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1.
Brain Res ; 1830: 148810, 2024 May 01.
Artículo en Inglés | MEDLINE | ID: mdl-38365130

RESUMEN

Genetic selection for high growth rate has resulted in spectacular progress in feed efficiency in chickens. As feed intake and water consumption (WC) are associated and both are affected by environmental conditions, we evaluated WC and its hypothalamic regulation in three broiler-based research lines and their ancestor jungle fowl (JF) under heat stress (HS) conditions. Slow growing ACRB, moderate growing 95RB, fast growing MRB, and JF were exposed to daily chronic cyclic HS (36 °C, 9 h/d) or thermoneutral temperature (24 °C). HS increased WC in the MRB only. Arginine vasopressin (AVP) mRNA levels were decreased by HS in the MRB. Within the renin-angiotensin-aldosterone system (RAAS) system, renin expression was increased by HS in the JF, ACRB, and 95RB, while angiotensin I-converting enzyme (ACE), angiotensin II receptors (type 1, AT1, and type 2, AT2) were affected by line. The expression of aquaporin (AQP2, 7, 9, 10, 11, and 12) genes was upregulated by HS, whereas AQP4 and AQP5 expressions were influenced by line. miRNA processing components (Dicer1, Ago2, Drosha) were significantly different among the lines, but were unaffected by HS. In summary, this is the first report showing the effect of HS on hypothalamic water channel- and noncoding RNA biogenesis-related genes in modern chicken populations and their ancestor JF. These results provide a novel framework for future research to identify new molecular mechanisms and signatures involved in water homeostasis and adaptation to HS.


Asunto(s)
Acuaporina 2 , Pollos , Animales , Pollos/metabolismo , Acuaporina 2/metabolismo , Calor , Respuesta al Choque Térmico , ARN no Traducido/metabolismo , Alimentación Animal/análisis , Suplementos Dietéticos , Dieta/veterinaria
2.
Int J Mol Sci ; 25(2)2024 Jan 19.
Artículo en Inglés | MEDLINE | ID: mdl-38279264

RESUMEN

Hepatocellular carcinoma (HCC) presents a significant global health challenge due to limited early detection methods, primarily relying on conventional approaches like imaging and alpha-fetoprotein (AFP). Although non-coding RNAs (ncRNAs) show promise as potential biomarkers in HCC, their true utility remains uncertain. We conducted a comprehensive review of 76 articles, analyzing 88 circulating lncRNAs in 6426 HCC patients. However, the lack of a standardized workflow protocol has hampered holistic comparisons across the literature. Consequently, we herein confined our meta-analysis to only a subset of these lncRNAs. The combined analysis of serum highly upregulated in liver cancer (HULC) gene expression with homeobox transcript antisense intergenic RNA (HOTAIR) and urothelial carcinoma-associated 1 (UCA1) demonstrated markedly enhanced sensitivity and specificity in diagnostic capability compared to traditional biomarkers or other ncRNAs. These findings could have substantial implications for the early diagnosis and tailored treatment of HCC.


Asunto(s)
Carcinoma Hepatocelular , Carcinoma de Células Transicionales , Neoplasias Hepáticas , ARN Largo no Codificante , Neoplasias de la Vejiga Urinaria , Humanos , Carcinoma Hepatocelular/diagnóstico , Carcinoma Hepatocelular/genética , Carcinoma Hepatocelular/patología , Neoplasias Hepáticas/diagnóstico , Neoplasias Hepáticas/genética , Neoplasias Hepáticas/patología , ARN Largo no Codificante/metabolismo , Genes Homeobox , ARN sin Sentido , Carcinoma de Células Transicionales/genética , Regulación Neoplásica de la Expresión Génica , Neoplasias de la Vejiga Urinaria/genética , ARN no Traducido , Biomarcadores , Perfilación de la Expresión Génica , Biomarcadores de Tumor/genética
3.
Front Endocrinol (Lausanne) ; 14: 1269334, 2023.
Artículo en Inglés | MEDLINE | ID: mdl-37900144

RESUMEN

Introduction: Male reproduction is under the control of the hypothalamus-pituitary-gonadal (HPG) axis. The endocannabinoid system (ECS) and the kisspeptin system (KS) are two major signaling systems in the central and peripheral control of reproduction, but their possible interaction has been poorly investigated in mammals. This manuscript analyzes their possible reciprocal modulation in the control of the HPG axis. Materials and methods: Adolescent male rats were treated with kisspeptin-10 (Kp10) and endocannabinoid anandamide (AEA), the latter alone or in combination with the type 1 cannabinoid receptor (CB1) antagonist rimonabant (SR141716A). The hypothalamic KS system and GnRH expression, circulating sex steroids and kisspeptin (Kiss1) levels, and intratesticular KS and ECS were evaluated by immunohistochemical and molecular methods. Non-coding RNAs (i.e., miR145-5p, miR-132-3p, let7a-5p, let7b-5p) were also considered. Results: Circulating hormonal values were not significantly affected by Kp10 or AEA; in the hypothalamus, Kp10 significantly increased GnRH mRNA and aromatase Cyp19, Kiss1, and Kiss1 receptor (Kiss1R) proteins. By contrast, AEA treatment affected the hypothalamic KS at the protein levels, with opposite effects on the ligand and receptor, and SR141716A was capable of attenuating the AEA effects. Among the considered non-coding RNA, only the expression of miR145-5p was positively affected by AEA but not by Kp10 treatment. Localization of Kiss1+/Kiss1R+ neurons in the arcuate nucleus revealed an increase of Kiss1R-expressing neurons in Kp10- and AEA-treated animals associated with enlargement of the lateral ventricles in Kp10-treated animals. In the brain and testis, the selected non-coding RNA was differently modulated by Kp10 or AEA. Lastly, in the testis, AEA treatment affected the KS at the protein levels, whereas Kp10 affected the intragonadal levels of CB1 and FAAH, the main modulator of the AEA tone. Changes in pubertal transition-related miRNAs and the intratesticular distribution of Kiss1, Kiss1R, CB1, and CB2 following KP and AEA treatment corroborate the KS-ECS crosstalk also showing that the CB1 receptor is involved in this interplay. Conclusion: For the first time in mammals, we report the modulation of the KS in both the hypothalamus and testis by AEA and revealed the KP-dependent modulation of CB1 and FAAH in the testis. KP involvement in the progression of spermatogenesis is also suggested.


Asunto(s)
Kisspeptinas , MicroARNs , Masculino , Ratas , Animales , Kisspeptinas/genética , Kisspeptinas/metabolismo , Receptores de Kisspeptina-1/genética , Endocannabinoides/farmacología , Endocannabinoides/metabolismo , Rimonabant/metabolismo , Rimonabant/farmacología , Hipotálamo/metabolismo , Hormona Liberadora de Gonadotropina/metabolismo , Mamíferos/metabolismo , Reproducción , ARN no Traducido/metabolismo , MicroARNs/metabolismo
4.
Genomics ; 115(6): 110709, 2023 Nov.
Artículo en Inglés | MEDLINE | ID: mdl-37739021

RESUMEN

Recent studies on marine organisms have made use of third-generation sequencing technologies such as Pacific Biosciences (PacBio) and Oxford Nanopore Technologies (ONT). While these specialized bioinformatics tools have different algorithmic designs and performance capabilities, they offer scalability and can be applied to various datasets. We investigated the effectiveness of PacBio and ONT RNA sequencing methods in identifying the venom of the jellyfish species Nemopilema nomurai. We conducted a detailed analysis of the sequencing data from both methods, focusing on key characteristics such as CD, alternative splicing, long-chain noncoding RNA, simple sequence repeat, transcription factor, and functional transcript annotation. Our findings indicate that ONT generally produced higher raw data quality in the transcriptome analysis, while PacBio generated longer read lengths. PacBio was found to be superior in identifying CDs and long-chain noncoding RNA, whereas ONT was more cost-effective for predicting alternative splicing events, simple sequence repeats, and transcription factors. Based on these results, we conclude that PacBio is the most specific and sensitive method for identifying venom components, while ONT is the most cost-effective method for studying venogenesis, cnidocyst (venom gland) development, and transcription of virulence genes in jellyfish. Our study has implications for future sequencing technologies in marine jellyfish, and highlights the power of full-length transcriptome analysis in discovering potential therapeutic targets for jellyfish dermatitis.


Asunto(s)
Venenos de Cnidarios , Escifozoos , Animales , ARN , Análisis de Secuencia de ARN , ARN no Traducido , Secuenciación de Nucleótidos de Alto Rendimiento/métodos
5.
Theranostics ; 13(8): 2616-2631, 2023.
Artículo en Inglés | MEDLINE | ID: mdl-37215575

RESUMEN

Alternative splicing (AS) is a common and conserved process in eukaryotic gene regulation. It occurs in approximately 95% of multi-exon genes, greatly enriching the complexity and diversity of mRNAs and proteins. Recent studies have found that in addition to coding RNAs, non-coding RNAs (ncRNAs) are also inextricably linked with AS. Multiple different types of ncRNAs are generated by AS of precursor long non-coding (pre-lncRNAs) or precursor messenger RNAs (pre-mRNAs). Furthermore, ncRNAs, as a novel class of regulators, can participate in AS regulation by interacting with the cis-acting elements or trans-acting factors. Several studies have implicated abnormal expression of ncRNAs and ncRNA-related AS events in the initiation, progression, and therapy resistance in various types of cancers. Therefore, owing to their roles in mediating drug resistance, ncRNAs, AS-related factors and AS-related novel antigens may serve as promising therapeutic targets in cancer treatment. In this review, we summarize the interaction between ncRNAs and AS processes, emphasizing their great influences on cancer, especially on chemoresistance, and highlighting their potential values in clinical treatment.


Asunto(s)
Neoplasias , ARN Largo no Codificante , Humanos , Empalme Alternativo/genética , ARN no Traducido/genética , ARN no Traducido/metabolismo , ARN Largo no Codificante/genética , ARN Largo no Codificante/metabolismo , Neoplasias/tratamiento farmacológico , Neoplasias/genética
6.
Eur J Pharmacol ; 950: 175755, 2023 Jul 05.
Artículo en Inglés | MEDLINE | ID: mdl-37119959

RESUMEN

Despite, melatonin is mainly known as a regulatory factor for circadian rhythm, its notable role in other fundamental biological processes, such as redox homeostasis and programmed cell death, has been found. In this line, a growing body of evidence indicated that melatonin could apply an inhibitory effect on the tumorigenic processes. Hence, melatonin might be considered an efficient adjuvant agent for cancer treatment. Besides, the physiological and pathological functions of non-coding RNAs (ncRNAs) in various disease, particularly cancers, have been expanded over the past two decades. It is well-established that ncRNAs can modulate the gene expression at various levels. Thereby, ncRNAs can regulate the numerous biological processes, including cell proliferation, cell metabolism, apoptosis, and cell cycle. Recently, targeting the ncRNAs expression provides a novel insight in the therapeutic approaches for cancer treatment. Moreover, accumulating investigations have revealed that melatonin could impact the expression of different ncRNAs in a multiple disorders, including cancer. Therefore, in the precent study, we discuss the potential roles of melatonin in modulating the expression of ncRNAs and the related molecular pathways in different types of cancer. Also, we highlighted its importance in therapeutic application and translational medicine in cancer treatment.


Asunto(s)
Melatonina , Neoplasias , Humanos , Melatonina/farmacología , Melatonina/uso terapéutico , ARN no Traducido/genética , Neoplasias/tratamiento farmacológico , Neoplasias/genética , Ciclo Celular
7.
J Nutr Biochem ; 112: 109207, 2023 02.
Artículo en Inglés | MEDLINE | ID: mdl-36402249

RESUMEN

Squalene is a key minor component of virgin olive oil, the main source of fat in the Mediterranean diet, and had shown to improve the liver metabolism in rabbits and mice. The present research was carried out to find out whether this effect was conserved in a porcine model of hepatic steatohepatitis and to search for the lipidomic changes involved. The current study revealed that a 0.5% squalene supplementation to a steatotic diet for a month led to hepatic accumulation of squalene and decreased triglyceride content as well as area of hepatic lipid droplets without influencing cholesterol content or fiber areas. However, ballooning score was increased and associated with the hepatic squalene content. Of forty hepatic transcripts related to lipid metabolism and hepatic steatosis, only citrate synthase and a non-coding RNA showed decreased expressions. The hepatic lipidome, assessed by liquid chromatography-mass spectrometry in a platform able to analyze 467 lipids, revealed that squalene supplementation increased ceramide, Cer(36:2), and phosphatidylcholine (PC[32:0], PC[33:0] and PC[34:0]) species and decreased cardiolipin, CL(69:5), and triglyceride (TG[54:2], TG[55:0] and TG[55:2]) species. Plasma levels of interleukin 12p40 increased in pigs receiving the squalene diet. The latter also modified plasma lipidome by increasing TG(58:12) and decreasing non-esterified fatty acid (FA 14:0, FA 16:1 and FA 18:0) species without changes in total NEFA levels. Together this shows that squalene-induced changes in hepatic and plasma lipidomic profiles, non-coding RNA and anti-inflammatory interleukin are suggestive of an alleviation of the disease despite the increase in the ballooning score.


Asunto(s)
Enfermedad del Hígado Graso no Alcohólico , Escualeno , Porcinos , Ratones , Animales , Conejos , Escualeno/metabolismo , Escualeno/farmacología , Lipidómica , Triglicéridos/metabolismo , Fosfolípidos/metabolismo , Dieta Alta en Grasa , Hígado/metabolismo , Enfermedad del Hígado Graso no Alcohólico/metabolismo , Suplementos Dietéticos , ARN no Traducido/metabolismo , ARN no Traducido/farmacología
8.
Int J Mol Sci ; 23(17)2022 Aug 26.
Artículo en Inglés | MEDLINE | ID: mdl-36077101

RESUMEN

Mitochondrial epigenetic alterations are closely related to Alzheimer's disease (AD), which is described in this review. Reports of the alteration of mitochondrial DNA (mtDNA) methylation in AD demonstrate that the disruption of the dynamic balance of mtDNA methylation and demethylation leads to damage to the mitochondrial electron transport chain and the obstruction of mitochondrial biogenesis, which is the most studied mitochondrial epigenetic change. Mitochondrial noncoding RNA modifications and the post-translational modification of mitochondrial nucleoproteins have been observed in neurodegenerative diseases and related diseases that increase the risk of AD. Although there are still relatively few mitochondrial noncoding RNA modifications and mitochondrial nuclear protein post-translational modifications reported in AD, we have reason to believe that these mitochondrial epigenetic modifications also play an important role in the AD process. This review provides a new research direction for the AD mechanism, starting from mitochondrial epigenetics. Further, this review summarizes therapeutic approaches to targeted mitochondrial epigenetics, which is the first systematic summary of therapeutic approaches in the field, including folic acid supplementation, mitochondrial-targeting antioxidants, and targeted ubiquitin-specific proteases, providing a reference for therapeutic targets for AD.


Asunto(s)
Enfermedad de Alzheimer , Enfermedad de Alzheimer/tratamiento farmacológico , Enfermedad de Alzheimer/genética , Metilación de ADN , ADN Mitocondrial/genética , ADN Mitocondrial/metabolismo , Epigénesis Genética , Humanos , Proteínas Mitocondriales/metabolismo , ARN no Traducido/genética , ARN no Traducido/metabolismo
9.
Zhongguo Zhong Yao Za Zhi ; 47(17): 4551-4559, 2022 Sep.
Artículo en Chino | MEDLINE | ID: mdl-36164859

RESUMEN

Ischemic stroke is one of the main causes of death and long-term disability worldwide, which seriously affects the quality of life of patients and brings a heavy economic burden to families and society. Epidemiological studies have shown that stroke has become the second leading cause of death and major disabling disease in the world, with the characteristics of high morbidity, high recurrence, and high mortality. Epigenetic mechanism is the molecular process where gene expression and function in each cell are dynamically regulated and interconnected and a biological mechanism that changes genetic performance without changing the DNA sequence, including DNA methylation, histone modifications, and non-coding RNA. However, the research on epigenetics is currently focused on other diseases such as tumors. Recent studies have found that epigenetics has received extensive attention in the past few decades as a key factor involved in the pathophysiological process of ischemic stroke. The present study introduced the mediation of epigenetics in the induction of stroke, summarized the potential drug targets for these mechanisms in the treatment of stroke, and further explored the significance of traditional Chinese medicine(TCM) against cerebral ischemia injury based on TCM classification of stroke.


Asunto(s)
Accidente Cerebrovascular Isquémico , Accidente Cerebrovascular , Metilación de ADN , Epigénesis Genética , Humanos , Accidente Cerebrovascular Isquémico/genética , Calidad de Vida , ARN no Traducido/genética , ARN no Traducido/metabolismo , Accidente Cerebrovascular/genética
10.
Oxid Med Cell Longev ; 2022: 4330681, 2022.
Artículo en Inglés | MEDLINE | ID: mdl-35656022

RESUMEN

The dietary flavonoid quercetin is ubiquitously distributed in fruits, vegetables, and medicinal herbs. Quercetin has been a focal point in recent years due to its versatile health-promoting benefits and high pharmacological values. It has well documented that quercetin exerts anticancer actions by inhibiting cell proliferation, inducing apoptosis, and retarding the invasion and metastasis of cancer cells. However, the exact mechanism of quercetin-mediated cancer chemoprevention is still not fully understood. With the advances in high-throughput sequencing technologies, the intricate oncogenic signaling networks have been gradually characterized. Increasing evidence on the close association between noncoding RNA (ncRNAs) and cancer etiopathogenesis emphasizes the potential of ncRNAs as promising molecular targets for cancer treatment. Available experimental studies indicate that quercetin can dominate multiple cancer-associated ncRNAs, hence repressing carcinogenesis and cancer development. Thus, modulation of ncRNAs serves as a key mechanism responsible for the anticancer effects of quercetin. In this review, we focus on the chemopreventive effects of quercetin on cancer pathogenesis by targeting cancer-relevant ncRNAs, supporting the viewpoint that quercetin holds promise as a drug candidate for cancer chemoprevention and chemotherapy. An in-depth comprehension of the interplay between quercetin and ncRNAs in the inhibition of cancer development and progression will raise the possibility of developing this bioactive compound as an anticancer agent that could be highly efficacious and safe in clinical practice.


Asunto(s)
Antineoplásicos , Neoplasias , Antineoplásicos/farmacología , Antioxidantes/farmacología , Humanos , Neoplasias/tratamiento farmacológico , Neoplasias/prevención & control , Quercetina/farmacología , Quercetina/uso terapéutico , ARN no Traducido/genética
11.
Rev. cuba. hematol. inmunol. hemoter ; 38(2): e1502, abr.-jun. 2022. tab
Artículo en Español | LILACS, CUMED | ID: biblio-1408451

RESUMEN

Introducción: Los exosomas son vesículas extracelulares de tamaño nanométrico, que se generan cuando los endosomas multivesiculares se fusionan con la membrana plasmática y el contenido de las vesículas intraluminales se libera en el espacio extracelular. Son producidos por casi todos los tipos de células, en condiciones fisiológicas y patológicas. Transportan proteínas, lípidos y ácido ribonucleico (ARN) no codificante, desde la célula madre hasta la célula receptora, estos son considerados un punto clave en la regeneración de tejidos, lo que se ha demostrado en una serie de estudios, con diferentes tejidos corporales, como piel, cartílago, pancreático y tejidos cardiovasculares. Objetivo: Explicar los aspectos generales y posibles usos de los exosomas en el campo médico. Métodos: Se realizó una búsqueda de información mediante consulta en las bases de datos SciELO PubMed, Science Direct y Lilacs, en los idiomas español e inglés, con diferentes combinaciones de palabras claves y términos MESH como: exosomes, neovascularization, wound healing, immunity, micro RNA, immunology, therapy, classification. Se efectuó un análisis y resumen de la información revisada. Conclusiones: En la actualidad, los exosomas se han convertido en objeto de investigación para diversos tratamientos, medicamentos y uso como marcadores moleculares. Se destacan en terapias contra el cáncer, la inmunomodulación, la estimulación o supresión de la angiogénesis, regeneración cutánea, cicatrización y curación de heridas; por lo que de forma general resultan prometedores en el ámbito de las ciencias médicas(AU)


Introduction: Exosomes are nano-sized extracellular vesicles, which are generated when multivesicular endosomes fuse with the plasma membrane and the content of intraluminal vesicles released into the extracellular space. Are produced by almost all types of cells, under physiological and pathological conditions and they transport proteins, lipids and non-coding RNA (ribonucleic acid), from the stem cell to the recipient cell, these are considered a key point in tissue regeneration, which has been shown in a series of studies, with different body tissues, such as skin, cartilage, pancreatic and cardiovascular tissues. Objective: To explain the general aspects and possible uses of exosomes in the medical field. Methods: A search for information was carried out by consulting the Scielo, PubMed, ScienceDirect and Lilacs databases, in Spanish and English, with different combinations of keywords and MESH terms such as: exosomes, neovascularization, wound healing, immunity, microRNA, immunology, therapy, classification. Then, an analysis and summary of the reviewed information was carried out. Conclusions: Currently, exosomes have become the object of research for various treatments, drugs, and their use as molecular markers. They stand out in cancer therapies, immunomodulation, stimulation or suppression of angiogenesis, skin regeneration, and wound healing, which is why they are generally promising in the field of medical sciences(AU)


Asunto(s)
Endosomas , ARN no Traducido , Alergia e Inmunología , Cicatrización de Heridas
12.
Biogerontology ; 23(3): 289-306, 2022 06.
Artículo en Inglés | MEDLINE | ID: mdl-35587318

RESUMEN

The aging of skin is a biological process affected by environmental or genetic factors. Exposure to ultraviolet (UV) radiation is the main environmental factor causing skin aging. Cumulative UV-induced photodamage of the skin tissue is associated with premature cellular senescence, extracellular degradation, and inflammatory responses in photoaging processes. Non-coding RNAs (ncRNAs) are untranslated transcripts and master regulators of protein-coding genes. ncRNAs have a critical regulatory role in maintaining skin structure, skin barrier function, morphogenesis, and development. Altered ncRNA expression has been reported in various skin disorders such as photoaging and skin cancers. ncRNAs contribute to the suppression and promotion of photoaging by modulating signaling pathways such as mitogen-activated protein kinase (MAPK) pathway and regulating inflammatory cytokines, matrix metalloproteinases (MMPs), and senescence-associated genes. Elucidation of the functions of ncRNAs will improve the identification of molecular mechanisms underlying photoaging, and can be used in the development of therapeutic approaches in skin health and prevention of sun-induced aging. This review summarized the currently described ncRNAs and their functions in photoaging.


Asunto(s)
Envejecimiento de la Piel , Enfermedades de la Piel , Humanos , ARN no Traducido/genética , Transducción de Señal/genética , Piel/metabolismo , Envejecimiento de la Piel/genética , Rayos Ultravioleta/efectos adversos
13.
Genes (Basel) ; 12(12)2021 12 17.
Artículo en Inglés | MEDLINE | ID: mdl-34946953

RESUMEN

Despite the enormous burden of Alzheimer's disease and related dementias (ADRD) on patients, caregivers, and society, only a few treatments with limited efficacy are currently available. While drug development conventionally focuses on disease-associated proteins, RNA has recently been shown to be druggable for therapeutic purposes as well. Approximately 70% of the human genome is transcribed into non-protein-coding RNAs (ncRNAs) such as microRNAs, long ncRNAs, and circular RNAs, which can adopt diverse structures and cellular functions. Many ncRNAs are specifically enriched in the central nervous system, and their dysregulation is implicated in ADRD pathogenesis, making them attractive therapeutic targets. In this review, we first detail why targeting ncRNAs with small molecules is a promising therapeutic strategy for ADRD. We then outline the process from discovery to validation of small molecules targeting ncRNAs in preclinical studies, with special emphasis on primary high-throughput screens for identifying lead compounds. Screening strategies for specific ncRNAs will also be included as examples. Key challenges-including selecting appropriate ncRNA targets, lack of specificity of small molecules, and general low success rate of neurological drugs and how they may be overcome-will be discussed throughout the review.


Asunto(s)
Enfermedad de Alzheimer/tratamiento farmacológico , ARN no Traducido/efectos de los fármacos , Bibliotecas de Moléculas Pequeñas/farmacología , Enfermedad de Alzheimer/genética , Demencia/tratamiento farmacológico , Demencia/genética , Evaluación Preclínica de Medicamentos/métodos , Humanos , MicroARNs/efectos de los fármacos , MicroARNs/genética , ARN Circular/efectos de los fármacos , ARN Circular/genética , ARN Largo no Codificante/efectos de los fármacos , ARN Largo no Codificante/genética , ARN no Traducido/genética
14.
Cell Mol Biol (Noisy-le-grand) ; 67(2): 1-7, 2021 Sep 29.
Artículo en Inglés | MEDLINE | ID: mdl-34817345

RESUMEN

Natural products have historically been invaluable as a premium source of therapeutic agents. Recent advancements in genomics and structural biology have portrayed a high-resolution landscape of the diversity of proteins targeted by pharmacologically active products from natural sources. Natural product research has generated valuable wealth of information and cutting-edge research-works have leveraged our conceptual knowledge altogether to a new level. Wogonin (5,7-dihydroxy-8-methoxyflavone) is an O-methylated flavone and has attracted noteworthy appreciation because of its ability to pharmacologically target plethora of cell signaling pathways in different cancers. In this mini-review, we have gathered scattered pieces of available scientific evidence to summarize how wogonin pharmaceutically targeted Wnt/?-catenin, JAK/STAT, VEGF/VEGFR and TRAIL-driven apoptotic pathways in wide variety of cancers. We have also critically analyzed how wogonin prevented carcinogenesis and metastasis in tumor-bearing mice. Although researchers have uncovered pleiotropic role of wogonin in the regulation of different oncogenic signaling cascades but there are visible knowledge gaps in our understanding related to regulation of non-coding RNAs by wogonin. Future studies must converge on the unraveling of additional drug targets for wogonin to achieve a fuller and realistic understanding of the chemopreventive properties of wogonin.


Asunto(s)
Apoptosis/efectos de los fármacos , Medicamentos Herbarios Chinos/farmacología , Flavanonas/farmacología , Neoplasias/metabolismo , Scutellaria/química , Transducción de Señal/efectos de los fármacos , Animales , Medicamentos Herbarios Chinos/química , Flavanonas/química , Regulación Neoplásica de la Expresión Génica/efectos de los fármacos , Humanos , Neoplasias/genética , Neoplasias/patología , ARN no Traducido/genética , Receptores de Factores de Crecimiento Endotelial Vascular/metabolismo , Factor A de Crecimiento Endotelial Vascular/metabolismo , Vía de Señalización Wnt/efectos de los fármacos , beta Catenina/metabolismo
15.
BMC Plant Biol ; 21(1): 518, 2021 Nov 08.
Artículo en Inglés | MEDLINE | ID: mdl-34749653

RESUMEN

BACKGROUND: Several mechanisms regulating gene expression contribute to restore and reestablish cellular homeostasis so that plants can adapt and survive in adverse situations. MicroRNAs (miRNAs) play roles important in the transcriptional and post-transcriptional regulation of gene expression, emerging as a regulatory molecule key in the responses to plant stress, such as cold, heat, drought, and salt. This work is a comprehensive and large-scale miRNA analysis performed to characterize the miRNA population present in oil palm (Elaeis guineensis Jacq.) exposed to a high level of salt stress, to identify miRNA-putative target genes in the oil palm genome, and to perform an in silico comparison of the expression profile of the miRNAs and their putative target genes. RESULTS: A group of 79 miRNAs was found in oil palm, been 52 known miRNAs and 27 new ones. The known miRNAs found belonged to 28 families. Those miRNAs led to 229 distinct miRNA-putative target genes identified in the genome of oil palm. miRNAs and putative target genes differentially expressed under salinity stress were then selected for functional annotation analysis. The regulation of transcription, DNA-templated, and the oxidation-reduction process were the biological processes with the highest number of hits to the putative target genes, while protein binding and DNA binding were the molecular functions with the highest number of hits. Finally, the nucleus was the cellular component with the highest number of hits. The functional annotation of the putative target genes differentially expressed under salinity stress showed several ones coding for transcription factors which have already proven able to result in tolerance to salinity stress by overexpression or knockout in other plant species. CONCLUSIONS: Our findings provide new insights into the early response of young oil palm plants to salinity stress and confirm an expected preponderant role of transcription factors - such as NF-YA3, HOX32, and GRF1 - in this response. Besides, it points out potential salt-responsive miRNAs and miRNA-putative target genes that one can utilize to develop oil palm plants tolerant to salinity stress.


Asunto(s)
MicroARNs/metabolismo , Aceite de Palma/metabolismo , Factores de Transcripción/metabolismo , Regulación de la Expresión Génica de las Plantas , MicroARNs/genética , ARN no Traducido/genética , ARN no Traducido/metabolismo , Tolerancia a la Sal/fisiología , Análisis de Secuencia de ARN , Factores de Transcripción/genética
16.
Int J Mol Sci ; 22(20)2021 Oct 18.
Artículo en Inglés | MEDLINE | ID: mdl-34681864

RESUMEN

Macronutrient elements including nitrogen (N), phosphorus (P), potassium (K), calcium (Ca), magnesium (Mg), and sulfur (S) are required in relatively large and steady amounts for plant growth and development. Deficient or excessive supply of macronutrients from external environments may trigger a series of plant responses at phenotypic and molecular levels during the entire life cycle. Among the intertwined molecular networks underlying plant responses to macronutrient stress, noncoding RNAs (ncRNAs), mainly microRNAs (miRNAs) and long ncRNAs (lncRNAs), may serve as pivotal regulators for the coordination between nutrient supply and plant demand, while the responsive ncRNA-target module and the interactive mechanism vary among elements and species. Towards a comprehensive identification and functional characterization of nutrient-responsive ncRNAs and their downstream molecules, high-throughput sequencing has produced massive omics data for comparative expression profiling as a first step. In this review, we highlight the recent findings of ncRNA-mediated regulation in response to macronutrient stress, with special emphasis on the large-scale sequencing efforts for screening out candidate nutrient-responsive ncRNAs in plants, and discuss potential improvements in theoretical study to provide better guidance for crop breeding practices.


Asunto(s)
Plantas/genética , ARN de Planta , ARN no Traducido , Estrés Fisiológico/genética , Calcio/metabolismo , Regulación de la Expresión Génica de las Plantas , Magnesio/metabolismo , MicroARNs , Fósforo/metabolismo , Fenómenos Fisiológicos de las Plantas , Potasio/metabolismo
17.
Int J Mol Sci ; 22(11)2021 May 27.
Artículo en Inglés | MEDLINE | ID: mdl-34071976

RESUMEN

Myocardial infarction is one of the major causes of mortality worldwide and is a main cause of heart failure. This disease appears as a final point of atherosclerotic plaque progression, destabilization, and rupture. As a consequence of cardiomyocytes death during the infarction, the heart undergoes unfavorable cardiac remodeling, which results in its failure. Therefore, therapies aimed to limit the processes of atherosclerotic plaque progression, cardiac damage during the infarction, and subsequent remodeling are urgently warranted. A hopeful therapeutic option for the future medicine is targeting and regulating non-coding RNA (ncRNA), like microRNA, circular RNA (circRNA), or long non-coding RNA (lncRNA). In this review, the approaches targeted at ncRNAs participating in the aforementioned pathophysiological processes involved in myocardial infarction and their outcomes in preclinical studies have been concisely presented.


Asunto(s)
Infarto del Miocardio/genética , Infarto del Miocardio/patología , ARN no Traducido/genética , Remodelación Ventricular/genética , Animales , Biomarcadores , Manejo de la Enfermedad , Progresión de la Enfermedad , Susceptibilidad a Enfermedades , Evaluación Preclínica de Medicamentos , Terapia Genética , Humanos , Terapia Molecular Dirigida , Infarto del Miocardio/terapia , Miocitos Cardíacos/metabolismo , Placa Aterosclerótica/etiología , Placa Aterosclerótica/metabolismo , Placa Aterosclerótica/patología , Placa Aterosclerótica/terapia
18.
Front Immunol ; 12: 630571, 2021.
Artículo en Inglés | MEDLINE | ID: mdl-33968023

RESUMEN

Tetraspanin family of proteins participates in numerous fundamental signaling pathways involved in viral transmission, virus-specific immunity, and virus-mediated vesicular trafficking. Studies in the identification of novel therapeutic candidates and strategies to target West Nile virus, dengue and Zika viruses are highly warranted due to the failure in development of vaccines. Recent evidences have shown that the widely distributed tetraspanin proteins may provide a platform for the development of novel therapeutic approaches. In this review, we discuss the diversified and important functions of tetraspanins in exosome/extracellular vesicle biology, virus-host interactions, virus-mediated vesicular trafficking, modulation of immune mechanism(s), and their possible role(s) in host antiviral defense mechanism(s) through interactions with noncoding RNAs. We also highlight the role of tetraspanins in the development of novel therapeutics to target arthropod-borne flaviviral diseases.


Asunto(s)
Infecciones por Flavivirus/tratamiento farmacológico , Interacciones Microbiota-Huesped/fisiología , Tetraspaninas/fisiología , Exosomas/fisiología , Vesículas Extracelulares/fisiología , Humanos , Inmunomodulación , ARN no Traducido/fisiología
19.
DNA Cell Biol ; 40(6): 821-832, 2021 Jun.
Artículo en Inglés | MEDLINE | ID: mdl-34030482

RESUMEN

Chemoresistance is one of the major obstacles encountered in ovarian cancer (OC) therapy. Long noncoding RNA PART1 has been reported to be involved in the tumorigenesis of several types of cancers. However, the biological role of PART1 in the chemoresistance of OC is still unclear. In this study, it was found that the expression levels of PART1 and CHRAC1 were increased and miR-512-3p expression was decreased in cisplatin (DDP)-resistant OC cell lines. The depletion of PART1 enhanced the DDP sensitivity of DDP-resistant OC cells, as indicated by the inhibition of cell proliferation, migration, and invasion, and promotion of cell apoptosis. In the upstream mechanism exploration, we discovered that PART1 was induced by YY1 transcription factor. Moreover, it was identified that miR-512-3p was a target of PART1, and PART1 regulated the DDP resistance of OC through miR-512-3p. In addition, we screened the candidate genes of miR-512-3p., and confirmed that CHRAC1 was the downstream gene of miR-512-3p. Furthermore, the knockdown of CHRAC1 inhibited proliferation, migration, and invasion, and accelerated apoptosis of DDP-resistant OC cells, which was counteracted after the inhibition of miR-512-3p. Finally, we observed that PART1 regulated the expression of CHRAC1 through miR-512-3p. In conclusion, we demonstrated that YY1-induced PART1 accelerated DDP resistance of OC through miR-512-3p/CHRAC1 axis, suggesting PART1 may be a promising therapeutic target for DDP-resistant OC patients.


Asunto(s)
Proteínas de Unión al ADN/metabolismo , Resistencia a Antineoplásicos , MicroARNs/metabolismo , Nucleoproteínas/metabolismo , Neoplasias Ováricas/metabolismo , ARN no Traducido/fisiología , Factor de Transcripción YY1/fisiología , Apoptosis , Línea Celular Tumoral , Proliferación Celular , Cisplatino/farmacología , Femenino , Regulación Neoplásica de la Expresión Génica , Humanos
20.
Sci Rep ; 11(1): 9211, 2021 04 28.
Artículo en Inglés | MEDLINE | ID: mdl-33911151

RESUMEN

Ginseng rusty root symptom (GRS) is one of the primary diseases of ginseng. It leads to a severe decline in the quality of ginseng and significantly affects the ginseng industry. The regulatory mechanism of non-coding RNA (ncRNA) remains unclear in the course of disease. This study explored the long ncRNAs (lncRNAs), circular RNAs (circRNAs), and microRNAs (miRNAs) in GRS tissues and healthy ginseng (HG) tissues and performed functional enrichment analysis of the screened differentially expressed ncRNAs. Considering the predictive and regulatory effects of ncRNAs on mRNAs, we integrated ncRNA and mRNA data to analyze and construct relevant regulatory networks. A total of 17,645 lncRNAs, 245 circRNAs, and 299 miRNAs were obtained from HG and GRS samples, and the obtained ncRNAs were characterized, including the classification of lncRNAs, length and distribution of circRNA, and the length and family affiliations of miRNAs. In the analysis of differentially expressed ncRNA target genes, we found that lncRNAs may be involved in the homeostatic process of ginseng tissues and that lncRNAs, circRNAs, and miRNAs are involved in fatty acid-related regulation, suggesting that alterations in fatty acid-related pathways may play a key role in GRS. Besides, differentially expressed ncRNAs play an essential role in regulating transcriptional translation processes, primary metabolism such as starch and sucrose, and secondary metabolism such as alkaloids in ginseng tissues. Finally, we integrated the correlations between ncRNAs and mRNAs, constructed corresponding interaction networks, and identified ncRNAs that may play critical roles in GRS. These results provide a basis for revealing GRS's molecular mechanism and enrich our understanding of ncRNAs in ginseng.


Asunto(s)
Basidiomycota/fisiología , Resistencia a la Enfermedad/genética , Redes Reguladoras de Genes , Panax/genética , Enfermedades de las Plantas/genética , Proteínas de Plantas/genética , ARN no Traducido/genética , Resistencia a la Enfermedad/inmunología , Perfilación de la Expresión Génica , Regulación de la Expresión Génica de las Plantas , Panax/crecimiento & desarrollo , Panax/microbiología , Enfermedades de las Plantas/microbiología , Proteínas de Plantas/metabolismo , Raíces de Plantas
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