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2.
Carbohydr Polym ; 335: 122075, 2024 Jul 01.
Artigo em Inglês | MEDLINE | ID: mdl-38616096

RESUMO

Polyethylene oxide (PEO) solid electrolytes, acknowledged for their safety advantages over liquid counterparts, confront inherent challenges, including low ionic conductivity, restricted lithium ion migration, and mechanical fragility, notably pronounced in lithium­sulfur batteries due to the polysulfide shuttling phenomenon. To address these limitations, we integrate a quaternary ammonium cation-modified cellulose (QACC) nanofiber, electrospun with cellulose acetate (CA) from recycled cigarette filters, into the PEO electrolyte matrix. The nitrogen atom within the quaternary ammonium group exhibits a pronounced affinity for polysulfide compounds, effectively curtailing polysulfide migration. Concurrently, Lewis acid-base interactions between quaternary ammonium groups and lithium salt anions facilitate the release of additional Li+, achieving a lithium-ion transference number 1.5 times higher than its pure PEO counterpart. Furthermore, the introduction of a larger trifluoromethanesulfonimide (TFSI) group on the QACC macromolecule (TFSI-QACC) disrupts the ordered arrangement of PEO macromolecules, resulting in a noteworthy enhancement in ionic conductivity, reaching 2.07 × 10-4 S cm-1 at 60 °C, thus addressing the challenge of low PEO electrolyte conductivity. Moreover, the nanofiber enhances the mechanical strength of the PEO electrolyte from 0.49 to 7.50 MPa, mitigating safety concerns related to lithium dendrites puncturing the electrolyte. Consequently, the composite PEO demonstrates exemplary performance in lithium symmetrical batteries, enduring 500 h of continuous operation and completing 100 cycles at both room and elevated temperatures. This integrated approach, transitioning from waste to wealth, adeptly addresses a spectrum of challenges in the efficiency of solid-state electrolytes, holding considerable promise for advancing lithium­sulfur battery technology.

3.
Zhongguo Zhong Yao Za Zhi ; 49(4): 902-911, 2024 Feb.
Artigo em Chinês | MEDLINE | ID: mdl-38621897

RESUMO

Alzheimer's disease(AD), vascular dementia(VD), and traumatic brain injury(TBI) are more common cognitive impairment diseases characterized by high disability and mortality rates, imposing a heavy burden on individuals and their families. Although AD, VD, and TBI have different specific mechanisms, their pathogenesis is closely related to the nucleotide-binding oligome-rization domain-like receptor protein 3(NLRP3). The NLRP3 inflammasome is involved in neuroinflammatory responses, mediating microglial polarization, regulating the reduction of amyloid ß-protein(Aß) deposition, neurofibrillary tangles(NFTs) formation, autophagy regulation, and maintaining brain homeostasis, and synaptic stability, thereby contributing to the development of AD, VD, and TBI. Previous studies have shown that traditional Chinese medicine(TCM) can alleviate neuroinflammation, promote microglial polarization towards the M2 phenotype, reduce Aß deposition and NFTs formation, regulate autophagy, and maintain brain homeostasis by intervening in NLRP3 inflammasome, hence exerting a role in preventing and treating cognitive impairment-related diseases, reducing psychological and economic pressure on patients, and improving their quality of life. Therefore, this article elucidated the role of NLRP3 inflammasome in AD, VS, and TBI, and provided a detailed summary of the latest research results on TCM intervention in NLRP3 inflammasome for the prevention and treatment of these diseases, aiming to inherit the essence of TCM and provide references and foundations for clinical prevention and treatment of cognitive impairment-related diseases with TCM. Meanwhile, this also offers insights and directions for further research in TCM for the prevention and treatment of cognitive impairment-related diseases.


Assuntos
Doença de Alzheimer , Disfunção Cognitiva , Humanos , Inflamassomos/metabolismo , Proteína 3 que Contém Domínio de Pirina da Família NLR/genética , Proteína 3 que Contém Domínio de Pirina da Família NLR/metabolismo , Peptídeos beta-Amiloides/metabolismo , Medicina Tradicional Chinesa , Qualidade de Vida , Doença de Alzheimer/tratamento farmacológico , Doença de Alzheimer/prevenção & controle , Disfunção Cognitiva/tratamento farmacológico , Disfunção Cognitiva/prevenção & controle
4.
Foodborne Pathog Dis ; 2024 Apr 01.
Artigo em Inglês | MEDLINE | ID: mdl-38557159

RESUMO

The urgent need for comprehensive and systematic analyses of Shigella as the key pathogen led us to meticulously explore the epidemiology and molecular attributes of Shigella isolates. Accordingly, we procured 24 isolates (10 from Xinjiang and 14 from Wuhan, China) and performed serotype identification and antimicrobial susceptibility testing. Resistance gene detection and homology analysis by polymerase chain reaction and pulsed-field gel electrophoresis (PFGE), respectively, were performed for genetic diversity analysis. All isolates were identified as Shigella flexneri, with 70% (35.4-91.9%) and 30% (8.1-64.6%) of the Xinjiang isolates and 85.7% (56.2-97.5%) and 14.3% (2/14, 2.5-43.9%) of the Wuhan isolates belonging to serotype 2a and serotype 2b, respectively. All isolates displayed resistance to at least two antibiotics and complete resistance to ampicillin. Multidrug resistance (MDR) was recorded in 70.8% (48.8-86.6%) of isolates, with Xinjiang isolates exhibiting relatively higher resistance to ampicillin-sulbactam, piperacillin, ceftriaxone, and aztreonam. Conversely, Wuhan isolates displayed higher MDR and resistance to tetracycline, ciprofloxacin, levofloxacin, and cefepime relative to Xinjiang isolates. Molecular scrutiny of antibiotic-resistance determinants revealed that blaTEM was the main mechanism of ampicillin resistance, blaCTX-M was the main gene for resistance to third- and fourth-generation cephalosporins, and tetB was the predominant gene associated with tetracycline resistance. Four Xinjiang and seven Wuhan isolates shared T1-clone types (>85%), and two Xinjiang and one Wuhan isolates were derived from the T6 clone with a high similarity of 87%. Six PFGE patterns (T1, T2, T5, T6-3, T8, and T10) of S. flexneri were associated with MDR. Thus, there is a critical need for robust surveillance and control strategies in managing Shigella infections, along with the development of targeted interventions and antimicrobial stewardship programs tailored to the distinct characteristics of Shigella isolates in different regions of China.

5.
Front Vet Sci ; 11: 1320308, 2024.
Artigo em Inglês | MEDLINE | ID: mdl-38585297

RESUMO

Introduction: Alveolar echinococcosis (AE) is a parasitic disease caused by E. multilocularis metacestodes and it is highly prevalent in the northern hemisphere. We have previously found that vaccination with E. multilocularis-Leucine aminopeptidase (EM-LAP) could inhibit the growth and invasion of E. multilocularis in host liver, and Ubenimex, a broad-spectrum inhibitor of LAP, could also inhibit E. multilocularis invasion but had a limited effect on the growth and development of E. multilocularis. Methods: In this study, the therapeutic effect of Ubenimex combined with Albendazole on AE was evaluated. Mice were intraperitoneally injected with protoscoleces and imaging examination was performed at week 8 and week 16 to detect cyst change. During this period, mice were intraperitoneally injected with Ubenimex and intragastrically administered with Albendazole suspension. At last, the therapeutic effect was evaluated by morphological and pathological examination and liver function. Results: The results revealed that the combined treatment could inhibit the growth and infiltration of cysts in BALB/c mice infected with E. multilocularis protoscoleces. The weight, number, invasion and fibrosis of cysts were reduced in mice treated with Ubenimex in combination with Albendazole. The same effect was achieved by the single Ubenimex treatment because of its inhibitory effect on LAP activity, but it was less effective in inhibiting the growth of cysts. The levels of ALT, AST, TBIL, DBIL, ALP, and γ-GT were reduced after the combined treatment, indicating that treatment with both Ubenimex and Albendazole could alleviate liver damage. Discussion: This study suggests that the combined treatment with Ubenimex and Albendazole could be a potential therapeutic strategy for E. multilocularis infections.

7.
Adv Sci (Weinh) ; : e2309348, 2024 Mar 18.
Artigo em Inglês | MEDLINE | ID: mdl-38498682

RESUMO

Tertiary lymphoid structure (TLS) can predict the prognosis and sensitivity of tumors to immune checkpoint inhibitors (ICIs) therapy, whether it can be noninvasively predicted by radiomics in hepatocellular carcinoma with liver transplantation (HCC-LT) has not been explored. In this study, it is found that intra-tumoral TLS abundance is significantly correlated with recurrence-free survival (RFS) and overall survival (OS). Tumor tissues with TLS are characterized by inflammatory signatures and high infiltration of antitumor immune cells, while those without TLS exhibit uncontrolled cell cycle progression and activated mTOR signaling by bulk and single-cell RNA-seq analyses. The regulators involved in mTOR signaling (RHEB and LAMTOR4) and S-phase (RFC2, PSMC2, and ORC5) are highly expressed in HCC with low TLS. In addition, the largest cohort of HCC patients is studied with available radiomics data, and a classifier is built to detect the presence of TLS in a non-invasive manner. The classifier demonstrates remarkable performance in predicting intra-tumoral TLS abundance in both training and test sets, achieving areas under receiver operating characteristic curve (AUCs) of 92.9% and 90.2% respectively. In summary, the absence of intra-tumoral TLS abundance is associated with mTOR signaling activation and uncontrolled cell cycle progression in tumor cells, indicating unfavorable prognosis in HCC-LT.

8.
Bioelectrochemistry ; 158: 108680, 2024 Mar 08.
Artigo em Inglês | MEDLINE | ID: mdl-38493575

RESUMO

Electrochemical immunosensors have gained considerable attention in detecting human disease markers due to their excellent specificity, high sensitivity, and facile operation. Herein, a rational-designed sandwich-type electrochemical immunosensor is constructed for the sensitive detection of cardiac troponin I (cTnI) using nitrogen-doped carbon nanotubes loaded with gold nanoparticles (Au NPs/N-CNTs) as substrate and highly active mesoporous palladium-nitrogen nanocubes (meso-PdN NCs) as secondary antibody markers. Benefitting from its large specific surface area (638.04 m2 g-1) and high nitrogen content, novel polydopamine (PDA)/ halloysite nanotubes (HNTs) hybrid derived one-dimensional (1D) N-CNTs can provide more binding sites for the in-situ growth of Au NPs to connect Ab1. Furthermore, as an ideal substrate material, Au NPs/N-CNTs exhibit finely tuned mesoporous structures and outstanding conductivity, which facilitate the mass and electron transfer during the electrocatalysis process. Besides, highly concave surfaces and crystalline mesopores of meso-PdN NCs expose more surfaces and crevices, providing abundant reactive sites for H2O2 reduction. Remarkably, the as-obtained immunosensor presented a wide linear range (from 10 fg mL-1 to 100 ng mL-1) and an excellent low detection limit (9.85 fg mL-1). This study may offer new insights into the precise fabrication of efficient electrochemical immunosensors for various clinical diagnosis applications.

9.
Artigo em Inglês | MEDLINE | ID: mdl-38485099

RESUMO

PURPOSE: Radiation-induced intestinal injury (RIII) commonly occur during abdominal-pelvic cancer radiation therapy; however, no effective prophylactic or therapeutic agents are available to manage RIII currently. This study aimed to clarify the potential of probiotic consortium supplementation in alleviating RIII. METHODS AND MATERIALS: Male C57BL/6J mice were orally administered a probiotic mixture comprising Bifidobacterium longum BL21, Lactobacillus paracasei LC86, and Lactobacillus plantarum Lp90 for 30 days before exposure to 13 Gy of whole abdominal irradiation. The survival rates, clinical scores, and histologic changes in the intestines of mice were assessed. The impacts of probiotic consortium treatment on intestinal stem cell proliferation, differentiation, and epithelial barrier function; oxidative stress; and inflammatory cytokines were evaluated. A comprehensive examination of the gut microbiota composition was conducted through 16S rRNA sequencing, while changes in metabolites were identified using liquid chromatography-mass spectrometry. RESULTS: The probiotic consortium alleviated RIII, as reflected by increased survival rates, improved clinical scores, and mitigated mucosal injury. The probiotic consortium treatment exhibited enhanced therapeutic effects at the histologic level compared with individual probiotic strains, although there was no corresponding improvement in survival rates and colon length. Moreover, the probiotic consortium stimulated intestinal stem cell proliferation and differentiation, enhanced the integrity of the intestinal epithelial barrier, and regulated redox imbalance and inflammatory responses in irradiated mice. Notably, the treatment induced a restructuring of the gut microbiota composition, particularly enriching short-chain fatty acid-producing bacteria. Metabolomic analysis revealed distinctive metabolic changes associated with the probiotic consortium, including elevated levels of anti-inflammatory and antiradiation metabolites. CONCLUSIONS: The probiotic consortium attenuated RIII by modulating the gut microbiota and metabolites, improving inflammatory symptoms, and regulating oxidative stress. These findings provide new insights into the maintenance of intestinal health with probiotic consortium supplementation and will facilitate the development of probiotic-based therapeutic strategies for RIII in clinical practice.

10.
ACS Appl Mater Interfaces ; 16(14): 17531-17539, 2024 Apr 10.
Artigo em Inglês | MEDLINE | ID: mdl-38530924

RESUMO

Porphyrins and their derivatives possess high molar extinction coefficients and strong electron-donating abilities and have been widely used in organic solar cells (OSCs). Though porphyrins can be easily functionalized at the four meso-positions and the eight ß-positions, nearly all porphyrin photovoltaic materials are reported to be functionalized at the meso-positions, and the porphyrin photovoltaic materials functionalized at the ß-positions are to be explored. Herein, the regioselective ß-positions of a porphyrin are first brominated without using rare metal iridium catalysts, and then, after two more reactions, two antipodal ß-substituted porphyrin donors EHDPP-Por and BODPP-Por are synthesized, in which four DPP (diketopyrrolopyrrole) units are connected symmetrically with acetylene at four of the ß-positions, for OSCs. The all-small-molecule organic solar cells based on EHDPP-Por:Y6 and BODPP-Por:Y6 active layers achieved power conversion efficiencies of 10.19 and 10.99%, respectively, which are higher than most of the binary OSCs based on the porphyrins functionalized at the meso-positions, demonstrating that ß-functionalized porphyrins are very promising for OSCs.

11.
J Org Chem ; 89(6): 3926-3930, 2024 Mar 15.
Artigo em Inglês | MEDLINE | ID: mdl-38441005

RESUMO

2- or 4-Pyridyl benzylic amines represent a privileged motif in drug discovery. However, the formation of heterocyclic benzylic amines with fully substituted α-carbons can require the execution of lengthy synthetic routes, which limit their application. Addition of various nucleophilic agents to Ellman's imines has been well established; however, there is no precedented literature reported for pyridyl-type nucleophiles, which are very important for medicinal chemistry. In this letter, we disclose the development of a one-step synthesis of heterocyclic benzylic amines with fully substituted α-carbons from heteroaryl halides and sulfinyl imines. Starting from 2,4-dibromopyridine, regioselective synthesis of 2- or 4-pyridyl benzylic amines could be achieved by choosing toluene or MTBE as a solvent.

12.
Front Microbiol ; 15: 1340262, 2024.
Artigo em Inglês | MEDLINE | ID: mdl-38505559

RESUMO

Introduction: The relationship between gut microbiota and peripheral artery disease (PAD) remains understudied. While traditional risk factors like smoking and hyperlipidemia are well-understood, our study aims to determine the potential causative association of gut microbiota with PAD using Mendelian Randomization. Methods: Data from the International MiBioGen Consortium and the FinnGen research project were used to study 211 bacterial taxa. Instrumental variables, comprising 2079 SNPs, were selected based on significance levels and linkage disequilibrium. Analyses were conducted utilizing the inverse-variance weighted (IVW) method and other statistical MR techniques to mitigate biases, processed in R (v4.3.1) with the TwosampleMR package. Results: Three bacterial taxa, namely genus Coprococcus2, RuminococcaceaeUCG004, and RuminococcaceaeUCG010, emerged as protective factors against PAD. In contrast, family. FamilyXI and the genus Lachnoclostridium and LachnospiraceaeUCG001 were identified as risk factors. Conclusion: Our findings hint at a causative association between certain gut microbiota and PAD, introducing new avenues for understanding PAD's etiology and developing effective treatments. The observed associations now warrant further validation in varied populations and detailed exploration at finer taxonomic levels.

13.
Sci Rep ; 14(1): 6594, 2024 03 19.
Artigo em Inglês | MEDLINE | ID: mdl-38503861

RESUMO

Numerous studies have indicated a connection between psychiatric symptoms, specifically anxiety and depression, and gastroesophageal reflux. However, the precise nature of the link between the severity of gastroesophageal reflux disease and the severity of anxiety and depression remains uncertain. Here, we gathered 24-h pH monitoring data and baseline patient information from a cohort of 518 individuals. Additionally, we evaluated their psychological well-being using the Hospital Anxiety and Depression Scale. The relationship between baseline characteristics and varying degrees of anxiety, depression, and gastroesophageal reflux disease (GERD) was assessed using R software version 4.1.3 and logistic regression models. The findings indicate a statistically significant variation in anxiety levels based on gender, as well as a significant disparity in depression groups when considering age and literacy levels. Kruskal-Wallis test analysis revealed a significant positive correlation between the severity of anxiety and depression and the 24-h pH monitoring results in our patient cohort. As the anxiety and depression levels increased, the rank mean for each examination result also increased. Logistic regression modeling analysis showed that a higher anxiety level was associated with a higher level of GERD. In the presence of mild anxiety, there is a statistically significant association with a higher incidence of GERD with an odds ratio (OR) of 2.64 (95% CI 1.50, 4.64). Similarly, the moderately severe anxiety group also exhibits a causal relationship with an increased GERD incidence, with an OR of 6.84 (95% CI 3.92, 12.17). Additionally, moderate to severe depression is associated with a higher incidence of GERD, with an OR of 2.32 (95% CI 1.23, 4.37). The prevalence of GERD was greater among males compared to females (OR 2.29, 95% CI 1.51-3.49). Additionally, an elevated body mass index (BMI) demonstrated a positive correlation with the susceptibility to GERD (OR 1.07, 95% CI 1.01-1.14). Increasing age may promote the occurrence of GERD in patients. These findings may help to provide a better basis for psychological or pharmacological interventions for GERD patients with psychosomatic symptoms in the future, and provide a reference basis for clinical treatment of the disease.


Assuntos
Depressão , Refluxo Gastroesofágico , Masculino , Feminino , Humanos , Depressão/epidemiologia , Depressão/psicologia , Modelos Logísticos , Refluxo Gastroesofágico/complicações , Refluxo Gastroesofágico/epidemiologia , Refluxo Gastroesofágico/diagnóstico , Ansiedade/epidemiologia , Ansiedade/psicologia , Transtornos de Ansiedade/complicações
14.
Aging (Albany NY) ; 16(7): 6135-6146, 2024 Mar 27.
Artigo em Inglês | MEDLINE | ID: mdl-38546384

RESUMO

Dysfunction of tight junction proteins-associated damage to the blood-brain barrier (BBB) plays an important role in the pathogenesis of ischemic stroke. Lifibrate, an inhibitor of cholinephosphotransferase (CPT), has been used as an agent for serum lipid lowering. However, the protective effects of Lifibrate in ischemic stroke and the underlying mechanism have not been clearly elucidated. Here, we employed an in vivo mice model of MCAO and an OGD/R model in vitro. In the mice models, neurological deficit scores and infarct volume were assessed. Evans Blue solution was used to detect the BBB permeability. The TEER was examined to determine brain endothelial monolayer permeability. Here, we found that Lifibrate improved neurological dysfunction in stroke. Additionally, increased BBB permeability during stroke was significantly ameliorated by Lifibrate. Correspondingly, the reduced expression of the tight junction protein ZO-1 was restored by Lifibrate at both the mRNA and protein levels. Using an in vitro model, we found that Lifibrate ameliorated OGD/R-induced injury in human bEnd.3 brain microvascular endothelial cells by increasing cell viability but reducing the release of LDH. Importantly, Lifibrate suppressed the increase in endothelial monolayer permeability and the reduction in TEER induced by OGD/R via the rescue of ZO-1 expression. Mechanistically, Lifibrate blocked activation of the MLCK/ p-MLC signaling pathway in OGD/R-stimulated bEnd.3 cells. In contrast, overexpression of MLCK abolished the protective effects of Lifibrate in endothelial monolayer permeability, TEER, as well as the expression of ZO-1. Our results provide a basis for further investigation into the neuroprotective mechanism of Lifibrate during stroke.

15.
J Med Chem ; 67(5): 3778-3794, 2024 Mar 14.
Artigo em Inglês | MEDLINE | ID: mdl-38482826

RESUMO

It is an urgent need to tackle the global crisis of multidrug-resistant bacterial infections. We report here an innovative strategy for large-scale screening of new antibacterial agents using a whole bacteria-based DNA-encoded library (DEL) of vancomycin derivatives via peripheral modifications. A bacterial binding affinity assay was established to select the modification fragments in high-affinity compounds. The optimal resynthesized derivatives demonstrated excellently enhanced activity against various resistant bacterial strains and provided useful structures for vancomycin derivatization. This work presents the new concept in a natural product-templated DEL and in antibiotic discovery through bacterial affinity screening, which promotes the fight against drug-resistant bacteria.


Assuntos
Antibacterianos , Vancomicina , Vancomicina/farmacologia , Vancomicina/química , Antibacterianos/química , Bactérias/metabolismo , Farmacorresistência Bacteriana Múltipla , DNA , Testes de Sensibilidade Microbiana
16.
Angew Chem Int Ed Engl ; 63(13): e202319489, 2024 Mar 22.
Artigo em Inglês | MEDLINE | ID: mdl-38308123

RESUMO

Alveolar echinococcosis (AE) is a zoonotic parasitic disease, resulting from being infected with the metacestode larvae of the tapeworm Echinococcus multilocularis (E. multilocularis). Novel prophylactic and therapeutic interventions are urgently needed since the current chemotherapy displays limited efficiency in AE treatment. Bioengineered nano cellular membrane vesicles are widely used for displaying the native conformational epitope peptides because of their unique structure and biocompatibility. In this study, four T-cells and four B-cells dominant epitope peptides of E. multilocularis with high immunogenicity were engineered into the Vero cell surface to construct a membrane vesicle nanovaccine for the treatment of AE. The results showed that the nanovesicle vaccine can efficiently activate dendritic cells, induce specific T/B cells to form a mutually activated circuit, and inhibit E. multilocularis infection. This study presents for the first time a nanovaccine strategy that can completely eliminate the burden of E. multilocularis.


Assuntos
Equinococose , Echinococcus multilocularis , Vacinas , Animais , Imunoterapia , 60547 , Epitopos , Peptídeos
17.
iScience ; 27(2): 108823, 2024 Feb 16.
Artigo em Inglês | MEDLINE | ID: mdl-38303714

RESUMO

The late Ediacaran Jiangchuan biota, from the Dengying Formation in eastern Yunnan, is well-known for its diverse macroalgal fossils, opening a window onto eukaryotic-dominated ecosystems from the late Neoproterozoic of South China. Although multiple lines of evidence suggest that metazoans had already evolved by the late Ediacaran, animal fossils have not yet been formally described from this locality. Here, we report a putative disc-shaped macrofossil from the Jiangchuan biota, Lobodiscus tribrachialis gen. et sp. nov. This specimen shows the triradial symmetry characteristic of trilobozoans, a group of Ediacaran macrofossils previously documented in Australia and Russia. Lobodiscus could record the youngest known occurrence of trilobozoans, strengthening taxonomic and ecological continuities between the Ediacaran "White Sea" and "Nama" assemblages. Our findings may expand the known paleogeographical distribution of trilobozoans and provide data for Ediacaran biostratigraphic correlations across the Yangtze block and globally, helping to track the diversification of early metazoan-grade organisms.

18.
FASEB J ; 38(3): e23457, 2024 Feb 15.
Artigo em Inglês | MEDLINE | ID: mdl-38318648

RESUMO

Aging is associated with chronic, low-level inflammation which may contribute to cardiovascular pathologies such as hypertension and atherosclerosis. This chronic inflammation may be opposed by endogenous mechanisms to limit inflammation, for example, by the actions of annexin A1 (ANXA1), an endogenous glucocorticoid-regulated protein that has anti-inflammatory and pro-resolving activity. We hypothesized the pro-resolving mediator ANXA1 protects against age-induced changes in blood pressure (BP), cardiovascular structure and function, and cardiac senescence. BP was measured monthly in conscious mature (4-month) and middle-aged (12-month) ANXA1-deficient (ANXA1-/- ) and wild-type C57BL/6 mice. Body composition was measured using EchoMRI, and both cardiac and vascular function using ultrasound imaging. Cardiac hypertrophy, fibrosis and senescence, vascular fibrosis, elastin, and calcification were assessed histologically. Gene expression relevant to structural remodeling, inflammation, and cardiomyocyte senescence were also quantified. In C57BL/6 mice, progression from 4 to 12 months of age did not affect the majority of cardiovascular parameters measured, with the exception of mild cardiac hypertrophy, vascular calcium, and collagen deposition. Interestingly, ANXA1-/- mice exhibited higher BP, regardless of age. Additionally, age progression had a marked impact in ANXA1-/- mice, with markedly augmented vascular remodeling, impaired vascular distensibility, and body composition. Consistent with vascular dysfunction, cardiac dysfunction, and hypertrophy were also evident, together with markers of senescence and inflammation. These findings suggest that endogenous ANXA1 plays a critical role in regulating BP, cardiovascular function, and remodeling and delays cardiac senescence. Our findings support the development of novel ANXA1-based therapies to prevent age-related cardiovascular pathologies.


Assuntos
Anexina A1 , Pressão Sanguínea , Remodelação Vascular , Animais , Camundongos , Anexina A1/genética , Anexina A1/metabolismo , Cardiomegalia , Fibrose , Inflamação/patologia , Camundongos Endogâmicos C57BL , Camundongos Knockout
19.
BMC Pregnancy Childbirth ; 24(1): 126, 2024 Feb 12.
Artigo em Inglês | MEDLINE | ID: mdl-38347456

RESUMO

Chimerism results from the fusion of two zygotes in a single embryo, whereas mosaicism results from mitotic errors in a single zygote. True human chimerism is rare, with fewer than 100 cases reported in the literature. Here, we report a case in which the fetus was identified as having tetragametic chimerism based on short tandem repeat - polymerase chain reaction analysis of the family observed during amniocentesis for advanced maternal age. The chimerism occurred via the fertilization of two ova by two spermatozoa, followed by the fusion of early embryos. The genotypes of the two amniotic fluid samples obtained successively by one puncture were completely different, and the sex chromosomes were XY. Karyotyping and copy number variation sequencing showed no abnormalities. The fetus was delivered at term and the phenotype of the newborn was normal.


Assuntos
Quimerismo , Variações do Número de Cópias de DNA , Feminino , Humanos , Recém-Nascido , Masculino , Gravidez , Amniocentese , Cariotipagem , Fenótipo
20.
Int Immunopharmacol ; 129: 111637, 2024 Mar 10.
Artigo em Inglês | MEDLINE | ID: mdl-38335653

RESUMO

The small intestine exhibits remarkable sensitivity to ionizing radiation (IR), which significantly hampers the effectiveness of radiotherapy in the treatment of abdominal and pelvic tumors. Unfortunately, no effective medications are available to treat radiation-induced intestinal damage (RIID). Fraxin (7-hydroxy-6-methoxycoumarin 8-glucoside), is a coumarin derivative extracted from the Chinese herb Cortex Fraxini. Several studies have underscored the anti-inflammatory, antibacterial, antioxidant, and immunomodulatory properties of fraxin. However, the efficacy of fraxin at preventing or mitigating RIID remains unclear. Thus, the present study aimed to investigate the protective effects of fraxin against RIID in vitro and in vivo and to elucidate the underlying mechanisms. The study findings revealed that fraxin markedly ameliorated intestinal injuries induced by 13 Gy whole abdominal irradiation (WAI), which was accompanied by a significant increase in the population of Lgr5+ intestinal stem cells (ISCs) and Ki67+ progeny. Furthermore, fraxin mitigated WAI-induced intestinal barrier damage, and reduced oxidative stress and intestinal inflammation in mice. Transcriptome sequencing of fraxin-treated mice revealed upregulation of IL-22, a pleiotropic cytokine involved in regulating the function of intestinal epithelial cells. Moreover, in both human intestinal epithelial cells and ex vivo cultured mouse intestinal organoids, fraxin effectively ameliorated IR-induced damage by promoting the expression of IL-22. The radioprotective effects of fraxin were partially negated in the presence of an IL-22-neutralizing antibody. In summary, fraxin is demonstrated to possess the ability to alleviate RIID and maintain intestinal homeostasis, suggesting that fraxin might serve as a strategy for mitigating accidental radiation exposure- or radiotherapy-induced RIID.


Assuntos
Cumarínicos , Intestinos , Camundongos , Humanos , Animais , Cumarínicos/farmacologia , Cumarínicos/uso terapêutico , Antioxidantes , Radiação Ionizante
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