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1.
Injury ; 55(8): 111710, 2024 Jun 26.
Artigo em Inglês | MEDLINE | ID: mdl-38976928

RESUMO

OBJECTIVE: Deep vein thrombosis (DVT) provoked by orthopedic trauma is increasing in pediatric hospitalized patients. The purpose of our study is to identify the prevalence of acute DVT in pediatric and adolescent orthopedic trauma hospitalized patients and focus on evaluating the anticoagulation strategies and the clinical outcomes after a confirmed acute DVT. METHODS: Patients (age ≤18 years) with a confirmed acute DVT admitted for orthopedic trauma between September 2017 and December 2023 were included. Patients were classified into the non-anticoagulation (NA), the in-hospital anticoagulation (IHA), and the in-and-out-of-hospital anticoagulation (IOHA) groups based on their anticoagulation regimen. Efficacy outcomes were the venous thromboembolism (VTE) recurrence within 3 months and change in thrombus burden by repeat imaging at 2 weeks after discharge compared with baseline. Safety outcomes were major bleeding (MB) and clinically relevant non-major bleeding (CRNMB) within 3 months. RESULTS: Of the 11,206 pediatric and adolescent orthopedic trauma inpatients, 94(median age,16 [15, 18] years) were diagnosed with acute DVT, with an incidence of 0.84 %, of which 8(8.5 %) received NA, 41(43.6 %) received IHA, and 45(47.9 %) received IOHA. After the diagnosis of DVT, of patients who received anticoagulation, 97.9 % were treated with rivaroxaban as an oral anticoagulant, and 71.7 % received an LMWH course of ≥5 days before starting rivaroxaban therapy. With a median anticoagulation course of 22(8, 37.3) days, the duration in the IOHA was significantly longer than the IHA (37 days vs. 8 days, p = 0.000). No patients experienced recurrent VTE and MB at 3 months, and 1 received IOHA had a CRNMB event (0 % vs. 0 % vs. 2.2 %, p = 1.000). Thrombus resolution was significantly higher in patients who received anticoagulation therapy (IOHA 91.1 % vs. IHA 80.5 % vs. NA 37.5 %, P = 0.002), and thrombus-no relevant change was significantly lower in patients who received the IOHA strategy compared with the other groups (4.4 % vs. 19.5 % vs. 62.5 %, P = 0.000). CONCLUSIONS: A rivaroxaban-predominant IOHA strategy significantly reduced the thrombotic burden without increasing the risk of bleeding for the treatment of DVT in adolescents with orthopedic trauma. Duration of anticoagulation therapy <6 weeks appears appropriate for adolescent orthopedic trauma-related DVT.

2.
Gut ; 2024 Jul 13.
Artigo em Inglês | MEDLINE | ID: mdl-38960582

RESUMO

OBJECTIVE: Our study aimed to explore the influence of gut microbiota and their metabolites on intracranial aneurysms (IA) progression and pinpoint-related metabolic biomarkers derived from the gut microbiome. DESIGN: We recruited 358 patients with unruptured IA (UIA) and 161 with ruptured IA (RIA) from two distinct geographical regions for conducting an integrated analysis of plasma metabolomics and faecal metagenomics. Machine learning algorithms were employed to develop a classifier model, subsequently validated in an independent cohort. Mouse models of IA were established to verify the potential role of the specific metabolite identified. RESULTS: Distinct shifts in taxonomic and functional profiles of gut microbiota and their related metabolites were observed in different IA stages. Notably, tryptophan metabolites, particularly indoxyl sulfate (IS), were significantly higher in plasma of RIA. Meanwhile, upregulated tryptophanase expression and indole-producing microbiota were observed in gut microbiome of RIA. A model harnessing gut-microbiome-derived tryptophan metabolites demonstrated remarkable efficacy in distinguishing RIA from UIA patients in the validation cohort (AUC=0.97). Gut microbiota depletion by antibiotics decreased plasma IS concentration, reduced IA formation and rupture in mice, and downregulated matrix metalloproteinase-9 expression in aneurysmal walls with elastin degradation reduction. Supplement of IS reversed the effect of gut microbiota depletion. CONCLUSION: Our investigation highlights the potential of gut-microbiome-derived tryptophan metabolites as biomarkers for distinguishing RIA from UIA patients. The findings suggest a novel pathogenic role for gut-microbiome-derived IS in elastin degradation in the IA wall leading to the rupture of IA.

3.
Front Chem ; 12: 1416329, 2024.
Artigo em Inglês | MEDLINE | ID: mdl-38947956

RESUMO

5-Hydroxymethylfurfural (HMF), serving as a versatile platform compound bridging biomass resource and the fine chemicals industry, holds significant importance in biomass conversion processes. The electrooxidation of HMF plays a crucial role in yielding the valuable product (2,5-furandicarboxylic acid), which finds important applications in antimicrobial agents, pharmaceutical intermediates, polyester synthesis, and so on. Defect engineering stands as one of the most effective strategies for precisely synthesizing electrocatalytic materials, which could tune the electronic structure and coordination environment, and further altering the adsorption energy of HMF intermediate species, consequently increasing the kinetics of HMF electrooxidation. Thereinto, the most routine and effective defect are the anionic vacancies and cationic vacancies. In this concise review, the catalytic reaction mechanism for selective HMF oxidation is first elucidated, with a focus on the synthesis strategies involving both anionic and cationic vacancies. Recent advancements in various catalytic oxidation systems for HMF are summarized and synthesized from this perspective. Finally, the future research prospects for selective HMF oxidation are discussed.

4.
Zhonghua Yi Xue Yi Chuan Xue Za Zhi ; 41(7): 776-782, 2024 Jul 10.
Artigo em Chinês | MEDLINE | ID: mdl-38946357

RESUMO

OBJECTIVE: To retrospectively analyze the clinical characteristics of 193 Chinese patients with McCune-Albright syndrome (MAS). METHODS: By using keywords "McCune-Albright syndrome", "Albright syndrome", or " fibrous dysplasia " as the search terms, 193 cases of MAS reported in China from January 1990 to November 2022 from the Wanfang data, CNKI, VIP, PubMed, and Embase databases were obtained, and their clinical data was retrospectively analyzed. Intergroup comparisons were carried out by using t test, Mann-Whitney U test, and X2 test. RESULTS: The 193 MAS patients had included 42 males and 151 females, with the median first-visit age of females being younger than males. The typical triad group had accounted for 46.1% of patients, and the middle first-visit and diagnosis age was younger than the atypical group. The primary reason for first-visit in males of MAS was fibrous dysplasia (FD), whilst that in females of MAS was peripheral precocious puberty (PPP). FD has occurred in 84.5% of the patients, with an average age of onset age being 6.1 years old, and 90% was ≤ 16 years of age. Endocrine hyperfunction was found in 79.3% of the patients, with a higher proportion in females compared with males (P < 0.05). Pituitary involvement was seen in 21.8% of the patients, and the incidence of craniofacial FD and cranial nerve compression was significantly higher in those with elevated growth hormone (GH) than without (P < 0.05). Café-au-Lait Spots were noted in 86.5% of the patients, and 28.3% (28/99) had located on the different side of FD. CONCLUSION: Most MAS patients had atypical manifestations and multi-systemic involvement. It is more common and occurs earlier in females. The most common reasons for initial diagnosis in male and female patients were FD and PPP, respectively. Patients with elevated GH should be examined for cranial nerve compression.


Assuntos
Displasia Fibrosa Poliostótica , Humanos , Displasia Fibrosa Poliostótica/genética , Masculino , Feminino , Criança , Adolescente , China , Pré-Escolar , Adulto , Estudos Retrospectivos , Adulto Jovem , Lactente , Povo Asiático/genética , Pessoa de Meia-Idade , População do Leste Asiático
5.
Int J Biol Macromol ; 276(Pt 1): 133897, 2024 Jul 15.
Artigo em Inglês | MEDLINE | ID: mdl-39019368

RESUMO

Liquid metal (LM) based electromagnetic interference (EMI) shielding materials with high conductivity and continuous deformation capacity are important needs for meeting modern advanced electronic equipment. However, an independent free-standing film with LM is difficult to achieve due to its unique fluidity properties. Here, a simple alternating filtration film-forming method was utilized to orderly construct a sandwiched EMI shielding film with LM stabilized by bio-based oxhide gelatin (gel) as the intermediate conductive layer, and two films of aramid nanofibers/oxhide gel (ANF/gel) as the external insulating protective layers. This design not only prevents LM from being exposed to environmental conditions, but also reduces the risk of chemical corrosion in practical applications. Under optimal LM addition conditions, the sandwiched film (0.3-3 L) exhibited better EMI shielding performance of 50.4 dB in the X-band than the blended film (0.7 dB), as well as excellent mechanical properties (tensile strength of 65.8 MPa, strain 8.6 %). More importantly, the sandwiched film still maintained reliable EMI shielding performance after being experienced largely physical deformation. This study provides a new solution for preparing LM-based EMI shielding composites, and is expected to arouse pursuit of high EMI shielding effects of bio-based gel while also paying attention to their safety.

6.
J Ethnopharmacol ; 333: 118454, 2024 Oct 28.
Artigo em Inglês | MEDLINE | ID: mdl-38852638

RESUMO

ETHNOPHARMACOLOGICAL RELEVANCE: Minimal persistent inflammation (MPI) is a major contributor to the recurrence of allergic rhinitis (AR). The traditional Chinese herbal medicine known as Bimin Kang Mixture (BMK) have been used in clinics for decades to treat AR, which can relieve AR symptoms, reduce inflammatory response and improve immune function. However, its mechanism in controlling MPI is still unclear. AIM OF THE STUDY: This study aims to assess the therapeutic effect of BMK on MPI, and elaborate the mechanism involved in BMK intervention in BCL11B regulation of type 2 innate lymphoid cell (ILC2) plasticity in the treatment of MPI. MATERIAL AND METHODS: The effect of BMK (9.1 ml/kg) and Loratadine (15.15 mg/kg) on MPI was evaluated based on symptoms, pathological staining, and ELISA assays. RT-qPCR and flow cytometry were also employed to assess the expression of BCL11B, IL-12/IL-12Rß2, and IL-18/IL-18Rα signaling pathways associated with ILC2 plasticity in the airway tissues of MPI mice following BMK intervention. RESULTS: BMK restored the airway epithelial barrier, and markedly reduced inflammatory cells (eosinophils, neutrophils) infiltration (P < 0.01) and goblet cells hyperplasia (P < 0.05). BCL11B expression positively correlated with the ILC2 proportion in the lungs and nasal mucosa of AR and MPI mice (P < 0.01). BMK downregulated BCL11B expression (P < 0.05) and reduced the proportion of ILC2, ILC3 and ILC3-like ILC2 subsets (P < 0.05). Moreover, BMK promoted the conversion of ILC2 into an ILC1-like phenotype through IL-12/IL-12Rß2 and IL-18/IL-18Rα signaling pathways in MPI mice. CONCLUSION: By downregulating BCL11B expression, BMK regulates ILC2 plasticity and decreases the proportion of ILC2, ILC3, and ILC3-like ILC2 subsets, promoting the conversion of ILC2 to ILC1, thus restoring balance of ILC subsets in airway tissues and control MPI.


Assuntos
Medicamentos de Ervas Chinesas , Linfócitos , Rinite Alérgica , Animais , Rinite Alérgica/tratamento farmacológico , Rinite Alérgica/imunologia , Camundongos , Medicamentos de Ervas Chinesas/farmacologia , Medicamentos de Ervas Chinesas/uso terapêutico , Linfócitos/efeitos dos fármacos , Linfócitos/imunologia , Linfócitos/metabolismo , Camundongos Endogâmicos BALB C , Imunidade Inata/efeitos dos fármacos , Inflamação/tratamento farmacológico , Feminino , Masculino , Transdução de Sinais/efeitos dos fármacos , Plasticidade Celular/efeitos dos fármacos , Proteínas Repressoras , Proteínas Supressoras de Tumor
7.
J Stroke Cerebrovasc Dis ; 33(8): 107833, 2024 Jun 24.
Artigo em Inglês | MEDLINE | ID: mdl-38925449

RESUMO

BACKGROUND AND PURPOSE: Flow-diversion treatment for intracranial aneurysms has been associated with the development of in-stent stenosis (ISS) for unclear reasons. We assess whether the size of the stent relative to that of the vessel (the stent-to-vessel diameter ratio, or SVR) may be predictive of the development of ISS after treatment with flow diverters. METHODS: We retrospectively reviewed patients with unruptured intracranial aneurysms who underwent flow-diversion treatment using either the Pipeline or Tubridge embolization device from September 2018 to September 2022. The relationship between SVR and ISS was analyzed. Multiple logistic regression models were used to determine the significant predictors. RESULTS: A total of 458 patients with 481 aneurysms were included. In a mean angiographic follow-up of 10.73 ± 3.97 months, ISS was detected in 68 cases (14.1 %). After adjusting for candidate variables, a higher distal SVR (DSVR) was associated with an increased risk of ISS (adjusted odds ratio [aOR] = 3.420, 95 % confidence interval [CI] = 1.182 - 9.889, p = 0.023). We conducted a subgroup analysis of the two different flow diverters to assess the effects of their individual characteristics. Our results showed a significant association between the DSVR and the incidence of ISS in both the Pipeline (aOR = 4.033, 95 % CI = 1.156-14.072, p = 0.029) and Tubridge groups (aOR = 11.981, 95 % CI=1.005-142.774, p = 0.049). CONCLUSION: A higher DSVR was associated with an increased risk of ISS. This may help neurointerventionalists select an appropriate stent size when conducting flow-diversion treatment for intracranial aneurysms.

8.
Plant J ; 2024 Jun 12.
Artigo em Inglês | MEDLINE | ID: mdl-38865101

RESUMO

Anthocyanin is an important pigment responsible for plant coloration and beneficial to human health. Kale (Brassica oleracea var. acephala), a primary cool-season flowers and vegetables, is an ideal material to study anthocyanin biosynthesis and regulation mechanisms due to its anthocyanin-rich leaves. However, the underlying molecular mechanism of anthocyanin accumulation in kale remains poorly understood. Previously, we demonstrated that BoDFR1 is a key gene controlling anthocyanin biosynthesis in kale. Here, we discovered a 369-bp InDel variation in the BoDFR1 promoter between the two kale inbred lines with different pink coloration, which resulted in reduced transcriptional activity of the BoDFR1 gene in the light-pink line. With the 369-bp insertion as a bait, an R2R3-MYB repressor BoMYB4b was identified using the yeast one-hybrid screening. Knockdown of the BoMYB4b gene led to increased BoDFR1 expression and anthocyanin accumulation. An E3 ubiquitin ligase, BoMIEL1, was found to mediate the degradation of BoMYB4b, thereby promoting anthocyanin biosynthesis. Furthermore, the expression level of BoMYB4b was significantly reduced by light signals, which was attributed to the direct repression of the light-signaling factor BoMYB1R1 on the BoMYB4b promoter. Our study revealed that a novel regulatory module comprising BoMYB1R1, BoMIEL1, BoMYB4b, and BoDFR1 finely regulates anthocyanin accumulation in kale. The findings aim to establish a scientific foundation for genetic improvement of leaf color traits in kale, meanwhile, providing a reference for plant coloration studies.

9.
Huan Jing Ke Xue ; 45(6): 3389-3401, 2024 Jun 08.
Artigo em Chinês | MEDLINE | ID: mdl-38897760

RESUMO

Clarifying the mechanism of influence of urban form on carbon emissions is an important prerequisite for achieving urban carbon emission reduction. Taking the Yangtze River Economic Belt as an example, this study elaborated on the general mechanism of urban form on carbon emissions, used multi-source data to quantitatively evaluate the urban form, and explored the impacts of urban form indicators on carbon emissions from 2005 to 2020 at global and sub-regional scales with the help of spatial econometric models and geodetector, respectively. The results showed that:① The carbon emissions of the Yangtze River Economic Belt increased from 2 365.31 Mt to 4 230.67 Mt, but the growth rate gradually decreased. Its spatial distribution pattern was bipolar, with high-value areas mainly distributed in core cities such as Shanghai and Chongqing and low-value areas concentrated in the western regions of Sichuan and Yunnan. ② The area of construction land in the study area expanded over the past 15 years, but the population density of construction land had been decreasing. The degree of urban fragmentation was decreasing, and the difference between cities was also progressively narrowing. The average regularity of urban shape improved, and the compactness increased significantly. ③ All indicators of urban scale had significant positive effects on carbon emissions at the global scale, urban fragmentation had a significant negative effect in 2005, and the effective mesh size (MESH) indicator of urban compactness showed a significant negative correlation with carbon emissions in the study period. ④ Total class area, patch density, and effective mesh size had the most significant impacts on carbon emissions in upstream cities. Effective mesh size, mean perimeter-area ratio, and total class area had higher influences in midstream cities. Effective mesh size, percentage of like adjacencies, and largest patch index were the key factors to promote carbon reduction in downstream cities. Cities in different regions should comprehensively consider the impacts of various urban form indicators on carbon emissions and then optimize their urban form to promote sustainable development.

11.
Nat Commun ; 15(1): 4995, 2024 Jun 11.
Artigo em Inglês | MEDLINE | ID: mdl-38862474

RESUMO

RNF214 is an understudied ubiquitin ligase with little knowledge of its biological functions or protein substrates. Here we show that the TEAD transcription factors in the Hippo pathway are substrates of RNF214. RNF214 induces non-proteolytic ubiquitylation at a conserved lysine residue of TEADs, enhances interactions between TEADs and YAP, and promotes transactivation of the downstream genes of the Hippo signaling. Moreover, YAP and TAZ could bind polyubiquitin chains, implying the underlying mechanisms by which RNF214 regulates the Hippo pathway. Furthermore, RNF214 is overexpressed in hepatocellular carcinoma (HCC) and inversely correlates with differentiation status and patient survival. Consistently, RNF214 promotes tumor cell proliferation, migration, and invasion, and HCC tumorigenesis in mice. Collectively, our data reveal RNF214 as a critical component in the Hippo pathway by forming a signaling axis of RNF214-TEAD-YAP and suggest that RNF214 is an oncogene of HCC and could be a potential drug target of HCC therapy.


Assuntos
Carcinoma Hepatocelular , Proliferação de Células , Proteínas de Ligação a DNA , Neoplasias Hepáticas , Transdução de Sinais , Fatores de Transcrição de Domínio TEA , Fatores de Transcrição , Ubiquitinação , Proteínas de Sinalização YAP , Carcinoma Hepatocelular/metabolismo , Carcinoma Hepatocelular/genética , Carcinoma Hepatocelular/patologia , Neoplasias Hepáticas/metabolismo , Neoplasias Hepáticas/patologia , Neoplasias Hepáticas/genética , Humanos , Animais , Fatores de Transcrição/metabolismo , Fatores de Transcrição/genética , Camundongos , Proteínas de Ligação a DNA/metabolismo , Proteínas de Ligação a DNA/genética , Proteínas de Sinalização YAP/metabolismo , Linhagem Celular Tumoral , Fatores de Transcrição de Domínio TEA/metabolismo , Proteínas Adaptadoras de Transdução de Sinal/metabolismo , Proteínas Adaptadoras de Transdução de Sinal/genética , Progressão da Doença , Camundongos Nus , Movimento Celular/genética , Masculino , Regulação Neoplásica da Expressão Gênica , Via de Sinalização Hippo , Células HEK293 , Ubiquitina-Proteína Ligases/metabolismo , Ubiquitina-Proteína Ligases/genética , Feminino , Proteínas Nucleares/metabolismo , Proteínas Nucleares/genética
12.
Int J Biol Macromol ; 273(Pt 2): 133082, 2024 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-38878923

RESUMO

The Shark-derived immunoglobulin new antigen receptors (IgNARs) have gained increasing attention for their high solubility, exceptional thermal stability, and intricate sequence variation. In this study, we immunized whitespotted bamboo shark (Chiloscyllium plagiosum) to create phage display library of variable domains of IgNAR (VNARs) for screening against Human Serum Albumin (HSA), a versatile vehicle in circulation due to its long in vivo half-life. We identified two HSA-binding VNAR clones, 2G5 and 2G6, and enhanced their expression in E. coli with the FKPA chaperone. 2G6 exhibited a strong binding affinity of 13 nM with HSA and an EC50 of 1 nM. In vivo study with a murine model further provided initial validation of 2G6's ability to prolong circulation time by binding to HSA. Additionally, we employed computational molecular docking to predict the binding affinities of both 2G6 and its humanized derivative, H2G6, to HSA. Our analysis unveiled that the complementarity-determining regions (CDR1 and CDR3) are pivotal in the antigen recognition process. Therefore, our study has advanced the understanding of the potential applications of VNARs in biomedical research aimed at extending drug half-life, holding promise for future therapeutic and diagnostic progressions.


Assuntos
Simulação de Acoplamento Molecular , Albumina Sérica Humana , Tubarões , Animais , Humanos , Albumina Sérica Humana/química , Albumina Sérica Humana/metabolismo , Camundongos , Receptores de Antígenos/química , Receptores de Antígenos/genética , Receptores de Antígenos/metabolismo , Ligação Proteica , Biblioteca de Peptídeos , Sequência de Aminoácidos
13.
Nano Lett ; 24(27): 8427-8435, 2024 Jul 10.
Artigo em Inglês | MEDLINE | ID: mdl-38920280

RESUMO

Metal selenides show outstanding sodium-ion storage performance when matched with an ether-based electrolyte. However, the intrinsic origin of improvement and deterministic interface characteristics have not been systematically elucidated. Herein, employing FeSe2 anode as the model system, the electrochemical kinetics of metal selenides in ether and ester-based electrolytes and associated solid electrolyte interphase (SEI) are investigated in detail. Based on the galvanostatic intermittent titration technique and in situ electrochemical impedance spectroscopy, it is found that the ether-based electrolyte can ensure fast Na+ transfer and low interface impedance. Additionally, the ether-derived thin and smooth double-layer SEI, which is critical in facilitating ion transport, maintaining structural stability, and inhibiting electrolyte overdecomposition, is concretely visualized by transmission electron microscopy, atomic force microscopy, and depth-profiling X-ray photoelectron spectroscopy. This work provides a deep understanding of the optimization mechanism of electrolytes, which can guide available inspiration for the design of practical electrode materials.

14.
Drug Des Devel Ther ; 18: 2287-2297, 2024.
Artigo em Inglês | MEDLINE | ID: mdl-38915869

RESUMO

Objective: Catalpol, as a natural medicine small-molecule drug, has been proven to have anti-inflammatory and antioxidant pharmacological effects. Methods: The effect of catalpol on oxidative damage of mouse epidermal fibroblast L929 model and its mechanism were investigated by using hydrogen peroxide model, CCK8 method, flow cytometry, and Western blot. Results: The effect of catalpol on Nrf2/HO-1 signaling pathway was further studied to improve oxidative stress in cell models. The results showed that catalpol had no cytotoxicity to L929 cells, and inhibited the apoptosis of L929 cells after oxidative damage in a concentration-dependent manner, thus playing a role in cell protection. The oxidative damage of cells was inhibited by up-regulating the expression of the signature protein of Nrf2/HO-1 signaling pathway and inhibiting the interstitial formation of cells. Conclusion: This study is a preliminary study on the protective function of catalpol against oxidation and apoptosis in dermal fibroblasts, which can provide a theoretical basis and drug guidance for promoting skin wound healing in the later stage.


Assuntos
Fibroblastos , Heme Oxigenase-1 , Glucosídeos Iridoides , Fator 2 Relacionado a NF-E2 , Estresse Oxidativo , Transdução de Sinais , Glucosídeos Iridoides/farmacologia , Fator 2 Relacionado a NF-E2/metabolismo , Fibroblastos/efeitos dos fármacos , Fibroblastos/metabolismo , Estresse Oxidativo/efeitos dos fármacos , Animais , Camundongos , Transdução de Sinais/efeitos dos fármacos , Heme Oxigenase-1/metabolismo , Relação Dose-Resposta a Droga , Apoptose/efeitos dos fármacos , Células Cultivadas , Peróxido de Hidrogênio/farmacologia , Peróxido de Hidrogênio/antagonistas & inibidores , Antioxidantes/farmacologia , Pele/efeitos dos fármacos , Pele/metabolismo , Pele/patologia , Relação Estrutura-Atividade , Linhagem Celular , Proteínas de Membrana
15.
Curr Microbiol ; 81(8): 243, 2024 Jun 27.
Artigo em Inglês | MEDLINE | ID: mdl-38935166

RESUMO

Clostridium perfringens is one of the critical causative agents causing diarrhea in piglets, with significant economic losses to the pig industry. Under normal gut microbiota homeostasis and well-managed barns, diarrhea caused by C. perfringens could be controlled. Some reports show that probiotics, such as Bacillus subtilis, are beneficial in preventing necrotic enteritis (NE) in chickens, but few reports on piglets. Clostridium perfringens was found in the piglets' diarrhea with intestinal microbiota dysbiosis in our survey. Bacillus subtilis G2B9-Q, which was isolated from the feces of healthy pigs, was found to have anti-Clostridium activity after screening. Clostridium perfringens was used to challenge mice by intraperitoneal injection for modeling to evaluate the anti-infective activity of cell-free supernatant (CFS) of B. subtilis G2B9-Q and different concentrations of B. subtilis G2B9-Q by oral administration. The results showed that G2B9-Q can mitigate intestinal lesions caused by C. perfringens infection, reduce inflammatory reactions, and modulate intestinal microbiota. The CFS of G2B9-Q can alleviate the pathological damage of intestinal tissues caused by C. perfringens infection, reduce the concentration of TNF-α and IL-10 in the sera of mice, as well as the relative expression levels of alpha toxin (CPA), perfringolysin O (PFO) toxin, IL-10, IL-22, and TNF-α in the jejunum and colon tissues, and alleviate the changes in gut microbiota structure caused by C. perfringens infection, which showed better therapeutic effects and indicated that the metabolites of G2B9-Q are essential mediators for their beneficial effects. Therefore, the CFS of G2B9-Q could potentially replace antibiotics in treating C. perfringens infection.


Assuntos
Bacillus subtilis , Infecções por Clostridium , Clostridium perfringens , Microbioma Gastrointestinal , Probióticos , Animais , Infecções por Clostridium/imunologia , Infecções por Clostridium/microbiologia , Bacillus subtilis/genética , Clostridium perfringens/imunologia , Camundongos , Probióticos/administração & dosagem , Microbioma Gastrointestinal/efeitos dos fármacos , Intestinos/microbiologia , Intestinos/imunologia , Suínos , Diarreia/microbiologia , Diarreia/imunologia , Fezes/microbiologia , Modelos Animais de Doenças
16.
Cell Death Dis ; 15(6): 400, 2024 Jun 07.
Artigo em Inglês | MEDLINE | ID: mdl-38849380

RESUMO

Emerging evidence demonstrates that pyroptosis has been implicated in the pathogenesis of asthma. Gasdermin D (GSDMD) is the pyroptosis executioner. The mechanism of GSDMD in asthma remains unclear. The aim of this study was to elucidate the potential role of GSDMD in asthmatic airway inflammation and remodeling. Immunofluorescence staining was conducted on airway epithelial tissues obtained from both asthma patients and healthy controls (HCs) to evaluate the expression level of N-GSDMD. ELISA was used to measure concentrations of cytokines (IL-1ß, IL-18, IL-17A, and IL-10) in serum samples collected from asthma patients and healthy individuals. We demonstrated that N-GSDMD, IL-18, and IL-1ß were significantly increased in samples with mild asthma compared with those from the controls. Then, wild type and Gsdmd-knockout (Gsdmd-/-) mice were used to establish asthma model. We performed histopathological staining, ELISA, and flow cytometry to explore the function of GSDMD in allergic airway inflammation and tissue remodeling in vivo. We observed that the expression of N-GSDMD, IL-18, and IL-1ß was enhanced in OVA-induced asthma mouse model. Gsdmd knockout resulted in attenuated IL-18, and IL-1ß production in both bronchoalveolar lavage fluid (BALF) and lung tissue in asthmatic mice. In addition, Gsdmd-/- mice exhibit a significant reduction in airway inflammation and remodeling, which might be associated with reduced Th17 inflammatory response and M2 polarization of macrophages. Further, we found that GSDMD knockout may improve asthmatic airway inflammation and remodeling through regulating macrophage adhesion, migration, and macrophage M2 polarization by targeting Notch signaling pathway. These findings demonstrate that GSDMD deficiency profoundly alleviates allergic inflammation and tissue remodeling. Therefore, GSDMD may serve as a potential therapeutic target against asthma.


Assuntos
Asma , Modelos Animais de Doenças , Peptídeos e Proteínas de Sinalização Intracelular , Camundongos Knockout , Ovalbumina , Proteínas de Ligação a Fosfato , Animais , Asma/genética , Asma/patologia , Asma/metabolismo , Proteínas de Ligação a Fosfato/metabolismo , Proteínas de Ligação a Fosfato/genética , Camundongos , Peptídeos e Proteínas de Sinalização Intracelular/metabolismo , Peptídeos e Proteínas de Sinalização Intracelular/genética , Humanos , Remodelação das Vias Aéreas , Feminino , Inflamação/patologia , Inflamação/metabolismo , Inflamação/genética , Camundongos Endogâmicos C57BL , Masculino , Citocinas/metabolismo , Piroptose , Pulmão/patologia , Pulmão/metabolismo , Gasderminas
17.
Expert Opin Drug Saf ; : 1-7, 2024 May 22.
Artigo em Inglês | MEDLINE | ID: mdl-38778546

RESUMO

BACKGROUND: Potentially inappropriate medication (PIM) use is a common problem among older patients. This study aimed to compare the prevalence of PIMs in older patients with newly diagnosed non-small cell lung cancer (NSCLC), and to identify the correlates of PIMs. RESEARCH DESIGN AND METHODS: A secondary analysis of a prospective cohort study was conducted. Patients were enrolled from January 2014 to December 2020 and information were extracted from patients' electronic medical records (EMRs). We evaluated the PIMs using four different PIM criteria. The concordance among the four PIM criteria was calculated using kappa tests. The possible risk factors associated with PIMs were analyzed by multivariate logistic regression. RESULTS: The prevalence of at least one PIM identified by the four criteria ranged from 25.1% to 48.2% among 514 patients. There was moderate consistency between the GO-PIM scale and the AGS/Beers criteria, while poor consistency with the other criteria (the STOPP criteria and the Chinese criteria). Polypharmacy was found to be significantly associated with the occurrence of PIMs in all criteria (p < 0.001). CONCLUSIONS: Our results showed a high prevalence of PIMs in older patients with NSCLC, which was significantly associated with polypharmacy, and the consistency across the four criteria was poor-to-moderate.

18.
Cell Regen ; 13(1): 11, 2024 May 23.
Artigo em Inglês | MEDLINE | ID: mdl-38780677

RESUMO

The family of secreted dimeric proteins known as the Transforming Growth Factor-ß (TGF-ß) family plays a critical role in facilitating intercellular communication within multicellular animals. A recent symposium on TGF-ß Biology - Signaling, Development, and Diseases, held on December 19-21, 2023, in Hangzhou, China, showcased some latest advances in our understanding TGF-ß biology and also served as an important forum for scientific collaboration and exchange of ideas. More than twenty presentations and discussions at the symposium delved into the intricate mechanisms of TGF-ß superfamily signaling pathways, their roles in normal development and immunity, and the pathological conditions associated with pathway dysregulation.

19.
United European Gastroenterol J ; 12(6): 772-779, 2024 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-38753528

RESUMO

OBJECTIVES: Detection of early neoplastic lesions is crucial for improving the survival rates of patients with gastric cancer. Optical enhancement mode 2 is a new image-enhanced endoscopic technique that offers bright images and can improve the visibility of neoplastic lesions. This study aimed to compare the detection of neoplastic lesions with optical enhancement mode 2 and white-light imaging (WLI) in a high-risk population. METHODS: In this prospective multicenter randomized controlled trial, patients were randomly assigned to optical enhancement mode 2 or WLI groups. Detection of suspicious neoplastic lesions during the examinations was recorded, and pathological diagnoses served as the gold standard. RESULTS: A total of 1211 and 1219 individuals were included in the optical enhancement mode 2 and WLI groups, respectively. The detection rate of neoplastic lesions was significantly higher in the optical enhancement mode 2 group (5.1% vs. 1.9%; risk ratio, 2.656 [95% confidence interval, 1.630-4.330]; p < 0.001). The detection rate of neoplastic lesions with an atrophic gastritis background was significantly higher in the optical enhancement mode 2 group (8.6% vs. 2.6%, p < 0.001). The optical enhancement mode 2 group also had a higher detection rate among endoscopists with different experiences. CONCLUSIONS: Optical enhancement mode 2 was more effective than WLI for detecting neoplastic lesions in the stomach, and can serve as a new method for screening early gastric cancer in clinical practice. CLINICAL REGISTRY: United States National Library of Medicine (https://www. CLINICALTRIALS: gov), ID: NCT040720521.


Assuntos
Detecção Precoce de Câncer , Gastroscopia , Aumento da Imagem , Neoplasias Gástricas , Humanos , Neoplasias Gástricas/diagnóstico por imagem , Neoplasias Gástricas/patologia , Neoplasias Gástricas/diagnóstico , Masculino , Feminino , Pessoa de Meia-Idade , Estudos Prospectivos , Gastroscopia/métodos , Detecção Precoce de Câncer/métodos , Idoso , Aumento da Imagem/métodos , Gastrite Atrófica/diagnóstico , Gastrite Atrófica/patologia , Gastrite Atrófica/diagnóstico por imagem , Adulto
20.
Spectrochim Acta A Mol Biomol Spectrosc ; 318: 124436, 2024 Oct 05.
Artigo em Inglês | MEDLINE | ID: mdl-38776667

RESUMO

In this work, we propose a Multi-dot Ensemble Regression AI detector (MER) based on the Lambert-Beer law. We pre-trained a model using the infrared spectral data of target additives collected in advance to detect the target additives in unknown oil samples. The algorithm's feasibility was validated by assessing the content of additives in a series of simulated commercial oil samples that were not part of the training set. We established models for three common lubricating oil additives (anti-friction, anti-wear, and antioxidant agents), demonstrating their effectiveness in oil sample detection. Additionally, by comparing with other algorithms, we established the superiority of MER in small-sample learning scenarios.

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