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1.
Front Endocrinol (Lausanne) ; 15: 1406442, 2024.
Article de Anglais | MEDLINE | ID: mdl-39040677

RÉSUMÉ

Background: Diabetes ranks among the most widespread diseases globally, with the kidneys being particularly susceptible to its vascular complications. The identification of proteins for pathogenesis and novel drug targets remains imperative. This study aims to investigate roles of circulating inflammatory proteins in diabetic renal complications. Methods: Data on the proteins were derived from a genome-wide protein quantitative trait locus (pQTL) study, while data on diabetic renal complications came from the FinnGen study. In this study, proteome-wide Mendelian randomization (MR) and colocalization analyses were used to assess the relationship between circulating inflammatory proteins and diabetic renal complications. Results: MR approach indicated that elevated levels of interleukin 12B (IL-12B) (OR 1.691, 95%CI 1.179-2.427, P=4.34×10-3) and LIF interleukin 6 family cytokine (LIF) (OR 1.349, 95%CI 1.010-1.801, P=4.23×10-2) increased the risk of type 1 diabetes (T1D) with renal complications, while higher levels of fibroblast growth factor 19 (FGF19) (OR 1.202, 95%CI 1.009-1.432, P=3.93×10-2), fibroblast growth factor 23 (FGF23) (OR 1.379, 95%CI 1.035-1.837, P=2.82×10-2), C-C motif chemokine ligand 7 (CCL7) (OR 1.385, 95%CI 1.111-1.725, P=3.76×10-3), and TNF superfamily member 14 (TNFSF14) (OR 1.244, 95%CI 1.066-1.451, P=5.63×10-3) indicated potential risk factors for type 2 diabetes (T2D) with renal complications. Colocalization analysis supported these findings, revealing that most identified proteins, except for DNER, likely share causal variants with diabetic renal complications. Conclusion: Our study established associations between specific circulating inflammatory proteins and the risk of diabetic renal complications, suggesting these proteins as targets for further investigation into the pathogenesis and potential therapeutic interventions for T1D and T2D with renal complications.


Sujet(s)
Néphropathies diabétiques , Analyse de randomisation mendélienne , Protéome , Humains , Néphropathies diabétiques/sang , Néphropathies diabétiques/génétique , Néphropathies diabétiques/métabolisme , Néphropathies diabétiques/étiologie , Protéome/métabolisme , Protéome/analyse , Mâle , Diabète de type 1/sang , Diabète de type 1/complications , Diabète de type 1/génétique , Diabète de type 1/métabolisme , Femelle , Locus de caractère quantitatif , Étude d'association pangénomique , Inflammation/sang , Inflammation/métabolisme , Facteurs de croissance fibroblastique/sang , Facteurs de croissance fibroblastique/génétique , Diabète de type 2/sang , Diabète de type 2/complications , Diabète de type 2/métabolisme , Diabète de type 2/génétique , Marqueurs biologiques/sang , Adulte d'âge moyen
2.
Phys Rev E ; 109(6-1): 064104, 2024 Jun.
Article de Anglais | MEDLINE | ID: mdl-39020913

RÉSUMÉ

In percolation of patchy disks on lattices, each site is occupied by a disk, and neighboring disks are regarded as connected when their patches contact. Clusters of connected disks become larger as the patchy coverage of each disk χ increases. At the percolation threshold χ_{c}, an incipient cluster begins to span the whole lattice. For systems of disks with n symmetric patches on Archimedean lattices, a recent work [Wang et al., Phys. Rev. E 105, 034118 (2022)2470-004510.1103/PhysRevE.105.034118] found symmetric properties of χ_{c}(n), which are due to the coupling of the patches' symmetry and the lattice geometry. How does χ_{c} behave with increasing n if the patches are randomly distributed on the disks? We consider two typical random distributions of the patches, i.e., the equilibrium distribution and a distribution from random sequential adsorption. Combining Monte Carlo simulations and the critical polynomial method, we numerically determine χ_{c} for 106 models of different n on the square, honeycomb, triangular, and kagome lattices. The rules governing χ_{c}(n) are investigated in detail. They are quite different from those for disks with symmetric patches and could be useful for understanding similar systems.

3.
Biomed Opt Express ; 15(7): 4253-4263, 2024 Jul 01.
Article de Anglais | MEDLINE | ID: mdl-39022546

RÉSUMÉ

Retinal vascular health holds paramount importance for healthy vision. Many technologies have been developed to examine retinal vasculature non-destructively, including fundus cameras, optical coherence tomography angiography (OCTA), fluorescein angiography (FA), and so on. However, there is a lack of a proper phantom simulating the critical features of the real human retina to calibrate and evaluate the performance of these technologies. In this work, we present a rapid, high-resolution, and economical technology based on 3D printed mold-based soft lithography and spin coating for the fabrication of a multivascular network and multilayer structural retinal phantom with the appropriate optical properties. The feasibility of the retinal phantom as a test device was demonstrated with an OCTA system and a confocal retinal ophthalmoscope. Experiment results prove that the retinal phantom could provide an objective evaluation of the OCTA and confocal retinal ophthalmoscope. Furthermore, the microfluidic phantoms enabled by this fabrication technology may support the development and evaluation of other techniques.

4.
J Environ Manage ; 364: 121430, 2024 Jul.
Article de Anglais | MEDLINE | ID: mdl-38875983

RÉSUMÉ

Optimization and control of wastewater treatment process (WTP) can contribute to cost reduction and efficiency. A wastewater treatment process multi-objective optimization (WTPMO) framework is proposed in this paper to provide suggestions for decision-making in setting parameters of WTP. Firstly, the prediction models based on Extreme Gradient Boosting (XGB) with Bayesian optimization (BO) are developed for predicting effluent water quality (EQ) and energy consumption (EC) for different influent quality and process parameter settings. Then, the SHapley Additive exPlanations (SHAP) algorithm is used to complement the interpretability of machine learning to quantitatively evaluate the impact of different features on the predicted targets. Finally, the Non-dominated Sorting Genetic Algorithm II (NSGA-II) with the Technique for Ordering Preferences on Similarity of Ideal Solutions (TOPSIS) is introduced to solve and make decisions on the multi-objective optimization problem. The WTPMO applicability is validated on Benchmark Simulation Model 1 (BSM1). The results show that BOXGB achieves accurate prediction for EQ and EC with R2 values of 0.923 and 0.965, respectively, indicating that BO can effectively select the model hyperparameters in XGB. Based on SHAP supplemented the interpretability of the model to fully explain how the influent water quality and decision variables affect the EQ and EC of the WTP. In addition, the optimized process parameters are determined based on NSGA-II and TOPSIS, and the EC optimization rate is 1.552% while guaranteeing water quality compliance. Overall, this research can effectively achieve the optimization of WTP, ensure that the effluent water quality meets the standards while reducing energy consumption, assist Wastewater treatment plants (WWTPs) to achieve more intelligent and efficient operation and maintenance management, and provide strong support for environmental protection and sustainable development goals.


Sujet(s)
Algorithmes , Théorème de Bayes , Apprentissage machine , Élimination des déchets liquides , Eaux usées , Qualité de l'eau , Élimination des déchets liquides/méthodes , Purification de l'eau/méthodes , Modèles théoriques
5.
J Opt Soc Am A Opt Image Sci Vis ; 41(6): 1027-1036, 2024 Jun 01.
Article de Anglais | MEDLINE | ID: mdl-38856410

RÉSUMÉ

The correlation and polarization singularities as the important parameters of a radially polarized Gaussian Schell-model vortex beam propagating in oceanic turbulence have been investigated in detail. On the one hand, the correlation singularity of the beam will first split, and then generate new correlation singularities, and finally vanish in pairs. The longer the propagating distance, the larger the rate of dissipation of mean-square temperature, and the lower initial correlation lengths reduce the stability of correlation singularities. On the other hand, polarization singularities also split during transmission. The different initial correlation lengths cause the uneven distribution of polarization singularities, and the high order topological charge leads to the generation of new polarization singularities at short distances. Our numerical findings may be of great significance for detection and imaging of the oceanic optical telecommunication links.

6.
Front Oncol ; 14: 1343239, 2024.
Article de Anglais | MEDLINE | ID: mdl-38764584

RÉSUMÉ

Ovarian cancer is a prevalent malignant tumor of the female reproductive system, often remaining concealed until it reaches an advanced stage. The standard treatment protocol includes cytoreductive surgery for ovarian cancer plus postoperative consolidation chemotherapy and maintenance therapy, although it carries a high recurrence rate. During the treatment period, chemotherapy can lead to bone marrow suppression, a condition known as Chemotherapy-Induced Myelosuppression (CIM). This suppression may necessitate dose reduction or chemotherapy treatment cycle delay. In severe cases, CIM can result in infection, fever, and potential harm to the patient's life. Here, we report a case of a female patient with ovarian malignant tumor of biochemical recurrence who treated with chemotherapy combined with Trilaciclib, following previous perioperative chemotherapy with occurrence of severe CIM. It involves an intravenous injection of Trilaciclib before chemotherapy, which significantly abates the side effects of chemotherapy, reduces the occurrence of severe CIM, improves the patients' quality of life, and decreases the economic burden of hospitalization. We hope that this retrospective analysis of the case may serve as a reference in preventing and treating severe CIM during chemotherapy in some patients with malignant tumors, ultimately benefiting more patients with tumors.

7.
Article de Anglais | MEDLINE | ID: mdl-38747701

RÉSUMÉ

Two Gram-stain-negative strains, designed SYSU M86414T and SYSU M84420, were isolated from marine sediment samples of the South China Sea (Sansha City, Hainan Province, PR China). These strains were aerobic and could grow at pH 6.0-8.0 (optimum, pH 7.0), 4-37 °C (optimum, 28 °C), and in the presence of 0-10 % NaCl (w/v; optimum 3 %). The predominant respiratory menaquinone of strains SYSU M86414T and SYSU M84420 was MK-6. The primary cellular polar lipid was phosphatidylethanolamine. The major cellular fatty acids (>10 %) in both strains were iso-C15 : 0, iso-C15 : 1 G, and iso-C17 : 0 3-OH. The DNA G+C content of strains SYSU M86414T and SYSU M84420 were both 42.10 mol%. Phylogenetic analyses based on 16S rRNA gene sequences and core genes indicated that these novel strains belonged to the genus Flagellimonas and strain SYSU M86414T showed the highest 16S rRNA gene sequence similarity to Flagellimonas marinaquae JCM 11811T (98.83 %), followed by Flagellimonas aurea BC31-1-A7T (98.62 %), while strain SYSU M84420 had highest 16S rRNA gene sequence similarity to F. marinaquae JCM 11811T (98.76 %) and F. aurea BC31-1-A7T (98.55 %). Based on the results of polyphasic analyses, strains SYSU M86414T and SYSU M84420 should be considered to represent a novel species of the genus Flagellimonas, for which the name Flagellimonas halotolerans sp. nov. is proposed. The type strain of the proposed novel isolate is SYSU M86414T (=GDMCC 1.3806T=KCTC 102040T).


Sujet(s)
Techniques de typage bactérien , Composition en bases nucléiques , ADN bactérien , Acides gras , Sédiments géologiques , Phylogenèse , ARN ribosomique 16S , Eau de mer , Analyse de séquence d'ADN , Vitamine K2 , Chine , ARN ribosomique 16S/génétique , Sédiments géologiques/microbiologie , Acides gras/analyse , Eau de mer/microbiologie , ADN bactérien/génétique , Vitamine K2/analogues et dérivés , Vitamine K2/analyse , Phosphatidyléthanolamine , Données de séquences moléculaires
8.
Sheng Wu Gong Cheng Xue Bao ; 40(5): 1365-1379, 2024 May 25.
Article de Chinois | MEDLINE | ID: mdl-38783803

RÉSUMÉ

Globally, colorectal cancer (CRC) ranks as the third most common cancer and the second leading cause of cancer-related fatalities. According to the World Health Organization, there are over 1.9 million annual cases of CRC diagnosed worldwide, resulting in more than 900 000 deaths. In recent years, chimeric antigen receptor T (CAR-T) cell therapy has shown clinical success in treating certain hematological malignancies and is now being explored for its potential in targeting solid tumors like CRC. Currently, CAR-T cell therapies targeting carcinoembryonic antigen (CEA), natural killer group 2, member D ligand (NKG2DL), and other markers have achieved remarkable results in clinical trials, albeit encountering significant challenges. This review summarizes the promising targets of CAR-T cell therapy for CRC and highlights progress made in clinical trials and preclinical studies. Additionally, the review discusses the challenges faced by CAR-T cell therapy in CRC treatment, including a shortage of tumor-specific antigens, cytokine release syndrome, adverse tumor microenvironment, and limited infiltration of CAR-T cells. In summary, this review provides an overview of the latest research progress and challenges in CAR-T cell therapy for CRC, aiming to contribute fresh insights for the clinical treatment of this disease.


Sujet(s)
Tumeurs colorectales , Immunothérapie adoptive , Récepteurs chimériques pour l'antigène , Humains , Tumeurs colorectales/thérapie , Tumeurs colorectales/immunologie , Récepteurs chimériques pour l'antigène/immunologie , Antigène carcinoembryonnaire/immunologie , Microenvironnement tumoral , Antigènes néoplasiques/immunologie , Lymphocytes T/immunologie , Récepteurs aux antigènes des cellules T/immunologie , Animaux
10.
Inflamm Res ; 73(6): 997-1018, 2024 Jun.
Article de Anglais | MEDLINE | ID: mdl-38615296

RÉSUMÉ

BACKGROUND: ALI/ARDS is a syndrome of acute onset characterized by progressive hypoxemia and noncardiogenic pulmonary edema as the primary clinical manifestations. Necroptosis is a form of programmed cell necrosis that is precisely regulated by molecular signals. This process is characterized by organelle swelling and membrane rupture, is highly immunogenic, involves extensive crosstalk with various cellular stress mechanisms, and is significantly implicated in the onset and progression of ALI/ARDS. METHODS: The current body of literature on necroptosis and ALI/ARDS was thoroughly reviewed. Initially, an overview of the molecular mechanism of necroptosis was provided, followed by an examination of its interactions with apoptosis, pyroptosis, autophagy, ferroptosis, PANOptosis, and NETosis. Subsequently, the involvement of necroptosis in various stages of ALI/ARDS progression was delineated. Lastly, drugs targeting necroptosis, biomarkers, and current obstacles were presented. CONCLUSION: Necroptosis plays an important role in the progression of ALI/ARDS. However, since ALI/ARDS is a clinical syndrome caused by a variety of mechanisms, we emphasize that while focusing on necroptosis, it may be more beneficial to treat ALI/ARDS by collaborating with other mechanisms.


Sujet(s)
Lésion pulmonaire aigüe , Nécroptose , Humains , Lésion pulmonaire aigüe/anatomopathologie , Lésion pulmonaire aigüe/immunologie , Animaux , /anatomopathologie , Autophagie , Apoptose
11.
STAR Protoc ; 5(2): 102994, 2024 Jun 21.
Article de Anglais | MEDLINE | ID: mdl-38568815

RÉSUMÉ

Here, we present a protocol for 3D printing heart tissues using thiol-norbornene photoclick collagen (NorCol). We describe steps for synthesizing NorCol, preparing bioink and the support bath, and cell-laden printing. We then detail procedures for the loading of C2C12 cells into NorCol, ensuring structural integrity and cell viability after printing. This protocol is adaptable to various cell lines and allows for the printing of diverse complex structures, which can be used in drug screening and disease modeling.


Sujet(s)
Collagène , Monoterpènes de type norbornane , Impression tridimensionnelle , Thiols , Ingénierie tissulaire , Animaux , Thiols/composition chimique , Collagène/composition chimique , Souris , Ingénierie tissulaire/méthodes , Monoterpènes de type norbornane/composition chimique , Myocarde/cytologie , Myocarde/métabolisme , Lignée cellulaire , Structures d'échafaudage tissulaires/composition chimique , Coeur , Survie cellulaire/effets des médicaments et des substances chimiques
12.
Int J Gen Med ; 17: 1395-1403, 2024.
Article de Anglais | MEDLINE | ID: mdl-38617055

RÉSUMÉ

Background: Circular RNAs (circRNAs) exhibit unique patterns of expression and high levels of stability in patient plasma samples such that they represent ideal non-invasive biomarkers that can be leveraged to detect a wide array of diseases including endometrial cancer (EC). This study was designed to identify circRNAs with potential diagnostic utility in serum samples from EC patients while also evaluating the utility of macrophage migration inhibitory factor (MIF) as a biomarker when screening for this form of cancer in the clinic. Methods: Levels of circEPSTI1 and MIF were assessed in the plasma of EC patients and healthy subjects (n=186 each) through qPCR and ELISAs. The diagnostic utility of these biomarkers was assessed with receiver operating characteristic curve (ROC) analyses. Results: Relative to healthy subjects, EC patient serum contained significantly elevated circEPSTI1 and MIF. An association was noted between circEPSTI1 expression in stages, histologic grade, and residual tumor. ROC curves confirmed that serum circEPSTI1 levels distinguished between controls and patients with EC with an Area of 0.835 and serum MIF levels distinguished between controls and patients with EC with an Area of 0.6646. When instead diagnosing patients based on the combination of MIF and circEPSTI1, the Area further rose to 0.8604. Conclusion: Assessing the combination of circEPSTI1 and MIF may be a viable approach to reliably diagnosing EC.

13.
BMC Pediatr ; 24(1): 157, 2024 Mar 05.
Article de Anglais | MEDLINE | ID: mdl-38443865

RÉSUMÉ

BACKGROUND: Chorioamnionitis (CA) can cause multiple organ injuries in premature neonates, particularly to the lungs. Different opinions exist regarding the impact of intrauterine inflammation on neonatal respiratory distress syndrome (NRDS) and bronchopulmonary dysplasia (BPD). We aim to systematically review the relationship between CA or Funisitis (FV) and lung injury among preterm infants. METHODS: We electronically searched PubMed, EMbase, the Cochrane library, CNKI, and CMB for cohort studies from their inception to March 15, 2023. Two reviewers independently screened literature, gathered data, and did NOS scale of included studies. The meta-analysis was performed using RevMan 5.3. RESULTS: Sixteen observational studies including 68,397 patients were collected. Meta-analysis showed CA or FV increased the lung injury risk (OR = 1.43, 95%CI: 1.06-1.92). Except for histological chorioamnionitis (HCA) (OR = 0.72, 95%CI: 0.57-0.90), neither clinical chorioamnionitis (CCA) (OR = 1.86, 95%CI: 0.93-3.72) nor FV (OR = 1.23, 95%CI: 0.48-3.15) nor HCA with FV (OR = 1.85, 95%CI: 0.15-22.63) had statistical significance in NRDS incidence. As a result of stratification by grade of HCA, HCA (II) has a significant association with decreased incidence of NRDS (OR = 0.48, 95%CI: 0.35-0.65). In terms of BPD, there is a positive correlation between BPD and CA/FV (CA: OR = 3.18, 95%CI: 1.68-6.03; FV: OR = 6.36, 95%CI: 2.45-16.52). Among CA, HCA was positively associated with BPD (OR = 2.70, 95%CI: 2.38-3.07), whereas CCA was not associated with BPD (OR = 2.77, 95%CI: 0.68-11.21). HCA and moderate to severe BPD (OR = 25.38, 95%CI: 7.13-90.32) showed a positive correlation, while mild BPD (OR = 2.29, 95%CI: 0.99-5.31) did not. CONCLUSION: Currently, evidence suggests that CA or FV increases the lung injury incidence in premature infants. For different types of CA and FV, HCA can increase the incidence of BPD while decreasing the incidence of NRDS. And this "protective effect" only applies to infants under 32 weeks of age. Regarding lung injury severity, only moderate to severe cases of BPD were positively correlated with CA.


Sujet(s)
Dysplasie bronchopulmonaire , Chorioamnionite , Lésion pulmonaire , Syndrome de détresse respiratoire du nouveau-né , Nouveau-né , Femelle , Grossesse , Nourrisson , Humains , Chorioamnionite/épidémiologie , Prématuré , Inflammation , Dysplasie bronchopulmonaire/épidémiologie , Dysplasie bronchopulmonaire/étiologie , Syndrome de détresse respiratoire du nouveau-né/épidémiologie , Syndrome de détresse respiratoire du nouveau-né/étiologie
14.
Syst Appl Microbiol ; 47(2-3): 126501, 2024 May.
Article de Anglais | MEDLINE | ID: mdl-38460344

RÉSUMÉ

Two novel actinobacteria, designated as SYSU M7M538T and SYSU M7M531, were isolated from oral of Eumetopias jubatus in Zhuhai Chimelong Ocean Kingdom, China. The cells of these microorganisms stained Gram-positive and were rod shaped. These strains were facultative anaerobic, and catalase-positive. Optimal growth occurred at 37 °C and pH 7.0 over 7 days of cultivation. Both strains possessed diphosphatidylglycerol, phosphatidylglycerol and phosphocholine as the major polar lipids. The main menaquinone was MK-9(H4). The major fatty acids were C16:0, C17:1w8c, C17:0, C18:1w9c and C18:0. Analyses of genome sequences revealed that the genome size of SYSU M7M538T was 2.1 Mbp with G + C content of 52.5 %, while the genome size of SYSU M7M531 was 2.3 Mbp with G + C content of 52.7 %. The ANI and 16S rRNA gene analysis results showed that the pairwise similarities between the two strains and other recognized Nitriliruptoria species were less than 64.9 % and 89.0 %, respectively. Phylogenetic analysis of the 16S rRNA gene sequences indicated that strains SYSU M7M538T and SYSU M7M531 formed a well-separated phylogenetic branch distinct from other orders of Nitriliruptoria. Based on the data presented here, these two strains are considered to represent a novel species of a novel genus, for which the name Stomatohabitans albus gen. nov., sp. nov., with the type strain SYSU M7M538T (=KCTC 59113T = GDMCC 1.4286T), are proposed. We also propose that these organisms represent a novel family named Stomatohabitantaceae fam. nov. of a novel order Stomatohabitantales ord. nov.


Sujet(s)
Actinobacteria , Techniques de typage bactérien , Composition en bases nucléiques , ADN bactérien , Acides gras , Phylogenèse , ARN ribosomique 16S , Analyse de séquence d'ADN , ARN ribosomique 16S/génétique , Acides gras/analyse , Acides gras/composition chimique , Actinobacteria/classification , Actinobacteria/isolement et purification , Actinobacteria/génétique , ADN bactérien/génétique , Chine , Animaux , Vitamine K2/analyse , Vitamine K2/composition chimique , Vitamine K2/analogues et dérivés , Génome bactérien/génétique , Bouche/microbiologie , Anaérobiose
16.
Nutrients ; 16(6)2024 Mar 11.
Article de Anglais | MEDLINE | ID: mdl-38542707

RÉSUMÉ

As one of the malignant diseases globally, cancer seriously endangers human physical and mental health because of its high morbidity and mortality. Conventional cancer treatment strategies, such as surgical resection and chemoradiotherapy, are effective at the early stage of cancer but have limited efficacy for advanced cancer. Along with cancer progress and treatment, resistance develops gradually within the population of tumor cells. As a consequence, drug resistance become the major cause that leads to disease progression and poor clinical prognosis in some patients. The mechanisms of cancer drug resistance are quite complex and involve various molecular and cellular mechanisms. Therefore, exploring the mechanisms and finding specific targets are becoming imperative to overcome drug resistance. In recent years, plant-derived natural products have been evaluated as potential therapeutic candidates against cancer with drug resistance due to low side effects and high anticancer efficacy. A growing number of studies have shown that natural products can achieve superior antitumor effects through multiple signaling pathways. The mechanisms include regulation of multiple drug resistance (MDR)-related genes, inhibition of the phosphatidylinositol 3-kinase (PI3K)/protein kinase B (AKT) signaling pathway, induction of autophagy, and blockade of the cell cycle. This paper reviews the molecular and cellular mechanisms of cancer drug resistance, as well as the therapeutic effects and mechanisms of plant-derived natural products against cancer drug resistance. It provides references for developing therapeutic medication for drug-resistant cancer treatment with high efficacy and low side effects.


Sujet(s)
Produits biologiques , Tumeurs , Humains , Phosphatidylinositol 3-kinases/métabolisme , Produits biologiques/pharmacologie , Produits biologiques/usage thérapeutique , Tumeurs/traitement médicamenteux , Tumeurs/anatomopathologie , Protéines proto-oncogènes c-akt/métabolisme , Résistance aux médicaments antinéoplasiques , Transduction du signal , Lignée cellulaire tumorale
17.
J Lipid Res ; 65(4): 100534, 2024 Apr.
Article de Anglais | MEDLINE | ID: mdl-38522750

RÉSUMÉ

The deposition of cholesterol-rich lipoproteins in the arterial wall triggers macrophage inflammatory responses, which promote atherosclerosis. The NLRP3 inflammasome aggravates atherosclerosis; however, cellular mechanisms connecting macrophage cholesterol accumulation to inflammasome activation are poorly understood. We investigated the mechanisms of NLRP3 inflammasome activation in cholesterol-loaded macrophages and in atherosclerosis-prone Ldlr-/- mice with defects in macrophage cholesterol efflux. We found that accumulation of cholesterol in macrophages treated with modified LDL or cholesterol crystals, or in macrophages defective in the cholesterol efflux promoting transporters ABCA1 and ABCG1, leads to activation of NLRP3 inflammasomes as a result of increased cholesterol trafficking from the plasma membrane to the ER, via Aster-B. In turn, the accumulation of cholesterol in the ER activates the inositol triphosphate-3 receptor, CaMKII/JNK, and induces NLRP3 deubiquitylation by BRCC3. An NLRP3 deubiquitylation inhibitor or deficiency of Abro1, an essential scaffolding protein in the BRCC3-containing cytosolic complex, suppressed inflammasome activation, neutrophil extracellular trap formation (NETosis), and atherosclerosis in vivo. These results identify a link between the trafficking of cholesterol to the ER, NLRP3 deubiquitylation, inflammasome activation, and atherosclerosis.


Sujet(s)
Athérosclérose , Calcium-Calmodulin-Dependent Protein Kinase Type 2 , Cholestérol , Réticulum endoplasmique , Protéine-3 de la famille des NLR contenant un domaine pyrine , Animaux , Protéine-3 de la famille des NLR contenant un domaine pyrine/métabolisme , Athérosclérose/métabolisme , Athérosclérose/anatomopathologie , Souris , Cholestérol/métabolisme , Calcium-Calmodulin-Dependent Protein Kinase Type 2/métabolisme , Réticulum endoplasmique/métabolisme , Inflammasomes/métabolisme , Macrophages/métabolisme , Souris de lignée C57BL , Transport biologique , Souris knockout
18.
JCO Oncol Pract ; 20(4): 517-524, 2024 Apr.
Article de Anglais | MEDLINE | ID: mdl-38301188

RÉSUMÉ

PURPOSE: Hypomagnesemia is a common side effect of platinum-based chemotherapy and predicts poor overall survival in some cancers. Standard magnesium replacement strategies are often inadequate for maintaining magnesium levels. We hypothesized that a daily dietary magnesium replacement approach through magnesium-rich foods would help maintain adequate magnesium levels during platinum-based treatment. MATERIALS AND METHODS: We conducted a prospective feasibility study of magnesium-rich diets in patients 18 years and older with previously untreated ovarian cancer scheduled to receive carboplatin-containing chemotherapy of at least six consecutive cycles. Education about magnesium-rich diets was provided at enrollment and then weekly during chemotherapy. Feasibility was defined as ≥60% completion of dietary recalls and ≥280 mg average daily dietary magnesium intake across all patients. RESULTS: Twenty-one of 26 patients enrolled completed at least five chemotherapy cycles and were included in the analysis. Adherence to the study diet was 76%. Daily dietary magnesium intake was 100.5 mg at baseline and increased throughout each cycle: 6% of patients at baseline, 24% after the first cycle, and 67% after the fifth cycle reached ≥280-mg/day magnesium intake. Seven (33%) of 21 had at least one incident of hypomagnesemia. Patients who were adherent had significantly lower incidence of hypomagnesemia (19% v 80%, P = .03) and less need for intravenous magnesium (6% v 60%, P = .03) than those who were nonadherent. CONCLUSION: The study achieved primary feasibility objectives of retention and adherence to the study intervention. Weekly education about magnesium-rich diets was effective in increasing dietary magnesium intake. Adequate dietary magnesium appeared to be protective against hypomagnesemia.


Sujet(s)
Magnésium , Tumeurs de l'ovaire , Humains , Femelle , Carboplatine/effets indésirables , Magnésium/pharmacologie , Magnésium/usage thérapeutique , Études prospectives , Tumeurs de l'ovaire/traitement médicamenteux , Tumeurs de l'ovaire/induit chimiquement
19.
Environ Pollut ; 346: 123638, 2024 Apr 01.
Article de Anglais | MEDLINE | ID: mdl-38401633

RÉSUMÉ

Individuals typically spend most of their lives indoors, predominantly in spaces like offices and residences. Consequently, prolonged indoor exposure underscores the critical significance of maintaining optimal indoor air quality (IAQ) to safeguard one's health. The primary impediment to attaining efficient regulation of Indoor Air Quality (IAQ) is the challenge of monitoring the IAQ parameters, particularly within the immediate vicinity of an individual's breathing space. Current heating, ventilation, and air conditioning systems lack the ability to rapidly predict and optimize the quality of indoor air. The objective of this study is to acquire the distribution features of indoor pollutants and precise indoor environment data in order to efficiently forecast and enhance the IAQ. To achieve this objective, a proposed surrogate model was developed using computational fluid dynamics (CFD). Notably, the Kriging surrogate model can rapidly predict IAQ while using a limited number of CFD runs. CFD are widely used as numerical simulation methods to obtain the accurate information. Surrogate models can rapidly forecast indoor environmental conditions using CFD simulation data simultaneously. Optimization algorithms can efficiently achieve desirable indoor ambient conditions, offering highly effective and intelligent control techniques for indoor atmospheric ventilation.


Sujet(s)
Polluants atmosphériques , Pollution de l'air intérieur , Polluants environnementaux , Humains , Pollution de l'air intérieur/analyse , Polluants atmosphériques/analyse , Simulation numérique , Logement , Surveillance de l'environnement/méthodes
20.
Diabetes Metab Syndr Obes ; 17: 517-531, 2024.
Article de Anglais | MEDLINE | ID: mdl-38327734

RÉSUMÉ

Purpose: To evaluate the association of the systemic immune-inflammatory index (SII) and systemic inflammatory response index (SIRI) with the clinical and pathological features and progression of diabetic kidney disease (DKD). Patients and Methods: We analyzed 303 patients with type 2 diabetes mellitus (T2DM), classifying them into distinct groups: T2DM, early DKD (EDKD), and clinical DKD (Cli-DKD). Variations in SII and SIRI levels across these groups and their association with renal function were assessed. Logistic regression analysis was used to identify independent risk factors for DKD. Additionally, in 43 patients with biopsy-confirmed DKD, we analyzed the relationship between SII, SIRI, and pathological changes. Kaplan-Meier survival analysis and the Cox proportional hazards model were used to assess the influence of SII and SIRI levels on outcomes in patients with DKD. Results: SII and SIRI were significantly higher in the Cli-DKD group than in the T2DM and EDKD groups, and were positively correlated with the urinary albumin-creatinine ratio and negatively correlated with estimated glomerular filtration rate. Notably, SIRI was identified as an independent risk factor for DKD development. Additionally, a lower SII score was associated with a higher cumulative survival rate. Conclusion: This study demonstrates an association between SII, SIRI, and renal function in patients with T2DM. A high SIRI was an independent risk factor for DKD, while an elevated SII was associated with an increased risk of kidney disease progression in biopsy-confirmed DKD cases. Our findings underscore the potential implications of utilizing SII and SIRI as cost-effective and readily available inflammatory indicators for monitoring DKD in primary care settings.

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