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1.
J Exp Bot ; 2021 Oct 12.
Artigo em Inglês | MEDLINE | ID: mdl-34636403

RESUMO

In plants, glucose (Glc) plays important roles, as a nutrient and signal molecule, in the regulation of growth and development. However, the function of Glc in fiber development of Upland cotton (Gossypium hirsutum) is unclear. Here, using gas chromatography-mass spectrometry (GC-MS), we found that the Glc content in fibers was higher than that in ovules during the fiber elongation stage. In vitro ovule cultures revealed that lower Glc concentrations promoted cotton fiber elongation, while higher concentrations had inhibitory effects. The hexokinase inhibitor N-acetyl-glucosamine (NAG) inhibited cotton fiber elongation in the cultured ovules, indicating that Glc-mediated fiber elongation depends on the Glc signal transduced by hexokinase. RNA sequencing (RNA-seq) analysis and hormone content detection showed that 150 mM Glc significantly activated brassinosteroid (BR) biosynthesis, and the expression of signaling-related genes have also increased, which promoted fiber elongation. And in vitro ovule cultures clarified that BR induced cotton fiber elongation in a dose-dependent manner. In hormone recovery experiments, only BR compensated for the inhibitory effects of NAG on fiber elongation in a Glc-containing medium. However, the ovules cultured with a BR biosynthetic inhibitor brassinazole (BRZ) and from the BR-deficient cotton mutant pag1 had greatly reduced fiber elongation levels at all the tested Glc concentrations, demonstrating that Glc does not compensate for the inhibition of fiber elongation caused by BR biosynthetic defects, which suggested that BR signaling pathway works downstream of Glc during cotton fiber elongation. Altogether, our study showed that Glc occupies an enviable place and crosstalk occurs between Glc and BR signaling during modulation of fiber elongation.

2.
Aging (Albany NY) ; 13(17): 21421-21434, 2021 09 02.
Artigo em Inglês | MEDLINE | ID: mdl-34475271

RESUMO

We investigated the relationship between low lean mass (LLM) and lower urinary tract symptoms (LUTS) using the 2005-2006 National Health and Nutrition Examination Survey (NHANES) dataset. We enrolled 959 men with an average age of 52.08 ± 7.91 years and performed weighted multiple regression analysis to determine the independent relationship between exposure variables (LLM, alternate LLM) and outcomes variables (urinary hesitancy, incomplete emptying, urinary frequency, nocturia, daytime LUTS, clinical LUTS) after adjusting for confounding factors. The prevalence of urinary hesitancy (OR = 7.76, P < 0.0001), incomplete emptying (OR = 2.49, P = 0.0070), urinary frequency (OR = 3.28, P < 0.0001), daytime LUTS (OR = 3.88, P < 0.0001) and clinical LUTS (OR = 8.11, P < 0.0001) was significantly higher among men with LLM compared to men without LLM. Moreover, alternate LLM (ALLM) was positively associated with urinary hesitancy (OR = 17.97, P < 0.0001), incomplete emptying (OR = 4.68, P = 0.0003), daytime LUTS (OR = 2.47, P = 0.0136) and clinical LUTS (OR = 12.18, P < 0.0001). These findings demonstrate that both LLM and ALLM were associated with a higher risk of LUTS in men aged ≥ 40 years, which suggested that early management and treatment of lean mass loss may improve or alleviate LUTS.

3.
Mater Horiz ; 8(10): 2834-2841, 2021 Oct 04.
Artigo em Inglês | MEDLINE | ID: mdl-34486000

RESUMO

Soft biological tissues and muscles composed of semiflexible networks exhibit rapid strain-hardening behaviors to protect them from accidental rupture. In contrast, synthetic soft elastomers, usually featuring flexible networks, lack such behaviors, leading to a notorious issue when applying them to a promising artificial muscle technology (dielectric elastomer, DE), that is electromechanical instability (EMI) induced premature breakdown. We report that a facile thermomechanical training method can adaptively reconstruct the network of a soft triblock copolymer elastomer to transform its flexible network strands into semiflexible ones without extra chemical modifications and additives so that the electro-actuation performance is significantly enhanced by avoiding EMI. The free-standing actuators of trained elastomers exhibit a large stable electro-actuation strain and a high theoretical energy density (133%, 307 kJ m-3 at 158.1 V µm-1), and the capacity of actuating at low-temperature environments (-15 °C).

4.
Int J Infect Dis ; 112: 173-182, 2021 Sep 12.
Artigo em Inglês | MEDLINE | ID: mdl-34520845

RESUMO

OBJECTIVE: To evaluate the long-term consequences of COVID-19 survivors one year after recovery, and to identify the risk factors associated with abnormal patterns in chest imaging manifestations or impaired lung function. METHODS: COVID-19 patients were recruited and prospectively followed up with symptoms, health-related quality of life, psychological questionnaires, 6-minute walking test, chest computed tomography (CT), pulmonary function tests, and blood tests. Multivariable logistic regression models were used to evaluate the association between the clinical characteristics and chest CT abnormalities or pulmonary function. RESULTS: Ninety-four patients with COVID-19 were recruited between January 16 and February 6, 2021. Muscle fatigue and insomnia were the most common symptoms. Chest CT scans were abnormal in 71.28% of participants. The results of multivariable regression showed an increased odds in age. Ten patients had diffusing capacity of the lung for carbon monoxide (DLCO) impairment. Urea nitrogen concentration on admission was significantly associated with impaired DLCO. IgG levels and neutralizing activity were significantly lower compared with those in the early phase. CONCLUSIONS: One year after hospitalization for COVID-19, a cohort of survivors were mainly troubled with muscle fatigue and insomnia. Pulmonary structural abnormalities and pulmonary diffusion capacities were highly prevalent in surviving COVID-19 patients. It is necessary to intervene in the main target population for long-term recovery.

5.
Front Immunol ; 12: 728783, 2021.
Artigo em Inglês | MEDLINE | ID: mdl-34421930

RESUMO

Forkhead box protein 3 (Foxp3+)-expressing regulatory T (Treg) cells are a unique CD4+T cell subset that suppresses excessive immune responses. The epigenetic plasticity and metabolic traits of Treg cells are crucial for the acquisition of their phenotypic and functional characteristics. Therefore, alterations to the epigenetics and metabolism affect Treg cell development and function. Recent evidence reveals that altering the metabolic pathways and generation of metabolites can regulate the epigenetics of Treg cells. Specifically, some intermediates of cell metabolism can directly act as substrates or cofactors of epigenetic-modifying enzymes. Here, we describe the metabolic and epigenetic features during Treg cell development, and discuss how metabolites can contribute to epigenetic alterations of Treg cells, which affects Treg cell activation, differentiation, and function.

6.
Int J Biol Macromol ; 187: 867-879, 2021 Sep 30.
Artigo em Inglês | MEDLINE | ID: mdl-34339786

RESUMO

The wall-associated kinases (WAKs) and WAK-like kinases (WAKLs) form a group of receptor-like kinases (RLKs) with extracellular domains tightly linked to the cell wall. The WAKs/WAKLs have been known to be involved in plant growth, development, and stress responses. However, the functions of WAKs/WAKLs are less well known in cotton. In this study, 58, 66, and 99 WAK/WAKL genes were identified in Gossypium arboreum, G. raimondii, and G. hirsutum, respectively. Phylogenetic analysis showed they were classified into five groups, with two groups specific to cotton. Collinearity analysis revealed that segmental and tandem duplications resulted in expansion of the WAK/WAKL gene family in cotton. Moreover, the Ka/Ks ratios indicated this family was exposed to purifying selection pressure during evolution. The structures of the GhWAK/WAKL genes and encoded proteins suggested the functions of WAKs/WAKLs in cotton were conserved. Transient expression of four WAK/WAKL-GFP fusion constructs in Arabidopsis protoplasts indicated that they were localized on the plasma membrane. The cis-elements in the GhWAK/WAKL promoters were responsive to multiple phytohormones and abiotic stresses. Expression profiling showed that GhWAK/WAKL genes were induced by various abiotic stresses. This study provides insights into the evolution of WAK/WAKL genes and presents fundamental information for further analysis in cotton.

7.
Trop Med Int Health ; 2021 Jul 23.
Artigo em Inglês | MEDLINE | ID: mdl-34297877

RESUMO

OBJECTIVE: Tuberculous pleurisy (TP) is a common disease of extrapulmonary tuberculosis, but its diagnosis is challenging. Recently, studies have found that the pleural fluid interferon gamma release assay (PF-IGRA) has important diagnostic value in TP, but the sample size of these studies was small, and the conclusions were inconsistent. Therefore, this study evaluated the diagnostic value of PF-IGRA in TP through a meta-analysis. METHODS: We conducted a literature search in multiple databases to identify studies and calculated the sensitivity, specificity, positive likelihood ratio (PLR), negative likelihood ratio (NLR), diagnostic odds ratio (DOR), summary receiver operating characteristic (SROC) curve and area under the curve (AUC). RESULTS: All 26 publications, including 30 case-control studies, were eventually included in the meta-analysis. The results showed that the pooled sensitivity, specificity, PLR, NLR, DOR and AUC with their 95% confidence intervals were 0.90 (0.88-0.91), 0.87 (0.85-0.89), 7.64 (4.46-13.07), 0.13 (0.09-0.19), 65.45 (32.13-133.33) and 0.9508, respectively. The subgroup analysis suggested that the sensitivity, specificity and AUC of PF-IGRA for TP in areas with a high tuberculosis burden were significantly higher than those in areas with a low tuberculosis burden. The sensitivity and AUC of the enzyme-linked immunosorbent assay method were higher than those of the enzyme-linked immunosorbent assay method for IGRA, but the specificity was similar. More importantly, PF-IGRA combined with adenosine deaminase (ADA) could increase the diagnostic value of TP. CONCLUSIONS: The current meta-analysis indicated that PF-IGRA has high diagnostic value in diagnosing TP, especially in areas with a high TB burden. We recommended that the combination of PF-IGRA and ADA is the best way to diagnose TP.

8.
Genes (Basel) ; 12(6)2021 05 27.
Artigo em Inglês | MEDLINE | ID: mdl-34071968

RESUMO

Cotton is one of the most important fiber and oil crops in the world. Chloroplast genomes harbor their own genetic materials and are considered to be highly conserved. Transfer RNAs (tRNAs) act as "bridges" in protein synthesis by carrying amino acids. Currently, the variation and evolutionary characteristics of tRNAs in the cotton chloroplast genome are poorly understood. Here, we analyzed the structural variation and evolution of chloroplast tRNA (cp tRNA) based on eight diploid and two allotetraploid cotton species. We also investigated the nucleotide evolution of chloroplast genomes in cotton species. We found that cp tRNAs in cotton encoded 36 or 37 tRNAs, and 28 or 29 anti-codon types with lengths ranging from 60 to 93 nucleotides. Cotton chloroplast tRNA sequences possessed specific conservation and, in particular, the Ψ-loop contained the conserved U-U-C-X3-U. The cp tRNAs of Gossypium L. contained introns, and cp tRNAIle contained the anti-codon (C-A-U), which was generally the anti-codon of tRNAMet. The transition and transversion analyses showed that cp tRNAs in cotton species were iso-acceptor specific and had undergone unequal rates of evolution. The intergenic region was more variable than coding regions, and non-synonymous mutations have been fixed in cotton cp genomes. On the other hand, phylogeny analyses indicated that cp tRNAs of cotton were derived from several inferred ancestors with greater gene duplications. This study provides new insights into the structural variation and evolution of chloroplast tRNAs in cotton plants. Our findings could contribute to understanding the detailed characteristics and evolutionary variation of the tRNA family.


Assuntos
Evolução Molecular , Genes de Cloroplastos , Variação Estrutural do Genoma , Gossypium/genética , RNA de Transferência/genética , Códon/genética , Gossypium/classificação , Filogenia
9.
Biochim Biophys Acta Mol Cell Res ; 1868(10): 119084, 2021 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-34166715

RESUMO

In our previous study, it showed that P-3F, a podophyllotoxin derivative, causes the increased level of p53 expression by enhancing p53 stability, resulting from blockage of the Mdm2-p53 feedback loop via nucleolus-to-nucleoplasm translocation of Rps27a in human cervical cancer HeLa cell line. However, the mechanism of regulating Rps27a localization remains to be studied. In the current study, it has been demonstrated that the level of protein interacting with carboxyl terminus 1 (PICT1), originally identified as a tumor suppressor, was decreased in a concentration-dependent manner in response to P-3F, leading to inhibition of human cervical cancer cell lines proliferation. Also remarkably, reduction of serine phosphorylation of STMN1 at position 16 induced by P-3F was required in the downregulation of PICT1, in which p53 activity was likely to be directly involved. Note as well that, PICT1 also played an important role in p53 stability enhancement by inhibiting Mdm2-mediated p53 ubiquitination due to Rps27a translocation from the nucleolus to the nucleoplasm to interact with Mdm2 following treatment with P-3F. Collectively, these findings indicated that P-3F, a microtubule polymerization inhibitor, promotes the decreased level of PICT1 expression, which is critical for regulating the Rps27a-Mdm2-p53 pathway against cervical cancer.

10.
Ecotoxicol Environ Saf ; 220: 112398, 2021 Sep 01.
Artigo em Inglês | MEDLINE | ID: mdl-34116333

RESUMO

Presently, toxicological assessment of multiple veterinary antimicrobials has not been performed on mammals. In this study, we assessed the short-term toxicity of enrofloxacin (E) combined with colistin (C) and quinocetone (Q). Young male rats were orally dosed drug mixtures and single drugs in 14 consecutive days, each at the dose of 20, 80, and 400 mg/(kg·BW) for environmental toxicologic study. The results showed that at the high dose treatment, the combination of E + C+Q significantly decreased body intake, lymphocytes count on rats; significantly increased the values of Alanine aminotransferase (ALT), Glutamic oxaloacetic transaminase (AST) and, cholinesterase (CHE); it also got the severest histopathological changes, where sinusoidal congestion and a large number of black particles in sinusoids were observed. This means E + C+Q in the high dose groups was able to cause significant damage to the liver. Other combinations or doses did not induce significant liver damage. Transcriptome analysis was then performed on rats in high dose group for further research. For E + C and E + Q, an amount of 375 and 480 differently expressed genes were filtered out, revealing their possible underlying effect on genomes. For E + C+Q, a weighted gene co-expression network analysis was performed and 96 hub genes were identified to reveal the specific effect induced by this combination. This study indicates that joint toxicity should be taken into consideration when involving the risk assessment of these antimicrobials.


Assuntos
Anti-Infecciosos/toxicidade , Colistina/toxicidade , Enrofloxacina/toxicidade , Expressão Gênica/efeitos dos fármacos , Fígado/efeitos dos fármacos , Quinoxalinas/toxicidade , Drogas Veterinárias/toxicidade , Alanina Transaminase/metabolismo , Animais , Anti-Infecciosos/administração & dosagem , Anti-Infecciosos/farmacologia , Aspartato Aminotransferases/metabolismo , Colistina/administração & dosagem , Combinação de Medicamentos , Resíduos de Drogas , Enrofloxacina/administração & dosagem , Exposição Ambiental , Perfilação da Expressão Gênica , Humanos , Fígado/enzimologia , Fígado/patologia , Masculino , Quinoxalinas/administração & dosagem , Ratos Sprague-Dawley , Fatores de Tempo , Drogas Veterinárias/administração & dosagem
11.
Mol Cancer Res ; 19(9): 1454-1464, 2021 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-34016745

RESUMO

Wnt signaling is believed to be an important contributor to tumor development and has been reported to be modulated by secreted frizzled-related proteins (SFRP). Nevertheless, the role of secreted frizzled-related protein 4 (SFRP4) in tumorigenesis remains controversial. We aim to explore its biological function in gastric cancer. Genomes analysis based on the Gene Expression Omnibus (GEO) dataset was used to find the differential gene expression between different tumor-node-metastasis (TNM) stages of gastric cancer. IHC was used to determine the relationship between SFRP4 expression and clinicopathologic characteristics in patients with gastric cancer. The influence of SFRP4 on tumor progression was evaluated by CCK-8, colony formation, cell apoptosis, and cell cycle in vitro, as well as xenograft model in vivo. The methylation status of SFRPs was examined in gastric cancer specimens by quantitative methylation analysis. SFRP4 was most upregulated in advanced gastric cancer. High intratumoral SFRP4 expression, which was associated with tumor invasion and metastasis, was also a poor prognostic indicator for patients with gastric cancer. In vitro and in vivo studies revealed that SFRP4 could promote tumor growth; however, IWR-1 could suppress tumor growth mediated by SFRP4 overexpression. Mechanistic exploration found that SFRP4 was overexpressed by the decrease of promoter methylation and thus could competitively antagonize the inhibitory effect of SFRP1 on Wnt pathway activation and tumor progression in gastric cancer. IMPLICATIONS: In gastric cancer, the expression of SFRP4 was upregulated by decreased methylation. High intratumoral SFRP4 expression could activate the Wnt pathway to promote tumor progression and predict poor survival of patients with gastric cancer.

12.
Curr Med Sci ; 41(2): 287-296, 2021 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-33877544

RESUMO

Block of proliferation 1 (BOP1) is a key protein involved in ribosome maturation and affects cancer progression. However, its role in gastric cancer (GC) remains unknown. This study aimed to explore the expression of BOP1 in GC and its potential mechanisms in regulating GC growth, and the relationship between BOP1 level in cancer tissues and survival was also analyzed. The expression of BOP1 was examined by immunohistochemistry (IHC) in a cohort containing 387 patients with primary GC. Cultured GC cells were treated by siRNA to knock down the BOP1 expression, and examined by CCK-8 assay and plate clone formation to assess cell proliferation in vitro. Apoptotic rate of cultured GC cells was detected by flow cytometry with double staining of AnnxinV/PI. The xenografted mouse model was used to assess GC cell proliferation in vivo. Western blot and IHC were also performed to detect the expression levels of BOP1, p53 and p21. Patients with higher level of BOP1 in cancer tissues had significantly poorer survival. BOP1 silencing significantly suppressed GC cell proliferation both in vitro and in vivo. It blocked cell cycle at G0/G1 phase and led to apoptosis of GC cells via upregulating p53 and p21. BOP1 silencing-induced suppression of cell proliferation was partly reversed by pifithrin-α (a p53 inhibitor). Our study demonstrated that BOP1 up-regulation may be a hallmark of GC and it may regulate proliferation of GC cells by activating p53. BOP1 might be considered a novel biomarker of GC proliferation, and could be a potential indicator of prognosis of GC patients. BOP1 might also be a potential target for the treatment of GC patients if further researched.

13.
J Drug Target ; : 1-8, 2021 May 03.
Artigo em Inglês | MEDLINE | ID: mdl-33896301

RESUMO

Intracellular Ca2+ ions as second messenger played key role in cell behaviour, which was often overlooked in traditional antitumor treatment. Disrupting Ca2+ ion homeostasis by Ca2+ overload might switch ions signal from 'regulating' to 'destroying'. Inspired by this, a biomimetic Ca2+ nanogenerator was constructed. Briefly, the curcumin (CUR) was loaded into mesoporous calcium carbonate nanoparticles (MCC NPs), and then coated with platelet (PLT) membrane. Upon reaching tumour cells by PLT membrane-mediated tumour targeting effect, PLT@MCC/CUR would instantaneously decompose in acidic lysosomes, concurrently accompanying with Ca2+ generation and CUR release. The CUR could further facilitate Ca2+ release from endoplasmic reticulum (ER) and inhibit Ca2+ efflux, aggravating Ca2+ overload to disrupt mitochondrial Ca2+ homeostasis for mitochondria apoptosis signalling pathway activation. Interestingly, such effect was ineffective in normal cells, realising the tumour-specific therapeutic therapy. Based on ions interference strategy, PLT@MCC/CUR herein offered synergistic combination of Ca2+ overload therapy and chemotherapy, which would pave the way towards more effective nanotherapeutics.

14.
Medicine (Baltimore) ; 100(14): e25386, 2021 Apr 09.
Artigo em Inglês | MEDLINE | ID: mdl-33832127

RESUMO

BACKGROUND: Post-stroke depression has seriously affected the rehabilitation and quality of life of patients, and there is no reliable treatment plan at present. Nursing plays an important role in the recovery of patients, some studies have pointed out that traditional Chinese medicine emotional therapy has advantages in improving post-stroke depression and promoting rehabilitation, but it is lack of evidence-based basis. The purpose of this study is to systematically evaluate the effect of traditional Chinese medicine emotional therapy on the improvement of post-stroke depression. METHOD: We will search CNKI, Wanfang, VIP and CBM, PubMed, Embase, Web of Science and the Cochrane Library database, and search the randomized controlled trial on traditional Chinese medicine emotional therapy in patients with post-stroke depression from the establishment of the database to February 2021. The language is limited to English and Chinese. The quality of the included study is independently extracted and the literature quality is evaluated by 2 researchers. And meta-analysis is performed on the included literature using RevMan5.3 software. RESULT: In this study, the effect of traditional Chinese medicine emotional therapy on the improvement of post-stroke depression is evaluated by patient psychiatric scale score, compliance evaluation, quality of life evaluation and other indicators. CONCLUSION: This study will provide reliable evidence-based basis for establishing a reasonable and effective nursing scheme for patients with post-stroke depression. ETHICS AND DISSEMINATION: Private information from individuals will not be published. This systematic review also does not involve endangering participant rights. Ethical approval will not be required. The results may be published in a peer-reviewed journal or disseminated at relevant conferences. OSF REGISTRATION NUMBER: DOI 10.17605/OSF.IO/KA7G3.


Assuntos
Depressão/terapia , Medicina Tradicional Chinesa/métodos , Acidente Vascular Cerebral/enfermagem , Acidente Vascular Cerebral/psicologia , Adulto , Gerenciamento de Dados , Feminino , Humanos , Masculino , Qualidade de Vida , Ensaios Clínicos Controlados Aleatórios como Assunto , Acidente Vascular Cerebral/complicações
15.
Int J Mol Sci ; 22(8)2021 Apr 14.
Artigo em Inglês | MEDLINE | ID: mdl-33919933

RESUMO

Vacuolar sodium/proton (Na+/H+) antiporters (NHXs) can stabilize ion contents to improve the salt tolerance of plants. Here, GhNHX3D was cloned and characterized from upland cotton (Gossypium hirsutum). Phylogenetic and sequence analyses showed that GhNHX3D belongs to the vacuolar-type NHXs. The GhNHX3D-enhanced green fluorescent protein (eGFP) fusion protein localized on the vacuolar membrane when transiently expressed in Arabidopsis protoplasts. The quantitative real-time PCR (qRT-PCR) analysis showed that GhNHX3D was induced rapidly in response to salt stress in cotton leaves, and its transcript levels increased with the aggravation of salt stress. The introduction of GhNHX3D into the salt-sensitive yeast mutant ATX3 improved its salt tolerance. Furthermore, silencing of GhNHX3D in cotton plants by virus-induced gene silencing (VIGS) increased the Na+ levels in the leaves, stems, and roots and decreased the K+ content in the roots, leading to greater salt sensitivity. Our results indicate that GhNHX3D is a member of the vacuolar NHX family and can confer salt tolerance by adjusting the steady-state balance of cellular Na+ and K+ ions.


Assuntos
Antiporters/genética , Gossypium/genética , Estresse Salino/genética , Trocadores de Sódio-Hidrogênio/genética , Antiporters/química , Arabidopsis/genética , Regulação da Expressão Gênica de Plantas/genética , Gossypium/crescimento & desenvolvimento , Gossypium/fisiologia , Folhas de Planta/genética , Folhas de Planta/crescimento & desenvolvimento , Raízes de Plantas/genética , Raízes de Plantas/crescimento & desenvolvimento , Plantas Geneticamente Modificadas/genética , Estresse Salino/fisiologia , Tolerância ao Sal/genética , Trocadores de Sódio-Hidrogênio/química , Vacúolos/enzimologia
16.
J Neuroinflammation ; 18(1): 98, 2021 Apr 20.
Artigo em Inglês | MEDLINE | ID: mdl-33879167

RESUMO

BACKGROUND: Multiple sclerosis (MS) is a debilitating neurological disease caused by autoimmune destruction of the myelin sheath. Experimental autoimmune encephalomyelitis (EAE) is a widely used animal model for the pathogenesis of MS. We and others have previously demonstrated that IL-17 is critical for the pathogenesis of EAE. The concentration of IL-17 is significantly higher in the sera of MS patients than in healthy controls and correlates with disease activity. Moreover, anti-IL-17 neutralizing antibody demonstrated promising efficacy in a phase II trial in MS patients, further substantiating a key pathogenic role for IL-17 in MS. While Th17 and IL-17 are emerging as a bona fide drivers for neuroinflammation, it remains unclear what effector molecule executes the inflammatory tissue destruction in Th17-driven EAE. METHODS: By microarray analysis, we found STEAP4 is a downstream molecule of IL-17 signaling in EAE. We then used STEAP4 global knockout mice and STEAP4 conditional knockout mice to test its role in the pathogenesis of EAE. RESULTS: Here, we report that the metalloreductase, STEAP4, is a key effector molecule that participates and contributes to the pathogenesis of Th17-mediated neuroinflammation in experimental autoimmune encephalomyelitis. STEAP4 knockout mice displayed delayed onset and reduced severity of EAE induced by active immunization. The reduced disease phenotype was not due to any impact of STEAP4 deficiency on myelin reactive T cells. In contrast, STEAP4 knockout mice were resistant to passively induced EAE, pointing to a role for STEAP4 in the effector stage of EAE. Notably, STEAP4 was only induced the spinal cord of EAE mice that received Th17 cells but not Th1 cells. Consistently, STEAP4 deficiency protected from only Th17 but not Th1-induced EAE. Finally, using Nestin-Cre STEAP4fl/fl mice, we showed that ablation of STEAP4 expression in the resident cells in the central nervous system attenuated disease severity in both active immunization and passive Th17 transfer-induced EAE. CONCLUSION: In this study, we identified STEAP4 as a Th17-specific effector molecule that participates and contributes to the pathogenesis of neuroinflammation, thus potentially provide a novel target for MS therapy.

17.
J Exp Med ; 218(5)2021 05 03.
Artigo em Inglês | MEDLINE | ID: mdl-33835145

RESUMO

AIM2 is widely known for its role as a cytosolic dsDNA receptor that activates the inflammasome. In this issue of JEM, Ma et al. (2021. J. Exp. Med.https://doi.org/10.1084/jem.20201796) describe an inflammasome-independent function of AIM2 in microglia that restrains neuroinflammation via a novel crosstalk between AIM2 and cGAS signaling.


Assuntos
Proteínas de Ligação a DNA , Inflamassomos , DNA , Proteínas de Ligação a DNA/metabolismo , Nucleotidiltransferases , Transdução de Sinais
18.
Exp Lung Res ; 47(4): 173-182, 2021.
Artigo em Inglês | MEDLINE | ID: mdl-33678109

RESUMO

Lung adenocarcinoma (LUAD), one of the most common cancers, is a major threat to people's health due to its high mortality, and the survival of most patients suffering LUAD remains poor. This study aimed to explore the mechanism of Deleted in Liver Cancer 1 (DLC1) as a tumor suppressor underlying the occurrence and progression of LUAD. As revealed by bioinformatics analysis and qRT-PCR, DLC1 was significantly down-regulated in LUAD tumor tissue and cells. A series of cellular experiments including CCK-8, wound healing and Transwell assays were performed to detect the effect of DLC1 on the biological function of LUAD cells. It was found that overexpressing DLC1 significantly inhibited LUAD cell proliferative, migratory and invasive abilities, while knockdown of DLC1 promoted these abilities. Gene Set Enrichment Analysis (GSEA) and dual-luciferase assay were used to explore the downstream signaling pathway of DLC1, finding that DLC1 could remarkably inhibit the activity of mitogen-activated protein kinase (MAPK) signaling pathway. Western blot implemented for MAPK signaling pathway-related proteins further identified that DLC1 restrained the activation of MAPK/ERK signaling pathway. Furthermore, rescue experiments suggested that DLC1 inhibited LUAD cell proliferation and invasion by suppressing the MAPK/ERK signaling pathway. Overall, our study discussed the DLC1-dependent mechanism involved in LUAD. We found that the up-regulation of DLC1 may inhibit the malignant progression of LUAD by suppressing MAPK signaling pathway, which supports the view that DLC1 may serve as a molecular target for the targeted therapy of LUAD patients.

19.
Technol Cancer Res Treat ; 20: 1533033821990036, 2021.
Artigo em Inglês | MEDLINE | ID: mdl-33754907

RESUMO

BACKGROUND: miR-301b-3p is reported in various human cancers for its abnormal expression, while the role and molecular mechanisms in lung adenocarcinoma (LUAD) remain unclear, and this is the focus of the present study. MATERIALS AND METHODS: TCGA database was consulted to know gene expression in LUAD tissue. CCK-8, colony formation assay and Transwell assay were applied to identify the role of target genes in regulating LUAD cell biological properties. Bioinformatics analysis plus dual-luciferase assay were performed to validate the potential connection between genes. RESULTS: miR-301b-3p and DLC1 were the target genes of this study and respectively differentially up-regulated and down-regulated in LUAD. Functional experiments indicated that miR-301b-3p contributed to cancer cell proliferation, migration and invasion, while this effect was reversed with overexpressed DLC1 which was identified as a direct target of and regulated by miR-301b-3p. CONCLUSIONS: Collectively, miR-301b-3p was identified to actively function on LUAD malignant progression by suppressing DLC1 expression. This discovery provides a novel therapeutic strategy for LUAD patients, which helps improve the survival of patients.

20.
BMC Plant Biol ; 21(1): 103, 2021 Feb 18.
Artigo em Inglês | MEDLINE | ID: mdl-33602134

RESUMO

BACKGROUND: The overall genetic distribution and divergence of cloned genes among bread wheat varieties that have occurred during the breeding process over the past few decades in Ningxia Province, China, are poorly understood. Here, we report the genetic diversities of 44 important genes related to grain yield, quality, adaptation and resistance in 121 Ningxia and 86 introduced wheat cultivars and advanced lines. RESULTS: The population structure indicated characteristics of genetic components of Ningxia wheat, including landraces of particular genetic resources, introduced varieties with rich genetic diversities and modern cultivars in different periods. Analysis of allele frequencies showed that the dwarfing alleles Rht-B1b at Rht-B1 and Rht-D1b at Rht-D1, 1BL/1RS translocation, Hap-1 at GW2-6B and Hap-H at Sus2-2B are very frequently present in modern Ningxia cultivars and in introduced varieties from other regions but absent in landraces. This indicates that the introduced wheat germplasm with numerous beneficial genes is vital for broadening the genetic diversity of Ningxia wheat varieties. Large population differentiation between modern cultivars and landraces has occurred in adaptation genes. Founder parents carry excellent allele combinations of important genes, with a higher number of favorable alleles than modern cultivars. Gene flow analysis showed that six founder parents have greatly contributed to breeding improvement in Ningxia Province, particularly Zhou 8425B, for yield-related genes. CONCLUSIONS: Varieties introduced from other regions with rich genetic diversity and landraces with well-adapted genetic resources have been applied to improve modern cultivars. Founder parents, particularly Zhou 8425B, for yield-related genes have contributed greatly to wheat breeding improvement in Ningxia Province. These findings will greatly benefit bread wheat breeding in Ningxia Province as well as other areas with similar ecological environments.


Assuntos
Proteínas de Plantas/genética , Triticum/genética , Adaptação Fisiológica , Alelos , China , Frequência do Gene , Melhoramento Vegetal , Proteínas de Plantas/metabolismo , Triticum/crescimento & desenvolvimento , Triticum/fisiologia
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