Your browser doesn't support javascript.
loading
Mostrar: 20 | 50 | 100
Resultados 1 - 20 de 4.587
Filtrar
1.
Heliyon ; 10(7): e28434, 2024 Apr 15.
Artigo em Inglês | MEDLINE | ID: mdl-38560099

RESUMO

Background: A conclusive evidence regarding the optimal concentration and volume of local anesthetic for quadratus lumborum block is lacking. Methods: In this single-center, prospective, randomized, controlled study, 60 patients scheduled for laparoscopic colorectal surgery were randomly assigned to 3 different combinations of volume and concentration of ropivacaine (3 mg/kg) - Group 0.25%, Group 0.375% and Group 0.5%. All subjects received ultrasound-guided posterior quadratus lumborum block prior to the induction. The primary outcome was the complete sensory block rate of surgical site measured at 30 min after quadratus lumborum block, after extubation, at 12, 24, and 48 h after operation. Secondary outcomes were the changes in hemodynamic parameters before and after incision (ΔSBP, ΔDBP and ΔHR), postoperative pain score, the sufentanil consumption after surgery, length of stay and adverse reactions. Results: The sensory block rate of surgical site at 5 time points differed significantly among the three groups (P < 0.001). Both Group 0.375% (P < 0.001) and Group 0.5% (P < 0.001) had a higher sensory block rate than Group 0.25%, but no significant difference was observed between the former two. Group 0.375% and Group 0.5% had lower postoperative pain scores, lower sufentanil consumption after surgery and shorter length of stay. No statistical difference was observed in ΔSBP, ΔDBP, ΔHR and the incidence of adverse reactions. Conclusions: 0.375% and 0.5% ropivacaine in posterior quadratus lumborum block provide better sensory block of surgical site when compared to 0.25% in laparoscopic colorectal surgery. Trial registration number: Chinese Clinical Trials Registry (ChiCTR2100043949).

2.
Biomed Pharmacother ; 174: 116542, 2024 Apr 02.
Artigo em Inglês | MEDLINE | ID: mdl-38574620

RESUMO

Previous studies have demonstrated that the underlying mechanisms of myocardial ischemia/reperfusion injury (MIRI) are complex and involve multiple types of regulatory cell death, including ferroptosis, apoptosis, and autophagy. Thus, we aimed to identify the mechanisms underlying MIRI and validate the protective role of epigallocatechin-3-gallate (EGCG) and its related mechanisms in MIRI. An in vivo and in vitro models of MIRI were constructed. The results showed that pretreatment with EGCG could attenuate MIRI, as indicated by increased cell viability, reduced lactate dehydrogenase (LDH) activity and apoptosis, inhibited iron overload, abnormal lipid metabolism, preserved mitochondrial function, decreased infarct size, maintained cardiac function, decreased reactive oxygen species (ROS) level, and reduced TUNEL-positive cells. Additionally, EGCG pretreatment could attenuate ferroptosis, apoptosis, and autophagy induced by MIRI via upregulating 14-3-3η protein levels. Furthermore, the protective effects of EGCG could be abolished with pAd/14-3-3η-shRNA or Compound C11 (a 14-3-3η inhibitor) but not pAd/NC-shRNA. In conclusion, EGCG pretreatment attenuated ferroptosis, apoptosis, and autophagy by mediating 14-3-3η and protected cardiomyocytes against MIRI.

3.
Trends Plant Sci ; 2024 Apr 08.
Artigo em Inglês | MEDLINE | ID: mdl-38594153

RESUMO

To resist biotic attacks, plants have evolved a sophisticated, receptor-based immune system. Cell-surface immune receptors, which are either receptor-like kinases (RLKs) or receptor-like proteins (RLPs), form the front line of the plant defense machinery. RLPs lack a cytoplasmic kinase domain for downstream immune signaling, and leucine-rich repeat (LRR)-containing RLPs constitutively associate with the RLK SOBIR1. The RLP/SOBIR1 complex was proposed to be the bimolecular equivalent of genuine RLKs. However, it appears that the molecular mechanisms by which RLP/SOBIR1 complexes and RLKs mount immunity show some striking differences. Here, we summarize the differences between RLP/SOBIR1 and RLK signaling, focusing on the way these receptors recruit the BAK1 co-receptor and elaborating on the negative crosstalk taking place between the two signaling networks.

4.
ACS Sens ; 2024 Apr 21.
Artigo em Inglês | MEDLINE | ID: mdl-38644577

RESUMO

A core-shell nanostructure of gold nanoparticles@covalent organic framework (COF) loaded with palladium nanoparticles (AuNPs@COF-PdNPs) was designed for the rapid monitoring of catalytic reactions with surface-enhanced Raman spectroscopy (SERS). The nanostructure was prepared by coating the COF layer on AuNPs and then in situ synthesizing PdNPs within the COF shell. With the respective SERS activity and catalytic performance of the AuNP core and COF-PdNPs shell, the nanostructure can be directly used in the SERS study of the catalytic reaction processes. It was shown that the confinement effect of COF resulted in the high dispersity of PdNPs and outstanding catalytic activity of AuNPs@COF-PdNPs, thus improving the reaction rate constant of the AuNPs@COF-PdNPs-catalyzed hydrogenation reduction by 10 times higher than that obtained with Au/Pd NPs. In addition, the COF layer can serve as a protective shell to make AuNPs@COF-PdNPs possess excellent reusability. Moreover, the loading of PdNPs within the COF layer was found to be in favor of avoiding intermediate products to achieve a high total conversion rate. AuNPs@COF-PdNPs also showed great catalytic activities toward the Suzuki-Miyaura coupling reaction. Taken together, the proposed core-shell nanostructure has great potential in monitoring and exploring catalytic processes and interfacial reactions.

5.
Small ; : e2307485, 2024 Apr 16.
Artigo em Inglês | MEDLINE | ID: mdl-38623988

RESUMO

Severe burn wounds usually destroy key cells' functions of the skin resulting in delayed re-epithelization and wound regeneration. Promoting key cells' activities is crucial for burn wound repair. It is well known that keratinocyte growth factor-2 (KGF-2) participates in the proliferation and morphogenesis of epithelial cells while acidic fibroblast growth factor (aFGF) is a key mediator for fibroblast and endothelial cell growth and differentiation. However, thick eschar and the harsh environment of a burn wound often decrease the delivery efficiency of fibroblast growth factor (FGF) to the wound site. Therefore, herein a novel microneedle patch for sequential transdermal delivery of KGF-2 and aFGF is fabricated to enhance burn wound therapy. aFGF is first loaded in the nanoparticle (NPaFGF) and then encapsulated NPaFGF with KGF-2 in the microneedle patch (KGF-2/NPaFGF@MN). The result shows that KGF-2/NPaFGF@MN can successfully get across the eschar and sequentially release KGF-2 and aFGF. Additional data demonstrated that KGF-2/NPaFGF@MN achieved a quicker wound closure rate with reduced necrotic tissues, faster re-epithelialization, enhanced collagen deposition, and increased neo-vascularization. Further evidence suggests that improved wound healing is regulated by significantly elevated expressions of hypoxia-inducible factor-1 alpha (HIF-1ɑ) and heat shock protein 90 (Hsp90) in burn wounds. All these data proved that KGF-2/NPaFGF@MN is an effective treatment for wound healing of burns.

6.
Zhongguo Zhong Yao Za Zhi ; 49(3): 717-727, 2024 Feb.
Artigo em Chinês | MEDLINE | ID: mdl-38621875

RESUMO

Transcriptome sequencing was employed to mine the simple sequence repeat(SSR) locus information of Saposhnikovia divaricata and design specific primers, which aimed to provide a basis for the research on the genetic diversity of S. divaricata germplasm resources. The seed purity, 1 000-seed weight, germination rate, and seed vigor were determined. MISA was used to obtain the SSR locus information from 12 606 unigene longer than 1 kb in the transcriptome database. Forty-three pairs of SSR primers designed in Primer 3 were used to analyze the polymorphism of 28 S. divaricata samples of different sources. The results showed that there were differences in the seed purity, 1 000-seed weight, germination rate, vigor, and seed length and width among S. divaricata samples of different sources. Particularly, the germination rate and seed vigor had significant differences, and HB-ZJK1, NMG-CF4, NMG-BT, NMG-HLE1, and NMG-CF2 had significantly higher 1 000-seed weight, germination rate, and seed vigor than the samples of other sources. Among the 86 233 unigene, 12 606(14.62%) unigene contained 15 958 SSR loci, with one SSR locus every 5 009 bp on average. The SSR loci were mainly single nucleotide and dinucleotide repeats, which were dominated by G/C and TC/AG, respectively. All the primers were screened by using 28 S. divaricata sample from different habitats, and the primers corresponding to the amplification products with clear bands and stable polymorphism were obtained. The clustering results of the biological characteristics and genetic diversity of the 28 S. divaricata samples were basically consistent, and the samples of the same origin(HB-AG1, HB-AG2, HB-ZJK1, and HB-ZJK2) generally gathered together and had close genetic relationship. The SSRs in S. divaricata transcriptome has high frequency, rich types, and high polymorphism, which provides candidate molecular markers for the germplasm identification, genetic map construction, and molecular-assisted breeding.


Assuntos
Apiaceae , Transcriptoma , Polimorfismo Genético , Repetições de Microssatélites/genética , Apiaceae/genética , Etiquetas de Sequências Expressas
7.
Eur J Pharmacol ; 971: 176524, 2024 May 15.
Artigo em Inglês | MEDLINE | ID: mdl-38561102

RESUMO

The present study aimed to explore how resveratrol (Res) confers myocardial protection by attenuating ferroptosis. In vivo and in vitro myocardial ischemia/reperfusion injury (MIRI) models were established, with or without Res pretreatment. The results showed that Res pretreatment effectively attenuated MIRI, as evidenced by increased cell viability, reduced lactate dehydrogenase activity, decreased infarct size, and maintained cardiac function. Moreover, Res pretreatment inhibited MIRI-induced ferroptosis, as shown by improved mitochondrial integrity, increased glutathione level, decreased prostaglandin-endoperoxide synthase 2 level, inhibited iron overload, and abnormal lipid peroxidation. Of note, Res pretreatment decreased or increased voltage-dependent anion channel 1/glutathione peroxidase 4 (VDAC1/GPX4) expression, which was increased or decreased via anoxia/reoxygenation (A/R) treatment, respectively. However, the overexpression of VDAC1 via pAd/VDAC1 and knockdown of GPX4 through Si-GPX4 reversed the protective effect of Res in A/R-induced H9c2 cells, whereas the inhibition of GPX4 with RSL3 abolished the protective effect of Res on mice treated with ischemia/reperfusion.Interestingly, knockdown of VDAC1 by Si-VDAC1 promoted the protective effect of Res on A/R-induced H9c2 cells and the regulation of GPX4. Finally, the direct interaction between VDAC1 and GPX4 was determined using co-immunoprecipitation. In conclusion, Res pretreatment could protect the myocardium against MIRI-induced ferroptosis via the VDAC1/GPX4 signaling pathway.


Assuntos
Ferroptose , Traumatismo por Reperfusão Miocárdica , Animais , Camundongos , Miócitos Cardíacos , Resveratrol/farmacologia , Canal de Ânion 1 Dependente de Voltagem , Isquemia , Hipóxia , Traumatismo por Reperfusão Miocárdica/prevenção & controle , Reperfusão
8.
Opt Express ; 32(6): 9255-9275, 2024 Mar 11.
Artigo em Inglês | MEDLINE | ID: mdl-38571164

RESUMO

Dwell time scheduling is a critical stage of deterministic polishing for ultra-precision fabrication of optics. Recently the dwell time algorithms for deterministic polishing have been widely studied. Nevertheless, there exist some shortcomings when those methods were applied in the industry, including low computational efficiency, large memory consumption, insufficiently-considered dynamic constraints, poor smoothness of the feedrate profile, and reliance on non-open CNC interpolator. To overcome those deficiencies, this work proposes a highly-efficient dwell time algorithm under the dynamic constraints of machine tools. The method calculates the initial dwell time density (DTD) sequence through non-blind deconvolution algorithm, and provides the feasible set of DTD profiles based on trigonometric-spline model. And the DTD repairing tactics are developed based on a self-adaptive offset algorithm under confined feedrate and acceleration. Finally, a C1-continuous DTD profile satisfying dynamic constraints is generated. A real-time interpolator based on trigonometric-spline DTD profile is developed. The simulation results show that the proposed method generates a C1-continuous feedrate profile rigidly respecting dynamic constraints, and preserves the ideal dwell time gradient distribution, achieving a more ideal residual error with high computational efficiency compared with the previous methods. The comparative experiments demonstrate that the proposed method performs better in suppressing the multi-frequency errors compared with the previous methods, and achieves high computational efficiency. The algorithm is applicable to highly-precise and highly-efficient fabrication of large-aperture optical components.

9.
Heliyon ; 10(7): e29055, 2024 Apr 15.
Artigo em Inglês | MEDLINE | ID: mdl-38576565

RESUMO

Background: Anaplastic thyroid cancer (ATC), a rare and aggressive malignancy with a poor prognosis, has shown promise with the approved dabrafenib/trametinib combination for BRAFV600E mutation. Co-occurring PI3KCA mutations, identified as negative prognostic factors in lung cancer with BRAFV600E mutation, emphasize the need to target both pathways. Exploring trametinib and alpelisib combination becomes crucial for ATC. Methods: A patient-derived xenograft (PDX) and primary cell line were obtained from an ATC patient with BRAF and PI3KCA co-mutation. Individual testing of targeted therapies against BRAF, MEK, and PI3KCA was followed by a combination treatment. Synergistic effects were evaluated using the combination index. Immunoblotting assessed the efficacy, with validation performed using a PDX model. Results: In this study, the ATC0802 cell line and PDX were established from a refractory ATC patient. NGS revealed BRAF and PI3KCA co-mutations pre- and post-dabrafenib/trametinib treatment. Trametinib/alpelisib combination showed synergy, suppressing both pERK and pAKT levels, unlike monotherapies or BRAF knockdown. The combination induced apoptosis and, in the PDX model, demonstrated superior tumor growth inhibition compared to monotherapies. Conclusions: The combination of trametinib and alpelisib showed promise as a strategy for treating ATC with co-mutations in BRAF and PI3KCA, both in vitro and in vivo. This combination offers insights into overcoming resistance to BRAF-targeted treatments in ATC with mutations in BRAF and PI3KCA.

10.
Adv Sci (Weinh) ; : e2402516, 2024 Apr 06.
Artigo em Inglês | MEDLINE | ID: mdl-38582500

RESUMO

Cuproptosis is a newly discovered form of programmed cell death significantly depending on the transport efficacy of copper (Cu) ionophores. However, existing Cu ionophores, primarily small molecules with a short blood half-life, face challenges in transporting enough amounts of Cu ions into tumor cells. This work describes the construction of carrier-free nanoparticles (Ce6@Cu NPs), which self-assembled by the coordination of Cu2+ with the sonosensitizer chlorin e6 (Ce6), facilitating sonodynamic-triggered combination of cuproptosis and ferroptosis. Ce6@Cu NPs internalized by U87MG cells induce a sonodynamic effect and glutathione (GSH) depletion capability, promoting lipid peroxidation and eventually inducing ferroptosis. Furthermore, Cu+ concentration in tumor cells significantly increases as Cu2+ reacts with reductive GSH, resulting in the downregulation of ferredoxin-1 and lipoyl synthase. This induces the oligomerization of lipoylated dihydrolipoamide S-acetyltransferase, causing proteotoxic stress and irreversible cuproptosis. Ce6@Cu NPs possess a satisfactory ability to penetrate the blood-brain barrier, resulting in significant accumulation in orthotopic U87MG-Luc glioblastoma. The sonodynamic-triggered combination of ferroptosis and cuproptosis in the tumor by Ce6@Cu NPs is evidenced both in vitro and in vivo with minimal side effects. This work represents a promising tumor therapeutic strategy combining ferroptosis and cuproptosis, potentially inspiring further research in developing logical and effective cancer therapies based on cuproptosis.

11.
World J Gastroenterol ; 30(9): 1121-1131, 2024 Mar 07.
Artigo em Inglês | MEDLINE | ID: mdl-38577194

RESUMO

BACKGROUND: Traditional esophagogastroduodenoscopy (EGD), an invasive examination method, can cause discomfort and pain in patients. In contrast, magnetically controlled capsule endoscopy (MCE), a noninvasive method, is being applied for the detection of stomach and small intestinal diseases, but its application in treating esophageal diseases is not widespread. AIM: To evaluate the safety and efficacy of detachable string MCE (ds-MCE) for the diagnosis of esophageal diseases. METHODS: Fifty patients who had been diagnosed with esophageal diseases were prospectively recruited for this clinical study and underwent ds-MCE and conventional EGD. The primary endpoints included the sensitivity, specificity, positive predictive value, negative predictive value, and diagnostic accuracy of ds-MCE for patients with esophageal diseases. The secondary endpoints consisted of visualizing the esophageal and dentate lines, as well as the subjects' tolerance of the procedure. RESULTS: Using EGD as the gold standard, the sensitivity, specificity, positive predictive value, negative predictive value, and diagnostic accuracy of ds-MCE for esophageal disease detection were 85.71%, 86.21%, 81.82%, 89.29%, and 86%, respectively. ds-MCE was more comfortable and convenient than EGD was, with 80% of patients feeling that ds-MCE examination was very comfortable or comfortable and 50% of patients believing that detachable string v examination was very convenient. CONCLUSION: This study revealed that ds-MCE has the same diagnostic effects as traditional EGD for esophageal diseases and is more comfortable and convenient than EGD, providing a novel noninvasive method for treating esophageal diseases.


Assuntos
Endoscopia por Cápsula , Doenças do Esôfago , Humanos , Endoscopia por Cápsula/métodos , Estudos Prospectivos , Doenças do Esôfago/diagnóstico , Endoscopia do Sistema Digestório/métodos , Sensibilidade e Especificidade
12.
Shanghai Kou Qiang Yi Xue ; 33(1): 49-53, 2024 Feb.
Artigo em Chinês | MEDLINE | ID: mdl-38583024

RESUMO

PURPOSE: To study the antimicrobial effect of different concentrations of new bioactive glass(BG) on common bacteria in apical periodontitis of deciduous teeth. METHODS: The diameter (mm) of the inhibitory rings formed after treatment of Enterococcus faecalis, Porphyromonas gingivalis and Clostridium nucleatum with the new bioactive glass was detected and observed by paper diffusion method, and the minimal inhibitory concentration(MIC), minimal bactericidal concentration (MBC) and minimal biofilm eradication concentration (MBEC) of E. faecalis, P. gingivalis and C. pseudomallei were determined. The mixed plaques of the three bacteria were treated with 20, 40, 60 and 80 mg/mL of the new bioactive glass for 24 h. The results were analyzed by laser confocal microscopy. The antibacterial effect of the new bioactive glass on the mixed plaque was observed by confocal laser scanning microscopy (CLSM). Statistical analysis was performed with GraphPad Prism 10.0 software. RESULTS: The new bioactive glass showed strong antibacterial potential against the common bacteria of apical periodontitis; the MBEC of the new bioactive glass on the plaque was significantly greater than MIC and MBC of Enterococcus faecalis, Porphyromonas gingivalis and Clostridium nucleatum, and as the concentration of the new bioactive glass increased, the number of dead bacteria in the mixed plaque increased, and there was significant difference from that of the blank control group (P<0.05). CONCLUSIONS: The novel bioactive glass shows significant antibacterial efficacy against Enterococcus faecalis, Porphyromonas gingivalis and Clostridium nucleatum, which are the common bacteria in apical periodontitis of deciduous teeth.


Assuntos
Antibacterianos , Periodontite Periapical , Humanos , Antibacterianos/farmacologia , Antibacterianos/uso terapêutico , Porphyromonas gingivalis , Dente Decíduo , Biofilmes
13.
Food Sci Nutr ; 12(4): 2346-2363, 2024 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-38628176

RESUMO

A safety evaluation was performed of Symbiota®, which is made by a proprietary anaerobic fermentation process of soybean with multistrains of probiotics and a yeast. The battery of genotoxicity studies showed that Symbiota® has no genotoxic effects. Safety and tolerability were further assessed by acute or repeated dose 28- and 90-day rodent studies, and no alterations in clinical observations, ophthalmological examination, blood chemistry, urinalysis, or hematology were observed between the control group and the different dosing groups (1.5, 5, and 15 mL/kg/day). There were no adverse effects on specific tissues or organs in terms of weight and histopathology. Importantly, the Symbiota® treatment did not perturb hormones and other endocrine-related endpoints. Of note, the No-Observed-Adverse-Effect-Level was determined to be 15 mL/kg/day in rats. Moreover, a randomized, double-blind, placebo-controlled clinical trial was recently conducted with healthy volunteers who consumed 8 mL/day of placebo or Symbiota® for 8 weeks. Only mild adverse events were reported in both groups, and the blood chemistry and blood cell profiles were also similar between the two groups. In summary, this study concluded that the oral consumption of Symbiota® at 8 mL/day by the general population does not pose any human health concerns.

15.
Integr Cancer Ther ; 23: 15347354241242120, 2024.
Artigo em Inglês | MEDLINE | ID: mdl-38590244

RESUMO

OBJECTIVES: To evaluate the effects of Reishimmune-S, a fungal immunomodulatory peptide, on the quality of life (QoL) and natural killer (NK) cell subpopulations in patients receiving adjuvant endocrine therapy (ET) for breast cancer (BC). METHODS: Patients who received adjuvant ET for stage I-III hormone receptor-positive BC without active infection were enrolled in this prospective pilot study. Reishimmune-S was administered sublingually daily for 6 months. QoL scores, circulating immune cell levels, including lymphocyte/NK cell subpopulations, and plasma levels of interleukin (IL)-6 and tumor necrosis factor (TNF)-α were measured at baseline and every 4 weeks. Data were analyzed using linear mixed-effect regression models. RESULTS: Nineteen participants were included in the analyses. One patient with underlying asthma did not complete the study owing to the occurrence of skin rashes 15 days after the initiation of Reishimmune-S. No other adverse events were reported. Reishimmune-S supplementation significantly improved the cognitive function at 3 months and significantly decreased the fatigue and insomnia levels at 3 and 6 months, respectively. There was no significant change in the global health/QoL score between baseline and week 4 of treatment. The proportion of CD19+ lymphocytes was significantly higher at 3 and 6 months, and that of NKG2A+ and NKp30+ NK cells was significantly lower at 6 months than at baseline. In addition, fatigue positively correlated with the proportion of NKp30+ NK cells (ß ± standard error: 24.48 ± 8.75, P = .007 in the mixed-effect model). CONCLUSIONS: Short-term supplementation with Reishimmune-S affected the circulating immune cell composition and exerted positive effects on cognitive function, fatigue, and insomnia in patients with BC undergoing adjuvant ET, providing a potential approach for the management of treatment-related adverse reactions in this patient population.


Assuntos
Neoplasias da Mama , Distúrbios do Início e da Manutenção do Sono , Humanos , Feminino , Neoplasias da Mama/psicologia , Qualidade de Vida , Estudos Prospectivos , Projetos Piloto , Fator de Necrose Tumoral alfa , Células Matadoras Naturais , Suplementos Nutricionais , Fadiga/induzido quimicamente
16.
J Agric Food Chem ; 2024 Apr 19.
Artigo em Inglês | MEDLINE | ID: mdl-38639643

RESUMO

The use of convertible immobilized enzyme carriers is crucial for biphasic catalytic reactions conducted in Pickering emulsions. However, the intense mechanical forces during the conversion process lead to enzyme leakage, affecting the stability of the immobilized enzymes. In this study, a CO2-responsive switchable Janus (CrSJ) nanoparticle (NP) was developed using silica NP, with one side featuring aldehyde groups and the other side adsorbing N,N-dimethyldodecylamine. A switchable Pickering emulsion catalytic system for biphasic interface reactions was prepared by covalently immobilizing lipase onto the CrSJ NPs. The CO2-responsive nature of the CrSJ NPs allowed for rapid conversion of the Pickering emulsion, and covalent immobilization substantially reduced lipase leakage while enhancing the stability of the immobilization during the conversion process. Impressively, after repeated transformations, the Pickering emulsion still maintains its original structure. Following 10 consecutive cycles of esterification and hydrolysis reactions, the immobilized enzyme's activity remains at 77.7 and 79.5% of its initial activity, respectively. The Km of the CrSJ catalytic system showed no significant change compared to the free enzyme, while its Vmax values were 1.2 and 1.6 times that of the free enzyme in esterification and hydrolysis reactions, respectively.

17.
Int J Mol Sci ; 25(7)2024 Mar 28.
Artigo em Inglês | MEDLINE | ID: mdl-38612598

RESUMO

Severe acute pancreatitis (SAP), a widespread inflammatory condition impacting the abdomen with a high mortality rate, poses challenges due to its unclear pathogenesis and the absence of effective treatment options. Isorhamnetin (ISO), a naturally occurring flavonoid, demonstrates robust antioxidant and anti-inflammatory properties intricately linked to the modulation of mitochondrial function. However, the specific protective impact of ISO on SAP remains to be fully elucidated. In this study, we demonstrated that ISO treatment significantly alleviated pancreatic damage and reduced serum lipase and amylase levels in the mouse model of SAP induced by sodium taurocholate (STC) or L-arginine. Utilizing an in vitro SAP cell model, we found that ISO co-administration markedly prevented STC-induced pancreatic acinar cell necrosis, primarily by inhibiting mitochondrial ROS generation, preserving ATP production, maintaining mitochondrial membrane potential, and preventing the oxidative damage and release of mitochondrial DNA. Mechanistically, our investigation identified that high-temperature requirement A2 (HtrA2) may play a central regulatory role in mediating the protective effect of ISO on mitochondrial dysfunction in STC-injured acinar cells. Furthermore, through an integrated approach involving bioinformatics analysis, molecular docking analysis, and experimental validation, we uncovered that ISO may directly impede the histone demethylation activity of KDM5B, leading to the restoration of pancreatic HtrA2 expression and thereby preserving mitochondrial function in pancreatic acinar cells following STC treatment. In conclusion, this study not only sheds new light on the intricate molecular complexities associated with mitochondrial dysfunction during the progression of SAP but also underscores the promising value of ISO as a natural therapeutic option for SAP.


Assuntos
Doenças Mitocondriais , Pancreatite , Quercetina/análogos & derivados , Animais , Camundongos , Pancreatite/tratamento farmacológico , Doença Aguda , Simulação de Acoplamento Molecular , Mitocôndrias , Transdução de Sinais
18.
Front Physiol ; 15: 1386413, 2024.
Artigo em Inglês | MEDLINE | ID: mdl-38645688

RESUMO

Lysosomes-associated membrane proteins (LAMPs), a family of glycosylated proteins and major constituents of the lysosomal membranes, play a dominant role in various cellular processes, including phagocytosis, autophagy and immunity in mammals. However, their roles in aquatic species remain poorly known. In the present study, three lamp genes were cloned and characterized from Micropterus salmoides. Subsequently, their transcriptional levels in response to different nutritional status were investigated. The full-length coding sequences of lamp1, lamp2 and lamp3 were 1251bp, 1224bp and 771bp, encoding 416, 407 and 256 amino acids, respectively. Multiple sequence alignment showed that LAMP1-3 were highly conserved among the different fish species, respectively. 3-D structure prediction, genomic survey, and phylogenetic analysis were further confirmed that these genes are widely existed in vertebrates. The mRNA expression of the three genes was ubiquitously expressed in all selected tissues, including liver, brain, gill, heart, muscle, spleen, kidney, stomach, adipose and intestine, lamp1 shows highly transcript levels in brain and muscle, lamp2 displays highly expression level in heart, muscle and spleen, but lamp3 shows highly transcript level in spleen, liver and kidney. To analyze the function of the three genes under starvation stress in largemouth bass, three experimental treatment groups (fasted group and refeeding group, control group) were established in the current study. The results indicated that the expression of lamp1 was significant induced after starvation, and then returned to normal levels after refeeding in the liver. The expression of lamp2 and lamp3 exhibited the same trend in the liver. In addition, in the spleen and the kidney, the transcript level of lamp1 and lamp2 was remarkably increased in the fasted treatment group and slightly decreased in the refed treatment group, respectively. Collectively, our findings suggest that three lamp genes may have differential function in the immune and energetic organism in largemouth bass, which is helpful in understanding roles of lamps in aquatic species.

19.
Opt Lett ; 49(8): 2137-2140, 2024 Apr 15.
Artigo em Inglês | MEDLINE | ID: mdl-38621095

RESUMO

Superradiant phase transitions play a fundamental role in understanding the mechanism of collective light-matter interaction at the quantum level. Here we investigate multiple superradiant phases and phase transitions with different symmetry-breaking patterns in a two-mode V-type Dicke model. Interestingly, we show that there exists a quadruple point where one normal phase, one global symmetry-breaking superradiant phase, and two local symmetry-breaking superradiant phases meet. Such a global phase results from the phase competition between two local superradiant phases and cannot occur in the standard Λ- and Ξ-type three-level configurations in quantum optics. Moreover, we exhibit a sequential first-order quantum phase transition from one local to the global again to the other local superradiant phase. Our study opens up a perspective of exploring multilevel quantum critical phenomena with global symmetry breaking.

20.
Phys Rev Lett ; 132(13): 136001, 2024 Mar 29.
Artigo em Inglês | MEDLINE | ID: mdl-38613301

RESUMO

The polar Kerr effect and the closely related anomalous charge Hall effect are among the most distinguishing signatures of the superconducting state in Sr_{2}RuO_{4}, as well as in several other compounds. These effects are often thought to be derived from chiral superconducting pairing, and different mechanisms have been invoked for the explanation. However, the intrinsic mechanisms proposed previously often involve unrealistically strong interband Cooper pairing. We show in this Letter that, even without interband pairing, nonunitary superconducting states can support the intrinsic anomalous charge Hall effect, thanks to the quantum geometric properties of the Bloch electrons. The key here is to have a normal-state spin Hall effect, for which a nonzero spin-orbit coupling is essential. A finite charge Hall effect then naturally arises at the onset of a spin-polarized nonunitary superconducting pairing. It depends on both the spin polarization and the normal-state electron Berry curvature, the latter of which is the imaginary part of the quantum geometric tensor of the Bloch states. Applying our results to the weakly paired Sr_{2}RuO_{4} we conclude that, if the reported Kerr effect is of intrinsic origin, the superconducting state is most likely nonunitary and has odd parity. Our theory may be generalized to other superconductors that exhibit the polar Kerr effect.

SELEÇÃO DE REFERÊNCIAS
DETALHE DA PESQUISA
...