Your browser doesn't support javascript.
loading
Mostrar: 20 | 50 | 100
Resultados 1 - 20 de 5.716
Filtrar
1.
mBio ; 12(4): e0147021, 2021 Aug 31.
Artigo em Inglês | MEDLINE | ID: mdl-34465024

RESUMO

To reveal the dynamic features of cellular systems, such as the correlation among phenotypes, a time or condition series set of samples is typically required. Here, we propose intra-ramanome correlation analysis (IRCA) to achieve this goal from just one snapshot of an isogenic population, via pairwise correlation among the cells of the thousands of Raman peaks in single-cell Raman spectra (SCRS), i.e., by taking advantage of the intrinsic metabolic heterogeneity among individual cells. For example, IRCA of Chlamydomonas reinhardtii under nitrogen depletion revealed metabolite conversions at each time point plus their temporal dynamics, such as protein-to-starch conversion followed by starch-to-triacylglycerol (TAG) conversion, and conversion of membrane lipids to TAG. Such among-cell correlations in SCRS vanished when the starch-biosynthesis pathway was knocked out yet were fully restored by genetic complementation. Extension of IRCA to 64 microalgal, fungal, and bacterial ramanomes suggests the IRCA-derived metabolite conversion network as an intrinsic metabolic signature of isogenic cellular population that is reliable, species-resolved, and state-sensitive. The high-throughput, low cost, excellent scalability, and general extendibility of IRCA suggest its broad applications. IMPORTANCE Each isogenic population of cells is characterized by many phenotypes, which change with time and condition. Correlations among such phenotypes are fundamental to system function, yet revelation of such links typically requires multiple samples. Here, we showed that, by exploiting the intrinsic metabolic heterogeneity among individual cells, such interphenotype correlations can be unveiled via just one snapshot of an isogenic cellular population. Specifically, a network of potential metabolite conversions can be reconstructed using intra-ramanome correlation analysis (IRCA), by pairwise correlation of the thousands of Raman peaks or combination of peaks among single-cell Raman spectra sampled from just one instance of the cellular population. The ability to rapidly and noninvasively reveal intermetabolite conversions from just one snapshot of one sample should usher in many new opportunities in functional profiling of cellular systems.

2.
J Exp Clin Cancer Res ; 40(1): 278, 2021 Sep 01.
Artigo em Inglês | MEDLINE | ID: mdl-34470658

RESUMO

BACKGROUND: Glioblastoma multiforme (GBM), a lethal brain tumor, remains the most daunting challenge in cancer therapy. Overexpression and constitutive activation of PDGFs and PDGFRα are observed in most GBM; however, available inhibitors targeting isolated signaling pathways are minimally effective. Therefore, better understanding of crucial mechanisms underlying GBM is needed for developing more effective targeted therapies. METHODS: Target genes controlled by HIF1α in GBM were identified by analysis of TCGA database and by RNA-sequencing of GBM cells with HIF1α knockout by sgRNA-Cas9 method. Functional roles of HIF1α, PDGFs and PDGFRs were elucidated by loss- or gain-of-function assays or chemical inhibitors, and compared in response to oxygen tension. Pharmacological efficacy and gene expression in mice with intracranial xenografts of primary GBM were analyzed by bioluminescence imaging and immunofluorescence. RESULTS: HIF1α binds the PDGFD proximal promoter and PDGFRA intron enhancers in GBM cells under normoxia or mild-hypoxia to induce their expression and maintain constitutive activation of AKT signaling, which in turn increases HIF1α protein level and activity. Paradoxically, severe hypoxia abrogates PDGFRα expression despite enhancing HIF1α accumulation and corresponding PDGF-D expression. Knockout of HIF1A, PDGFD or PDGFRA in U251 cells inhibits cell growth and invasion in vitro and eradicates tumor growth in vivo. HIF1A knockdown in primary GBM extends survival of xenograft mice, whereas PDGFD overexpression in GL261 shortens survival. HIF1α inhibitor Echinomycin induces GBM cell apoptosis and effectively inhibits growth of GBM in vivo by simultaneously targeting HIF1α-PDGFD/PDGFRα-AKT feedforward pathway. CONCLUSIONS: HIF1α orchestrates expression of PDGF-D and PDGFRα for constitutive activation of AKT pathway and is crucial for GBM malignancy. Therefore, therapies targeting HIF1α should provide an effective treatment for GBM.

3.
Pharmacol Res ; 173: 105752, 2021 Sep 02.
Artigo em Inglês | MEDLINE | ID: mdl-34481072

RESUMO

Traditional Chinese medicine (TCM) formula is widely used for thousands of years in clinical practice. With the development of artificial intelligence, deep learning models may help doctors prescribe reasonable formulas. Meanwhile, current studies of formula recommendation only focus on the observable clinical symptoms and lack of molecular information. Here, inspired by the theory of TCM network pharmacology, we propose an intelligent formula recommendation system based on deep learning (FordNet), fusing the information of phenotype and molecule. We collected more than 20,000 electronic health records from TCM Master Li Jiren's experience from 2013 to March 2020. In the FordNet system, the feature of diagnosis description is extracted by convolution neural network and the feature of TCM formula is extracted by network embedding, which fusing the molecular information. A hierarchical sampling strategy for data augmentation is designed to effectively learn training samples. Based on the expanded samples, a deep neural network based quantitative optimization model is developed for TCM formula recommendation. FordNet performs significantly better than baseline methods (hit ratio of top 10 improved by 46.9% compared with the best baseline random forest method). Moreover, the molecular information helps FordNet improve 17.3% hit ratio compared with the model using only macro information. Clinical evaluation shows that FordNet can well learn the effective experience of TCM Master and obtain excellent recommendation results. Our study, for the first time, proposes an intelligent recommendation system for TCM formula integrating phenotype and molecule information, which has potential to improve clinical diagnosis and treatment, and promote the shift of TCM research pattern from "experience based, macro" to "data based, macro-micro combined" as well as the development of TCM network pharmacology.

4.
Ultrason Sonochem ; 78: 105742, 2021 Aug 30.
Artigo em Inglês | MEDLINE | ID: mdl-34487981

RESUMO

Traditional soaking method takes days to remove cassava cyanide. Ten minutes of ultrasonic pretreatment (UPT) was found to be a new effective method to eliminate both cyanogenic glycosides and hydrogen cyanide in cassava. Here, the parameters of UPT were optimized and the underlying mechanisms were investigated. 40.36% and 24.95% of hydrogen cyanide and cyanogenic glycosides in cassava juice were eliminated under 10 min of UPT (45℃, 81 W). UPT before boiling enhanced the total cyanide elimination to 41.94%. The degradation patterns of hydrogen cyanide and cyanogenic glycosides were different. Ultrasound directly eliminated hydrogen cyanide and indirectly degraded cyanogenic glycosides through promoting enzymatic hydrolysis. The ß-glucosidase activity was increased by 17.99% induced by ultrasound. This was supported by the movement of hydrophobic residual and the rearrangement of the secondary structure of the molecular as found in fluorescence, CD, FTIR, DSC and TG analysis. This study revealed that UPT acted as a fast and simple technical way in improving cassava safety.

5.
World Neurosurg ; 2021 Sep 04.
Artigo em Inglês | MEDLINE | ID: mdl-34492391

RESUMO

OBJECTIVE: To evaluate seizure outcome in patients with seizure-associated dural arteriovenous fistulas (DAVFs). METHODS: Between 2001 and 2019, 1198 consecutive patients underwent treatment for DAVFs in our neuroscience institute. Among these, 48 patients presented with initial seizure before treatment. The seizure outcome after treatment were assessed by patients' medical records, updated clinical information, and, when necessary, direct patient contact. RESULTS: Cortical venous reflux was present in all 48 patients with a history of seizure, including 36 cases with single fistula and 12 cases with multiple DAVFs. Complete angiographic occlusion of DAVFs was achieved in all patients at the latest follow-up. There were no immediate or long-term persistent complications after treatment. At 1-year follow-up, 54.2% (26/48) of the patients were seizure-free, and 29.2% (14/48) were medication-free. At 2-year follow-up, 81.3% (39/48) were seizure-free, and 64.6% (31/48) were medication-free. At the last follow-up (mean 7.9 years), 93.8% (45/48) were seizure-free, and 81.3% (39/48) were medication-free. Fewer than 5 seizures before treatment and a seizure history of <3 months before treatment were 2 independent predictive factors for higher seizure-free rate at 1-year follow-up (before P < 0.05) as well as independent predictive factors for higher medication-free rate at 2-year follow-up (both P < 0.05). CONCLUSIONS: DAVF-related seizures can be effectively controlled through treatment of DAVF. Short seizure history and fewer seizures before treatment predict satisfactory seizure outcome after DAVF treatment, which indicates early treatment for seizure-associated DAVFs.

6.
Int J Pharm ; 608: 121078, 2021 Sep 06.
Artigo em Inglês | MEDLINE | ID: mdl-34500059

RESUMO

Cancer is still a major threat for human life, and the cancer immunotherapy can be more optimized to prolong life. However, the effect of immunotherapy is not encouraging. In order to achieve outstanding immune effect, it is necessary to strengthen antigens uptake of antigen presenting cells. Adjuvants were added to vaccines to achieve this purpose, which could be divided into two types: as an immunostimulatory molecule, the innate immunities of the body were triggered; or as a delivery carrier, and antigens were cross-delivery through the "cytoplasmic pathway" and released at a specific location. This paper reviewed the relevant research status of tumor vaccine immune adjuvants in recent years. Among the review, the function, combination strategies and derivatives of lipid A were discussed in detail. In addition, some suggestions on the existing problems and research direction of lipids as tumor vaccine adjuvants were put forward.

7.
J Colloid Interface Sci ; 607(Pt 1): 357-366, 2021 Sep 02.
Artigo em Inglês | MEDLINE | ID: mdl-34509110

RESUMO

Gas sensors have become increasingly significant because of the rapid development in electronic devices that are applied in detecting noxious gases. Adjusting the crystal phase structure of sensing materials can optimize the band gap and oxygen-adsorptive capacity, which influences the gas sensing characteristics. Therefore, titanium dioxide (TiO2) materials with different crystal phase structures including rutile TiO2 nanorods (R-TiO2 NRs), anatase TiO2 nanoparticles (A-TiO2 NRs) and brookite TiO2 nanorods (B-TiO2 NRs) were synthesized successfully via one-step hydrothermal process, respectively. The gas sensing characteristics were also investigated systematically. The sensors based on R-TiO2 NRs displayed the higher response value (12.3) to 100 ppm acetone vapor at 320 °C compared to A-TiO2 NRs (4.1) and B-TiO2 NRs (2.3). Furthermore, gas sensors based on R-TiO2 NRs exhibited excellent repeatability under six cycles and good selectivity to acetone. The outstanding sensing properties of gas sensors based on R-TiO2 NRs can be ascribed to relatively narrow band gap and more oxygen vacancies of rutile phase, which showed a probable way for design gas sensors based on metal oxide semiconductors with remarkable gas sensing performances by the crystal phase adjustment engineering in the future.

8.
Spectrochim Acta A Mol Biomol Spectrosc ; 265: 120365, 2021 Sep 07.
Artigo em Inglês | MEDLINE | ID: mdl-34509893

RESUMO

Sulfur quantum dots (S-dots) show great potential for applications in various field, due to their favorable biocompatibility, high stability, and antibacterial properties. However, the use of S-dots in chemical sensing is limited by the lack of functional groups on the surface. In this work, a fluorescence glutathione (GSH) assay is developed based on the GSH modulated quenching effect of Cu2O nanoparticles (NP) on S-dots. The fluorescence of S-dots is effectively quenched after forming complex with Cu2O NP through a static quenching effect (SQE). Introducing of GSH can trigger the decomposition of Cu2O NP into GSH-Cu(I) complex, which leads to the weaken of SQE and the partial recover of the fluorescence. The intensity of recovered fluorescence shows a positive correlation with the concentration of GSH in the concentration range of 20 to 500 µM. The fluorescence GSH assay shows excellent selectivity and robustness towards various interferences and high concentration salt, which endow the successful detection of GSH in human blood sample. The presented results provide a new door for the design of fluorescence assays, which also provides a platform for the applications in nanomedicine and environmental science.

9.
Int J Mol Sci ; 22(17)2021 Sep 02.
Artigo em Inglês | MEDLINE | ID: mdl-34502441

RESUMO

Sweet potato (Ipomoea batatas) is one of the largest food crops in the world. Due to its abundance of starch, sweet potato is a valuable ingredient in food derivatives, dietary supplements, and industrial raw materials. In addition, due to its ability to adapt to a wide range of harsh climate and soil conditions, sweet potato is a crop that copes well with the environmental stresses caused by climate change. However, due to the complexity of the sweet potato genome and the long breeding cycle, our ability to modify sweet potato starch is limited. In this review, we cover the recent development in sweet potato breeding, understanding of starch properties, and the progress in sweet potato genomics. We describe the applicational values of sweet potato starch in food, industrial products, and biofuel, in addition to the effects of starch properties in different industrial applications. We also explore the possibility of manipulating starch properties through biotechnological means, such as the CRISPR/Cas-based genome editing. The ability to target the genome with precision provides new opportunities for reducing breeding time, increasing yield, and optimizing the starch properties of sweet potatoes.

10.
J Oral Sci ; 2021 Sep 13.
Artigo em Inglês | MEDLINE | ID: mdl-34511587

RESUMO

PURPOSE: In order to promote osseointegration and shorten the healing time after dental implant operations, this study was conducted to develop a chair-side plasma treatment system in which Ti implants were used as a coaxial internal electrode to rapidly enhance their surface hydrophilicity. METHODS: Surface hydrophilicity was evaluated by measurement of the water contact angle and the defined wetting time. Changes in temperature and chemical composition were analyzed using infrared thermal imaging and X-ray photoelectron spectroscopy (XPS), respectively. The biocompatibility of the treated implants was examined in an animal experiment. RESULTS: A marked improvement of hydrophilicity was demonstrated by a decrease in the water contact angle of the treated implant to 0° and wetting of the whole surface within 3 s of water contact. The Ti implant hydrophilization mechanism was explained as a decrease in the degree of hydrocarbon contamination. The surface temperature of the treated implant was close to that of the human body, and good osseointegration was observed in the in vivo experiment. CONCLUSION: The plasma treatment system developed here is a promising chair-side procedure for rapidly enhancing the surface hydrophilicity of Ti implants in clinical operations without any need to consider the degradation of hydrophilicity caused by long-term storage.

11.
Nonlinear Dyn ; : 1-15, 2021 Sep 06.
Artigo em Inglês | MEDLINE | ID: mdl-34511723

RESUMO

The currently ongoing COVID-19 pandemic confronts governments and their health systems with great challenges for disease management. Epidemiological models play a crucial role, thereby assisting policymakers to predict the future course of infections and hospitalizations. One difficulty with current models is the existence of exogenous and unmeasurable variables and their significant effect on the infection dynamics. In this paper, we show how a method from nonlinear control theory can complement common compartmental epidemiological models. As a result, one can estimate and predict these exogenous variables requiring the reported infection cases as the only data source. The method allows to investigate how the estimates of exogenous variables are influenced by non-pharmaceutical interventions and how imminent epidemic waves could already be predicted at an early stage. In this way, the concept can serve as an "epidemometer" and guide the optimal timing of interventions. Analyses of the COVID-19 epidemic in various countries demonstrate the feasibility and potential of the proposed approach. The generic character of the method allows for straightforward extension to different epidemiological models.

12.
Front Public Health ; 9: 712190, 2021.
Artigo em Inglês | MEDLINE | ID: mdl-34513787

RESUMO

Fever is one of the typical symptoms of coronavirus disease (COVID-19). We aimed to investigate the association between early fever (EF) and clinical outcomes in COVID-19 patients. A total of 1,014 COVID-19 patients at the Leishenshan Hospital were enrolled and classified into the EF and non-EF groups based on whether they had fever within 5 days of symptom onset. Risk factors for clinical outcomes in patients with different levels of disease severity were analyzed using multivariable analyses. Time from symptom onset to symptom alleviation, CT image improvement, and discharge were longer for patients with moderate and severe disease in the EF group than in the non-EF group. Multivariable analysis showed that sex, EF, eosinophil number, C-reactive protein, and IL-6 levels were positively correlated with the time from symptom onset to hospital discharge in moderate cases. The EF patients showed no significant differences in the development of acute respiratory distress syndrome, compared with the non-EF patients. The Kaplan-Meier curve showed no obvious differences in survival between the EF and non-EF patients. However, EF patients with increased temperature showed markedly lower survival than the non-EF patients with increased temperature. EF had no significant impact on the survival of critically ill patients, while an increase in temperature was identified as an independent risk factor. EF appears to be a predictor of longer recovery time in moderate/severe COVID-19 infections. However, its value in predicting mortality needs to be considered for critically ill patients with EF showing increasing temperature.


Assuntos
COVID-19 , Estado Terminal , Febre/epidemiologia , Humanos , Estudos Retrospectivos , SARS-CoV-2
13.
Talanta ; 235: 122791, 2021 Dec 01.
Artigo em Inglês | MEDLINE | ID: mdl-34517649

RESUMO

A new type of temperature-sensitive imprinted composite membranes(ICMs) was developed. Poly N,N-diethylacrylamide (DEA) blocks, as temperature-sensitive polymer, were grafted onto the substrate of the imprinted polymer separation layer to endow membranes with better adsorption effect. The comprehensive properties of the imprinted composite membranes were adequately tested and evaluated in detail. Results showed that ReO4- -ICMs (Re-ICMs) with temperature-sensitive recognition sites could adjust the structure of the imprinted holes at different temperatures, which presented excellent performance in the selective separation and purification of ReO4-. The prepared Re-ICMs exhibit the maximum adsorption capacity of 0.1639 mmol/g at 35 °C with the equilibrium adsorption time of 2 h. After ten adsorption/desorption cycles, Re-ICMs could still maintain 73.5% of the original adsorption capacity, the separation degree of ReO4-/MnO4- was only reduced from the initial 24.5 to 15.9, and the desorption ratio dropped from 80.4% to 68.4%, indicating that Re-ICMs have excellent adsorption and separation performance and reusability.


Assuntos
Impressão Molecular , Adsorção , Biomimética , Polímeros , Temperatura
14.
Spectrochim Acta A Mol Biomol Spectrosc ; 265: 120345, 2021 Sep 02.
Artigo em Inglês | MEDLINE | ID: mdl-34492512

RESUMO

In recent years, fluorescent probes based on chemical reactions have been widely investigated as a powerful and noninvasive method for the diagnosis of diseases. ß-Galactosidase (ß-gal), a typical lysosomal glycosidase, over expressed in senescent cells and primary ovarian cancer cells, which has been considered as an important biomarker cell senescence and primary ovarian cancers. Fluorescent probes for the determination of ß-gal provide an excellent choice for visualization of cell senescence. In this work, a turn on fluorescent probe (HBT-gal) for ß-gal activity was developed based on the enzymatic hydrolysis of glycosidic bonds. HBT-gal showed little fluorescence in aqueous buffer excited at 415 nm, while emitted green fluorescence centered at ∼ 492 nm upon incubated with ß-gal. The sensing scheme showed high selectivity and sensitivity for ß-gal activity with a limit of detection calculated as low as 0.19 mU/mL. Moreover, HBT-gal was successfully applied to image ß-gal activity in senescent Hep G2 cells treated with H2O2. Therefore, probe HBT-gal demonstrated a potential usage for the determination of cell senescence using ß-gal as a biomarker.

15.
Cell Metab ; 2021 Sep 01.
Artigo em Inglês | MEDLINE | ID: mdl-34478633

RESUMO

Metabolic dysfunction is becoming a predominant risk for the development of many comorbidities. Ischemic heart disease (IHD) still imposes the highest disease burden among all cardiovascular diseases worldwide. However, the contributions of metabolic risk factors to IHD over time have not been fully characterized. Here, we analyzed the global disease burden of IHD and 15 associated general risk factors from 1990 to 2019 by applying the methodology framework of the Global Burden of Disease Study. We found that the global death cases due to IHD increased steadily during that time frame, while the mortality rate gradually declined. Notably, metabolic risk factors have become the leading driver of IHD, which also largely contributed to the majority of IHD-related deaths shifting from developed countries to developing countries. These findings suggest an urgent need to implement effective measures to control metabolic risk factors to prevent further increases in IHD-related deaths.

16.
J Exp Med ; 218(11)2021 Nov 01.
Artigo em Inglês | MEDLINE | ID: mdl-34473196

RESUMO

Autosomal dominant (AD) NFKB1 deficiency is thought to be the most common genetic etiology of common variable immunodeficiency (CVID). However, the causal link between NFKB1 variants and CVID has not been demonstrated experimentally and genetically, and there has been insufficient biochemical characterization and enrichment analysis. We show that the cotransfection of NFKB1-deficient HEK293T cells (lacking both p105 and its cleaved form p50) with a κB reporter, NFKB1/p105, and a homodimerization-defective RELA/p65 mutant results in p50:p65 heterodimer-dependent and p65:p65 homodimer-independent transcriptional activation. We found that 59 of the 90 variants in patients with CVID or related conditions were loss of function or hypomorphic. By contrast, 258 of 260 variants in the general population or patients with unrelated conditions were neutral. None of the deleterious variants displayed negative dominance. The enrichment in deleterious NFKB1 variants of patients with CVID was selective and highly significant (P = 2.78 × 10-15). NFKB1 variants disrupting NFKB1/p50 transcriptional activity thus underlie AD CVID by haploinsufficiency, whereas neutral variants in this assay should not be considered causal.

17.
Front Immunol ; 12: 705378, 2021.
Artigo em Inglês | MEDLINE | ID: mdl-34526987

RESUMO

Intrahepatic cholangiocarcinoma (ICC) is highly invasive and carries high mortality due to limited therapeutic strategies. In other solid tumors, immune checkpoint inhibitors (ICIs) target cytotoxic T lymphocyte-associated antigen 4 (CTLA-4) and programmed death 1 (PD1), and the PD1 ligand PD-L1 has revolutionized treatment and improved outcomes. However, the relationship and clinical significance of CTLA-4 and PD-L1 expression in ICC remains to be addressed. Deciphering CTLA-4 and PD-L1 interactions in ICC enable targeted therapy for this disease. In this study, immunohistochemistry (IHC) was used to detect and quantify CTLA-4, forkhead box protein P3 (FOXP3), and PD-L1 in samples from 290 patients with ICC. The prognostic capabilities of CTLA-4, FOXP3, and PD-L1 expression in ICC were investigated with the Kaplan-Meier method. Independent risk factors related to ICC survival and recurrence were assessed by the Cox proportional hazards models. Here, we identified that CTLA-4+ lymphocyte density was elevated in ICC tumors compared with peritumoral hepatic tissues (P <.001), and patients with a high density of CTLA-4+ tumor-infiltrating lymphocytes (TILsCTLA-4 High) showed a reduced overall survival (OS) rate and increased cumulative recurrence rate compared with patients with TILsCTLA-4 Low (P <.001 and P = .024, respectively). Similarly, patients with high FOXP3+ TILs (TILsFOXP3 High) had poorer prognoses than patients with low FOXP3+ TILs (P = .021, P = .034, respectively), and the density of CTLA-4+ TILs was positively correlated with FOXP3+ TILs (Pearson r = .31, P <.001). Furthermore, patients with high PD-L1 expression in tumors (TumorPD-L1 High) and/or TILsCTLA-4 High presented worse OS and a higher recurrence rate than patients with TILsCTLA-4 LowTumorPD-L1 Low. Moreover, multiple tumors, lymph node metastasis, and high TumorPD-L1/TILsCTLA-4 were independent risk factors of cumulative recurrence and OS for patients after ICC tumor resection. Furthermore, among ICC patients, those with hepatolithiasis had a higher expression of CTLA-4 and worse OS compared with patients with HBV infection or undefined risk factors (P = .018). In conclusion, CTLA-4 is increased in TILs in ICC and has an expression profile distinct from PD1/PD-L1. TumorPD-L1/TILsCTLA-4 is a predictive factor of OS and ICC recurrence, suggesting that combined therapy targeting PD1/PD-L1 and CTLA-4 may be useful in treating patients with ICC.

18.
Thorac Cancer ; 2021 Sep 17.
Artigo em Inglês | MEDLINE | ID: mdl-34532982

RESUMO

A thymoma is a type of thymic tumor which is rarely malignant that is frequently reported in adult patients. A number of thymoma-related immune disorders are observed including autoimmune diseases, which suggests a strong connection between thymoma development and immunological mechanisms. Characterized by association with humoral and cellular immunodeficiency, thymoma patients are susceptible to opportunistic infections by environmental factors. Recent reports have suggested that viral infection may play a role in the etiological mechanisms of thymoma development associated with dysregulated immunity. In this review, we summarize the case reports and studies related to viral infection, such as CMV, EBV and HSV, that probably play a part in the pathogenesis of thymoma and related diseases. Furthermore, we demonstrate the underlying mechanisms by which viruses may induce the occurrence of thymoma with autoimmune diseases. Lastly, we discuss the potential application of antiviral therapy in the treatment of thymic diseases.

19.
Cell Metab ; 2021 Sep 16.
Artigo em Inglês | MEDLINE | ID: mdl-34536344

RESUMO

Myocardial ischemia-reperfusion (MIR) injury is a major cause of adverse outcomes of revascularization after myocardial infarction. To identify the fundamental regulator of reperfusion injury, we performed metabolomics profiling in plasma of individuals before and after revascularization and identified a marked accumulation of arachidonate 12-lipoxygenase (ALOX12)-dependent 12-HETE following revascularization. The potent induction of 12-HETE proceeded by reperfusion was conserved in post-MIR in mice, pigs, and monkeys. While genetic inhibition of Alox12 protected mouse hearts from reperfusion injury and remodeling, Alox12 overexpression exacerbated MIR injury. Remarkably, pharmacological inhibition of ALOX12 significantly reduced cardiac injury in mice, pigs, and monkeys. Unexpectedly, ALOX12 promotes cardiomyocyte injury beyond its enzymatic activity and production of 12-HETE but also by its suppression of AMPK activity via a direct interaction with its upstream kinase TAK1. Taken together, our study demonstrates that ALOX12 is a novel AMPK upstream regulator in the post-MIR heart and that it represents a conserved therapeutic target for the treatment of myocardial reperfusion injury.

20.
Artigo em Inglês | MEDLINE | ID: mdl-34536568

RESUMO

Small proteins specifically refer to proteins consisting of less than 100 amino acids translated from small open reading frames (sORFs), which were usually missed in previous genome annotation. The significance of small proteins has been revealed in current years, along with the discovery of their diverse functions. However, systematic annotation of small proteins is still insufficient. SmProt was specially developed to provide valuable information on small proteins for scientific community. Here we present the update of SmProt, which emphasizes reliability of translated sORFs, genetic variants in translated sORFs, disease-specific sORF translation events or sequences, and remarkably increased data volume. More components such as non-ATG translation initiation, function, and new sources are also included. SmProt incorporated 638,958 unique small proteins curated from 3,165,229 primary records, which were computationally predicted from 419 ribosome profiling (Ribo-seq) datasets or collected from literature and other sources from 370 cell lines or tissues in 8 species (Homo sapiens, Mus musculus, Rattus norvegicus, Drosophila melanogaster, Danio rerio, Saccharomyces cerevisiae, Caenorhabditis elegans, and Escherichia coli). In addition, small protein families identified from human microbiomes were also collected. All datasets in SmProt are free to access, and available for browse, search, and bulk downloads at http://bigdata.ibp.ac.cn/SmProt/.

SELEÇÃO DE REFERÊNCIAS
DETALHE DA PESQUISA
...