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1.
Phys Rev Lett ; 130(9): 096901, 2023 Mar 03.
Artigo em Inglês | MEDLINE | ID: mdl-36930917

RESUMO

The ac conduction of epitaxially grown SmB_{6} thin films and superconducting heterostructures of SmB_{6}/YB_{6} are investigated via time-domain terahertz spectroscopy. A two-channel model of thickness-dependent bulk states and thickness-independent surface states accurately describes the measured conductance of bare SmB_{6} thin films, demonstrating the presence of surface states in SmB_{6}. While the observed reductions in the simultaneously measured superconducting gap, transition temperature, and superfluid density of SmB_{6}/YB_{6} heterostructures relative to bare YB_{6} indicate the penetration of proximity-induced superconductivity into the SmB_{6} overlayer; the corresponding SmB_{6}-thickness independence between different heterostructures indicates that the induced superconductivity is predominantly confined to the interface surface state of the SmB_{6}. This study demonstrates the ability of terahertz spectroscopy to probe proximity-induced superconductivity at an interface buried within a heterostructure, and our results show that SmB_{6} behaves as a predominantly insulating bulk surrounded by conducting surface states in both the normal and induced-superconducting states in both terahertz and dc responses, which is consistent with the topological Kondo insulator picture.

2.
Analyst ; 148(7): 1543-1551, 2023 Mar 27.
Artigo em Inglês | MEDLINE | ID: mdl-36880438

RESUMO

A new method and platform has been developed for direct transfer, electrophoretic separation, and pre-concentration of swabbed samples using the principles of thread-based electrofluidics. A direct electrokinetic injection has been observed for a variety of analytes ranging from small molecules to proteins. The effect of physicochemical interactions of the analyte with the swab and the thread on the transfer efficiency has been studied by exploring different swab and thread combinations. For fluorescein, using a polyurethane swab, 98% and 94% transfer efficiencies were observed on mercerised cotton and nylon thread, while only 80% transfer efficiency was observed on polyester thread, respectively. A 97% transfer of fluorescein was observed on the nylon thread when a flocked nylon swab was used, while only 47% transfer was observed when a cotton swab was used. A successful transfer has been observed for both liquid and dry samples from either pre-wetted or dry swabs in both the presence and absence of any surrounding electrolytes. The platform has been further adapted for multiplexed analysis, where a sample from a single swab was transferred onto two parallel thread systems with ca. 50% distribution between them. The method has been validated for transfer, separation, and pre-concentration of DNA from blood. It has also been successfully used to directly analyse dried blood samples using a commercial sampling device, Neoteryx Mitra.

3.
Molecules ; 28(5)2023 Feb 24.
Artigo em Inglês | MEDLINE | ID: mdl-36903391

RESUMO

This study aims to evaluate the effect of berberine-based carbon quantum dots (Ber-CDs) on improving 5-fluorouracil (5-FU)-induced intestinal mucositis in C57BL/6 mice, and explored the mechanisms behind this effect. Thirty-two C57BL/6 mice were divided into four groups: normal control (NC), 5-FU-induced intestinal mucositis model (5-FU), 5-FU + Ber-CDs intervention (Ber-CDs), and 5-FU + native berberine intervention (Con-CDs). The Ber-CDs improved body weight loss in 5-FU-induced mice with intestinal mucositis compared to the 5-FU group. The expressions of IL-1ß and NLRP3 in spleen and serum in Ber-CDs and Con-Ber groups were significantly lower than those in the 5-FU group, and the decrease was more significant in the Ber-CDs group. The expressions of IgA and IL-10 in the Ber-CDs and Con-Ber groups were higher than those in the 5-FU group, but the up-regulation was more significant in the Ber-CDs group. Compared with the 5-FU group, the relative contents of Bifidobacterium, Lactobacillus and the three main SCFAs in the colon contents were significantly increased the Ber-CDs and Con-Ber groups. Compared with the Con-Ber group, the concentrations of the three main short-chain fatty acids in the Ber-CDs group were significantly increased. The expressions of Occludin and ZO-1 in intestinal mucosa in the Ber-CDs and Con-Ber groups were higher than those in the 5-FU group, and the expressions of Occludin and ZO-1 in the Ber-CDs group were more higher than that in the Con-Ber group. In addition, compared with the 5-FU group, the damage of intestinal mucosa tissue in the Ber-CDs and Con-Ber groups were recovered. In conclusion, berberine can attenuate intestinal barrier injury and oxidative stress in mice to mitigate 5-fluorouracil-induced intestinal mucositis, moreover, the above effects of Ber-CDs were more significant than those of native berberine. These results suggest that Ber-CDs may be a highly effective substitute for natural berberine.


Assuntos
Berberina , Enteropatias , Mucosite , Pontos Quânticos , Animais , Camundongos , Mucosite/induzido quimicamente , Fluoruracila/farmacologia , Berberina/farmacologia , Ocludina/metabolismo , Camundongos Endogâmicos C57BL , Mucosa Intestinal/metabolismo , Enteropatias/metabolismo , Ácidos Graxos Voláteis/metabolismo , Estresse Oxidativo
4.
Clin Neurol Neurosurg ; 227: 107640, 2023 Feb 25.
Artigo em Inglês | MEDLINE | ID: mdl-36870089

RESUMO

BACKGROUND: Some peripheral blood markers have been demonstrated to be correlated with the re-formation of chronic subdural hematoma (CSDH). The aim of this study was to identify the correlation between nutritional/inflammatory peripheral blood markers and CSDH. METHODS: 188 CSDH patients and 188 age-matched healthy controls were included in this research. The clinical characteristics and peripheral blood markers associated with nutritional or inflammatory status were obtained and analyzed. Conditional logistic regression analysis was applied to identify the potential CSDH risk factors. All the participants were divided into 3 groups based on the tertiles of change in risk factors. The Cochran-Armitage test and one way ANOVA were applied to identify the association between baseline characteristics and independent risk factors. Moreover, the net reclassification index (NRI) and integrated discrimination index (IDI) were calculated to evaluate the improvement in model performance after adding the independent risk factors in the conventional model. RESULTS: The logistic regression analysis demonstrated that the increased albumin (OR, 0.615; 95 %CI,0.489-0.773; P < 0.001) and lymphocyte count (OR, 0.141; 95 %CI,0.025-0.796; P = 0.027) were associated with lower risk of CSDH. Moreover, addition of albumin and lymphocyte to conventional risk factors significantly improved the risk prediction of CSDH(NRI: 46.47 %, P < 0.001; IDI: 30.92 %, P < 0.001; NRI: 22.45 %, P = 0.027; IDI: 1.23 %, P = 0.037, respectively) CONCLUSION: The decreased albumin and lymphocyte levels were correlated with a high risk of chronic subdural hematoma. The nutritional and inflammatory serum markers should be put great attention because these markers may play roles in finding the cause of CSDH and predicting its risk.

5.
J Colloid Interface Sci ; 641: 747-757, 2023 Mar 20.
Artigo em Inglês | MEDLINE | ID: mdl-36965345

RESUMO

As a viable replacement to commercial graphite anodes, silicon (Si) anodes have gained much attention from academics because of their considerable theoretical specific capacity and appropriate reaction voltage. Nevertheless, some limitations still exist in developing silicon anodes, including significant volume expansion and poor electrical conductivity. Herein, the carbon nanotubes (CNTs) interconnected yolk-shell silicon/carbon anodes (YS-Si@CoNC) were prepared via the chelation competition induced polymerization (CCIP) approach. The YS-Si@CoNC anode, designed in this study, demonstrates improved performance. At the current density of 0.5 A g-1 and 1 A g-1, a capacity of 1001 mAh g-1 and 956.5 mAh g-1 can be achieved after 150 cycles and after 300 cycles, respectively. In particular, at the current density of 5 A g-1, the reversible specific capacity of 688 mAh g-1 is realized. The exceptional outcomes are mainly attributed to the internal voids that adequately alleviate the volumetric expansion and the CNTs and carbon shells that provide an efficient conducting matrix to fasten the diffusion of electrons and lithium-ions. Our research presents a convenient way of designing Si/C anode materials with a yolk-shell structure to guarantee impressive electrical conductivity and robust structural integrity for high-performance LIBs.

6.
Sci Rep ; 13(1): 4703, 2023 Mar 22.
Artigo em Inglês | MEDLINE | ID: mdl-36949172

RESUMO

The blasting mechanism underlying drilling and blasting of underwater rocks, as an important component of the engineering blasting technology, has not been systematically studied. Laboratory model experiments are expensive and take a long time, while field tests fail to obtain timeous breakage and accumulation effects of underwater blasting, and may even be impossible. Considering this, a model experiment of underwater concrete bench blasting was designed, and the motion of blasted blocks was observed and evaluated with a high-speed camera. Then, numerical simulation was conducted based on Fluent and an engineering discrete element method coupling program complied using the application programming interface. Results show that the blocks form a bulge in the underwater blasting experiment under action of blast waves and expansion in the first period of bubble pulsation. Then, some blocks shrink in the first period of bubble pulsation. As the charge increases, the blast load exerts larger disturbance on the block group, resulting in significant motion of blasted blocks along the vertical direction. At the same time, the horizontal displacement of blasted blocks in the throwing direction increases.

7.
Trials ; 24(1): 207, 2023 Mar 20.
Artigo em Inglês | MEDLINE | ID: mdl-36941714

RESUMO

BACKGROUND: Chronic subdural hematomas (CSDHs) are one of the most common neurosurgical conditions. The standard surgical technique includes burr-hole craniostomy, followed by intraoperative irrigation and placement of subdural closed-system drainage. The drainage is generally removed after 48 h, which can be described as fixed-time drainage strategy. According to literature, the recurrence rate is 5-33% with this strategy. In our retrospective study, postoperative hematoma volume was found to significantly increase the risk of recurrence. Based on these results, an exhaustive drainage strategy is conducted to minimize postoperative hematoma volume and achieve a low recurrence rate and good outcomes. METHODS: This is a prospective, multicenter, open-label, blinded endpoint randomized controlled trial designed to include 304 participants over the age of 18-90 years presenting with a symptomatic CSDH verified on cranial computed tomography or magnetic resonance imaging. Participants will be randomly allocated to perform exhaustive drainage (treatment group) or fixed-time drainage (control group) after a one-burr hole craniostomy. The primary endpoint will be recurrence indicating a reoperation within 6 months. DISCUSSION: This study will validate the effect and safety of exhaustive drainage after one-burr hole craniostomy in reducing recurrence rates and provide critical information to improve CSDH surgical management. TRIAL REGISTRATION: Clinicaltrials.gov, NCT04573387. Registered on October 5, 2020.


Assuntos
Hematoma Subdural Crônico , Humanos , Adulto , Pessoa de Meia-Idade , Estudos Retrospectivos , Estudos Prospectivos , Hematoma Subdural Crônico/diagnóstico por imagem , Hematoma Subdural Crônico/cirurgia , Recidiva , Drenagem/efeitos adversos , Drenagem/métodos , Resultado do Tratamento , Craniotomia/efeitos adversos , Ensaios Clínicos Controlados Aleatórios como Assunto , Estudos Multicêntricos como Assunto
9.
Front Genet ; 14: 1094838, 2023.
Artigo em Inglês | MEDLINE | ID: mdl-36845398

RESUMO

Gastric cancer (GC) is highly heterogeneous and GC patients have low overall survival rates. It is also challenging to predict the prognosis of GC patients. This is partly because little is known about the prognosis-related metabolic pathways in this disease. Hence, our objective was to identify GC subtypes and genes related to prognosis, based on changes in the activity of core metabolic pathways in GC tumor samples. Differences in the activity of metabolic pathways in GC patients were analyzed using Gene Set Variation Analysis (GSVA), leading to the identification of three clinical subtypes by non-negative matrix factorization (NMF). Based on our analysis, subtype 1 showed the best prognosis while subtype 3 exhibited the worst prognosis. Interestingly, we observed marked differences in gene expression between the three subtypes, through which we identified a new evolutionary driver gene, CNBD1. Furthermore, we used 11 metabolism-associated genes identified by LASSO and random forest algorithms to construct a prognostic model and verified our results using qRT-PCR (five matched clinical tissues of GC patients). This model was found to be both effective and robust in the GSE84437 and GSE26253 cohorts, and the results from multivariate Cox regression analyses confirmed that the 11-gene signature was an independent prognostic predictor (p < 0.0001, HR = 2.8, 95% CI 2.1-3.7). The signature was found to be relevant to the infiltration of tumor-associated immune cells. In conclusion, our work identified significant GC prognosis-related metabolic pathways in different GC subtypes and provided new insights into GC-subtype prognostic assessment.

10.
Polymers (Basel) ; 15(3)2023 Jan 27.
Artigo em Inglês | MEDLINE | ID: mdl-36771946

RESUMO

Ion exchange membranes are widely used for water treatment and ion separation by electrodialysis. One of the ways to increase the efficiency of industrial membranes is their modification with various dopants. To improve the membrane permselectivity, a simple strategy of the membrane surface modification was proposed. Heterogeneous RALEX-CM membranes were surface-modified by ceria with a phosphate-functionalized surface. Despite a decrease in ionic conductivity of the prepared composite membranes, their cation transport numbers slightly increase. Moreover, the modified membranes show a threefold increase in Ca2+/Na+ permselectivity (from 2.1 to 6.1) at low current densities.

11.
Front Oncol ; 13: 1083085, 2023.
Artigo em Inglês | MEDLINE | ID: mdl-36824145

RESUMO

Objective: Primary spinal anaplastic ependymoma (PSAE) is an extremely rare disease. We aim to report the largest PSAE cohort, evaluate the treatments, and investigate the prognostic factors for progression-free survival (PFS). Methods: Clinical data collected from the authors' institute and literature articles were pooled and described. Survival analysis and multivariable Cox regression analysis were performed to evaluate therapies and investigate prognostic factors for PFS. Results: Our cohort included 22 females and 16 males, with a median age of 33 years. PSAE developed mostly on cervical and cervicothoracic levels. The median length measured 3 segments. Half of PSAE were intramedullary. Pain was the most common symptom. The median duration of symptoms was 6 months. Neurological statuses were improved in 76% following treatments, whereas clinical tumor progression occurred in 41.7%. The estimated median progression-free survival was 132 months, and the estimated median survival was 192 months. The median Ki-67 index was 15%. Patients aged less than or equal to 25 experienced worse neurological statuses and more repeated progression. Age less than or equal to 25 (HR 10.312, 95%CI 1.535-69.260, p=0.016), gross total resection (HR 0.116, 95%CI 0.020-0.688, p=0.018), and radiotherapy (HR 0.084, 95%CI 0.009-0.804, p=0.032) are three prognostic factors for tumor progression. Conclusion: Tumor progression remains a big concern in the clinical course of PSAE. Being aged above 25, undergoing GTR, and accepting adjuvant radiotherapy put patients at lower risk for tumor progression. Younger patients might have worse neurological statuses compared with those aged over 25.

12.
J Med Chem ; 66(5): 3484-3498, 2023 03 09.
Artigo em Inglês | MEDLINE | ID: mdl-36812150

RESUMO

We report the first attempt of double-spot structural modification on a side-chain moiety of sulfonium-type α-glucosidase inhibitors isolated from genus Salacia. A series of sulfonium salts with benzylidene acetal linkage at the C3' and C5' positions were designed and synthesized. In vitro enzyme inhibition evaluation showed that compounds with a strong electron-withdrawing group attached at the ortho position on the phenyl ring present stronger inhibitory activities. Notably, the most potent inhibitor 21b (1.0 mpk) can exhibit excellent hypoglycemic effects in mice, which can still compete with those of acarbose (20.0 mpk). Molecular docking of 21b demonstrated that besides conventional interacting patterns, the newly introduced benzylidene acetal moiety plays an important role in anchoring the whole molecule in a concave pocket of the enzyme. The successful identification of 21b as a lead compound for new drug discovery may provide a means for structure modification and diversification of the distinguished sulfonium-type α-glucosidase inhibitors.


Assuntos
Inibidores de Glicosídeo Hidrolases , Hipoglicemiantes , Camundongos , Animais , Hipoglicemiantes/farmacologia , Hipoglicemiantes/uso terapêutico , Hipoglicemiantes/química , Relação Estrutura-Atividade , Simulação de Acoplamento Molecular , Acetais , alfa-Glucosidases/metabolismo , Estrutura Molecular
13.
J Biomech ; 149: 111483, 2023 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-36787673

RESUMO

Medialization laryngoplasty is one of the primary surgical interventions in the treatment of glottal insufficiency due to vocal fold paralysis, paresis, or atrophy. During the surgery, an implant is laterally inserted into the larynx to medialize the affected vocal fold toward glottal midline, with the goal of improving glottal closure during phonation and voice production efficiency. While implants of different materials and geometry designs have been used, the effect of implant design on the voice outcome remains unclear. In this simulation study, the effect of implant stiffness was investigated in an MRI-based model of the vocal folds after medialization laryngoplasty. The results showed that implant stiffness had a significant impact on the phonation threshold pressure, glottal area waveform, and fundamental frequency, but only small effect on the closed quotient and other acoustic measures of the produced voice. The effect of implant stiffness also exhibited variability, depending on the stiffness conditions of the vocal fold and paraglottic tissues, indicating that individual differences need to be considered during the planning of medialization laryngoplasty.


Assuntos
Laringoplastia , Laringe , Prega Vocal/diagnóstico por imagem , Prega Vocal/cirurgia , Laringoplastia/métodos , Qualidade da Voz , Laringe/cirurgia , Imageamento por Ressonância Magnética
14.
Elife ; 122023 02 21.
Artigo em Inglês | MEDLINE | ID: mdl-36805107

RESUMO

Serial focussed ion beam scanning electron microscopy (FIB/SEM) enables imaging and assessment of subcellular structures on the mesoscale (10 nm to 10 µm). When applied to vitrified samples, serial FIB/SEM is also a means to target specific structures in cells and tissues while maintaining constituents' hydration shells for in situ structural biology downstream. However, the application of serial FIB/SEM imaging of non-stained cryogenic biological samples is limited due to low contrast, curtaining, and charging artefacts. We address these challenges using a cryogenic plasma FIB/SEM. We evaluated the choice of plasma ion source and imaging regimes to produce high-quality SEM images of a range of different biological samples. Using an automated workflow we produced three-dimensional volumes of bacteria, human cells, and tissue, and calculated estimates for their resolution, typically achieving 20-50 nm. Additionally, a tag-free localisation tool for regions of interest is needed to drive the application of in situ structural biology towards tissue. The combination of serial FIB/SEM with plasma-based ion sources promises a framework for targeting specific features in bulk-frozen samples (>100 µm) to produce lamellae for cryogenic electron tomography.


Assuntos
Tomografia com Microscopia Eletrônica , Imageamento Tridimensional , Humanos , Microscopia Eletrônica de Varredura , Tomografia com Microscopia Eletrônica/métodos , Íons , Imageamento Tridimensional/métodos
15.
Artigo em Inglês | MEDLINE | ID: mdl-36774657

RESUMO

Soft body armor greatly improves the comfort and security of the wearers. Although laminates based on high-performance fabrics have been adopted, it remains an enormous challenge to develop fabric laminates having flexibility, low bulge deformation, and ballistic protection capability simultaneously. Herein, we report a bullet-proof bicontinuous hydrogel (BH)/ultrahigh-molecular weight polyethylene fabric (UPF) composite. The presence of the BH significantly improves the impact resistance performance of the UPF, without compromising its flexibility. In specific, the multiscale energy dissipation structures composed of hydrogen bond associations in the chain scale, bicontinuous phase structures in the nanoscale, and fibers in the microscale are broken to dissipate energy. As a result, the impact energy of the bullet is greatly absorbed and the bulge height of the composites is significantly reduced in contrast to the neat UPF laminates. This study indicates that the flexible BH-UPF composites with multiscale energy dissipation structures have a promising application in soft body armor.

16.
J Mater Chem B ; 11(4): 905-913, 2023 01 25.
Artigo em Inglês | MEDLINE | ID: mdl-36598076

RESUMO

High performance hydrogels have essential applications in many fields such as tissue engineering and soft robot. Herein, we develop an impact resistant hydrogel composed of bicontinuous structures of polymer-hard phase and polymer-soft phase. This unique bicontinuous phase structure is formed by modulating various hydrogen bonding interactions. During loading, the polymer-hard phase is broken accompanied by the dissociation of hydrogen bonds to dissipate energy, while the polymer-soft phase distributes the load to avoid stress concentration, thus enabling the bicontinuous hydrogel to achieve excellent strength and toughness simultaneously. Furthermore, the fracture of hierarchical energy dissipation structures efficiently reduces impact strength and increases buffer time. Owing to the synergy of the bicontinuous phase structure and hierarchical energy dissipation, the resulting bicontinuous hydrogel remains intact even if it undergoes impact at a strain rate of ∼13 000 s-1. Based on these findings, it is expected that the bicontinuous hydrogel has a potential application in the field of articular cartilage repair.


Assuntos
Cartilagem Articular , Hidrogéis , Hidrogéis/química , Engenharia Tecidual , Polímeros/química , Ligação de Hidrogênio
17.
Acta Pharm ; 73(1): 121-132, 2023 Mar 01.
Artigo em Inglês | MEDLINE | ID: mdl-36692460

RESUMO

The activation of the monocyte-macrophage system and the damage to the renal and pancreatic tissue are common complications in patients with diabetes induced by hyper-glycemia. This study aimed to evaluate the effect and mechanism of butyrate (NaB), a metabolite of intestinal flora, on inhibiting the inflammatory response of human monocyte-macrophages (THP-1 cells) induced by high glucose and the damage of pancreatic and renal tissue in diabetic mice. The results showed that high concentration glucose significantly up-regulated the expressions of IL-1ß, TNF-α, and NLRP3 in THP-1 cells and mouse spleen, and that NaB could inhibit the overexpression of those genes. The abundance of Beclin-1, LC3B and reactive oxygen species (ROS) in THP-1 cells is increased due to the high glucose concentration, and NaB can inhibit the genes responsible for upregulating the expression. In diabetic mice, vacuolar degeneration of renal tubules was observed. Then we observed that some of the epithelial cells of the renal tubules were exfoliated and some formed tubules. NaB could alleviate these pathological lesions, but NaB cannot alleviate pancreatic injury. Our results indicated that NaB could be used for the prevention and adjuvant treatment of diabetic kidney injury.


Assuntos
Diabetes Mellitus Experimental , Nefropatias Diabéticas , Hiperglicemia , Humanos , Camundongos , Animais , Ácido Butírico/farmacologia , Nefropatias Diabéticas/tratamento farmacológico , Nefropatias Diabéticas/prevenção & controle , Nefropatias Diabéticas/metabolismo , Diabetes Mellitus Experimental/complicações , Diabetes Mellitus Experimental/tratamento farmacológico , Rim/metabolismo , Rim/patologia , Hiperglicemia/complicações , Hiperglicemia/tratamento farmacológico , Hiperglicemia/patologia , Glucose
18.
J Mater Chem B ; 2023 Jan 19.
Artigo em Inglês | MEDLINE | ID: mdl-36655770

RESUMO

Photo-reactive polymers are important for biomaterials, including devices with a 3D-structure. Here, different types of photo-reactive polymers were prepared and utilised for immobilisation of growth factors. They were synthesised by conjugation of gelatin with the azidophenyl group or by copolymerisation of the azidophenyl group-coupled methacrylate with poly(ethylene glycol) methacrylate. The azidophenyl content and the zeta potential of the prepared polymers were measured. After spin coating of polymers, the thickness and the water contact angle of coated layers were measured. The amount of the immobilised epidermal growth factor (EGF) was determined using fluorescence labelling. Cell adhesion responded to the nature of photo-reactive polymers but did not depend on the immobilised EGF. However, cell growth was dependent on the amount of immobilised EGF and was significantly affected by the nature of photo-reactive polymers. The study shows that the properties of the photo-immobilisation matrix significantly influence the biological activity.

19.
Adv Healthc Mater ; : e2202658, 2023 Jan 18.
Artigo em Inglês | MEDLINE | ID: mdl-36652529

RESUMO

The inflammatory cascade after spinal cord injury (SCI) causes necrotizing apoptosis of local stem cells, which limits nerve regeneration. Therefore, coordinating the inflammatory immune response and neural stem cell (NSC) functions is key to promoting the recovery of central nervous system function. In this study, a hydrogel "perfusion" system and electrospinning technology are integrated, and a "concrete" composite support for the repair of nerve injuries is built. The hydrogel's hydrophilic properties activate macrophage integrin receptors to mediate polarization into anti-inflammatory subtypes and cause a 10% increase in polarized M2 macrophages, thus reprogramming the SCI immune microenvironment. Programmed stromal cell-derived factor-1α and brain-derived neurotrophic factor released from the composite increase recruitment and neuronal differentiation of NSCs by approximately four- and twofold, respectively. The fiber system regulates the SCI immune inflammatory microenvironment, recruits endogenous NSCs, promotes local blood vessel germination and maturation, and improves nerve function recovery in a rat SCI model. In conclusion, the engineering fiber composite improves the local inflammatory response. It promotes nerve regeneration through a hydrophilic programmed cytokine-delivery system, which further improves and supplements the immune response mechanism regulated by the inherent properties of the biomaterial. The new fiber composite may serve as a new treatment approach for SCI.

20.
Molecules ; 28(2)2023 Jan 04.
Artigo em Inglês | MEDLINE | ID: mdl-36677551

RESUMO

5-Fluorouracil (5-FU) is a common anti-tumor drug, but there is no effective treatment for its side effect, intestinal mucositis. The inflammatory reaction of macrophages in intestinal mucosa induced by 5-FU is an important cause of intestinal mucositis. In this study, we investigated the anti-inflammatory effects of the three important short-chain fatty acids (SCFAs), including sodium acetate (NaAc), sodium propionate (NaPc), and sodium butyrate (NaB), on human mononuclear macrophage-derived THP-1 cells induced by 5-FU. The expressions of intracellular ROS, pro-inflammatory/anti-inflammatory cytokines, as well as the nuclear factor-κB/NLR family and pyrin domain-containing protein 3 (NF-κB/NLRP3) signaling pathway proteins were determined. Furthermore, the cell metabolites were analyzed by untargeted metabolomics techniques. Our results revealed that the three SCFAs inhibited pro-inflammatory factor expressions, including IL-1ß and IL-6, when treated with 5-FU (p < 0.05). The ROS expression and NF-κB activity of 5-FU-treated THP-1 cells were inhibited by the three SCFAs pre-incubated (p < 0.05). Moreover, NLRP3 knockdown abolished 5-FU-induced IL-1ß expression (p < 0.05). Further experiments showed that the three SCFAs affected 20 kinds of metabolites that belong to amino acid and phosphatidylcholine metabolism in THP-1 cells. These significantly altered metabolites were involved in amino acid metabolism and glycerolphospholipid and sphingolipid metabolism. It is the first time that three important SCFAs (NaAc, NaPc, and NaB) were identified as inhibiting 5-FU-induced macrophage inflammation through inhibiting ROS/NF-κB/NLRP3 signaling pathways and regulating glycerolphospholipid and sphingolipid metabolism.


Assuntos
Mucosite , NF-kappa B , Humanos , NF-kappa B/metabolismo , Proteína 3 que Contém Domínio de Pirina da Família NLR/metabolismo , Inflamassomos/metabolismo , Fluoruracila/farmacologia , Células THP-1 , Espécies Reativas de Oxigênio/metabolismo , Transdução de Sinais , Ácidos Graxos Voláteis/farmacologia , Inflamação/induzido quimicamente , Inflamação/tratamento farmacológico , Anti-Inflamatórios/farmacologia , Esfingolipídeos
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