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1.
EMBO J ; 41(22): e111038, 2022 11 17.
Artigo em Inglês | MEDLINE | ID: mdl-36215698

RESUMO

Impaired clearance of beta-amyloid (Aß) is a primary cause of sporadic Alzheimer's disease (AD). Aß clearance in the periphery contributes to reducing brain Aß levels and preventing Alzheimer's disease pathogenesis. We show here that erythropoietin (EPO) increases phagocytic activity, levels of Aß-degrading enzymes, and Aß clearance in peripheral macrophages via PPARγ. Erythropoietin is also shown to suppress Aß-induced inflammatory responses. Deletion of EPO receptor in peripheral macrophages leads to increased peripheral and brain Aß levels and exacerbates Alzheimer's-associated brain pathologies and behavioral deficits in AD-model mice. Moreover, erythropoietin signaling is impaired in peripheral macrophages of old AD-model mice. Exogenous erythropoietin normalizes impaired EPO signaling and dysregulated functions of peripheral macrophages in old AD-model mice, promotes systemic Aß clearance, and alleviates disease progression. Erythropoietin treatment may represent a potential therapeutic approach for Alzheimer's disease.


Assuntos
Doença de Alzheimer , Eritropoetina , Animais , Camundongos , Doença de Alzheimer/patologia , Peptídeos beta-Amiloides/metabolismo , Eritropoetina/farmacologia , Eritropoetina/uso terapêutico , Encéfalo/metabolismo , Macrófagos/metabolismo , Camundongos Transgênicos , Modelos Animais de Doenças
2.
Microb Cell Fact ; 23(1): 33, 2024 Jan 24.
Artigo em Inglês | MEDLINE | ID: mdl-38267983

RESUMO

Growing evidence has demonstrated that cold and humid environmental stress triggers gastrointestinal (GI) disorders. In this study, we explored the effects of intestinal microbiota homeostasis on the intestinal mucus barrier and GI disorders by cold and humid environmental stress. Moreover, the inner link between the intestinal mucosal microbiota and metabolites in mice with cold and humid environmental stress was interpreted by integrative analysis of PacBio HiFi sequencing microbial genomics and targeted metabolomics. In the current study, we found (1) after the cold and wet cold and humid environmental stress intervened in the intestinal microbiota disorder and homeostasis mice respectively, the bacterial culturing and fluorescein diacetate (FDA) microbial activity detection of intestinal microbiota including feces, intestinal contents, and intestinal mucosa suggested that the cold and humid environmental stress decreased the colony of culturable bacteria and microbial activity, in which intestinal microbiota disorder aggravated the injury of the intestinal mucus barrier and the GI symptoms related to cold and humid environmental stress; (2) the serum amino acid transferases such as glutamate pyruvic transa (GPT), and glutamic oxaloacetic transaminase (GOT) in cold and humid environmental stressed mice increased significantly, indicating that the intestinal microbiota adapted to cold and humid environmental stress by regulating the host's amino acid metabolism; (3) the integrative analysis of multi-omics illustrated a prediction model based on the microbiota Lactobacillus reuteri abundance and host amino acid level that can predict intestinal mucoprotein Muc2 with an adjusted R2 of 75.0%. In conclusion, the cold and humid environmental stress regulates the neurotransmitter amino acids metabolic function both in intestinal mucosal microbiota and host serum by adjusting the composition of the dominant bacterial population Lactobacillus reuteri, which contributes to the intestinal mucus barrier injury and GI disorders caused by cold and humid environmental stress.


Assuntos
Microbioma Gastrointestinal , Microbiota , Animais , Camundongos , Mucosa Intestinal , Homeostase , Aminoácidos
3.
BMC Nurs ; 23(1): 431, 2024 Jun 25.
Artigo em Inglês | MEDLINE | ID: mdl-38918784

RESUMO

OBJECTIVE: To explore the perception of good death of patients with end-stage cancer by nurses in the oncology department. METHOD: In the study we used a phenomenological approach and semi-structured interviews. A total of 11 nurses from the oncology department of a Grade A hospital in Taizhou were interviewed on the cognition of good death from July 1 to September 30, 2022. Colaizzi's analysis method was used to analyse the interview data. This study followed the consolidated criteria for reporting qualitative research (COREQ). RESULT: Four themes were identified: a strong sense of responsibility and mission; To sustain hope and faith; The important role of family members; Improve patients' quality of life. CONCLUSION: The nurses in the department of oncology have a low level of knowledge about the "good death", and the correct understanding and view of the "good death" is the premise of the realization of " good death". The ability of nursing staff to improve the "good death", attention, and meet the needs and wishes of individuals and families, is the guarantee of the realization of "good death".

4.
Am J Respir Crit Care Med ; 206(12): 1495-1507, 2022 12 15.
Artigo em Inglês | MEDLINE | ID: mdl-35876129

RESUMO

Rationale: It remains unclear how gastroesophageal reflux disease (GERD) affects allograft microbial community composition in lung transplant recipients and its impact on lung allograft inflammation and function. Objectives: Our objective was to compare the allograft microbiota in lung transplant recipients with or without clinically diagnosed GERD in the first year after transplant and assess associations between GERD, allograft microbiota, inflammation, and acute and chronic lung allograft dysfunction (ALAD and CLAD). Methods: A total of 268 BAL samples were collected from 75 lung transplant recipients at a single transplant center every 3 months after transplant for 1 year. Ten transplant recipients from a separate transplant center provided samples before and after antireflux Nissen fundoplication surgery. Microbial community composition and density were measured using 16S ribosomal RNA gene sequencing and quantitative polymerase chain reaction, respectively, and inflammatory markers and bile acids were quantified. Measurements and Main Results: We observed a range of allograft community composition with three discernible types (labeled community state types [CSTs] 1-3). Transplant recipients with GERD were more likely to have CST1, characterized by high bacterial density and relative abundance of the oropharyngeal colonizing genera Prevotella and Veillonella. GERD was associated with more frequent transitions to CST1. CST1 was associated with lower inflammatory cytokine concentrations than pathogen-dominated CST3 across the range of microbial densities observed. Cox proportional hazard models revealed associations between CST3 and the development of ALAD/CLAD. Nissen fundoplication decreased bacterial load and proinflammatory cytokines. Conclusions: GERD was associated with a high bacterial density, Prevotella- and Veillonella-dominated CST1. CST3, but not CST1 or GERD, was associated with inflammation and early development of ALAD and CLAD. Nissen fundoplication was associated with a reduction in microbial density in BAL fluid samples, especially the CST1-specific genus, Prevotella.


Assuntos
Refluxo Gastroesofágico , Transplante de Pulmão , Microbiota , Humanos , Estudos Retrospectivos , Refluxo Gastroesofágico/complicações , Pulmão , Inflamação , Aloenxertos
5.
Respir Res ; 23(1): 219, 2022 Aug 26.
Artigo em Inglês | MEDLINE | ID: mdl-36028826

RESUMO

BACKGROUND: Bronchoalveolar lavage (BAL) is a key tool in respiratory medicine for sampling the distal airways. BAL bile acids are putative biomarkers of pulmonary microaspiration, which is associated with poor outcomes after lung transplantation. Compared to BAL, large airway bronchial wash (LABW) samples the tracheobronchial space where bile acids may be measurable at more clinically relevant levels. We assessed whether LABW bile acids, compared to BAL bile acids, are more strongly associated with poor clinical outcomes in lung transplant recipients. METHODS: Concurrently obtained BAL and LABW at 3 months post-transplant from a retrospective cohort of 61 lung transplant recipients were analyzed for taurocholic acid (TCA), glycocholic acid (GCA), and cholic acid by mass spectrometry and 10 inflammatory proteins by multiplex immunoassay. Associations between bile acids with inflammatory proteins and acute lung allograft dysfunction were assessed using Spearman correlation and logistic regression, respectively. Time to chronic lung allograft dysfunction and death were evaluated using multivariable Cox proportional hazards and Kaplan-Meier methods. RESULTS: Most bile acids and inflammatory proteins were higher in LABW than in BAL. LABW bile acids correlated with inflammatory proteins within and between sample type. LABW TCA and GCA were associated with acute lung allograft dysfunction (OR = 1.368; 95%CI = 1.036-1.806; P = 0.027, OR = 1.064; 95%CI = 1.009-1.122; P = 0.022, respectively). No bile acids were associated with chronic lung allograft dysfunction. Adjusted for risk factors, LABW TCA and GCA predicted death (HR = 1.513; 95%CI = 1.014-2.256; P = 0.042, HR = 1.597; 95%CI = 1.078-2.366; P = 0.020, respectively). Patients with LABW TCA in the highest tertile had worse survival compared to all others. CONCLUSIONS: LABW bile acids are more strongly associated than BAL bile acids with inflammation, acute lung allograft dysfunction, and death in lung transplant recipients. Collection of LABW may be useful in the evaluation of microaspiration in lung transplantation and other respiratory diseases.


Assuntos
Transplante de Pulmão , Transplantados , Ácidos e Sais Biliares , Biomarcadores , Lavagem Broncoalveolar , Líquido da Lavagem Broncoalveolar , Estudos de Coortes , Humanos , Pulmão , Estudos Retrospectivos
6.
Langmuir ; 36(6): 1523-1529, 2020 Feb 18.
Artigo em Inglês | MEDLINE | ID: mdl-31995982

RESUMO

Hollow nanostructures of metal sulfides have gained tremendous attention in catalysis, biomedicine, and energy storage and conversion owing to their intriguing structural features and fascinating physicochemical properties. Here, we reported a hard template-engaged cation exchange method to fabricate a family of binary or ternary metal sulfide (CuS, Ag2S, Bi2S3, CuxBi1-xS, ZnxCo1-xS, ZnxCd1-xS, ZnxNi1-xS, and ZnxMn1-xS) hollow microspheres via adjusting the reaction kinetic parameters including solvent and temperature in the presence of unique ZnS composite microspheres. Particularly, the shell layer thickness of metal sulfide hollow microspheres could be modulated by manipulating the reaction temperature during the cation exchanging procedure. Meanwhile, the desired elementary composition of ternary metal sulfide hollow microspheres could be achieved by varying the mole ratio and species of the metal source. This synthetic strategy could be extended to rationally design and construct other metal sulfide hollow nanostructures and provide a deep insight into the nucleation and growth process of the metal sulfide hollow microspheres with well-controlled composition and microstructures.

7.
Chem Rec ; 20(8): 882-892, 2020 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-32319734

RESUMO

In this mini-review, we highlighted the recent progresses in the controlled synthesis of metal sulfides hollow nanostructures via hard template technique. After a brief introduction about the formation mechanism of the inorganic hollow nanostructures via hard template technique, the discussions primarily focused on the emerging development of metal sulfides hollow nanostructures. Various synthetic strategies were summarized concerning the use of the hard template engaged strategies to fabricate various metal sulfides hollow nanostructures, such as hydrothermal method, solvothermal method, ion-exchange, sulfidation or calcination etc. Finally, the perspectives and summaries have been presented to demonstrate that a facile synthetic technique would be widely used to fabricate metal sulfides hollow nanostructures with multi-shells and components.

8.
Nanotechnology ; 31(46): 465102, 2020 Nov 13.
Artigo em Inglês | MEDLINE | ID: mdl-32857735

RESUMO

The biological effects of nanoparticles are of great importance for the in-depth understanding of safety issues in biomedical applications. Induction of autophagy is a cellular response after nanoparticle exposure. Bismuth sulfide nanoparticles (Bi2S3 NPs) are often used as a CT contrast agent because of their excellent photoelectric conversion ability. Yet there has been no previous detailed study other than a cell toxicity assessment. In this study, three types of Bi2S3 NPs with different shapes (Bi2S3 nano rods (BSNR), hollow microsphere Bi2S3 NPs (BSHS) and urchin-like hollow microsphere Bi2S3 NPs (ULBSHS)) were used to evaluatecytotoxicity, autophagy induction, cell migration and invasion in human hepatocellular carcinoma cells (HepG2). Results showed that all three Bi2S3 NPs lead to blockage in autophagic flux, causing p62 protein accumulation. The cell death caused by these Bi2S3 NPs is proved to be autophagy related, rather than related to apoptosis. Moreover, Bi2S3 NPs can reduce the migration and invasion in HepG2 cells in an autophagy-dependent manner. ULBSHS is the most cytotoxic among three Bi2S3 NPs and has the best tumor metastasis suppression. These results demonstrated that, even with relatively low toxicity of Bi2S3 NPs, autophagy blockage may still substantially influence cell fate and thus significantly impact their biomedical applications, and that surface topography is a key factor regulating their biological response.


Assuntos
Autofagia/efeitos dos fármacos , Bismuto/efeitos adversos , Movimento Celular/efeitos dos fármacos , Citotoxinas/efeitos adversos , Nanopartículas/efeitos adversos , Sulfetos/efeitos adversos , Bismuto/química , Bismuto/toxicidade , Citotoxinas/química , Citotoxinas/toxicidade , Células Hep G2 , Humanos , Nanopartículas/química , Nanopartículas/toxicidade , Sulfetos/química , Sulfetos/toxicidade
9.
Zhongguo Zhong Yao Za Zhi ; 45(11): 2595-2600, 2020 Jun.
Artigo em Chinês | MEDLINE | ID: mdl-32627494

RESUMO

Diabetic kidney disease(DKD) has become a primary cause of end-stage kidney disease, without any effective treatment available. In this study, we assessed the protective effect of Guanxin Danshen Formulation(GXDSF) on diabetic nephropathy in db/db mice. The db/m and db/db mice were randomly divided into 4 groups: control group, model group, metformin group, and GXDSF group. After 8 weeks' treatment with GXDSF, metformin or normal saline, the mice were sacrificed, and the blood and kidney tissues were collected for the further analysis. Compared with the model group, TG, TCH and LDL levels significantly decreased in the GXDSF group. The results from HE and PAS staining showed that db/db mice exhibited abnormal kidney tissues with increased glomerular volume, basement-membrane thickening and mesangial cell proliferation, which could be significantly alleviated by GXDSF treatment. GXDSF treatment also reduced serum creatinine and BUN. Meanwhile, GXDSF treatment markedly elevated GSH-PX levels, while reduced LDH and MDA levels in the kidney tissues. Western blot assay showed that GXDSF evidently up-regulated protein levels of ERα and p-Akt, and subsequently promoted HO-1 expression mediated by Nrf2. These data collectively indicated that GXDSF protects db/db mice against DN by regulating ERα and Nrf2-mediated HO-1 expression.


Assuntos
Diabetes Mellitus , Nefropatias Diabéticas , Salvia miltiorrhiza , Animais , Creatinina , Rim , Glomérulos Renais , Camundongos , Fator 2 Relacionado a NF-E2
10.
Langmuir ; 35(2): 489-494, 2019 01 15.
Artigo em Inglês | MEDLINE | ID: mdl-30561206

RESUMO

Monodisperse sub-10 nm core-shell nanocrystals have been extensively studied owing to their important applications in catalysis, bioimaging, nanomedicine, and so on. In this work, an amorphous shell component crystallization strategy has been proposed to prepare high quality sub-10 nm NaYF4:Yb/Er@NaGdF4 core-shell nanocrystals successfully via a sequential growth process. The dynamic light scattering technique has been used to investigate the secondary nucleation and growth process forming the core-shell nanocrystals. The size and morphology evolution of the core-shell nanocrystals reveals that the secondary nucleation of the shell component is unavoidable after hot-injecting the shell precursor at high temperatures, which was followed by dissolution and recrystallization (an Ostwald ripening process) to partially produce the core-shell nanocrystals. The present study demonstrates that the size of seed nanocrystals and the injection temperature of the shell component precursor play a vital role in the formation of core-shell nanostructures completely. This work will provide an alternative strategy for precisely controlling the fabrication of sub-10 nm core-shell nanostructures for various applications.

11.
Langmuir ; 34(31): 9264-9271, 2018 08 07.
Artigo em Inglês | MEDLINE | ID: mdl-30005165

RESUMO

Magnetically recyclable photocatalyst has drawn considerable research interest because of its importance in practical applications. Herein, we demonstrate a facile hydrothermal process to fabricate magnetic core-shell microspheres of Fe3O4@Zn xCd1- xS, successfully using Fe3O4@ZnS core-shell microspheres as sacrificed templates. The as-prepared magnetically recyclable photocatalysts show efficient photochemical reduction of Cr(VI) under irradiation of visible light. The photochemical reduction mechanism has been studied to illustrate the reduction-oxidation ability of the photogenerated electrons (e-) and holes (h+), which play an important role in the reduction of Cr(VI) to Cr(III) and oxidation of organic dyes. The as-prepared Fe3O4@Zn0.55Cd0.45S core-shell microspheres show good chemical stability and only a slight decrease in the photocatalytic activity after four recycles. In particular, the as-prepared photocatalysts could be easily recycled and reused by an external magnetic field. Therefore, this work would provide a facile chemical approach for controlled synthesis of magnetic nanostructures combined with alloyed semiconductor photocatalysts for wastewater treatment.

12.
J Org Chem ; 81(1): 238-49, 2016 Jan 04.
Artigo em Inglês | MEDLINE | ID: mdl-26618373

RESUMO

The chemoselective transformation of diarylethanones via either aerobic oxidative cleavage to give arylmethanoic acids or tandem aerobic oxidation/benzilic acid rearrangement/decarboxylation to give diarylmethanones has been developed. The transformation is controllable and applicable to a broad spectrum of substrates and affords the desired products in good to excellent yields. Mechanistic insights with control reactions, (1)H NMR tracking, and single-crystal X-ray diffraction reveal a complex mechanistic network in which two common intermediates, α-ketohydroperoxide and diarylethanedione, and three plausible pathways are proposed and verified. These pathways are interlinked and can be switched reasonably by changing the reaction conditions. This method enables scalable synthesis and access to a number of valuable compounds, including vitamin B3, diphenic acid, and the nonsteroidal anti-inflammatory drug ketoprofen. The present protocol represents a step forward in exploiting complex mechanistic networks to control reaction pathways, achieving divergent syntheses from the same class of starting materials.

13.
Guang Pu Xue Yu Guang Pu Fen Xi ; 36(12): 4052-7, 2016 Dec.
Artigo em Chinês | MEDLINE | ID: mdl-30256555

RESUMO

As a highly active free radical in vivo, peroxynitrite can damage various biological macromolecules and cause a series of major diseases, which is of great significance to determine its content and reactive mechanism. It is very difficult to capture the dynamic process of peroxynitrite due to its active property and fast reacted rate. In this paper, we firstly explored the kinetic characteristics of peroxynitrite and tyrosine with the presence of Hemoglobin and Hemin by using flow injection analyzer. The results showed that the oxidation processes of peroxynitrite and tyrosine catalyzed with hemoglobin and hemin were in accordance with Michaelis-Menten's dynamics law; Based on the Michaelis constant (K(m)) and the maximum initial rate (V(max)), we deduced the reaction mechanism that peroxynitrite, catalyzed by mimic enzymes, directly oxidized tyrosine combined with mimic enzymes, rather than decomposed to · OH and O(-2)·; In addition, we detected the rate constant of the reaction catalyzed by these two kinds of enzymes at different temperature and pH, resulting that the optimum conditions of hemoglobin to catalyze this system were 25 ℃ and pH 8, the rate constant was 1.035×10(6) mol·L(-1) · s(-1), while hemin was 37 ℃ and pH 9.5, the rate constant was 6.842×10(5) mol·L(-1) · s(-1); Comparing the kinetic parameters, K(m)Hb(4.46 µmol·L(-1))V(Hemin)(max)(0.026 ΔIF/s), we discovered that the rate constant of hemoglobin in optimum condition was greater than that in hemin, and the catalytic activity of hemoglobin was higher than that of hemin. All these results have provided kinetic parameters for the study of determining the content of peroxynitrite and exploring its reaction mechanism with enzymatic method. It also laid a theoretical foundation for developing new diagnosis technology to prevent and cure diseases caused by free radicals in vivo.


Assuntos
Ácido Peroxinitroso/química , Tirosina/química , Catálise , Radicais Livres , Concentração de Íons de Hidrogênio , Cinética , Nitratos , Oxirredução
14.
Am J Chin Med ; 52(1): 253-274, 2024.
Artigo em Inglês | MEDLINE | ID: mdl-38351702

RESUMO

Berberine (BBR) is a principal component of Rhizoma coptidis known for its therapeutic potential in treating diseases such as type 2 diabetes mellitus (T2DM) and obesity. Despite the trace levels of BBR in plasma, it's believed that its metabolites play a pivotal role in its biological activities. While BBR is recognized to promote GLP-1 production in intestinal L cells, the cytoprotective effects of its metabolites on these cells are yet to be explored. The present study investigates the effects of BBR metabolites on GLP-1 secretion and the underlying mechanisms. Our results revealed that, out of six BBR metabolites, berberrubine (BBB) and palmatine (PMT) significantly increased the production and glucose-stimulated secretion of GLP-1 in GLUTag cells. Notably, both BBB and PMT could facilitate GLP-1 and insulin secretion and enhance glucose tolerance in standard mice. Moreover, a single dose of PMT could markedly increase plasma GLP-1 and improve glucose tolerance in mice with obesity induced by a high-fat diet. In palmitic acid or TNF[Formula: see text]-treated GLUTag cells, BBB and PMT alleviated cell death, oxidative stress, and mitochondrial dysfunction. Furthermore, they could effectively reverse inflammation-induced inhibition of the Akt signaling pathway. In general, these insights suggest that the beneficial effects of orally administered BBR on GLP-1 secretion are largely attributed to the pharmacological activity of BBB and PMT by their above cytoprotective effects on L cells, which provide important ideas for stimulating GLP-1 secretion and the treatment of T2DM.


Assuntos
Berberina , Diabetes Mellitus Tipo 2 , Doenças Mitocondriais , Camundongos , Animais , Berberina/farmacologia , Berberina/uso terapêutico , Diabetes Mellitus Tipo 2/tratamento farmacológico , Peptídeo 1 Semelhante ao Glucagon/metabolismo , Peptídeo 1 Semelhante ao Glucagon/farmacologia , Peptídeo 1 Semelhante ao Glucagon/uso terapêutico , Glucose , Obesidade/metabolismo , Estresse Oxidativo , Doenças Mitocondriais/tratamento farmacológico
15.
World J Gastroenterol ; 30(9): 1237-1249, 2024 Mar 07.
Artigo em Inglês | MEDLINE | ID: mdl-38577174

RESUMO

BACKGROUND: Pancreatic ductal adenocarcinoma (PDAC) is a highly fatal disease with limited effective treatment especially after first-line chemotherapy. The human epidermal growth factor receptor 2 (HER-2) immunohistochemistry (IHC) positive is associated with more aggressive clinical behavior and shorter overall survival in PDAC. CASE SUMMARY: We present a case of multiple metastatic PDAC with IHC mismatch repair proficient but HER-2 IHC weakly positive at diagnosis that didn't have tumor regression after first-line nab-paclitaxel plus gemcitabine and PD-1 inhibitor treatment. A novel combination therapy PRaG 3.0 of RC48 (HER2-antibody-drug conjugate), radiotherapy, PD-1 inhibitor, granulocyte-macrophage colony-stimulating factor and interleukin-2 was then applied as second-line therapy and the patient had confirmed good partial response with progress-free-survival of 6.5 months and overall survival of 14.2 month. She had not developed any grade 2 or above treatment-related adverse events at any point. Percentage of peripheral CD8+Temra and CD4+Temra were increased during first two activation cycles of PRaG 3.0 treatment containing radiotherapy but deceased to the baseline during the maintenance cycles containing no radiotherapy. CONCLUSION: PRaG 3.0 might be a novel strategy for HER2-positive metastatic PDAC patients who failed from previous first-line approach and even PD-1 immunotherapy but needs more data in prospective trials.


Assuntos
Carcinoma Ductal Pancreático , Neoplasias Pancreáticas , Receptor ErbB-2 , Humanos , Feminino , Gencitabina , Desoxicitidina/uso terapêutico , Estudos Prospectivos , Inibidores de Checkpoint Imunológico/uso terapêutico , Paclitaxel/uso terapêutico , Neoplasias Pancreáticas/tratamento farmacológico , Carcinoma Ductal Pancreático/tratamento farmacológico , Protocolos de Quimioterapia Combinada Antineoplásica/uso terapêutico , Albuminas/uso terapêutico
16.
J Heart Lung Transplant ; 43(6): 973-982, 2024 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-38211836

RESUMO

BACKGROUND: Aspiration is a known risk factor for adverse outcomes post-lung transplantation. Airway bile acids are the gold-standard biomarker of aspiration; however, they are released into the duodenum and likely reflect concurrent gastrointestinal dysmotility. Previous studies investigating total airway pepsin have found conflicting results on its relationship with adverse outcomes post-lung transplantation. These studies measured total pepsin and pepsinogen in the airways. Certain pepsinogens are constitutively expressed in the lungs, while others, such as pepsinogen A4 (PGA4), are not. We sought to evaluate the utility of measuring airway PGA4 as a biomarker of aspiration and predictor of adverse outcomes in lung transplant recipients (LTRs) early post-transplant. METHODS: Expression of PGA4 was compared to other pepsinogens in lung tissue. Total pepsin and PGA4 were measured in large airway bronchial washings and compared to preexisting markers of aspiration. Two independent cohorts of LTRs were used to assess the relationship between airway PGA4 and chronic lung allograft dysfunction (CLAD). Changes to airway PGA4 after antireflux surgery were assessed in a third cohort of LTRs. RESULTS: PGA4 was expressed in healthy human stomach but not lung. Airway PGA4, but not total pepsin, was associated with aspiration. Airway PGA4 was associated with an increased risk of CLAD in two independent cohorts of LTRs. Antireflux surgery was associated with reduced airway PGA4. CONCLUSIONS: Airway PGA4 is a marker of aspiration that predicts CLAD in LTRs. Measuring PGA4 at surveillance bronchoscopies can help triage high-risk LTRs for anti-reflux surgery.


Assuntos
Aloenxertos , Biomarcadores , Transplante de Pulmão , Humanos , Transplante de Pulmão/efeitos adversos , Masculino , Feminino , Pessoa de Meia-Idade , Biomarcadores/metabolismo , Aspiração Respiratória/diagnóstico , Aspiração Respiratória/etiologia , Aspiração Respiratória/metabolismo , Pepsinogênio C/metabolismo , Pepsinogênio C/sangue , Adulto , Disfunção Primária do Enxerto/diagnóstico , Disfunção Primária do Enxerto/metabolismo , Disfunção Primária do Enxerto/etiologia , Doença Crônica , Pulmão/metabolismo , Pulmão/fisiopatologia , Complicações Pós-Operatórias/diagnóstico , Valor Preditivo dos Testes
17.
J Mol Endocrinol ; 73(2)2024 Aug 01.
Artigo em Inglês | MEDLINE | ID: mdl-38941267

RESUMO

Pregnancy requires metabolic adaptations in order to meet support fetal growth with nutrient availability. In this study, the influence of pregnancy on metabolically active organs (adipose tissues in particular) was investigated. Our results showed that maternal weight and adipose mass presented dynamic remodeling in the periparturient mice. Meanwhile, pregnancy mice displayed obvious glucose intolerance and insulin resistance in late pregnancy as compared to non-pregnancy, which were partially reversed at parturition. Further analyses revealed that different fat depots exhibited site-specific adaptions of morphology and functionality as pregnancy advanced. Brown and inguinal white adipose tissue (BAT and IngWAT) exhibited obviously decreased thermogenic activity; by contrast, gonadal white adipose tissue (GonWAT) displayed remarkably increased lipid mobilization. Notably, we found that mammary gland differentiation was enhanced in IngWAT, followed by BAT but not in GonWAT. These result indicated that brown and white adipose tissues might synergistically play a crucial role in maintaining the maximum of energy supply for mother and fetus, which facilitates the mammary duct luminal epithelium development as well as the growth and development of fetus. Accompanied with adipose adaptation, however, our results revealed that the liver and pancreas also displayed significant metabolic adaptability, which together tended to trigger the risk of maternal metabolic diseases. Importantly, pregnancy-dependent obesity in our mice model resembled the disturbed metabolic phenotypes of pregnant women such as hyperglyceridemia and hypercholesterolemia. Our findings in this study could provide valuable clues for better understanding the underlying mechanisms of metabolic maladaptation and facilitate the development of the prevention and treatment of metabolic diseases.


Assuntos
Adaptação Fisiológica , Tecido Adiposo Marrom , Tecido Adiposo Branco , Animais , Tecido Adiposo Branco/metabolismo , Gravidez , Feminino , Tecido Adiposo Marrom/metabolismo , Camundongos , Resistência à Insulina , Obesidade/metabolismo , Obesidade/patologia , Glândulas Mamárias Animais/metabolismo , Glândulas Mamárias Animais/crescimento & desenvolvimento , Termogênese , Metabolismo Energético , Fígado/metabolismo
18.
Imeta ; 3(3): e199, 2024 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-38898986

RESUMO

The drug response phenotype is determined by a combination of genetic and environmental factors. The high clinical conversion failure rate of gene-targeted drugs might be attributed to the lack of emphasis on environmental factors and the inherent individual variability in drug response (IVDR). Current evidence suggests that environmental variables, rather than the disease itself, are the primary determinants of both gut microbiota composition and drug metabolism. Additionally, individual differences in gut microbiota create a unique metabolic environment that influences the in vivo processes underlying drug absorption, distribution, metabolism, and excretion (ADME). Here, we discuss how gut microbiota, shaped by both genetic and environmental factors, affects the host's ADME microenvironment within a new evaluation system for drug-microbiota interactions. Furthermore, we propose a new top-down research approach to investigate the intricate nature of drug-microbiota interactions in vivo. This approach utilizes germ-free animal models, providing foundation for the development of a new evaluation system for drug-microbiota interactions.

19.
Materials (Basel) ; 16(4)2023 Feb 15.
Artigo em Inglês | MEDLINE | ID: mdl-36837244

RESUMO

A high sintering temperature is required to acquire excellent performance in the production of porcelain but results in high fuel consumption. To prepare the porcelain with outstanding performance at a lower temperature, a self-produced additive containing calcium (CaK) was added into a three-component system of kaolinite-feldspar-quartz. XRD and SEM were used to characterize the samples. The toughening mechanism and Gibbs free energy were investigated. After introducing the CaK, the bending strength of the porcelain fired at 1513 K increased from 56.32 ± 0.65 MPa to 95.31 ± 0.63 MPa, which was 21.83% higher than that of the porcelain without CaK at an optimal firing temperature of 1603 K. The main crystal phase of the sample comprised mullite and quartz in the raw materials at 1453~1603 K. The anorthite was observed at 1453 K and interlocked with needle-shaped mullite at 1513 K in the porcelain after adding CaK, which resulted in the higher bending strength. Quantitative analysis indicated that the amount of anorthite decreased at 1513 K and disappeared at 1543 K; the amount of mullite increased with temperature. The Gibbs free energy of the reaction (CaO•Al2O3•2SiO2 + 2(Al2O3•2SiO2) → 3Al2O3•2SiO2 + CaO + 4SiO2) at high temperature was negative, which suggested that the formation of mullite (3Al2O3•2SiO2) from anorthite (CaO•Al2O3•2SiO2) was possible. These findings implied that the addition of CaK contributed to the appropriate phase composition and microstructure, and the excellent performance of the porcelain at a lower temperature. In addition, the transformation between anorthite and mullite was possible in the special raw material system. The results are of interest in producing anorthite/mullite ceramics at reduced sintering temperatures and the conversion between anorthite and mullite.

20.
Front Endocrinol (Lausanne) ; 14: 1133167, 2023.
Artigo em Inglês | MEDLINE | ID: mdl-36798665

RESUMO

Introduction: Previous study has indicated Dubosiella newyorkensis may act as a potential probiotic in age-related diseases. However, its detailed role in aging has not yet been promulgated. This study aimed to explore the potential anti-aging role of Dubosiella newyorkensis by comparing the anti-aging effect of resveratrol in young and old mice. Method: Measurement of intestinal aging-related factors in colon and serum, and vascular endothelial function-related factors in serum were performed by enzyme-linked immunosorbent assay (ELISA). Gut microbial analysis of intestinal contents were identified by 16S rRNA gene sequencing. Results: The effect of Dubosiella newyorkensis on reducing malondialdehyde (MDA) and increasing superoxide dismutase (SOD) in aged mice were greater than that of resveratrol. While the effect of Dubosiella newyorkensis on nitric oxide (NO) level was less than that of resveratrol, the reduction of vascular endothelial growth factor (VEGF) and pentosidine (PTD) was better than that of resveratrol in young mice. In young mice, Dubosiella newyorkensis promoted an increase in the beneficial genus Lactobacillus, Bifidobacterium and Ileibacterium less effectively as compared with resveratrol treatment. In aged mice, Dubosiella newyorkensis promoted the increase of Bifidobacterium, Ileibacterium less effectively than resveratrol, and promoted the increase of Akkermansia, Staphylococcus, Verrucomicrobiota expression better as compared with resveratrol treatment. Both young and old mice showed the same results for the remaining markers, including changes in gut microbial composition and predictions of function. Conclusion: Dubosiella newyorkensis has similar anti-aging functions with resveratrol. Dubosiella newyorkensis may even be more effective than resveratrol in reducing oxidative stress, improving vascular endothelial function, and redistributing gut microbiota. The research provides an innovative strategy of Dubosiella newyorkensis to improve aging.


Assuntos
Microbioma Gastrointestinal , Camundongos , Animais , Resveratrol/farmacologia , RNA Ribossômico 16S , Fator A de Crescimento do Endotélio Vascular , Envelhecimento
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