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1.
Heliyon ; 10(17): e37367, 2024 Sep 15.
Article de Anglais | MEDLINE | ID: mdl-39296114

RÉSUMÉ

Severe pneumonia (SP) is a prevalent respiratory ailment characterized by high mortality and poor prognosis. Current scoring systems for pneumonia are not only time-consuming but also exhibit limitations in early SP prediction. To address this gap, this study aimed to develop a machine-learning model using inflammatory markers from peripheral blood for early prediction of SP. A total of 204 pneumonia patients from seven medical centers were studied, with 143 (68 SP cases) in the training cohort and 61 (32 SP cases) in the test cohort. Clinical characteristics and laboratory test results were collected at diagnosis. Various models including Logistic Regression, Random Forest, Naïve Bayes, XGBoost, Support Vector Machine, and Decision Tree were built and evaluated. Seven predictors-age, sex, WBC count, T-lymphocyte count, NLR, CRP, TNF-α, IL-4/IFN-γ ratio, IL-6/IL-10 ratio-were selected through LASSO regression and clinical insight. The XGBoost model, exhibiting best performance, achieved an AUC of 0.901 (95 % CI: 0.827 to 0.985) in the test cohort, with an accuracy of 0.803, sensitivity of 0.844, specificity of 0.759, and F1_score of 0.818. Indeed, SHAP analysis emphasized the significance of elevated WBC counts, older age, and elevated CRP as the top predictors. The use of inflammatory biomarkers in this concise predictive model shows significant potential for the rapid assessment of SP risk, thereby facilitating timely preventive interventions.

2.
Quant Imaging Med Surg ; 14(8): 5902-5914, 2024 Aug 01.
Article de Anglais | MEDLINE | ID: mdl-39144019

RÉSUMÉ

Background: Bone age assessment (BAA) is crucial for the diagnosis of growth disorders and the optimization of treatments. However, the random error caused by different observers' experiences and the low consistency of repeated assessments harms the quality of such assessments. Thus, automated assessment methods are needed. Methods: Previous research has sought to design localization modules in a strongly or weakly supervised fashion to aggregate part regions to better recognize subtle differences. Conversely, we sought to efficiently deliver information between multi-granularity regions for fine-grained feature learning and to directly model long-distance relationships for global understanding. The proposed method has been named the "Multi-Granularity and Multi-Attention Net (2M-Net)". Specifically, we first applied the jigsaw method to generate related tasks emphasizing regions with different granularities, and we then trained the model on these tasks using a hierarchical sharing mechanism. In effect, the training signals from the extra tasks created as an inductive bias, enabling 2M-Net to discover task relatedness without the need for annotations. Next, the self-attention mechanism acted as a plug-and-play module to effectively enhance the feature representation capabilities. Finally, multi-scale features were applied for prediction. Results: A public data set of 14,236 hand radiographs, provided by the Radiological Society of North America (RSNA), was used to develop and validate 2M-Net. In the public benchmark testing, the mean absolute error (MAE) between the bone age estimates of the model and of the reviewer was 3.98 months (3.89 months for males and 4.07 months for females). Conclusions: By using the jigsaw method to construct a multi-task learning strategy and inserting the self-attention module for efficient global modeling, we established 2M-Net, which is comparable to the previous best method in terms of performance.

3.
World J Clin Cases ; 12(19): 3898-3907, 2024 Jul 06.
Article de Anglais | MEDLINE | ID: mdl-38994318

RÉSUMÉ

BACKGROUND: Percutaneous hepatobiliary drainage (PTCD) is an effective method for the treatment of biliary obstruction and other diseases, but postoperative complications are still one of the important problems faced by patients. Continuous nursing is a comprehensive nursing model that plays an important role in postoperative recovery. The purpose of this study was to investigate the effect of continuous nursing on the incidence of complications in patients after PTCD surgery through meta-analysis and to evaluate its efficacy and safety. AIM: To evaluate the effect of extended nursing on the incidence of complications in discharged patients after percutaneous transhepatic biliary drainage (PTBD). METHODS: Randomized controlled studies on PTBD postdischarge extended care were identified in the CNKI, Wanfang, VIP, CBM, PubMed, Cochrane Library, Embase, Web of Science, and other databases. The quality of the included studies was evaluated using the Joanna Briggs Institute of Australia literature quality evaluation tool, and a meta-analysis of the included studies was performed with RevMan 5.4 software. RESULTS: Finally, 9 studies were included, with a total sample size of 854 patients (425 patients in the control group and 429 patients in the intervention group). Meta-analysis revealed that extended care effectively reduced biliary tract infection (RR: 0.42, 95%CI: 0.30-0.57), puncture wound infection (RR: 0.19, 95%CI: 0.06-0.65), catheter protrusion or displacement in discharged patients after PTBD (RR: 0.31, 95%CI: 0.18-0.54), catheter blockage (RR: 0.23, 95%CI: 0.13-0.42), skin infection around the drainage tube (RR: 0.30, 95%CI: 0.12-0.77), and catheter-related readmissions (RR: 0.34, 95%CI: 0.18-0.65) (P < 0.05). CONCLUSION: Compared with conventional discharge care, extended care can effectively reduce the occurrence of complications such as biliary tract infection, puncture wound infection, catheter prolapse or displacement, catheter blockage, skin infection around the drainage tube, and catheter-related readmission in discharged patients after PTBD.

4.
JCI Insight ; 9(14)2024 Jun 06.
Article de Anglais | MEDLINE | ID: mdl-38842940

RÉSUMÉ

Loss of ferroptosis contributes to the development of human cancer, and restoration of ferroptosis has been demonstrated as a potential therapeutic strategy in cancer treatment. However, the mechanisms of how ferroptosis escape contributes to ovarian cancer (OV) development are not well elucidated. Here, we show that ferroptosis negative regulation signatures correlated with the tumorigenesis of OV and were associated with poor prognosis, suggesting that restoration of ferroptosis represents a potential therapeutic strategy in OV. High-throughput drug screening with a kinase inhibitor library identified MEK inhibitors as ferroptosis inducers in OV cells. We further demonstrated that MEK inhibitor-resistant OV cells were less vulnerable to trametinib-induced ferroptosis. Mechanistically, mTOR/eIF4E binding protein 1 (4EBP1) signaling promoted solute carrier family 7 member 11 (SLC7A11) protein synthesis, leading to ferroptosis inhibition in MEK inhibitor-resistant cells. Dual inhibition of MEK and mTOR/4EBP1 signaling restrained the protein synthesis of SLC7A11 via suppression of the mTOR/4EBP1 axis to reactivate ferroptosis in resistant cells. Together, these findings provide a promising therapeutic option for OV treatment through ferroptosis restoration by the combined inhibition of MEK and mTOR/4EBP1 pathways.


Sujet(s)
Protéines adaptatrices de la transduction du signal , Système y+ de transport d'acides aminés , Ferroptose , Tumeurs de l'ovaire , Inhibiteurs de protéines kinases , Sérine-thréonine kinases TOR , Ferroptose/effets des médicaments et des substances chimiques , Humains , Femelle , Tumeurs de l'ovaire/traitement médicamenteux , Tumeurs de l'ovaire/anatomopathologie , Tumeurs de l'ovaire/métabolisme , Tumeurs de l'ovaire/génétique , Lignée cellulaire tumorale , Système y+ de transport d'acides aminés/métabolisme , Système y+ de transport d'acides aminés/génétique , Système y+ de transport d'acides aminés/antagonistes et inhibiteurs , Animaux , Protéines adaptatrices de la transduction du signal/métabolisme , Protéines adaptatrices de la transduction du signal/génétique , Souris , Inhibiteurs de protéines kinases/pharmacologie , Inhibiteurs de protéines kinases/usage thérapeutique , Sérine-thréonine kinases TOR/métabolisme , Protéines du cycle cellulaire/métabolisme , Protéines du cycle cellulaire/génétique , Transduction du signal/effets des médicaments et des substances chimiques , Résistance aux médicaments antinéoplasiques/effets des médicaments et des substances chimiques , Pyridones/pharmacologie , Pyridones/usage thérapeutique , Pyrimidinones/pharmacologie , Pyrimidinones/usage thérapeutique
5.
Macromol Biosci ; : e2400112, 2024 Jun 08.
Article de Anglais | MEDLINE | ID: mdl-38850262

RÉSUMÉ

PP mesh is a widely used prosthetic material in hernia repair. However, visceral adhesion is one of the worst complications of this operation. Hence, an anti-adhesive PP mesh is developed by coating porous polyvinyl alcohol (PVA) hydrogel on PP surface via freezing-thawing process method. The compressive modulus of porous PVA hydrogel coating is first regulated by the addition of porogen sodium bicarbonate (NaHCO3) at various quality ratios with PVA. As expected, the porous hydrogel coating displayed modulus more closely resembling that of native abdominal wall tissue. In vitro tests demonstrate the modified PP mesh show superior coating stability, excellent hemocompatibility, and good cytocompatibility. In vivo experiments illustrate that PP mesh coated by the PVA4 hydrogel that mimicked the modulus of native abdominal wall could prevent adhesion effectively. Based on this, the rapamycin (RPM) is loaded into the porous PVA4 hydrogel coating to further improve anti-adhesive property of PP mesh. The Hematoxylin and eosin (H&E) and Masson trichrome (MT) staining results verified that the resulting mesh could alleviate the inflammation response and reduce the deposition of collagen around the implantation zone. The biomimetic mechanical property and anti-adhesive property of modified PP mesh make it a valuable candidate for application in hernioplasty.

6.
Orbit ; : 1, 2024 Jun 12.
Article de Anglais | MEDLINE | ID: mdl-38864585
7.
Front Plant Sci ; 15: 1367176, 2024.
Article de Anglais | MEDLINE | ID: mdl-38855469

RÉSUMÉ

Background: Phosphorus in the soil is mostly too insoluble for plants to utilize, resulting in inhibited aboveground biomass, while Carex can maintain their aboveground biomass through the presence of dauciform roots. However, dauciform roots lead to both morphological and physiological changes in the root system, making their primary mechanism unclear. Methods: A greenhouse experiment was conducted on three Carex species, in which Al-P, Ca-P, Fe-P, and K-P were employed as sole phosphorus sources. The plants were harvested and assessed after 30, 60 and 90 days. Results: (1) The density of dauciform roots was positively correlated with root length and specific root length, positively influencing aboveground biomass at all three stages. (2) The aboveground phosphorus concentration showed a negative correlation with both dauciform root density and aboveground biomass in the first two stages, which became positive in the third stage. (3) Aboveground biomass correlated negatively with the aboveground Al concentration, and positively with Ca and Fe concentration (except Al-P). (4) Root morphological traits emerged as critical factors in dauciform roots' promotion of aboveground biomass accumulation. Conclusion: Despite the difference among insoluble phosphorus, dauciform roots have a contributing effect on aboveground growth status over time, mainly by regulating root morphological traits. This study contributes to our understanding of short-term variation in dauciform roots and their regulatory mechanisms that enhance Carex aboveground biomass under low available phosphorus conditions.

8.
Sci Total Environ ; 945: 173912, 2024 Oct 01.
Article de Anglais | MEDLINE | ID: mdl-38871329

RÉSUMÉ

Coral reef ecosystems have been severely ravaged by global warming and eutrophication. Eutrophication often originates from nitrogen (N) overloading that creates stoichiometric phosphorus (P) limitation, which can be aggravated by sea surface temperature rises that enhances stratification. However, how P-limitation interacts with thermal stress to impact coral-Symbiodiniaceae mutualism is poorly understood and underexplored. Here, we investigated the effect of P-limitation (P-depleted vs. P-replete) superimposed on heat stress (31 °C vs. 25 °C) on a Symbiodinium strain newly isolated from the coral host by a 14-day incubation experiment. The heat and P-limitation co-stress induced an increase in alkaline phosphatase activity and reppressed cell division, photosynthetic efficiency, and expression of N uptake and assimilation genes. Moreover, P limitation intensified downregulation of carbon fixation (light and dark reaction) and metabolism (glycolysis) pathways in heat stressed Symbiodinium. Notably, co-stress elicited a marked transcriptional downregulation of genes encoding photosynthates transporters and microbe-associated molecular patterns, potentially undermining the mutualism potential. This work sheds light on the interactive effects of P-limitation and heat stress on coral symbionts, indicating that nutrient imbalance in the coral reef ecosystem can intensify heat-stress effects on the mutualistic capacity of Symbiodiniaceae.


Sujet(s)
Anthozoa , Récifs de corail , Dinoflagellida , Réaction de choc thermique , Phosphore , Symbiose , Phosphore/métabolisme , Anthozoa/physiologie , Animaux , Dinoflagellida/physiologie , Réaction de choc thermique/physiologie , Température élevée , Réchauffement de la planète
9.
Int J Biol Macromol ; 270(Pt 1): 132061, 2024 Jun.
Article de Anglais | MEDLINE | ID: mdl-38705326

RÉSUMÉ

Polypropylene (PP) mesh is the most widely used prosthetic material in hernia repair. However, the efficacy of implanted PP mesh is often compromised by adhesion between viscera and PP mesh. Thus, there is a recognized need for developing an anti-adhesive PP mesh. Here, a composite hydrogel coated PP mesh with the prevention of adhesion after hernia repair was designed. The composite hydrogel coating was prepared from polyvinyl alcohol (PVA) and hyaluronic acid (HA) by using the freezing-thawing (FT) method. To overcome the shortcoming of the long time of the traditional freezing-thawing method, a small molecule 3,4-dihydroxyphenylacetic acid (DHPA) was introduced to promote the formation of composite hydrogel. The as-prepared composite hydrogel coating displayed modulus more closely resembling that of native abdominal wall tissue. In vitro studies illustrated that the resulting meshes showed excellent coating stability, hemocompatibility, and non-cytotoxicity. In vivo experiments using a rat abdominal wall defect model demonstrated that the composite hydrogel coated PP mesh could prevent the formation of adhesion, alleviate the inflammatory response, and reduce the deposition of collagen around the damaged tissue. These disclosed results manifested that the PP mesh coated with HA/PVA composite hydrogel might be a promising application in preventing adhesion for hernia repair.


Sujet(s)
Acide hyaluronique , Polypropylènes , Poly(alcool vinylique) , Filet chirurgical , Acide hyaluronique/composition chimique , Acide hyaluronique/pharmacologie , Poly(alcool vinylique)/composition chimique , Animaux , Polypropylènes/composition chimique , Rats , Adhérences tissulaires/prévention et contrôle , Hydrogels/composition chimique , Hydrogels/pharmacologie , Mâle , Paroi abdominale/chirurgie , Humains , Rat Sprague-Dawley , Matériaux revêtus, biocompatibles/composition chimique , Matériaux revêtus, biocompatibles/pharmacologie , Test de matériaux , Herniorraphie/méthodes
10.
Nanoscale ; 16(23): 11019-11027, 2024 Jun 13.
Article de Anglais | MEDLINE | ID: mdl-38804105

RÉSUMÉ

Micro-nanomotors (MNMs) are micro/nanoscale intelligent devices with vast potential in the fields of drug delivery, precision medicine, biosensing, and environmental remediation. Their primary advantage lies in their ability to convert various forms of external energy (such as magnetic, ultrasonic, and light energy) into their own propulsive force. Additionally, MNMs offer high controllability and modifiability, enabling them to navigate in the microscopic world. Importantly, recent research has harnessed the unique advantages of MNMs to synergize their capabilities in neuromodulation. This mini-review presents the significant progress and pioneering achievements in the use of MNMs for neuromodulation, with the aim of inspiring readers to explore the broader biomedical applications of these MNMs. Through continuous innovation and diligent exploration, MNMs show promise to have a profound impact on the field of biomedicine.


Sujet(s)
Systèmes de délivrance de médicaments , Humains , Nanotechnologie , Animaux , Nanostructures/composition chimique , Techniques de biocapteur
11.
BMC Med ; 22(1): 189, 2024 May 07.
Article de Anglais | MEDLINE | ID: mdl-38715017

RÉSUMÉ

BACKGROUND: Sleep loss is a common public health problem that causes hyperalgesia, especially that after surgery, which reduces the quality of life seriously. METHODS: The 48-h sleep restriction (SR) mouse model was created using restriction chambers. In vivo imaging, transmission electron microscopy (TEM), immunofluorescence staining and Western blot were performed to detect the status of the blood-spinal cord barrier (BSCB). Paw withdrawal mechanical threshold (PWMT) was measured to track mouse pain behavior. The role of infiltrating regulatory T cells (Tregs) and endothelial cells (ECs) in mouse glycolysis and BSCB damage were analyzed using flow cytometry, Western blot, CCK-8 assay, colorimetric method and lactate administration. RESULTS: The 48-h SR made mice in sleep disruption status and caused an acute damage to the BSCB, resulting in hyperalgesia and neuroinflammation in the spinal cord. In SR mice, the levels of glycolysis and glycolysis enzymes of ECs in the BSCB were found significantly decreased [CON group vs. SR group: CD31+Glut1+ cells: p < 0.001], which could cause dysfunction of ECs and this was confirmed in vitro. Increased numbers of infiltrating T cells [p < 0.0001] and Treg population [p < 0.05] were detected in the mouse spinal cord after 48-h SR. In the co-cultured system of ECs and Tregs in vitro, the competition of Tregs for glucose resulted in the glycolysis disorder of ECs [Glut1: p < 0.01, ENO1: p < 0.05, LDHα: p < 0.05; complete tubular structures formed: p < 0.0001; CCK8 assay: p < 0.001 on 24h, p < 0.0001 on 48h; glycolysis level: p < 0.0001]. An administration of sodium lactate partially rescued the function of ECs and relieved SR-induced hyperalgesia. Furthermore, the mTOR signaling pathway was excessively activated in ECs after SR in vivo and those under the inhibition of glycolysis or co-cultured with Tregs in vitro. CONCLUSIONS: Affected by glycolysis disorders of ECs due to glucose competition with infiltrating Tregs through regulating the mTOR signaling pathway, hyperalgesia induced by 48-h SR is attributed to neuroinflammation and damages to the barriers, which can be relieved by lactate supplementation.


Sujet(s)
Cellules endothéliales , Glucose , Hyperalgésie , Privation de sommeil , Moelle spinale , Lymphocytes T régulateurs , Animaux , Lymphocytes T régulateurs/immunologie , Souris , Glucose/métabolisme , Cellules endothéliales/métabolisme , Moelle spinale/métabolisme , Moelle spinale/anatomopathologie , Mâle , Privation de sommeil/complications , Glycolyse/physiologie , Modèles animaux de maladie humaine , Souris de lignée C57BL
12.
J Geriatr Cardiol ; 21(2): 211-218, 2024 Feb 28.
Article de Anglais | MEDLINE | ID: mdl-38544493

RÉSUMÉ

BACKGROUND: Hypertension usually clusters with multiple comorbidities. However, the association between cardiometabolic multimorbidity (CMM) and mortality in hypertensive patients is unclear. This study aimed to investigate the association between CMM and all-cause and cardiovascular disease (CVD) mortality in Chinese patients with hypertension. METHODS: The data used in this study were from the China National Survey for Determinants of Detection and Treatment Status of Hypertensive Patients with Multiple Risk Factors (CONSIDER), which comprised 5006 participants aged 19-91 years. CMM was defined as the presence of one or more of the following morbidities: diabetes mellitus, dyslipidemia, chronic kidney disease, coronary heart disease, and stroke. Cox proportional hazard models were used to calculate the hazard ratios (HR) with 95% CI to determine the association between the number of CMMs and both all-cause and CVD mortality. RESULTS: Among 5006 participants [mean age: 58.6 ± 10.4 years, 50% women (2509 participants)], 76.4% of participants had at least one comorbidity. The mortality rate was 4.57, 4.76, 8.48, and 16.04 deaths per 1000 person-years in hypertensive patients without any comorbidity and with one, two, and three or more morbidities, respectively. In the fully adjusted model, hypertensive participants with two cardiometabolic diseases (HR = 1.52, 95% CI: 1.09-2.13) and those with three or more cardiometabolic diseases (HR = 2.44, 95% CI: 1.71-3.48) had a significantly elevated risk of all-cause mortality. The findings were similar for CVD mortality but with a greater increase in risk magnitude. CONCLUSIONS: In this study, three-fourths of hypertensive patients had CMM. Clustering with two or more comorbidities was associated with a significant increase in the risk of all-cause and cardiovascular mortality among hypertensive patients, suggesting more intensive treatment and control in this high-risk patient group.

13.
Echocardiography ; 41(3): e15801, 2024 Mar.
Article de Anglais | MEDLINE | ID: mdl-38519840

RÉSUMÉ

OBJECTIVE: This study aimed to analyze myocardial work in patients with atrial fibrillation (AF) using a noninvasive pressure strain loop (PSL) technique to provide a basis for the quantitative assessment of left ventricular (LV) systolic function. METHODS: LV myocardial work of 107 AF patients (56 with paroxysmal atrial fibrillation and 51 with persistent atrial fibrillation) and 55 healthy individuals were assessed by the noninvasive PSL and then compared. RESULTS: Global longitudinal strain (GLS) in absolute values, global work index (GWI), global constructive work (GCW), and global work efficiency (GWE) were significantly lower in the AF group than control group, whereas peak strain dispersion (PSD) and global wasted work (GWW) were significantly higher (P < .05). Further subdivision according to the AF type revealed that, compared with the controls, GLS in absolute values and GWE decreased significantly; PSD and GWW increased significantly in the paroxysmal AF group (P < .05). Nevertheless, GWI and GCW were not significantly different between paroxysmal AF and control groups (P > .05). Compared to paroxysmal AF, persistent AF induced a further decrease in absolute GLS and GWE and a further increase in GWW (P < .05), but PSD did not increase further (P > .05). Multiple linear regression analysis showed that GWI and GCW were independently associated with systolic blood pressure. GWW was associated with types of AF and left atrial volume index (LAVI). GWE was correlated with age, types of AF, disease duration, and LAVI. Receiver operating characteristic curve analysis showed that the area under the curve predicting myocardial injury was higher for GWE and GWW than for GLS (area under the curve:  .880,  .846, and  .821, respectively). CONCLUSIONS: Non-invasive PSL can quantitatively assess LV systolic function in patients with different kinds of AF and detect early subclinical myocardial injury in patients with paroxysmal AF. GWE and GWW outperform GLS and LV ejection fraction when assessing myocardial injury. Systolic blood pressure, type of AF, LVAI, disease duration, and age may be associated with myocardial injury in patients with AF.


Sujet(s)
Fibrillation auriculaire , Lésions traumatiques du coeur , Humains , Fibrillation auriculaire/imagerie diagnostique , Myocarde , Fonction ventriculaire gauche , Atrium du coeur , Débit systolique
14.
Anesth Analg ; 2024 Mar 18.
Article de Anglais | MEDLINE | ID: mdl-38507554

RÉSUMÉ

BACKGROUND: Neuropathic pain (NP) is a highly challenging condition with complex pathological mechanisms, and the spinal gamma aminobutyric acid A receptor receptor plays a crucial role in its progression. Recent studies have revealed a potential interaction between neuroplastin 65 (NP65) and gamma aminobutyric acid A receptor α2 subunit (GABAAR-α2) on the cell surface. We hypothesize that NP65 is involved in the pathogenesis of NP by regulating the level of GABAAR-α2. METHODS: A chronic constrictive injury (CCI) pain model was established in male Sprague-Dawley rats to verify the change in spinal NP65 expression. Alterations in pain behavior and GABAAR-α2 protein expression were observed after intrathecal injection of NP65 overexpressing adeno-associated virus (AAV) in CCI rats. In vitro investigations on Neuroblastoma 2a cells, the effect of NP65 on GABAAR-α2 expression via the calcineurin-nuclear factor of activated T-cell 4 (CaN-NFATc4) signaling pathway was evaluated by manipulating NP65 expression. RESULTS: The expression level of NP65 protein and mRNA in the CCI group were significantly decreased (P < .05; analysis of variance [ANOVA]). After intrathecal injection of NP65, overexpression of AAV and pain behavior in CCI rats were significantly alleviated, and levels of GABAAR-α2 were upregulated. In vitro experiments verified alterations in the expression of GABAAR-α2, CaN, and phosphorylated NFATc4 on the application of NP65 with plasmid or small interfering RNA, respectively. After the application of the specific CaN inhibitor cyclosporine A (CsA), the changes in NP65 expression did not produce subsequent alterations in the expression of GABAAR-α2, CaN, or phosphorylated NFATc4 proteins. CONCLUSIONS: NP65 modulates the level of GABAAR-α2 through the CaN-NFATc4 signaling pathway, which may serve as the underlying mechanism of NP.

15.
Ann Neurol ; 96(1): 74-86, 2024 Jul.
Article de Anglais | MEDLINE | ID: mdl-38501714

RÉSUMÉ

OBJECTIVE: To determine the association between the preoperative Bioenergetic Health Index (BHI) of platelets and the occurrence of postoperative delirium (POD) in elderly patients. METHODS: Elderly patients scheduled for major abdominal surgery under general anesthesia were included. The presence of POD was assessed within the 3 days after surgery. Seahorse XF analysis and transmission electron microscopy were utilized to evaluate the mitochondrial metabolism and morphology of platelets. RESULTS: A total of 20 out of 162 participants developed POD. Participants with POD showed lower preoperative Mini-Mental State Examination scores and total protein levels, fewer educational years, longer surgery duration, higher mean platelet volume, and lower platelet BHI compared with those without POD. Damaged mitochondria with swollen appearance and distorted cristae was detected in platelets from participants with POD. Preoperative platelet BHI was independently associated with the occurrence of POD after adjusting for age, education, preoperative Mini-Mental State Examination score, preoperative mean platelet volume and total protein levels, surgical type and duration, and lymphocyte counts on the first postoperative day (OR 0.11, 95% CI 0.03-0.37, p < 0.001). The areas under the receiver operating curves for predicting POD were 0.83 (95% CI 0.76-0.88) for platelet BHI. It showed a sensitivity of 85.00% and specificity of 73.24%, with an optimal cutoff value of 1.61. Using a serial combination (mean platelet volume followed by BHI) yielded a sensitivity of 80.00% and specificity of 82.39%. INTERPRETATION: Preoperative platelet BHI was independently associated with the occurrence of POD in elderly patients and has the potential as a screening biomarker for POD risk. ANN NEUROL 2024;96:74-86.


Sujet(s)
Marqueurs biologiques , Plaquettes , Mitochondries , Complications postopératoires , Humains , Sujet âgé , Mâle , Femelle , Plaquettes/métabolisme , Marqueurs biologiques/sang , Mitochondries/métabolisme , Complications postopératoires/diagnostic , Complications postopératoires/sang , Sujet âgé de 80 ans ou plus , Délire avec confusion/sang , Délire avec confusion/diagnostic , Délire avec confusion/étiologie
16.
Acc Chem Res ; 57(5): 763-775, 2024 Mar 05.
Article de Anglais | MEDLINE | ID: mdl-38386871

RÉSUMÉ

ConspectusPolycyclic (hetero)aromatic hydrocarbons (PAHs) have emerged as a focal point in current interdisciplinary research, spanning the realms of chemistry, physics, and materials science. Possessing distinctive optical, electronic, and magnetic properties, these π-functional materials exhibit significant potential across diverse applications, including molecular electronic devices, organic spintronics, and biomedical functions, among others. Despite the extensive documentation of various PAHs over the decades, the efficient and precise synthesis of π-extended PAHs remains a formidable challenge, hindering their broader application. This challenge is primarily attributed to the intricate and often elusive nature of their synthesis, compounded by issues related to low solubility and unfavored stability.The development of π-building blocks that can be facilely and modularly transformed into diverse π-frameworks constitutes a potent strategy for the creation of novel PAH materials. For instance, based on the classic perylene diimide (PDI) unit, researchers such as Würthner, Wang, and Nuckolls have successfully synthesized a plethora of structurally diverse PAHs, as well as numerous other π-functional materials. However, until now the availability of such versatile building blocks is still severely limited, especially for those simultaneously having a facile preparation process, adequate solubilizing groups, favored material stability, and critically, rich possibilities for structural extension spaces.In this Account, we present an overview of our invention of a highly versatile bay-/ortho-octa-substituted perylene building block, designated as Per-4Br, for the construction of a series of novel PAH scaffolds with tailor-made structures and rich optoelectronic and magnetic properties. First, starting with a brief discussion of current challenges associated with the bottom-up synthesis of π-extended PAHs, we rationalize the key features of Per-4Br that enable facile access to new PAH molecules including its ease of large-scale preparation, favored material stability and solubility, and multiple flexible reaction sites, with a comparison to the PDI motif. Then, we showcase our rational design and sophisticated synthesis of a body of neutral or charged, closed- or open-shell, curved, or planar PAHs via controlled annulative π-extensions in different directions such as peripheral, diagonal, or multiple dimensions of the Per-4Br skeleton. In this part, the fundamental structure-property relationships between molecular conformations, electronic structures, and self-assembly behaviors of these PAHs and their unique physiochemical properties such as unusual open-shell ground states, global aromaticity, state-associated/stimuli-responsive magnetic activity, and charge transport characteristics will be emphatically elaborated. Finally, we offer our perspective on the continued advancement of π-functional materials based on Per-4Br, which, we posit, may stimulate heightened research interest in the versatile structural motifs typified by Per-4Br, consequently catalyzing further progress in the realm of organic π-functional materials.

17.
Int J Biol Macromol ; 262(Pt 2): 130078, 2024 Mar.
Article de Anglais | MEDLINE | ID: mdl-38340914

RÉSUMÉ

Mucoadhesive films based on tamarind seed polysaccharide and guar gum (TSP-GG) were formulated for buccal delivery of resveratrol. Resveratrol-bovine serum albumin nanoparticles (Res-BSA) were prepared and dispersed in TSP-GG to improve its buccal mucoadhesiveness. The impregnation of Res-BSA induced the dense internal structures of TSP-GG and improved its strength and rigidity. Structural characterization showed that resveratrol existed in an amorphous state in the films containing Res-BSA, and hydrogen bonding was formed between Res-BSA and the film matrices. The films containing Res-BSA exhibited good uniformity in thickness, weight, and resveratrol content, and their surface pH was near neutral, ranging between 6.78 and 7.09. Increasing Res-BSA content reduced the water contact angle of TSP-GG (from 75.9° to 59.6°). The swelling and erosion studies indicated the favorable hydration capacity and erosion resistance of the films containing Res-BSA. Additionally, the addition of Res-BSA imparted enhanced ex vivo mucoadhesive force, in the range of 1.53 N to 1.98 N, and extended ex vivo residence time, between 17.9 h and 18.9 h, to TSP-GG. The current study implied that the composite systems of TSP-GG and Res-BSA may be a novel platform for buccal mucosal delivery of resveratrol.


Sujet(s)
Galactanes , Mannanes , Nanoparticules , Gommes végétales , Tamarindus , Vecteurs de médicaments/composition chimique , Resvératrol , Sérumalbumine bovine , Tamarindus/composition chimique , Polyosides/composition chimique , Nanoparticules/composition chimique , Systèmes de délivrance de médicaments
18.
Curr Pharm Des ; 30(8): 639-647, 2024.
Article de Anglais | MEDLINE | ID: mdl-38347771

RÉSUMÉ

BACKGROUND: Human disease onset and progression are strongly associated with aberrant long noncoding RNA (lncRNA) expression, highlighting the functional regulatory role of lncRNA. Actin filament-associated protein 1-antisense RNA 1 (AFAP1-AS1), a member of lncRNAs, is located on the antisense strand of Actin filament-associated protein 1 (AFAP1). METHODS: We conducted a comprehensive review of AFAP1-AS1's functions in gynecology and urogenital systems using the "PubMed" database. RESULTS: Our analysis reveals that AFAP1-AS1 is overexpressed and engages in the initiation and process of gynecological and urogenital diseases. The regulatory mechanisms employed by AFAP1-AS1 involve four major strategies: gene-level effects, competition for microRNA (miRNA) repression, protein binding, participation in signaling networks that influence cellular processes such as proliferative phenotype, migration, invasiveness, epithelial-mesenchymal transition (EMT), cycle regulation, drug resistance, and more. Furthermore, AFAP1-AS1 is implicated in guiding clinicopathological characteristics. CONCLUSION: AFAP1-AS1 holds promise as a potent diagnostics and treatment option for gynecological and genitourinary systems in the future.


Sujet(s)
ARN long non codant , Humains , ARN long non codant/génétique , ARN long non codant/métabolisme , Femelle , Appareil urogénital/métabolisme , Animaux
19.
Environ Toxicol ; 39(4): 2390-2404, 2024 Apr.
Article de Anglais | MEDLINE | ID: mdl-38164749

RÉSUMÉ

Ulcerative colitis (UC) is an idiopathic chronic intestinal inflammation. An increasing body of evidence shows that macrophages play an important role in the pathogenesis of UC. Interferon regulatory factor 4 (IRF4) is crucial for the development of autoimmune diseases via regulating immune cells. This research was designed to explore the function of IRF4 in UC and its association with macrophage polarization. The in vitro model of UC was established by stimulating colonic epithelial cells with tumor necrosis factor α (TNF-α). A mouse model of UC was constructed by injecting C57BL/6 mice with dextran sulfate sodium salt. Flow cytometry was used to assess percentage of CD11b+ CD86+ and CD11b+ CD206+ cells in bone marrow macrophages. Occult blood tests were used to detect hematochezia. Hematoxylin and eosin staining assay was used to assess colon pathological changes. Enzyme-linked immunosorbent assay (ELISA) was used to detect concentrations of inflammatory cytokines. The interaction of IRF4 and B-cell lymphoma 6 (Bcl6) was confirmed using GST pull-down and coimmunoprecipitation assays. Our findings revealed that IRF4 promoted cell apoptosis and stimulated M1 macrophage polarization in vitro. Furthermore, IRF4 aggravated symptoms of the mouse model of UC and aggravated M1 macrophage polarization in vivo. IRF4 negatively regulated Bcl6 expression. Downregulation of Bcl6 promoted apoptosis and M1 macrophage polarization in the presence of IRF4 in vitro and in vivo. Moreover, Bcl6 positively mediated the Janus kinase 2 (JAK2)/signal transducer and activator of transcription 3 (STAT3) signaling pathway. In conclusion, IRF4 aggravated UC progression through promoting M1 macrophage polarization via Bcl6/JAK2/STAT3 pathway. These findings suggested that IRF4 might be a good target to competitively inhibit or to treat with UC.


Sujet(s)
Rectocolite hémorragique , Animaux , Souris , Rectocolite hémorragique/induit chimiquement , Modèles animaux de maladie humaine , Inflammation/métabolisme , Facteurs de régulation d'interféron/métabolisme , Macrophages , Souris de lignée C57BL , Protéines proto-oncogènes c-bcl-6/métabolisme , Facteur de transcription STAT-3/métabolisme
20.
Anesth Analg ; 139(2): 411-419, 2024 Aug 01.
Article de Anglais | MEDLINE | ID: mdl-38241681

RÉSUMÉ

BACKGROUND: The microglial activation has been implicated in cancer-induced bone pain. Recent studies have revealed that microglia mediate synaptic pruning in the central nervous system, where the cluster of differentiation 47-signal regulatory protein α (CD47-SIRPα) axis creates a "don't eat me" signal and elicits an antiphagocytic effect to protect synapses against elimination. To date, the synaptic phagocytosis in microglia has never been investigated in the murine cancer-induced bone pain model. The present experiments sought to explore whether microglia phagocytize synapses in mice with bone cancer pain as well as the possible mechanisms. METHODS: Male C3H/HeN mice were used to induce bone cancer pain. Minocycline and S-ketamine were injected into D14. The number of spontaneous flinches (NSF) and paw withdrawal mechanical thresholds (PWMT) were measured on D0, D4, D7, D10, D14, D21, and D28. Hematoxylin and eosin staining presented bone lesions. Western blotting examined the Gephyrin, CD47, and SIRPα expression. Flow cytometry evaluated the proportion of SIRPα + cells in the spine. Immunofluorescence and 3-dimensional reconstruction showed the Gephyrin puncta inside microglial lysosomes. RESULTS: Mice embedded with tumor cells induced persistent spontaneous pain and mechanical hyperalgesia. Hematoxylin and eosin staining revealed bone destruction and tumor infiltration in marrow cavities. Microglia underwent a responsive and proliferative burst (t = -16.831, P < .001). Western blotting manifested lowered Gephyrin expression in the tumor group (D4, D7, D10, D14, D21, and D28: P < .001). Immunofluorescence and 3-dimensional reconstruction showed larger volumes of Gephyrin puncta inside microglial lysosomes (t = -23.273, P < .001; t = -27.997, P < .001). Treatment with minocycline or S-ketamine exhibited pain relief and antiphagocytic effects (t = -6.191, P < .001, t = -7.083, P < .001; t = -20.767, P < .001, t = -17.080, P < .001; t = 11.789, P < .001, t = 16.777, P < .001; t = 8.868, P < .001, t = 21.319, P < .001). Last but not least, the levels of CD47 and SIRPα proteins were downregulated (D10: P = .004, D14, D21, and D28: P < .001; D10, D14, D21, and D28: P < .001). Flow cytometry and immunofluorescence substantiated reduced microglial SIRPα (t = 11.311, P < .001; t = 12.189, P < .001). CONCLUSIONS: Microglia-mediated GABAergic synapse pruning in the spinal cord dorsal horn in bone cancer pain mice, which might be associated with the declined CD47-SIRPα signal. Our research uncovered an innovative mechanism that highlighted microglia-mediated synaptic phagocytosis in a murine cancer-induced bone pain model.


Sujet(s)
Tumeurs osseuses , Antigènes CD47 , Douleur cancéreuse , Modèles animaux de maladie humaine , Souris de lignée C3H , Microglie , Phagocytose , Récepteurs immunologiques , Animaux , Microglie/effets des médicaments et des substances chimiques , Microglie/métabolisme , Mâle , Phagocytose/effets des médicaments et des substances chimiques , Douleur cancéreuse/métabolisme , Douleur cancéreuse/étiologie , Douleur cancéreuse/physiopathologie , Tumeurs osseuses/complications , Tumeurs osseuses/métabolisme , Tumeurs osseuses/anatomopathologie , Souris , Récepteurs immunologiques/métabolisme , Antigènes CD47/métabolisme , Corne dorsale de la moelle spinale/métabolisme , Corne dorsale de la moelle spinale/effets des médicaments et des substances chimiques , Synapses/effets des médicaments et des substances chimiques , Synapses/anatomopathologie , Synapses/métabolisme , Minocycline/pharmacologie , Comportement animal/effets des médicaments et des substances chimiques
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