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1.
DNA Cell Biol ; 2022 May 09.
Artigo em Inglês | MEDLINE | ID: mdl-35533015

RESUMO

The liver of poultry is the primary site of lipid synthesis. The excessive production of lipids accumulates in liver tissues causing lipid metabolism disorders, which result in fatty liver disease and have a transgenerational effect of acquired phenotypes. However, its specific mechanisms have not yet been fully understood. In this study, the differentially expressed miR-375 as well as its target gene MAP3K1 (mitogen-activated protein kinase kinase kinase 1) were screened out by interaction network analysis of microRNA sequencing results and transcriptome profiling in the fatty liver group of the F0-F3 generation (p < 0.05 or p < 0.01). Furthermore, the results showed that the number of lipid droplets and triglyceride content were significantly decreased after upregulation of miR-375 in primary hepatocyte culture in vitro (p < 0.05 or p < 0.01). The MAP3K1 knockdown group exhibited the opposite trends (p < 0.05 or p < 0.01). P53, Bcl-x, PMP22, and CDKN2C related to cell proliferation were significantly upregulated or downregulated after knocking down MAP3K1 (p < 0.05). This research uniquely revealed that silencing miR-375 inhibits lipid biosynthesis and promotes cell proliferation, which may be due to the partial regulation of the expression level of MAP3K1, thereby further participating in the transgenerational inheritance process of regulating liver lipid metabolism. These results reveal the pathogenesis of fatty liver in noncoding RNA and provide good candidate genes for breeding progress of disease resistance in chickens.

2.
Theriogenology ; 183: 1-9, 2022 Apr 15.
Artigo em Inglês | MEDLINE | ID: mdl-35189562

RESUMO

Sertoli cells (SCs), the only somatic constituent of the testicular seminiferous epithelium, are vital to spermatogenesis. We previously found that vitamin C (ascorbic acid, AA) can reprogram the transcriptome, and promote the proliferation and reproductive function of pig immature SCs (iSCs). However, the global change of microRNAs (miRNA) expression and its effect on pig iSCs as induced by vitamin C treatment is still unknown. Here, we performed small RNA sequencing on pig iSCs after 250 µM AA2P (l-ascorbic acid 2-phosphate sesquimagnesium salt hydrate) treatment for 36h. Total number of detected miRNAs ranged from 326 to 335 known, and 400-570 novel miRNAs. Of the top ten highly expressed miRNAs, we found that 8 were common (miR-21-5p, let-7i-5p, miR-30a-5p, let-7f-5p, let-7g, miR-100, miR-10a-5p and miR-30d), which were predicted to target mRNAs involved in cell development and differentiation. We identified 78 differentially expressed (DE) miRNAs (|log2 (Fold Change)|≥1; Padj.<0.05), including 7 known and 71 novel miRNAs. We further selected 13 highly and stably expressed DE miRNAs (4 up-regulated: miR-184, novel-miR-610, novel-miR-316 and novel-miR-1274; 9 down-regulated: miR-222, miR-221-5p, miR-221-3p, miR-210, miR-146b, miR-146a-5p, novel-miR-182, novel-miR-1088 and novel-miR-1016), and performed integrated analysis on the miRNA-mRNA regulatory network. DE mRNAs negatively targeted by these 13 DE miRNAs were enriched in multiple GO and KEGG signaling pathways (e.g. pyruvate and steroid metabolic processes, developmental process in reproduction, response to oxidative stress, Glycolysis/Gluconeogenesis and HIF-1). We validated 8 DE miRNAs and their 12 DE mRNA targets, most of them showed expression patterns consistent with (mi)RNA-seq results. Taken together, our findings demonstrate that vitamin C could induce the global change of miRNAs, which possibly regulate cell proliferation, energy metabolism and male reproduction as induced by vitamin C treatment on pig iSCs.


Assuntos
MicroRNAs , Células de Sertoli , Animais , Ácido Ascórbico/farmacologia , Perfilação da Expressão Gênica/veterinária , Masculino , MicroRNAs/genética , MicroRNAs/metabolismo , RNA Mensageiro/metabolismo , Células de Sertoli/metabolismo , Suínos , Transcriptoma
3.
Sci Transl Med ; 14(626): eabf0992, 2022 01 05.
Artigo em Inglês | MEDLINE | ID: mdl-34985967

RESUMO

High CD8+ T cell infiltration in colorectal cancer (CRC) should suggest a favorable prognosis and a satisfactory response to immunotherapy; however, the vast majority of patients with CRC do not benefit from immunotherapy due to poor T cell infiltration. Therefore, a better understanding of the mechanisms for T cell exclusion from CRC tumors is needed. Tribbles homolog 3 (TRIB3) has been implicated as an oncoprotein, but its role in regulating antitumor immune responses has not been defined. Here, we demonstrated that TRIB3 inhibits CD8+ T cell infiltration in various CRC mouse models. We showed that TRIB3 was acetylated by acetyltransferase P300, which inhibited ubiquitination and subsequent proteasomal degradation of TRIB3. Ectopically expressed TRIB3 inhibited signal transducer and activator of transcription 1 (STAT1) activation and STAT1-mediated CXCL10 transcription by enhancing the epidermal growth factor receptor signaling pathway, causing a reduction in tumor-infiltrating T cells. Genetic ablation of Trib3 or pharmacological acceleration of TRIB3 degradation with a P300 inhibitor increased T cell recruitment and sensitized CRCs to immune checkpoint blockade therapy. These findings identified TRIB3 as a negative modulator of CD8+ T cell infiltration in CRCs, highlighting a potential therapeutic target for treating immunologically "cold" CRCs.


Assuntos
Proteínas de Ciclo Celular , Neoplasias Colorretais , Evasão da Resposta Imune , Proteínas Repressoras , Animais , Linfócitos T CD8-Positivos , Proteínas de Ciclo Celular/metabolismo , Quimiocina CXCL10/metabolismo , Neoplasias Colorretais/patologia , Humanos , Imunoterapia , Camundongos , Proteínas Repressoras/metabolismo , Fator de Transcrição STAT1/metabolismo , Transdução de Sinais
4.
Theriogenology ; 177: 1-10, 2022 Jan 01.
Artigo em Inglês | MEDLINE | ID: mdl-34653791

RESUMO

Chloroquine (CQ) could function as a lysosomotropic agent to inhibit the endolysosomal trafficking in the autophagy pathway, and is widely used on malarial, tumor and recently COVID-19. However, the effect of CQ treatment on porcine immature Sertoli cells (iSCs) remains unclear. Here we showed that CQ could reduce iSC viability in a dose-dependent manner. CQ treatment (20 µM) on iSCs for 36h could elevate oxidative stress, damage mitochondrial function and promote apoptosis, which could be partially rescued by melatonin (MT) (10 nM). Transcriptome profiling identified 1611 differentially expressed genes (DEGs) (776 up- and 835 down-regulated) (20 µM CQ vs. DMSO), mainly involved in MAPK cascade, cell proliferation/apoptosis, HIF-1, PI3K-Akt and lysosome signaling pathways. In contrast, only 467 (224 up- and 243 down-regulated) DEGs (CQ + MT vs. DMSO) could be found after MT (10 nM) addition, enriched in cell cycle, regulation of apoptotic process, lysosome and reproduction pathways. Therefore, the partial rescue effects of MT on CQ treatment were confirmed by multiple assays (cell viability, ROS level, mitochondrial function, apoptosis, and mRNA levels of selected genes). Collectively, CQ treatment could impair porcine iSC viability by deranging the signaling pathways related to apoptosis and autophagy, which could be partially rescued by MT supplementation.


Assuntos
COVID-19 , Melatonina , Doenças dos Suínos , Animais , Apoptose , Autofagia , COVID-19/tratamento farmacológico , COVID-19/veterinária , Cloroquina/farmacologia , Masculino , Melatonina/farmacologia , Fosfatidilinositol 3-Quinases , SARS-CoV-2 , Células de Sertoli , Suínos
5.
J Nutr Sci Vitaminol (Tokyo) ; 67(5): 257-265, 2021.
Artigo em Inglês | MEDLINE | ID: mdl-34719610

RESUMO

Serum 25-hydroxyvitamin D [25(OH)D] concentration represents the body's reserves of vitamin D, which is mostly used by clinicians to evaluate the storage status of vitamin D in the body. The present study aimed to investigate the serum vitamin D components in different health status of minors to correctly evaluate the vitamin D storage in vivo. A total of 2,270 minors were included in the study, which was divided into healthy group (1,204 cases) and disease group (1,066 cases, including 270 short stature, 433 respiratory infections, 175 malnutrition and 188 tic disorder subjects). The levels of 25-hydroxyvitamin D2 [25(OH)D2] and 25-hydroxyvitamin D3 [25(OH)D3] were measured by UHPLC-MS/MS in all subjects, and the 25(OH)D3 activity equivalents [25(OH)D3-AE] and 25(OH)D were calculated. In addition, the 3-epi-25-hydroxyvitamin D3 [3-epi-25(OH)D3] concentrations of 278 subjects (including 147 healthy and 131 disease subjects) were measured by random sampling. 25(OH)D2, 25(OH)D3, 25(OH)D and 25(OH)D3-AE levels in disease group were significantly lower than those in healthy group (p<0.001). According to the level of 25(OH)D, the sufficiency of vitamin D [25(OH)D≥30 ng/mL] was 65.4% in healthy group and 50.5% in disease group. When the 25(OH)D2 activity was converted into 25(OH)D3-AE, 53.2% of the patients in the healthy group had sufficiency vitamin D, and 39.1% in the disease group. The 3-epi-25(OH)D3 level in the disease group was significantly lower than that in the healthy group (p<0.001). Not only the 25(OH)D, but also the both of 25(OH)D2 and 25(OH)D3 levels may overestimate the vitamin D status in subjects. For accurate evaluation, at least the serum levels of 25(OH)D2, 25(OH)D3 and 3-epi-25(OH)D3 should be determined simultaneously.


Assuntos
Menores de Idade , Espectrometria de Massas em Tandem , 25-Hidroxivitamina D 2 , Cromatografia Líquida de Alta Pressão , Humanos , Vitamina D , Vitaminas
6.
Nat Commun ; 12(1): 6525, 2021 11 11.
Artigo em Inglês | MEDLINE | ID: mdl-34764271

RESUMO

The cereal endosperm is a major factor determining seed size and shape. However, the molecular mechanisms of endosperm development are not fully understood. Long noncoding RNAs (lncRNAs) function in various biological processes. Here we show a lncRNA, MISSEN, that plays an essential role in early endosperm development in rice (Oryza sativa). MISSEN is a parent-of-origin lncRNA expressed in endosperm, and negatively regulates endosperm development, leading to a prominent dent and bulge in the seed. Mechanistically, MISSEN functions through hijacking a helicase family protein (HeFP) to regulate tubulin function during endosperm nucleus division and endosperm cellularization, resulting in abnormal cytoskeletal polymerization. Finally, we revealed that the expression of MISSEN is inhibited by histone H3 lysine 27 trimethylation (H3K27me3) modification after pollination. Therefore, MISSEN is the first lncRNA identified as a regulator in endosperm development, highlighting the potential applications in rice breeding.


Assuntos
Oryza/metabolismo , RNA Longo não Codificante/metabolismo , RNA de Plantas/metabolismo , Sementes/metabolismo , Regulação da Expressão Gênica de Plantas , Oryza/genética , Proteínas de Plantas/genética , Proteínas de Plantas/metabolismo , RNA Longo não Codificante/genética , RNA de Plantas/genética , Sementes/genética
7.
Oxid Med Cell Longev ; 2021: 4846951, 2021.
Artigo em Inglês | MEDLINE | ID: mdl-34349873

RESUMO

OBJECTIVE: Many studies have identified causal and promotive roles of oxidative stress (OxS) and oxidative damage caused by OxS in the occurrence and progression of cancer. Many biomarkers in the blood circulation of patients may change correspondingly with the development of tumors. This study is aimed at investigating the correlation between OxS and serum trace element (TE) levels of patients with different types of cancer. METHODS: 1143 different types of cancer patients and 178 healthy controls from Mar. 2018 to Aug. 2020 in Mianyang Central Hospital were involved in this study. Their levels of OxS parameters (including total oxidant status (TOS), total antioxidant status (TAS), and oxidant stress index (OSI)) and the concentrations of serum TEs (including Cu, Zn, Fe, and Se) were determined. RESULTS: Compared with healthy controls, all types of cancer patients had higher TOS level (all P adj < 0.001) and OSI level (z = 6.228 ~ 9.909, all P adj < 0.001) and lower TAS level (all P adj < 0.001). Compared with healthy controls, the changes of four TE levels in serum were different in different types of cancer patients, among which Cu increased in all groups, but there was no statistical difference in gastric and brain cancer; Se decreased in all groups, but there was no statistical difference in gastric, colorectal, esophageal, and other cancer; Zn was significantly decreased in breast cancer patients (P adj < 0.001); there was no statistical difference in the change of Fe in liver, kidney, and other cancer. Spearman correlation showed that the change of Cu concentration was most closely related to the three OxS parameters and was strongly correlated in the observed several types of tumors (r s > 0.6). Multinomial logistic regression showed that the risks of different tumors are related to the level change of multiple TEs and OxS parameters (ORTOS = 1.19 ~ 2.82, OROSI = 2.56 ~ 4.70, ORTAS = 0.20 ~ 0.46, ORCu = 0.73 ~ 1.44, ORZn = 0.81 ~ 0.91, ORFe = 0.68 ~ 1.18, and ORSe = 0.22 ~ 0.45, all P < 0.006). CONCLUSIONS: The OxS exists in the occurrence and development of cancer, which may be related to the changes of certain trace elements. In order to evaluate OxS correctly, it is necessary to detect TAS and TOS and at the same time, their ratio OSI should be detected. Assessment of markers representing the overall level of OxS and TEs may guarantee improved the monitoring of disease occurrence and development risk in cancer patients.


Assuntos
Biomarcadores Tumorais/sangue , Neoplasias/classificação , Neoplasias/patologia , Estresse Oxidativo , Oligoelementos/sangue , Estudos de Casos e Controles , Feminino , Seguimentos , Humanos , Masculino , Pessoa de Meia-Idade , Neoplasias/sangue , Prognóstico
8.
Theriogenology ; 173: 183-192, 2021 Oct 01.
Artigo em Inglês | MEDLINE | ID: mdl-34392171

RESUMO

Sertoli cells, important constituents of the somatic niche, supports the growth and development of spermatogonia. Heat stress (HS), among multiple intrinsic and external factors, can induce physiological and biochemical changes in Sertoli cells. However, the underlying molecular mechanism remains largely unclear. Here, we showed that acute heat stress (43 °C, 0.5 h) could reduce cell viability, promote apoptosis, and increase the lactate production of porcine immature Sertoli cells (iSCs) cultured in vitro. Then, transcriptome sequencing identified 126 immediately and 3372 prolonged responded differentially expressed genes (DEGs) after acute heat stress (43 °C, 0.5 h) (HS0.5), and 36 h recovery culture following heat stress (HS0.5-R36), respectively. Enrichment analyses found different signaling pathways: immediate changes including cell response to heat, regulation of cellular response to stress, heat shock protein binding, chaperon-mediated protein folding, and sterol biosynthetic process, but prolonged changes mainly involving cell cycle, regulation of apoptotic process/cell proliferation, reproductive process, P53, PI3K-Akt and Glycolysis/Gluconeogenesis. Furthermore, transcriptional patterns of 9 DEGs (Dnajb1, Traf6, Insig1, Gadd45g, Hdac6, Fkbp4, Serpine1, Pfkp and Galm), and 6 heat shock proteins (HSPs) (Hspa6, Hspb1, Hspd1, HSP90aa1, HSP90ab1 and Hsph1) were validated, as well as the protein pattern of HSP90AA1 via immunostaining and western blot. Taken together, heat stress could initiate immediate changes of heat shock-related genes, and reprogram transcriptome and signaling pathways affecting the viability, apoptosis and metabolite production of pig iSCs.


Assuntos
Células de Sertoli , Transcriptoma , Animais , Resposta ao Choque Térmico/genética , Lactatos , Masculino , Fosfatidilinositol 3-Quinases/metabolismo , Células de Sertoli/metabolismo , Suínos
9.
Mol Ther Nucleic Acids ; 25: 173-185, 2021 Sep 03.
Artigo em Inglês | MEDLINE | ID: mdl-34458003

RESUMO

Given the relentless renewal ability of intestinal crypt-base stem cells, small intestine in the gastrointestinal (GI) tract is more vulnerable to radiation-induced disruption. Through promoting epithelial integrity and reducing intracellular reactive oxygen species (ROS) levels, hypoxia-inducible factors (HIFs) have been proved to exhibit radioprotective effects in the GI tract. Therefore, enhancing stability or transcriptional activity of HIFs might be a therapeutic strategy for developing radioprotectors. Factor inhibiting HIF (FIH or HIF-1AN) can hamper transcriptional capacity of HIF-1α via interacting with Asn803 in its C-terminal domain. Previously, we discovered promoting HIF-1α transcriptional activity in vitro by FIH inhibitor-N-oxalyl-D-phenylalanine (NOFD) exerts radioprotection on cells. However, the radioprotective effect of FIH inhibitor on the GI tract and its competing endogenous RNA (ceRNA) regulatory network from the FIH/HIF axis has never been addressed. Here we verified radioprotection of NOFD for the GI tract by an animal model and performed whole-transcriptome analysis to fully elucidate the radioprotective mechanism from the FIH/HIF axis against GI syndrome. We identified two novel circular RNAs (circRNAs) (circRNA_2909 and circRNA_0323) and two long non-coding RNAs (lncRNAs) (NONMMUT140549.1 and NONMMUT148249.1) that promote expression of HIF1A and NOS2 in the HIF-1 pathway by sponging microRNAs (miRNAs), especially mmu-miR-92a-1-5p. The de-repression of HIF-1α transcriptional capacity by inhibiting FIH proteomic activity suggests a new therapeutic strategy in alleviating radiation-induced GI syndrome.

10.
Plant Cell ; 33(8): 2685-2700, 2021 08 31.
Artigo em Inglês | MEDLINE | ID: mdl-34003932

RESUMO

MEIOSIS ARRESTED AT LEPTOTENE1 (MEL1), a rice (Oryza sativa) Argonaute (AGO) protein, has been reported to function specifically at premeiotic and meiotic stages of germ cell development and is associated with a novel class of germ cell-specific small noncoding RNAs called phased small RNAs (phasiRNAs). MEL1 accumulation is temporally and spatially regulated and is eliminated after meiosis. However, the metabolism and turnover (i.e. the homeostasis) of MEL1 during germ cell development remains unknown. Here, we show that MEL1 is ubiquitinated and subsequently degraded via the proteasome pathway in vivo during late sporogenesis. Abnormal accumulation of MEL1 after meiosis leads to a semi-sterile phenotype. We identified a monocot-specific E3 ligase, XBOS36, a CULLIN RING-box protein, that is responsible for the degradation of MEL1. Ubiquitination at four K residues at the N terminus of MEL1 by XBOS36 induces its degradation. Importantly, inhibition of MEL1 degradation either by XBOS36 knockdown or by MEL1 overexpression prevents the formation of pollen at the microspore stage. Further mechanistic analysis showed that disrupting MEL1 homeostasis in germ cells leads to off-target cleavage of phasiRNA target genes. Our findings thus provide insight into the communication between a monocot-specific E3 ligase and an AGO protein during plant reproductive development.


Assuntos
Oryza/fisiologia , Proteínas de Plantas/metabolismo , Esporos/crescimento & desenvolvimento , Ubiquitina/metabolismo , Proteínas Argonauta/genética , Proteínas Argonauta/metabolismo , Regulação da Expressão Gênica de Plantas , Lisina/metabolismo , Meiose , Oryza/genética , Proteínas de Plantas/genética , Plantas Geneticamente Modificadas , Pólen/genética , Pólen/crescimento & desenvolvimento , Complexo de Endopeptidases do Proteassoma/metabolismo , Proteólise , RNA de Plantas/genética , RNA de Plantas/metabolismo , Pequeno RNA não Traduzido/genética , Pequeno RNA não Traduzido/metabolismo , Esporos/genética , Ubiquitina-Proteína Ligases/genética , Ubiquitina-Proteína Ligases/metabolismo , Ubiquitinação
11.
Int J Mol Sci ; 22(9)2021 Apr 29.
Artigo em Inglês | MEDLINE | ID: mdl-33947059

RESUMO

Crop domestication, which gives rise to a number of desirable agronomic traits, represents a typical model system of plant evolution. Numerous genomic evidence has proven that noncoding RNAs such as microRNAs and phasiRNAs, as well as protein-coding genes, are selected during crop domestication. However, limited data shows plant long noncoding RNAs (lncRNAs) are also involved in this biological process. In this study, we performed strand-specific RNA sequencing of cultivated rice Oryza sativa ssp. japonica and O. sativa ssp. indica, and their wild progenitor O. rufipogon. We identified a total of 8528 lncRNAs, including 4072 lncRNAs in O. rufipogon, 2091 lncRNAs in japonica rice, and 2365 lncRNAs in indica rice. The lncRNAs expressed in wild rice were revealed to be shorter in length and had fewer exon numbers when compared with lncRNAs from cultivated rice. We also identified a number of conserved lncRNAs in the wild and cultivated rice. The functional study demonstrated that several of these conserved lncRNAs are associated with domestication-related traits in rice. Our findings revealed the feature and conservation of lncRNAs during rice domestication and will further promote functional studies of lncRNAs in rice.


Assuntos
Domesticação , Estudo de Associação Genômica Ampla , Oryza/genética , RNA Longo não Codificante/genética , RNA de Plantas/genética , Sequência de Bases , Sequência Conservada , Produtos Agrícolas/genética , Éxons/genética , Biblioteca Gênica , Anotação de Sequência Molecular , RNA Longo não Codificante/isolamento & purificação , RNA de Plantas/isolamento & purificação , Alinhamento de Sequência , Homologia de Sequência do Ácido Nucleico , Especificidade da Espécie , Transcriptoma
12.
J Allergy Clin Immunol ; 147(4): 1402-1412, 2021 04.
Artigo em Inglês | MEDLINE | ID: mdl-32791162

RESUMO

BACKGROUND: Co-trimoxazole, a sulfonamide antibiotic, is used to treat a variety of infections worldwide, and it remains a common first-line medicine for prophylaxis against Pneumocystis jiroveci pneumonia. However, it can cause severe cutaneous adverse reaction (SCAR), including Stevens-Johnson syndrome, toxic epidermal necrolysis, and drug reaction with eosinophilia and systemic symptoms. The pathomechanism of co-trimoxazole-induced SCAR remains unclear. OBJECTIVE: We aimed to investigate the genetic predisposition of co-trimoxazole-induced SCAR. METHODS: We conducted a multicountry case-control association study that included 151 patients with of co-trimoxazole-induced SCAR and 4631 population controls from Taiwan, Thailand, and Malaysia, as well as 138 tolerant controls from Taiwan. Whole-genome sequencing was performed for the patients and population controls from Taiwan; it further validated the results from Thailand and Malaysia. RESULTS: The whole-genome sequencing study (43 case patients vs 507 controls) discovered that the single-nucleotide polymorphism rs41554616, which is located between the HLA-B and MICA loci, had the strongest association with co-trimoxazole-induced SCAR (P = 8.2 × 10-9; odds ratio [OR] = 7.7). There were weak associations of variants in co-trimoxazole-related metabolizing enzymes (CYP2D6, GSTP1, GCLC, N-acetyltransferase [NAT2], and CYP2C8). A replication study using HLA genotyping revealed that HLA-B∗13:01 was strongly associated with co-trimoxazole-induced SCAR (the combined sample comprised 91 case patients vs 2545 controls [P = 7.2 × 10-21; OR = 8.7]). A strong HLA association was also observed in the case patients from Thailand (P = 3.2 × 10-5; OR = 3.6) and Malaysia (P = .002; OR = 12.8), respectively. A meta-analysis and phenotype stratification study further indicated a strong association between HLA-B∗13:01 and co-trimoxazole-induced drug reaction with eosinophilia and systemic symptoms (P = 4.2 × 10-23; OR = 40.1). CONCLUSION: This study identified HLA-B∗13:01 as an important genetic factor associated with co-trimoxazole-induced SCAR in Asians.


Assuntos
Antibacterianos/efeitos adversos , Anti-Infecciosos Urinários/efeitos adversos , Hipersensibilidade a Drogas/genética , Predisposição Genética para Doença , Antígenos HLA-B/genética , Combinação Trimetoprima e Sulfametoxazol/efeitos adversos , Adolescente , Adulto , Idoso , Estudos de Casos e Controles , Feminino , Humanos , Malásia/epidemiologia , Masculino , Pessoa de Meia-Idade , Polimorfismo de Nucleotídeo Único , Taiwan/epidemiologia , Tailândia/epidemiologia , Sequenciamento Completo do Genoma , Adulto Jovem
13.
Biomed Pharmacother ; 131: 110700, 2020 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-33152906

RESUMO

OBJECTIVE: This study aimed to assess the effect and mechanism of i-type lysozyme on cutaneous wound healing animal model and Multiple cell models both in vivo and in vitro. METHODS: Therefore, to evaluate its regenerative efficacy on wound healing process, we daily applied i-type lysozyme on murine full-thickness excisional wounds. After sacrifice on indicated days, skin tissues around surgical defects were harvested and assessed for re-epithelialization, granulation tissue formation, neovascularization and remodeling. To elucidate the underlying mechanisms, i-type lysozyme was analyzed for its tissue regenerative potency on the proliferation, invasion, migration and tube formation against keratinocytes, fibroblasts and endothelial cells. Antioxidant and antimicrobial experiments were also conducted to elucidate protective ability of i-type lysozyme to wound bed. RESULTS: It displayed excellent bi-directional regulation in wound repair, with significant acceleration of epidermal and dermal regeneration as well as the efficient attenuation of excessive collagen deposition and fibrosis in the surgical lesion. I-type lysozyme treatment augmented the proliferation and migration of HaCaT, NIH 3T3 and HUVECs, enhanced the invasion of HaCaT and HUVECs as well as accelerated tube formation of HUVECs. Additionally, it significantly recovered the proliferation of H2O2-damaged cells, whereas represented no microbicidal effect under effective concentration of wound healing. CONCLUSION: Our findings demonstrate the bi-directional regulation of i-type lysozyme in wound healing process through promoting tissue regeneration while hampering scar formation, implying that it is a promising therapeutic agent for wound repair.


Assuntos
Muramidase/farmacologia , Cicatrização/efeitos dos fármacos , Animais , Movimento Celular/efeitos dos fármacos , Colágeno/metabolismo , Células HaCaT , Células Endoteliais da Veia Umbilical Humana , Humanos , Queratinócitos/efeitos dos fármacos , Masculino , Camundongos , Camundongos Endogâmicos BALB C , Células NIH 3T3 , Reepitelização/efeitos dos fármacos , Regeneração/efeitos dos fármacos , Cicatrização/fisiologia
14.
Nat Commun ; 11(1): 6031, 2020 11 27.
Artigo em Inglês | MEDLINE | ID: mdl-33247135

RESUMO

Plant spermatogenesis is a complex process that directly affects crop breeding. A rapid change in gene abundance occurs at early meiosis prophase, when gene regulation is selective. However, how these genes are regulated remains unknown. Here, we show that rice reproductive phasiRNAs are essential for the elimination of a specific set of RNAs during meiotic prophase I. These phasiRNAs cleave target mRNAs in a regulatory manner such that one phasiRNA can target more than one gene, and/or a single gene can be targeted by more than one phasiRNA to efficiently silence target genes. Our investigation of phasiRNA-knockdown and PHAS-edited transgenic plants demonstrates that phasiRNAs and their nucleotide variations are required for meiosis progression and fertility. This study highlights the importance of reproductive phasiRNAs for the reprogramming of gene expression during meiotic progression and establishes a basis for future studies on the roles of phasiRNAs with a goal of crop improvement.


Assuntos
Regulação da Expressão Gênica de Plantas , Meiose/genética , Oryza/citologia , Oryza/genética , RNA de Plantas/metabolismo , Sequência de Bases , Fertilidade/genética , Gametogênese Vegetal/genética , Modelos Biológicos , Nucleotídeos/genética , Proteínas de Plantas/genética , Proteínas de Plantas/metabolismo , Plantas Geneticamente Modificadas , Pólen/citologia , Pólen/genética , Clivagem do RNA , RNA de Plantas/genética , Reprodutibilidade dos Testes
15.
Theriogenology ; 158: 309-320, 2020 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-33007716

RESUMO

Vitamin C (ascorbic acid, AA) can regulate antioxidation and affect many cellular processes. However, the effect of AA on the reproduction of male animals remains less explored. Here, we showed that by supplementing exogenous AA to porcine immature Sertoli cells (iSCs), AA could promote the proliferation, suppress apoptosis, and decrease the global nucleic acid methylation (5 mC and m6A) levels of iSCs. After we profiled mRNA and long non-coding RNA (lncRNA) expression by transcriptome sequencing on iSCs (treated by 250 µM AA for 36 h), 1232 mRNAs and 937 lncRNAs were identified to be differentially expressed (DE). Gene enrichment analysis found multiple significantly enriched biological pathways, including oxidoreductase activity, cell proliferation and apoptosis, regulation of hormone level, regulation of catalytic activity, developmental process, ATP metabolism and reproductive process. Specifically, for the reproductive process, 49 up- and 36 down-regulated DE mRNAs (including highly expressed genes, such as Tfcp2l1, Hmgcs1, Mmp7, Fndc3a, and Zfp36l1) are involved. Moreover, AA supplementation could promote the secretion of anti-müllerian hormone, inhibin B and lactate, and enhance the activity of lactate dehydrogenase as well. Taken together, AA could promote the reproductive function of pig iSCs, potentially through reprogramming the global transcriptome, and elevating hormone secretion and metabolite production.


Assuntos
RNA Longo não Codificante , Transcriptoma , Animais , Ácido Ascórbico/farmacologia , Perfilação da Expressão Gênica/veterinária , Masculino , RNA Mensageiro , Células de Sertoli , Suínos
16.
Proc Natl Acad Sci U S A ; 117(1): 727-732, 2020 01 07.
Artigo em Inglês | MEDLINE | ID: mdl-31871204

RESUMO

The intine, the inner layer of the pollen wall, is essential for the normal development and germination of pollen. However, the composition and developmental regulation of the intine in rice (Oryza sativa) remain largely unknown. Here, we identify a microRNA, OsmiR528, which regulates the formation of the pollen intine and thus male fertility in rice. The mir528 knockout mutant aborted pollen development at the late binucleate pollen stage, significantly decreasing the seed-setting rate. We further demonstrated that OsmiR528 affects pollen development by directly targeting the uclacyanin gene OsUCL23 (encoding a member of the plant-specific blue copper protein family of phytocyanins) and regulating intine deposition. OsUCL23 overexpression phenocopied the mir528 mutant. The OsUCL23 protein localized in the prevacuolar compartments (PVCs) and multivesicular bodies (MVBs). We further revealed that OsUCL23 interacts with a member of the proton-dependent oligopeptide transport (POT) family of transporters to regulate various metabolic components, especially flavonoids. We propose a model in which OsmiR528 regulates pollen intine formation by directly targeting OsUCL23 and in which OsUCL23 interacts with the POT protein on the PVCs and MVBs to regulate the production of metabolites during pollen development. The study thus reveals the functions of OsmiR528 and an uclacyanin during pollen development.


Assuntos
Metaloproteínas/genética , MicroRNAs/metabolismo , Oryza/fisiologia , Proteínas de Plantas/genética , Pólen/metabolismo , Regulação da Expressão Gênica de Plantas , Microscopia Eletrônica de Transmissão , Plantas Geneticamente Modificadas , Pólen/ultraestrutura
17.
Plant Biotechnol J ; 18(3): 679-690, 2020 03.
Artigo em Inglês | MEDLINE | ID: mdl-31419052

RESUMO

Plant defence is multilayered and is essential for surviving in a changing environment. The discovery of long noncoding RNAs (lncRNAs) has dramatically extended our understanding of post-transcriptional gene regulation in diverse biological processes. However, the expression profile and function of lncRNAs in disease resistance are still largely unknown, especially in monocots. Here, we performed strand-specific RNA sequencing of rice leaves infected by Xanthomonas oryzae pv. Oryzae (Xoo) in different time courses and systematically identified 567 disease-responsive rice lncRNAs. Target analyses of these lncRNAs showed that jasmonate (JA) pathway was significantly enriched. To reveal the interaction between lncRNAs and JA-related genes, we studied the coexpression of them and found 39 JA-related protein-coding genes to be interplayed with 73 lncRNAs, highlighting the potential modulation of lncRNAs in JA pathway. We subsequently identified an lncRNA, ALEX1, whose expression is highly induced by Xoo infection. A T-DNA insertion line constructed using enhancer trap system showed a higher expression of ALEX1 and exerted a significant resistance to rice bacterial blight. Functional study revealed that JA signalling is activated and the endogenous content of JA and JA-Ile is increased. Overexpressing ALEX1 in rice further confirmed the activation of JA pathway and resistance to bacterial blight. Our findings reveal the expression of pathogen-responsive lncRNAs in rice and provide novel insights into the connection between lncRNAs and JA pathway in the regulation of plant disease resistance.


Assuntos
Ciclopentanos/metabolismo , Resistência à Doença , Oryza/genética , Oxilipinas/metabolismo , Doenças das Plantas/genética , RNA Longo não Codificante/genética , Regulação da Expressão Gênica de Plantas , Doenças das Plantas/microbiologia , Proteínas de Plantas/genética , Xanthomonas/patogenicidade
18.
Plant Physiol ; 182(1): 204-214, 2020 01.
Artigo em Inglês | MEDLINE | ID: mdl-31694901

RESUMO

MicroRNAs (miRNAs) are small noncoding RNAs of ∼21 nt in length, which have regulatory roles in many biological processes. In animals, proper functioning of the circadian clock, which is closely linked to the fitness of almost all living organisms, is regulated by miRNAs. However, to date, there have been no reports of the roles of miRNA in regulation of the plant circadian rhythm. Here, we report a natural variant of miR397 that lengthens the circadian period and controls flowering time in Arabidopsis (Arabidopsis thaliana). Highly conserved among angiosperms, the miRNA miR397 has two members in Arabidopsis: miR397a and miR397b. However, only miR397b significantly delayed flowering. Our results suggest that miR397b controls flowering by targeting CASEIN KINASE II SUBUNIT BETA3 (CKB3), in turn modulating the circadian period of CIRCADIAN CLOCK ASSOCIATED1 (CCA1). We further demonstrated that CCA1 directly bound to the promoter of MIR397B and suppressed its expression, forming a miR397b-CKB3-CCA1 circadian regulation feedback circuit. Evolutionary analysis revealed that miR397b is a newly evolved genetic variant in Arabidopsis, and the miR397b targeting mode may have a role in enhancing plant fitness. Our results provide evidence for miRNA-mediated circadian regulation in plants and suggest the existence of a feedback loop to manipulate plant flowering through the regulation of circadian rhythm.


Assuntos
Proteínas de Arabidopsis/metabolismo , Arabidopsis/metabolismo , Arabidopsis/fisiologia , Ritmo Circadiano/fisiologia , MicroRNAs/metabolismo , Arabidopsis/genética , Proteínas de Arabidopsis/genética , Ritmo Circadiano/genética , Regulação da Expressão Gênica de Plantas/genética , Regulação da Expressão Gênica de Plantas/fisiologia , MicroRNAs/genética , Fatores de Transcrição/genética , Fatores de Transcrição/metabolismo
19.
Arthritis Res Ther ; 21(1): 267, 2019 12 04.
Artigo em Inglês | MEDLINE | ID: mdl-31801580

RESUMO

BACKGROUND: The information concerning non-invasive, easily obtainable, and accurate biomarkers for diagnosis of lupus nephritis (LN) is extremely limited. The aim of this study was to evaluate the diagnostic performance of cystatin C (CysC) and complement component 1q (C1q) for LN. METHODS: A case-control study that included 905 patients with systemic lupus erythematosus (SLE) without LN (group SLE), 334 patients with active lupus nephritis (group LNA), 255 patients with inactive lupus nephritis (group LNI), and 497 healthy individuals (group HC) was performed in Mianyang Central Hospital from March 2017 to December 2018. The serum levels of CysC, C1q, urea (Urea), and creatinine (Creat) were measured, and 2 estimated glomerular filtration rates (eGFRCysC and eGFRCreat) were calculated by equations which were based on serum CysC established by our group and the modification of diet in renal disease (MDRD), respectively. ANOVA analysis or Kruskal-Wallis test was used for comparing the differences among the groups, and receiver operating characteristic (ROC) curve was applied to identify the diagnostic efficiencies of individual or combined multiple indicators. RESULTS: Significantly elevated CysC and decreased C1q were observed in the LNA and LNI groups, which was in contrast to their levels in the SLE and HC groups. CysC (AUC = 0.906) or eGFRCysC (AUC = 0.907) assessed the highest diagnostic performance on LNA when detected individually, followed by C1q (AUC = 0.753). Joint utilization of C1q and CysC achieved very good performance (AUC = 0.933) which approximated to the best one observed in the combinations of C1q, Urea, CysC, eGFRCreat, and Creat (AUC = 0.975). CONCLUSION: The separately detected CysC (eGFRCysC) and C1q were superior to the conventional biomarkers Urea, Creat, and eGFRCreat in the diagnosis of LNA. Moreover, although the combined detection of Urea, Creat, C1q, CysC, and eGFRCreat had the greatest diagnostic performance, the joint utilization of CysC and C1q could be prioritized for rapid discrimination of LNA if the economic burden is taken into consideration.


Assuntos
Biomarcadores/sangue , Complemento C1q/análise , Cistatina C/sangue , Nefrite Lúpica/sangue , Nefrite Lúpica/diagnóstico , Adolescente , Adulto , Idoso , Idoso de 80 Anos ou mais , Estudos de Casos e Controles , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Adulto Jovem
20.
PLoS Genet ; 15(5): e1008120, 2019 05.
Artigo em Inglês | MEDLINE | ID: mdl-31116744

RESUMO

N6-Methyladenosine (m6A) RNA methylation plays important roles during development in different species. However, knowledge of m6A RNA methylation in monocots remains limited. In this study, we reported that OsFIP and OsMTA2 are the components of m6A RNA methyltransferase complex in rice and uncovered a previously unknown function of m6A RNA methylation in regulation of plant sporogenesis. Importantly, OsFIP is essential for rice male gametogenesis. Knocking out of OsFIP results in early degeneration of microspores at the vacuolated pollen stage and simultaneously causes abnormal meiosis in prophase I. We further analyzed the profile of rice m6A modification during sporogenesis in both WT and OsFIP loss-of-function plants, and identified a rice panicle specific m6A modification motif "UGWAMH". Interestingly, we found that OsFIP directly mediates the m6A methylation of a set of threonine protease and NTPase mRNAs and is essential for their expression and/or splicing, which in turn regulates the progress of sporogenesis. Our findings revealed for the first time that OsFIP plays an indispensable role in plant early sporogenesis. This study also provides evidence for the different functions of the m6A RNA methyltransferase complex between rice and Arabidopsis.


Assuntos
Gametogênese Vegetal , Regulação da Expressão Gênica de Plantas , Metiltransferases/genética , Oryza/genética , Proteínas de Plantas/genética , Subunidades Proteicas/genética , Adenosina/análogos & derivados , Motivos de Aminoácidos , Arabidopsis/genética , Arabidopsis/crescimento & desenvolvimento , Arabidopsis/metabolismo , Mutação com Perda de Função , Prófase Meiótica I , Metilação , Metiltransferases/metabolismo , Nucleosídeo-Trifosfatase/genética , Nucleosídeo-Trifosfatase/metabolismo , Oryza/crescimento & desenvolvimento , Oryza/metabolismo , Proteínas de Plantas/metabolismo , Pólen/genética , Pólen/crescimento & desenvolvimento , Pólen/metabolismo , Subunidades Proteicas/metabolismo , RNA de Plantas , Especificidade da Espécie
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