Your browser doesn't support javascript.
loading
Mostrar: 20 | 50 | 100
Resultados 1 - 20 de 62
Filtrar
Más filtros

Banco de datos
País/Región como asunto
Tipo del documento
Intervalo de año de publicación
1.
Cytokine ; 179: 156585, 2024 07.
Artículo en Inglés | MEDLINE | ID: mdl-38579428

RESUMEN

The pathophysiology of several illnesses, including cancer and autoimmune diseasesdepends on human regulatory T cells (Tregs), and abnormalities in these cells may function as triggers for these conditions. Cancer and autoimmune, and gynecological diseases are associated with the differentiation of the proinflammatory T cell subset TH17 and its balance with the production of Treg. Recently, long non-coding RNAs (lncRNAs) have become important regulatory molecules in a wide range of illnesses. During epigenetic regulation, they can control the expression of important genes at several levels by affecting transcription, post-transcriptional actions, translation, and protein modification. They might connect with different molecules, such as proteins, DNA and RNA, and their structural composition is intricate. Because lncRNAs regulatebiological processes, including cell division, death, and growth, they are linked to severaldiseases. A notable instance of this is the lncRNA NEAT1, which has been the subject of several investigations to ascertain its function in immune cell development. In the context of immune cell development, several additional lncRNAs have been connected to Treg cell differentiation. In this work, we summarize current findings about the diverse functions of lncRNAs in Treg cell differentiation and control of the Th17/Treg homeostasis in autoimmune disorders, cancers, as well as several gynecological diseases where Tregs are key players.


Asunto(s)
Enfermedades Autoinmunes , Diferenciación Celular , ARN Largo no Codificante , Linfocitos T Reguladores , Humanos , ARN Largo no Codificante/genética , ARN Largo no Codificante/inmunología , Linfocitos T Reguladores/inmunología , Enfermedades Autoinmunes/inmunología , Enfermedades Autoinmunes/genética , Diferenciación Celular/inmunología , Diferenciación Celular/genética , Animales , Células Th17/inmunología , Neoplasias/inmunología , Neoplasias/genética , Enfermedades del Sistema Inmune/inmunología , Enfermedades del Sistema Inmune/genética
2.
FASEB J ; 37(4): e22868, 2023 04.
Artículo en Inglés | MEDLINE | ID: mdl-36961246

RESUMEN

Today, human organoids are becoming an integrated part of genomics and epigenomics, as they provide a platform that can be used for the definite study of molecular and cellular mechanisms occurring at different stages of development, particularly organogenesis, within the human body. Airway development is a complex process heavily influenced by epigenetic regulatory mechanisms in response to environmental changes, and as such, human lung organoids are an indispensable asset for further exploration of these mechanisms as a mode of transition from human in vitro to human ex vivo studies. Cultured primarily in compounds mimicking the extracellular matrix, such as Matrigel, these lung organoids have helped us to come to a better understanding of the role of polycomb repressive complex 2 (PRC2) and enhancer of zeste homolog 2 (EZH2) in lung epithelial cell differentiation and airway development, which was first reported in the FASEB journal in 2019. The following is an extended account of how the histone methylation-regulating PRC2 comes to play in the molding of the human bronchial tree, along with further epigenetic insights based on more recently developed human lung organoids.


Asunto(s)
Epigenómica , Complejo Represivo Polycomb 2 , Humanos , Complejo Represivo Polycomb 2/genética , Señales (Psicología) , Proteína Potenciadora del Homólogo Zeste 2/metabolismo , Diferenciación Celular , Epigénesis Genética , Cromatina/genética , Pulmón/metabolismo , Organoides/metabolismo
3.
Cell Biol Int ; 48(1): 3-19, 2024 Jan.
Artículo en Inglés | MEDLINE | ID: mdl-37947445

RESUMEN

Mesenchymal stem cells (MSCs) are recognized for their remarkable ability to differentiate into multiple cell types. They are also known to possess properties that can fight cancer, leading to attempts to modify MSCs for use in anticancer treatments. However, MSCs have also been found to participate in pathways that promote tumor growth. Many studies have been conducted to explore the potential of MSCs for clinical applications, but the results have been inconclusive, possibly due to the diverse nature of MSC populations. Furthermore, the conflicting roles of MSCs in inhibiting tumors and promoting tumor growth hinder their adaptation to anticancer therapies. Antitumorigenic and protumorigenic properties of MSCs in urological cancers such as bladder, prostate, and renal are not as well established, and data comparing them are still limited. MSCs hold significant promise as a vehicle for delivering anticancer agents and suicide genes to tumors. Presently, numerous studies have concentrated on the products derived from MSCs, such as extracellular vesicles (EVs), as a form of cell-free therapy. This work aimed to review and discuss the current knowledge of MSCs and their EVs in urological cancer therapy.


Asunto(s)
Vesículas Extracelulares , Células Madre Mesenquimatosas , Neoplasias Urológicas , Masculino , Humanos , Vejiga Urinaria , Próstata , Riñón , Vesículas Extracelulares/metabolismo , Neoplasias Urológicas/terapia , Neoplasias Urológicas/metabolismo , Células Madre Mesenquimatosas/metabolismo
4.
Cell Biochem Funct ; 42(2): e3962, 2024 Mar.
Artículo en Inglés | MEDLINE | ID: mdl-38491792

RESUMEN

Colorectal cancer (CRC) is one of the main causes of cancer-related deaths. However, the surgical control of the CRC progression is difficult, and in most cases, the metastasis leads to cancer-related mortality. Mesenchymal stem/stromal cells (MSCs) with potential translational applications in regenerative medicine have been widely researched for several years. MSCs could affect tumor development through secreting exosomes. The beneficial properties of stem cells are attributed to their cell-cell interactions as well as the secretion of paracrine factors in the tissue microenvironment. For several years, exosomes have been used as a cell-free therapy to regulate the fate of tumor cells in a tumor microenvironment. This review discusses the recent advances and current understanding of assessing MSC-derived exosomes for possible cell-free therapy in CRC.


Asunto(s)
Neoplasias Colorrectales , Exosomas , Vesículas Extracelulares , Células Madre Mesenquimatosas , Humanos , Comunicación Celular , Microambiente Tumoral
5.
J Tissue Viability ; 33(1): 18-26, 2024 Feb.
Artículo en Inglés | MEDLINE | ID: mdl-38042701

RESUMEN

Diabetic wounds, as one of the most important complications of diabetes, face many challenges in treatment. Herein we investigated whether decellularized human amniotic membrane (dAM) loaded with epigallocatechin-3-gallate (EGCG) could promote healing in diabetic rats. Sixty diabetic rats were randomly planned into the untreated group, dAM group, EGCG group, and dAM + EGCG group. On days 7, 14, and 21, five rats from each group were sampled for stereological, molecular, and tensiometrical assessments. Our finding revealed that the wound closure rate, the total volumes of new epidermis and dermis, the numerical densities of fibroblasts, blood vessels, collagen density as well as tensiometrical parameters of the healed wounds were considerably increased in the treated groups than in the untreated group, and these changes were more obvious in the dAM + EGCG ones. Furthermore, the expression of TGF-ß, bFGF, and VEGF genes were significantly upregulated in all treated groups compared to the untreated group and were greater in the dAM + EGCG group. This is while expression of TNF-α and IL-1ß, as well as cell numerical densities of neutrophils and macrophages decreased more considerably in the dAM + EGCG group in comparison to the other groups. In conclusion, it was found that using both dAM transplantation and EGCG has more effect on diabetic wound healing.


Asunto(s)
Catequina/análogos & derivados , Diabetes Mellitus Experimental , Humanos , Ratas , Animales , Diabetes Mellitus Experimental/complicaciones , Amnios/metabolismo , Cicatrización de Heridas , Colágeno/farmacología
6.
Mol Cancer ; 22(1): 169, 2023 10 09.
Artículo en Inglés | MEDLINE | ID: mdl-37814270

RESUMEN

The use of nanotechnology has the potential to revolutionize the detection and treatment of cancer. Developments in protein engineering and materials science have led to the emergence of new nanoscale targeting techniques, which offer renewed hope for cancer patients. While several nanocarriers for medicinal purposes have been approved for human trials, only a few have been authorized for clinical use in targeting cancer cells. In this review, we analyze some of the authorized formulations and discuss the challenges of translating findings from the lab to the clinic. This study highlights the various nanocarriers and compounds that can be used for selective tumor targeting and the inherent difficulties in cancer therapy. Nanotechnology provides a promising platform for improving cancer detection and treatment in the future, but further research is needed to overcome the current limitations in clinical translation.


Asunto(s)
Nanopartículas , Neoplasias , Humanos , Neoplasias/diagnóstico , Neoplasias/tratamiento farmacológico , Nanotecnología/métodos , Sistemas de Liberación de Medicamentos/métodos , Portadores de Fármacos , Composición de Medicamentos
7.
Cancer Cell Int ; 23(1): 162, 2023 Aug 11.
Artículo en Inglés | MEDLINE | ID: mdl-37568193

RESUMEN

Lung cancer continues to be the leading cause of cancer-related death worldwide. In the last decade, significant advancements in the diagnosis and treatment of lung cancer, particularly NSCLC, have been achieved with the help of molecular translational research. Among the hopeful breakthroughs in therapeutic approaches, advances in targeted therapy have brought the most successful outcomes in NSCLC treatment. In targeted therapy, antagonists target the specific genes, proteins, or the microenvironment of tumors supporting cancer growth and survival. Indeed, cancer can be managed by blocking the target genes related to tumor cell progression without causing noticeable damage to normal cells. Currently, efforts have been focused on improving the targeted therapy aspects regarding the encouraging outcomes in cancer treatment and the quality of life of patients. Treatment with targeted therapy for NSCLC is changing rapidly due to the pace of scientific research. Accordingly, this updated study aimed to discuss the tumor target antigens comprehensively and targeted therapy-related agents in NSCLC. The current study also summarized the available clinical trial studies for NSCLC patients.

8.
Cell Mol Neurobiol ; 43(7): 3277-3299, 2023 Oct.
Artículo en Inglés | MEDLINE | ID: mdl-37414973

RESUMEN

MicroRNAs (miRNAs) are non-coding RNAs with only 20-22 nucleic acids that inhibit gene transcription and translation by binding to mRNA. MiRNAs have a diverse set of target genes and can alter most physiological processes, including cell cycle checkpoints, cell survival, and cell death mechanisms, affecting the growth, development, and invasion of various cancers, including gliomas. So optimum management of miRNA expression is essential for preserving a normal biological environment. Due to their small size, stability, and capability of specifically targeting oncogenes, miRNAs have emerged as a promising marker and new biopharmaceutical targeted therapy for glioma patients. This review focuses on the most common miRNAs associated with gliomagenesis and development by controlling glioma-determining markers such as angiogenesis. We also summarized the recent research about miRNA effects on signaling pathways, their mechanistic role and cellular targets in the development of gliomas angiogenesis. Strategies for miRNA-based therapeutic targets, as well as limitations in clinical applications, are also discussed.


Asunto(s)
Neoplasias Encefálicas , Glioma , MicroARNs , Humanos , MicroARNs/genética , MicroARNs/metabolismo , Neoplasias Encefálicas/genética , Neoplasias Encefálicas/terapia , Neoplasias Encefálicas/metabolismo , Glioma/genética , Glioma/terapia , Glioma/metabolismo , Transducción de Señal/genética , Oncogenes , Regulación Neoplásica de la Expresión Génica
9.
Cell Commun Signal ; 21(1): 43, 2023 02 24.
Artículo en Inglés | MEDLINE | ID: mdl-36829187

RESUMEN

Oncolytic viruses (OVs) infect, multiply, and finally remove tumor cells selectively, causing no damage to normal cells in the process. Because of their specific features, such as, the ability to induce immunogenic cell death and to contain curative transgenes in their genomes, OVs have attracted attention as candidates to be utilized in cooperation with immunotherapies for cancer treatment. This treatment takes advantage of most tumor cells' inherent tendency to be infected by certain OVs and both innate and adaptive immune responses are elicited by OV infection and oncolysis. OVs can also modulate tumor microenvironment and boost anti-tumor immune responses. Mesenchymal stem cells (MSC) are gathering interest as promising anti-cancer treatments with the ability to address a wide range of cancers. MSCs exhibit tumor-trophic migration characteristics, allowing them to be used as delivery vehicles for successful, targeted treatment of isolated tumors and metastatic malignancies. Preclinical and clinical research were reviewed in this study to discuss using MSC-released OVs as a novel method for the treatment of cancer. Video Abstract.


Asunto(s)
Células Madre Mesenquimatosas , Neoplasias , Viroterapia Oncolítica , Virus Oncolíticos , Humanos , Virus Oncolíticos/fisiología , Viroterapia Oncolítica/métodos , Neoplasias/patología , Inmunoterapia , Células Madre Mesenquimatosas/patología , Microambiente Tumoral
10.
BMC Endocr Disord ; 23(1): 171, 2023 Aug 11.
Artículo en Inglés | MEDLINE | ID: mdl-37568117

RESUMEN

BACKGROUND: Metabolic syndrome (MetS), as a cluster of cardiometabolic risk factors, is a global public health concern due to its increasing prevalence. Considering the previous evidence of the association between carbohydrate quality and cardiometabolic risk factors, our study was aimed to evaluate any possible association between carbohydrate quality index (CQI) and cardiometabolic risk factors among obese adults. METHODS: In this cross-sectional study, 336 apparently healthy individuals with obesity were participated. Dietary intake was assessed by a semi-quantitative Food Frequency Questionnaire (FFQ), including 168 food items validated for the Iranian population. CQI was calculated with three components of solid carbohydrates to total carbohydrates ratio, dietary fiber intake, and dietary glycemic index (GI). Body composition was determined by bioelectrical impedance analysis (BIA). Blood pressure was measured by sphygmomanometer and enzymatic methods were used to evaluate serum lipid, glucose, and insulin concentrations. RESULTS: Subjects in the third quartile of CQI had significantly lower systolic blood pressure (SBP) (P = 0.03) and diastolic blood pressure (DBP) (P = 0.01). Participants in the higher quartiles of CQI had more intake of energy, carbohydrates, fat, saturated fatty acid (SFA), and mono-saturated fatty acid (MUFA) (P < 0.05). Moreover, the homeostasis model assessment of insulin resistance (HOMA-IR) was decreased in the second quartile of CQI [odds ratio (OR) = 0.146, P = 0.01) after adjustment for age, body mass index (BMI), sex, physical activity, socioeconomic status (SES) and energy intake. CONCLUSION: According to our findings, a higher quality of dietary carbohydrates, determined by CQI, could be associated with a lower risk of hypertension.


Asunto(s)
Carbohidratos de la Dieta , Resistencia a la Insulina , Adulto , Humanos , Carbohidratos de la Dieta/efectos adversos , Estudios Transversales , Irán/epidemiología , Factores de Riesgo , Obesidad/epidemiología
11.
Environ Res ; 233: 116490, 2023 09 15.
Artículo en Inglés | MEDLINE | ID: mdl-37354932

RESUMEN

The multidisciplinary approaches in treatment of cancer appear to be essential in term of bringing benefits of several disciplines and their coordination in tumor elimination. Because of the biological and malignant features of cancer cells, they have ability of developing resistance to conventional therapies such as chemo- and radio-therapy. Pancreatic cancer (PC) is a malignant disease of gastrointestinal tract in which chemotherapy and radiotherapy are main tools in its treatment, and recently, nanocarriers have been emerged as promising structures in its therapy. The bioresponsive nanocarriers are able to respond to pH and redox, among others, in targeted delivery of cargo for specific treatment of PC. The loading drugs on the nanoparticles that can be synthetic or natural compounds, can help in more reduction in progression of PC through enhancing their intracellular accumulation in cancer cells. The encapsulation of genes in the nanoparticles can protect against degradation and promotes intracellular accumulation in tumor suppression. A new kind of therapy for cancer is phototherapy in which nanoparticles can stimulate both photothermal therapy and photodynamic therapy through hyperthermia and ROS overgeneration to trigger cell death in PC. Therefore, synergistic therapy of phototherapy with chemotherapy is performed in accelerating tumor suppression. One of the important functions of nanotechnology is selective targeting of PC cells in reducing side effects on normal cells. The nanostructures are capable of being surface functionalized with aptamers, proteins and antibodies to specifically target PC cells in suppressing their progression. Therefore, a specific therapy for PC is provided and future implications for diagnosis of PC is suggested.


Asunto(s)
Hipertermia Inducida , Nanopartículas Multifuncionales , Nanopartículas , Neoplasias , Neoplasias Pancreáticas , Humanos , Doxorrubicina/química , Doxorrubicina/farmacología , Doxorrubicina/uso terapéutico , Fototerapia , Nanopartículas/química , Neoplasias Pancreáticas/tratamiento farmacológico , Línea Celular Tumoral , Neoplasias Pancreáticas
12.
Inflamm Res ; 71(9): 1003-1009, 2022 Sep.
Artículo en Inglés | MEDLINE | ID: mdl-35909187

RESUMEN

Among the countless endeavours made at elucidating the pathogenesis of COVID-19, those aimed at the histopathological alterations of type 2 alveolar epithelial cells (AT2) are of outstanding relevance to the field of lung physiology, as they are the building blocks of the pulmonary alveoli. A merit of high regenerative and proliferative capacity, exocytotic activity resulting in the release of extracellular vesicles (EVs) is particularly high in AT2 cells, especially in those infected with SARS-CoV-2. These AT2 cell-derived EVs, containing the genetic material of the virus, might enter the bloodstream and make their way into the cardiovascular system, where they may infect cardiomyocytes and bring about a series of events leading to heart failure. As surfactant protein C, a marker of AT2 cell activity and a constituent of the lung surfactant complex, occurs abundantly inside the AT2-derived EVs released during the inflammatory stage of COVID-19, it could potentially be used as a biomarker for predicting impending heart failure in those patients with a history of cardiovascular disease.


Asunto(s)
COVID-19 , Vesículas Extracelulares , Insuficiencia Cardíaca , Células Epiteliales Alveolares , Células Cultivadas , Humanos , Inflamación , Proteína C , SARS-CoV-2 , Tensoactivos
13.
Cancer Cell Int ; 21(1): 431, 2021 Aug 16.
Artículo en Inglés | MEDLINE | ID: mdl-34399734

RESUMEN

Recent studies on the pathophysiology of COVID-19 are indicating that the Angiotensin convertase enzyme 2 (ACE-2) and transmembrane serine protease 2 (TMPRSS2) can act as a major component in the fusion of SARS-Cov-2 with target cells. It has also been observed that the expression of ACE-2 and TMPRSS2 can be altered in malignancies. Shedding light on this matter could be crucial since the COVID-19 pandemic interfered with many gastrointestinal cancer screening programs. Herein we discuss the possibility of severe forms of COVID-19 in patients with gastrointestinal cancers due to the gastrointestinal entry route of SARS-CoV-2 into the human body. The disruption of cancer screening programs caused by the current COVID-19 pandemic could therefore have massive negative health impact on patients affected by gastrointestinal malignancies.

14.
Acta Neurochir (Wien) ; 157(10): 1819-23; discussion 1823, 2015 Oct.
Artículo en Inglés | MEDLINE | ID: mdl-26287268

RESUMEN

BACKGROUND: Robotic assistance for the placement of pedicle screws has been established as a safe technique. Nonetheless rare instances of screw misplacement have been reported.The aim of the present retrospective study is to assess whether experience and time affect the accuracy of screws placed with the help of the SpineAssist™ robot system. METHODS: Postoperative computed tomography (CT) scans of 258 patients requiring thoracolumbar pedicle screw instrumentation from 2008 to 2013 were reviewed. Overall, 13 surgeons performed the surgeries. A pedicle breach of >3 mm was graded as a misplacement. Surgeons were dichotomised into an early and experienced period in increments of five surgeries. RESULTS: In 258 surgeries, 1,265 pedicle screws were placed with the aid of the robot system. Overall, 1,217 screws (96.2 %) were graded as acceptable. When displayed by surgeon, the development of percent misplacement rates peaked between 5 and 25 surgeries in 12 of 13 surgeons. The overall misplacement rate in the first five surgeries was 2.4 % (6/245). The misplacement rate rose to 6.3 % between 11 and 15 surgeries (10/158; p = 0.20), and reached a significant peak between 16 and 20 surgeries with a rate of 7.1 % (8/112; p = 0.03). Afterwards, misplacement rates declined. CONCLUSIONS: A major peak in screw inaccuracies occurred between cases 10 and 20, and a second, smaller one at about 40 surgeries. One potential explanation could be a transition from decreased supervision (unskilled but aware) to increased confidence of a surgeon (unskilled but unaware) who adopts this new technique prior to mastering it (skilled). We therefore advocate ensuring competent supervision for new surgeons at least during the first 25 procedures of robotic spine surgery to optimise the accuracy of robot-assisted pedicle screws.


Asunto(s)
Robótica/educación , Fusión Vertebral/educación , Cirujanos/educación , Cirugía Asistida por Computador/educación , Competencia Clínica , Humanos , Curva de Aprendizaje , Tornillos Pediculares , Robótica/métodos , Fusión Vertebral/métodos , Cirugía Asistida por Computador/métodos
15.
Eur Spine J ; 23(11): 2416-22, 2014 Nov.
Artículo en Inglés | MEDLINE | ID: mdl-24929808

RESUMEN

PURPOSE: To clarify whether vascular endothelial growth factor receptor 2 (VEGFR2) and inducible nitric oxide synthase (iNOS) are involved in the angiogenesis and recurrence of spinal chordoma tissues and influence the overall survival. METHODS: All patients affected by a spinal chordoma surgically treated between 1986 and 2007 were reviewed. We examined the expression of VEGFR2 and iNOS with immunohistochemistry using a tissue microarray containing 120 chordoma samples. Local recurrence and overall survival (OS) were analyzed. RESULTS: A series of 40 chordoma patients who underwent surgery for a total of 120 lesions (including 80 recurrent lesions) were identified (sacrum 77.5 %, lumbar spine 17.5 %, cervical/thoracic spine 5 %). Surgical margins were wide in 30 (75 %), marginal in 8 (20 %) and intralesional in 2 (5 %) patients. Median follow-up was 120 months. The 5- and 10-year OS of the entire series of patients was 78.6 and 30 %, respectively. There were five primary chordomas (12.5 %) with moderate and 35 (87.5 %) with strong expression of VEGFR-2. All recurrent spinal chordomas displayed strong expression of VEGFR-2. The expression of iNOS was predominately moderate to high in primary chordomas: There were 15 tumors (37.5 %) with moderate and 25 tumors (62.5 %) with strong expression. All recurrent chordomas displayed strong expression of iNOS. CONCLUSION: The high expression of VEGFR-2 and iNOS affected the OS. The OS at 10 years was only 30 %.


Asunto(s)
Cordoma/metabolismo , Cordoma/mortalidad , Óxido Nítrico Sintasa de Tipo II/metabolismo , Neoplasias de la Columna Vertebral/metabolismo , Neoplasias de la Columna Vertebral/mortalidad , Receptor 2 de Factores de Crecimiento Endotelial Vascular/metabolismo , Adolescente , Adulto , Anciano , Anciano de 80 o más Años , Biomarcadores de Tumor/metabolismo , Cordoma/cirugía , Femenino , Estudios de Seguimiento , Humanos , Inmunohistoquímica , Masculino , Persona de Mediana Edad , Recurrencia Local de Neoplasia/metabolismo , Pronóstico , Neoplasias de la Columna Vertebral/cirugía , Adulto Joven
16.
Top Curr Chem (Cham) ; 382(3): 23, 2024 Jul 04.
Artículo en Inglés | MEDLINE | ID: mdl-38965117

RESUMEN

In recent years, there has been a notable increase in the scientific community's interest in rational protein design. The prospect of designing an amino acid sequence that can reliably fold into a desired three-dimensional structure and exhibit the intended function is captivating. However, a major challenge in this endeavor lies in accurately predicting the resulting protein structure. The exponential growth of protein databases has fueled the advancement of the field, while newly developed algorithms have pushed the boundaries of what was previously achievable in structure prediction. In particular, using deep learning methods instead of brute force approaches has emerged as a faster and more accurate strategy. These deep-learning techniques leverage the vast amount of data available in protein databases to extract meaningful patterns and predict protein structures with improved precision. In this article, we explore the recent developments in the field of protein structure prediction. We delve into the newly developed methods that leverage deep learning approaches, highlighting their significance and potential for advancing our understanding of protein design.


Asunto(s)
Aprendizaje Profundo , Conformación Proteica , Proteínas , Proteínas/química , Proteínas/metabolismo , Bases de Datos de Proteínas , Algoritmos
17.
Pathol Res Pract ; 254: 155050, 2024 Feb.
Artículo en Inglés | MEDLINE | ID: mdl-38199132

RESUMEN

Despite great advances in diagnostic and treatment options for cancer, like chemotherapy surgery, and radiation therapy it continues to remain a major global health concern. Further research is necessary to find new biomarkers and possible treatment methods for cancer. MicroRNAs (miRNAs), tiny non-coding RNAs found naturally in the body, can influence the activity of several target genes. These genes are often disturbed in diseases like cancer, which perturbs functions like differentiation, cell division, cell cycle, apoptosis and proliferation. MiR-146a is a commonly and widely used miRNA that is often overexpressed in malignant tumors. The expression of miR-146a has been correlated with many pathological and physiological changes in cancer cells, such as the regulation of various cell death paths. It's been established that the control of cell death pathways has a huge influence on cancer progression. To improve our understanding of the interrelationship between miRNAs and cancer cell apoptosis, it's necessary to explore the impact of miRNAs through the alteration in their expression levels. Research has demonstrated that the appearance and spread of cancer can be mitigated by moderating the expression of certain miRNA - a commencement of treatment that presents a hopeful approach in managing cancer. Consequently, it is essential to explore the implications of miR-146a with respect to inducing different forms of tumor cell death, and evaluate its potential to serve as a target for improved chemotherapy outcomes. Through this review, we provide an outline of miR-146a's biogenesis and function, as well as its significant involvement in apoptosis. As well, we investigate the effects of exosomal miR-146a on the promotion of apoptosis in cancer cells and look into how it could possibly help combat chemotherapeutic resistance.


Asunto(s)
MicroARNs , Neoplasias , Humanos , MicroARNs/genética , MicroARNs/metabolismo , Apoptosis/genética , Neoplasias/genética , Biomarcadores
18.
Life Sci ; 340: 122449, 2024 Mar 01.
Artículo en Inglés | MEDLINE | ID: mdl-38253310

RESUMEN

AIMS: Cognitive impairment poses a considerable health challenge in the context of type 2 diabetes mellitus (T2DM), emphasizing the need for effective interventions. This study delves into the therapeutic efficacy of quercetin, a natural flavonoid, in mitigating cognitive impairment induced by T2DM in murine models. MATERIALS AND METHODS: Serum exosome samples were obtained from both T2DM-related and healthy mice for transcriptome sequencing, enabling the identification of differentially expressed mRNAs and long noncoding RNAs (lncRNAs). Subsequent experiments were conducted to ascertain the binding affinity between mmu-miR-129-5p, NEAT1 and BDNF. The structural characteristics and dimensions of isolated exosomes were scrutinized, and the expression levels of exosome-associated proteins were quantified. Primary mouse hippocampal neurons were cultured for in vitro validation, assessing the expression of pertinent genes as well as neuronal vitality, proliferation, and apoptosis capabilities. For in vivo validation, a T2DM mouse model was established, and quercetin treatment was administered. Changes in various parameters, cognitive ability, and the expression of insulin-related proteins, along with pivotal signaling pathways, were monitored. KEY FINDINGS: Analysis of serum exosomes from T2DM mice revealed dysregulation of NEAT1, mmu-miR-129-5p, and BDNF. In vitro investigations demonstrated that NEAT1 upregulated BDNF expression by inhibiting mmu-miR-129-5p. Overexpression of mmu-miR-129-5p or silencing NEAT1 resulted in the downregulation of insulin-related protein expression, enhanced apoptosis, and suppressed neuronal proliferation. In vivo studies validated that quercetin treatment significantly ameliorated T2DM-related cognitive impairment in mice. SIGNIFICANCE: These findings suggest that quercetin holds promise in inhibiting hippocampal neuron apoptosis and improving T2DM-related cognitive impairment by modulating the NEAT1/miR-129-5p/BDNF pathway within serum exosomes.


Asunto(s)
Disfunción Cognitiva , Diabetes Mellitus Experimental , Diabetes Mellitus Tipo 2 , Insulinas , MicroARNs , ARN Largo no Codificante , Animales , Ratones , ARN Largo no Codificante/genética , ARN Largo no Codificante/metabolismo , Quercetina/farmacología , Factor Neurotrófico Derivado del Encéfalo/genética , Diabetes Mellitus Tipo 2/complicaciones , Diabetes Mellitus Tipo 2/tratamiento farmacológico , Diabetes Mellitus Tipo 2/genética , Diabetes Mellitus Experimental/complicaciones , Proliferación Celular/genética , MicroARNs/genética , MicroARNs/metabolismo , Disfunción Cognitiva/tratamiento farmacológico , Disfunción Cognitiva/genética
19.
Cell Cycle ; 23(4): 405-434, 2024 Feb.
Artículo en Inglés | MEDLINE | ID: mdl-38640424

RESUMEN

Angiotensin-converting enzyme 2 (ACE2) is identified as the functional receptor for severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), the causative agent of the ongoing global coronavirus disease-2019 (COVID-19) pandemic. This study aimed to elucidate potential therapeutic avenues by scrutinizing approved drugs through the identification of the genetic signature associated with SARS-CoV-2 infection in individuals with asthma. This exploration was conducted through an integrated analysis, encompassing interaction networks between the ACE2 receptor and common host (co-host) factors implicated in COVID-19/asthma comorbidity. The comprehensive analysis involved the identification of common differentially expressed genes (cDEGs) and hub-cDEGs, functional annotations, interaction networks, gene set variation analysis (GSVA), gene set enrichment analysis (GSEA), and module construction. Interaction networks were used to identify overlapping disease modules and potential drug targets. Computational biology and molecular docking analyzes were utilized to discern functional drug modules. Subsequently, the impact of the identified drugs on the expression of hub-cDEGs was experimentally validated using a mouse model. A total of 153 cDEGs or co-host factors associated with ACE2 were identified in the COVID-19 and asthma comorbidity. Among these, seven significant cDEGs and proteins - namely, HRAS, IFNG, JUN, CDH1, TLR4, ICAM1, and SCD-were recognized as pivotal host factors linked to ACE2. Regulatory network analysis of hub-cDEGs revealed eight top-ranked transcription factors (TFs) proteins and nine microRNAs as key regulatory factors operating at the transcriptional and post-transcriptional levels, respectively. Molecular docking simulations led to the proposal of 10 top-ranked repurposable drug molecules (Rapamycin, Ivermectin, Everolimus, Quercetin, Estradiol, Entrectinib, Nilotinib, Conivaptan, Radotinib, and Venetoclax) as potential treatment options for COVID-19 in individuals with comorbid asthma. Validation analysis demonstrated that Rapamycin effectively inhibited ICAM1 expression in the HDM-stimulated mice group (p < 0.01). This study unveils the common pathogenesis and genetic signature underlying asthma and SARS-CoV-2 infection, delineated by the interaction networks of ACE2-related host factors. These findings provide valuable insights for the design and discovery of drugs aimed at more effective therapeutics within the context of lung disease comorbidities.


Asunto(s)
Enzima Convertidora de Angiotensina 2 , Asma , Tratamiento Farmacológico de COVID-19 , COVID-19 , Comorbilidad , Reposicionamiento de Medicamentos , Simulación del Acoplamiento Molecular , SARS-CoV-2 , Reposicionamiento de Medicamentos/métodos , Asma/tratamiento farmacológico , Asma/genética , Enzima Convertidora de Angiotensina 2/genética , Enzima Convertidora de Angiotensina 2/metabolismo , Animales , Humanos , COVID-19/genética , COVID-19/virología , Ratones , SARS-CoV-2/efectos de los fármacos , SARS-CoV-2/genética , SARS-CoV-2/metabolismo , Redes Reguladoras de Genes/efectos de los fármacos , Biología Computacional/métodos , MicroARNs/genética , MicroARNs/metabolismo
20.
Curr Probl Cardiol ; 48(5): 101108, 2023 May.
Artículo en Inglés | MEDLINE | ID: mdl-35016988

RESUMEN

Sedentary lifestyle and dyslipidemia are well-recognized risk factors for cardiovascular diseases (CVD). Changes in blood lipid profile (total cholesterol (TC), triglycerides, high-density lipoprotein [HDL], and low-density lipoprotein [LDL]) due to the exercise may be beneficial for decreasing CVD-related events. In this review we aimed to investigate the effect of different types of exercise on lipid profile components in people with different health conditions and age ranges. A systematic search was performed covering PubMed, Web of Science, and Google Scholar for English articles from 2010 until November 2021. Finally, 31 studies were included in our study. Results showed that exercise in younger individuals sometimes resulted in no significant changes of any of the variables or some of them; however, efficient improvement was observed in all studies of older and middle-age groups. In terms of health condition and gender; healthy individuals, overweight people, subjects with type 2 diabetes and obesity, and male participants found to have benefited more from the exercise. In patients with chronic kidney diseases lipid profile improvement was not significant. The cardiac rehabilitation program, particularly comprehensive cardiac rehabilitation, proved to be more beneficial than exercise alone in the case of cardiovascular patients and those at elevated risk of CVD. In conclusion exercise is beneficial in terms of improving lipid profile but for younger population, and those with kidney problems and CVD patients, more further preparations are needed under the supervision of experts in the field of sports and medicine to achieve the desired result. Also, more studies are needed for these groups in order to provide a definite and reliable conclusion.


Asunto(s)
Enfermedades Cardiovasculares , Diabetes Mellitus Tipo 2 , Humanos , Masculino , Persona de Mediana Edad , Enfermedades Cardiovasculares/epidemiología , Enfermedades Cardiovasculares/etiología , Enfermedades Cardiovasculares/prevención & control , Ejercicio Físico , Lípidos , Triglicéridos
SELECCIÓN DE REFERENCIAS
DETALLE DE LA BÚSQUEDA