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1.
Food Chem ; 399: 133867, 2023 Jan 15.
Artigo em Inglês | MEDLINE | ID: mdl-35994856

RESUMO

This study aimed to investigate changes of fat globules and their membranes, and further analyze evolution of lipid profile of lipid rafts in membranes during heat processing of cow milk. Size of fat globules increased from 3.16 µm to 3.70 µm and ζ-potential decreased from -0.53 mV to -0.38 mV after thermal treatment, suggesting that fat globule membrane was destroyed and fat globule occurred coalescence. Glycerophospholipids and cholesterol in fat globule membrane decreased while sphingomyelin increased after thermal treatment. Results of lipidomics show that total of 38 species of 5 lipids molecule showed ability to differentiate the samples. At high temperatures, highly unsaturated glycerophospholipids and sterol lipids were lost from rafts, meanwhile, sphingomyelin and ceramide increased in this region. Significant change of lipid profile in the raft region during thermal treatment suggested a potential relationship between lipid rafts and fat globule coalescence behavior.


Assuntos
Glicolipídeos , Esfingomielinas , Animais , Bovinos , Feminino , Glicerofosfolipídeos , Glicoproteínas , Gotículas Lipídicas , Microdomínios da Membrana
2.
Neural Regen Res ; 18(1): 141-149, 2023 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-35799534

RESUMO

Neuroinflammation and the NACHT, LRR, and PYD domains-containing protein 3 inflammasome play crucial roles in secondary tissue damage following an initial insult in patients with traumatic brain injury (TBI). Maraviroc, a C-C chemokine receptor type 5 antagonist, has been viewed as a new therapeutic strategy for many neuroinflammatory diseases. We studied the effect of maraviroc on TBI-induced neuroinflammation. A moderate-TBI mouse model was subjected to a controlled cortical impact device. Maraviroc or vehicle was injected intraperitoneally 1 hour after TBI and then once per day for 3 consecutive days. Western blot, immunohistochemistry, and TUNEL (terminal deoxynucleotidyl transferase-mediated dUTP nick-end labeling) analyses were performed to evaluate the molecular mechanisms of maraviroc at 3 days post-TBI. Our results suggest that maraviroc administration reduced NACHT, LRR, and PYD domains-containing protein 3 inflammasome activation, modulated microglial polarization from M1 to M2, decreased neutrophil and macrophage infiltration, and inhibited the release of inflammatory factors after TBI. Moreover, maraviroc treatment decreased the activation of neurotoxic reactive astrocytes, which, in turn, exacerbated neuronal cell death. Additionally, we confirmed the neuroprotective effect of maraviroc using the modified neurological severity score, rotarod test, Morris water maze test, and lesion volume measurements. In summary, our findings indicate that maraviroc might be a desirable pharmacotherapeutic strategy for TBI, and C-C chemokine receptor type 5 might be a promising pharmacotherapeutic target to improve recovery after TBI.

3.
Front Endocrinol (Lausanne) ; 13: 987812, 2022.
Artigo em Inglês | MEDLINE | ID: mdl-36120437

RESUMO

Objective: This study aimed to explore the impact of the sperm DNA fragmentation index (DFI) on the clinical outcomes in women undergoing artificial insemination by husband intrauterine insemination (AIH-IUI). Methods: In this retrospective study, the value of sperm DFI was detected by sperm chromatin structure assay (SCSA) in a semen analysis collected before fertility treatment (basal DFI) in 1,500 IUI cycles at the infertility clinic of Northern Jiangsu People's Hospital Reproductive Medicine Center from Jan 2016 to April 2021. Receiver operating characteristic (ROC) curves were used to calculate the cut-off value for the clinical outcomes of IUI, including the biochemical pregnancy rate, clinical pregnancy rate, delivery rate, and live birth rate, and multivariate logistic regression was conducted to analyse the risk factors for clinical outcomes after IUI. Result: In 1,500 IUI cycles, the results showed that there were no statistically significant differences between the normal DFI group and the abnormal DFI group in biochemical pregnancy rate (14.41% vs. 11.3%, P = 0.386), clinical pregnancy rate (12.9% vs. 10.5%, P = 0.433), delivery rate (11.0% vs. 8.9%, P = 0.456), live birth rate (10.9% vs. 8.9%, P = 0.484) or pregnancy loss rate (14.6% vs. 15.4%, P = 1.000). Conclusion: Sperm DFI alone may have limited predictive power for IUI clinical outcomes.


Assuntos
Cromatina , Sêmen , Fragmentação do DNA , Feminino , Humanos , Inseminação Artificial/métodos , Masculino , Gravidez , Estudos Retrospectivos , Espermatozoides
4.
Animals (Basel) ; 12(18)2022 Sep 18.
Artigo em Inglês | MEDLINE | ID: mdl-36139325

RESUMO

This study aimed to investigate the role of chitosan oligosaccharide (COS) as an additive in the feed of laying hens with fatty liver syndrome (FLS). Effects on production performance, egg quality as well as ovarian function were determined. A total of 360 Lohmann Pink-shell laying hens (28 weeks old) were randomly assigned to 5 groups (6 replicates × 12 birds). Hens were fed with a basal diet and a high-energy low-protein (HELP) diet supplemented with 0, 200, 400 and 800 mg/kg COS. COS reversed the lowered laying rates, increased feed-to-egg ratios and decreased albumen heights and Haugh units induced by the HELP diet. Additionally, COS improved the ovarian morphologies damaged by the HELP diet. Furthermore, COS enhanced antioxidant enzyme activities, reduced malonaldehyde levels and downregulated the mRNA expressions of nuclear factor kappa B, pro-inflammation cytokine genes and pro-apoptosis-related genes, while it upregulated the mRNA expression of anti-apoptosis-related genes in the ovaries of HELP-diet-fed hens. These findings suggested that dietary COS supplementation could improve production performance and egg quality in laying hens with FLS, and these beneficial effects were linked to improved ovarian morphology, which was attributed to decreased oxidative stress, inflammation and apoptosis in the ovaries.

5.
Expert Opin Ther Pat ; 2022 Sep 19.
Artigo em Inglês | MEDLINE | ID: mdl-36120913

RESUMO

INTRODUCTION: Cyclin-dependent kinase 12 (CDK12) belongs to the CDK family of serine/threonine protein kinases and associates with cyclin K to exert its biological functions, including regulating gene transcription, mRNA processing and translation. Increasing evidences demonstrate the importance of CDK12 in various human cancers, illustrating its potential as both biomarker and therapeutic target. In addition, CDK12 is also a promising target for the treatment of myotonic dystrophy type 1. Efforts have been taken to discover small molecule inhibitors to validate this important therapeutic target. AREAS COVERED: This review covers the patented CDK12 inhibitors from 2016 to present, as well as these from peer-reviewed literature. It provides the reader an update of the discovery strategies, chemical structures and molecular profiling of all available CDK12 inhibitors. EXPERT OPINION: CDK12 inhibitors with various mechanism of actions have been discovered and it is a great set of tools to evaluate the therapeutic potential of CDK12 in different disease models. CDK12 inhibitors have shown promising results in myotonic dystrophy type 1 mouse model and several preclinical cancer models either as single agent or combination with other anti-cancer agents. Its therapeutic value awaits more rigorous preclinical testing and further clinical investigation.

6.
Epilepsy Behav ; 135: 108876, 2022 Sep 08.
Artigo em Inglês | MEDLINE | ID: mdl-36088785

RESUMO

OBJECTIVE: Although clinical trials have demonstrated that cathodal transcranial direct current stimulation (tDCS) is effective for seizure reduction, its long-term efficacy is unknown. This study aimed to determine the long-term effects of repeated cathodal long tDCS sessions on seizure suppression in patients with refractory epilepsy. METHODS: Patients were recruited to participate in an extended phase of a previous randomized, double-blind, sham-controlled, three-arm, parallel, multicenter study on tDCS. The patients were divided into an active tDCS group (20 min of tDCS per day) and an intensified tDCS group (2 × 20 min of tDCS per day). Each tDCS session lasted 2 weeks and the patients underwent repeated sessions at intervals of 2 to 6 months. The cathode was placed over the epileptogenic focus with the current intensity set as 2 mA. Seizure frequency reduction from baseline was analyzed using the Wilcoxon signed-rank test for two related samples. A generalized estimating equation model was used to estimate group, time, and interaction effects. RESULTS: Among the 19 patients who participated in the extended phase, 11 were in the active tDCS group and underwent 2-16 active tDCS sessions, and eight were in the intensified tDCS group and underwent 3-11 intensified tDCS sessions. Seizure reduction was significant from the first to the seventh follow-up, with a median seizure frequency reduction of 41.7%-83.3% (p < 0.05). Compared to the regular tDCS protocol, each intensified tDCS session substantially decreased seizure frequency by 0.3680 (p < 0.05). One patient experienced an increase of 8.5%-232.8% in the total number of seizures during three treatment sessions and follow-ups. CONCLUSION: Repeated long cathodal tDCS sessions yielded significant and progressive long-term seizure reductions in patients with refractory focal epilepsy.

7.
Nurs Open ; 2022 Sep 13.
Artigo em Inglês | MEDLINE | ID: mdl-36101973

RESUMO

AIM: Early mobilization (EM) improves critical illness survivors' clinical outcomes. This study examines ICU quasi-specialty nurses' EM-related knowledge, attitudes and practices (KAP). DESIGN: This cross-sectional study was conducted at a provincial ICU specialty nurse training site from 2019 to 2021. KAP data were collected using a self-report questionnaire. METHODS: Participants were registered nurses enrolled in the training programme; 485 nurses from 188 hospitals completed the questionnaire. RESULTS: Of the participants, 37.7% had EM training, and 30.7% reported their wards performed EM. Median (IQR) scores for knowledge, attitudes and practices were 14.0 (4.0), 47.0 (9.0) and 37.0 (8.0), belonging to medium, high and medium levels. Scores were lowest for EM scope, implementation indicators and out-of-bed mobilization. There were significant deviations in KAP scores amongst nurses at different levels of hospitals with EM training and whose departments performed EM. Significant positive correlations between knowledge and practice, and attitude and practice were identified.

8.
Front Genet ; 13: 930826, 2022.
Artigo em Inglês | MEDLINE | ID: mdl-36118863

RESUMO

Background: Studies have reported that RNA-binding proteins (RBPs) are dysregulated in multiple cancers and are correlated with the progression and prognosis of disease. However, the functions of RBPs in non-small cell lung cancer (NSCLC) remain unclear. The present study aimed to explore the function of RBPs in NSCLC and their prognostic and therapeutic value. Methods: The mRNA expression profiles, DNA methylation data, gene mutation data, copy number variation data, and corresponding clinical information on NSCLC were downloaded from The Cancer Genome Atlas, Gene Expression Omnibus, and the University of California Santa Cruz Xena databases. The differentially expressed RBPs were identified between tumor and control tissues, and the expression and prognostic value of these RBPs were systemically investigated by bioinformatics analysis. A quantitative polymerase chain reaction (qPCR) was performed to validate the dysregulated genes in the prognostic signature. Results: A prognostic RBP-related signature was successfully constructed based on eight RBPs represented as a risk score using least absolute shrinkage and selection operator (LASSO) regression analysis. The high-risk group had a worse overall survival (OS) probability than the low-risk group (p < 0.001) with 1-, 3-, and 5-year area under the receiver operator characteristic curve values of 0.671, 0.638, and 0.637, respectively. The risk score was associated with the stage of disease (p < 0.05) and was an independent prognostic factor for NSCLC when adjusted for age and UICC stage (p < 0.001, hazard ratio (HR): 1.888). The constructed nomogram showed a good predictive value. The P53, focal adhesion, and NOD-like receptor signaling pathways were the primary pathways in the high-risk group (adjusted p value <0.05). The high-risk group was correlated with increased immune infiltration (p < 0.05), upregulated relative expression levels of programmed cell death 1 (PD1) (p = 0.015), cytotoxic T-lymphocyte-associated protein 4 (CTLA4) (p = 0.042), higher gene mutation frequency, higher tumor mutational burden (p = 0.034), and better chemotherapy response (p < 0.001). The signature was successfully validated using the GSE26939, GSE31210, GSE30219, and GSE157009 datasets. Dysregulation of these genes in patients with NSCLC was confirmed using the qPCR in an independent cohort (p < 0.05). Conclusion: An RBP-related signature was successfully constructed to predict prognosis in NSCLC, functioning as a reference for individualized therapy, including immunotherapy and chemotherapy.

9.
IEEE Trans Biomed Eng ; PP2022 Sep 19.
Artigo em Inglês | MEDLINE | ID: mdl-36121950

RESUMO

Hepatocellular carcinoma (HCC) and intrahepatic cholangiocarcinoma (ICC) are the most common malignancy arising from primary liver cancer (PLC). Liver ultrasound (US) has been the main approach for the early screening and differential diagnosis. Since ultrasonic findings of PLC are closely associated with tumor growth pattern, histological morphology, tumor staging, and other factors, ultrasonic imaging findings overlap partially. Besides, qualitative assessment is highly dependent on expertise. To improve the diagnostic objectiveness, we propose a novel transport-based anatomical-functional metric learning (T-AFML) method to quantify imaging similarity of both the gray-scale US and dynamic contrast-enhanced US view. Considering that the hemodynamic changes vary with individuals, we introduce a temporally regularized optimal transport to align the local enhancement patterns automatically. To sufficiently exploit ultrasonic findings similarity from different modalities, a selector-based metric integration mechanism is adopted to adaptively select a dominant modality accounting for the similarity measure. In this retrospective study, we collected a total of 174 liver cancer patients consists of 105 HCC and 69 ICC, and our method achieves the superior diagnostic accuracy and sensitivity of 88.41% and 86.16%, respectively, demonstrating its efficacy in quantifying multi-modal ultrasonic findings similarity for PLC diagnosis.

10.
Water Res ; 224: 119108, 2022 Sep 13.
Artigo em Inglês | MEDLINE | ID: mdl-36122448

RESUMO

Heavy metals and pesticides (HMPs) are common contaminants due to their extensive use worldwide. Diffusive gradients in thin films (DGT) are a good method for measuring the bioavailable concentration of pollutants. This study represents the first evaluation of HMP toxicity in aquatic biota using the DGT technique in sediments. Zhelin Bay was selected as the case study site because it has been contaminated by pollutants. Nonmetric multidimensional scaling (NMS) analysis reveals that a diverse range of pollutants (V, Cr, Ni, Cu, Zn, As, Se, InHg, Mo, Cd, Sb, W, Pb, CLP, PYR) are mainly influenced by sediment characteristics. Assessment of single HMP toxicity found that the risk quotient (RQ) values for Mn, Cu, inorganic Hg (InHg), chlorpyrifos (CLP) and diuron (DIU) are significantly higher than 1, indicating that the adverse effects of these single HMPs should not be ignored. The combined toxicity of HMP mixtures based on probabilistic ecotoxicological risk assessment shows that Zhelin Bay surface sediments had a medium probability (54.6%) of toxic effects to aquatic biota.

11.
Stat Methods Med Res ; : 9622802221122403, 2022 Sep 21.
Artigo em Inglês | MEDLINE | ID: mdl-36128906

RESUMO

Dichotomous response data observed over multiple time points, especially data that exhibit longitudinal structures, are important in many applied fields. The multivariate probit model has been an attractive tool in such situations for its ability to handle correlations among the outcomes, typically by modeling the covariance (correlation) structure of the latent variables. In addition, a multivariate probit model facilitates controlled imputations for nonignorable dropout, a phenomenon commonly observed in clinical trials of experimental drugs or biologic products. While the model is relatively simple to specify, estimation, particularly from a Bayesian perspective that relies on Markov chain Monte Carlo sampling, is not as straightforward. Here we compare five sampling algorithms for the correlation matrix and discuss their merits: a parameter-expanded Metropolis-Hastings algorithm (Zhang et al., 2006), a parameter-expanded Gibbs sampling algorithm (Talhouk et al., 2012), a parameter-expanded Gibbs sampling algorithm with unit constraints on conditional variances (Tang, 2018), a partial autocorrelation parameterization approach (Gaskins et al., 2014), and a semi-partial correlation parameterization approach (Ghosh et al., 2021). We describe each algorithm, use simulation studies to evaluate their performance, and focus on comparison criteria such as computational cost, convergence time, robustness, and ease of implementations. We find that the parameter-expanded Gibbs sampling algorithm by Talhouk et al. (2012) often has the most efficient convergence with relatively low computational complexity, while the partial autocorrelation parameterization approach is more flexible for estimating the correlation matrix of latent variables for typical late phase longitudinal studies.

12.
Mol Biol Cell ; : mbcE22070279, 2022 Sep 21.
Artigo em Inglês | MEDLINE | ID: mdl-36129766

RESUMO

The biogenesis of lipid droplets (LDs), key organelles for cellular lipid storage and homeostasis, remains poorly understood. Seipin is essential to normal LD biogenesis but exactly how seipin regulates LD initiation remains to be elucidated. Our previous results suggested that seipin may bind anionic phospholipids such as PI(3)P. Here, we investigate if PI(3)P is functionally linked to seipin and if PI(3)P can also impact LD biogenesis. In seipin-deficient cells, there were enlarged PI(3)P puncta where its effector, DFCP1, also appeared to congregate. Reducing cellular PI(3)P partially rescued the defective LD initiation caused by seipin deficiency. Increasing PI(3)P impeded the lipidation of nascent LDs. We further demonstrated that DFCP1 localized to LDs and facilitated the efficient lipidation of nascent LDs. However, the normal function and localization of DFCP1 were disrupted when cellular PI(3)P homeostasis was perturbed. Our results thus identify PI(3)P as a novel regulator of LD initiation and suggest that PI(3)P may impact the biogenesis of LDs through DFCP1.

13.
Front Med (Lausanne) ; 9: 928245, 2022.
Artigo em Inglês | MEDLINE | ID: mdl-36059823

RESUMO

Introduction: To evaluate the safety and anterior chamber structure of implantation of the Evolution (EVO) implantable Collamer lens (EVO-ICL) in patients with short white-to-white (WTW) corneal diameters. Materials and methods: The study population was divided into two groups: the experimental group (34 eyes of 34 patients) with WTW corneal diameters of ≤10.6 mm and the control group (59 eyes of 59 patients) with WTW corneal diameters of >10.6 mm. The outcome measures included uncorrected distance visual acuity, corrected distance visual acuity, refractive power, intraocular pressure (IOP), anterior chamber angle, depth, volume, and vault. Results: The safety indices of the experimental and control groups were 1.17 ± 0.30 and 1.12 ± 0.14, respectively (P > 0.05); the effectiveness indices were 1.16 ± 0.31 and 1.07 ± 0.17, respectively (P > 0.05). The simulation curves of the expected and actual corrections in the experimental and control groups were y = 0.9876x - 0.0927 and y = 0.9799x + 0.0343, respectively. There were no significant differences between the IOPs and anterior chamber structures of the two groups (P > 0.05). The average vaults of the experimental and control groups were 395.76 ± 155.32 and 389.49 ± 135.01 µm, respectively (P > 0.05). Conclusion: EVO-ICL implantation in patients with short WTW corneal diameters (≤ 10.6 mm) was determined to be a safe, effective, and predictable method for correcting myopia. The changes in the anterior chamber structure were still within normal limits after the surgery, the IOP remained stable, and the ideal vault was achieved after the surgery.

14.
Gigascience ; 112022 Sep 03.
Artigo em Inglês | MEDLINE | ID: mdl-36056732

RESUMO

BACKGROUND: Maternal proteins have important roles during early embryonic development. However, our understanding of maternal proteins is still very limited. The integrated analysis of mouse uniparental (parthenogenetic) and biparental (fertilized) embryos at the protein level creates a protein expression landscape that can be used to explore preimplantation mouse development. RESULTS: Using label-free quantitative mass spectrometry (MS) analysis, we report on the maternal proteome of mouse parthenogenetic embryos at pronucleus, 2-cell, 4-cell, 8-cell, morula, and blastocyst stages and highlight dynamic changes in protein expression. In addition, comparison of proteomic profiles of parthenogenotes and fertilized embryos highlights the different fates of maternal proteins. Enrichment analysis uncovered a set of maternal proteins that are strongly correlated with the subcortical maternal complex, and we report that in parthenogenotes, some of these maternal proteins escape the fate of protein degradation. Moreover, we identified a new maternal factor-Fbxw24, and highlight its importance in early embryonic development. We report that Fbxw24 interacts with Ddb1-Cul4b and may regulate maternal protein degradation in mouse. CONCLUSIONS: Our study provides an invaluable resource for mechanistic analysis of maternal proteins and highlights the role of the novel maternal factor Fbw24 in regulating maternal protein degradation during preimplantation embryo development.


Assuntos
Partenogênese , Proteômica , Animais , Blastocisto/metabolismo , Desenvolvimento Embrionário , Feminino , Camundongos , Gravidez , Proteoma/metabolismo
15.
Comput Struct Biotechnol J ; 20: 4626-4635, 2022.
Artigo em Inglês | MEDLINE | ID: mdl-36090818

RESUMO

Lung cancer is a major cause of cancer-associated deaths worldwide, and lung adenocarcinoma (LUAD) is the most common lung cancer subtype. Micro RNAs (miRNAs) regulate the pattern of gene expression in multiple cancer types and have been explored as potential drug development targets. To develop an oncomiR-based panel, we identified miRNA candidates that show differential expression patterns and are relevant to the worse 5-year overall survival outcomes in LUAD patient samples. We further evaluated various combinations of miRNA candidates for association with 5-year overall survival and identified a four-miRNA panel: miR-9-5p, miR-1246, miR-31-3p, and miR-3136-5p. The combination of these four miRNAs outperformed any single miRNA for predicting 5-year overall survival (hazard ratio [HR]: 3.47, log-rank p-value = 0.000271). Experiments were performed on lung cancer cell lines and animal models to validate the effects of these miRNAs. The results showed that singly transfected antagomiRs largely inhibited cell growth, migration, and invasion, and the combination of all four antagomiRs considerably reduced cell numbers, which is twice as effective as any single miRNA-targeted transfected. The in vivo studies revealed that antagomiR-mediated knockdown of all four miRNAs significantly reduced tumor growth and metastatic ability of lung cancer cells compared to the negative control group. The success of these in vivo and in vitro experiments suggested that these four identified oncomiRs may have therapeutic potential.

16.
Artigo em Inglês | MEDLINE | ID: mdl-36091593

RESUMO

Objective: To observe the difference between peripheral blood T lymphocytes subsets and cycokines in children with severe adenovirus pneumonia and nonsevere adenovirus pneumonia, and to investigate their clinical value in the prognosis of severe pneumonia. Methods: 215 children with adenovirus pneumonia and 30 healthy volunteers (which was set as the control group) in our hospital from January 2017 to May 2019 were enrolled in the study. There were 47 children with severe pneumonia in the severe group and 168 nonsevere pneumonia children in the nonsevere group. The flow cytometry and ELISA methods were used to detect the serum levels of CD3 +, CD4 +, CD8 + T cells and interleukin-2 (IL-2), IL-4, IL-6, IL-10, tumor necrosis factor-α (TNF-α), interferon-γ (IFN-γ). Results: (1) The levels of CD3 (%) T cells, CD4 (%) T cells, and CD4/CD8 ratio values of children with adenovirus pneumonia were lower than these of normal children (P < 0.05). And the levels of CD3 (%) T cells, CD4 (%) T cells, and CD4/CD8 ratio values of children in the severe group were lower than these of children in the nonsevere group (P < 0.05). (2) The levels of IL-2, IL-6, IL-10, TNF-α, and IFN-γ values of children with adenovirus pneumonia were lower than these of normal children (P < 0.05). And the levels of IL-2, IL-6, IL-10, TNF-α, and IFN-γ of children in the severe group were higher than these of children in the nonsevere group (P < 0.05). (3) Among the 47 children with severe adenoviral pneumonia, 39 received systematic treatment in our hospital. According to the treatment effect, 39 children were divided into the effective group (n = 25) and the ineffective group (n = 14). (4) The CD3 (%), CD4 (%), and CD4/CD8 ratios of the children in the effective group were higher than those in the ineffective group (P < 0.05). (5) The levels of IL-2, IL-6, IL-10, TNF-α, and IFN-γ in the effective group were lower than those in the ineffective group (P < 0.05). Conclusion: The immunophenotype of peripheral blood T lymphocytes and cycokines could be helpful to judge the severity of adenovirus pneumonia, which could be used as the objective indexes to evaluate the prognosis of children with severe adenovirus pneumonia.

17.
Immunotherapy ; 2022 Sep 12.
Artigo em Inglês | MEDLINE | ID: mdl-36097695

RESUMO

Background: The therapeutic efficacy of dendritic cell (DC)-immunotherapy for large hepatoma in mice is unsatisfactory. Materials & methods: DC-based immunotherapy was used to treat Hepa1-6 tumors measuring 6 ± 1 mm in diameter, enhanced by boosting tumor antigens. Results: CD4+ and CD8+ T-cells were contracted and transformed into memory phenotypic cells after DC-based vaccination. When T-cells were re-stimulated, T-cells obtained from mice boosted by tumor antigen injection showed highest proliferation capacity. When mice with large tumors were treated, DC-based vaccination boosted by tumor antigen and an additional DC-infusion yielded curative rates of 50% and 23.1%, respectively. Conclusion: DC vaccination induced effector memory cells. Antigen presentation recalled by DC or tumor antigens increased the curative rate in mice with large tumors.


Hepatocellular carcinoma is the most common liver malignancy and is often found at advanced stage. Immune checkpoint inhibitor combined with a molecular targeting agent is a new strategy for the treatment of advanced hepatocellular carcinoma and yields 30% of objective response rate. However, we still need another treatment for the patients who are not responsive to immune checkpoint inhibitor combined with a molecular targeting agent. Dendritic cell-based immunotherapy is one of the treatments for advanced hepatocellular carcinoma. In this animal study, dendritic cells can activate T-lymphocytes to kill cancer cells. Dendritic cells can also induce memory T-lymphocytes, which can be reactive by boost tumor antigens and increase therapeutic efficacy. This treatment strategy, dendritic cell infusion followed by tumor-antigen injection, can be translated into clinical practice in the future.

18.
Int J Mol Sci ; 23(18)2022 Sep 11.
Artigo em Inglês | MEDLINE | ID: mdl-36142451

RESUMO

Endocrine therapy (ET) of selective estrogen receptor modulators (SERMs), selective estrogen receptor downregulators (SERDs), and aromatase inhibitors (AIs) has been used as the gold standard treatment for hormone-receptor-positive (HR+) breast cancer. Despite its clinical benefits, approximately 30% of patients develop ET resistance, which remains a major clinical challenge in patients with HR+ breast cancer. The mechanisms of ET resistance mainly focus on mutations in the ER and related pathways; however, other targets still exist from ligand-independent ER reactivation. Moreover, mutations in the ER that confer resistance to SERMs or AIs seldom appear in SERDs. To date, little research has been conducted to identify a critical target that appears in both SERMs/SERDs and AIs. In this study, we conducted comprehensive transcriptomic and proteomic analyses from two cohorts of The Cancer Genome Atlas Breast Invasive Carcinoma (TCGA-BRCA) to identify the critical targets for both SERMs/SERDs and AIs of ET resistance. From a treatment response cohort with treatment response for the initial ET regimen and an endocrine therapy cohort with survival outcomes, we identified candidate gene sets that appeared in both SERMs/SERDs and AIs of ET resistance. The candidate gene sets successfully differentiated progress/resistant groups (PD) from complete response groups (CR) and were significantly correlated with survival outcomes in both cohorts. In summary, this study provides valuable clinical implications for the critical roles played by candidate gene sets in the diagnosis, mechanism, and therapeutic strategy for both SERMs/SERDs and AIs of ET resistance for the future.

19.
Nutrients ; 14(18)2022 Sep 16.
Artigo em Inglês | MEDLINE | ID: mdl-36145206

RESUMO

The incidence and prevalence of inflammatory bowel disease (IBD) have been increasing globally and progressively in recent decades. Barley leaf (BL) is a nutritional supplement that is shown to have health-promoting effects on intestinal homeostasis. Our previous study demonstrated that BL could significantly attenuate Citrobacter rodentium (CR)-induced colitis, but whether it exerts a prophylactic or therapeutic effect remains elusive. In this study, we supplemented BL before or during CR infestation to investigate which way BL acts. The results showed that BL supplementation prior to infection significantly reduced the disease activity index (DAI) score, weight loss, colon shortening, colonic wall swelling, and transmissible murine colonic hyperplasia. It significantly reduced the amount of CR in the feces and also markedly inhibited the extraintestinal transmission of CR. Meanwhile, it significantly reduced the levels and expression of tumor necrosis factor-alpha (TNF-α), interferon-gamma (IFNγ), and interleukin-1ß (IL1ß). In addition, pretreatment with BL improved CR-induced gut microbiota dysbiosis by reducing the content of Proteobacteria, while increasing the content of Lactobacillus. In contrast, the effect of BL supplementation during infestation on the improvement of CR-induced colitis was not as good as that of pretreatment with BL. In conclusion, BL protects against CR-caused colitis in a preventive manner.

20.
Sci Total Environ ; 852: 158474, 2022 Sep 01.
Artigo em Inglês | MEDLINE | ID: mdl-36058333

RESUMO

Drought events have considerable direct and indirect economic, environmental, and social impacts, but few studies have analyzed and assessed future changes in drought disasters from a risk perspective to guide responses and adaptations thoroughly. Studying the potential climate-related impacts on future crop yield is therefore urgently needed. Intercomparison of the three Shared Socio-economic Pathway (SSP) scenarios based drought risks and yield loss of China was carried out using the climate models from the Coupled Model Intercomparison Project Phase 6 (CMIP6), and the hotspots of high drought risk regions were identified. This study found that the areas affected by severe maize drought (loss ratio larger than 0.2) accounted for 16.13 %, 20.79 %, and 18.87 % of the total national corn areas under three low, medium-to-high and high emission scenarios (SSP1-2.6, SSP3-7.0, SSP5-8.5) respectively. The northwest China maize region, the ecotone between agriculture and animal husbandry, and the western central northern China maize region have relatively high loss risk. Compared with SSP1-2.6, the yield loss rates increased with 70.73 % and 61.52 % of national corn areas for SSP3-7.0 and SSP5-8.5, respectively. There is a decrease in the areas with low-risk and a significant increase in the areas with high-risk for SSP3-7.0 and SSP5-8.5 compared to the SSP1-2.6. These results may provide theoretical support for agricultural drought risk reduction and adaptation planning to ensure food security under climate change.

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