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1.
Proc Natl Acad Sci U S A ; 121(19): e2402550121, 2024 May 07.
Artigo em Inglês | MEDLINE | ID: mdl-38691590

RESUMO

Earlier sum frequency generation (SFG) experiments involve one infrared and one visible laser, and a measurement of the intensity of the response, yielding data on the surface sensitive properties of the sample. Recently, both the real and imaginary components of the susceptibility were measured in two different sets of experiments. In one set, a broadband infrared laser was used, permitting observations at very short times, while in another set the infrared laser was narrowband, permitting higher spectral resolution. The differences in the spectrum obtained by the two will be most evident in studying narrow absorption bands, e.g., the band due to dangling OH bonds at a water interface. The direct comparisons in the integrated amplitude (sum rule) of the imaginary part of the dangling OH bond region differ by a factor of 3. Due to variations in experimental setup and data processing, corrections were made for the quartz reference, Fresnel factors, and the incident visible laser wavelength. After the corrections, the agreement differs now by the factors of 1.1 within broadband and narrowband groups and the two groups now differ by a factor of 1.5. The 1.5 factor may arise from the extra heating of the more powerful broadband laser system on the water surface. The convolution from the narrowband SFG spectrum to the broadband SFG spectrum is also investigated and it does not affect the sum rule. Theory and narrowband experiments are compared using the sum rule and agree to a factor of 1.3 with no adjustable parameters.

2.
BMC Cancer ; 24(1): 496, 2024 Apr 18.
Artigo em Inglês | MEDLINE | ID: mdl-38637761

RESUMO

Ferroptosis has important value in cancer treatment. It is significant to explore the new ferroptosis-related lncRNAs prediction model in Hepatocellular carcinoma (HCC) and the potential molecular mechanism of ferroptosis-related lncRNAs. We constructed a prognostic multi-lncRNA signature based on ferroptosis-related differentially expressed lncRNAs in HCC. qRT-PCR was applied to determine the expression of lncRNA in HCC cells. The biological roles of NRAV in vitro and in vivo were determined by performing a series of functional experiments. Furthermore, dual-luciferase reporter and RNA immunoprecipitation (RIP) assays were used to confirm the interaction of NRAV with miR-375-3P. We identified 6 differently expressed lncRNAs associated with the prognosis of HCC. Kaplan-Meier analyses revealed the high-risk lncRNAs signature associated with poor prognosis of HCC. Moreover, the AUC of the lncRNAs signature showed utility in predicting HCC prognosis. Further functional experiments show that the high expression of NRAV can strengthen the viciousness of HCC. Interestingly, we found that NRAV can enhance iron export and ferroptosis resistance. Further study showed that NRAV competitively binds to miR-375-3P and attenuates the inhibitory effect of miR-375-3P on SLC7A11, affecting the prognosis of patients with HCC. In conclusion, We developed a novel ferroptosis-related lncRNAs prognostic model with important predictive value for the prognosis of HCC. NRAV is important in ferroptosis induction through the miR-375-3P/SLC7A11 axis.


Assuntos
Carcinoma Hepatocelular , Ferroptose , Neoplasias Hepáticas , MicroRNAs , RNA Longo não Codificante , Humanos , Carcinoma Hepatocelular/genética , RNA Longo não Codificante/genética , Ferroptose/genética , Neoplasias Hepáticas/genética , MicroRNAs/genética , Prognóstico , Sistema y+ de Transporte de Aminoácidos/genética
3.
World J Microbiol Biotechnol ; 40(5): 161, 2024 Apr 13.
Artigo em Inglês | MEDLINE | ID: mdl-38613738

RESUMO

Rhizopus nigricans (R. nigricans), one of the fungi that grows the fastest, is frequently discovered in postharvest fruits, it's the main pathogen of strawberry root rot. Flavonoids in Sedum aizoon L. (FSAL) is a kind of green and safe natural substance extracted from Sedum aizoon L. which has antifungal activity. In this study, the minimum inhibitory concentration (MIC) of FSAL on R. nigricans and cell apoptosis tests were studied to explore the inhibitory effect of FSAL on R. nigricans. The effects of FSAL on mitochondria of R. nigricans were investigated through the changes of mitochondrial permeability transition pore(mPTP), mitochondrial membrane potential(MMP), Ca2+ content, H2O2 content, cytochrome c (Cyt c) content, the related enzyme activity and related genes of mitochondria. The results showed that the MIC of FSAL on R. nigricans was 1.800 mg/mL, with the addition of FSAL (1.800 mg/mL), the mPTP openness of R. nigricans increased and the MMP reduced. Resulting in an increase in Ca2+ content, accumulation of H2O2 content and decrease of Cyt c content, the activity of related enzymes was inhibited and related genes were up-regulated (VDAC1, ANT) or down-regulated (SDHA, NOX2). This suggests that FSAL may achieve the inhibitory effect of fungi by damaging mitochondria, thereby realizing the postharvest freshness preservation of strawberries. This lays the foundation for the development of a new plant-derived antimicrobial agent.


Assuntos
Fragaria , Rhizopus , Sedum , Flavonoides/farmacologia , Peróxido de Hidrogênio , Citocromos c , Mitocôndrias
4.
J Am Chem Soc ; 146(17): 11657-11668, 2024 May 01.
Artigo em Inglês | MEDLINE | ID: mdl-38641862

RESUMO

All protein-directed syntheses of metal nanoclusters (NCs) and nanoparticles (NPs) have attracted considerable attention because protein scaffolds provide a unique metal coordination environment and can adjust the shape and morphology of NCs and NPs. However, the detailed formation mechanisms of NCs or NPs directed by protein templates remain unclear. In this study, by taking advantage of the ferritin nanocage as a biotemplate to monitor the growth of Fe-O NCs as a function of time, we synthesized a series of iron NCs with different sizes and shapes and subsequently solved their corresponding three-dimensional atomic-scale structures by X-ray protein crystallography and cryo-electron microscopy. The time-dependent structure analyses revealed the growth process of these Fe-O NCs with the 4-fold channel of ferritin as nucleation sites. To our knowledge, the newly biosynthesized Fe35O23Glu12 represents the largest Fe-O NCs with a definite atomic structure. This study contributes to our understanding of the formation mechanism of iron NCs and provides an effective method for metal NC synthesis.


Assuntos
Ferritinas , Tamanho da Partícula , Ferritinas/química , Nanopartículas Metálicas/química , Ferro/química , Modelos Moleculares , Cristalografia por Raios X , Compostos Férricos/química
5.
Plant Physiol Biochem ; 208: 108480, 2024 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-38437751

RESUMO

It is well established that programmed cell death (PCD) occurred in broccoli during postharvest senescence, but no studies have been conducted on the regulation of broccoli cytochrome f by mannose treatment and its relationship with PCD. In this study, we treated broccoli buds with mannose to investigate the changes in color, total chlorophyll content, gene expression related to chlorophyll metabolism, chloroplast structure, and cytochrome f determination during postharvest storage. In addition, to investigate the effect of cytochrome f on PCD, we extracted cytochrome f from broccoli and treated Nicotiana tabacum L. cv Bright Yellow 2 (BY-2) cells with extracted cytochrome f from broccoli at various concentrations. The results showed that cytochrome f can induce PCD in tobacco BY-2 cells, as evidenced by altered cell morphology, nuclear chromatin disintegration, DNA degradation, decreased cell viability, and increased caspase-3-like protease production. Taken together, our study indicated that mannose could effectively delay senescence of postharvest broccoli by inhibiting the expression of gene encoding cytochrome f which could induce PCD.


Assuntos
Brassica , Brassica/genética , Citocromos f/metabolismo , Manose/metabolismo , Manose/farmacologia , Nicotiana/genética , Apoptose , Clorofila/metabolismo
6.
Cell Commun Signal ; 22(1): 173, 2024 03 11.
Artigo em Inglês | MEDLINE | ID: mdl-38462636

RESUMO

BACKGROUND: Targeting the tumor microenvironment (TME) has emerged as a promising strategy in cancer treatment, particularly through the utilization of immune checkpoint blockade (ICB) agents such as PD-1/PD-L1 inhibitors. Despite partial success, the presence of tumor-associated macrophages (TAMs) contributes to an immunosuppressive TME that fosters tumor progression, and diminishes the therapeutic efficacy of ICB. Blockade of the CD47/SIRPα pathway has proven to be an effective intervention, that restores macrophage phagocytosis and yields substantial antitumor effects, especially when combined with PD-1/PD-L1 blockade. Therefore, the identification of small molecules capable of simultaneously blocking CD47/SIRPα and PD-1/PD-L1 interactions has remained imperative. METHODS: SMC18, a small molecule with the capacity of targeting both SIRPα and PD-L1 was obtained using MST. The efficiency of SMC18 in interrupting CD47/SIRPα and PD-1/PD-L1 interactions was tested by the blocking assay. The function of SMC18 in enhancing the activity of macrophages and T cells was tested using phagocytosis assay and co-culture assay. The antitumor effects and mechanisms of SMC18 were investigated in the MC38-bearing mouse model. RESULTS: SMC18, a small molecule that dual-targets both SIRPα and PD-L1 protein, was identified. SMC18 effectively blocked CD47/SIRPα interaction, thereby restoring macrophage phagocytosis, and disrupted PD-1/PD-L1 interactions, thus activating Jurkat cells, as evidenced by increased secretion of IL-2. SMC18 demonstrated substantial inhibition of MC38 tumor growths through promoting the infiltration of CD8+ T and M1-type macrophages into tumor sites, while also priming the function of CD8+ T cells and macrophages. Moreover, SMC18 in combination with radiotherapy (RT) further improved the therapeutic efficacy. CONCLUSION: Our findings suggested that the small molecule compound SMC18, which dual-targets the CD47/SIRPα and PD-1/PD-L1 pathways, could be a candidate for promoting macrophage- and T-cell-mediated phagocytosis and immune responses in cancer immunotherapy.


Assuntos
Inibidores de Checkpoint Imunológico , Neoplasias , Animais , Camundongos , Inibidores de Checkpoint Imunológico/farmacologia , Inibidores de Checkpoint Imunológico/uso terapêutico , Receptor de Morte Celular Programada 1 , Linfócitos T CD8-Positivos , Antígeno CD47/metabolismo , Antígeno B7-H1 , Fagocitose , Imunoterapia , Neoplasias/tratamento farmacológico , Neoplasias/patologia , Microambiente Tumoral
7.
Ann Med ; 56(1): 2332406, 2024 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-38547537

RESUMO

BACKGROUND: Interstitial lung disease (ILD) is the most widespread and fatal pulmonary complication of rheumatoid arthritis (RA). Existing knowledge on the prevalence and risk factors of rheumatoid arthritis-associated interstitial lung disease (RA-ILD) is inconclusive. Therefore, we designed this review to address this gap. MATERIALS AND METHODS: To find relevant observational studies discussing the prevalence and/or risk factors of RA-ILD, EMBASE, Web of Science, PubMed, and the Cochrane Library were explored. The pooled odds ratios (ORs) / hazard ratios (HRs) with 95% confidence intervals (CIs) were estimated with a fixed/ random effects model. While subgroup analysis, meta-regression analysis and sensitivity analysis were carried out to determine the sources of heterogeneity, the I2 statistic was utilized to assess between-studies heterogeneity. Funnel plots and Egger's test were employed to assess publication bias. Following the Preferred Reporting Items for Systematic Review and Meta-Analysis (PRISMA) guidelines, our review was conducted. RESULTS: A total of 56 studies with 11,851 RA-ILD patients were included in this meta-analysis. The pooled prevalence of RA-ILD was 18.7% (95% CI 15.8-21.6) with significant heterogeneity (I2 = 96.4%). The prevalence of RA-ILD was found to be more likely as a result of several identified factors, including male sex (ORs = 1.92 95% CI 1.70-2.16), older age (WMDs = 6.89, 95% CI 3.10-10.67), having a smoking history (ORs =1.91, 95% CI 1.48-2.47), pulmonary comorbidities predicted (HRs = 2.08, 95% CI 1.89-2.30), longer RA duration (ORs = 1.03, 95% CI 1.01-1.05), older age of RA onset (WMDs =4.46, 95% CI 0.63-8.29), positive RF (HRs = 1.15, 95%CI 0.75-1.77; ORs = 2.11, 95%CI 1.65-2.68), positive ACPA (ORs = 2.11, 95%CI 1.65-2.68), higher ESR (ORs = 1.008, 95%CI 1.002-1.014), moderate and high DAS28 (≥3.2) (ORs = 1.87, 95%CI 1.36-2.58), rheumatoid nodules (ORs = 1.87, 95% CI 1.18-2.98), LEF use (ORs = 1.42, 95%CI 1.08-1.87) and steroid use (HRs= 1.70, 1.13-2.55). The use of biological agents was a protective factor (HRs = 0.77, 95% CI 0.69-0.87). CONCLUSION(S): The pooled prevalence of RA-ILD in our study was approximately 18.7%. Furthermore, we identified 13 risk factors for RA-ILD, including male sex, older age, having a smoking history, pulmonary comorbidities, older age of RA onset, longer RA duration, positive RF, positive ACPA, higher ESR, moderate and high DAS28 (≥3.2), rheumatoid nodules, LEF use and steroid use. Additionally, biological agents use was a protective factor.


Assuntos
Artrite Reumatoide , Doenças Pulmonares Intersticiais , Nódulo Reumatoide , Humanos , Masculino , Nódulo Reumatoide/complicações , Prevalência , Artrite Reumatoide/complicações , Artrite Reumatoide/epidemiologia , Fatores de Risco , Doenças Pulmonares Intersticiais/epidemiologia , Doenças Pulmonares Intersticiais/etiologia , Esteroides
8.
Langmuir ; 2024 Feb 06.
Artigo em Inglês | MEDLINE | ID: mdl-38320153

RESUMO

The sorbent concentration (Cs) effect and sorbate initial concentration (C0) effect are common phenomena observed in the study of adsorption kinetics at solid-liquid interfaces. That is, adsorption rate constants simulated with classical kinetic equations, such as the pseudo-second-order (PSO) model, for a given system vary with Cs and C0. The classical kinetic equations cannot predict or describe the "Cs-effect" and "C0-effect" (called "C-effects" here). In the current work, the dynamic partition coefficient of sorbate between solid and liquid phases (Kt) was used to describe the adsorption kinetic processes. Based on the surface component activity (SCA) model, which assumes the activity coefficients of the surface components (fs) are not equal to unity but rather a function of Cs and the adsorption capacity (or C0) and referring to the classical PSO model, a new kinetic equation was established, called the "SCA-PSO kinetic model", and its two parameters, the intrinsic equilibrium partition coefficient (Ke0) and the intrinsic rate constant (k20), are independent of Cs and C0. In addition, the new model relates Kt and the rate constant (k2) to Cs and C0 via fs, and can thus describe the C-effects. The fs can be estimated from the change of equilibrium partition coefficient (Ke) with Cs and C0. The new model predicts that with the increase of Cs and C0, Ke decreases while k2 increases. Its rationality was confirmed by the literature-reported adsorption kinetic data of heavy metals on inorganic and biomass sorbents with the C-effects.

9.
Sci Total Environ ; 918: 170628, 2024 Mar 25.
Artigo em Inglês | MEDLINE | ID: mdl-38325476

RESUMO

The one-time application of common urea blended with controlled-release urea (CRU) is considered effective for improving nitrogen use efficiency and grain yield and reducing the greenhouse gas emissions of summer maize in intensive agricultural systems. However, the trade-off between the economic and environmental performances of different blended fertilizer treatments for different maize varieties remains unclear. Therefore, a consecutive two-year field experiment was conducted in the North China Plain to study the effects of different ratios of CRU and common urea on the yield, nitrous oxide (N2O) emissions, yield-scaled total N2O emissions, greenhouse gas intensity (GHGI), and net ecosystem economic benefit (NEEB) in 2021 and 2022. Four N fertilizer treatments with equal rate at 180 kg N ha-1 were applied as N180U (all Urea), N180C1(1/3CRU), N180C2(2/3CRU), and N180C (all CRU), and two maize varieties (JNK728-yellow ripe variety and ZD958-green ripe variety) were used. The N180C1 and N180C2 treatments produced the highest grain yield in varieties JNK728 and ZD958 (9.4-11.5 t ha-1 and 9.0-11.0 t ha-1), respectively. Compared to the N180U treatment (conventional method), the N180C1 treatment reduced the GHGI (24.8 %-25.9 %) and increased the NEEB (33.1 %-33.4 %) in the JNK728 variety, whereas the N180C2 treatment reduced the GHGI (16.9 %-28.8 %) and increased the NEEB (27.2 %-48.1 %) in the ZD958 variety. The study concludes that a one-time application of blended nitrogen fertilizer in suitable varieties can minimize the GHGI and maximize the NEEB, which is an effective strategy for balancing yield and nitrogen efficiency in the summer maize system in the North China Plain.


Assuntos
Gases de Efeito Estufa , Gases de Efeito Estufa/análise , Solo , Zea mays , Preparações de Ação Retardada , Ureia , Fertilizantes/análise , Ecossistema , Metano/análise , Agricultura/métodos , Nitrogênio , Grão Comestível/química , Óxido Nitroso/análise , China
10.
Metallomics ; 16(2)2024 02 07.
Artigo em Inglês | MEDLINE | ID: mdl-38263542

RESUMO

Four Ru(II)-centered isomeric complexes [RuCl(5cqn)(Val)(NO)] (1-4) were synthesized with 5cqn (5-chloro-8-hydroxyquinoline) and chiral Val (Val = L- or D-valine) as co-ligand, and their structures were confirmed using the X-ray diffraction method. The cytotoxicity and photodynamic activity of the isomeric complexes and their human serum albumin (HSA) complex adducts were evaluated. Both the isomeric complexes and their HSA complex adducts significantly affected HeLa cell proliferation, with an IC50 value in the range of 0.3-0.5 µM. The photo-controlled release of nitric oxide (NO) in solution was confirmed using time-resolved Fourier transform infrared and electron paramagnetic resonance spectroscopy techniques. Furthermore, photoinduced NO release in living cells was observed using a selective fluorescent probe for NO. Moreover, the binding constants (Kb) of the complexes with HSA were calculated to be 0.17-1.98 × 104 M-1 and the average number of binding sites (n) was found to be close to 1, it can serve as a crucial carrier for delivering metal complexes. The crystal structure of the HSA complex adduct revealed that one [RuCl(H2O)(NO)(Val)]+ molecule binds to a pocket in domain I. This study provides insight into possible mechanism of metabolism and potential applications for nitrosylruthenium complexes.


Assuntos
Antineoplásicos , Complexos de Coordenação , Humanos , Antineoplásicos/farmacologia , Óxido Nítrico , Albumina Sérica Humana/metabolismo , Células HeLa , Sítios de Ligação , Complexos de Coordenação/farmacologia , Complexos de Coordenação/química
11.
Tissue Cell ; 87: 102304, 2024 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-38219450

RESUMO

Blood vessels are the tubes through which blood flows and are divided into three types: millimeter-scale arteries, veins, and capillaries as well as micrometer-scale capillaries. Arteries and veins are the conduits that carry blood, while capillaries are where blood exchanges substances with tissues. Blood vessels are mainly composed of collagen fibers, elastic fibers, glycosaminoglycans and other macromolecular substances. There are about 19 feet of blood vessels per square inch of skin in the human body, which shows how important blood vessels are to the human body. Because cardiovascular disease and vascular trauma are common in the population, a great number of researches have been carried out in recent years by simulating the structures and functions of the person's own blood vessels to create different levels of tissue-engineered blood vessels that can replace damaged blood vessels in the human body. However, due to the lack of effective oxygen and nutrient delivery mechanisms, these tissue-engineered vessels have not been used clinically. Therefore, in order to achieve better vascularization of engineered vascular tissue, researchers have widely explored the design methods of vascular systems of various sizes. In the near future, these carefully designed and constructed tissue engineered blood vessels are expected to have practical clinical applications. Exploring how to form multi-scale vascular networks and improve their compatibility with the host vascular system will be very beneficial in achieving this goal. Among them, 3D printing has the advantages of high precision and design flexibility, and the decellularized matrix retains active ingredients such as collagen, elastin, and glycosaminoglycan, while removing the immunogenic substance DNA. In this review, technologies and advances in 3D printing and decellularization-based artificial blood vessel manufacturing methods are systematically discussed. Recent examples of vascular systems designed are introduced in details, the main problems and challenges in the clinical application of vascular tissue restriction are discussed and pointed out, and the future development trends in the field of tissue engineered blood vessels are also prospected.


Assuntos
Substitutos Sanguíneos , Humanos , Substitutos Sanguíneos/análise , Engenharia Tecidual/métodos , Matriz Extracelular/química , Colágeno , Impressão Tridimensional , Alicerces Teciduais
12.
J Virol ; 98(1): e0143723, 2024 Jan 23.
Artigo em Inglês | MEDLINE | ID: mdl-38084957

RESUMO

SARS-CoV-2 belongs to the subgenus Sarbecovirus, which universally encodes the accessory protein ORF6. SARS-CoV-2 ORF6 is an antagonist of the interferon (IFN)-mediated antiviral response and plays an important role in viral infections. However, the mechanism by which the host counteracts the function of ORF6 to restrict viral replication remains unclear. In this study, we found that most ORF6 proteins encoded by sarbecoviruses could be ubiquitinated and subsequently degraded via the proteasome pathway. Through extensive screening, we identified that the deubiquitinase USP1, which effectively and broadly deubiquitinates sarbecovirus ORF6 proteins, stabilizes ORF6 proteins, resulting in enhanced viral replication. Therefore, ubiquitination and deubiquitination of ORF6 are important for antagonizing IFN-mediated antiviral signaling and influencing the virulence of SARS-CoV-2. These findings highlight an essential molecular mechanism and may provide a novel target for therapeutic interventions against viral infections.IMPORTANCEThe ORF6 proteins encoded by sarbecoviruses are essential for effective viral replication and infection and are important targets for developing effective intervention strategies. In this study, we confirmed that sarbecovirus ORF6 proteins are important antagonists of the host immune response and identified the regulatory mechanisms of ubiquitination and deubiquitination of most sarbecovirus ORF6 proteins. Moreover, we revealed that DUB USP1 prevents the proteasomal degradation of all ORF6 proteins, thereby promoting the virulence of SARS-CoV-2. Thus, impeding ORF6 function is helpful for attenuating the virulence of sarbecoviruses. Therefore, our findings provide a deeper understanding of the molecular mechanisms underlying sarbecovirus infections and offer potential new therapeutic targets for the prevention and treatment of these infections.


Assuntos
SARS-CoV-2 , Proteínas Virais , Viroses , Humanos , Enzimas Desubiquitinantes , Interferons/metabolismo , SARS-CoV-2/genética , SARS-CoV-2/metabolismo , Coronavírus Relacionado à Síndrome Respiratória Aguda Grave/fisiologia , Proteases Específicas de Ubiquitina/genética , Proteases Específicas de Ubiquitina/metabolismo , Proteínas Virais/genética , Proteínas Virais/metabolismo
13.
Int Immunopharmacol ; 126: 111216, 2024 Jan 05.
Artigo em Inglês | MEDLINE | ID: mdl-37977072

RESUMO

BACKGROUND: M1/M2 macrophage polarization affects patient outcomes after myocardial infarction (MI). The relationship between milk fat globule-epidermal growth factor 8 (MFG-E8) and Ca2+/calmodulin-dependent protein kinase II (CaMKII) on macrophage polarization after MI is unknown. To investigate the functional role of MFG-E8 in modulating cardiac M1/M2 macrophage polarization after MI, especially its influence on CaMKII signaling. METHODS: Human ventricular tissue and blood were obtained from patients with MI and controls. MFG-E8-KO mice were constructed (C57BL/6). The mice were randomized to WT-sham, sham-MFG-E8-KO, WT-PBS, rmMFG-E8 (WT injected with rmMFG-E8 10 min after MI), and MFG-E8-KO. The mouse macrophage cell line RAW264.7 was obtained. CaMKII, p-CaMKII, Akt, and NF-κB p65 were determined by qRT-PCR, western blot, and immunofluorescence. RESULTS: The MFG-E8 levels were significantly enhanced after MI in the hearts and plasma of patients with MI compared with controls. The MFG-E8 levels were significantly increased in the hearts and plasma of mice after MI. MFG-E8 was derived from cardiac fibroblasts. The administration of rmMFG-E8 improved ventricular remodeling and cardiac function after MI. rmMFG-E8 did not suppress infiltrating monocyte/macrophages into the peri-infarct area. rmMFG-E8 suppressed the polarization of macrophages to the M1 phenotype and promoted the polarization of macrophages to the M2 phenotype. rmMFG-E8 suppressed CaMKII-dependent signaling in macrophages. CONCLUSIONS: MFG-E8 and CaMKII appear to collaboratively regulate myocardial remodeling and M1/M2 macrophage polarization after MI. These observations suggest new roles for MFG-E8 in inhibiting M1 but promoting M2 macrophage polarization.


Assuntos
Proteína Quinase Tipo 2 Dependente de Cálcio-Calmodulina , Infarto do Miocárdio , Animais , Humanos , Camundongos , Antígenos de Superfície/genética , Fator VIII , Camundongos Endogâmicos C57BL
14.
Ecotoxicol Environ Saf ; 269: 115810, 2024 Jan 01.
Artigo em Inglês | MEDLINE | ID: mdl-38100849

RESUMO

BACKGROUND: Jujuboside B (JuB) is the main bioactive saponin component of Chinese anti-insomnia herbal medicine Ziziphi Spinosae Semen, which has been reported to possess varied pharmacological functions. Even though it has been traditionally used to treat inflammation- and toxicity-related diseases, the effects of JuB on acetaminophen (APAP) overdose-induced hepatotoxicity have not been determined yet. METHODS: C57BL/6 J mice were pre-treated with JuB (20 or 40 mg/kg) for seven days before APAP (400 mg/kg) injection. After 24 h of APAP treatment, serum, and liver tissues were collected to evaluate the therapeutic effects. To investigate whether the Nrf2-STING signaling pathway is involved in the protective effects of JuB against APAP-induced hepatotoxicity, the mice received the DMXAA (the specific STING agonist) or ML385 (the specific Nrf2 inhibitor) during the administration of JuB, and Hematoxylin-eosin staining, Real-time PCR, immunohistochemical, and western blot were performed. RESULTS: JuB pretreatment reversed APAP-induced CYP2E1 accumulations and alleviated APAP-induced acute liver injury. Furthermore, JuB treatment significantly inhibited oxidative stress and the pro-inflammatory cytokines, as well as alleviated hepatocyte apoptosis induced by APAP. Besides, our result also demonstrated that JuB treatment upregulated the levels of total Nrf2, facilitated its nuclear translocation, upregulated the expression of HO-1 and NQO-1, and inhibited the APAP-induced STING pathway activation. Finally, we verified that the beneficial effects of JuB were weakened by DMXAA and ML385. CONCLUSION: Our study suggested that JuB could ameliorate APAP-induced hepatic damage and verified a previously unrecognized mechanism by which JuB prevented APAP-induced hepatotoxicity through adjusting the Nrf2-STING pathway.


Assuntos
Doença Hepática Induzida por Substâncias e Drogas , Saponinas , Animais , Camundongos , Acetaminofen/toxicidade , Acetaminofen/metabolismo , Fator 2 Relacionado a NF-E2/genética , Fator 2 Relacionado a NF-E2/metabolismo , Substâncias Protetoras/farmacologia , Doença Hepática Induzida por Substâncias e Drogas/tratamento farmacológico , Doença Hepática Induzida por Substâncias e Drogas/etiologia , Doença Hepática Induzida por Substâncias e Drogas/prevenção & controle , Camundongos Endogâmicos C57BL , Transdução de Sinais , Estresse Oxidativo , Fígado , Saponinas/farmacologia , Saponinas/uso terapêutico
15.
J Agric Food Chem ; 71(49): 19739-19748, 2023 Dec 13.
Artigo em Inglês | MEDLINE | ID: mdl-38041637

RESUMO

Previously, we reported that marine yeast Scheffersomyces spartinae exhibited biocontrol efficacy against the gray mold of strawberries caused by Botrytis cinerea. Herein, tryptophol, a quorum-sensing molecule, was identified in the metabolites of S. spartinae. Subsequently, we found that 25 µM tryptophol promoted population density, biofilm formation, and cell aggregation of S. spartinae. Furthermore, 25 µM tryptophol improved the biocontrol efficacy of S. spartinae against B. cinerea in vitro and in the strawberry fruit. Under a scanning electronic microscope, tryptophol facilitated colonization and biofilm formation on strawberry wounds, showing that tryptophol increased the biocontrol efficacy of S. spartinae via quorum sensing. Transcriptome analysis revealed that tryptophol upregulated the gene expression of SDS3, DAL81, DSE1, SNF5, SUN41, FLO8, and HOP1, which was associated with cell adhesion or biofilm formation. Thus, to the best of our knowledge, this study was the first to report that tryptophol improved the biocontrol efficacy of S. spartinae via quorum sensing.


Assuntos
Fragaria , Percepção de Quorum , Saccharomyces cerevisiae
16.
Front Cardiovasc Med ; 10: 1236008, 2023.
Artigo em Inglês | MEDLINE | ID: mdl-38028498

RESUMO

Aims: Recent studies have shown that mineralocorticoid receptor antagonists (MRAs) can decrease mortality in patients with heart failure; however, the application of MRAs in current clinical practice is limited because of adverse effects such as hyperkalemia that occur with treatment. Therefore, this meta-analysis used the number needed to treat (NNT) to assess the efficacy and safety of MRAs in patients with chronic heart failure. Methods: We meta-analysed randomized controlled trials (RCTs) which contrasted the impacts of MRAs with placebo. As of March 2023, all articles are published in English. The primary outcome was major adverse cardiovascular events (MACE), and secondary outcomes included all-cause mortality, cardiovascular death, myocardial infarction (MI), stroke, and adverse events. Results: We incorporated seven studies with a total of 9,056 patients, 4,512 of whom received MRAs and 4,544 of whom received a placebo, with a mean follow-up period of 2.1 years. MACE, all-cause mortality, and cardiovascular mortality were all reduced by MRAs, with corresponding numbers needed to treat for benefit (NNTB) of 37, 28, and 34; as well as no impact on MI or stroke. MRAs increased the incidence of hyperkalemia and gynecomastia, with the corresponding mean number needed to treat for harm (NNTH) of 18 and 52. Conclusions: This study showed that enabling one patient with HF to avoid MACE required treating 37 patients with MRAs for 2.1 years. MRAs reduce MACE, all-cause mortality, and cardiovascular death; however, they increase the risk of hyperkalemia and gynecomastia.

17.
Front Public Health ; 11: 1272149, 2023.
Artigo em Inglês | MEDLINE | ID: mdl-38026403

RESUMO

Background: Seasons were found to be related to the occurrences of venous thromboembolism (VTE) in hospitalized patients. No previous study has explored whether seasons were associated with VTE risk in pregnant women. This study aimed to investigate the relationships between the season of delivery and VTE risk during hospitalization among pregnant women. Methods: This is a multi-center retrospective cohort study of pregnant women. Participants were those who delivered at seven designated sites in Hubei Province, China, during the period from January 2017 to December 2022. They were categorized according to their season/month of delivery. Information on new-onset VTE during hospitalization was followed. Results: Approximately 0.28% (104/37,778) of the pregnant women developed new-onset VTE during hospitalization for delivery. After adjustment, compared with participants in the spring group, participants in the summer, autumn, and winter groups had an increased risk of VTE during hospitalization. The ORs were 2.59 [1.30, 5.15], 2.83 [1.43, 5.60], and 2.35 [1.17, 4.75] for the summer, autumn, and winter groups, respectively. Pregnant women in the combined group (summer + autumn + winter) had an increased risk of VTE during hospitalization than those in the spring group (OR, 2.59 [1.39, 4.85]). By restricting the analyses among pregnant women without in vitro fertilization, gestational diabetes mellitus, and preterm, the results still remained robust. Compared with participants who delivered in March, April, and May, participants who delivered in June, July, September, November, December, and February had a higher risk of VTE during hospitalization. Conclusion: This study demonstrated that pregnant women who delivered in summer, autumn, and winter had an increased VTE risk during hospitalization compared with those who delivered in spring.


Assuntos
Tromboembolia Venosa , Recém-Nascido , Humanos , Feminino , Gravidez , Tromboembolia Venosa/epidemiologia , Gestantes , Estações do Ano , Estudos Retrospectivos , Hospitalização
18.
Micromachines (Basel) ; 14(10)2023 Oct 18.
Artigo em Inglês | MEDLINE | ID: mdl-37893380

RESUMO

In our previous studies, the silicon drift detector (SDD) structure with a constant spiral ring cathode gap (g) and a given surface electric field has been partially investigated based on the physical model that gives an analytical solution to the integrals in the calculations. Those results show that the detector has excellent electrical characteristics with a very homogeneous carrier drift electric field. In order to cope with the implementation of the theoretical approach with a complete set of technical parameters, this paper performs different theoretical algorithms for the technical implementation of the detector performance using the Taylor expansion method to construct a model for cases where the parameter "j" is a non-integer, approximating the solution with finite terms. To verify the accuracy of this situation, we performed a simulation of the relevant electrical properties using the Sentaurus TCAD tool 2018. The electrical properties of the single and double-sided detectors are first compared, and then the effects of different equal gaps g (g = 10 µm, 20 µm, and 25 µm, respectively) on the electrical properties of the double-sided detectors are analyzed and demonstrated. By analyzing and comparing the electrical characteristics data from the simulation results, we can show that the double-sided structure has a larger transverse drift electric field, which improves the spatial position resolution as well as the response speed. The effect of the gap size on the electrical characteristics of the detector is also analyzed by analyzing three different gap bifacial detectors, and the results show that a 10 µm equal gap is the optimal design. Such results can be used in applications requiring large-area SDD, such as the pulsar X-ray autonomous navigation. in the future to provide navigation and positioning space services for spacecraft deep-space exploration.

19.
J Endovasc Ther ; : 15266028231205718, 2023 Oct 26.
Artigo em Inglês | MEDLINE | ID: mdl-37882181

RESUMO

PURPOSE: Up to now, the indications of inferior vena cava filter placement still remain controversial in the academic field. The aim of this study was to determine the risk factors of detachment of thrombus and to evaluate the necessity of inferior vena cava filter placement to prevent fatal pulmonary embolism. MATERIALS AND METHODS: A total of 2892 patients participated in the multicenter prospective observational study from January 1, 2018, to December 31, 2018, and underwent retrievable inferior vena cava filter (RIVCF) placement in 103 centers in China. The primary endpoint of the study was RIVCF trapped embolus detected by inferior vena cava venography/ultrasound/computed tomography scanning or visible macroscopic thrombus before or during RIVCF retrieval. The relative factors of RIVCF trapped embolus were analyzed accordingly. RESULTS: The average age of the patients was 61.0 (50.0-71.0) years. Retrievable inferior vena cava filter trapped embolus occurred in 308 patients (10.65%). The fracture location, surgery location, and endovascular intervention differed between RIVCF trapped embolus and non-RIVCF trapped embolus groups (p<0.001, respectively). By multivariate analysis, RIVCF trapped embolus were less common in older patients (odds ratio [OR]=0.998; p<0.001) and more common in patients with below-the-knee fracture (OR=1.093, p=0.038), thigh fracture (OR=1.118, p=0.007), and pelvis surgery (OR=1.067, p=0.016). In addition, compared with patients without endovascular intervention, patients with percutaneous mechanical thrombectomy (PMT) + catheter-directed thrombolysis (CDT) were more prone to develop RIVCF trapped embolus (OR=1.060, p=0.010). However, RIVCF trapped embolus was less common in patients with CDT (OR=0.961, p=0.004). CONCLUSIONS: Lower limb fracture, pelvis surgery, and PMT + CDT are prone to cause trapped embolus. As a trapped embolus often represents the possibility of severe pulmonary embolism, lower limb fracture, pelvis surgery, and PMT + CDT could be risk factors of fatal pulmonary embolism. Due to the low incidence of trapped embolus, it is not necessary to place filters in elderly patients and CDT-only patients. CLINICAL IMPACT: The purpose of this paper is to standardize the use of inferior vena cava filter and avoid unnecessary filter implantation through the summary and analysis of a large number of clinical data. At the same time, more attention should be paid to and active treatment should be given to high-risk groups of pulmonary embolism.

20.
Int J Syst Evol Microbiol ; 73(10)2023 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-37831063

RESUMO

Light yellowish-white colonies of a bacterial strain, designated LNNU 24178T, were isolated from the rhizosphere soil of halophyte Suaeda aralocaspica (Bunge) Freitag and Schütze grown at Shihezi district, Xinjiang, PR China. Cells were Gram-stain-negative, non-flagellum-forming, rod-shaped and non-motile. The results of phylogenetic analysis based on the 16S rRNA gene sequence indicated that LNNU 24178T represented a member of the genus Luteimonas and shared the highest sequence similarity with Luteimonas yindakuii CGMCC 1.13927T (97.1 %) and lower sequence similarity (< 97.0 %) to other known species. The genomic DNA G+C content of LNNU 24178T was 68.8 %. The average nucleotide identity (ANI) values between LNNU 24178T and Luteimonas yindakuii CGMCC 1.13927T, Luteimonas mephitis DSM 12574T, Luteimonas arsenica 26-35T and Luteimonas huabeiensis HB2T were 78.7, 78.6, 78.4 and 80.0 %, respectively. The digital DNA-DNA hybridisation (dDDH) values between LNNU 24178T and L. yindakuii CGMCC 1.13927T, L. mephitis DSM 12574T, L. arsenica 26-35T and L. huabeiensis HB2T were 22.0, 22.3, 22.2 and 23.5 %, respectively. The respiratory quinone detected in LNNU 24178T was ubiquinone-8 (Q-8). The major fatty acids (> 5.0 %) of LNNU 24178T were identified as iso-C15 : 0 (33.9 %), iso-C17 : 0 (8.7 %), iso-C11 : 0 (6.2 %), iso-C16 : 0 (5.7 %), C16 : 0 (5.3 %) and summed feature 9 (iso-C17 : 1ω9c/10-methyl C16 : 0) (21.1 %). The major polar lipids of LNNU 24178T were diphosphatidylglycerol (DPG), phosphatidylglycerol (PG), phosphatidylethanolamine (PE), one unidentified phospholipid (PL), one unidentified glycolipid (GL) and three unidentified lipids. According to the data obtained from phenotypic, chemotaxonomic and phylogenetic analyses, strain LNNU 24178T represents a novel species of the genus Luteimonas, for which the name Luteimonas suaedae sp. nov. is proposed, with LNNU 24178T (= CGMCC 1.17331T= KCTC 62251T) as the type strain.


Assuntos
Ácidos Graxos , Rizosfera , Ácidos Graxos/química , Filogenia , RNA Ribossômico 16S/genética , DNA Bacteriano/genética , Composição de Bases , Técnicas de Tipagem Bacteriana , Análise de Sequência de DNA , Fosfolipídeos
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