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1.
Eur J Immunol ; : e2350655, 2024 Jul 07.
Artigo em Inglês | MEDLINE | ID: mdl-38973083

RESUMO

Sepsis arises from an uncontrolled inflammatory response triggered by infection or stress, accompanied by alteration in cellular energy metabolism, and a strong correlation exists between these factors. Alpha-ketoglutarate (α-KG), an intermediate product of the TCA cycle, has the potential to modulate the inflammatory response and is considered a crucial link between energy metabolism and inflammation. The scavenger receptor (SR-A5), a significant pattern recognition receptor, assumes a vital function in anti-inflammatory reactions. In the current investigation, we have successfully illustrated the ability of α-KG to mitigate inflammatory factors in the serum of septic mice and ameliorate tissue damage. Additionally, α-KG has been shown to modulate metabolic reprogramming and macrophage polarization. Moreover, our findings indicate that the regulatory influence of α-KG on sepsis is mediated through SR-A5. We also elucidated the mechanism by which α-KG regulates SR-A5 expression and found that α-KG reduced the N6-methyladenosine level of macrophages by up-regulating the m6A demethylase ALKBH5. α-KG plays a crucial role in inhibiting inflammation by regulating SR-A5 expression through m6A demethylation during sepsis. The outcomes of this research provide valuable insights into the relationship between energy metabolism and inflammation regulation, as well as the underlying molecular regulatory mechanism.

2.
Anal Chem ; 2024 Jul 11.
Artigo em Inglês | MEDLINE | ID: mdl-38989829

RESUMO

Accelerating the migration of interfacial carriers in heterojunctions is crucial for achieving highly sensitive photoelectrochemical (PEC) sensing. In this study, we developed three-dimensional (3D)/two-dimensional (2D) CuInS2/red phosphorus nanosheet (CuInS2/RP NS) n-n heterojunction functional materials with enhanced interfacial charge transfer capabilities for PEC sensing. The 3D CuInS2 serves as a conductive layer, providing excellent electronic conductivity and superior electron absorption and transport properties. In contrast, the ultrathin RP NS acts as a transport layer that enhances carrier mobility. The 3D/2D heterojunction ensures a large interface contact surface, shortening the carrier transport distance. A well-aligned band position generates a substantial built-in electric field, providing a significant driving force for efficient carrier separation and migration, thereby improving response sensitivity. A PEC aptamer sensor was constructed based on the synthesized heterostructure for ciprofloxacin detection. The detection limit of the CuInS2/RP NS aptamer sensor for ciprofloxacin is 2.03 × 10-15 mg·mL-1, with a linear range from 1.0 × 10-14 to 1.0 × 10-5 mg·mL-1. This work presents a strategy for enhancing the photoelectric response by modulating the interface structure of heterojunctions, thereby opening new prospects for the application of highly sensitive PEC sensors in antibiotic detection.

3.
Infect Drug Resist ; 17: 2823-2832, 2024.
Artigo em Inglês | MEDLINE | ID: mdl-39005857

RESUMO

Introduction: Recent studies suggested the potential benefits of extended infusion times to optimize the treatment efficacy of ceftazidime/avibactam, which indicated that the current pharmacokinetic/pharmacodynamic (PK/PD) target may not be sufficient, especially for severe infections. The purpose of this study is to assess the adequacy of dosing strategies and infusion durations of ceftazidime/avibactam when applying higher PK/PD targets. Methods: This study utilized published PK parameters to conduct Monte Carlo simulations. Different dosages including the recommended regimen based on renal function were simulated and evaluated by the probability of target attainment (PTA) and cumulative fraction of response (CFR). Different PK/PD targets were set for ceftazidime and avibactam. MIC distributions from various sources were used to calculate the CFR. Results: Multiple PK/PD targets have been set in this study, All recommended dosage could easily achieve the target of 50%fT ≥ MIC (ceftazidime) and 50%fT ≥ CT=1.0 mg/L (avibactam). However, for severe infection patients with normal renal function and augmented renal clearance at the recommended dosage (2000 mg/500 mg, every 8 hours), the infusion duration needs to be extended to 3 hours and 4 hours to achieve the targets of 100%fT ≥ MIC and 100%fT ≥ CT=1.0 mg/L. Only continuous infusion at higher dosages achieved 100%fT ≥ 4×MIC and 100%fT ≥ CT=4.0 mg/L targets to all currently recommended regimens. According to the varying MIC distributions, higher concentrations are needed for Pseudomonas aeruginosa, with the attainment rates vary across different regions. Conclusion: The current recommended dosing regimen of ceftazidime/avibactam is insufficient for severe infection patients, and continuous infusion is suggested.

4.
Front Immunol ; 15: 1412470, 2024.
Artigo em Inglês | MEDLINE | ID: mdl-39007153

RESUMO

The etiology of Guillain-Barré syndrome (GBS) may be autoimmune. About two-thirds of patients typically experience their first symptoms within 5 days to 3 weeks after common infectious diseases, surgery, or vaccination. Infection is a triggering factor for over 50% of patients. In recent years, a growing number of studies have indicated that some immune checkpoint inhibitors and COVID-19 may also contribute to the occurrence of GBS. However, drugs are considered a rare cause of GBS. The patient in our case was a 70-year-old man who developed GBS after initiating secukinumab for psoriasis. Upon diagnosis suggesting a potential association between secukinumab and the development of GBS, as per the Naranjo adverse drug reaction (ADR) probability scale, we decided to discontinue the drug. Following this intervention, along with the administration of immunoglobulin, the patient exhibited a significant improvement in extremity weakness. The association of GBS with secukinumab treatment, as observed in this case, appears to be uncommon. The underlying mechanisms that may link secukinumab to the development of GBS are not yet fully understood and warrant further scientific inquiry and rigorous investigation. However, we hope that this report can raise greater awareness and vigilance among medical professionals to enhance the safety of patients' medication.


Assuntos
Anticorpos Monoclonais Humanizados , Síndrome de Guillain-Barré , Psoríase , Humanos , Síndrome de Guillain-Barré/induzido quimicamente , Síndrome de Guillain-Barré/etiologia , Anticorpos Monoclonais Humanizados/efeitos adversos , Anticorpos Monoclonais Humanizados/uso terapêutico , Idoso , Masculino , Psoríase/tratamento farmacológico , Psoríase/complicações , SARS-CoV-2 , COVID-19/complicações
5.
Chem Sci ; 15(25): 9733-9741, 2024 Jun 26.
Artigo em Inglês | MEDLINE | ID: mdl-38939145

RESUMO

Highly efficient degradation of antibiotics is a huge challenge due to the extremely stable molecules and the potential for biological resistance. However, conventional degradation methods are limited to lower degradation rate, higher energy consumption and secondary pollution. Herein, we report a new Cu-based metal-organic framework (MOF), featuring classical planar trinuclear [Cu3(µ3-O)]4+ clusters within the pores. The presence of the rich open metal sites and the large pore ratio, as well as the high catalytic activity of Cu2+ ions, are conducive to boosting the degradation of various antibiotics (>95%) under the activation of peroxymonosulfate. Remarkably, this is the first MOF to achieve such exceptional catalytic performance under neutral and even alkaline conditions, which exceeds those of most reported materials. Mechanism investigation demonstrates that multiple active species were produced and promoted the degradation synergistically during the advanced oxidation processes.

6.
Am J Health Promot ; : 8901171241258375, 2024 Jun 03.
Artigo em Inglês | MEDLINE | ID: mdl-38831423

RESUMO

PURPOSE: Presenting a chain mediation model to investigate whether mobile phone dependence results in a reduction in health-related quality of life (HRQoL) among Chinese college students, through the mediating effect of chronotype and sleep quality. DESIGN AND SETTING: A cross-sectional survey was conducted on students from a Chinese university using a validated structured questionnaire. SAMPLE: 2014 freshmen. MEASURES: The study measured the students' level of mobile phone dependence using the Self-rating Questionnaire for Adolescent Problematic Mobile Phone Use. Chronotype and sleep quality were measured by the Chinese version of the Morningness-Eveningness Questionnaire (MEQ) and the Pittsburgh Sleep Quality Index (PSQI), respectively. HRQoL was evaluated using the five-level EuroQol five-dimensional questionnaire (EQ-5D-5L), including a descriptive system and a visual analog scale (VAS). ANALYSIS: Descriptive statistical analysis, correlation analysis, and mediation analysis. RESULTS: Mobile phone dependence had a significant negative effect on HRQoL as indicated by both the EQ-5D-5L index score and EQ-VAS score (P < .001 for both). Additionally, it was found to significantly predict chronotype (MEQ score) (ß = -.546, P < .001) and sleep quality (PSQI score) (ß = .163, P < .001). Chronotype negatively predict sleep quality (ß = -.058, P < .001), and sleep quality was a significant negative predictor of HRQoL (EQ-5D-5L index score, ß = -.008, P < .001; EQ-VAS score, ß = -1.576, P < .001). CONCLUSION: Mobile phone dependence negatively impacts students' HRQoL through chronotype and sleep quality, and there is a chain mediating effect. Students should consider making lifestyle changes to improve their HRQoL and promote health.

7.
Chin J Nat Med ; 22(6): 541-553, 2024 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-38906601

RESUMO

Thromboangiitis obliterans (TAO) is a rare, chronic, progressive, and segmental inflammatory disease characterized by a high rate of amputation, significantly compromising the quality of life of patients. Si-Miao-Yong-An decoction (SMYA), a traditional prescription, exhibits anti-inflammatory, anti-thrombotic, and various other pharmacological properties. Clinically, it was fully proved to be effective for TAO therapy, but the specific therapeutic effect of SMYA on TAO has been unknown. Thus, deep unveiling the mechanism of SMYA in TAO for identifying clinical therapeutic targets is extremely important. In this study, we observed elevated levels of IL-17A in the peripheral blood mononuclear cells (PBMCs) of TAO patients, whereas the expression of miR-548j-5p was significantly decreased. A negative correlation between the levels of miR-548j-5p and IL-17A was also demonstrated. In vitro experiments showed that overexpression of miR-548j-5p led to a decrease in IL-17A levels, whereas downregulation of miR-548j-5p showed the opposite effect. Using a dual luciferase assay, we confirmed that miR-548j-5p directly targets IL-17A. Furthermore, serum containing SMYA effectively decreased IL-17A levels by increasing the expression of miR-548j-5p. More importantly, the results of in vivo tests indicated that SMYA mitigated the development of TAO by inhibiting IL-17A through the upregulation of miR-548j-5p in vascular tissues. In conclusion, SMYA significantly enhances the expression of miR-548j-5p, thereby reducing the levels of the target gene IL-17A and alleviating TAO. Our research not only identifies novel targets and pathways for the clinical diagnosis and treatment of TAO but also advances the innovation in traditional Chinese medicine through the elucidation of the SMYA/miR-548j-5p/IL-17A regulatory axis in the pathogenesis of TAO.


Assuntos
Medicamentos de Ervas Chinesas , Interleucina-17 , MicroRNAs , Transdução de Sinais , Tromboangiite Obliterante , Tromboangiite Obliterante/tratamento farmacológico , Tromboangiite Obliterante/genética , Tromboangiite Obliterante/metabolismo , MicroRNAs/genética , MicroRNAs/metabolismo , Interleucina-17/genética , Interleucina-17/metabolismo , Humanos , Medicamentos de Ervas Chinesas/farmacologia , Animais , Transdução de Sinais/efeitos dos fármacos , Masculino , Camundongos , Feminino , Pessoa de Meia-Idade , Leucócitos Mononucleares/efeitos dos fármacos , Leucócitos Mononucleares/metabolismo , Adulto , Camundongos Endogâmicos C57BL
8.
Bioprocess Biosyst Eng ; 47(6): 841-850, 2024 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-38676737

RESUMO

D-Allulose 3-epimerase (DAE) is a vital biocatalyst for the industrial synthesis of D-allulose, an ultra-low calorie rare sugar. However, limited thermostability of DAEs hinders their use at high-temperature production. In this research, hyperthermophilic TI-DAE (Tm = 98.4 ± 0.7 ℃) from Thermotoga sp. was identified via in silico screening. A comparative study of the structure and function of site-directed saturation mutagenesis mutants pinpointed the residue I100 as pivotal in maintaining the high-temperature activity and thermostability of TI-DAE. Employing TI-DAE as a biocatalyst, D-allulose was produced from D-fructose with a conversion rate of 32.5%. Moreover, TI-DAE demonstrated excellent catalytic synergy with glucose isomerase CAGI, enabling the one-step conversion of D-glucose to D-allulose with a conversion rate of 21.6%. This study offers a promising resource for the enzyme engineering of DAEs and a high-performance biocatalyst for industrial D-allulose production.


Assuntos
Thermotoga , Thermotoga/enzimologia , Thermotoga/genética , Carboidratos Epimerases/genética , Carboidratos Epimerases/química , Carboidratos Epimerases/metabolismo , Carboidratos Epimerases/biossíntese , Racemases e Epimerases/genética , Racemases e Epimerases/metabolismo , Racemases e Epimerases/química , Proteínas de Bactérias/genética , Proteínas de Bactérias/química , Proteínas de Bactérias/biossíntese , Frutose/metabolismo , Frutose/biossíntese , Frutose/química , Estabilidade Enzimática , Biocatálise , Mutagênese Sítio-Dirigida , Temperatura Alta
9.
Front Cardiovasc Med ; 11: 1356286, 2024.
Artigo em Inglês | MEDLINE | ID: mdl-38572308

RESUMO

Background: Deep vein thrombosis (DVT) is associated with aberrant gene expression that is a common peripheral vascular disease. Here, we aimed to elucidate that the epigenetic modification of forkhead box protein 3 (FOXP3) at the post-transcriptional level, which might be the key trigger leading to the down-regulation of FOXP3 expression in DVT. Methods: In order to explore the relationship between microRNAs (miRNAs) and FOXP3, mRNA and microRNA microarray analysis were performed. Dual luciferase reporter assay was used to verify the upstream miRNAs of FOXP3. Quantitative real-time polymerase chain reaction, flow cytometry and Western blot were used to detect the relative expression of miR-6132 and FOXP3. Additionally, DVT models were established to investigate the role of miR-6132 by Murine Doppler Ultrasound and Hematoxylin-Eosin staining. Results: Microarray and flow cytometry results showed that the FOXP3 expression was decreased while miR-6132 level was increased substantially in DVT, and there was significant negative correlation between miR-6132 and FOXP3. Moreover, we discovered that overexpressed miR-6132 reduced FOXP3 expression and aggravated DVT formation, while miR-6132 knockdown increased FOXP3 expression and alleviated DVT formation. Dual luciferase reporter assay validated the direct binding of miR-6132 to FOXP3. Conclusion: Collectively, our data elucidate a new avenue through which up-regulated miR-6132 contributes to the formation and progression of DVT by inhibiting FOXP3 expression.

10.
Am J Ophthalmol ; 264: 154-161, 2024 Mar 29.
Artigo em Inglês | MEDLINE | ID: mdl-38556185

RESUMO

PURPOSE: To comprehensively identify the corneal biomechanical differences measured by Corvis ST between different degrees of myopia and emmetropia. DESIGN: Systematic review and meta-analysis. METHODS: Electronic databases, including PubMed, Embase, and Web of Science, were systematically searched for studies comparing the corneal biomechanics among various degrees of myopes and emmetropes using Corvis ST. The weighted mean differences and 95% confidence intervals were calculated. Meta-analysis was performed in high and nonhigh myopes and in myopes and emmetropes, respectively. RESULTS: Eleven studies were included in this study. The meta-analysis among myopes and emmetropes included 1947 myopes and 621 emmetropes, and 443 high myopes and 449 nonhigh myopes were included in the meta-analysis among high and nonhigh myopia. Myopes showed the cornea with significantly longer time at the first applanation (A1t) and lower length at the second applanation (A2L) than emmetropes. High myopes showed significantly greater A1t, velocity at the second applanation (A2v), deformation amplitude at the highest concavity (HC-DA), and peak distance at the highest concavity (HC-PD) and decreased time at the second applanation (A2t) and radius of the highest concavity (HC-R). CONCLUSIONS: Corneal biomechanics is different in myopia, especially in high myopia. Compared with nonhigh myopes, the corneas of high myopes deformed slower during the first applanation, faster during the second applanation, and showed greater deformation amplitude, indicating greater elasticity and viscidity.

11.
Chemistry ; 30(26): e202304334, 2024 May 08.
Artigo em Inglês | MEDLINE | ID: mdl-38388776

RESUMO

Sensing of benzene vapor is a hot spot due to the volatile drastic carcinogen even at trace concentration. However, achieving convenient and rapid detection is still a challenge. As a sort of functional porous material, metal-organic frameworks (MOFs) have been developed as detection sensors by adsorbing benzene vapor and converting it into other signals (fluorescence intensity/wavelength, chemiresistive, weight or color, etc.). Supramolecular interaction between benzene molecules and the host framework, aperture size/shape and structural flexibility are influential factors in the performance of MOF-based sensors. Therefore, enhancing the host-guest interactions between the host framework and benzene molecules, or regulating the diffusion rate of benzene molecules by changing the aperture size/shape and flexibility of the host framework to enhance the detection signal are effective strategies for constructing MOF-based sensors. This concept highlights several types of MOF-based sensors for the detection of benzene vapor.

12.
Artigo em Inglês | MEDLINE | ID: mdl-38305308

RESUMO

BACKGROUND: Saponin of Schizocapsa plantaginea Hance I (SSPH I),a bioactive saponin found in Schizocapsa plantaginea, exhibits significant anti-proliferation and antimetastasis in lung cancer. OBJECTIVE: To explore the anti-metastatic effects of SSPH I on non-small cell lung cancer (NSCLC) with emphasis on epithelial-mesenchymal transition (EMT) both in vitro and vivo. METHODS: The effects of SSPH I at the concentrations of 0, 0.875,1.75, and 3.5 µM on A549 and PC9 lung cancer cells were evaluated using colony formation assay, CCK-8 assay, transwell assay and wound-healing assay. The actin cytoskeleton reorganization of PC9 and A549 cells was detected using the FITC-phalloidin fluorescence staining assay. The proteins related to EMT (N-cadherin, E-cadherin and vimentin), p- PI3K, p- AKT, p- mTOR and p- ERK1/2 were detected by Western blotting. A mouse model of lung cancer metastasis was established by utilizing 95-D cells, and the mice were treated with SSPH I by gavage. RESULTS: The results suggested that SSPH I significantly inhibited the migration and invasion of NSCLC cells under a non-cytotoxic concentration. Furthermore, SSPH I at a non-toxic concentration of 0.875 µM inhibited F-actin cytoskeleton organization. Importantly, attenuation of EMT was observed in A549 cells with upregulation in the expression of epithelial cell marker E-cadherin and downregulation of the mesenchymal cell markers vimentin as well as Ncadherin. Mechanistic studies revealed that SSPH I inhibited MAPK/ERK1/2 and PI3K/AKT/mTOR signaling pathways. CONCLUSION: SSPH I inhibited EMT, migration, and invasion of NSCLC cells by suppressing MAPK/ERK1/2 and PI3K/AKT/mTOR signaling pathways, suggesting that the natural compound SSPH I could be used for inhibiting metastasis of NSCLC.

13.
BMC Ophthalmol ; 24(1): 59, 2024 Feb 12.
Artigo em Inglês | MEDLINE | ID: mdl-38342901

RESUMO

BACKGROUND: Several studies have previously reported the normal values of corneal volume (CV) in various populations, whereas little is known about the CV distribution in healthy young Chinese adults. Our study aimed to investigate the distribution of CV and its relationships with other ocular biometric parameters among healthy young Chinese adults. METHODS: A total of 1645 eyes from 1645 students at Dali University in Yunnan Province, China, were analyzed. Pentacam was used to measure CV. Central corneal thickness (CCT) and biomechanically corrected intraocular pressure (bIOP) were evaluated by Corvis-ST. Other biometrical parameters, including axial length (AL), keratometry, and white-to-white (WTW) distance, were measured using IOL Master. RESULTS: The mean age of the study population was 19.01 ± 0.92 years, and 68.81% of them were women. The CV was normally distributed in the whole sample, with a mean value of 61.23 ± 3.22 mm3. CV and CCT were significantly smaller in the Yi ethnic group than in the Han ethnic group (p < 0.01). CCT (coefficient: 0.085; p < 0.001) and keratometry (coefficient: 0.422; p < 0.001) were positively correlated with CV, while AL (coefficient: -0.204; p < 0.001), WTW distance (coefficient: -0.236; p < 0.001) and bIOP (coefficient: -0.06; p < 0.001) were inversely associated with CV. CONCLUSIONS: Our study provides an age-specific distribution of CV among healthy young Chinese adults. CCT, keratometry, AL, WTW distance and bIOP were important factors associated with CV.


Assuntos
Córnea , Pressão Intraocular , Adulto , Humanos , Feminino , Adolescente , Adulto Jovem , Masculino , Estudos Transversais , China/epidemiologia , Tonometria Ocular , Biometria
14.
Eye (Lond) ; 38(9): 1654-1659, 2024 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-38402288

RESUMO

BACKGROUND/OBJECTIVES: To determine the relationship between corneal stress-strain index (SSI) and retinal nerve fibre layer (RNFL) thickness. SUBJECTS/METHODS: 1645 healthy university students from a university-based study contributed to the analysis. The RNFL thickness was measured by high-definition optical coherence tomography (HD-OCT), axial length (AL) was measured by IOL Master, and corneal biomechanics including SSI, biomechanical corrected intraocular pressure (bIOP), and central corneal thickness (CCT) were measured by Corvis ST. Multivariate linear regression was performed to evaluate the relationship between the SSI and RNFL thickness after adjusting for potential covariates. RESULTS: The mean age of the participants was 19.0 ± 0.9 years, and 1132 (68.8%) were women. Lower SSI was significantly associated with thinner RNFL thickness ( ß =8.601, 95% confidence interval [CI] 2.999-14.203, P = 0.003) after adjusting for age, CCT, bIOP, and AL. No significant association between SSI and RNFL was found in men, while the association was significant in women in the fully adjusted model. The association was significant in the nonhigh myopic group ( P for trend = 0.021) but not in the highly myopic group. Eyes with greater bIOP and lower SSI had significantly thinner RNFL thickness. CONCLUSIONS: Eyes with lower SSI had thinner RNFL thickness after adjusting for potential covariates, especially those with higher bIOP. Our findings add novel evidence of the relationship between corneal biomechanics and retinal ganglion cell damage.


Assuntos
Córnea , Pressão Intraocular , Fibras Nervosas , Células Ganglionares da Retina , Tomografia de Coerência Óptica , Humanos , Feminino , Masculino , Córnea/fisiopatologia , Córnea/patologia , Córnea/diagnóstico por imagem , Tomografia de Coerência Óptica/métodos , Fibras Nervosas/patologia , Fibras Nervosas/fisiologia , Adulto Jovem , Células Ganglionares da Retina/patologia , Células Ganglionares da Retina/fisiologia , Pressão Intraocular/fisiologia , Voluntários Saudáveis , Estudos Transversais , Fenômenos Biomecânicos , Comprimento Axial do Olho/patologia , Adulto
15.
Diabetes Metab Syndr Obes ; 17: 675-689, 2024.
Artigo em Inglês | MEDLINE | ID: mdl-38352234

RESUMO

Purpose: To investigate the intestinal inflammatory response and the abundance of intestinal bacteria in rats with high-fat diet (HFD)-induced nonalcoholic fatty liver disease (NAFLD) and assess the intervention effects of taurine (TAU). Methods: Forty male Sprague-Dawley rats were randomly divided into five groups: group I, normal diet and normal saline gavage; group II, normal diet and TAU gavage; group III, HFD and normal saline gavage; group IV, HFD and TAU gavage (from the 1st week); group V, HFD and TAU gavage (from the 10th week). At the end of the 16th week, all the animals were sacrificed. Body weight, liver weight, liver function, and serum lipid levels were measured. The histopathologies of the liver and ileum were observed. The mRNA and protein expression levels of interleukin 17 (IL-17) and IL-10 in the ileum were detected by reverse transcription quantitative polymerase chain reaction (qPCR) and immunohistochemistry. Three types of bacteria were detected in intestinal feces using the 16S rDNA qPCR method. Results: The ileal IL-17 level in group III was significantly higher than those in the other four groups (P < 0.01). The ileal IL-10 mRNA levels in group IV was significantly higher than those in groups III and V (P < 0.05), and IL-10 protein MOD levels in group III was significantly lower than those in the other four groups (P < 0.01). The numbers of Lactobacillus in group III were significantly lower than those in the other four groups (P < 0.01 or P < 0.05). The numbers of Bifidobacteria in groups IV and V were significantly increased compared with that in group III (P < 0.05). Conclusion: TAU may down-regulate the expression of IL-17, up-regulate the expression of IL-10 and regulate the intestinal flora, and alleviate the liver and intestinal damage in rats with HFD-induced NAFLD.

16.
Biochem Biophys Res Commun ; 698: 149536, 2024 Feb 26.
Artigo em Inglês | MEDLINE | ID: mdl-38271834

RESUMO

The nuclear factor erythroid 2-related factor 2 (NRF2) is a transcription factor usually hyperactivated in hepatocellular carcinoma (HCC). In addition, about 14 % of HCC patients carry mutation in NRF2 or Kelch-like ECH-associated protein 1 (Keap1), a NRF2 inhibitor, both of which lead to constitutive activation of NRF2. It has been widely reported that NRF2 plays important roles in the proliferation, differentiation and metastasis of tumor cells. But as an important gene involved in antioxidation and anti-inflammation, little studies have focused on its role in tumor immune escape. Here we found that NRF2 gain-of-function mutation leads to reduced expression of STING and decreased infiltration of peripheral immune cells through which way it helps the tumor cells to evade from immune surveillance. This phenomenon can be reversed by STING overexpression. Our study also revealed that NRF2 mutation greatly reduced the effect of STING activating based immunotherapy. It is important to simultaneously inhibit the activity of NRF2 when using STING agonist for the treatment of HCC patients carrying NRF2 mutation.


Assuntos
Carcinoma Hepatocelular , Neoplasias Hepáticas , Proteínas de Membrana , Fator 2 Relacionado a NF-E2 , Evasão Tumoral , Humanos , Carcinoma Hepatocelular/patologia , Proteína 1 Associada a ECH Semelhante a Kelch/genética , Proteína 1 Associada a ECH Semelhante a Kelch/metabolismo , Neoplasias Hepáticas/patologia , Mutação , Fator 2 Relacionado a NF-E2/genética , Fator 2 Relacionado a NF-E2/metabolismo , Transdução de Sinais , Proteínas de Membrana/genética , Proteínas de Membrana/metabolismo
17.
Materials (Basel) ; 17(2)2024 Jan 10.
Artigo em Inglês | MEDLINE | ID: mdl-38255521

RESUMO

Asphalt concrete is widely used in hydraulic structure facilities as an impermeable structure in alpine cold regions, and its dynamic mechanical properties are influenced by the strain rate and specimen size. However, the specimen size has an important effect on mechanical properties; few systematic studies have investigated on the size effect of hydraulic asphalt concrete (HAC) under dynamic or static loading rates. In the present study, four sizes of cylindrical roller-compacted hydraulic asphalt concrete (RCHAC) specimens with heights of 50 mm, 100 mm, 150 mm, and 200 mm were prepared and tested under different loading rates ranging from 10-5 s-1 to 10-2 s-1 to investigate the size effects of mechanical properties and failure modes at the temperature of 5 °C. The effect of strain rate on the size effects of the compressive strength and the elastic modulus of RCHAC have also been explored. These tests indicate that when the specimen size increases, the compressive strength and failure degree decrease, while the elastic modulus increases. When the height increases from 50 mm to 200 mm, the compressive strength at different strain rates decreased by more than 50%. Furthermore, the elastic modulus increased by about 211.8% from 0.51 GPa to 1.59 GPa at a strain rate of 10-5 s-1, and increased by 150% from 5.08 GPa to 12.71 GPa at a strain rate of 10-2 s-1. As the strain rate increases, the variation trends with the size of the compressive strength, elastic modulus, and failure degree are distinctly intensified. A modified dynamic size effect law, which incorporates both the specimen size and strain rate, is proposed and verified to illustrate the dynamic size effect for the RCHAC under different loading rates.

18.
Knee ; 47: 53-62, 2024 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-38244239

RESUMO

BACKGROUND: Currently, in the field of total joint arthroplasty (TJA), there are no studies that have demonstrated the value of the sequential application of hydrogen peroxide, povidone-iodine, and physiological saline during the surgical procedure in decreasing postoperative infections in total knee arthroplasty (TKA), and in decreasing the incidence of periprosthetic joint infections (PJI) in particular. This study aimed to assess the efficacy of the sequential application of hydrogen peroxide, povidone-iodine, and physiological saline in reducing postoperative infections in TKA. METHODS: The study prospectively included 4743 patients, with Group A (2371, 49.9%) receiving sequential intraoperative application of hydrogen peroxide, povidone-iodine, and physiological saline irrigation of the incision, and Group B (2372, 50.1%) receiving intraoperative application of physiological saline irrigation of the incision only, to collect the patients' baseline data and clinical characteristics, and to statistically assess the incidence of superficial infections and the PJI during the follow up period to evaluate the clinical value of the study. RESULTS: The baseline levels of patients in Groups A and B were comparable. There were 132 (2.8%) lost visits during the study period. The incidence of superficial infections within 30 days after surgery was 0.22% in Group A and 1.17% in Group B, the difference between the two groups was statistically significant (P = 0.007). The incidence of PJI was 0.17% in Group A and 1.26% in Group B, the difference between the two groups was statistically significant (P = 0.0121). CONCLUSION: Sequential application of hydrogen peroxide, povidone-iodine, and physiological saline to irrigate incision in TKA can significantly reduce the incidence of postoperative superficial infections and PJI. The scientific and rational application of this therapy intraoperatively greatly reduces the incidence of PJI and postoperative superficial infections, which is of great benefit to the patient's prognosis.


Assuntos
Anti-Infecciosos Locais , Artroplastia do Joelho , Peróxido de Hidrogênio , Povidona-Iodo , Infecções Relacionadas à Prótese , Solução Salina , Infecção da Ferida Cirúrgica , Humanos , Artroplastia do Joelho/efeitos adversos , Povidona-Iodo/administração & dosagem , Povidona-Iodo/uso terapêutico , Peróxido de Hidrogênio/administração & dosagem , Masculino , Feminino , Estudos Prospectivos , Anti-Infecciosos Locais/administração & dosagem , Idoso , Pessoa de Meia-Idade , Infecção da Ferida Cirúrgica/prevenção & controle , Infecção da Ferida Cirúrgica/epidemiologia , Infecção da Ferida Cirúrgica/etiologia , Infecções Relacionadas à Prótese/prevenção & controle , Infecções Relacionadas à Prótese/etiologia , Infecções Relacionadas à Prótese/epidemiologia , Solução Salina/administração & dosagem , Irrigação Terapêutica/métodos , Incidência
19.
Graefes Arch Clin Exp Ophthalmol ; 262(1): 121-132, 2024 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-37401934

RESUMO

PURPOSE: To assess the associations of corneal biomechanical properties as measured by the Corvis ST with refractive errors and ocular biometry in an unselected sample of young adults. METHODS: A total of 1645 healthy university students underwent corneal biomechanical parameters measurement by the Corvis ST. The refractive status of the participants was measured using an autorefractor without cycloplegia. Ocular biometric parameters were measured using the IOL Master. RESULTS: After adjusting for the effect of age, sex, biomechanical-corrected intraocular pressure and central corneal thickness, axial length was significantly associated with A1 velocity (A1v, ß = -10.47), A2 velocity (A2v, ß = 4.66), A2 deflection amplitude (A2DeflA, ß = -6.02), HC deflection amplitude (HC-DeflA, ß = 5.95), HC peak distance (HC-PD, ß = 2.57), deformation amplitude ratio max (DA Rmax, ß = -0.36), Ambrósio's relational thickness to the horizontal profile (ARTh, ß = 0.002). For axial length / corneal radius ratio, only A1v (ß = -2.01), A1 deflection amplitude (A1DeflA, ß = 2.30), HC-DeflA (ß = 1.49), HC-PD (ß = -0.21), DA Rmax (ß = 0.07), stress-strain index (SSI, ß = -0.29), ARTh (ß < 0.001) were significant associates. A1v (ß = 23.18), HC-DeflA (ß = -15.36), HC-PD (ß = 1.27), DA Rmax (ß = -0.66), SSI (ß = 3.53), ARTh (ß = -0.02) were significantly associated with spherical equivalent. CONCLUSION: Myopic eyes were more likely to have more deformable corneas and corneas in high myopia were easier to deform and were even softer compared with those in the mild/moderate myopia.


Assuntos
Córnea , Miopia , Humanos , Adulto Jovem , Refração Ocular , Pressão Intraocular , Tonometria Ocular , Miopia/diagnóstico , Fenômenos Biomecânicos
20.
Int J Surg ; 110(2): 832-838, 2024 Feb 01.
Artigo em Inglês | MEDLINE | ID: mdl-38000073

RESUMO

BACKGROUND: Ondansetron has been reported to attenuate the incidence of spinal anaesthesia-induced hypotension (SAIH) and norepinephrine requirement during caesarean section. However, no quantitative study has evaluated the extent of this effect. This study aimed to determine the dose-response of prophylactic infusion of norepinephrine to prevent SAIH in parturients who received intravenous ondansetron or placebo before spinal anaesthesia for caesarean section. The median effective dose (ED 50 ) and 90% effective dose (ED 90 ) were compared to evaluate the effect of ondansetron versus placebo on the norepinephrine requirement. MATERIALS AND METHODS: One hundred fifty parturients undergoing caesarean section were randomized to receive either 0.1 mg/kg ondansetron (group O) or saline control (group C) 10 min before spinal anaesthesia. The parturients were randomly assigned to one of five different norepinephrine infusion groups: 0.02, 0.04, 0.06, 0.08 or 0.10 µg/kg/min. An effective infusion dose of norepinephrine was defined as non-occurrence of hypotension during the study period. The values for ED 50 and ED 90 of norepinephrine infusion were determined using probit regression. Differences between the two groups were evaluated by comparing the relative median potency with 95% CIs. RESULTS: The ED 50 values were 0.033 (95% CIs, 0.024-0.043) µg/kg/min in group C and 0.021 (95% CIs, 0.013-0.029) µg/kg/min in group O. The ED 90 values were 0.091 (95% CIs 0.068-0.147) µg/kg/min in group C and 0.059 (95% CIs 0.044-0.089) µg/kg/min in group O, respectively. The estimate of the relative median potency for norepinephrine in group C versus group O was 0.643 (95% CIs, 0.363-0.956). The incidence of side effects was comparable between groups. No significant difference in neonatal outcomes. CONCLUSION: Intravenous ondansetron 0.1 mg/kg before spinal anaesthesia significantly reduced the dose requirement of prophylactic norepinephrine infusion in parturients undergoing elective caesarean section. This finding is potentially useful for clinical practice and further research.


Assuntos
Raquianestesia , Hipotensão , Recém-Nascido , Gravidez , Humanos , Feminino , Ondansetron/uso terapêutico , Norepinefrina , Cesárea/efeitos adversos , Raquianestesia/efeitos adversos , Hipotensão/induzido quimicamente , Hipotensão/prevenção & controle , Método Duplo-Cego
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