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1.
J Biol Chem ; 300(7): 107415, 2024 May 28.
Artículo en Inglés | MEDLINE | ID: mdl-38815863

RESUMEN

While deubiquitinase ATXN3 has been implicated as a potential oncogene in various types of human cancers, its role in colon adenocarcinoma remains understudied. Surprisingly, our findings demonstrate that ATXN3 exerts an antitumor effect in human colon cancers through potentiating Galectin-9-induced apoptosis. CRISPR-mediated ATXN3 deletion unexpectedly intensified colon cancer growth both in vitro and in xenograft colon cancers. At the molecular level, we identified ATXN3 as a bona fide deubiquitinase specifically targeting Galectin-9, as ATXN3 interacted with and inhibited Galectin-9 ubiquitination. Consequently, targeted ATXN3 ablation resulted in reduced Galectin-9 protein expression, thereby diminishing Galectin-9-induced colon cancer apoptosis and cell growth arrest. The ectopic expression of Galectin-9 fully reversed the growth of ATXN3-null colon cancer in mice. Furthermore, immunohistochemistry staining revealed a significant reduction in both ATXN3 and Galectin-9 protein expression, along with a positive correlation between them in human colon cancer. Our study identifies the first Galectin-9-specific deubiquitinase and unveils a tumor-suppressive role of ATXN3 in human colon cancer.

2.
Small ; : e2400344, 2024 Mar 18.
Artículo en Inglés | MEDLINE | ID: mdl-38497503

RESUMEN

Organic supramolecular photocatalysts have garnered widespread attention due to their adjustable structure and exceptional photocatalytic activity. Herein, a novel bis-dicarboxyphenyl-substituent naphthalenediimide self-assembly supramolecular photocatalyst (SA-NDI-BCOOH) with efficient dual-functional photocatalytic performance is successfully constructed. The large molecular dipole moment and short-range ordered stacking structure of SA-NDI-BCOOH synergistically create a giant internal electric field (IEF), resulting in a remarkable 6.7-fold increase in its charge separation efficiency. Additionally, the tetracarboxylic structure of SA-NDI-BCOOH greatly enhances its hydrophilicity. Thus, SA-NDI-BCOOH demonstrates efficient dual-functional activity for photocatalytic hydrogen and oxygen evolution, with rates of 372.8 and 3.8 µmol h-1 , respectively. Meanwhile, a notable apparent quantum efficiency of 10.86% at 400 nm for hydrogen evolution is achieved, prominently surpassing many reported supramolecular photocatalysts. More importantly, with the help of dual co-catalysts, it exhibits photocatalytic overall water splitting activity with H2 and O2 evolution rates of 3.2 and 1.6 µmol h-1 . Briefly, this work sheds light on enhancing the IEF by controlling the molecular polarity and stacking structure to dramatically improve the photocatalytic performance of supramolecular materials.

3.
Plant Cell ; 33(10): 3331-3347, 2021 10 11.
Artículo en Inglés | MEDLINE | ID: mdl-34323980

RESUMEN

For grain crops such as rice (Oryza sativa), grain size substantially affects yield. The histone acetyltransferase GRAIN WEIGHT 6a (GW6a) determines grain size and yield in rice. However, the gene regulatory network underlying GW6a-mediated regulation of grain size has remained elusive. In this study, we show that GW6a interacts with HOMOLOG OF DA1 ON RICE CHROMOSOME 3 (HDR3), a ubiquitin-interacting motif-containing ubiquitin receptor. Transgenic rice plants overexpressing HDR3 produced larger grains, whereas HDR3 knockout lines produce smaller grains compared to the control. Cytological data suggest that HDR3 modulates grain size in a similar manner to GW6a, by altering cell proliferation in spikelet hulls. Mechanistically, HDR3 physically interacts with and stabilizes GW6a in an ubiquitin-dependent manner, delaying protein degradation by the 26S proteasome. The delay in GW6a degradation results in dramatic enhancement of the local acetylation of H3 and H4 histones. Furthermore, RNA sequencing analysis and chromatin immunoprecipitation assays reveal that HDR3 and GW6a bind to the promoters of and modulate a common set of downstream genes. In addition, genetic analysis demonstrates that HDR3 functions in the same genetic pathway as GW6a to regulate the grain size. Therefore, we identified the grain size regulatory module HDR3-GW6a as a potential target for crop yield improvement.


Asunto(s)
Grano Comestible/crecimiento & desarrollo , Oryza/genética , Proteínas de Plantas/genética , Grano Comestible/genética , Histona Acetiltransferasas/genética , Histona Acetiltransferasas/metabolismo , Oryza/enzimología , Oryza/crecimiento & desarrollo , Proteínas de Plantas/metabolismo
4.
Opt Lett ; 49(8): 1941-1944, 2024 Apr 15.
Artículo en Inglés | MEDLINE | ID: mdl-38621046

RESUMEN

Snapshot multispectral imaging (SMSI) has attracted much attention in recent years for its compact structure and superior performance. High-level image analysis based on SMSI, such as object classification and recognition, usually takes the image reconstruction as the first step, which hinders its application in many important real-time scenarios. Here we demonstrate the first, to our knowledge, reconstruction-free strategy for object detection with SMSI in the short-wave infrared (SWIR) band. The implementation of our SMSI is based on a modified 4f system which modulates the light with a random phase mask, and the distinctive point spread function in each narrowband endows the system with spectrum resolving ability. A deep learning network with a CenterNet structure is trained to detect a small object by constructing a dataset with the PSF of our SMSI system and the sky images as background. Our results indicate that a small object with a spectral feature can be detected directly with the compressed image output by our SMSI system. This work paves the way toward the use of SMSI to detect a multispectral object in practical applications.

5.
Cardiol Young ; 34(1): 86-91, 2024 Jan.
Artículo en Inglés | MEDLINE | ID: mdl-37226303

RESUMEN

To explore effect of comprehensive nursing in postoperative ICU of children with CHD. The subjects were 50 cases of children with CHD treated in our hospital: 25 cases in the control group: routine nursing, and 25 cases in the observation group: comprehensive nursing intervention. The effective rate of 92.00% in the observation group was significantly higher. The serum-free calcium value (1.07 ± 0.11) mmol/L of the observation group on the first day after surgery was significantly lower, and the observation group's creatine phosphate, the daily average dosage of creatine phosphate per unit body weight was significantly higher. 96.00% of patients in the observation group were significantly higher in nursing satisfaction. The complication rate of 8.00% in observation group was significantly lower. In order to successfully complete the operation schedule and improve the postoperative recovery effect of children, high requirements are placed on nursing staff. The comprehensive nursing method used in the postoperative ICU of children with CHD can reduce the incidence of postoperative complications and improve nursing satisfaction.


Asunto(s)
Unidades de Cuidados Intensivos , Complicaciones Posoperatorias , Niño , Humanos , Fosfocreatina , Complicaciones Posoperatorias/epidemiología , Complicaciones Posoperatorias/prevención & control , Periodo Posoperatorio
6.
J Am Acad Dermatol ; 88(6): 1300-1307, 2023 06.
Artículo en Inglés | MEDLINE | ID: mdl-36806645

RESUMEN

BACKGROUND: Patients with refractory erythema of rosacea have limited treatment options. OBJECTIVE: To evaluate the efficacy and safety of a 12-week course of paroxetine for moderate-to-severe erythema of rosacea. METHODS: In a multicenter, randomized, double-blinded, placebo-controlled trial, patients with refractory erythema of rosacea were randomly assigned (1:1) to receive paroxetine 25 mg daily or placebo for 12 weeks. RESULTS: Overall, 97 patients completed the study (paroxetine: 49; placebo: 48). The primary end point was the proportion of participants achieving Clinical Erythema Assessment success (defined as Clinical Erythema Assessment score of 0, 1, or ≥2-grade improvement from baseline) at week 12; this was significantly greater in the paroxetine group than in the placebo group (42.9% vs 20.8%, P = .02). Some secondary end points were met, such as flushing success with point reductions ≥2 (44.9% vs 25.0%, P = .04) and improvement in overall flushing (2.49 ± 3.03 vs 1.68 ± 2.27, P = .047), burning sensation (46.9% vs 18.8%, P = .003), and depression (P = .041). The most reported adverse events associated with paroxetine were dizziness, lethargy, nausea, dyspepsia, and muscle tremors. LIMITATIONS: Only a single-dosage regimen of paroxetine within a 12-week study was evaluated. CONCLUSIONS: Paroxetine is an effective and well-tolerated alternative treatment for moderate-to-severe erythema of rosacea.


Asunto(s)
Paroxetina , Rosácea , Humanos , Paroxetina/uso terapéutico , Estudios Prospectivos , Rosácea/complicaciones , Rosácea/tratamiento farmacológico , Eritema/tratamiento farmacológico , Eritema/etiología , Resultado del Tratamiento , Método Doble Ciego
7.
Bioorg Chem ; 141: 106842, 2023 12.
Artículo en Inglés | MEDLINE | ID: mdl-37769523

RESUMEN

Ubiquitin-specific protease 22 (USP22) plays a prominent role in tumor development, invasion, metastasis and immune reprogramming, which has been proposed as a potential therapeutic target for cancer. Herein, we employed a structure-based discovery and biological evaluation and discovered that Rottlerin (IC50 = 2.53 µM) and Morusin (IC50 = 8.29 µM) and as selective and potent USP22 inhibitors. Treatment of HCT116 cells and A375 cells with each of the two compounds resulted in increased monoubiquitination of histones H2A and H2B, as well as reduced protein expression levels of Sirt1 and PD-L1, all of which are known as USP22 substrates. Additionally, our study demonstrated that the administration of Rottlerin or Morusin resulted in an increase H2Bub levels, while simultaneously reducing the expression of Sirt1 and PD-L1 in a manner dependent on USP22. Furthermore, Rottlerin and Morusin were found to enhance the degradation of PD-L1 and Sirt1, as well as increase the polyubiquitination of endogenous PD-L1 and Sirt1 in HCT116 cells. Moreover, in an in vivo syngeneic tumor model, Rottlerin and Morusin exhibited potent antitumor activity, which was accompanied by an enhanced infiltration of T cells into the tumor tissues. Using in-depth molecular dynamics (MD) and binding free energy calculation, conserved residue Leu475 and non-conserved residue Arg419 were proven to be crucial for the binding affinity and inhibitory function of USP22 inhibitors. In summary, our study established a highly efficient approach for USP22-specific inhibitor discovery, which lead to identification of two selective and potent USP22 inhibitors as potential drugs in anticancer therapy.


Asunto(s)
Antígeno B7-H1 , Sirtuina 1 , Humanos , Sirtuina 1/metabolismo , Benzopiranos , Bioensayo
8.
Skin Res Technol ; 29(6): e13321, 2023 Jun.
Artículo en Inglés | MEDLINE | ID: mdl-37357644

RESUMEN

BACKGROUND: Cutaneous squamous cell carcinoma (CSCC) is a severe malignancy derived from the skin. Mounting evidence suggests that circular RNAs (circRNAs) participate in diverse biological functions in human cancers, containing CSCC. However, the biological functions and underlying mechanism of hsa_circ_0005085 in CSCC have not been clearly studied. METHODS: Expression levels of hsa_circ_0005085, microRNA-186-5p (miR-186-5p), and Laminin subunit gamma 1 (LAMC1) were detected by reverse transcription-quantitative polymerase chain reaction. Cell counting kit-8 assay, colony formation assay, and 5-Ethynyl-2'-deoxyuridine assay were used to assess cell proliferation. Transwell assay was conducted to detect cell migration and invasion. Cell apoptosis was analyzed by flow cytometry. Protein expression of LAMC1, E-cadherin, Snail, and slug were assessed using western blot assay. Using bioinformatics software, the binding between miR-186-5p and hsa_circ_0005085 or LAMC1 was predicted, followed by verification using a dual-luciferase reporter and RNA-Immunoprecipitation. The mouse xenograft model was established to investigate the role of hsa_circ_0005085 in vivo. RESULTS: Hsa_circ_0005085 level was downregulated in CSCC tissues and cells. Overexpression of hsa_circ_0005085 inhibited cell proliferation, migration, invasion, epithelial-mesenchymal transition (EMT), and promoted cell apoptosis in CSCC. MiR-186-5p could restore the effect of hsa_circ_0005085 overexpression on CSCC cells, and the knockdown of LAMC1 reversed the regulation of the miR-186-5p inhibitor. In mechanism, hsa_circ_0005085 served as a sponge for miR-186-5p to regulate LAMC1 expression. Overexpression of hsa_circ_0005085 reduced growth of tumor via miR-186-5p/LAMC1 axis in vivo. CONCLUSION: In our study, hsa_circ_0005085 might inhibit CSCC development by targeting the miR-186-5p/LAMC1 axis, which might provide a promising therapeutic target for CSCC.


Asunto(s)
Carcinoma de Células Escamosas , MicroARNs , Neoplasias Cutáneas , Animales , Humanos , Ratones , Vendajes , Carcinoma de Células Escamosas/genética , Proliferación Celular , Modelos Animales de Enfermedad , MicroARNs/genética , Neoplasias Cutáneas/genética
9.
J Ultrasound Med ; 42(8): 1663-1673, 2023 Aug.
Artículo en Inglés | MEDLINE | ID: mdl-36591796

RESUMEN

OBJECTIVES: To assess the diagnostic value of qualitative and quantitative contrast-enhanced ultrasound (CEUS) for pathological subtypes of small solid renal masses (sSRMs). METHODS: Patients with sSRMs confirmed by surgical pathology from January 2019 to November 2021 were retrospectively identified. All patients were divided into 3 groups: clear cell renal cell carcinoma (ccRCC) group, none-ccRCC group (renal cell carcinoma other than ccRCC), and angiomyolipoma (AML) group. The mass position, size, echogenicity and blood flow signals were compared. The speed of wash-in, wash-out, the degree of peak enhancement and the homogeneity at peak enhancement, the presence of pseudocapsule sign in CEUS imaging were qualitatively evaluated. Peak enhancement, wash-in area under the curve (WiAUC), rise time, time to peak, wash-in rate (WiR), wash-in perfusion index (WiPI) and tumor-to-cortex enhancement ratio of the above parameters in CEUS imaging were quantitatively evaluated. RESULTS: Of 105 patients, 105 sSRMs (66 ccRCC, 18 none-ccRCC, 21 AML) were enrolled in this study. No significant differences were found on location, size and echogenicity among 3 groups (all P > .05). The proportion of fast-washout and hypo-enhancement were highest in none-ccRCC group. Heterogeneous enhancement was detected in 87.88% in ccRCC group which is significantly higher than other 2 groups. Hundred percent of the AML showed no pseudocapsule sign, which is the highest among the 3 groups. Peak enhancement, WiAUC, WiR, WiPI of ccRCC group were the highest among the 3 groups. CONCLUSIONS: Qualitative and quantitative CEUS not only has the diagnostic value in distinguishing AML from malignant sSRMs, but also helps to differentiate the pathological subtypes of sSRMs.


Asunto(s)
Angiomiolipoma , Carcinoma de Células Renales , Neoplasias Renales , Leucemia Mieloide Aguda , Humanos , Carcinoma de Células Renales/diagnóstico por imagen , Estudios Retrospectivos , Medios de Contraste , Neoplasias Renales/diagnóstico por imagen , Ultrasonografía/métodos , Angiomiolipoma/diagnóstico por imagen , Angiomiolipoma/patología
10.
Int J Mol Sci ; 24(9)2023 Apr 23.
Artículo en Inglés | MEDLINE | ID: mdl-37175435

RESUMEN

Despite the many strategies employed to slow the spread of cancer, the development of new anti-tumor drugs and the minimization of side effects have been major research hotspots in the anti-tumor field. Natural drugs are a huge treasure trove of drug development, and they have been widely used in the clinic as anti-tumor drugs. Selaginella species in the family Selaginellaceae are widely distributed worldwide, and they have been well-documented in clinical practice for the prevention and treatment of cancer. Biflavonoids are the main active ingredients in Selaginella, and they have good biological and anti-tumor activities, which warrant extensive research. The promise of biflavonoids from Selaginella (SFB) in the field of cancer therapy is being realized thanks to new research that offers insights into the multi-targeting therapeutic mechanisms and key signaling pathways. The pharmacological effects of SFB against various cancers in vitro and in vivo are reviewed in this review. In addition, the types and characteristics of biflavonoid structures are described in detail; we also provide a brief summary of the efforts to develop drug delivery systems or combinations to enhance the bioavailability of SFB monomers. In conclusion, SFB species have great potential to be developed as adjuvant or even primary therapeutic agents for cancer, with promising applications.


Asunto(s)
Antineoplásicos , Biflavonoides , Selaginellaceae , Biflavonoides/farmacología , Biflavonoides/uso terapéutico , Biflavonoides/química , Extractos Vegetales/farmacología , Selaginellaceae/química , Antineoplásicos/farmacología , Antineoplásicos/uso terapéutico , Antineoplásicos/química , Disponibilidad Biológica
11.
Nat Mater ; 20(10): 1431-1439, 2021 Oct.
Artículo en Inglés | MEDLINE | ID: mdl-33958770

RESUMEN

It is believed that the slow liquid diffusion and geometric frustration brought by a rapid, deep quench inhibit fast crystallization and promote vitrification. Here we report fast crystal growth in charged colloidal systems under deep supercooling, where liquid diffusion is extremely low. By combining experiments and simulations, we show that this process occurs via wall-induced barrierless ordering consisting of two coupled steps: the step-like advancement of the rough interface that disintegrates frustration, followed by defect repairing inside the newly formed solid phase. The former is a diffusionless collective process, whereas the latter controls crystal quality. We further show that the intrinsic mechanical instability of a disordered glassy state subject to the crystal growth front allows for domino-like fast crystal growth even at ultra-low temperatures. These findings contribute to a deeper understanding of fast crystal growth and may be useful for applications related to vitrification prevention and crystal-quality control.

12.
PLoS Biol ; 17(5): e3000252, 2019 05.
Artículo en Inglés | MEDLINE | ID: mdl-31112550

RESUMEN

Rapamycin (Rap) and its derivatives, called rapalogs, are being explored in clinical trials targeting cancer and neurodegeneration. The underlying mechanisms of Rap actions, however, are not well understood. Mechanistic target of rapamycin (mTOR), a lysosome-localized protein kinase that acts as a critical regulator of cellular growth, is believed to mediate most Rap actions. Here, we identified mucolipin 1 (transient receptor potential channel mucolipin 1 [TRPML1], also known as MCOLN1), the principle Ca2+ release channel in the lysosome, as another direct target of Rap. Patch-clamping of isolated lysosomal membranes showed that micromolar concentrations of Rap and some rapalogs activated lysosomal TRPML1 directly and specifically. Pharmacological inhibition or genetic inactivation of mTOR failed to mimic the Rap effect. In vitro binding assays revealed that Rap bound directly to purified TRPML1 proteins with a micromolar affinity. In both healthy and disease human fibroblasts, Rap and rapalogs induced autophagic flux via nuclear translocation of transcription factor EB (TFEB). However, such effects were abolished in TRPML1-deficient cells or by TRPML1 inhibitors. Hence, Rap and rapalogs promote autophagy via a TRPML1-dependent mechanism. Given the demonstrated roles of TRPML1 and TFEB in cellular clearance, we propose that lysosomal TRPML1 may contribute a significant portion to the in vivo neuroprotective and anti-aging effects of Rap via an augmentation of autophagy and lysosomal biogenesis.


Asunto(s)
Lisosomas/metabolismo , Sirolimus/farmacología , Serina-Treonina Quinasas TOR/metabolismo , Canales de Potencial de Receptor Transitorio/metabolismo , Autofagia/efectos de los fármacos , Factores de Transcripción Básicos con Cremalleras de Leucinas y Motivos Hélice-Asa-Hélice/metabolismo , Calcio/farmacología , Núcleo Celular/efectos de los fármacos , Núcleo Celular/metabolismo , Fibroblastos/efectos de los fármacos , Fibroblastos/metabolismo , Células HEK293 , Células HeLa , Humanos , Activación del Canal Iónico/efectos de los fármacos , Lisosomas/efectos de los fármacos , Modelos Biológicos , Unión Proteica/efectos de los fármacos , Sirolimus/análogos & derivados , Sirolimus/química
13.
Appl Opt ; 61(9): 2432-2437, 2022 Mar 20.
Artículo en Inglés | MEDLINE | ID: mdl-35333263

RESUMEN

Tantalum aluminum carbide (Ta4AlC3) phase ceramic (MAX) material has attracted much attention because of its high conductivity, high strength, corrosion resistance, and good optical properties. However, there are too few reports on lasers with Ta4AlC3-based saturable absorbers (SAs). We prepared and characterized a Ta4AlC3-based SA whose nonlinear absorption performances were achieved at a 2 µm waveband range and which was used in a passively Q-switched (PQS) Tm:YAP laser. In the PQS mode, a maximum average output power of 0.78 W was achieved with the central output wavelength of 1991.86 nm from a PQS Tm:YAP laser, corresponding to a pulse duration of 926 ns at 143.8 kHz.

14.
J Tissue Viability ; 31(4): 678-686, 2022 Nov.
Artículo en Inglés | MEDLINE | ID: mdl-36028386

RESUMEN

OBJECTIVES: In this study, we have investigated the effect of Astragaloside IV on keratinocytes' proliferation, migration, oxidative stress, apoptosis, inflammation, and relevant signaling pathway, using human keratinocytes exposed to high glucose. BACKGROUND: Astragaloside IV is one of the main active ingredients of Astragalus membranaceus (Fisch.) Bunge. Previous studies have found that Astragaloside IV exerts positive effects in various disease models and promotes wound healing. METHODS: Cell proliferation and migration of keratinocytes, oxidative stress indicators, cell apoptosis rate, inflammatory factors, and key proteins in the TGF-ß/Smad signaling pathway were evaluated by molecular biology/biochemical techniques, fluorescence microscope, and flow cytometry. RESULTS: High glucose inhibited the cell proliferation and migration of keratinocytes, upregulated the levels of MDA, ROS, IL-6, IL-8, and Smad7, and decreased the levels of SOD, IL-10, TGF-ß1, p-Smad2, and p-Smad3. Astragaloside IV attenuated the dysfunction of keratinocytes, oxidative stress, cell apoptosis, and inflammation, but activated TGF-ß/Smad signaling pathway. Meanwhile, the addition of SB431542 (the inhibitor of TGF-ß/Smad signaling pathway) eliminated the impact of Astragaloside IV on high glucose-induced keratinocytes. CONCLUSIONS: These results strongly suggest that Astragaloside IV may be a potential drug candidate for accelerating diabetic wound healing, by protecting keratinocytes against damages induced by high glucose and TGF-ß/Smad pathway is involved in this process at the cellular level.


Asunto(s)
Queratinocitos , Factor de Crecimiento Transformador beta , Humanos , Factor de Crecimiento Transformador beta/farmacología , Transducción de Señal , Inflamación , Glucosa/efectos adversos
15.
Zhongguo Zhong Yao Za Zhi ; 47(11): 2899-2908, 2022 Jun.
Artículo en Zh | MEDLINE | ID: mdl-35718510

RESUMEN

Chinese medicinal materials are the precious resources of China and favored by patients at home and abroad because of their natural sources and curative effects. Pesticides are often used to prevent and control diseases and insect pests and regulate the growth of Chinese medicinal plants, so as to improve the yield and quality of Chinese medicinal materials. Most of the pesticides can play a role in pest control through systemic action, stomach toxicity, contact, fumigation and other ways, especially the systemic pesticides can kill hidden pests by entering the Chinese medicinal plants. Despite the good pest control effect, it is difficult to remove the systemic pesticides by simple cleaning, which poses a great risk to the safety of Chinese medicinal materials. At the same time, excessive or non-standard use of pesticides leads to serious pesticide residues in Chinese medicinal materials, which affects not only the quality and efficacy of the materials and harm human health but also the international development of Chinese medicinal materials industry. Pesticide residues have become a bottleneck affecting the industry development and hindering the export of Chinese medicinal materials. Therefore, it is of great significance to study how to quickly, sensitively, and accurately detect and remove pesticide residues in Chinese medicinal materials. We reviewed the common pesticide residues in Chinese medicinal materials in recent years in terms of characteristics, harm, and detection and removal techniques, and discussed the future development of the detection and removal deve-lopment. With this review, we aimed to provide a reference for the quality control of Chinese medicinal materials and promote the healthy development of Chinese medicine industry.


Asunto(s)
Residuos de Plaguicidas , Plaguicidas , Plantas Medicinales , Fumigación , Humanos , Medicina Tradicional China , Residuos de Plaguicidas/análisis , Plaguicidas/análisis , Plaguicidas/toxicidad
16.
Plant Biotechnol J ; 19(6): 1110-1124, 2021 06.
Artículo en Inglés | MEDLINE | ID: mdl-33369825

RESUMEN

Cotton seeds are typically covered by lint and fuzz fibres. Natural 'fuzzless' mutants are an ideal model system for identifying genes that regulate cell initiation and elongation. Here, using a genome-wide association study (GWAS), we identified a ~ 6.2 kb insertion, larINDELFZ , located at the end of chromosome 8, composed of a ~ 5.0 kb repetitive sequence and a ~ 1.2 kb fragment translocated from chromosome 12 in fuzzless Gossypium arboreum. The presence of larINDELFZ was associated with a fuzzless seed and reduced trichome phenotypes in G. arboreum. This distant insertion was predicted to be an enhancer, located ~ 18 kb upstream of the dominant-repressor GaFZ (Ga08G0121). Ectopic overexpression of GaFZ in Arabidopsis thaliana and G. hirsutum suggested that GaFZ negatively modulates fuzz and trichome development. Co-expression and interaction analyses demonstrated that GaFZ might impact fuzz fibre/trichome development by repressing the expression of genes in the very-long-chain fatty acid elongation pathway. Thus, we identified a novel regulator of fibre/trichome development while providing insights into the importance of noncoding sequences in cotton.


Asunto(s)
Gossypium , Tricomas , Fibra de Algodón , Regulación de la Expresión Génica de las Plantas/genética , Estudio de Asociación del Genoma Completo , Gossypium/genética , Tricomas/genética
17.
New Phytol ; 229(4): 2091-2103, 2021 02.
Artículo en Inglés | MEDLINE | ID: mdl-33129229

RESUMEN

Improving yield is a primary mission for cotton (Gossypium hirsutum) breeders; development of cultivars with suitable architecture for high planting density (HPDA) can increase yield per unit area. We characterized a natural cotton mutant, AiSheng98 (AS98), which exhibits shorter height, shorter branch length, and more acute branch angle than wild-type. A copy number variant at the HPDA locus on Chromosome D12 (HPDA-D12), encoding a dehydration-responsive element-binding (DREB) transcription factor, GhDREB1B, strongly affects plant architecture in the AS98 mutant. We found an association between a tandem duplication of a c. 13.5 kb segment in HPDA-D12 and elevated GhDREB1B expression resulting in the AS98 mutant phenotype. GhDREB1B overexpression confers a significant decrease in plant height and branch length, and reduced branch angle. Our results suggest that fine-tuning GhDREB1B expression may be a viable engineering strategy for modification of plant architecture favorable to high planting density in cotton.


Asunto(s)
Variaciones en el Número de Copia de ADN , Gossypium , Fibra de Algodón , Regulación de la Expresión Génica de las Plantas , Gossypium/genética , Fenotipo , Factores de Transcripción/genética
18.
Environ Toxicol ; 36(8): 1618-1627, 2021 Aug.
Artículo en Inglés | MEDLINE | ID: mdl-33908139

RESUMEN

More and more evidence has identified that long non-coding RNAs (lncRNAs) are involved in various biological process of numerous diseases. It has been reported that long intergenic non-protein coding RNA 473 (LINC00473) was associated with pre-eclampsia (PE) development. However, role and molecular mechanism of LINC00473 in PE remains elusive. Therefore, we designed this research to figure out the specific biological function of LINC00473 in trophoblasts. Firstly, we testified expressions of LINC00473 in trophoblasts of PE with RT-qPCR analysis. Then, to probe biological function of LINC00473 in trophoblasts of PE, CCK-8 assay, trans-well assays and western blot analysis were conducted in Wish and JAR cells. As for verifying interaction of microRNA-15a-5p (miR-15a-5p) and LINC00473 or lipopolysaccharide induced TNF factor (LITAF), RNA pull-down and luciferase reporter assays were carried out. Finally, rescue experiments were conducted to probe regulatory pattern of the LINC00473/miR-15a-5p/LITAF axis in trophoblasts of PE. As a result, LINC00473 presented a significant upregulation in trophoblasts of PE. Moreover, LINC00473 knockdown induced trophoblast viability, migration, invasion, and epithelial-to-mesenchymal transition (EMT) in trophoblasts. Additionally, miR-15a-5p interacted with LINC00473 and miR-15a-5p was negatively regulated by LINC00473 in trophoblasts. Simultaneously, miR-15a-5p negatively modulated LITAF in trophoblasts. Moreover, LITAF overexpression or miR-15a-5p downregulation reversed the promotive impact of silenced LINC00473 on trophoblast viability, migration, invasion and EMT. In conclusion, LINC00473 regulated migration and invasion in trophoblasts via the miR-15a-5p/LITAF axis. Our study may provide a novel insight for clinical treatment of PE.


Asunto(s)
MicroARNs , Preeclampsia , Movimiento Celular , Regulación hacia Abajo , Femenino , Humanos , Lipopolisacáridos , Proteínas Nucleares , Embarazo , ARN Largo no Codificante , Factores de Transcripción , Trofoblastos
19.
J Tissue Viability ; 30(2): 190-195, 2021 May.
Artículo en Inglés | MEDLINE | ID: mdl-33551241

RESUMEN

Wound healing is a complex and important physiological process that maintains the integrity of skin after various injuries. Abnormal wound healing, especially of chronic wounds, impairs normal physical function. Therefore, the search for effective and safe healing agents is one of the main concerns. Histatins are histidine-rich low molecular weight peptides that are expressed in the saliva of both humans and higher primates. Histatins have two main biological effects, cell stimulation and bacteria killing, with the former playing an important role in wound healing by promoting epithelial cell and fibroblast migration and angiogenesis and enhancing the re-epithelialization of the wounded area. Because of these biological effects, histatins have been shown to be promising agents of improved wound healing. Histatins are categorized into many subtypes, of which histatin 1 and its hydrolysates are the most effective in promoting wound healing. This review addresses the bioactivity of histatins in wound healing, such as their stimulatory effects on epithelial cells and fibroblasts, and elucidates the possible mechanisms by which histatin subtypes induce their biological effects.


Asunto(s)
Histatinas/farmacología , Cicatrización de Heridas/efectos de los fármacos , Células Endoteliales/efectos de los fármacos , Histatinas/fisiología , Humanos , Saliva/química , Saliva/fisiología , Piel/lesiones
20.
BMC Genomics ; 21(1): 340, 2020 May 04.
Artículo en Inglés | MEDLINE | ID: mdl-32366264

RESUMEN

BACKGROUND: Root systems are critical for plant growth and development. The Casparian strip in root systems is involved in stress resistance and maintaining homeostasis. Casparian strip membrane domain proteins (CASPs) are responsible for the formation of Casparian strips. RESULTS: To investigate the function of CASPs in cotton, we identified and characterized 48, 54, 91 and 94 CASPs from Gossypium arboreum, Gossypium raimondii, Gossypium barbadense and Gossypium hirsutum, respectively, at the genome-wide level. However, only 29 common homologous CASP genes were detected in the four Gossypium species. A collinearity analysis revealed that whole genome duplication (WGD) was the primary reason for the expansion of the genes of the CASP family in the four cotton species. However, dispersed duplication could also contribute to the expansion of the GaCASPs gene family in the ancestors of G. arboreum. Phylogenetic analysis was used to cluster a total of 85 CASP genes from G. arboreum and Arabidopsis into six distinct groups, while the genetic structure and motifs of CASPs were conserved in the same group. Most GaCASPs were expressed in diverse tissues, with the exception of that five GaCASPs (Ga08G0113, Ga08G0114, Ga08G0116, Ga08G0117 and Ga08G0118) that were highly expressed in root tissues. Analyses of the tissue and subcellular localization suggested that GaCASP27 genes (Ga08G0117) are membrane protein genes located in the root. In the GaCASP27 silenced plants and the Arabidopsis mutants, the lateral root number significantly increased. Furthermore, GaMYB36, which is related to root development was found to regulate lateral root growth by targeting GaCASP27. CONCLUSIONS: This study provides a fundamental understanding of the CASP gene family in cotton and demonstrates the regulatory role of GaCASP27 on lateral root growth and development.


Asunto(s)
Gossypium/metabolismo , Proteínas de la Membrana/fisiología , Proteínas de Plantas/fisiología , Raíces de Plantas/crecimiento & desarrollo , Secuencias de Aminoácidos/genética , Mapeo Cromosómico , Duplicación de Gen , Perfilación de la Expresión Génica , Regulación de la Expresión Génica de las Plantas , Genoma de Planta/genética , Gossypium/clasificación , Gossypium/genética , Gossypium/crecimiento & desarrollo , Proteínas de la Membrana/genética , Proteínas de la Membrana/metabolismo , Familia de Multigenes , Filogenia , Proteínas de Plantas/genética , Proteínas de Plantas/metabolismo , Raíces de Plantas/clasificación , Raíces de Plantas/genética , Raíces de Plantas/metabolismo
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