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1.
Anim Biotechnol ; : 1-14, 2022 Nov 02.
Artigo em Inglês | MEDLINE | ID: mdl-36322696

RESUMO

The yak is an agricultural animal with strong disease resistance in Qinghai-Tibet Plateau. Immune organs are directly involved in the body's immune response and protect it from external aggression. In this study, we characterized and evaluated the main markers of interleukin (IL)-1ß, IL-17a, hypoxia inducer factor-1 (HIF-1)α, and heat shock protein 90 (HSP90) in the lymph nodes, spleen, thymus, and hemal nodes of adult yaks using network informatics, molecular cloning, immunohistochemistry, real-time quantitative polymerase chain reaction (RT-qPCR), and western blotting. We first cloned the IL-1ß and IL-17a mRNA of yaks. A significant feature was the higher IL-1ß and IL-17a expression in the lymph nodes than in the spleen, hemal nodes, and thymus. Immunohistochemistry and immunofluorescence revealed that IL-1ß and IL-17a cells were mainly located in the paracortex area of the lymph nodes and the T-cell-dependent area in the hemal nodes and spleen. Several HIF-1α proteins were detected in the cortex of the hemal nodes mantle, while HSP90 was detected in the lymphoid nodules of the hemal nodes and lymph nodes. This study sheds light on the relationship between the morphology and function of these organs and provides an important reference for studies on the participation of yak immune organs in immune responses.

2.
Food Chem ; 405(Pt A): 134825, 2022 Nov 03.
Artigo em Inglês | MEDLINE | ID: mdl-36356360

RESUMO

Dithiothreitol (DTT) was adopted as a nucleophile to develop a new acid-catalyzed degradation method for grape seed proanthocyanidin extraction (GSPE). Backpropagation neural network and Box-Behnken design were employed and compared to establish the optimized degradation conditions. GSPE was reacted with DTT at a ratio of 1:1 under mild conditions with 0.14 M HCl at 40.8 °C for 60 min. Three monomeric proanthocyanidins and six novel flavan-3-ol-DTT conjugates consisting of three pairs of diastereomers were simultaneously obtained with a high yield (929 mg/g). All the degradation products showed protective effects against Aß25-35-induced neurotoxicity in PC-12 cells and prevented Aß25-35 aggregation based on the results from MTT and thioflavin T fluorescence assays, respectively. Detailed intermolecular interactions leading to the prevention of Aß25-35 aggregation were elucidated using molecular docking. This work would provide new compounds from functional foods that can be explored for their neuroprotective potential.

3.
Heart Lung ; 58: 62-68, 2022 Nov 17.
Artigo em Inglês | MEDLINE | ID: mdl-36403555

RESUMO

BACKGROUND: Atrial fibrillation (AF) is becoming increasingly common. Effective self-management during the "Blanking Period" is critical. The Information-Motivation-Behavioral skills (IMB) model can be used to study health behaviors in chronic disease patients, but it has not been studied in AF patients. OBJECTIVE: The goal of this study was to explore the influencing factors and interaction pathways of self-management behavior in AF patients during the "Blanking Period" using the IMB model. METHODS: From June to December 2021, a cross-sectional design was conducted. Patients with AF during the "Blanking Period" (N=220) were recruited. They filled out several quantitative questionnaires, including the Jessa Atrial Fibrillation Knowledge Questionnaire, the Confidence in Atrial Fibrillation Management Scale, the Perceived Social Support Scale, the All Aspects of Health Literacy Scale, and the Self-care Scale for Chronic Atrial Fibrillation Patients. Data were analyzed using correlation analysis, multiple regression analysis, and path analysis. RESULTS: Total score of self-management behavior was (33.83 ± 10.66). AF knowledge (ß = 0.252, P < 0.001), self-management confidence (ß = 0.219, P < 0.001), social support (ß = 0.291, P < 0.001), and health literacy (ß = 0.262, P < 0.001) were all positively correlated with patients' self-management behavior, accounting for 66.50 percent of the total variance. CONCLUSIONS: During the "Blanking Period", the IMB model can be used to predict the factors that influence self-management behavior in AF patients. By using IMB model, interventions targeting patient-specific influencing factors could improve self-management behavior and quality of life in AF patients.

4.
Nat Commun ; 13(1): 6673, 2022 Nov 05.
Artigo em Inglês | MEDLINE | ID: mdl-36335188

RESUMO

Controlled growth of well-oriented metal-organic framework nanoarrays on requisite surfaces is of prominent significance for a broad range of applications such as catalysis, sensing, optics and electronics. Herein, we develop a highly flexible soft nanobrush-directed synthesis approach for precise in situ fabrication of MOF nanoarrays on diverse substrates. The soft nanobrushes are constructed via surface-initiated living crystallization-driven self-assembly and their active poly(2-vinylpyridine) corona captures abundant metal cations through coordination interactions. This allows the rapid heterogeneous growth of MOF nanoparticles and the subsequent formation of MIL-100 (Fe), HKUST-1 and CUT-8 (Cu) nanoarrays with tailored heights of 220~1100 nm on silicon wafer, Ni foam and ceramic tube. Auxiliary functional components including metal oxygen clusters and precious metal nanoparticles can be readily incorporated to finely fabricate hybrid structures with synergistic features. Remarkably, the MIL-100 (Fe) nanoarrays doped with Keggin H3PMo10V2O40 dramatically boost formaldehyde selectivity up to 92.8% in catalytic oxidation of methanol. Moreover, the HKUST-1 nanoarrays decorated with Pt nanoparticles show exceptional sensitivity to H2S with a ppb-level detection limit.

5.
Front Microbiol ; 13: 990905, 2022.
Artigo em Inglês | MEDLINE | ID: mdl-36406459

RESUMO

Piglets with the same genetic background were used to investigate the effects of different lengths of suckling period on growth performance, hematology parameters, and fecal microbiota. All piglets were born by a sow (Landrace×Yorkshire). On day 14 postpartum, a total of 16 piglets [Duroc×(Landrace×Yorkshire)] with a similar initial body weight (2.48 ± 0.25 kg) were randomly assigned into two groups with four replicates per group, two pigs per replicate pen (one barrow and one gilt). On day 14 of age, experiment started, piglets from the first group were weaned (14W), whereas the others continued to receive milk until day 28 of age (28W). The experiment completed on day 70 of age, last 56 days. Growth performance parameters including body weight, average daily gain, feed intake, feed efficiency, and growth rate and hematology parameters including immunoglobulin A (IgA), immunoglobulin G (IgG), immunoglobulin M (IgM), albumin, globulin, and total protein were measured in this study. Additionally, a technique of 16S rRNA gene sequencing was used to analyze fecal microbiota for revealing how the changes in the lengths of suckling period on intestinal microbiota. We found that ultra-early weaning impaired growth performance of piglets, whose worse body weight, average daily gain, feed intake, feed efficiency, and growth rate were observed in 14W group at all measured timepoints in comparison with those in 28W group (P < 0.05). Moreover, higher contents of serum IgA (P = 0.028), IgG (P = 0.041), and IgM (P = 0.047), as well as lower contents of serum albumin (P = 0.002), albumin-to-globulin ratio (P = 0.003), and total protein (P = 0.004), were observed in 14W group in comparison with those in 28W group on day 28 of age, but not on day 70 of age. High-throughput pyrosequencing of 16S rRNA indicated that the intestinal microbiota richness in 14W group was lower than that in 28W group (P < 0.05); moreover, in comparison with 28W group at all sampling timepoints, fecal microbiota in 14W group showed more beneficial bacteria and fewer pathogenic bacteria (P < 0.05). Therefore, we considered that ultra-early weaning had positive effects on immune status and fecal microbiota composition in piglets, but negative effects on growth performance and fecal microbiota abundance.

6.
Front Vet Sci ; 9: 1022972, 2022.
Artigo em Inglês | MEDLINE | ID: mdl-36304416

RESUMO

There are studies on the hypoxia adaptation in yak, but there are few studies on the regulation of ferroptosis by hypoxia. This study was the first time to explore ferroptosis-related genes about hypoxia in yak. In this study, the oviduct epithelial cells between yak and bovine are performed by integrative analysis for functions, regulating network and hub genes. The results showed 29 up-regulated ferroptosis genes and 67 down-regulated ferroptosis genes, and GO-KEGG analysis showed that up-regulated differentially expressed genes (DEGs) were significantly enriched in ribosome pathway and oxidative phosphorylation pathway. Down-regulated DEGs were significantly enriched in longevity regulating pathway-mammal pathway. Mitophagy-Animal Pathway was a significant enrichment pathway for the up-regulated differentially expressed ferroptosis genes (DE-FRGs). HIF-1 signaling pathway is a significant pathway for the down-regulated DE-FRGs. By constructing DE-FRGs protein-protein interaction (PPI) network, 10 hub DE-FRGs (Jun, STAT3, SP1, HIF1A, Mapk1, Mapk3, Rela, Ulk1, CDKN1A, EPAS1) were obtained. The bta-mir-21-5p, bta-mir-10a and bta-mir-17-5p related to STAT3 were predicted. The results of this study indicated the important genes and pathways of the hypoxia in yak, and it was the first time to study ferroptosis genes and pathways related to the hypoxia adaptation by bulk-seq in yak. This study provided sufficient transcriptome datas for hypoxia adaptation.

7.
Diabetes Metab Syndr Obes ; 15: 3167-3179, 2022.
Artigo em Inglês | MEDLINE | ID: mdl-36268197

RESUMO

Objective: Insulin resistance (IR) is a major factor involved in the pathogenesis of metabolic dysfunction-associated fatty liver disease (MAFLD). Triglyceride-glucose (TyG) index, an easily detected surrogate marker of IR, has not been explored sufficiently on its relationship with incident MAFLD risk. This study sought to investigate the association of baseline TyG index with the risk of MAFLD in a Chinese cohort. Methods: This health check-up cohort was constructed with eligible 2056 Chinese from a community. The TyG index was calculated as ln (fasting triglyceride [mg/dL]×fasting glucose [mg/dL]/2). Cox proportion hazard models were used to evaluate the longitudinal association between baseline TyG index and the risk of MAFLD. Results: During an average follow-up of 2.5 ± 0.5 years, about 12.8% of the subjects developed MAFLD, and the incidence of MAFLD trended to increase with the quartile TyG index (P trend < 0.05). After adjusting for all confounders, TyG index was independently correlated with the risk of incident MAFLD (HR = 1.784, 95% CI = 1.383-2.302, P < 0.001), and the risk of MAFLD in the highest quartile of TyG index was two times higher than that in the lowest quartile (95% CI = 1.377-2.992, P = 0.001). The restricted cubic spline analysis showed that the relationship between TyG index and the risk of MAFLD was linear in males (P for total < 0.001; P for non-linearity = 0.746), but nonlinear in females (P for non-linearity = 0.040). Conclusion: A high baseline TyG index was independently associated with a high risk of incident MAFLD, and we might develop the strategy of MAFLD prevention based on the TyG index.

8.
Front Vet Sci ; 9: 997709, 2022.
Artigo em Inglês | MEDLINE | ID: mdl-36213393

RESUMO

Leukemia inhibitory factor (LIF) is a multipotent cytokine of the IL-6 family which plays a critical role in the maturation and development of oocytes. This study evaluated the influence of LIF on the maturation and development ability of yak oocytes, and the quality of subsequent blastocysts under in vitro culture settings. Different concentrations of LIF (0, 25, 50, and 100 ng/mL) were added during the in vitro culture of oocytes to detect the maturation rate of oocytes, levels of mitochondria, reactive oxygen species (ROS), actin, and apoptosis in oocytes, mRNA transcription levels of apoptosis and antioxidant-related genes in oocytes, and total cell number and apoptosis levels in subsequent blastocysts. The findings revealed that 50 ng/mL LIF could significantly increase the maturation rate (p < 0.01), levels of mitochondria (p < 0.01) and actin (p < 0.01), and mRNA transcription levels of anti-apoptotic and antioxidant-related genes in yak oocytes. Also, 50 ng/mL LIF could significantly lower the generation of ROS (p < 0.01) and apoptosis levels of oocytes (p < 0.01). In addition, blastocysts formed from 50 ng/mL LIF-treated oocytes showed significantly larger total cell numbers (p < 0.01) and lower apoptosis rates (p < 0.01) than the control group. In conclusion, the addition of LIF during the in vitro maturation of yak oocytes improved the quality and the competence of maturation and development in oocytes, as well as the quality of subsequent blastocysts. The result of this study provided some insights into the role and function of LIF in vitro yak oocytes maturation, as well as provided fundamental knowledge for assisted reproductive technologies in the yak.

9.
Small ; : e2204557, 2022 Oct 10.
Artigo em Inglês | MEDLINE | ID: mdl-36216775

RESUMO

Defect engineering of transition metal dichalcogenides (TMDCs) is important for improving electrocatalytic hydrogen evolution reaction (HER) performance. Herein, a facile and scalable atomic-level di-defect strategy over thermodynamically stable VSe2 nanoflakes, yielding attractive improvements in the electrocatalytic HER performance over a wide electrolyte pH range is reported. The di-defect configuration with controllable spatial relation between single-atom (SA) V defects and single Se vacancy defects effectively triggers the electrocatalytic HER activity of the inert VSe2 basal plane. When employed as a cathode, this di-defects decorated VSe2 electrocatalyst requires overpotentials of 67.2, 72.3, and 122.3 mV to reach a HER current density of 10 mA cm-2 under acidic, alkaline, and neutral conditions, respectively, which are superior to most previously reported non-noble metal HER electrocatalysts. Theoretical calculations reveal that the reactive microenvironment consists of two adjacent SA Mo atoms with two surrounding symmetric Se vacancies, yielding optimal water dissociation and hydrogen desorption kinetics. This study provides a scalable strategy for improving the electrocatalytic activity of other TMDCs with inert atoms in the basal plane.

10.
Artigo em Inglês | MEDLINE | ID: mdl-36218080

RESUMO

BACKGROUND: Fibro-adipogenic progenitors (FAPs) in the muscles have been found to interact closely with muscle progenitor/stem cells (MPCs) and facilitate muscle regeneration at normal conditions. However, it is not clear how FAPs may interact with MPCs in aged muscles. Senolytics have been demonstrated to selectively eliminate senescent cells and generate therapeutic benefits on ageing and multiple age-related disease models. METHODS: By studying the muscles and primary cells of age matched WT mice and Zmpste24-/- (Z24-/- ) mice, an accelerated ageing model for Hutchinson-Gilford progeria syndrome (HGPS), we examined the interaction between FAPs and MPCs in progeria-aged muscle, and the potential effect of senolytic drug fisetin in removing senescent FAPs and improving the function of MPCs. RESULTS: We observed that, compared with muscles of WT mice, muscles of Z24-/- mice contained a significantly increased number of FAPs (2.4-fold; n > =6, P < 0.05) and decreased number of MPCs (2.8-fold; n > =6, P < 0.05). FAPs isolated from Z24-/- muscle contained about 44% SA-ß-gal+ senescent cells, in contrast to about 3.5% senescent cells in FAPs isolated from WT muscle (n > =6, P < 0.001). The co-culture of Z24-/- FAPs with WT MPCs resulted in impaired proliferation and myogenesis potential of WT MPCs, with the number of BrdU positive proliferative cells being reduced for 3.3 times (n > =6, P < 0.001) and the number of myosin heavy chain (MHC)-positive myotubes being reduced for 4.5 times (n > =6, P < 0.001). The treatment of the in vitro co-culture system of Z24-/- FAPs and WT MPCs with the senolytic drug fisetin led to increased apoptosis of Z24-/- FAPs (14.5-fold; n > =6, P < 0.001) and rescued the impaired function of MPCs by increasing the number of MHC-positive myotubes for 3.1 times (n > =6, P < 0.001). Treatment of Z24-/- mice with fisetin in vivo was effective in reducing the number of senescent FAPs (2.2-fold, n > =6, P < 0.05) and restoring the number of muscle stem cells (2.6-fold, n > =6, P < 0.05), leading to improved muscle pathology in Z24-/- mice. CONCLUSIONS: These results indicate that the application of senolytics in the progeria-aged muscles can be an efficient strategy to remove senescent cells, including senescent FAPs, which results in improved function of muscle progenitor/stem cells. The senescent FAPs can be a potential novel target for therapeutic treatment of progeria ageing related muscle diseases.

11.
Nat Commun ; 13(1): 6214, 2022 Oct 20.
Artigo em Inglês | MEDLINE | ID: mdl-36266282

RESUMO

Large area and highly aligned polymer semiconductor sub-microwires were fabricated using the coaxial focused electrohydrodynamic jet printing technology. As indicated by the results, the sub-microwire arrays have smooth morphology, well reproducibility and controllable with a width of ~110 nm. Analysis shows that the molecular chains inside the sub-microwires mainly exhibited edge-on arrangement and the π-stacking direction (010) of the majority of crystals is parallel to the long axis of the sub-microwires. Sub-microwires based organic field effect transistors showed high mobility with an average of 1.9 cm2 V-1 s-1, approximately 5 times higher than that of thin film based organic field effect transistors. In addition, the number of sub-microwires can be conveniently controlled by the printing technique, which can subsequently concisely control the performance of organic field effect transistors. This work demonstrates that sub-microwires fabricated by the coaxial focused electrohydrodynamic jet printing technology create an alternative path for the applications of high-performance organic flexible device.

12.
Front Immunol ; 13: 987385, 2022.
Artigo em Inglês | MEDLINE | ID: mdl-36311744

RESUMO

Background: Systemic lupus erythematosus (SLE) is a complex, multisystem autoimmune disease that is characterized by the production of autoantibodies. Although accumulated evidence suggests that the dysregulation of long non-coding RNAs (lncRNAs) is involved in the pathogenesis of SLE, the genetic contributions of lncRNA coding genes to SLE susceptibility remain largely unknown. Here, we aimed to provide more evidence for the role of lncRNA coding genes to SLE susceptibility. Methods: The genetic association analysis was first adopted from the previous genome-wide association studies (GWAS) and was then validated in an independent cohort. PRDX6-AS1 is located at chr1:173204199-173446294. It spans a region of approximately 240 kb, and 297 single nucleotide polymorphisms (SNPs) were covered by the previous GWAS. Differential expression at the mRNA level was analyzed based on the ArrayExpress Archive database. Results: A total of 33 SNPs were associated with SLE susceptibility, with a P<1.68×10-4. The strongest association signal was detected at rs844649 (P=2.12×10-6), according to the previous GWAS. Combining the results from the GWAS Chinese cohort and our replication cohort, we pursued a meta-analysis approach and found a pronounced genetic association between PRDX6-AS1 rs844649 and SLE susceptibility (pmeta=1.24×10-13, OR 1.50, 95% CI: 1.34-1.67). The mRNA expression of PRDX6 was elevated in peripheral blood cells, peripheral blood mononuclear cells (PBMCs), and multiple cell subpopulations, such as B cells, CD4+ T cells, CD3+ cells, and monocytes in patients with SLE. The PRDX6 protein expression level was also increased in patients with SLE compared with healthy donors. Conclusion: Our study provides new evidence that variants located in lncRNA coding genes are associated with SLE susceptibility.


Assuntos
Lúpus Eritematoso Sistêmico , RNA Longo não Codificante , Humanos , Estudo de Associação Genômica Ampla , Predisposição Genética para Doença , RNA Longo não Codificante/genética , Leucócitos Mononucleares/metabolismo , Polimorfismo de Nucleotídeo Único , RNA Mensageiro/metabolismo , China/epidemiologia , Peroxirredoxina VI/genética , Peroxirredoxina VI/metabolismo
13.
Allergy ; 2022 Oct 13.
Artigo em Inglês | MEDLINE | ID: mdl-36229409

RESUMO

BACKGROUND: Haemophilus influenzae (H. influenzae), Streptococcus pneumoniae (pneumococcus) and influenza vaccines are administered in children to prevent infections caused by these pathogens. The benefits of vaccination for asthma control in children and the elicited immune response are not fully understood. This study aimed to investigate the impact of these vaccinations on respiratory infections, asthma symptoms, asthma severity and control status, pathogen colonization and in vitro immune responses to different stimulants mimicking infections in asthmatic children. METHODS: Children aged 4-6 years were recruited into the multicentre prospective PreDicta study conducted across five European countries. Information about vaccination history, infections, antibiotic use, inhaled corticosteroid (ICS) use and asthma symptoms in the last 12 months were obtained from questionnaires of the study. Nasopharyngeal samples were collected at the first visit to assess bacterial and viral colonization, and venous blood for isolation of peripheral blood mononuclear cells (PBMCs). The PBMCs were stimulated with phytohemagglutinin, R848, Poly I:C and zymosan. The levels of 22 cytokines and chemokines were measured in cell culture supernatants using a luminometric multiplex assay. RESULTS: One-hundred and forty asthmatic preschool children (5.3 ± 0.7 years) and 53 healthy children (5.0 ± 0.8 years) from the PreDicta cohort were included in the current study. Asthmatic children were associated with more frequent upper and lower respiratory infections, and more frequent and longer duration of antibiotic use compared with healthy children. In asthmatic children, sufficient H. influenzae vaccination was associated with a shorter duration of upper respiratory infection (URI) and overall use and average dose of ICS. The airway colonization was characterized by less pneumococcus and more rhinovirus. Pneumococcal vaccination was associated with a reduction in the use rate and average dose of ICS, improved asthma control, and less human enterovirus and more H. influenzae and rhinovirus (RV) airway colonization. Influenza vaccination in the last 12 months was associated with a longer duration of URI, but with a decrease in the occurrence of lower respiratory infection (LRI) and the duration of gastrointestinal (GI) infection and antibiotic use. Asthmatic preschoolers vaccinated with H. influenzae, pneumococcus or influenza presented higher levels of Th1-, Th2-, Th17- and regulatory T cells (Treg)-related cytokines in unstimulated PBMCs. Under stimulation, PBMCs from asthmatic preschoolers with pneumococcal vaccination displayed a predominant anti-inflammatory immune response, whereas PBMCs from asthmatic children with sufficient H. influenzae or influenza vaccination were associated with both pro- and anti-inflammatory immune responses. CONCLUSION: In asthmatic preschoolers, the standard childhood vaccinations to common respiratory pathogens have beneficial effects on asthma control and may modulate immune responses relevant to asthma pathogenesis.

14.
Cell Mol Immunol ; 19(11): 1263-1278, 2022 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-36180780

RESUMO

Serine metabolism is reportedly involved in immune cell functions, but whether and how serine metabolism regulates macrophage polarization remain largely unknown. Here, we show that suppressing serine metabolism, either by inhibiting the activity of the key enzyme phosphoglycerate dehydrogenase in the serine biosynthesis pathway or by exogenous serine and glycine restriction, robustly enhances the polarization of interferon-γ-activated macrophages (M(IFN-γ)) but suppresses that of interleukin-4-activated macrophages (M(IL-4)) both in vitro and in vivo. Mechanistically, serine metabolism deficiency increases the expression of IGF1 by reducing the promoter abundance of S-adenosyl methionine-dependent histone H3 lysine 27 trimethylation. IGF1 then activates the p38-dependent JAK-STAT1 axis to promote M(IFN-γ) polarization and suppress STAT6-mediated M(IL-4) activation. This study reveals a new mechanism by which serine metabolism orchestrates macrophage polarization and suggests the manipulation of serine metabolism as a therapeutic strategy for macrophage-mediated immune diseases.


Assuntos
Interleucina-4 , Serina , Interleucina-4/metabolismo , Serina/metabolismo , Ativação de Macrófagos , Macrófagos/metabolismo , Interferon gama/metabolismo
15.
Clin Lung Cancer ; 23(7): 608-619, 2022 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-36089482

RESUMO

INTRODUCTION: This study aimed to use 18F-fluorodeoxyglucose positron emission tomography and/or computed tomography (18FDG-PET/CT) imaging to evaluate the heterogeneous metabolic response between primary tumor and metastases in NSCLC after therapy and explored its correlation with prognosis. METHODS: The data of patients with NSCLC who underwent 18FDG-PET/CT before and after treatment were retrospectively analyzed. Heterogeneous metabolic response (HR), defined as the difference in metabolic response between any metastases and primary lesion, was evaluated using 18FDG-PET/CT. And the correlation between HR and clinical prognosis was also analyzed. RESULTS: A total of 56 patients with NSCLC including 56 primary lesions and 491 metastases were enrolled in the study. 46.4% (26/56) of patients had HR, especially in patients with stage IV disease and whose metastases with high metabolic burden. HR was significantly correlated with poorer overall survival (OS) and progression-free survival (PFS) (P < .001 and P = .045, respectively). The multivariate analysis suggested that HR was an unfavorable independent prognostic factor for OS (HR = 4.36; 95% CI, 2.00-9.49; P < .001) but not for PFS (P = .469). HR between lymph node metastases was correlated with shorter OS (P < .001) but not with PFS (P = .370). CONCLUSION: HR was observed between primary and metastatic lesions in NSCLC after treatment using PET/CT. HR is significantly associated with poor prognosis and is an independent prognostic factor for OS.


Assuntos
Carcinoma Pulmonar de Células não Pequenas , Neoplasias Pulmonares , Humanos , Fluordesoxiglucose F18 , Carcinoma Pulmonar de Células não Pequenas/patologia , Tomografia por Emissão de Pósitrons combinada à Tomografia Computadorizada/métodos , Estudos Retrospectivos , Tomografia por Emissão de Pósitrons , Prognóstico , Compostos Radiofarmacêuticos
16.
Biomed Pharmacother ; 155: 113731, 2022 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-36179491

RESUMO

BACKGROUND: Chemotherapy is one of the causes of ovarian injury and infertility. Although assisted reproductive technology helps young female patients with cancer become pregnant, preventing chemotherapy-induced ovarian injury will often possess even more significant benefits. OBJECTIVE: We aimed at demonstrating the hazardous effects and mechanisms of ovarian injury by chemotherapeutic agents, as well as demonstrating agents that protect the ovary from chemotherapy-induced injury. RESULTS: Chemotherapeutic agents cause death or accelerate activation of follicles and damage to the blood vessels in the ovary, resulting in inflammation. These often require drug development to protect the ovaries from injury. CONCLUSIONS: Our findings provide a basis for the development of drugs to protect the ovaries from injury. Although there are many preclinical studies on potential protective drugs, there is still an urgent need for a large number of clinical experiments to verify their potential use.


Assuntos
Antineoplásicos , Doenças Ovarianas , Gravidez , Humanos , Feminino , Folículo Ovariano , Antineoplásicos/farmacologia , Substâncias Protetoras/farmacologia
17.
Front Pharmacol ; 13: 960050, 2022.
Artigo em Inglês | MEDLINE | ID: mdl-36120310

RESUMO

American ginseng extract (AGE) is an efficient and low-toxic adjuvant for type 2 diabetes mellitus (T2DM). However, the metabolic mechanisms of AGE against T2DM remain unknown. In this study, a rat model of T2DM was created and administered for 28 days. Their biological (body weight and serum biochemical indicators) and pathological (pancreatic sections stained with HE) information were collected for further pharmacodynamic evaluation. Moreover, an ultra-performance liquid chromatography-mass spectrometry-based (UHPLC-MS/MS-based) untargeted metabolomics method was used to identify potential biomarkers of serum samples from all rats and related metabolic pathways. The results indicated that body weight, fasting blood glucose (FBG), fasting blood insulin (FINS), blood triglyceride concentration (TG), high-density lipoprotein cholesterol (HDL-C), insulin resistance index (HOMA-IR) and insulin sensitivity index (ISI), and impaired islet cells were significantly improved after the high dose of AGE (H_AGE) and metformin treatment. Metabolomics analysis identified 101 potential biomarkers among which 94 metabolites had an obvious callback. These potential biomarkers were mainly enriched in nine metabolic pathways linked to amino acid metabolism and lipid metabolism. Tryptophan metabolism and glutathione metabolism, as differential metabolic pathways between AGE and metformin for treating T2DM, were further explored. Further analysis of the aforementioned results suggested that the anti-T2DM effect of AGE was closely associated with inflammation, oxidative stress, endothelial dysfunction, dyslipidemia, immune response, insulin resistance, insulin secretion, and T2DM-related complications. This study can provide powerful support for the systematic exploration of the mechanism of AGE against T2DM and a basis for the clinical diagnosis of T2DM.

18.
Front Vet Sci ; 9: 960250, 2022.
Artigo em Inglês | MEDLINE | ID: mdl-36090173

RESUMO

In this study, we detected the expression of mRNAs, lncRNAs, and miRNAs in primary cultured leydig cells (LCs) and sertoli cells (SCs) of yak by RNA sequencing technology. A total of 84 differently expression mRNAs (DEmRNAs) (LCs vs. SCs: 15 up and 69 down), 172 differently expression lncRNAs (DElncRNAs) (LCs vs. SCs: 36 up and 136 down), and 90 differently expression miRNAs (DEmiRNAs) (LCs vs. SCs: 72 up and 18 down) were obtained between the two types of cells. GO enrichment and KEGG analysis indicated that the differential expression genes (DEGs) were more enriched in the regulation of actin cytoskeleton, Rap1/MAPK signaling pathway, steroid biosynthesis, focal adhesion, and pathways associated with metabolism. Targeted regulation relationship pairs of 3ß-HSD and MSTRG.54630.1, CNTLN and MSTRG.19058.1, BRCA2 and MSTRG.28299.4, CA2 and novel-miR-148, and ceRNA network of LAMC3-MSTRG.68870.1- bta-miR-7862/novel-miR-151/novel-miR-148 were constructed by Cytoscape software. In conclusion, the differences between LCs and SCs were mainly reflected in steroid hormone synthesis, cell proliferation and metabolism, and blood-testicular barrier (BTB) dynamic regulation, and 3ß-HSD, CNTLN, BRCA2, CA2, and LAMC3 may be the key factors causing these differences, which may be regulated by ncRNAs. This study provides a basic direction for exploring the differential regulation of LCs and SCs by ncRNAs.

19.
Foods ; 11(18)2022 Sep 19.
Artigo em Inglês | MEDLINE | ID: mdl-36141039

RESUMO

Salmonella Enteritidis (S. Enteritidis) can adapt to sublethal sodium hypochlorite conditions, which subsequently triggers stress resistance mechanisms in this pathogen. Hence, the current work aimed to reveal the underlying stress adaptation mechanisms in S. Enteritidis by phenotypic, proteomic, and physiological analyses. It was found that 130 ppm sodium hypochlorite resulted in a moderate inhibitory effect on bacterial growth and an increased accumulation of intracellular reactive oxygen species. In response to this sublethal treatment, a total of 492 proteins in S. Enteritidis showed significant differential abundance (p < 0.05; fold change >2.0 or <0.5), including 225 more abundant proteins and 267 less abundant proteins, as revealed by the tandem-mass-tags-based quantitative proteomics technology. Functional characterization further revealed that proteins related to flagellar assembly, two-component system, and phosphotransferase system were in less abundance, while those associated with ABC transporters were generally in more abundance. Specifically, the repression of flagellar-assembly-related proteins led to diminished swimming motility, which served as a potential energy conservation strategy. Moreover, altered abundance of lipid-metabolism-related proteins resulted in reduced cell membrane fluidity, which provided a survival advantage to S. Enteritidis. Taken together, these results indicate that S. Enteritidis employs multiple adaptation pathways to cope with sodium hypochlorite stress.

20.
Metallomics ; 14(10)2022 Oct 11.
Artigo em Inglês | MEDLINE | ID: mdl-36149330

RESUMO

Three ursolic acid-piperazine-dithiocarbamate ruthenium(II) polypyridyl complexes Ru1-Ru3 were designed and synthesized for evaluating antitumor activity. All the complexes exhibited high in vitro cytotoxicity against MGC-803, T24, HepG2, CNE2, MDA-MB-231, MCF-7, A549, and A549/DDP cell lines. Ru1, Ru2, and Ru3 were 11, 8 and 10 times, respectively, more active than cisplatin against A549/DDP. An in vivo study on MGC-803 xenograft mouse models demonstrated that representative Ru2 exhibited an effective inhibitory effect on tumor growth, showing stronger antitumor activity than cisplatin. Biological investigations suggested that Ru2 entered MGC-803 cells by a clathrin-mediated endocytic pathway, initially localizing in the lysosomes and subsequently escaping and localizing in the mitochondria. Mitochondrial swelling resulted in vacuolization, which induced vacuolation-associated cell death and necroptosis with the formation of necrosomes (RIP1-RIP3) and the uptake of propidium iodide. These results demonstrate that the potential of Ru2 as a chemotherapeutic agent to kill cancer cells via a dual mechanism represents an alternative way to eradicate apoptosis-resistant forms of cancer.


Assuntos
Antineoplásicos , Complexos de Coordenação , Rutênio , Animais , Antineoplásicos/farmacologia , Apoptose , Cisplatino/farmacologia , Clatrina/farmacologia , Complexos de Coordenação/farmacologia , Humanos , Camundongos , Necroptose , Ácido Oleanólico/análogos & derivados , Piperazina/farmacologia , Propídio/farmacologia , Rutênio/farmacologia
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