Your browser doesn't support javascript.
loading
Mostrar: 20 | 50 | 100
Resultados 1 - 20 de 4.514
Filtrar
1.
Blood ; 2024 Apr 04.
Artigo em Inglês | MEDLINE | ID: mdl-38574321

RESUMO

Platelet α-granules are rich in TGF-ß1 which is associated with myeloid-derived suppressor cell (MDSC) biology. Responders to thrombopoietin receptor agonists (TPO-RAs) revealed a parallel increase in the number of both platelets and MDSCs. Here, anti-CD61 immune-sensitized splenocytes were transferred into severe combined immunodeficient mice to establish an active murine model of immune thrombocytopenia (ITP). Subsequently, we demonstrated that TPO-RAs augmented the inhibitory activities of MDSCs by arresting plasma cells differentiation, reducing Fas ligand expression on cytotoxic T cells, and re-balancing T cell subsets. Mechanistically, transcriptome analysis confirmed the participation of TGF-ß/Smad pathways in TPO-RA-corrected-MDSCs, which was offset by Smad2/3 knockdown. In platelet TGF-ß1-deficient mice, TPO-RA-induced amplification and enhanced suppressive capacity of MDSCs was waived. Furthermore, our retrospective data revealed that ITP patients achieving complete platelet response showed superior long-term outcomes compared with those who only reach partial response. In conclusion, we demonstrate that platelet TGF-ß1 induces the expansion and functional reprogramming of MDSCs via the TGF-ß/Smad pathway. These data indicate that platelet recovery not only serves as an endpoint of treatment response, but also paves the way for immune homeostasis in immune-mediated thrombocytopenia.

2.
Emerg Microbes Infect ; : 2339942, 2024 Apr 08.
Artigo em Inglês | MEDLINE | ID: mdl-38584569

RESUMO

To investigate the epidemiology of ST20 carbapenem-resistant Klebsiella pneumoniae (CRKP) in China, and further explore the genomic characteristics of blaIMP-4 and blaNDM-1 coharboring isolates and plasmid contributions to resistance and fitness. Seven ST20 CRKP isolates were collected nationwide, and antimicrobial susceptibility testing was performed. Antimicrobial resistance genes, virulence genes, and plasmid replicons were identified via whole-genome sequencing, and clonality assessed via core-genome multilocus sequence typing. Furthermore, we found four dual-metallo-ß-lactamases (MBL)-harboring isolates, the gene location was detected by Southern blotting, and plasmid location analysis showed that blaIMP-4 was located on a separate plasmid, a self-conjugative fusion plasmid, or the bacterial chromosome. These isolates were subjected to long-read sequencing, the presence of blaIMP-4 in different locations was identified by genomic comparison, and transposon units were detected via inverse PCR. We subsequently found that blaIMP-4 on the fusion plasmid and bacterial chromosome was formed via intact plasmid recombination by the IS26 and ltrA, respectively, and the circular transposon unit was related to cointegration, however, blaIMP-4 in different locations did not affect the gene stability. The blaNDM-1-harboring plasmid contributed to the increased resistance to ß-lactams and shortened survival lag time which was revealed in plasmid cured isolates. In summary, the K. pneumoniae ST20 clone is a high-risk resistant clone. With the use of ceftazidime/avibactam, MBL-positive isolates, especially dual-MBL-harboring isolates, should be given additional attention.

3.
Artigo em Inglês | MEDLINE | ID: mdl-38580777

RESUMO

Allogeneic hematopoietic stem cell transplantation (allo-HSCT) offers rapid hematopoietic and immune reconstitution for aplastic anemia (AA). As a non-malignant disorder, attenuation of GVHD remains a clinical priority in AA patients. Our study sought to investigate the safety and efficacy of the prophylactic use of ruxolitinib in allogeneic HSCT. A total of 35 AA patients were retrospectively consecutively treated with allo-HSCT whereby ruxolitinib was added to the standard GVHD prophylaxis regimen (rux group). The addition of peri-transplant ruxolitinib did not impact the engraftment and graft function, while better recovery of CD4+ Tregs in the rux group was observed. Interestingly, the rux group demonstrated significantly lower incidence of bacterial/fungal infections (17.14% vs 45.71%). Compared to the control group, the rux group exhibited significantly lower incidence of moderate to severe aGVHD (17.1% vs 48.6%) with a trend toward lower severe aGVHD (8.6% vs 20%) and cGVHD (26.2 vs 38.3). The rux group also demonstrated a trend toward higher GVHD and failure-free survival (GFFS: 85.7% vs 68.6%) and lower TRM (2.9% vs 14.3%). Addition of ruxolitinib to standard GVHD prophylaxis regimen, thus, represents a safe and highly efficient method for the attenuation of GVHD with better outcome of allo-HSCT.

4.
Heliyon ; 10(7): e28696, 2024 Apr 15.
Artigo em Inglês | MEDLINE | ID: mdl-38586410

RESUMO

By analysing the factors influencing secondary vocational students' learning burnout in the context of social media, this study unearthed the underlying causes of learning burnout. It also determined the correlation paths among the factors influencing learning burnout, providing references for educational and pedagogical improvement. This contributes to preventing secondary vocational students' learning burnout and enhancing learning efficiency in secondary vocational schools. Combined with previous research results and a theoretical basis, this study identifies 10 influencing factors employing the Delphi method, and uses Interpretative Structural Modelling (ISM) and Matrice d' Impacts Croisés Multiplication Appliqués à un Classement (MICMAC) to elucidate the relationship between influencing factors of learning burnout among secondary vocational students in the context of social media. This study also constructs a corresponding mechanism model and subsequently proposes prevention and improvement strategies. The results show that the overdevelopment of social media, as driving factors, has the greatest impact on secondary vocational students' learning burnout. Simultaneously, it takes the lead in addressing cognitive bias among students, decreased self-control, and low learning efficiency, factors that contribute to learning burnout. This is particularly beneficial in alleviating the degree of learning burnout among secondary vocational students in the context of social media and improves overall learning outcomes for these students. The hierarchical structure and correlation paths identified in this study offer robust invaluable guidance for developing a scientific program to address the problem of learning burnout among this demographic. This includes implementing related educational practises, thereby reducing the unpredictability of the practical applications.

5.
Front Endocrinol (Lausanne) ; 15: 1184966, 2024.
Artigo em Inglês | MEDLINE | ID: mdl-38567304

RESUMO

Aim: To evaluate the effect of an extended culture period on birth weight among singletons born after vitrified-warmed embryo transfer. Methods: A retrospective cohort study was performed among 12400 women who gave birth to 1015, 1027, 687, and 9671 singletons after single blastocyst transfer, single cleavage-stage embryo transfer, double blastocyst transfer, and double cleavage-stage embryo transfer, respectively. Results: The unadjusted birth weight of singletons born after vitrified blastocyst transfer were heavier than those born after cleavage-stage transfer (ß=30.28, SE=13.17, P=0.022), as were the adjusted birth weights (ß=0.09, SE=0.03, P=0.007). In addition, there was a 37% increased odd of having an infant with high birth weight after vitrified blastocyst transfer compared with vitrified cleavage stage transfer (OR=1.37, 95% CI:1.07-1.77). Conclusion: The unadjusted and adjusted birth weight and odds of having an infant with high birth weight significantly increased after blastocyst transfer compared with cleavage-stage embryo transfer in vitrified-warmed cycles.


Assuntos
Transferência Embrionária , Vitrificação , Humanos , Feminino , Peso ao Nascer , Estudos Retrospectivos , Transferência de Embrião Único
6.
Curr Neurovasc Res ; 2024 Apr 02.
Artigo em Inglês | MEDLINE | ID: mdl-38571342

RESUMO

OBJECTIVE: Early Neurological Deterioration (END) is one of the complications in Acute ischemic stroke (AIS) and relates to prognosis. However, the reason why it occurs is still unclear. Our study is to investigate if CT perfusion (CTP) can predict END in patients with Minor Stroke and Large Vessel Occlusion after Intravenous Thrombolysis (IVT). METHODS: Patients who underwent IVT with Large Vessel Occlusion were enrolled continuously from January 2021 to August 2023. After evaluating the National Institutes of Health Stroke Scale (NIHSS) score, they were divided into the END group (n=21) and the Non-END group (n=20). Multivariate logistic regression analysis was performed to explore the factors of END. Receiver-operating characteristic (ROC) curve analysis was also used to assess the discriminative ability of CTP in predicting END. RESULTS: A total of 41 patients (mean age, 62.34 ± 10.82 years, 27 male) were finally included in the analysis; 21 patients had END, and 9 patients underwent Endovascular thrombectomy (EVT). Multivariate logistic regression analysis indicated that rCBV (OR=0.081, 95%CI=0.009- 0.721, p = 0.024) and admission-NIHSS (OR=1.990, 95%CI=1.049-3.772, p = 0.035) were significantly associated with END. The area under the curve (AUC) of rCBV and NIHSS to discriminate END were 0.708 and 0.758. We found patients with END had a higher modified Rankin Scale (mRS) in 3 months. CONCLUSIONS: The rCBV and NIHSS were associated with post-thrombolysis END and may become reliable markers to predicate END. END might predict a poor 3-month functional outcome.

7.
Transl Stroke Res ; 2024 Apr 01.
Artigo em Inglês | MEDLINE | ID: mdl-38558011

RESUMO

Intracerebral hemorrhage (ICH) is the most serious form of stroke and has limited available therapeutic options. As knowledge on ICH rapidly develops, cutting-edge techniques in the fields of surgical robots, regenerative medicine, and neurorehabilitation may revolutionize ICH treatment. However, these new advances still must be translated into clinical practice. In this review, we examined several emerging therapeutic strategies and their major challenges in managing ICH, with a particular focus on innovative therapies involving robot-assisted minimally invasive surgery, stem cell transplantation, in situ neuronal reprogramming, and brain-computer interfaces. Despite the limited expansion of the drug armamentarium for ICH over the past few decades, the judicious selection of more efficacious therapeutic modalities and the exploration of multimodal combination therapies represent opportunities to improve patient prognoses after ICH.

8.
Phys Chem Chem Phys ; 2024 Apr 02.
Artigo em Inglês | MEDLINE | ID: mdl-38563510

RESUMO

The deposition and intercalation of metal atoms can induce superconductivity in monolayer and bilayer graphenes. For example, it has been experimentally proved that Li-deposited graphene is a superconductor with critical temperature Tc of 5.9 K, Ca-intercalated bilayer graphene C6CaC6 and K-intercalated epitaxial bilayer graphene C8KC8 are superconductors with Tc of 2-4 K and 3.6 K, respectively. However, the Tc of them are relatively low. To obtain higher Tc in graphene-based superconductors, here we predict a new Ca-intercalated bilayer graphene C2CaC2, which shows higher Ca concentration than the C6CaC6. It is proved to be thermodynamically and dynamically stable. The electronic structure, electron-phonon coupling (EPC) and superconductivity of C2CaC2 are investigated based on first-principles calculations. The EPC of C2CaC2 mainly comes from the coupling between the electrons of C-pz orbital and the high- and low-frequency vibration modes of C atoms. The calculated EPC constant λ of C2CaC2 is 0.75, and the superconducting Tc is 18.9 K, which is much higher than other metal-intercalated bilayer graphenes. By further applying -4% biaxial compressive strain to C2CaC2, the Tc can be boosted to 26.6 K. Thus, the predicted C2CaC2 provides a new platform for realizing superconductivity with the highest Tc in bilayer graphenes.

9.
Diabetes Metab Syndr Obes ; 17: 1455-1466, 2024.
Artigo em Inglês | MEDLINE | ID: mdl-38562278

RESUMO

Background: Previous studies have shown that the prevalence of sarcopenia in patients with type 2 diabetes mellitus (T2DM) has increased significantly over the years. However, the risk factors for the association of sarcopenia in patients with T2DM are unknown. Therefore, we attempted to investigate the risk factors through measurement and analysis of the patients' data from April 2020 to April 2022. Methods: A total of 334 hospitalized patients with T2DM were divided into sarcopenia group (n=101) and non-sarcopenia group (n=233). Clinical factors were compared between the two groups and also between the two genders. Receiver operating characteristic curve (ROC) was used to analyze the ROC diagnostic ability of related factors in sarcopenia. Results: (1) Among the 334 patients, the overall prevalence of sarcopenia was 30.2%; 41.3% in men and 20.1% in women. (2) The multifactorial logistic regression analysis showed that gender (specifically for men; OR=4.997, 95% CI: 2.611-9.564), low body mass index (BMI) (OR=1.525, 95% CI: 1.353-1.718), lower 25(OH)D levels (OR=1.076, 95% CI:1.036-1.117), and lower IGF-1 (OR=1.013, 95% CI:1.006-1.020) were independent risk factors (P < 0.05). (3) ROC curve analysis results showed that BMI, 25 (OH) D, IGF-1, and testosterone (for men) had predictive significance for sarcopenia with T2DM (P < 0.05). However, the AUC of 25 (OH) D, IGF-1 and testosterone (for men) were all <0.7, while the AUC of BMI and the combined factors were all >0.7, has great predictive significance. Conclusion: The prevalence of sarcopenia in hospitalized patients with T2DM is higher in men than in women. Low BMI and lower serum levels of 25 (OH) D and IGF-1 are risk factors of sarcopenia in patients with T2DM. Low BMI, 25(OH)D, IGF-1, and testosterone (for men) all contributed to the prediction of sarcopenia, among which BMI and combined factors were more significant.

10.
J Clin Invest ; 134(7)2024 Apr 01.
Artigo em Inglês | MEDLINE | ID: mdl-38557487

RESUMO

Endothelial function and integrity are compromised after allogeneic bone marrow transplantation (BMT), but how this affects immune responses broadly remains unknown. Using a preclinical model of CMV reactivation after BMT, we found compromised antiviral humoral responses induced by IL-6 signaling. IL-6 signaling in T cells maintained Th1 cells, resulting in sustained IFN-γ secretion, which promoted endothelial cell (EC) injury, loss of the neonatal Fc receptor (FcRn) responsible for IgG recycling, and rapid IgG loss. T cell-specific deletion of IL-6R led to persistence of recipient-derived, CMV-specific IgG and inhibited CMV reactivation. Deletion of IFN-γ in donor T cells also eliminated EC injury and FcRn loss. In a phase III clinical trial, blockade of IL-6R with tocilizumab promoted CMV-specific IgG persistence and significantly attenuated early HCMV reactivation. In sum, IL-6 invoked IFN-γ-dependent EC injury and consequent IgG loss, leading to CMV reactivation. Hence, cytokine inhibition represents a logical strategy to prevent endothelial injury, thereby preserving humoral immunity after immunotherapy.


Assuntos
Transplante de Medula Óssea , Infecções por Citomegalovirus , Humanos , Recém-Nascido , Interleucina-6/genética , Imunidade Humoral , Imunoglobulina G , Antivirais
11.
Biomed Pharmacother ; 174: 116577, 2024 Apr 08.
Artigo em Inglês | MEDLINE | ID: mdl-38593704

RESUMO

INTRODUCTION: Total ginsenosides (TG), the major active constituents of ginseng, have been proven to be beneficial in treatment of Alzheimer's disease (AD). However, the underlying mechanism of TG remains unclear. METHODS: APP/PS1 mice and N2a/APP695 cells were used as in vivo and in vitro model, respectively. Morris water maze (MWM) was used to investigate behavioral changes of mice; neuronal pathological changes were assessed by hematoxylin and eosin (H&E) and nissl staining; immunofluorescence staining was used to examine amyloid beta (Aß) deposition; Western blotting and quantitative real-time polymerase chain reaction (qRT-PCR) were used to examine the expression of relative amyloidogenic genes and proteins. Moreover, the antagonist of PPARγ, GW9662, was used to determine whether the effects of TG on Aß production were associated with PPARγ activity. RESULTS: TG treatment increased the spatial learning and memory abilities of APP/PS1 mice while decreasing the Aß accumulation in the cortex and hippocampus. In N2a/APP695 cells, TG treatment attenuated the secretion of Aß1-40 and Aß1-42 acting as an PPARγ agonist by inhibiting the translocation of NF-κB p65. Additionally, TG treatment also decreased the expression of amyloidogenic pathway related gene BACE1, PS1 and PS2. CONCLUSIONS: TG treatment reduced the production of Aß both in vivo and in vitro. Activating PPARγ might be a potential therapeutic target of TG in facilitating Aß clearance and ameliorating cognitive deficiency in APP/PS1 mice.

12.
Skin Health Dis ; 4(2): e344, 2024 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-38577041

RESUMO

Hyperkeratosis of the nipples and areolae (HNA) is an uncommon skin disorder with no definite aetiology. We report a case of a 16-year-old boy, who presented with bilateral pigmentation and thickening of the nipples and areolae, accompanied with linear brown protrusions on the anterior neck and a velvet like appearance with pigmentation on the axillary bilaterlly. Based on clinical and histopathological, and dermatoscopic findings, the diagnosis of bilateral HNA accompanied by linear nevus and acanthosis nigricans was made. The skin lesions were improved by treatment with topical calcipotriol gel.

13.
Adv Sci (Weinh) ; : e2308986, 2024 Apr 08.
Artigo em Inglês | MEDLINE | ID: mdl-38588510

RESUMO

Activating autologous stem cells after the implantation of biomaterials is an important process to initiate bone regeneration. Although several studies have demonstrated the mechanism of biomaterial-mediated bone regeneration, a comprehensive single-cell level transcriptomic map revealing the influence of biomaterials on regulating the temporal and spatial expression patterns of mesenchymal stem cells (MSCs) is still lacking. Herein, the osteoimmune microenvironment is depicted around the classical collagen/nanohydroxyapatite-based bone repair materials via combining analysis of single-cell RNA sequencing and spatial transcriptomics. A group of functional MSCs with high expression of matrix Gla protein (Mgp) is identified, which may serve as a pioneer subpopulation involved in bone repair. Remarkably, these Mgp high-expressing MSCs (MgphiMSCs) exhibit efficient osteogenic differentiation potential and orchestrate the osteoimmune microenvironment around implanted biomaterials, rewiring the polarization and osteoclastic differentiation of macrophages through the Mdk/Lrp1 ligand-receptor pair. The inhibition of Mdk/Lrp1 activates the pro-inflammatory programs of macrophages and osteoclastogenesis. Meanwhile, multiple immune-cell subsets also exhibit close crosstalk between MgphiMSCs via the secreted phosphoprotein 1 (SPP1) signaling pathway. These cellular profiles and interactions characterized in this study can broaden the understanding of the functional MSC subpopulations at the early stage of biomaterial-mediated bone regeneration and provide the basis for materials-designed strategies that target osteoimmune modulation.

14.
Sports Med Open ; 10(1): 35, 2024 Apr 10.
Artigo em Inglês | MEDLINE | ID: mdl-38598018

RESUMO

BACKGROUND: Ankle sprains lead to an unexplained reduction of ankle eversion strength, and arthrogenic muscle inhibition (AMI) in peroneal muscles is considered one of the underlying causes. This study aimed to observe the presence of AMI in peroneal muscles among people with chronic ankle instability (CAI). METHODS: Sixty-three people with CAI and another sixty-three without CAI conducted maximal voluntary isometric contraction (MVIC) and superimposed burst (SIB) tests during ankle eversion, then fifteen people with CAI and fifteen without CAI were randomly invited to repeat the same tests to calculate the test-retest reliability. Electrical stimulation was applied to the peroneal muscles while the participants were performing MVIC, and the central activation ratio (CAR) was obtained by dividing MVIC torque by the sum of MVIC and SIB torques, representing the degree of AMI. RESULTS: The intra-class correlation coefficients were 0.77 (0.45-0.92) and 0.92 (0.79-0.97) for the affected and unaffected limbs among people with CAI, and 0.97 (0.91-0.99) and 0.93 (0.82-0.97) for the controlled affected and unaffected limbs among people without CAI; Significant group × limb interaction was detected in the peroneal CAR (p = 0.008). The CARs were lower among people with CAI in the affected and unaffected limbs, compared with those without CAI (affected limb = 82.54 ± 9.46%, controlled affected limb = 94.64 ± 6.37%, p < 0.001; unaffected limb = 89.21 ± 8.04%, controlled unaffected limb = 94.93 ± 6.01%, p = 0.016). The CARs in the affected limbs were lower than those in the unaffected limbs among people with CAI (p = 0.023). No differences between limbs were found for CAR in the people without CAI (p = 0.10). CONCLUSIONS: Bilateral AMI of peroneal muscles is observed among people with CAI. Their affected limbs have higher levels of AMI than the unaffected limbs.

15.
Comput Biol Med ; 174: 108395, 2024 Apr 02.
Artigo em Inglês | MEDLINE | ID: mdl-38599068

RESUMO

BACKGROUND: Intraoperative hypotension during cesarean section has become a serious complication for maternal and fetal healthy. It is commonly encountered by subarachnoid anesthesia. However, currently used control methods have varying degrees of side effects, such as drugs. The Root Cause Analysis (RCA) - Plan, Do, Check, Act (PDCA) is a new model of care that identifies the root causes of problems. The study aimed to demonstrate the usefulness of RCA-PDCA nursing methods in preventing intraoperative hypotension during cesarean section and to predict the occurrence of intraoperative hypotension through a machine learning model. METHODS: Patients who underwent cesarean section at Traditional Chinese Medicine of Southwest Medical University from January 2023 to December 2023 were retrospectively screened, and the data of their gestational times, age, height, weight, history of allergies, intraoperative vital signs, fetal condition, operative time, fluid out and in, adverse effects, use of vasopressor drugs, anxiety-depression-pain scores, and satisfaction were collected and analyzed. The statistically different features were screened and five machine learning models were used as predictive models to assess the usefulness of the RCA-PDCA model of care. RESULTS: (1) Compared with the general nursing model, the RCA-PDCA nursing model significantly reduces the incidence of intraoperative hypotension and postoperative complications in cesarean delivery, and the patient experience is comfortable and satisfactory. (2) Among the five machine learning models, the RF model has the best predictive performance, and the accuracy of the random forest model in preventing intraoperative hypotension is as high as 90%. CONCLUSION: Through computer machine learning model analysis, we prove the importance of the RCA-PDCA nursing method in the prevention of intraoperative hypotension during cesarean section, especially the Random Forest model which performed well and promoted the application of artificial intelligence computer learning methods in the field of medical analysis.

16.
World J Gastroenterol ; 30(10): 1405-1419, 2024 Mar 14.
Artigo em Inglês | MEDLINE | ID: mdl-38596488

RESUMO

BACKGROUND: Ulcerative colitis is a chronic inflammatory disease of the colon with an unknown etiology. Alkaline sphingomyelinase (alk-SMase) is specifically expressed by intestinal epithelial cells, and has been reported to play an anti-inflammatory role. However, the underlying mechanism is still unclear. AIM: To explore the mechanism of alk-SMase anti-inflammatory effects on intestinal barrier function and oxidative stress in dextran sulfate sodium (DSS)-induced colitis. METHODS: Mice were administered 3% DSS drinking water, and disease activity index was determined to evaluate the status of colitis. Intestinal permeability was evaluated by gavage administration of fluorescein isothiocyanate dextran, and bacterial translocation was evaluated by measuring serum lipopolysaccharide. Intestinal epithelial cell ultrastructure was observed by electron microscopy. Western blotting and quantitative real-time reverse transcription-polymerase chain reaction were used to detect the expression of intestinal barrier proteins and mRNA, respectively. Serum oxidant and antioxidant marker levels were analyzed using commercial kits to assess oxidative stress levels. RESULTS: Compared to wild-type (WT) mice, inflammation and intestinal permeability in alk-SMase knockout (KO) mice were more severe beginning 4 d after DSS induction. The mRNA and protein levels of intestinal barrier proteins, including zonula occludens-1, occludin, claudin-3, claudin-5, claudin-8, mucin 2, and secretory immunoglobulin A, were significantly reduced on 4 d after DSS treatment. Ultrastructural observations revealed progressive damage to the tight junctions of intestinal epithelial cells. Furthermore, by day 4, mitochondria appeared swollen and degenerated. Additionally, compared to WT mice, serum malondialdehyde levels in KO mice were higher, and the antioxidant capacity was significantly lower. The expression of the transcription factor nuclear factor erythroid 2-related factor 2 (Nrf2) in the colonic mucosal tissue of KO mice was significantly decreased after DSS treatment. mRNA levels of Nrf2-regulated downstream antioxidant enzymes were also decreased. Finally, colitis in KO mice could be effectively relieved by the injection of tertiary butylhydroquinone, which is an Nrf2 activator. CONCLUSION: Alk-SMase regulates the stability of the intestinal mucosal barrier and enhances antioxidant activity through the Nrf2 signaling pathway.


Assuntos
Colite Ulcerativa , Colite , Doença de Niemann-Pick Tipo A , Camundongos , Animais , Antioxidantes/uso terapêutico , Sulfato de Dextrana/toxicidade , Doença de Niemann-Pick Tipo A/metabolismo , Fator 2 Relacionado a NF-E2/metabolismo , Colite/tratamento farmacológico , Colo , Colite Ulcerativa/tratamento farmacológico , Mucosa Intestinal , Anti-Inflamatórios/uso terapêutico , Camundongos Knockout , RNA Mensageiro/metabolismo , Receptores Proteína Tirosina Quinases/metabolismo , Camundongos Endogâmicos C57BL , Modelos Animais de Doenças
17.
J Hazard Mater ; 469: 134031, 2024 May 05.
Artigo em Inglês | MEDLINE | ID: mdl-38518701

RESUMO

Sulfidated nano-scale zerovalent iron (S-nZVI) has emerged as an advanced functional nanomaterial for efficiently remediating Cr(VI) contamination in aqueous environments. However, there is an insufficient understanding of its coherent process, removal pathway, and hydrochemical reactive mechanisms, presenting potential challenges for its future environmental applications. To address this gap, this study successfully synthesized S-nZVI through a chemical precipitation method and effectively applied it for the removal of Cr(VI). Additional characterization revealed that the removal of Cr(VI) followed a sequence of rapid chemisorption and intraparticle diffusion processes, concomitant with an increase in pH and a decrease in oxidation-reduction potential. The remediation mechanism encompassed a synergistic reduction of Cr(VI) to Cr(III) and simultaneous immobilization via Cr2FeO4 coprecipitation. The highest Cr(VI) removal capacity of 75 mg/g was attained during dynamic removal experiments in the sand column packed with S-nZVI. Further computational analysis, employing density functional theory calculations based on the experimental data, revealed the involvement of multiple molecular orbitals of Cr(VI) in the removal process. It also elucidated a step-by-step reduction pathway for Cr(VI) characterized by decreasing free energy. These findings provide evidence-based insights into Cr(VI) remediation using S-nZVI and can serve as valuable technical support for future environmental management of heavy metals.

18.
Emerg Microbes Infect ; 13(1): 2332658, 2024 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-38517707

RESUMO

Carbapenem-resistant Enterobacterales (CRE), specifically those resistant to only ertapenem among carbapenems (ETP-mono-resistant), are increasingly reported, while the optimal therapy options remain uncertain. To investigate the prevalence and characteristics of ETP-mono-resistant CRE, CRE strains were systematically collected from 102 hospitals across China between 2018 and 2021. A 1:1 randomized matching study was conducted with ETP-mono-resistant strains to meropenem- and/or imipenem-resistant (MEM/IPM-resistant) strains. Antimicrobial susceptibility testing, whole-genome sequencing, carbapenem-hydrolysing activity and the expression of carbapenemase genes were determined. In total, 18.8% of CRE strains were ETP-mono-resistant, with relatively low ertapenem MIC values. ETP-mono-resistant strains exhibited enhanced susceptibility to ß-lactams, ß-lactam/ß-lactamase inhibitor combinations, levofloxacin, fosfomycin, amikacin and polymyxin than MEM/IPM-resistant strains (P < 0.05). Phylogenetic analysis revealed high genetic diversity among ETP-mono-resistant strains. Extended-spectrum ß-lactamases (ESBLs) and/or AmpC, as well as porin mutations, were identified as potential major mechanisms mediating ETP-mono-resistance, while the presence of carbapenemases was found to be the key factor distinguishing the carbapenem-resistant phenotypes between the two groups (P < 0.001). Compared with the MEM/IPM-resistant group, limited carbapenemase-producing CRE (CP-CRE) strains in the ETP-mono-resistant group showed a significantly lower prevalence of ESBLs and porin mutations, along with reduced expression of carbapenemase. Remarkably, spot assays combined with modified carbapenem inactivation method indicated that ETP-mono-resistant CP-CRE isolates grew at meropenem concentrations eightfold above their corresponding MIC values, accompanied by rapidly enhanced carbapenem-hydrolysing ability. These findings illustrate that ETP-mono-resistant CRE strains are relatively prevalent and that caution should be exercised when using meropenem alone for treatment. The detection of carbapenemase should be prioritized.


Assuntos
Antibacterianos , Carbapenêmicos , Ertapenem/farmacologia , Meropeném , Antibacterianos/farmacologia , Prevalência , Filogenia , Carbapenêmicos/farmacologia , beta-Lactamases/metabolismo , Proteínas de Bactérias/genética , Proteínas de Bactérias/metabolismo , Porinas/genética , Testes de Sensibilidade Microbiana
19.
Heliyon ; 10(5): e26642, 2024 Mar 15.
Artigo em Inglês | MEDLINE | ID: mdl-38434355

RESUMO

Alzheimer's disease (AD) is a progressive neurodegenerative disease characterized by memory loss, cognitive disorder, language dysfunction, and mental disability. The main neuropathological changes in AD mainly include amyloid plaque deposition, neurofibrillary tangles, synapse loss, and neuron reduction. However, the current anti-AD drugs do not demonstrate a favorable effect in altering the pathological course of AD. Moreover, long-term use of these drugs is usually accompanied with various side effects. Ginsenosides are the major active constituents of ginseng and have protective effects on AD through various mechanisms in both in vivo and in vitro studies. In this review, we focused on discussing the therapeutic potential effects and the mechanisms of pharmacological activities of ginsenosides in AD, to provide new insight for further research and clinical application of ginsenosides in the future. Recent studies on the pharmacological effects and mechanisms of ginsenosides were retrieved from Chinese National Knowledge Infrastructure, National Science and Technology Library, Wanfang Data, Elsevier, ScienceDirect, PubMed, SpringerLink, and the Web of Science database up to April 2023 using relevant keywords. Network pharmacology and bioinformatics analysis were used to predict the therapeutic effects and mechanisms of ginsenosides against AD. Ginsenosides presented a wide range of therapeutic and biological activities, including alleviating Aß deposition, decreasing tau hyperphosphorylation, regulating the cholinergic system, resisting oxidative stress, modulating Ca2+ homeostasis, as well as anti-inflammation and anti-apoptosis in neurons, respectively. For further developing the therapeutic potential as well as clinical applications, the network pharmacology approach was combined with a summary of published studies.

20.
Cardiovasc Diagn Ther ; 14(1): 84-100, 2024 Feb 15.
Artigo em Inglês | MEDLINE | ID: mdl-38434559

RESUMO

Background: Nicotinamide adenine dinucleotide phosphate oxidase 4 (NOX4)-mediated reactive oxygen species (ROS) has been reported to induce cardiomyocyte apoptosis, but its effect on pyroptosis of cardiomyocytes has been rarely reported. This paper aimed to explore the effects of NOX4-mediated ROS production on doxorubicin (DOX)-induced myocardial injury and pyroptosis through nucleotide-binding and oligomerization domain-like receptor protein 3 (NLRP3) inflammasome. Methods: HL-1 cells were treated with DOX or mice (30 mice were divided into five groups with six mice/group) underwent intraperitoneal injection with DOX (5 mg/kg, once a week, five times) to induce myocardial injury, followed by assessment of NOX4 and NLRP3 expression in cell supernatant and myocardial tissues. In cardiomyocyte HL-1 cells, cell proliferation was tested by MTT assay and the activity of ROS by probes. The superoxide dismutase (SOD) activity, malondialdehyde (MDA) content, and glutathione (GSH) activity were evaluated by kits. The expression of pyroptosis proteins was assessed by western blotting. Subsequently, the expression of NOX4 or NLRP3 was altered to determine the effect of NOX4 or NLRP3 expression on cardiomyocyte injury and pyroptosis. The animal models were utilized to evaluate the changes in the cardiac function of mice using an echocardiographic system, with these parameters measured including left ventricular ejection fraction (LVEF), left ventricular fractional shortening (LVFS), and left ventricular end-diastolic diameter (LVEDD). Furthermore, the content of myocardial injury markers and the protein expression of pyroptosis proteins were determined to evaluate myocardial injury in the mice. Results: DOX treatment led to cardiomyocyte injury and pyroptosis, as evidenced by weakened LVEF, LVFS, and cell proliferation (P<0.05), elevated LVEDD, ROS, and MDA (P<0.05), increased expression of pyroptosis proteins (P<0.05), and decreased SOD and GSH (P<0.05). Additionally, NOX4 and NLRP3 were highly-expressed (P<0.05) in cell supernatant and myocardial tissues. In DOX-induced HL-1 cells, the overexpression of NOX4 intensified ROS levels to aggravate cardiomyocyte injury and pyroptosis, which was reversed by treatment of the ROS scavenger N-acetyl-cysteine. Furthermore, it was revealed that the combination of short hairpin RNA (sh)-NOX4 and overexpressed (oe)-NLRP3 reversed the cardioprotective effects of sh-NOX4 and increased myocardial tissue or cell injury and pyroptosis in vitro and in vivo. No mice died during the animal experiments, and only two were ruled out due to a weight loss greater than 20%. Conclusions: NOX4-mediated ROS production activated NLRP3 inflammasome, thereby aggravating DOX-induced myocardial injury in vitro and in vivo.

SELEÇÃO DE REFERÊNCIAS
DETALHE DA PESQUISA
...