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1.
Adv Sci (Weinh) ; : e2403442, 2024 Sep 19.
Artículo en Inglés | MEDLINE | ID: mdl-39297413

RESUMEN

Effective inhibition of intestinal lipid uptake is an efficient strategy for the treatment of disorders related to lipid metabolism. Sterol O-acyltransferase 2 (SOAT2) is responsible for the esterification of free cholesterol and fatty acids into cholesteryl esters. We found that intestine-specific SOAT2 knockout (Soat2I-KO) mice was capable to prevent the development of dietary induced obesity due to reduced intestinal lipid absorption. Soat2 siRNA/CS-PLGA nanoparticle system was constructed to enable intestinal delivery and inhibition of Soat2. This nanoparticle system was composed of PLGA-block-PEG and chitosan specifically delivering Soat2 siRNAs into small intestines in mice, effectively inhibit intestinal lipid uptake and resolving obesity. In revealing the underlying mechanism by which intestinal SOAT2 regulating fatty acid uptake, enhanced CD36 ubiquitination degradation was found in enterocytes upon SOAT2 inhibition. Insufficient free cholesterol esterification promoted endoplasmic reticulum stress and recruitment of E3 ligase RNF5 to activate CD36 ubiquitination in SOAT2 knockdown enterocytes. This work demonstrates a potential modulatory function of intestinal SOAT2 on lipid uptake highlighting the therapeutic effect on obesity by targeting intestinal SOAT2, exhibiting promising translational relevance in the siRNA therapeutic-based treatment for obesity.

2.
iScience ; 27(8): 110328, 2024 Aug 16.
Artículo en Inglés | MEDLINE | ID: mdl-39184434

RESUMEN

Plasmas under atmospheric pressure offer a high-temperature environment for material synthesis, but electrode ablation compromises purity. Here, we introduce an atmospheric-pressure microwave plasma (AMP) operated without electrodes to overcome the existing limitations in pure material synthesis. The distribution of the electrostatic field intensity inside a waveguide during AMP excitation was examined via electrostatic field simulations. The lateral and radial gas temperature distributions were also studied using optical emission spectroscopy. The AMP exhibited a uniform ultrahigh temperature (9,000 K), a large volume (102-104 cm3), and a response time on the millisecond level. AMP efficiently synthesized silicon nanoparticles, graphene, and graphene@Si-Fe core-shell nanoparticles within tens of milliseconds, ensuring purity and size control. We propose the "heat impulse" metric for evaluating the plasma characteristics (n a, T g, and t) in material synthesis, extended to other high-temperature plasmas. AMP is compact, cost-effective, and easy to assemble, promising for eco-friendly mass production of pure materials.

3.
Drug Des Devel Ther ; 18: 2043-2061, 2024.
Artículo en Inglés | MEDLINE | ID: mdl-38863767

RESUMEN

Background: Despite its extensive utilization in Chinese hospitals for treating acute pancreatitis (AP) and related acute respiratory distress syndrome (ARDS), the active components and mechanisms underlying the action of Qingyi Granule (QYKL) remain elusive. Methods: This study consists of four parts. First, we used Mendelian randomization (MR) to investigate the causal relationship between AP, cytokine, and ARDS. Next, 321 patients were collected to evaluate the efficacy of QYKL combined with dexamethasone (DEX) in treating AP. In addition, we used UHPLC-QE-MS to determine the chemical constituents of QYKL extract and rat serum after the oral administration of QYKL. The weighted gene coexpression network analysis (WGCNA) method was used to find the main targets of AP-related ARDS using the GSE151572 dataset. At last, a AP model was established by retrograde injection of 5% sodium taurocholate. Results: MR showed that AP may have a causal relationship with ARDS by mediating cytokine storms. Retrospective study results showed early administration of QYKL was associated with a lower incidence of ARDS, mortality, admissions to the intensive care unit, and length of stay in AP patients compared to the Control group. Furthermore, we identified 23 QYKL prototype components absorbed into rat serum. WGCNA and differential expression analysis identified 1558 APALI-related genes. The prototype components exhibited strong binding activity with critical targets. QYKL has a significant protective effect on pancreatic and lung injury in AP rats, and the effect is more effective after combined treatment with DEX, which may be related to the regulation of the IL-6/STAT3 signaling pathway. Conclusion: By integrating MR, retrospective analysis, and systematic pharmacological methodologies, this study systematically elucidated the therapeutic efficacy of QYKL in treating AP-related ARDS, establishing a solid foundation for its medicinal use.


Asunto(s)
Medicamentos Herbarios Chinos , Pancreatitis , Síndrome de Dificultad Respiratoria , Medicamentos Herbarios Chinos/farmacología , Medicamentos Herbarios Chinos/química , Síndrome de Dificultad Respiratoria/tratamiento farmacológico , Pancreatitis/tratamiento farmacológico , Pancreatitis/metabolismo , Animales , Ratas , Humanos , Estudios Retrospectivos , Masculino , Ratas Sprague-Dawley , Dexametasona/farmacología , Dexametasona/administración & dosificación , Enfermedad Aguda , Femenino , Persona de Mediana Edad
4.
Am J Transl Res ; 16(5): 1484-1498, 2024.
Artículo en Inglés | MEDLINE | ID: mdl-38883347

RESUMEN

BACKGROUND: Rehabilitation after total knee arthroplasty (TKA) has become an indispensable part of the treatment strategy for degenerative joint disease. Despite some current research demonstrating efficacy of transcutaneous electrical acupoint stimulation (TEAS) for post-TKA rehabilitation, the evidence is not conclusive. OBJECTIVE: To systematically assess the evidence supporting TEAS for rehabilitation after TKA. METHODS: A literature search of the PubMed, Embase, The Cochrane Library, Chinese National Knowledge Infrastructure, Chinese Biomedical Literature Database, Wanfang, and Chinese Scientific Journal Data databases for relevant studies published up to October 16, 2023, was performed. Main indicators included visual analog scale (VAS) and functional scores; secondary indicators included range of motion (ROM), interleukin-6 (IL-6) and C-reactive protein (CRP) levels, and analgesia-related adverse events. Risk of bias was evaluated using the Cochrane Tool, and meta-analysis was performed using Review Manager version 5.4. RESULTS: Twenty RCTs with 1295 participants were included. TEAS improved several outcomes compared to control groups. The TEAS group had significantly greater pain reduction at postoperative 6 h, 12 h, 24 h, 48 h, 72 h, 7 days, and 14 days. Moreover, TEAS significantly improved the Hospital for Special Surgery Knee Score, Knee Society Score, and ROM. Patients who underwent TEAS exhibited a lower incidence of analgesia-related adverse events and lower IL-6 and CRP levels. CONCLUSIONS: Available evidence indicates that the application of TEAS in patients undergoing TKA is related to postoperative pain alleviation, functional improvement, and fewer adverse events associated with analgesia.

5.
NPJ Biofilms Microbiomes ; 10(1): 29, 2024 Mar 21.
Artículo en Inglés | MEDLINE | ID: mdl-38514648

RESUMEN

Early dysbiosis in the gut microbiota may contribute to the severity of acute pancreatitis (AP), however, a comprehensive understanding of the gut microbiome, potential pathobionts, and host metabolome in individuals with AP remains elusive. Hence, we employed fecal whole-metagenome shotgun sequencing in 82 AP patients and 115 matched healthy controls, complemented by untargeted serum metabolome and lipidome profiling in a subset of participants. Analyses of the gut microbiome in AP patients revealed reduced diversity, disrupted microbial functions, and altered abundance of 77 species, influenced by both etiology and severity. AP-enriched species, mostly potential pathobionts, correlated positively with host liver function and serum lipid indicators. Conversely, many AP-depleted species were short-chain fatty acid producers. Gut microflora changes were accompanied by shifts in the serum metabolome and lipidome. Specifically, certain gut species, like enriched Bilophila wadsworthia and depleted Bifidobacterium spp., appeared to contribute to elevated triglyceride levels in biliary or hyperlipidemic AP patients. Through culturing and whole-genome sequencing of bacterial isolates, we identified virulence factors and clinically relevant antibiotic resistance in patient-derived strains, suggesting a predisposition to opportunistic infections. Finally, our study demonstrated that gavage of specific pathobionts could exacerbate pancreatitis in a caerulein-treated mouse model. In conclusion, our comprehensive analysis sheds light on the gut microbiome and serum metabolome in AP, elucidating the role of pathobionts in disease progression. These insights offer valuable perspectives for etiologic diagnosis, prevention, and intervention in AP and related conditions.


Asunto(s)
Microbioma Gastrointestinal , Pancreatitis , Animales , Ratones , Humanos , Metagenoma , Enfermedad Aguda , Pancreatitis/etiología , ARN Ribosómico 16S/genética
6.
Expert Rev Proteomics ; 21(1-3): 115-123, 2024.
Artículo en Inglés | MEDLINE | ID: mdl-38372668

RESUMEN

INTRODUCTION: Around 20% of individuals diagnosed with acute pancreatitis (AP) may develop severe acute pancreatitis (SAP), possibly resulting in a mortality rate ranging from 15% to 35%. There is an urgent need to thoroughly understand the molecular phenotypes of SAP resulting from diverse etiologies. The field of translational research on AP has seen the use of several innovative proteomic methodologies via the ongoing improvement of isolation, tagging, and quantification methods. AREAS COVERED: This paper provides a comprehensive overview of differentially abundant proteins (DAPs) identified in AP by searching the PubMed/MEDLINE database (2003-2023) and adds significantly to the current theoretical framework. EXPERT OPINION: DAPs for potentially diagnosing AP based on proteomic identification need to be confirmed by multi-center studies that include larger samples. The discovery of DAPs in various organs at different AP stages via proteomic technologies is essential better to understand the pathophysiology of AP-related multiple organ dysfunction syndrome. Regarding the translational research of AP, novel approaches like single-cell proteomics and imaging using mass spectrometry may be used as soon as they become available.


Asunto(s)
Pancreatitis , Humanos , Pancreatitis/diagnóstico , Pancreatitis/complicaciones , Pancreatitis/metabolismo , Proteómica , Enfermedad Aguda , Insuficiencia Multiorgánica
7.
Gastroenterology ; 166(1): 178-190.e16, 2024 Jan.
Artículo en Inglés | MEDLINE | ID: mdl-37839499

RESUMEN

BACKGROUND & AIMS: Pancreatic ductal adenocarcinoma (PDAC) is one of the most fatal malignancies. Delayed manifestation of symptoms and lack of specific diagnostic markers lead patients being diagnosed with PDAC at advanced stages. This study aimed to develop a circular RNA (circRNA)-based biomarker panel to facilitate noninvasive and early detection of PDAC. METHODS: A systematic genome-wide discovery of circRNAs overexpressed in patients with PDAC was conducted. Subsequently, validation of the candidate markers in the primary tumors from patients with PDAC was performed, followed by their translation into a plasma-based liquid biopsy assay by analyzing 2 independent clinical cohorts of patients with PDAC and nondisease controls. The performance of the circRNA panel was assessed in conjunction with the plasma levels of cancer antigen 19-9 for the early detection of PDAC. RESULTS: Initially, a panel of 10 circRNA candidates was identified during the discovery phase. Subsequently, the panel was reduced to 5 circRNAs in the liquid biopsy-based assay, which robustly identified patients with PDAC and distinguished between early-stage (stage I/II) and late-stage (stage III/IV) disease. The areas under the curve of this diagnostic panel for the detection of early-stage PDAC were 0.83 and 0.81 in the training and validation cohorts, respectively. Moreover, when this panel was combined with cancer antigen 19-9 levels, the diagnostic performance for identifying patients with PDAC improved remarkably (area under the curve, 0.94) for patients in the validation cohort. Furthermore, the circRNA panel could also efficiently identify patients with PDAC (area under the curve, 0.85) who were otherwise deemed clinically cancer antigen 19-9-negative (<37 U/mL). CONCLUSIONS: A circRNA-based biomarker panel with a robust noninvasive diagnostic potential for identifying patients with early-stage PDAC was developed.


Asunto(s)
Adenocarcinoma , Carcinoma Ductal Pancreático , Neoplasias Pancreáticas , Humanos , ARN Circular/genética , Biomarcadores de Tumor/genética , Estudios de Casos y Controles , Estadificación de Neoplasias , Detección Precoz del Cáncer , Neoplasias Pancreáticas/diagnóstico , Neoplasias Pancreáticas/genética , Neoplasias Pancreáticas/patología , Carcinoma Ductal Pancreático/diagnóstico , Carcinoma Ductal Pancreático/genética , Antígeno CA-19-9 , Adenocarcinoma/patología
8.
Pharmacol Res ; 199: 107006, 2024 Jan.
Artículo en Inglés | MEDLINE | ID: mdl-38000562

RESUMEN

Gallbladder and biliary diseases (GBDs) are one of the most common digestive diseases. The connections between GBDs and several organs other than the liver have gradually surfaced accompanied by the changes in people's diet structure and the continuous improvement of medical diagnosis technology. Among them, cholecardia syndrome that takes the heart as the important target of GBDs complications has been paid close attention. However, there are still no systematic report about its corresponding clinical manifestations and pathogenesis. This review summarized recent reported types of cholecardia syndrome and found that arrhythmia, myocardial injury, acute coronary syndrome and heart failure are common in the general population. Besides, the clinical diagnosis rate of intrahepatic cholestasis of pregnancy (ICP) and Alagille syndrome associated with gene mutation is also increasing. Accordingly, the underlying pathogenesis including abnormal secretion of bile acid, gene mutation, translocation and deletion (JAG1, NOTCH2, ABCG5/8 and CYP7A1), nerve reflex and autonomic neuropathy were further revealed. Finally, the potential treatment measures and clinical medication represented by ursodeoxycholic acid were summarized to provide assistance for clinical diagnosis and treatment.


Asunto(s)
Síndrome de Alagille , Colestasis Intrahepática , Complicaciones del Embarazo , Femenino , Embarazo , Humanos , Síndrome de Alagille/complicaciones , Síndrome de Alagille/diagnóstico , Síndrome de Alagille/genética , Colestasis Intrahepática/complicaciones , Colestasis Intrahepática/tratamiento farmacológico , Ácido Ursodesoxicólico/uso terapéutico
9.
Epigenetics ; 19(1): 2283657, 2024 Dec.
Artículo en Inglés | MEDLINE | ID: mdl-38037805

RESUMEN

DNA methylation plays a key role in sex determination and differentiation in vertebrates. However, there are few studies on DNA methylation involved in chicken gonad development, and most focused on male hypermethylated regions (MHM). It is unclear whether there are specific differentially methylated regions (DMRs) in chicken embryonic gonads regulating sex determination and differentiation. Here, the DNA methylation maps showed that the difference of DNA methylation level between sexes was much higher at embryonic day 10 (E10) than that at embryonic day 6 (E6), and the significant differentially methylated regions at both stages were mainly distributed on the Z chromosome, including MHM1 and MHM2. The results of bisulphite sequencing PCR (BSP) and qRT-PCR showed hypomethylation of female MHM and upregulation of long non-coding RNAs (lncRNAs) whose promoter in the MHM region was consistent with the sequencing results, and similar results were in brain and muscle. In female sex-reversed gonads, the methylation pattern of MHM remained unchanged, and the expression levels of the three candidate lncRNAs were significantly decreased compared with those in females, but were significantly increased compared to males. The fluorescence in situ hybridization (FISH) results also showed that these lncRNAs were highly expressed in female embryonic gonads. The results of methyltransferase inhibitor and dual-luciferase reporter assay suggest that lncRNA expression may be regulated by DNA methylation within their promoters. Therefore, we speculated that MHM may be involved in cell-autonomous sex identity in chickens, and that lncRNAs regulated by MHM may be involved in female sexual differentiation.


Asunto(s)
Pollos , ARN Largo no Codificante , Embrión de Pollo , Femenino , Animales , Masculino , Pollos/genética , ARN Largo no Codificante/genética , ARN Largo no Codificante/metabolismo , Hibridación Fluorescente in Situ , Metilación de ADN , Gónadas
10.
J Med Virol ; 95(12): e29272, 2023 12.
Artículo en Inglés | MEDLINE | ID: mdl-38054501

RESUMEN

The impact of severe acute respiratory syndrome coronavirus 2 infection on the potential development of pancreatitis is a subject of ongoing debate within academic discourse. Establishing a causal link between COVID-19 and pancreatitis may not be fully supported by relying only on retrospective studies or case reports. This study examined the relationship between COVID-19 phenotypes and pancreatitis by Mendelian randomization (MR) method. The identification of instrumental variables (single nucleotide polymorphisms) that exhibit a robust association with the COVID-19 phenotypes was accomplished through a meticulous process of rigorous screening procedures. We included acute pancreatitis and chronic pancreatitis (CP) as the outcomes in the MR analysis, even though no definitive studies exist between COVID-19 and CP. A direct causal relationship between genetically predicted COVID-19 phenotypes and pancreatitis risk cannot be established. There is an ongoing debate over the designation of COVID-19 as a definitive cause of pancreatitis.


Asunto(s)
COVID-19 , Pancreatitis , Humanos , Enfermedad Aguda , COVID-19/complicaciones , Estudio de Asociación del Genoma Completo , Fenotipo , Polimorfismo de Nucleótido Simple , Estudios Retrospectivos , Análisis de la Aleatorización Mendeliana
11.
Huan Jing Ke Xue ; 44(12): 6754-6766, 2023 Dec 08.
Artículo en Chino | MEDLINE | ID: mdl-38098401

RESUMEN

To deeply understand the hydrological cycle process and the transformation mechanism of different water bodies in the grassland inland river basin, the atmospheric precipitation, river water, and groundwater in the Xilin River Basin were taken as the research objects, the hydrogen and oxygen stable isotopes were analyzed, and the multi-scale spatio-temporal characteristics were analyzed to explore the quantitative transformation relationship between different water bodies in the basin. The results showed that:① the Xilin River Basin had an obvious inland semi-arid climate, the atmospheric precipitation was the main source of recharge for the river water and groundwater, and the groundwater and river water experienced different degrees of non-equilibrium evaporation at the same time. ② The isotopic composition of the river water showed the characteristics of depletion in spring and autumn and enrichment in summer and showed a trend of increasing from upstream to downstream in space. The variation in δ18O in shallow and deep groundwater during the growing season was basically the same, and the main difference between the two occurred at the end of the growing season, that is, the former tended to be stable, whereas the latter showed an upward trend, which reflected that the deep groundwater had a lagged response to the infiltration and recharge of atmospheric precipitation and surface water, and both of them were depleted gradually from southeast to northwest in space. ③ Based on the estimation results of the endmember mixing model, the average recharge ratio of atmospheric precipitation and shallow groundwater to river water in summer was 52.69% and 47.31%, respectively, indicating that shallow groundwater was an important recharge source of river water in the inland river basin even during the rainy season. The results of this study provide theoretical guidance for water resource regulation and ecological environment protection in a typical semi-arid grassland inland river basin.

12.
Int J Nanomedicine ; 18: 6743-6761, 2023.
Artículo en Inglés | MEDLINE | ID: mdl-38026528

RESUMEN

Background: Numerous preclinical investigations have exhibited the beneficial impact of emodin (EMO) on the management of severe acute pancreatitis (SAP)-associated acute lung injury (ALI). However, the potential of EMO to mitigate organ damage through the modulation of exosome (Exo)-specific miRNA expression profiles remains unclear. Methods: The SAP rat model was established by retrograde injection of 5% sodium taurocholate into the pancreatic bile duct. Rats received intragastric administration of EMO at 2 h and 12 h post-modeling. Plasma and bronchoalveolar lavage fluid (BALF)-derived exosomes were isolated and purified from SAP rats treated with EMO. The therapeutic effects of these Exos in SAP rats were assessed using hematoxylin-eosin staining and measurement of inflammatory factor levels. MicroRNA (miRNA) sequencing was conducted on plasma and BALF-derived Exos, and rescue experiments were performed to investigate the function of NOVEL miR-29a-3p in the treatment of SAP using EMO. Results: EMO exhibits ameliorative effects on pancreatic and lung injury and inflammation in rats with SAP. Plasma/BALF-derived Exos from EMO-treated SAP rats also have therapeutic effects on SAP rats. The miRNA expression profile of plasma and BALF-derived Exos in SAP rats underwent significant changes upon exposure to EMO. In particular, 34 differentially expressed miRNAs (DEmiRNAs) were identified when comparing BALF-SAP+EMO-Exo and BALF-SAP-Exo. 39 DEmiRNAs were identified when comparing plasma-SAP+EMO-Exo to plasma-SAP-Exo. We found that SAP rats treated with Exos derived from BALF exhibited a more potent therapeutic response than those treated with Exos derived from plasma. EMO may rely on NOVEL-rno-miR-29a-3p expression to prevent pulmonary injury in SAP rats. Conclusion: The mechanism of action of EMO is observed to have a significant impact on the miRNA expression profile of Exos derived from plasma and BALF in SAP rats. NOVEL-rno-miR-29a-3p, which is specific to Exos, and is derived from BALF, may play a crucial role in the therapeutic efficacy of EMO.


Asunto(s)
Lesión Pulmonar Aguda , Emodina , Exosomas , MicroARNs , Pancreatitis , Ratas , Animales , Pancreatitis/inducido químicamente , Pancreatitis/tratamiento farmacológico , Emodina/farmacología , Enfermedad Aguda , Exosomas/metabolismo , Lesión Pulmonar Aguda/tratamiento farmacológico , MicroARNs/genética , MicroARNs/metabolismo
13.
Int J Mol Sci ; 24(15)2023 Jul 28.
Artículo en Inglés | MEDLINE | ID: mdl-37569514

RESUMEN

Acute lung injury/acute respiratory distress syndrome (ALI/ARDS), triggered by various pathogenic factors inside and outside the lungs, leads to diffuse lung injury and can result in respiratory failure and death, which are typical clinical critical emergencies. Severe acute pancreatitis (SAP), which has a poor clinical prognosis, is one of the most common diseases that induces ARDS. When SAP causes the body to produce a storm of inflammatory factors and even causes sepsis, clinicians will face a two-way choice between anti-inflammatory and anti-infection objectives while considering the damaged intestinal barrier and respiratory failure, which undoubtedly increases the difficulty of the diagnosis and treatment of SAP-ALI/ARDS. For a long time, many studies have been devoted to applying glucocorticoids (GCs) to control the inflammatory response and prevent and treat sepsis and ALI/ARDS. However, the specific mechanism is not precise, the clinical efficacy is uneven, and the corresponding side effects are endless. This review discusses the mechanism of action, current clinical application status, effectiveness assessment, and side effects of GCs in the treatment of ALI/ARDS (especially the subtype caused by SAP).


Asunto(s)
Lesión Pulmonar Aguda , Pancreatitis , Síndrome de Dificultad Respiratoria , Insuficiencia Respiratoria , Sepsis , Humanos , Glucocorticoides/uso terapéutico , Enfermedad Aguda , Pancreatitis/complicaciones , Síndrome de Dificultad Respiratoria/patología , Lesión Pulmonar Aguda/etiología , Lesión Pulmonar Aguda/complicaciones , Sepsis/complicaciones
14.
Nano Lett ; 23(18): 8808-8815, 2023 Sep 27.
Artículo en Inglés | MEDLINE | ID: mdl-37459604

RESUMEN

The development of advanced electrical equipment necessitates polymer dielectrics with a higher electric strength. Unfortunately, this bottleneck problem has yet to be solved because current material modification methods do not allow direct control of deep traps. Here, we propose a method for directly passivating deep traps. Measurements of nanoscale microregion charge characteristics and trap parameters reveal a significant reduction in the number of deep traps. The resulting polymer dielectric has an impressively high electrical strength, less surface charge accumulation, and a significantly increased flashover voltage and breakdown strength. In addition, the energy storage density is increased without sacrificing the charge-discharge efficiency. This reveals a new approach to increasing the energy storage density by reducing the trap energy levels at the electrode-dielectric interface. We further calculated and analyzed the microscopic physical mechanism of deep trap passivation based on density functional theory and characterized the contributions of orbital composition and orbital hybridization.

15.
Microbiol Spectr ; 11(4): e0366422, 2023 08 17.
Artículo en Inglés | MEDLINE | ID: mdl-37338348

RESUMEN

The pivotal roles of gut microbiota in severe acute pancreatitis-associated acute lung injury (SAP-ALI) are increasingly revealed, and recent discoveries in the gut-lung axis have provided potential approaches for treating SAP-ALI. Qingyi decoction (QYD), a traditional Chinese medicine (TCM), is commonly used in clinical to treat SAP-ALI. However, the underlying mechanisms remain to be fully elucidated. Herein, by using a caerulein plus lipopolysaccharide (LPS)-induced SAP-ALI mice model and antibiotics (Abx) cocktail-induced pseudogermfree mice model, we tried to uncover the roles of the gut microbiota by administration of QYD and explored its possible mechanisms. Immunohistochemical results showed that the severity of SAP-ALI and intestinal barrier functions could be affected by the relative depletion of intestinal bacteria. The composition of gut microbiota was partially recovered after QYD treatment with decreased Firmicutes/Bacteroidetes ratio and increased relative abundance in short-chain fatty acids (SCFAs)-producing bacteria. Correspondingly increased levels of SCFAs (especially propionate and butyrate) in feces, gut, serum, and lungs were observed, generally consistent with changes in microbes. Western-blot analysis and RT-qPCR results indicated that the AMPK/NF-κB/NLRP3 signaling pathway was activated after oral administration of QYD, which was found to be possibly related to the regulatory effects on SCFAs in the intestine and lungs. In conclusion, our study provides new insights into treating SAP-ALI through modulating the gut microbiota and has prospective practical value for clinical use in the future. IMPORTANCE Gut microbiota affects the severity of SAP-ALI and intestinal barrier function. During SAP, a significant increase in the relative abundance of gut pathogens (Escherichia, Enterococcus, Enterobacter, Peptostreptococcus, Helicobacter) was observed. At the same time, QYD treatment decreased pathogenic bacteria and increased the relative abundance of SCFAs-producing bacteria (Bacteroides, Roseburia, Parabacteroides, Prevotella, Akkermansia). In addition, The AMPK/NF-κB/NLRP3 pathway mediated by SCFAs along the gut-lung axis may play an essential role in preventing the pathogenesis of SAP-ALI, which allows for reduced systemic inflammation and restoration of the intestinal barrier.


Asunto(s)
Lesión Pulmonar Aguda , Microbioma Gastrointestinal , Pancreatitis , Ratones , Animales , Pancreatitis/tratamiento farmacológico , Pancreatitis/inducido químicamente , Pancreatitis/metabolismo , FN-kappa B/metabolismo , Proteína con Dominio Pirina 3 de la Familia NLR , Proteínas Quinasas Activadas por AMP/uso terapéutico , Enfermedad Aguda , Estudios Prospectivos , Lesión Pulmonar Aguda/tratamiento farmacológico , Lesión Pulmonar Aguda/inducido químicamente , Lesión Pulmonar Aguda/metabolismo , Ácidos Grasos Volátiles
16.
J Thromb Thrombolysis ; 56(2): 264-274, 2023 Aug.
Artículo en Inglés | MEDLINE | ID: mdl-37284999

RESUMEN

Patients with severe aortic stenosis (AS) after replacement of the transcatheter aortic valve (TAVR) are more likely to develop thrombotic complications such as cerebral embolism and artificial valve thrombosis. However, the mechanism is not yet well defined. We aimed to explore the plasma extracellular vesicles (EVs) levels and their role in the induction of procoagulant activity (PCA) in patients receiving TAVR alone or TAVR with percutaneous coronary intervention (PCI). EVs were analyzed with flow cytometer. Markers of platelet and endothelial cell activation were quantified using selective enzyme-linked immunosorbent assay (ELISA) kits. Procoagulant activity (PCA) was assessed by clotting time, purified clotting complex assays, and fibrin production assays. Our results confirmed that EVs with positive phosphatedylserin (PS+EV), platelet EVs (PEVs) and positive tissue factor EVs (TF+EVs) were higher in patients following TAVR than before TAVR, particularly in TAVR with PCI. Furthermore, endothelial-derived EVs (EEVs) were also higher in patients after TAVR with PCI than pre-TAVR, however, the EEVs levels in TAVR alone patients were gradually reduce than pre-TAVR. In addition, we further proved that total EVs contributed to dramatically shortened coagulation time, increased intrinsic/extrinsic factor Xa and thrombin generation in patients after TAVR, especially in TAVR with PCI. The PCA was markedly attenuated by approximately 80% with lactucin. Our study reveals a previously unrecognized link between plasma EV levels and hypercoagulability in patients after TAVR, especially TAVR with PCI. Blockade of PS+EVs may improve the hypercoagulable state and prognosis of patients.


Asunto(s)
Estenosis de la Válvula Aórtica , Enfermedad de la Arteria Coronaria , Intervención Coronaria Percutánea , Reemplazo de la Válvula Aórtica Transcatéter , Humanos , Reemplazo de la Válvula Aórtica Transcatéter/efectos adversos , Reemplazo de la Válvula Aórtica Transcatéter/métodos , Estenosis de la Válvula Aórtica/cirugía , Estenosis de la Válvula Aórtica/complicaciones , Intervención Coronaria Percutánea/efectos adversos , Intervención Coronaria Percutánea/métodos , Enfermedad de la Arteria Coronaria/complicaciones , Resultado del Tratamiento , Válvula Aórtica/cirugía , Factores de Riesgo
18.
Plant Physiol Biochem ; 200: 107762, 2023 Jul.
Artículo en Inglés | MEDLINE | ID: mdl-37207493

RESUMEN

Global warming causes topsoil temperatures to increase, which potentially leads to maize yield loss. We explored the effects of soil warming/cooling on root-shoot growth and maize grain yields by performing pot experiments with a heat-sensitive maize hybrid (HS208) and a normal maize hybrid (SD609) in warm temperate climate in 2019 and 2020. Our results reveal, for the first time, differences in root characteristics, leaf photosynthetic physiology, and yield responses to soil warming and cooling between normal and heat-sensitive maize varieties under a warm temperate climate. Soil warming (+2 and 4 °C) inhibited whole root growth by decreasing root length, volume, and dry mass weight, which indirectly reduced leaf photosynthetic capacity and decreased grain yield/plant by 15.10-24.10% versus control plants exposed to ambient temperature. Soil cooling (-2 °C) promoted root growth and leaf photosynthesis, and significantly increased grain yield of HS208 by 12.61%, although no significant change was found with SD609. It can be seen that under unfavorable conditions of global warming, selection of excellent stress-resistant hybrids plays an important role in alleviating the soil heat stress of maize in warm temperate climate regions.


Asunto(s)
Suelo , Zea mays , Zea mays/fisiología , Grano Comestible , Fotosíntesis/fisiología , Hojas de la Planta
19.
Br J Haematol ; 202(2): 369-378, 2023 07.
Artículo en Inglés | MEDLINE | ID: mdl-37157187

RESUMEN

Autologous haematopoietic stem cell transplantation (auto-HSCT) as a treatment for B-cell acute lymphoblastic leukaemia (B-ALL) has been rigorously debated in recent years. We retrospectively analysed the outcomes of 355 adult patients with B-ALL in first complete remission who had received auto-HSCT or allogeneic HSCT (allo-HSCT) in our centre. The treatment efficacy was evaluated from a model stratified on the risk classification and minimal residue disease (MRD) status after three chemotherapy cycles. Auto-HSCT demonstrated comparable 3-year overall survival (OS) (72.7% vs. 68.5%, p = 0.441) and leukaemia-free survival rates (62.8% vs. 56.1%, p = 0.383) compared to allo-HSCT for patients with negative MRD, while the advantage of lower non-relapse mortality (1.5% vs. 25.1%, p < 0.001) was offset by a higher cumulative incidence of relapse (CIR) rates (35.7% vs. 18.9%, p = 0.018), especially in high-risk patients. For patients at high risk and with positive MRD, there was a lower trend of 3-year OS (50.0% vs. 66.0%, p = 0.078) and significantly higher CIR rates (71.4% vs. 39.1%, p = 0.018) in auto-HSCT. However, no significant interaction was observed in the tests. In conclusion, auto-HSCT appears to be an attractive treatment for patients with negative MRD after three chemotherapy cycles. For MRD-positive patients, allo-HSCT may be a more effective treatment.


Asunto(s)
Linfoma de Burkitt , Trasplante de Células Madre Hematopoyéticas , Leucemia-Linfoma Linfoblástico de Células Precursoras B , Humanos , Adulto , Trasplante Autólogo , Quimioterapia de Mantención , Neoplasia Residual , Estudios Retrospectivos , Recurrencia Local de Neoplasia , Leucemia-Linfoma Linfoblástico de Células Precursoras B/terapia , Receptores de Complemento 3b
20.
Plant Physiol Biochem ; 198: 107694, 2023 May.
Artículo en Inglés | MEDLINE | ID: mdl-37062126

RESUMEN

Affected by climate warming, the impact of crop root zone warming (RZW) on maize seedling growth and nutrient uptake deserve attention. The characteristics of K uptake in maize under root zone warming and the combined impacts of potassium deficiency and RZW are still unclear. The present study aimed to investigate the effects of RZW on potassium absorption and photosynthesis of maize seedlings under the difference in potassium. The results showed that RZW and low potassium treatment significantly affected root shoot development and photosynthetic physiological characteristics of maize seedlings. Moreover, the interaction of RZW and potassium content had striking influence on maize seedlings. Under the normal potassium with root zone medium temperature treatment, the development of maize was the most vigorous. Under the dual stress of high root zone temperature and low potassium, the root absorption area, total potassium content and root activity were significantly reduced, which then influenced the light energy use efficiency and dry matter accumulation. Securing the supply of potassium fertilizer under high root zone temperature stress is useful to alleviate the impact of high temperature stress.


Asunto(s)
Potasio , Zea mays , Zea mays/fisiología , Temperatura , Fotosíntesis/fisiología , Plantones/fisiología
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