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1.
Front Immunol ; 15: 1325860, 2024.
Artigo em Inglês | MEDLINE | ID: mdl-38487523

RESUMO

Pancreatic cancer (PC) is one of the most malignant tumors in digestive system due to its highly invasive and metastatic properties. At present, conventional treatment strategies for PC show the limited clinical efficacy. Therefore, novel effective therapeutic strategies are urgently needed. Here, we report a case of complete remission of advanced PC induced by claudin18.2-targeted CAR-T cell therapy. The patient was a 72-year-old man who was diagnosed with pancreatic ductal adenocarcinoma 2 years ago, and he experienced tumor recurrence and multiple metastases after pancreaticoduodenectomy and multi-line chemotherapies, including liver, peritoneum, and cervical lymph node metastases. Then, the patient was referred to our department for further treatment of metastatic PC, and he was enrolled in a clinical trial of claudin18.2-targeted CAR-T cell therapy. After lymphodepleting chemotherapy, the patient received claudin18.2-targeted CAR-T cell infusion at a dose of 1.2 × 106 cells/kg on November 21, 2022. During CAR-T cell therapy, the patient experienced grade 2 cytokine release syndrome (CRS) and gastric mucosa injury, which were controlled by tocilizumab and conventional symptomatic and supportive treatment. The patient achieved a complete response (CR) 1 month after claudin18.2-targeted CAR-T cell therapy, and remained in clinical remission for 8 months. Unfortunately, the patient experienced claudin18.2-negative relapse in July, 2023. Despite antigen-negative relapse after claudin18.2-targeted CAR-T cell infusion, the patient achieved sustained remission for 8 months, which indicates that claudin18.2-targeted CAR-T cell therapy is an extremely effective therapeutic strategy for the treatment of advanced PC.


Assuntos
Neoplasias Pancreáticas , Receptores de Antígenos Quiméricos , Masculino , Humanos , Idoso , Recidiva Local de Neoplasia , Neoplasias Pancreáticas/terapia , Resposta Patológica Completa , Recidiva , Terapia Baseada em Transplante de Células e Tecidos
2.
Int J Biol Macromol ; 266(Pt 1): 130838, 2024 May.
Artigo em Inglês | MEDLINE | ID: mdl-38521322

RESUMO

Innovative antibacterial therapies using nanomaterials, such as photothermal (PTT) and photodynamic (PDT) treatments, have been developed for treating wound infections. However, creating secure wound dressings with these therapies faces challenges. The primary focus of this study is to prepare an antibacterial nanofiber dressing that effectively incorporates stable loads of functional nanoparticles and demonstrates an efficient synergistic effect between PTT and PDT. Herein, a composite nanofiber mat was fabricated, integrating spherical molybdenum disulfide (MoS2) nanoparticles. MoS2 was deposited onto polylactic acid (PLA) nanofiber mats using vacuum filtration, which was further stabilized by sodium carboxymethyl cellulose (CMC) adhesion and glutaraldehyde (GA) cross-linking. The composite nanofibers demonstrated synergistic antibacterial effects under NIR light irradiation, and the underlying mechanism was explored. They induce bacterial membrane permeability, protein leakage, and intracellular reactive oxygen species (ROS) elevation, ultimately leading to >95 % antibacterial activity against Staphylococcus aureus (S. aureus) and Escherichia coli (E. coli), which is higher than that of single thermotherapy (almost no antibacterial activity) or ROS therapy (about 80 %). In addition, the composite nanofiber mats exhibited promotion effects on infected wound healing in vivo. This study demonstrates the great prospects of composite nanofiber dressings in clinical treatment of bacterial-infected wounds.


Assuntos
Antibacterianos , Carboximetilcelulose Sódica , Dissulfetos , Escherichia coli , Molibdênio , Nanofibras , Fotoquimioterapia , Staphylococcus aureus , Molibdênio/química , Molibdênio/farmacologia , Dissulfetos/química , Dissulfetos/farmacologia , Nanofibras/química , Antibacterianos/farmacologia , Antibacterianos/química , Fotoquimioterapia/métodos , Carboximetilcelulose Sódica/química , Carboximetilcelulose Sódica/farmacologia , Staphylococcus aureus/efeitos dos fármacos , Animais , Escherichia coli/efeitos dos fármacos , Cicatrização/efeitos dos fármacos , Camundongos , Espécies Reativas de Oxigênio/metabolismo , Terapia Fototérmica/métodos , Bandagens
3.
J Appl Biomed ; 22(1): 23-32, 2024 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-38505967

RESUMO

Dictyophora indusiata, commonly known as bamboo fungus, is a type of edible mushroom that is highly popular worldwide for its rich flavor and nutritional value. It is also recognized for its pharmaceutical efficacy, with medicinal benefits attributed to its consumption. One of the most important components of Dictyophora indusiata is polysaccharide, which has been acknowledged as a promising regulator of biological response due to its immunostimulatory and anti-inflammatory properties. However, the specific roles of polysaccharide in modulating the NOD-like receptor protein 3 (NLRP3) inflammasome activation within macrophages remain relatively under-researched. To investigate this further, the mechanism by which Dictyophora indusiata polysaccharide (DIP) exerts its immunostimulatory activity in RAW 264.7 macrophages was analyzed. Results indicated that DIP has the potential to facilitate the priming of NLRP3 inflammasome activation by enhancing TLR4 expression, phosphorylation of IκB-α, and nuclear translocation of NF-κB p65 subunit. It was noted that DIP was unable to mediate the second step of NLRP3 inflammasome activation. The findings of this study provide compelling evidence that DIP has immunomodulatory effects by modulating the NLRP3 inflammasome in RAW264.7 macrophages.


Assuntos
Basidiomycota , Inflamassomos , NF-kappa B , NF-kappa B/metabolismo , Inflamassomos/metabolismo , Proteína 3 que Contém Domínio de Pirina da Família NLR/metabolismo , Receptor 4 Toll-Like/metabolismo , Proteínas NLR , Transdução de Sinais , Polissacarídeos/farmacologia
4.
Dalton Trans ; 53(9): 3975-3979, 2024 Feb 27.
Artigo em Inglês | MEDLINE | ID: mdl-38348674

RESUMO

We achieve a successful transition of Co4O4 molecules from a homogeneous to a heterogeneous system by modifying the functional groups at their termini. The resulting cocatalyst, denoted as Co4O4-poly, not only preserved the catalytic sites of Co4O4 molecules but also exhibited outstanding performance in catalyzing water oxidation.

5.
Adv Sci (Weinh) ; 11(17): e2400099, 2024 May.
Artigo em Inglês | MEDLINE | ID: mdl-38417112

RESUMO

Metal sulfide-based homojunction photocatalysts are extensively explored with improved photocatalytic performance. However, the construction of metal sulfide-based S-scheme homojunction remains a challenge. Herein, the fabrication of 2D CdIn2S4 nanosheets coated 3D CdIn2S4 octahedra (referred to as 2D/3D n-CIS/o-CIS) S-scheme homojunction photocatalyst is reported by simply adjustment of polyvinyl pyrrolidone amount during the solvothermal synthesis. The formation of S-scheme homojunction within n-CIS/o-CIS is systematically investigated via a series of characterizations, which can generate an internal electric field to facilitate the separation and migration of photogenerated electron-hole pairs. The 2D/3D n-CIS/o-CIS composite exhibits significantly improved photocatalytic activity and stability in the selective oxidation of phenylcarbinol (PhCH2OH) to benzaldehyde (PhCHO) when compared to pure n-CIS and o-CIS samples under visible light irradiation. It is hoped that this work can contribute novel insights into the development of metal sulfides S-scheme homojunction photocatalysts for solar energy conversion.

6.
Int J Cardiovasc Imaging ; 40(4): 789-799, 2024 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-38212592

RESUMO

To explore the association of ventricle epicardial fat volume (EFV) calculated by cardiac magnetic resonance (CMR) and the insulin resistance indicator of triglyceride-glucose (TyG) index in patients with chronic HF (CHF), this retrospective cohort study included adult CHF patients with confirmed diagnosis of heart failure from January 2018 to December 2020. All patients underwent 3.0T CMR, and EFV were measured under short-axis cine. Spearman correlation, multivariate linear regression, and restricted cubic spline (RCS) regression were used to analyze their association. There were 516 patients with CHF, of whom 69.8% were male. Median EFV was 57.14mL and mean TyG index was 8.48. Spearman correlation analysis showed that TyG index was significantly correlated with the EFV in CHF patients (r = 0.247, P < 0.001). Further analysis showed that TyG index levels were significantly associated with EFV as both continuous variables (Unstandardized ß = 6.556, P < 0.001) and across the increasing quartiles (ß = 7.50, 95% CI [1.41, 13.59], P < 0.05). RCS demonstrated there were a positive trend and linear association between EFV and TyG index in CHF patients (P for nonliearity = 0.941). In patients with CHF, the TyG index was positively and linearly associated with the EFV, which supports the metabolic roles of epicardial adipose tissue regarding insulin resistance.


Assuntos
Tecido Adiposo , Adiposidade , Insuficiência Cardíaca , Resistência à Insulina , Pericárdio , Idoso , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Tecido Adiposo/diagnóstico por imagem , Biomarcadores/sangue , Glicemia/metabolismo , Doença Crônica , Tecido Adiposo Epicárdico , Insuficiência Cardíaca/diagnóstico por imagem , Insuficiência Cardíaca/fisiopatologia , Insuficiência Cardíaca/sangue , Ventrículos do Coração/diagnóstico por imagem , Ventrículos do Coração/fisiopatologia , Imagem Cinética por Ressonância Magnética , Pericárdio/diagnóstico por imagem , Valor Preditivo dos Testes , Estudos Retrospectivos , Triglicerídeos/sangue , Função Ventricular Esquerda
7.
Phytomedicine ; 123: 155234, 2024 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-38042008

RESUMO

BACKGROUND: Liver injury is a prevalent global health concern, impacting a substantial number of individuals and leading to elevated mortality rates and socioeconomic burdens. Traditional primary treatment options encounter resource constraints and high costs, prompting exploration of alternative adjunct therapies, such as phytotherapy. Curcumin demonstrates significant therapeutic potential across various medical conditions, particularly emerging as a promising candidate for liver injury treatment. PURPOSE: This study aims to provide current evidence maps of curcumin and its analogs in the context of liver injury, covering aspects of biosafety, toxicology, and clinical trials. Importantly, it seeks to summarize the intricate mechanisms modulated by curcumin. METHODS: We conducted a comprehensive search of MEDLINE, Web of Science, and Embase up to July 2023. Titles and abstracts were reviewed to identify studies that met our eligibility criteria. The screening process involved three authors independently assessing the potential of curcumin mitigating liver injury and its disease consequences by reviewing titles, abstracts, and full texts. RESULTS: Curcumin and its analogs have demonstrated low toxicity in vitro and in vivo. However, the limited bioavailability has hindered their advanced use in liver injury. This limitation can potentially be addressed by nano-curcumin and emerging drug delivery systems. Curcumin plays a role in alleviating liver injury by modulating the antioxidant system, as well as cellular and molecular pathways. The specific mechanisms involve multiple pathways, such as NF-κB, p38/MAPK, and JAK2/STAT3, and the pro-apoptosis Bcl-2/Bax/caspase-3 axis in damaged cells. Additionally, curcumin targets nutritional metabolism, regulating the substance in liver cells and tissues. The microenvironment associated with liver injury, like extracellular matrix and immune cells and factors, is also regulated by curcumin. Initial evaluation of curcumin and its analogs through 12 clinical trials demonstrates their potential application in liver injury. CONCLUSION: Curcumin emerges as a promising phytomedicine for liver injury owing to its effectiveness in hepatoprotection and low toxicity profile. Nevertheless, in-depth investigations are warranted to unravel the complex mechanisms through which curcumin influences liver tissues and overall physiological milieu. Moreover, extensive clinical trials are essential to determine optimal curcumin dosage forms, maximizing its benefits and achieving favorable clinical outcomes.


Assuntos
Curcumina , Humanos , Curcumina/farmacologia , Fígado/metabolismo , Antioxidantes/farmacologia , NF-kappa B , Apoptose
8.
Biotechnol J ; 19(1): e2300136, 2024 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-37971189

RESUMO

The L-serine exporters ThrE and SerE play important roles in L-serine production by Corynebacterium glutamicum. Deletion of both thrE and serE decreased L-serine titer by 60%, suggesting the existence of other L-serine exporters. A comparative transcriptomics identified NCgl0254 and NCgl0255 as novel L-serine exporters. Further analysis of the contributions of ThrE, SerE, NCgl0254, and NCgl0255 found that SerE was the major L-serine exporter in C. glutamicum and these four L-serine exporters were responsible for 79.7% of L-serine export. Deletion of one L-serine exporter upregulated the transcription levels of the other three, which might be coursed by increased intracellular concentrations of L-serine. Overexpression of NCgl0254 and NCgl0255 increased L-serine titer by 20.8% in C. glutamicum A36, while overexpression of the four L-serine exporters increased L-serine production by 31.9% (41.1 g·L-1 ) in C. glutamicum A36. The identification of novel L-serine exporters in C. glutamicum will help to improve industrial production of L-serine.


Assuntos
Corynebacterium glutamicum , Corynebacterium glutamicum/genética , Serina , Proteínas de Bactérias/genética , Engenharia Metabólica
9.
Adv Sci (Weinh) ; 11(2): e2305919, 2024 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-37984864

RESUMO

Regulating the interfacial charge transfer behavior between cocatalysts and semiconductors remains a critical challenge for attaining efficient photoelectrochemical water oxidation reactions. Herein, using bismuth vanadate (BiVO4 ) photoanode as a model, it introduces an Au binding bridge as holes transfer channels onto the surfaces of BiVO4 , and the cyano-functionalized cobalt cubane (Co4 O4 ) molecules are preferentially immobilized on the Au bridge due to the strong adsorption of cyano groups with Au nanoparticles. This orchestrated arrangement facilitates the seamless transfer of photogenerated holes from BiVO4 to Co4 O4 molecules, forming an orderly charge transfer pathway connecting the light-absorbing layer to reactive sites. An exciting photocurrent density of 5.06 mA cm-2 at 1.23 V versus the reversible hydrogen electrode (3.4 times that of BiVO4 ) is obtained by the Co4 O4 @Au(A)/BiVO4 photoanode, where the surface charge recombination is almost completely suppressed accompanied by a surface charge transfer efficiency over 95%. This work represents a promising strategy for accelerating interfacial charge transfer and achieving efficient photoelectrochemical water oxidation reaction.

10.
Front Bioeng Biotechnol ; 11: 1295406, 2023.
Artigo em Inglês | MEDLINE | ID: mdl-38090713

RESUMO

Introduction: Ticagrelor is extensively utilized for the treatment of acute coronary syndromes (ACS), but its platelet aggregation inhibitory effects can potentially result in tissue bleeding, posing a serious risk to patients' lives. Methods: In this study, we developed highly sensitive full length anti-ticagrelor Quenchbodies (Q-bodies) for fast monitoring of ticagrelor both in solution and serum for the first time. Ticagrelor coupled with N- hydroxysuccinimide (Ticagrelor-NHS) ester was also designed and synthesized for interaction and biological activity detection. Results: Both ATTO-labeled MEDI2452 (2452A) Q-body and TAMRA-labeled IgG 152 (152T) Q-body demonstrated efficient detection of ticagrelor and its active metabolite (TAM). The 2452A Q-body exhibited a broader detection range, while the 152T Q-body displayed a lower limit of detection (LOD). Under physiological conditions (Ticagrelor:TAM, 3:1), the concentration of ticagrelor was further measured, yielding LOD values of 4.65 pg/mL and 2.75 pg/mL for the two Q-bodies, with half-maximal effect concentrations of 8.15 ng/mL and 3.0 ng/mL, respectively. Discussion: Compared with traditional liquid chromatography-mass spectrometry (LC-MS) methods, anti-ticagrelor Q-bodies have higher sensitivity and detection speed. It enabled the completion of analysis within 3 min, facilitating rapid preoperative detection of blood drug concentration in ACS to determine the feasibility of surgery and mitigate the risk of intraoperative and postoperative hemorrhage. The swift detection of ticagrelor holds promise for enhancing individualized drug administration, preventing adverse reactions, and providing preoperative guidance.

11.
Opt Express ; 31(24): 39717-39726, 2023 Nov 20.
Artigo em Inglês | MEDLINE | ID: mdl-38041287

RESUMO

Green micro-light emitting diodes (micro-LEDs) is one of the three primary color light sources as full-color display, which serves as a key research object in the field of micro-LED display. As the micro-LED size decreases, the surface-area-to-volume ratio of the device increases, leading to more serious damage on the sidewall by inductively coupled plasma (ICP) etching. The passivation process of SiO2 provides an effective method to reduce sidewall damage caused by ICP etching. In this work, green rectangular micro-LEDs with passivation layer thickness of 0∼600 nm was designed using the finite-difference time-domain (FDTD) simulation. In order to verify the simulation results, the micro-LED array was fabricated by parallel laser micro-lens array (MLA) lithography in high speed and large area. The effect of the SiO2 passivation layer thickness on the performance of the green micro-LED was analyzed, which shows that the passivation layer thickness-light extraction efficiency curve fluctuates periodically. For the sample with 90 nm thickness of SiO2 passivation layer, there exists a small leakage current and higher operating current density, and the maximum external quantum efficiency (EQE) is 2.8 times higher than micro-LED without SiO2 passivation layer.

12.
Drug Des Devel Ther ; 17: 3783-3801, 2023.
Artigo em Inglês | MEDLINE | ID: mdl-38146490

RESUMO

Purpose: This study was designed to evaluate the immune protective efficacy of the novel Streptococcus pneumoniae (S. pneumoniae) protein vaccine PiuA-PlyD4 through immunoinformatics prediction and in vitro and in vivo experiments. Methods: In this study, we conducted immunoinformatics prediction and protection analysis on the fusion protein PiuA-PlyD4. The epitope composition of the vaccine was analyzed based on the prediction of B-cell and helper T-cell epitopes. Meanwhile, the molecular docking of PiuA and TLR2/4 was simulated. After immunizing C57BL/6 mice with the prepared vaccine, the biological safety, immunogenicity and conservation were evaluated. By constructing different infection models and from the aspects of adhesion inhibition and cytokines, the protective effect of the fusion protein vaccine PiuA-PlyD4 on S. pneumoniae infection was explored. Results: PiuA-PlyD4 has abundant B-cell and helper T-cell epitopes and shows a high antigenicity score and structural stability. Molecular docking analysis suggested the potential interaction between PiuA and TLR2/4. The specific antibody titer of fusion protein antiserum was as high as (7.81±2.32) ×105. The protective effect of the immunized mice on nasal and lung colonization was significantly better than that of the control group, and the survival rate against S. pneumoniae infection of serotype 3 reached 50%. Cytokine detection showed that the humoral immune response, Th1, Th2 and Th17 cellular immune pathways were all involved in the process. Conclusion: The study indicates that PiuA-PlyD4, whether the results are predicted by immunoinformatics or experimentally validated in vivo and in vitro, has good immunogenicity and immunoreactivity and can provide effective protection against S. pneumoniae infection. Therefore, it can be considered a promising prophylactic vaccine candidate for S. pneumoniae.


Assuntos
Infecções Pneumocócicas , Vacinas , Animais , Camundongos , Streptococcus pneumoniae , Infecções Pneumocócicas/prevenção & controle , Epitopos de Linfócito T , Imunoinformática , Simulação de Acoplamento Molecular , Receptor 2 Toll-Like , Camundongos Endogâmicos C57BL , Citocinas , Epitopos de Linfócito B
13.
Front Plant Sci ; 14: 1274939, 2023.
Artigo em Inglês | MEDLINE | ID: mdl-37965030

RESUMO

Hami melon is prone to postharvest perishing. Melatonin is a signaling molecule involved in a variety of physiological processes in fruit, and it improves fruit quality. We hypothesized that melatonin treatment would improve the storage quality of Hami melon by altering its respiration and reactive oxygen species (Graphical abstract). Our results indicated that optimal melatonin treatment (0.5 mmol L-1) effectively slowed the softening, weight loss, and respiratory rate of the Hami melon fruit. Furthermore, melatonin markedly improved the antioxidant capacity of the fruit and protected it from oxidative damage by decreasing its contents of superoxide anions, hydrogen peroxide, and malondialdehyde. Melatonin significantly enhanced the activities of superoxide dismutase, catalase, ascorbate peroxidase, and peroxidase. The total phenol, total flavonoids, and ascorbic acid contents were maintained by melatonin treatment. This treatment also repressed the activities of lipase, lipoxygenase, and phospholipase D, which are related to lipid metabolism. Thus, exogenous melatonin can maintain postharvest organoleptic quality of Hami melon fruit by increasing its antioxidant activity and inhibiting reactive oxygen species production.

14.
Percept Mot Skills ; 130(6): 2582-2602, 2023 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-37918019

RESUMO

In this meta-analysis we explored whether Taekwondo practice has improved its participants' physical self-concepts. We also tested the mediating influence of factors in past research such as country, participant age, and measurement properties in their associations with these taekwondo effects. We reviewed extensive data collected from Chinese, English and Korean participants in articles listed in Cnki, Wanfang, PubMed, Web of Science, KISS, RISS, and DBPIA databases. First, we evaluated the methodological quality of these published articles with Review Manager 5.4 software according to the Cochrane System Evaluation Manual. Then, we used Comprehensive Meta-Analysis 3.7 software for statistical analysis. We based these analyses on nine research studies containing a total of 1154 participants. We found a significant association between taekwondo activity and an improved body self-concept (ES = .688, p < .001). Subgroup analyses showed a stronger association between these variables in Korea (ES = .90, p < .001) than in China (ES = .34, p < .001), a stronger association for children (ES = 1.04, p < .001) compared to adults (ES = .46, p < .001), and a stronger association with the modified version of the Physical Self-Description Questionnaire (PSDQ) (ES = .99, p < .001) than with the original PSDQ (ES = .57, p < .001). We concluded that practicing Taekwondo led to improved physical self-concept, especially in a younger population. In addition, the experimental design and measurement methods may influence the apparent link between these variables.


Assuntos
Artes Marciais , Adulto , Criança , Humanos , Autoimagem
15.
ACS Omega ; 8(41): 38481-38493, 2023 Oct 17.
Artigo em Inglês | MEDLINE | ID: mdl-37867710

RESUMO

The excessive use of antibiotics and consequent bacterial resistance have emerged as crucial public safety challenges for humanity. As a promising antibacterial treatment, using reactive oxygen species (ROS) can effectively address this problem and has the advantages of being highly efficient and having low toxicity. Herein, electrospinning and electrospraying were employed to fabricate magnesium oxide (MgO)-based nanoparticle composited polycaprolactone (PCL) nanofibrous dressings for the chemodynamic treatment of bacteria-infected wounds. By utilizing electrospraying, erythrocyte-like monoporous PCL microspheres incorporating silver (Ag)- and copper (Cu)-doped MgO nanoparticles were generated, and the unique microsphere-filament structure enabled efficient anchoring on nanofibers. The composite dressings produced high levels of ROS, as confirmed by the 2,7-dichloriflurescin fluorescent probe. The sustained generation of ROS resulted in efficient glutathione oxidation and a remarkable bacterial killing rate of approximately 99% against Staphylococcus aureus (S. aureus). These dressings were found to be effective at treating externally infected wounds. The unique properties of these composite nanofibrous dressings suggest great potential for their use in the medical treatment of bacteria-infected injuries.

16.
Exp Ther Med ; 26(5): 533, 2023 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-37869643

RESUMO

Exposure to hypoxia disrupts energy metabolism and induces inflammation. However, the pathways and mechanisms underlying energy metabolism disorders caused by hypoxic conditions remain unclear. In the present study, a hypoxic animal model was created and transcriptomic and non-targeted metabolomics techniques were applied to further investigate the pathways and mechanisms of hypoxia exposure that disrupt energy metabolism. Transcriptome results showed that 3,007 genes were significantly differentially expressed under hypoxic exposure, and Gene Ontology annotation analysis and Kyoto Encyclopaedia of Genes and Genomes (KEGG) enrichment analysis showed that the differentially expressed genes (DEGs) were mainly involved in energy metabolism and were significantly enriched in the tricarboxylic acid (TCA) cycle and oxidative phosphorylation (OXPHOS) pathway. The DEGs IDH3A, SUCLA2, and MDH2 in the TCA cycle and the DEGs NDUFA3, NDUFS7, UQCRC1, CYC1 and UQCRFS1 in the OXPHOS pathway were validated using mRNA and protein expression, and the results showed downregulation. The results of non-targeted metabolomics showed that 365 significant differential metabolites were identified under plateau hypoxia stress. KEGG enrichment analysis showed that the differential metabolites were mainly enriched in metabolic processes, such as energy, nucleotide and amino acid metabolism. Hypoxia exposure disrupted the TCA cycle and reduced the synthesis of amino acids and nucleotides by decreasing the concentration of cis-aconitate, α-ketoglutarate, NADH, NADPH and that of most amino acids, purines, and pyrimidines. Bioinformatics analysis was used to identify inflammatory genes related to hypoxia exposure and some of them were selected for verification. It was shown that the mRNA and protein expression levels of IL1B, IL12B, S100A8 and S100A9 in kidney tissues were upregulated under hypoxic exposure. The results suggest that hypoxia exposure inhibits the TCA cycle and the OXPHOS signalling pathway by inhibiting IDH3A, SUCLA2, MDH2, NDUFFA3, NDUFS7, UQCRC1, CYC1 and UQCRFS1, thereby suppressing energy metabolism, inducing amino acid and nucleotide deficiency and promoting inflammation, ultimately leading to kidney damage.

17.
Front Endocrinol (Lausanne) ; 14: 1162415, 2023.
Artigo em Inglês | MEDLINE | ID: mdl-37664852

RESUMO

Postmenopausal osteoporosis is the main cause of fractures in women. Resistance exercise has a positive effect on bone mineral density in postmenopausal osteoporosis patients, but its mechanism is unclear. The purpose of this study was to explore the mechanism of resistance exercise in improving ovariectomized osteoporotic rats based on the transcriptome sequencing technique. Eighteen female Sprague-Dawley rats were randomly divided into the sham-operated group, the non-exercise group, and the resistance exercise group. The rat model of postmenopausal osteoporosis was established by bilateral ovariectomy. Ten weeks after the operation, the resistance exercise group received 2 weeks of adaptive training, and 12 weeks of resistance exercise began in the 13th week. The rats were trained 5 days per week, in 4 sets of 3 repetitions per day. After the intervention, all rats were sacrificed, and the body weight, bone mineral density, trabecular bone microarchitecture, and bone biomechanics were examined. At the same time, RNA-seq and enrichment analysis of gene ontology and Kyoto Encyclopedia of Genes and Genomes were performed on the left tibias, followed by Elisa and RT-qPCR verification. It had been found that resistance exercise can effectively counteract the weight gain of ovariectomized osteoporotic rats, and has a good effect on bone mineral density and trabecular bone microarchitecture. Enrichment analysis showed that regulation of gene expression and osteoclast differentiation is the most closely related biological process and signaling pathway shared by RE/Ovx and NE/Ovx groups. Our results revealed that resistance exercise can play a role in inhibiting osteoclast activation and preventing the enhancement of osteoclast bone resorption function in ovariectomized osteoporotic rats by inhibiting Fos/Fosb-regulated TRAP activation and relieving Calcr inhibition, which has important application value in preventing bone loss caused by estrogen deficiency.


Assuntos
Osteoporose Pós-Menopausa , Osteoporose , Treinamento Resistido , Feminino , Ratos , Animais , Humanos , Osteoporose Pós-Menopausa/genética , Osteoporose Pós-Menopausa/prevenção & controle , Projetos Piloto , Transcriptoma , Ratos Sprague-Dawley , Osteoporose/genética
18.
J Mater Chem B ; 11(33): 8046-8055, 2023 08 24.
Artigo em Inglês | MEDLINE | ID: mdl-37539498

RESUMO

In most circumstances, wounds face the challenges of bacterial invasions and inappropriate inflammatory responses when they lack proper wound management. Endowing dressings with both antibacterial and anti-inflammatory functions is a compelling strategy for resolving the above issues. However, seizing the right moment to change the dressings and providing satisfactory management of wounds are still urgently required. Herein, an antibacterial and anti-inflammatory nanofibrous mat is proposed by encapsulating antibiotic gentamicin sulfate (GS) and anti-inflammatory drug ibuprofen (IB) into nanofibers via a coaxial electrospinning technique and is further decorated with Prussian blue nanocrystals (PBNCs) to enhance anti-inflammatory activity and, more importantly, to monitor bacterial infections and guide dressing changes in a timely manner. Such a nanofibrous mat releases most of the therapeutic drugs within 120 min and reveals excellent antibacterial activity and anti-inflammatory ability. Specifically, it can destroy both Staphylococcus aureus (S. aureus) and Escherichia coli (E. coli), as well as conspicuously reduce the production of reactive oxygen species (ROS) and the expression of pro-inflammatory cytokines in macrophages. In addition, the nanofibrous mat can be used for point-of-use diagnosis of living bacteria relying on the naked eye or color analysis, which exhibits the potential of monitoring wound infection and guiding dressing changes promptly. This finding demonstrates the theranostic applications of multifunctional nanofibrous mats in wound healing.


Assuntos
Nanofibras , Nanofibras/química , Antibacterianos/química , Antibacterianos/farmacologia , Anti-Inflamatórios/química , Anti-Inflamatórios/farmacologia , Staphylococcus aureus/efeitos dos fármacos , Escherichia coli/efeitos dos fármacos , Células RAW 264.7 , Animais , Camundongos , Espécies Reativas de Oxigênio/metabolismo
19.
Int J Biol Macromol ; 242(Pt 3): 125144, 2023 Jul 01.
Artigo em Inglês | MEDLINE | ID: mdl-37268080

RESUMO

Diabetic ulcer is a severe complication of diabetes that can lead to amputation due to the overproduction of pro-inflammatory factors and reactive oxygen species (ROS). In this study, a composite nanofibrous dressing was developed by combining Prussian blue nanocrystals (PBNCs) and heparin sodium (Hep) through electrospinning, electrospraying, and chemical deposition. The nanofibrous dressing (PPBDH) was designed to take advantage of the excellent pro-inflammatory factor-adsorbing capability of Hep and the ROS-scavenging capabilities of PBNCs, resulting in synergistic treatment. It is worth noting that the nanozymes were firmly anchored to the fiber surfaces through slight polymer swelling caused by the solvent during electrospinning, thereby guaranteeing the preservation of the enzyme-like activity levels of PBNCs. The PPBDH dressing was found to be effective in reducing intracellular ROS levels, protecting cells from ROS-induced apoptosis, and capturing excessive pro-inflammatory factors, including chemoattractant protein-1 (MCP-1) and interleukin-1ß (IL-1ß). Furthermore, a chronic wound healing evaluation conducted in vivo demonstrated that the PPBDH dressing was able to effectively alleviate the inflammatory response and accelerate wound healing. This research presents an innovative approach to fabricate nanozyme hybrid nanofibrous dressings, which have great potential in accelerating the healing of chronic and refractory wounds with uncontrolled inflammation.


Assuntos
Diabetes Mellitus , Nanofibras , Humanos , Espécies Reativas de Oxigênio/farmacologia , Nanofibras/química , Heparina/farmacologia , Cicatrização , Bandagens , Anti-Inflamatórios/farmacologia , Anti-Inflamatórios/uso terapêutico
20.
Langmuir ; 39(26): 8963-8973, 2023 Jul 04.
Artigo em Inglês | MEDLINE | ID: mdl-37339351

RESUMO

Fat crystals provided the strength of the colloidal network in W/O emulsions and stabilized water droplets. To understand the stabilizing effect of fat-regulated emulsions, W/O emulsions with different edible fats were fabricated. The result indicated that more stable W/O emulsions were produced by palm oil (PO) and palm stearin (PS), whose proportions of fatty acids were similar. Meanwhile, water droplets inhibited the crystallization of emulsified fats but participated in the formation of the colloidal network with fat crystals in emulsions, and the Avrami equation showed a slower crystallization rate of emulsified fats than the corresponding fat blends. However, water droplets participated in the formation of a colloidal network of fat crystals in emulsions, and the adjacent fat crystals were connected through a bridge constructed by water droplets. Fats in the emulsion containing palm stearin crystallized faster and more easily formed the ß-polymorph. The small-angle X-ray scattering (SAXS) data were interpreted by the unified fit model to determine the average size of crystalline nanoplatelets (CNPs). The larger CNPs (>100 nm) with a rough surface of emulsified fats and a uniform distribution of their aggregates was confirmed.

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