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1.
Artigo em Inglês | MEDLINE | ID: mdl-35576414

RESUMO

Graph convolutional network (GCN) outputs powerful representation by considering the structure information of the data to conduct representation learning, but its robustness is sensitive to the quality of both the feature matrix and the initial graph. In this article, we propose a novel multigraph fusion method to produce a high-quality graph and a low-dimensional space of original high-dimensional data for the GCN model. Specifically, the proposed method first extracts the common information and the complementary information among multiple local graphs to obtain a unified local graph, which is then fused with the global graph of the data to obtain the initial graph for the GCN model. As a result, the proposed method conducts the graph fusion process twice to simultaneously learn the low-dimensional space and the intrinsic graph structure of the data in a unified framework. Experimental results on real datasets demonstrated that our method outperformed the comparison methods in terms of classification tasks.

2.
Gene ; : 146557, 2022 May 11.
Artigo em Inglês | MEDLINE | ID: mdl-35568338

RESUMO

Plant small-RNAs regulate various biological processes by manipulating the expression of target genes at the transcriptional and post-transcriptional levels. However, little is known about the response and the functional roles of sRNAs, particularly small-interfering RNAs (siRNAs), in the soybean-soybean cyst nematode interaction. In this study, siRNA data from 24 sRNA libraries constructed from SCN-infected and non-SCN-infected resistant and susceptible soybean roots were analysed in silico. A total of 26 novel siRNAs including 17 phasiRNAs and 9 nat-siRNAs, as well as two phasiRNAs that were differentially expressed (DE) in three comparisons, were identified. Then, using qRT-PCR, the expression of majority of siRNAs was found to be downregulated after SCN infection, and the expression patterns of DE siRNAs were confirmed. Further functional annotation analyses revealed that the target genes of these siRNA were highly related to disease resistance, which included the genes coding for the NB-ARC domain, leucine-rich repeats, and Hs1pro-1 homologous proteins. Overall, the present research identified novel siRNAs and annotated their target genes, thereby laying the foundation for deciphering the roles of siRNAs in the soybean-SCN interaction.

3.
Nat Commun ; 13(1): 2430, 2022 May 04.
Artigo em Inglês | MEDLINE | ID: mdl-35508501

RESUMO

Platinum is the most efficient catalyst for hydrogen evolution reaction in acidic conditions, but its widespread use has been impeded by scarcity and high cost. Herein, Pt atomic clusters (Pt ACs) containing Pt-O-Pt units were prepared using Co/N co-doped carbon (CoNC) as support. Pt ACs are anchored to single Co atoms on CoNC by forming strong interactions. Pt-ACs/CoNC exhibits only 24 mV overpotential at 10 mA cm-2 and a high mass activity of 28.6 A mg-1 at 50 mV, which is more than 6 times higher than commercial Pt/C with any Pt loadings. Spectroscopic measurements and computational modeling reveal the enhanced hydrogen generation activity attributes to the charge redistribution between Pt and O atoms in Pt-O-Pt units, making Pt atoms the main active sites and O linkers the assistants, thus optimizing the proton adsorption and hydrogen desorption. This work opens an avenue to fabricate noble-metal-based ACs stabilized by single-atom catalysts with desired properties for electrocatalysis.

4.
Front Oncol ; 12: 859409, 2022.
Artigo em Inglês | MEDLINE | ID: mdl-35402239

RESUMO

Purpose: Treatment of epithelial ovarian cancer is evolving towards personalization and precision, which require patient-specific estimates of overall survival (OS) and progression-free survival (PFS). Patients and Methods: Medical records of 1173 patients who underwent debulking surgery in our center were comprehensively reviewed and randomly allocated into a derivation cohort of 879 patients and an internal validation cohort of 294 patients. Five hundred and seventy-seven patients from the other three cancer centers served as the external validation cohort. A novel nomogram model for PFS and OS was constructed based on independent predictors identified by multivariable Cox regression analysis. The predictive accuracy and discriminative ability of the model were measured using Harrell's concordance index (C-index) and calibration curve. Results: The C-index values were 0.82 (95% CI: 0.76-0.88) and 0.84 (95% CI: 0.78-0.90) for the PFS and OS models, respectively, substantially higher than those obtained with the FIGO staging system and most nomograms reported for use in epithelial ovarian cancer. The nomogram score could clearly classify the patients into subgroups with different risks of recurrence or postoperative mortality. The online versions of our nomograms are available at https://eocnomogram.shinyapps.io/eocpfs/ and https://eocnomogram.shinyapps.io/eocos/. Conclusion: A externally validated nomogram predicting OS and PFS in patients after R0 reduction surgery was established using a propensity score matching model. This nomogram may be useful in estimating individual recurrence risk and guiding personalized surveillance programs for patients after surgery, and it could potentially aid clinical decision-making or stratification for clinical trials.

5.
Artigo em Inglês | MEDLINE | ID: mdl-35445821

RESUMO

Hydrogarnets are vital intermediate products in the calcification- carbonation method, which is designed for Bayer red mud treatment. Their carbonation performance greatly depends on SiO2 substitution. In this study, different SiO2-substituted hydrogarnets were synthesized and characterized. Then, batch experiments were performed to evaluate the potential effects of important parameters such as CO2 pressure, and SiO2 substitution degree (x) on the carbonation process. The SiO2 substitution degrees of the hydrogarnets synthesized at 60, 120, 180, and 240°C were 0.27, 0.36, 0.70, and 0.73, respectively. As the SiO2 substitution degree increased, the hydrogarnet carbonation extents gradually declined. With an increase in CO2 pressure, the hydrogarnet carbonation percentages increased gradually and rose from 80.33% to 98.19% within 120 min. The phases detected in the carbonized products were strip-like aragonite as well as some calcite; the Al-rich and Si-rich phases in the carbonized products were amorphous.

6.
Artigo em Inglês | MEDLINE | ID: mdl-35380973

RESUMO

Graph neural networks (GNNs) conduct feature learning by taking into account the local structure preservation of the data to produce discriminative features, but need to address the following issues, i.e., 1) the initial graph containing faulty and missing edges often affect feature learning and 2) most GNN methods suffer from the issue of out-of-example since their training processes do not directly generate a prediction model to predict unseen data points. In this work, we propose a reverse GNN model to learn the graph from the intrinsic space of the original data points as well as to investigate a new out-of-sample extension method. As a result, the proposed method can output a high-quality graph to improve the quality of feature learning, while the new method of out-of-sample extension makes our reverse GNN method available for conducting supervised learning and semi-supervised learning. Experimental results on real-world datasets show that our method outputs competitive classification performance, compared to state-of-the-art methods, in terms of semi-supervised node classification, out-of-sample extension, random edge attack, link prediction, and image retrieval.

7.
Clin Transl Med ; 12(4): e546, 2022 04.
Artigo em Inglês | MEDLINE | ID: mdl-35474299

RESUMO

BACKGROUND: Ischemia-reperfusion injury (IRI) is considered an inherent component of organ transplantation that compromises transplant outcomes and organ availability. The ischemia-free liver transplantation (IFLT) procedure has been developed to avoid interruption of blood supply to liver grafts. It is unknown how IFLT might change the characteristics of graft IRI. METHODS: Serum and liver biopsy samples were collected from IFLT and conventional liver transplantation (CLT) recipients. Pathological, metabolomics, transcriptomics, and proteomics analyses were performed to identify the characteristic changes in graft IRI in IFLT. RESULTS: Peak aspartate aminotransferase (539.59 ± 661.76 U/L versus 2622.28 ± 3291.57 U/L) and alanine aminotransferase (297.64 ± 549.50 U/L versus 1184.16 ± 1502.76 U/L) levels within the first 7 days and total bilirubin levels by day 7 (3.27 ± 2.82 mg/dl versus 8.33 ± 8.76 mg/dl) were lower in the IFLT versus CLT group (all p values < 0.001). The pathological characteristics of IRI were more obvious in CLT grafts. The antioxidant pentose phosphate pathway remained active throughout the procedure in IFLT grafts and was suppressed during preservation and overactivated postrevascularization in CLT grafts. Gene transcriptional reprogramming was almost absent during IFLT but was profound during CLT. Proteomics analysis showed that "metabolism of RNA" was the major differentially expressed process between the two groups. Several proinflammatory pathways were not activated post-IFLT as they were post-CLT. The activities of natural killer cells, macrophages, and neutrophils were lower in IFLT grafts than in CLT grafts. The serum levels of 14 cytokines were increased in CLT versus IFLT recipients. CONCLUSIONS: IFLT can largely avoid the biological consequences of graft IRI, thus has the potential to improve transplant outcome while increasing organ utilization.


Assuntos
Transplante de Fígado , Traumatismo por Reperfusão , Alanina Transaminase , Humanos , Isquemia/patologia , Fígado/irrigação sanguínea , Fígado/metabolismo , Fígado/patologia , Transplante de Fígado/métodos , Traumatismo por Reperfusão/metabolismo , Traumatismo por Reperfusão/patologia
8.
BMC Surg ; 22(1): 130, 2022 Apr 07.
Artigo em Inglês | MEDLINE | ID: mdl-35392876

RESUMO

BACKGROUND: It is no consensus on the best management for patients with large hepatic hemangiomas. This study was designed to evaluate the efficacy and safety of percutaneous sclerotherapy compared to surgical resection for large hepatic hemangiomas. METHODS: A total of 89 patients with large hepatic hemangiomas from single center underwent either percutaneous sclerotherapy (n = 14) or surgical resection (n = 75) as first-line treatment was retrospectively studied, followed up for 9-24 months using ultrasound. Terms of intraoperative and postoperative information, postoperative complications, and treatment effectiveness were compared between the two groups. RESULTS: Percutaneous sclerotherapy had shorter operative time (p < 0.001), less blood loss, lower rate of prophylactic abdominal drainage (97.3% vs. 0%, p < 0.001), fewer minor complications (48.0% vs. 7.1%, p < 0.01), shorter hospital stay (p < 0.001), lower hospital cost (p < 0.001), higher Alb level (p < 0.001) and lower postoperative clinical index including ALT, AST and WBC (p < 0.001 for both) than did surgical resection. The major complications were demonstrated no significant difference between the two groups. In addition, the mean maximum cross-sectional areas of hemangioma dropped from 5044.1 ± 2058.0 mm2 to 1924.6 ± 1989.5 mm2 (65.2% reduction) during 9-24 months follow-up (p < 0.001) in the percutaneous sclerotherapy group, while all patients in the surgical resection group achieved complete response. CONCLUSION: Percutaneous sclerotherapy is the preferred method for the treatment of large hepatic hemangioma over surgical resection when compared with the items of postoperative recovery, blood loss, complications, hospital stays, and lower hospital costs. The reduction of the maximum cross-sectional area of hepatic hemangioma in the percutaneous sclerotherapy group is satisfactory.


Assuntos
Hemangioma , Neoplasias Hepáticas , Hemangioma/cirurgia , Humanos , Neoplasias Hepáticas/cirurgia , Estudos Retrospectivos , Escleroterapia , Resultado do Tratamento , Ultrassonografia de Intervenção
10.
Nutrients ; 14(5)2022 Feb 27.
Artigo em Inglês | MEDLINE | ID: mdl-35267978

RESUMO

High-fiber diet interventions have been proven to be beneficial for gut microbiota and glycemic control in diabetes patients. However, the effect of a low level of fiber in habitual diets remains unclear. This study aims to examine the associations of habitual dietary fiber intake with gut microbiome profiles among Chinese diabetes patients and identify differential taxa that mediated associations of dietary fiber with HbA1c level. Two cross-sectional studies and one longitudinal study were designed based on two follow-up surveys in a randomized trial conducted during 2015-2017. The study included 356 and 310 participants in the first and second follow-ups, respectively, with 293 participants in common in both surveys. Dietary fiber intake was calculated based on a 3-day 24-h diet recall at each survey and was classified into a lower or a higher group according to the levels taken based on the two surveys using 7.2 g/day as a cut-off value. HbA1c was assayed to assess glycemic status using a cut-off point of 7.0% and 8.0%. Microbiome was profiled by 16S rRNA sequencing. A high habitual dietary fiber intake was associated with a decrease in α-diversity in both the cross-sectional and longitudinal analyses. At the first follow-up, phylum Firmicutes and Fusobacteria were negatively associated with a higher dietary fiber intake (p < 0.05, Q < 0.15); at the second follow-up, genus Adlercreutzia, Prevotella, Ruminococcus, and Desulfovibrio were less abundant in patients taking higher dietary fiber (p < 0.05, Q < 0.15); genus Desulfovibrio and Ruminococcaceae (Unknown), two identified differential taxa by HbA1c level, were negatively associated with dietary fiber intake in both the cross-sectional and longitudinal analyses, and mediated the dietary fiber-HbA1c associations among patients taking dietary fiber ≥ 7.2 g/day (mediation effect ß [95%CI]: -0.019 [-0.043, -0.003], p = 0.018 and -0.019 [-0.046, -0.003], p = 0.016). Our results suggest that habitual dietary fiber intake has a beneficial effect on gut microbiota in Chinese diabetes patients. Further studies are needed to confirm our results.


Assuntos
Diabetes Mellitus Tipo 2 , Microbioma Gastrointestinal , China , Estudos Transversais , Fibras na Dieta/análise , Hemoglobina A Glicada/análise , Humanos , Estudos Longitudinais , RNA Ribossômico 16S
11.
Cell Cycle ; : 1-13, 2022 Mar 11.
Artigo em Inglês | MEDLINE | ID: mdl-35275048

RESUMO

As a common cause of liver injury, hepatic ischemia/reperfusion injury (HIRI) happens in various clinical conditions including trauma, hepatectomy and liver transplantation. Since transcription factor Yin Yang 1 (YY1) was reported to be downregulated after ischemia/reperfusion (I/R) injury, we focused on YY1 to explore its function in HIRI by functional assays like Cell Counting Kit-8 (CCK-8) assays and flow cytometry assays. The RT-qPCR assay revealed that YY1 was downregulated in hepatocytes after I/R injury. The function assays disclosed that YY1 facilitated cell viability and proliferation, but hindered cell apoptosis in hepatocytes after I/R injury. Through mechanism assays including luciferase reporter assay, RIP and RNA pulldown assay, miR-186-5p was found to bind with YY1 and promote hepatocyte apoptosis by targeting YY1. Subsequently, we verified that small nucleolar RNA host gene 1 (SNHG1) could sponge miR-186-5p to upregulate YY1. Importantly, we figured out that YY1 had a positive regulation on SNHG1. Along the way, YY1 was identified as the upstream transcription factor for SNHG1. In conclusion, our study unveiled a novel competing endogenous RNA (ceRNA) pattern of SNHG1/miR-186-5p/YY1 positive feedback loop in hepatic I/R injury, which might provide new insight into prevention of HIRI during liver transplantation or hepatic surgery.

12.
Magn Reson Med ; 87(6): 2901-2913, 2022 06.
Artigo em Inglês | MEDLINE | ID: mdl-35129226

RESUMO

PURPOSE: Quantitative T1 and T2 mapping in non-human primates with whole-brain coverage is challenged by the requirement of sub-millimeter resolution and the inhomogeneity of the transmit magnetic field (B1 + ) covering a large field of view. The goal of the current study is to develop a magnetic resonance fingerprinting (MRF) method for simultaneous T1 and T2 mapping of the entire macaque brain within feasible scan time. METHODS: A three-dimensional (3D) MRF sequence with both inversion- and T2 -preparation modules was developed and evaluated on a 9.4 T preclinical scanner. Data acquisition used a 3D stack-of-spirals trajectory, with undersampling along both the in-plane and the through-plane directions. The effect of B1 + inhomogeneity was accounted for by matching the acquired fingerprint to a dictionary simulated with the B1 + factors measured from a separate scan. In vitro and ex vivo studies were performed to evaluate the accuracy and the undersampling capacity of the MRF method. The application of the MRF method for in vivo, brain-wide T1 and T2 mapping was demonstrated on macaques at 4, 6, and 12 years of age. RESULTS: The MRF method enabled highly repeatable T1 and T2 mapping at high spatial resolution (0.35 × 0.35 × 1 mm3 ) with an acceleration factor of 24. In vivo studies showed significant age-related T2 reduction in deep gray nuclei including the globus pallidus, the putamen, and the caudate nucleus. CONCLUSIONS: This study demonstrates the first MRF study for brain-wide, multi-parametric quantification in non-human primates with sub-millimeter resolution.


Assuntos
Macaca , Imageamento por Ressonância Magnética , Animais , Encéfalo/diagnóstico por imagem , Processamento de Imagem Assistida por Computador/métodos , Imageamento por Ressonância Magnética/métodos , Espectroscopia de Ressonância Magnética , Imagens de Fantasmas
13.
Cell Res ; 32(3): 302-314, 2022 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-35110668

RESUMO

Methanobactins (Mbns) are a family of copper-binding peptides involved in copper uptake by methanotrophs, and are potential therapeutic agents for treating diseases characterized by disordered copper accumulation. Mbns are produced via modification of MbnA precursor peptides at cysteine residues catalyzed by the core biosynthetic machinery containing MbnB, an iron-dependent enzyme, and MbnC. However, mechanistic details underlying the catalysis of the MbnBC holoenzyme remain unclear. Here, we present crystal structures of MbnABC complexes from two distinct species, revealing that the leader peptide of the substrate MbnA binds MbnC for recruitment of the MbnBC holoenzyme, while the core peptide of MbnA resides in the catalytic cavity created by the MbnB-MbnC interaction which harbors a unique tri-iron cluster. Ligation of the substrate sulfhydryl group to the tri-iron center achieves a dioxygen-dependent reaction for oxazolone-thioamide installation. Structural analysis of the MbnABC complexes together with functional investigation of MbnB variants identified a conserved catalytic aspartate residue as a general base required for MbnBC-mediated MbnA modification. Together, our study reveals the similar architecture and function of MbnBC complexes from different species, demonstrating an evolutionarily conserved catalytic mechanism of the MbnBC holoenzymes.


Assuntos
Cobre , Ferro , Catálise , Cobre/metabolismo , Holoenzimas/química , Imidazóis , Oligopeptídeos
14.
Mol Nutr Food Res ; : e2100857, 2022 Feb 25.
Artigo em Inglês | MEDLINE | ID: mdl-35212448

RESUMO

SCOPE: Glycine is commonly used as an additive in bone health supplements, the activity and differentiation of bone mesenchymal stem cells (BMSCs) are essential to bone metabolism, but the effect of Glycine on bone metabolism and specific mechanism are not fully clarified. METHODS AND RESULTS: The ovariectomized rats to evaluate the effects of Glycine on bone quality and quantity is constructed; then used an ER signaling inhibitor (ICI182780) and an ERα deficient BMSCs to explore how Glycine mediated ERα regulating the osteogenic and adipogenic differentiation of BMSCs; furthermore, an autodock analysis is used to assess the affinity of Glycine and ERα. The results show that Glycine significantly moderated bone mass and bone microstructure in ovariectomized rats; Glycine stimulates the osteogenic differentiation and attenuates the adipogenic differentiation in OVX rats and BMSCs, and these effects could be abolished by ICI 182780; further docking experiment showes that Glycine and ERα have a stronger affinity, and finally proves that the impact of Glycine could be blocked by ERα. CONCLUSION: Glycine stimulates osteogenesis and attenuates adipogenesis in ovariectomized rats, which process may involve in ERα mediated ER signaling pathway.

15.
Neoplasma ; 69(2): 383-391, 2022 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-35225647

RESUMO

The incidence rate of esophageal squamous cell carcinoma (ESCC) has risen significantly in recent years. RNA binding protein (RBP) has been attracting increased attention in the treatment of ESCC. Therefore, the primary aim of this study was to explore the roles of the RBP Hu antigen R (HuR) in ESCC. The mRNA levels were detected via reverse transcription-quantitative PCR, while the expression levels of protein were evaluated using western blotting. Cell proliferation was estimated by cell counting kit-8 assay and colony formation assay. Flow cytometry was applied to measure cell apoptosis. Luciferase assay and RIP assay were applied to verify whether interferon-ß (IFN-ß) was targeted by HuR. The results unambiguously demonstrated that HuR was upregulated in ESCC. Overexpression of HuR alleviated chemosensitivity to cisplatin in ESCC cells, as evidenced by increased cell proliferation and decreased apoptosis. Moreover, IFN-ß was found to be a target of HuR and downregulated in ESCC cells. And overexpression of IFN-ß abrogated the effects of HuR on cisplatin-sensitivity of ESCC cells. Taken together, these findings suggested that HuR may alleviate the chemosensitivity of ESCC cells to cisplatin via binding to IFN-ß. Therefore, the HuR/IFN-ß axis may be a novel biomarker for improving the chemosensitivity of ESCC.


Assuntos
Neoplasias Esofágicas , Carcinoma de Células Escamosas do Esôfago , MicroRNAs , Apoptose , Linhagem Celular Tumoral , Proliferação de Células/genética , Cisplatino/farmacologia , Neoplasias Esofágicas/genética , Carcinoma de Células Escamosas do Esôfago/tratamento farmacológico , Carcinoma de Células Escamosas do Esôfago/genética , Carcinoma de Células Escamosas do Esôfago/metabolismo , Regulação Neoplásica da Expressão Gênica , Humanos , Interferon beta/genética , Interferon beta/metabolismo , Interferon beta/farmacologia , MicroRNAs/genética
17.
BMC Health Serv Res ; 22(1): 160, 2022 Feb 08.
Artigo em Inglês | MEDLINE | ID: mdl-35130901

RESUMO

BACKGROUND: The success of telescreening and the management of diabetic retinopathy (DR) in communities depends on stakeholder satisfaction, including both individuals with diabetes and community health center (CHC) staff. In this study, we investigated the satisfaction of both individuals with vision-threatening DR (VTDR) and CHC staff within the Shanghai Eye Disease Study (SEDS) comprehensive system for managing diabetic eye diseases at the primary care level. METHODS: The cross-sectional survey of patients receiving the service included 3,817 respondents with VTDR and focused on their satisfaction with the SEDS system, including the telescreening process, speed of feedback, interpretation of results, increased awareness of related diseases, and eye care services. The survey of the providers included 234 CHC staff respondents and focused on their satisfaction and the main barriers encountered during the implementation of the system. Sociodemographic characteristics and perceived barriers related to satisfaction were identified by conducting univariate and multivariate logistic regression analyses. RESULTS: The overall satisfaction of service recipients was 96.0%, and 75.8% of them were willing to undergo future telescreening for DR. The convenience of telescreening, organization of telescreening, and improvement in related disease awareness significantly correlated with satisfaction. Only 48.3% of the providers were satisfied with the SEDS system. The most frequently mentioned barriers to the development of the system were the inadequate levels of staffing (particularly technical staff), insufficient funding, and incomplete information transmission systems. CONCLUSIONS: Disparities between high patient satisfaction and low provider satisfaction with the SEDS system were mainly related to the current weak level of ophthalmic expertise in the CHCs and the low awareness of screening for diabetic eye diseases among both patients and providers.


Assuntos
Diabetes Mellitus , Retinopatia Diabética , China , Centros Comunitários de Saúde , Estudos Transversais , Retinopatia Diabética/terapia , Humanos , Programas de Rastreamento
18.
Micromachines (Basel) ; 13(2)2022 Feb 02.
Artigo em Inglês | MEDLINE | ID: mdl-35208376

RESUMO

Air microfluidic circuits have been widely concerned in the separation of atmospheric particulate matter, especially for portable particulate matter separation detection devices. Currently, no systematic approach for the design and optimization of an air-microfluidic system for PM separation has been reported in the literature. In this paper, a two-stage air microfluidic circuit is designed. The design process is divided into two stages: first, the preliminary design of the structure is completed according to aerodynamic theory. Then, the influences of various factors (such as flow channel width, tilt angle, flow rate, etc.) on the collection efficiency and particle wall loss are explored through numerical analysis to complete the optimization design of the structure. Finally, the air microfluidic circuit is prepared by MEMS processing technology and the particulate matter separation experiments are carried out. The developed two-stage air microfluidic circuit can realize the efficient separation of PM10 and PM2.5. Thus, the important factors affecting the collection efficiency and particle wall loss of air microfluidic circuit are clarified, and a systematic design theory method is formed.

19.
Nutr Res ; 99: 25-39, 2022 03.
Artigo em Inglês | MEDLINE | ID: mdl-35091275

RESUMO

Heat stress resulting from global warming is a serious threat to livestock and humans and can cause impaired metabolism, dysregulated immune functions, and even death. Liver transcriptome of the heat-stressed rabbits supplemented with oral Moringa oleifera leaf powder (MOLP) was performed with the hypothesis that antioxidative properties of MOLP might help to maintain homeostasis under heat stress environment. A total of 21 rabbits were divided into 3 groups (n = 7/group); control (CON, 25°C), heat stress (HS, 35°C for 7 hours daily), and HS supplemented with MOLP (HSM, 35°C) at 200 mg/kg body weight daily for 28 days. Serum analysis indicated that dietary MOLP (HSM) reduced glucose, total cholesterol, triglycerides, and low-density lipoprotein cholesterol contents compared with the HS group (P < .05). The HS group showed increased mRNA expression of interleukin (IL)-1α and IL-1ß (P < .05), whereas enhanced expression of Nrf2 was observed in HSM compared with the HS group indicates antioxidative capacity of MOLP. Up-regulated genes PCK1 and ANGPTL4 as indicated by transcriptome analysis can explain increased serum glucose and lipid levels in the HS group. Up-regulation of antiapoptotic gene BCL2A1 by MOLP may suggest protection from heat stress induced apoptosis. In HSM, the up-regulated IL-6 family genes dictate their importance for immune and survival response, whereas genes PIK3R5 and TLR-2 are vital in thermo-tolerance. Further, identification of marker genes elucidates stress regulation response. In conclusion, findings of current study reveal beneficial aspects of dietary MOLP on liver function in heat-stressed rabbits.


Assuntos
Moringa oleifera , Animais , Antioxidantes/metabolismo , Antioxidantes/farmacologia , Suplementos Nutricionais/análise , Resposta ao Choque Térmico , Metabolismo dos Lipídeos , Fígado/metabolismo , Moringa oleifera/metabolismo , Folhas de Planta/metabolismo , Pós , Coelhos , Transcriptoma , Regulação para Cima
20.
Nat Cell Biol ; 24(1): 88-98, 2022 01.
Artigo em Inglês | MEDLINE | ID: mdl-35027735

RESUMO

The accumulation of lipid peroxides is recognized as a determinant of the occurrence of ferroptosis. However, the sensors and amplifying process of lipid peroxidation linked to ferroptosis remain obscure. Here we identify PKCßII as a critical contributor of ferroptosis through independent genome-wide CRISPR-Cas9 and kinase inhibitor library screening. Our results show that PKCßII senses the initial lipid peroxides and amplifies lipid peroxidation linked to ferroptosis through phosphorylation and activation of ACSL4. Lipidomics analysis shows that activated ACSL4 catalyses polyunsaturated fatty acid-containing lipid biosynthesis and promotes the accumulation of lipid peroxidation products, leading to ferroptosis. Attenuation of the PKCßII-ACSL4 pathway effectively blocks ferroptosis in vitro and impairs ferroptosis-associated cancer immunotherapy in vivo. Our results identify PKCßII as a sensor of lipid peroxidation, and the lipid peroxidation-PKCßII-ACSL4 positive-feedback axis may provide potential targets for ferroptosis-associated disease treatment.


Assuntos
Coenzima A Ligases/metabolismo , Ferroptose/fisiologia , Peroxidação de Lipídeos/fisiologia , Proteína Quinase C beta/metabolismo , Animais , Sistemas CRISPR-Cas/genética , Linhagem Celular Tumoral , Técnicas de Inativação de Genes , Humanos , Imunoterapia/métodos , Camundongos , Camundongos Endogâmicos BALB C , Camundongos Endogâmicos C57BL , Neoplasias/terapia , Fosforilação , Proteína Quinase C beta/genética
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