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As human life expectancy continues to rise, becoming a pressing global concern, it brings into focus the underlying mechanisms of aging. The increasing lifespan has led to a growing elderly population grappling with age-related diseases (ARDs), which strains healthcare systems and economies worldwide. While human senescence was once regarded as an immutable and inexorable phenomenon, impervious to interventions, the emerging field of geroscience now offers innovative approaches to aging, holding the promise of extending the period of healthspan in humans. Understanding the intricate links between aging and pathologies is essential in addressing the challenges presented by aging populations. A substantial body of evidence indicates shared mechanisms and pathways contributing to the development and progression of various ARDs. Consequently, novel interventions targeting the intrinsic mechanisms of aging have the potential to delay the onset of diverse pathological conditions, thereby extending healthspan. In this narrative review, we discuss the most promising methods and interventions aimed at modulating aging, which harbor the potential to mitigate ARDs in the future. We also outline the complexity of senescence and review recent empirical evidence to identify rational strategies for promoting healthy aging.
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MicroRNAs (miRNAs) have emerged as crucial regulators of gene expression, playing pivotal roles in various biological processes, including cancer development and progression. Among them, miR-125b has garnered significant attention due to its multifaceted functional roles in human hepatocellular carcinoma (HCC). Extensive research has revealed that miR-125b plays a dual role in HCC, acting as both a tumor suppressor and an oncogene depending on the context. As a tumor suppressor, miR-125b exerts its inhibitory effects on HCC by targeting key oncogenic pathways and genes involved in cell proliferation, migration, invasion, and angiogenesis. Its downregulation in HCC is frequently observed and correlates with aggressive tumor characteristics and poor prognosis. Conversely, miR-125b can also function as an oncogene in specific HCC subtypes or under certain conditions. It has been shown to promote HCC growth, metastasis, and therapeutic resistance by targeting tumor suppressor genes, modulating the epithelial-mesenchymal transition (EMT) process, and enhancing cancer stem cell-like properties. The upregulation of miR-125b in HCC has been associated with advanced disease stages and unfavorable clinical outcomes. Furthermore, the dysregulation of miR-125b expression in HCC is influenced by a complex network of regulatory mechanisms. Understanding these regulatory mechanisms is crucial for deciphering the precise functional roles of miR-125b in HCC and exploring its potential as a diagnostic biomarker or therapeutic target. In the current review study, we comprehensively elucidated the diverse functional roles of miR-125b in HCC, providing a comprehensive overview of its regulatory mechanisms and impact on key cellular processes involved in HCC progression.
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Gynecologic cancers are a worldwide problem among women. Recently, molecular targeted therapy opened up an avenue for cancer diagnosis and treatment. Long non-coding RNAs (lncRNAs) are RNA molecules (> 200 nt) that are not translated into protein, and interact with DNA, RNA, and proteins. LncRNAs were found to play pivotal roles in cancer tumorigenesis and progression. Nuclear paraspeckle assembly transcript 1 (NEAT1) is a lncRNA that mediates cell proliferation, migration, and EMT in gynecologic cancers by targeting several miRNAs/mRNA axes. Therefore, NEAT1 may function as a potent biomarker for the prediction and treatment of breast, ovarian, cervical, and endometrial cancers. In this narrative review, we summarized various NEAT1-related signaling pathways that are critical in gynecologic cancers. Long non-coding RNA (lncRNA) by targeting various signaling pathways involved in its target genes can regulate the occurrence of gynecologic cancers.
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Long non-coding RNAs (lncRNAs) present pivotal roles in cancer tumorigenesis and progression. Recently, nuclear paraspeckle assembly transcript 1 (NEAT1) as a lncRNA has been shown to mediate cell proliferation, migration, and EMT in tumor cells. NEAT1 by targeting several miRNAs/mRNA axes could regulate cancer cell behavior. Therefore, NEAT1 may function as a potent biomarker for the prediction and treatment of some human cancers. In this review, we summarized various NEAT1-related signaling pathways that are critical in cancer initiation and progression.
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MicroRNAs , RNA Longo não Codificante , Humanos , Carcinogênese/genética , Linhagem Celular Tumoral , Proliferação de Células/genética , Transformação Celular Neoplásica/genética , Regulação Neoplásica da Expressão Gênica/genética , MicroRNAs/genética , RNA Longo não Codificante/metabolismoRESUMO
Cancer as a progressive and complex disease is caused by early chromosomal changes and stimulated cellular transformation. Previous studies reported that long non-coding RNAs (lncRNAs) play pivotal roles in the initiation, maintenance, and progression of cancer cells. LncRNA activated by TGF-ß (ATB) has been shown to be dysregulated in different types of cancer. Aberrant expression of lncRNA-ATB plays an important role in the progression of diverse malignancies. High expression of LncRNA-ATB is associated with cancer cell growth, proliferation, metastasis, and EMT. LncRNA-ATB by targeting various signaling pathways and microRNAs (miRNAs) can trigger cancer pathogenesis. Therefore, lncRNA-ATB can be a novel target for cancer prediction and diagnosis. In this review, we will focus on the function of lncRNA-ATB in various types of human cancers.
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MicroRNAs , RNA Longo não Codificante , Humanos , Fator de Crescimento Transformador beta/metabolismo , RNA Longo não Codificante/genética , RNA Longo não Codificante/metabolismo , MicroRNAs/genética , MicroRNAs/metabolismo , Transformação Celular Neoplásica/genética , Transdução de Sinais/genética , Regulação Neoplásica da Expressão GênicaRESUMO
INTRODUCTION: Retinoblastoma (RB) is the most common childhood tumor that can occur in the retina and develop in a sporadic or heritable form. Although various traditional treatment options have been used for patients with RB, identifying novel strategies for childhood cancers is necessary. MATERIAL AND METHODS: Recently, molecular-based targeted therapies have opened a greater therapeutic window for RB. Long non-coding RNAs (lncRNAs) presented a potential role as a biomarker for the detection of RB in various stages. CONCLUSION: LncRNAs by targeting several miRNA/transcription factors play critical roles in the stimulation or suppression of RB. In this review, we summarized recent progress on the functions of tumor suppressors or oncogenes lncRNAs in RB.
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MicroRNAs , RNA Longo não Codificante , Neoplasias da Retina , Retinoblastoma , Humanos , Criança , Retinoblastoma/genética , Retinoblastoma/patologia , RNA Longo não Codificante/genética , MicroRNAs/genética , Biomarcadores , Neoplasias da Retina/genética , Neoplasias da Retina/patologiaRESUMO
Breast cancer (BC) is the most common cancer and the prevalent type of malignancy among women. Multiple risk factors, including genetic changes, biological age, dense breast tissue, and obesity are associated with BC. The mitogen-activated protein kinases (MAPK) signaling pathway has a pivotal role in regulating biological functions such as cell proliferation, differentiation, apoptosis, and survival. It has become evident that the MAPK pathway is associated with tumorigenesis and may promote breast cancer development. The MAPK/RAS/RAF cascade is closely associated with breast cancer. RAS signaling can enhance BC cell growth and progression. B-Raf is an important kinase and a potent RAF isoform involved in breast tumor initiation and differentiation. Depending on the reasons for cancer, there are different strategies for treatment of women with BC. Till now, several FDA-approved treatments have been investigated that inhibit the MAPK pathway and reduce metastatic progression in breast cancer. The most common breast cancer drugs that regulate or inhibit the MAPK pathway may include Farnesyltransferase inhibitors (FTIs), Sorafenib, Vemurafenib, PLX8394, Dabrafenib, Ulixertinib, Simvastatin, Alisertib, and Teriflunomide. In this review, we will discuss the roles of the MAPK/RAS/RAF/MEK/ERK pathway in BC and summarize the FDA-approved prescription drugs that target the MAPK signaling pathway in women with BC.
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Neoplasias da Mama/tratamento farmacológico , Aprovação de Drogas , Proteínas Quinases Ativadas por Mitógeno/metabolismo , Medicamentos sob Prescrição/uso terapêutico , Transdução de Sinais/efeitos dos fármacos , Linhagem Celular Tumoral , Transformação Celular Neoplásica , Feminino , Humanos , Proteínas Quinases Ativadas por Mitógeno/genética , Estados Unidos , United States Food and Drug AdministrationRESUMO
The family of Tribbles proteins play many critical nonenzymatic roles and regulate a wide range of key signaling pathways. Tribbles homolog 2 (Trib2) is a pseudo serine/threonine kinase that functions as a scaffold or adaptor in various physiological and pathological processes. Trib2 can interact with E3 ubiquitin ligases and control protein stability of downstream effectors. This protein is induced by mitogens and enhances the propagation of several cancer cells, including myeloid leukemia, liver, lung, skin, bone, brain, and pancreatic. Thus, Trib2 can be a predictive and valuable biomarker for the diagnosis and treatment of cancer. Recent studies have illustrated that Trib2 plays a major role in cell fate determination of stem cells. Stem cells have the capacity to self-renew and differentiate into specific cell types. Stem cells are important sources for cell-based regenerative medicine and drug screening. Trib2 has been found to increase the self-renewal ability of embryonic stem cells, the reprogramming efficiency of somatic cells, and chondrogenesis. In this review, we will focus on the recent advances of Trib2 function in tumorigenesis and stem cell fate decisions. Video abstract.
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Carcinogênese/metabolismo , Carcinogênese/patologia , Linhagem da Célula , Proteínas Serina-Treonina Quinases/metabolismo , Células-Tronco/citologia , Humanos , Modelos Biológicos , Proteínas Serina-Treonina Quinases/químicaRESUMO
INTRODUCTION: The Helicobacter pylori infection and cytokine-mediated inflammatory responses play significant roles in the pathogenesis of gastric cancer (GC). This study was performed to determine the association between the risk of GC and genetic polymorphisms in interleukin (IL)-1ß and tumor necrosis factor-alpha (TNF-α). METHODS: The polymorphisms of IL-1ß and TNF-α genes were analyzed by polymerase chain reaction-restriction fragment length polymorphism (PCR-RFLP) in 290 patients who underwent endoscopy. Infection with H. pylori was diagnosed by histological analysis, rapid urease test, and PCR of gastric biopsy samples. Quantitative real-time PCR was performed to determine the relative mRNA expression levels. RESULTS: No significant difference was detected in allele frequency and genotype of all studied polymorphisms between chronic gastritis (CG), GC and healthy individuals. IL-1ß mRNA was down-regulated in both gastritis (relative quantification (RQ)=0.447) and the GC groups (RQ=0.151). In contrast, the expression of TNF-α was up-regulated in the GC group (RQ=2.817) compared to the gastritis group (RQ=0.861). CONCLUSIONS: The studied single-nucleotide polymorphisms are not risk factors for development of CG and GC. However, H. pylori infection causes a huge increase in the TNF-α expression in GC patients.
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BACKGROUND: Immediate Breast Reconstruction (IBR) is an additional surgical procedure that may increase postoperative complications (such as flap necrosis, infection, and hematoma) and delay the initial time for adjuvant chemotherapy in some patients. In this systematic and meta-analysis, we provide overall survival rates of patients who underwent mastectomy with and without IBR. METHODS: The following databases were systematically searched between 2015 to 2019 without language restrictions in PUBMED, EMBASE, Web of Science, and Cochrane Library. In addition, the relevant references in the list of all included articles were also checked. The search term included "breast cancer" and "breast reconstruction" "mastectomy". RESULTS: The sample size was a range from 339 to 5644 patients. The median age was 46.3 years. The results showed no significant differences in terms of overall survival between two groups. CONCLUSION: The results showed that IBR after mastectomy did not affect the overall survival.
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Spinal Cord Injury (SCI), as a devastating and life-altering neurological disorder, is one of the most serious health issues. Currently, the management of acute SCI includes pharmacotherapy and surgical decompression. Both the approaches have been observed to have adverse physiological effects on SCI patients. Therefore, novel therapeutic targets for the management of SCI are urgently required for developing cell-based therapies. Multipotent stem cells, as a novel strategy for the treatment of tissue injury, may provide an effective therapeutic option against many neurological disorders. Mesenchymal stem cells (MSCs) or multipotent stromal cells can typically self-renew and generate various cell types. These cells are often isolated from bone marrow (BM-MSCs), adipose tissues (AD-MSCs), umbilical cord blood (UCB-MSCs), and placenta (PMSCs). MSCs have remarkable potential for the development of regenerative therapies in animal models and humans with SCI. Herein, we summarize the therapeutic potential of human MSCs in the treatment of SCI.
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Medula Óssea/metabolismo , Transplante de Células-Tronco Mesenquimais , Células-Tronco Mesenquimais/metabolismo , Traumatismos da Medula Espinal/terapia , Tecido Adiposo/citologia , Animais , Humanos , Medula Espinal/fisiopatologiaRESUMO
Stroke is the leading cause of death and physical disability worldwide. Non-coding RNAs (ncRNAs) are endogenous molecules that play key roles in the pathophysiology and retrieval processes following ischemic stroke. The potential of ncRNAs, especially microRNAs (miRNAs) and long non-coding RNAs (lncRNAs) in neuroprotection and angiogenesis highlights their potential as targets for therapeutic intervention. In this review, we document the miRNAs and lncRNAs that have been reported to exert regulatory actions in neuroprotective and angiogenic processes through different mechanisms involving their interaction with target coding genes. We believe that exploration of the expression profiles and the possible functions of ncRNAs during the recovery processes will help comprehension of the molecular mechanisms responsible for neuroprotection and angiogenesis, and may also contribute to find biomarkers and targets for future stroke intervention.
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Isquemia Encefálica/metabolismo , AVC Isquêmico/metabolismo , Neovascularização Fisiológica/fisiologia , Neuroproteção/fisiologia , RNA não Traduzido/fisiologia , Animais , Isquemia Encefálica/genética , Isquemia Encefálica/prevenção & controle , Humanos , AVC Isquêmico/genética , AVC Isquêmico/prevenção & controleRESUMO
Spinal cord injury (SCI) as a serious public health issue and neurological insult is one of the most severe cause of long-term disability. To date, a variety of techniques have been widely developed to treat central nervous system injury. Currently, clinical treatments are limited to surgical decompression and pharmacotherapy. Because of their negative effects and inefficiency, novel therapeutic approaches are required in the management of SCI. Improvement and innovation of stem cell-based therapies have a huge potential for biological and future clinical applications. Human pluripotent stem cells (hPSCs) including embryonic stem cells (ESCs) and induced pluripotent stem cells (iPSCs) are defined by their abilities to divide asymmetrically, self-renew and ultimately differentiate into various cell lineages. There are considerable research efforts to use various types of stem cells, such as ESCs, neural stem cells (NSCs), and mesenchymal stem cells (MSCs) in the treatment of patients with SCI. Moreover, the use of patient-specific iPSCs holds great potential as an unlimited cell source for generating in vivo models of SCI. In this review, we focused on the potential of hPSCs in treating SCI.