and pore structure, turning their disadvantages into advantages, which caused a sharp increase in m-cresol mineralization. The positive effect of minerals on composite properties was investigated by characterization techniques, electrochemical analyses and density functional theory (DFT) calculations. It was found that the mesoporous structure of the mineral-regulated composites was further developed, with more carbon defects and reactive substances on its surface. Most importantly, silicate mediated iron conversion through strong interaction with H2O2, high work function gradient with electroactive iron, and excellent superoxide radical (•O2-) production capacity. It effectively improved the reversibility and kinetics of the entire electrocatalytic reaction. Within the Fe-NC311 electrocatalytic system, the m-cresol removal rate reached 99.55 ± 1.24%, surpassing most reported Fe-N-doped electrocatalysts. In addition, the adsorption and electrooxidation experiment confirmed that the synergistic effect of Fe-N doped porous carbon and silicate simultaneously promoted the capture of pollutants and the transformation of electroactive molecules, and hence effectively shortened the diffusion path of short-lived radicals, which was further supported by molecular dynamics simulation. Therefore, this research provides new insights into the problem of mineral limitations and opens an innovative approach for CGFS recycling and environmental remediation.

15.
Plant Cell ; 2024 Mar 27.
Artigo em Inglês | MEDLINE | ID: mdl-38536743

RESUMO

Cold stress affects plant immune responses, and this process may involve the salicylic acid (SA) signaling pathway. However, the underlying mechanism by which low temperature signals coordinate with SA signaling to regulate plant immunity remains unclear. Here, we found that low temperatures enhanced the disease resistance of Arabidopsis thaliana against Pseudomonas syringae pv. tomato (Pst) DC3000. This process required INDUCER OF CBF EXPRESSION 1 (ICE1), the core transcription factor in cold-signal cascades. ICE1 physically interacted with NON-EXPRESSER OF PR GENES 1 (NPR1), the master regulator of the SA signaling pathway. Enrichment of ICE1 on the PATHOGENESIS-RELATED GENE 1 (PR1) promoter and its ability to transcriptionally activate PR1 were enhanced by NPR1. Further analyses revealed that cold stress signals cooperate with SA signals to facilitate plant immunity against pathogen attack in an ICE1-dependent manner. Cold treatment promoted interactions of NPR1 and TGACG-BINDING FACTOR 3 (TGA3) with ICE1, and increased the ability of the ICE1-TGA3 complex to transcriptionally activate PR1. Together, our results characterize a critical role of ICE1 as an indispensable regulatory node linking low temperature-activated and SA-regulated immunity. Understanding this crucial role of ICE1 in coordinating multiple signals associated with immunity broadens our understanding of plant-pathogen interactions.

16.
J Nanobiotechnology ; 22(1): 126, 2024 Mar 23.
Artigo em Inglês | MEDLINE | ID: mdl-38519957

RESUMO

The successful reprogramming of impaired wound healing presents ongoing challenges due to the impaired tissue microenvironment caused by severe bacterial infection, excessive oxidative stress, as well as the inappropriate dosage timing during different stages of the healing process. Herein, a dual-layer hydrogel with sodium alginate (SA)-loaded zinc oxide (ZnO) nanoparticles and poly(N-isopropylacrylamide) (PNIPAM)-loaded Cu5.4O ultrasmall nanozymes (named programmed time-released multifunctional hydrogel, PTMH) was designed to dynamically regulate the wound inflammatory microenvironment based on different phases of wound repairing. PTMH combated bacteria at the early phase of infection by generating reactive oxygen species through ZnO under visible-light irradiation with gradual degradation of the lower layer. Subsequently, when the upper layer was in direct contact with the wound tissue, Cu5.4O ultrasmall nanozymes were released to scavenge excessive reactive oxygen species. This neutralized a range of inflammatory factors and facilitated the transition from the inflammatory phase to the proliferative phase. Furthermore, the utilization of Cu5.4O ultrasmall nanozymes enhanced angiogenesis, thereby facilitating the delivery of oxygen and nutrients to the impaired tissue. Our experimental findings indicate that PTMHs promote the healing process of diabetic wounds with bacterial infection in mice, exhibiting notable antibacterial and anti-inflammatory properties over a specific period of time.


Assuntos
Infecções Bacterianas , Óxido de Zinco , Animais , Camundongos , Hidrogéis/farmacologia , Espécies Reativas de Oxigênio , Óxido de Zinco/farmacologia , Anti-Inflamatórios , Antibacterianos/farmacologia
17.
Free Radic Res ; : 1-14, 2024 Mar 22.
Artigo em Inglês | MEDLINE | ID: mdl-38478853

RESUMO

Sepsis is a systemic inflammatory response syndrome caused by infection, which causes renal dysfunction known as sepsis-associated acute kidney injury (S-AKI). Ferroptosis is a form of lipid peroxidation dependent on iron and reactive oxygen species that differs from other forms of programmed cell death at the morphological and biochemical levels. Andrographolide (AG), a natural diterpenoid lactone compound extracted from Andrographis paniculata, has been shown to have therapeutic effects in kidney disease. In this study, we investigated the novel mechanism by which AG attenuates septic acute kidney injury by inhibiting ferroptosis in renal tubular epithelial cells (HK-2) through the Nrf2/FSP1 pathway. Cecum ligation and puncture (CLP)-induced septic rats and lipopolysaccharide (LPS)-induced HK-2 cells were used for in vivo and in vitro experiments. Firstly, in septic rats and HK-2 cells, AG effectively decreased the levels of kidney injury indicators, including blood creatinine, urea nitrogen, and markers of kidney injury such as neutrophil gelatinase-associated lipid transport protein and kidney injury molecule-1 (KIM-1). In addition, AG prevented ferroptotosis, by avoiding the accumulation of iron and lipid peroxidation, and an increase in SLC7A11 and GPX4 in AG-treated HK-2 cells. Furthermore, AG attenuated mitochondrial damage, including mitochondrial swelling, outer membrane rupture, and a reduction in mitochondrial cristae in LPS-treated HK-2 cells. Ferrostatin-1 (Fer-1), a ferroptosis inhibitor, significantly inhibited LPS-induced ferroptosis in HK-2 cells. Importantly, our results confirm that Nrf2/FSP1 is an important pathway for ferroptosis resistance. Nrf2 siRNA hindered the effect of AG in attenuating acute kidney injury and inhibiting ferroptosis. These findings demonstrate that Nrf2/FSP1-mediated HK-2 ferroptosis is associated with AG, alleviates septic acute kidney injury, and indicates a novel avenue for therapeutic interventions in the treatment of acute kidney injury in sepsis.

18.
Nat Commun ; 15(1): 2307, 2024 Mar 14.
Artigo em Inglês | MEDLINE | ID: mdl-38485920

RESUMO

Contractile rings are formed from cytoskeletal filaments during cell division. Ring formation is induced by specific crosslinkers, while contraction is typically associated with motor protein activity. Here, we engineer DNA nanotubes and peptide-functionalized starPEG constructs as synthetic crosslinkers to mimic this process. The crosslinker induces bundling of ten to hundred DNA nanotubes into closed micron-scale rings in a one-pot self-assembly process yielding several thousand rings per microliter. Molecular dynamics simulations reproduce the detailed architectural properties of the DNA rings observed in electron microscopy. Theory and simulations predict DNA ring contraction - without motor proteins - providing mechanistic insights into the parameter space relevant for efficient nanotube sliding. In agreement between simulation and experiment, we obtain ring contraction to less than half of the initial ring diameter. DNA-based contractile rings hold promise for an artificial division machinery or contractile muscle-like materials.


Assuntos
Nanotubos , Proteínas , Divisão Celular , Proteínas/metabolismo , Citoesqueleto de Actina/metabolismo , Miosinas/metabolismo , DNA/metabolismo
19.
Nat Commun ; 15(1): 2736, 2024 Mar 28.
Artigo em Inglês | MEDLINE | ID: mdl-38548785

RESUMO

Optimizing thermoelectric conversion efficiency requires the compromise of electrical and thermal properties of materials, which are hard to simultaneously improve due to the strong coupling of carrier and phonon transport. Herein, a one-pot approach realizing simultaneous second phase and Cu vacancies modulation is proposed, which is effective in synergistically optimizing thermoelectric performance in copper sulfides. Multiple lattice defects, including nanoprecipitates, dislocations, and nanopores are produced by adding a refined ratio of Sn and Se. Phonon transport is significantly suppressed by multiple mechanisms. An ultralow lattice thermal conductivity is therefore obtained. Furthermore, extra Se is added in the copper sulfide for optimizing electrical transport properties by inducing generating Cu vacancies. Ultimately, an excellent figure of merit of ~1.6 at 873 K is realized in the Cu1.992SSe0.016(Cu2SnSe4)0.004 bulk sample. The simple strategy of inducing compositional and structural modulation for improving thermoelectric parameters promotes low-cost high-performance copper sulfides as alternatives in thermoelectric applications.

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