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Cellular Signalling Aug 2023Long non-coding RNAs (lncRNAs) have been implicated in gastric cancer (GC) carcinogenesis and progression. However, the role of LINC00501 in GC growth and metastasis...
Long non-coding RNAs (lncRNAs) have been implicated in gastric cancer (GC) carcinogenesis and progression. However, the role of LINC00501 in GC growth and metastasis remains unclear. In this study, we found that LINC00501 was frequently upregulated in GC cells and tissues and was closely related to adverse GC clinicopathological features. Aberrant overexpression of LINC00501 promoted GC cell proliferation, invasion, and metastasis both in vitro and in vivo. Mechanistically, LINC00501 stabilized client protein STAT3 from deubiquitylation by directly interacting with cancer chaperone protein HSP90B1. Furthermore, the LINC00501-STAT3 axis modulated GC cell proliferation and metastasis. In turn, STAT3 bound directly to the LINC00501 promoter and positively activated LINC00501 expression, thus forming a positive feedback loop, thereby accelerating tumor growth, invasiveness, and metastasis. In addition, LINC00501 expression was positively correlated with STAT3 and p-STAT3 protein expression levels in gastric clinical samples. Our results reveal that LINC00501 acts as an oncogenic lncRNA and that the LINC00501-HSP90B1-STAT3 positive feedback loop contributes to GC development and progression, suggesting that LINC00501 may be a novel potential biomarker and treatment target for GC.
Topics: Humans; Cell Line, Tumor; Cell Movement; Cell Proliferation; Feedback; Gene Expression Regulation, Neoplastic; RNA, Long Noncoding; Signal Transduction; STAT3 Transcription Factor; Stomach Neoplasms
PubMed: 37156452
DOI: 10.1016/j.cellsig.2023.110711 -
International Journal of Nanomedicine 2023Aptamers are widely applied to diagnosis and therapy because of their targeting. However, the current progress of research into aptamers for the treatment of eye... (Review)
Review
Aptamers are widely applied to diagnosis and therapy because of their targeting. However, the current progress of research into aptamers for the treatment of eye disorders has not been well-documented. The current literature on aptamers was reviewed in this study. Aptamer-related drugs and biochemical sensors have been evaluated for several eye disorders within the past decade; S58 targeting TGF-β receptor II and pegaptanib targeting vascular endothelial growth factor (VEGF) are used to prevent fibrosis after glaucoma filtration surgery. Anti-brain-derived neurotrophic factor aptamer has been used to diagnose glaucoma. The first approved aptamer drug (pegaptanib) has been used to inhibit angiogenesis in age-related macular degeneration (AMD) and diabetic retinopathy (DR), and its efficacy and safety have been demonstrated in clinical trials. Aptamers, including E10030, RBM-007, AS1411, and avacincaptad pegol, targeting other angiogenesis-related biomarkers have also been discovered and subjected to clinical trials. Aptamers, such as C promoter binding factor 1, CD44, and advanced end products in AMD and DR, targeting other signal pathway proteins have also been discovered for therapy, and biochemical sensors for early diagnosis have been developed based on aptamers targeting VEGF, connective tissue growth factor, and lipocalin 1. Aptamers used for early detection and treatment of ocular tumors were derived from other disease biomarkers, such as CD71, nucleolin, and high mobility group A. In this review, the development and application of aptamers in eye disorders in recent years are systematically discussed, which may inspire a new link between aptamers and eye disorders. The aptamer development trajectory also facilitates the discovery of the pathogenesis and therapeutic strategies for various eye disorders.
Topics: Humans; Vascular Endothelial Growth Factor A; Ophthalmology; Macular Degeneration; Aptamers, Nucleotide; Diabetic Retinopathy; Glaucoma; Acceleration
PubMed: 37551274
DOI: 10.2147/IJN.S418115 -
Oncogene Sep 2023A Kinase Interacting Protein 1 (AKIP1) is found to be overexpressed in a variety of human cancers and associated with patients' worse prognosis. Several studies have...
A Kinase Interacting Protein 1 (AKIP1) is found to be overexpressed in a variety of human cancers and associated with patients' worse prognosis. Several studies have established AKIP1's malignant functions in tumor metastasis, angiogenesis, and chemoradiotherapy resistance. However, the mechanism of AKIP1 involved in accelerating glioblastoma (GBM) progression remains unknown. Here, we showed that the expression of AKIP1 was positively correlated with the glioma pathological grades. Down-regulating AKIP1 greatly impaired the proliferation, colony formation, and tumorigenicity of GBM cells. In terms of the mechanism, AKIP1 cooperates with transcriptional factor Yin Yang 1 (YY1)-mediated Heat Shock Protein 90 Alpha Family Class A Member 1 (HSP90AA1) transcriptional activation, enhancing the stability of Epidermal Growth Factor Receptor (EGFR). YY1 was identified as a potential transcriptional factor of HSP90AA1 and directly interacts with AKIP1. The overexpression of HSP90α significantly reversed AKIP1 depletion incurred EGFR instability and the blocked cell proliferation. Moreover, we further investigated the interacted pattern between EGFR and HSP90α. These findings established that AKIP1 acted as a critical oncogenic factor in GBM and uncovered a novel regulatory mechanism in EGFR aberrant expression.
Topics: Humans; Glioblastoma; ErbB Receptors; Cell Proliferation; Glioma; Cell Line, Tumor; Nuclear Proteins; Adaptor Proteins, Signal Transducing
PubMed: 37596322
DOI: 10.1038/s41388-023-02796-2 -
Journal of Advanced Research May 2024Triterpenoids are versatile secondary metabolites with a diverse array of physiological activities, possessing valuable pharmacological effects and influencing the... (Review)
Review
BACKGROUND
Triterpenoids are versatile secondary metabolites with a diverse array of physiological activities, possessing valuable pharmacological effects and influencing the growth and development of plants. As more triterpenoids in cereals are unearthed and characterized, their biological roles in plant growth and development are gaining recognition.
AIM OF THE REVIEW
This review provides an overview of the structures, biosynthetic pathways, and diverse biological functions of triterpenoids identified in cereals. Our goal is to establish a basis for further exploration of triterpenoids with novel structures and functional activities in cereals, and to facilitate the potential application of triterpenoids in grain breeding, thus accelerating the development of superior grain varieties.
KEY SCIENTIFIC CONCEPTS OF THE REVIEW
This review consolidates information on various triterpenoid skeletons and derivatives found in cereals, and summarizes the pivotal enzyme genes involved, including oxidosqualene cyclase (OSC) and other triterpenoid modifying enzymes like cytochrome P450, glycosyltransferase, and acyltransferase. Triterpenoid-modifying enzymes exhibit specificity towards catalytic sites within triterpenoid skeletons, generating a diverse array of functional triterpenoid derivatives. Furthermore, triterpenoids have been shown to significantly impact the nutritional value, yield, disease resistance, and stress response of cereals.
PubMed: 38788922
DOI: 10.1016/j.jare.2024.05.021 -
Biochemistry and Cell Biology =... Oct 2023Insulin-like growth factor-1 (IGF-1) is a critical modulator of cell growth and survival, making it a central part of maintaining essentially every biological system in... (Review)
Review
Insulin-like growth factor-1 (IGF-1) is a critical modulator of cell growth and survival, making it a central part of maintaining essentially every biological system in the body. Knowledge of the intricate mechanisms involved in activating IGF-1 signaling is not only key to understanding basic processes of growth and development, but also for addressing diseases, such as cancer and diabetes. This brief review explores how dysregulation of normal IGF-1 signaling can impact growth by examining its role in postnatal bone elongation. IGF-1 actions are dysregulated in autoimmune diseases, such as juvenile idiopathic arthritis and chronic kidney disease, which results in growth stunting. Conversely, childhood obesity results in growth acceleration, premature growth cessation, and ultimately, diminished bone quality, while systemic IGF-1 levels remain normal. Understanding the role of IGF-1 signaling in normal and dysregulated growth can add to other studies that address how this system regulates chronic diseases.
Topics: Child; Humans; Insulin-Like Growth Factor I; Chondrocytes; Growth Plate; Pediatric Obesity; Bone and Bones
PubMed: 37246759
DOI: 10.1139/bcb-2023-0025 -
Scientific Reports Oct 2023Pathological markers that can monitor the progression of gastric cancer (GC) may facilitate the diagnosis and treatment of patients with diffuse GC (DGC). To identify...
Pathological markers that can monitor the progression of gastric cancer (GC) may facilitate the diagnosis and treatment of patients with diffuse GC (DGC). To identify microRNAs (miRNAs) that can differentiate between early and advanced DGC in the gastric mucosa, miRNA expression profiling was performed using the NanoString nCounter method in human DGC tumors. Ectopic expression of miR-199a and miR-199b (miR-199a/b) in SNU601 human GC cells accelerated the growth rate, viability, and motility of cancer cells and increased the tumor volume and weight in a mouse xenograft model. To study their clinicopathological roles in patients with GC, miR-199a/b levels were measured in human GC tumor samples using in situ hybridization. High miR-199a/b expression level was associated with enhanced lymphovascular invasion, advanced T stage, and lymph-node metastasis. Using the 3'-untranslated region (UTR) luciferase assay, Frizzled-6 (FZD6) was confirmed to be a direct target of miR-199a/b in GC cells. siRNA-mediated depletion of FZD6 enhanced the motility of SNU601 cells, and addback of FZD6 restored cancer cell motility stimulated by miR-199a/b. In conclusion, miR-199a/b promotes DGC progression by targeting FZD6, implying that miR-199a/b can be used as prognostic and diagnostic biomarkers for the disease.
Topics: Humans; Animals; Mice; Stomach Neoplasms; MicroRNAs; Prognosis; Lymphatic Metastasis; Gene Expression Regulation, Neoplastic; Cell Line, Tumor; Cell Proliferation
PubMed: 37838767
DOI: 10.1038/s41598-023-44716-0 -
ELife Aug 2023In adult mammals, spermatogenesis embodies the complex developmental process from spermatogonial stem cells (SSCs) to spermatozoa. At the top of this developmental...
In adult mammals, spermatogenesis embodies the complex developmental process from spermatogonial stem cells (SSCs) to spermatozoa. At the top of this developmental hierarchy lie a series of SSC subpopulations. Their individual identities as well as the relationships with each other, however, remain largely elusive. Using single-cell analysis and lineage tracing, we discovered both in mice and humans the quiescent adult SSC subpopulation marked specifically by forkhead box protein C2 (FOXC2). All spermatogenic progenies can be derived from FOXC2 SSCs and the ablation of FOXC2 SSCs led to the depletion of the undifferentiated spermatogonia pool. During germline regeneration, FOXC2 SSCs were activated and able to completely restore the process. Germ cell-specific knockout resulted in an accelerated exhaustion of SSCs and eventually led to male infertility. Furthermore, FOXC2 prompts the expressions of negative regulators of cell cycle thereby ensures the SSCs reside in quiescence. Thus, this work proposes that the quiescent FOXC2 SSCs are essential for maintaining the homeostasis and regeneration of spermatogenesis in adult mammals.
Topics: Adult; Animals; Humans; Male; Mice; Cell Cycle; Cell Division; Spermatogonia; Stem Cells
PubMed: 37610429
DOI: 10.7554/eLife.85380 -
The Journal of Clinical Endocrinology... Jun 2024The assessment and treatment of children with growth retardation is increasingly complex, and due to availability of targeted genetic sequencing, an ever-expanding... (Review)
Review
CONTEXT
The assessment and treatment of children with growth retardation is increasingly complex, and due to availability of targeted genetic sequencing, an ever-expanding number of conditions impeding growth are being identified. Among endocrine-related etiologies of short stature amenable to hormonal treatment, defects in the growth hormone (GH)-insulin-like growth factor I axis remain pre-eminent, with a multiplicity of disorders causing decreased secretion or insensitivity to GH action. Sex steroids in puberty increase epiphyseal senescence and eventual growth plate closure. This is mediated mostly via estrogen receptor (ER)α in males and females, effects that can greatly limit time available for growth.
EVIDENCE ACQUISITION
Extensive literature review through PubMed and other search engines.
EVIDENCE SYNTHESIS
Therapeutic strategies to be considered in peripubertal and pubertal children with disordered growth are here discussed, including daily and weekly GH, low-dose sex steroids, gonadotropin hormone releasing hormone (GnRH) analogues in combination with GH, aromatase inhibitors (AIs) alone and in combination with GH in boys. When used for at least 2 to 3 years, GnRH analogues combined with GH can result in meaningful increases in height. AIs used with GH permit puberty to progress in boys without hindrance, selectively decreasing estrogen, and resulting in taller height. With more than 20 years of cumulative experience in clinical use of these medications, we discuss the safety profile of these treatments.
CONCLUSION
The approach of growth retardation in the peripubertal and pubertal years must consider the sex steroid milieu and the tempo of bone acceleration. Treatment of affected children in this period must be individualized.
Topics: Humans; Child; Growth Disorders; Human Growth Hormone; Puberty; Body Height; Male; Female; Aromatase Inhibitors; Gonadotropin-Releasing Hormone; Insulin-Like Growth Factor I; Adolescent
PubMed: 38181434
DOI: 10.1210/clinem/dgae011 -
Current Obesity Reports Dec 2023To review the upstream determinants of overweight and obesity in Europe, including food and built environments, and political, commercial, and socioeconomic determinants. (Review)
Review
PURPOSE OF REVIEW
To review the upstream determinants of overweight and obesity in Europe, including food and built environments, and political, commercial, and socioeconomic determinants.
RECENT FINDINGS
Overweight and obesity affect 60% of European adults, and one in three children, and are more common in individuals with low compared to high socioeconomic position (SEP). Individuals in low SEP groups are more exposed to unhealthy built and food environments, including higher exposure to unhealthy food marketing. Industries influencing the food system have much economic power, resulting in ignoring or silencing the role of ultra-processed foods and commercial practices in weight gain. Overall, effective policies to address overweight and obesity have been insufficiently implemented by governments. To accelerate implementation, strengthened political commitment is essential. Policies must also focus on the upstream, structural, and systemic drivers of overweight and obesity; be comprehensive; and target socioeconomic inequalities in diets and physical activity.
Topics: Child; Adult; Humans; Overweight; Obesity; Diet; Socioeconomic Factors; Weight Gain; Europe
PubMed: 37594616
DOI: 10.1007/s13679-023-00524-1 -
International Journal of Molecular... Apr 2024Skin aging is a complex process involving structural and functional changes and is characterized by a decrease in collagen content, reduced skin thickness, dryness, and... (Review)
Review
Skin aging is a complex process involving structural and functional changes and is characterized by a decrease in collagen content, reduced skin thickness, dryness, and the formation of wrinkles. This process is underpinned by multiple mechanisms including the free radical theory, inflammation theory, photoaging theory, and metabolic theory. The skin immune system, an indispensable part of the body's defense mechanism, comprises macrophages, lymphocytes, dendritic cells, and mast cells. These cells play a pivotal role in maintaining skin homeostasis and responding to injury or infection. As age advances, along with various internal and external environmental stimuli, skin immune cells may undergo senescence or accelerated aging, characterized by reduced cell division capability, increased mortality, changes in gene expression patterns and signaling pathways, and altered immune cell functions. These changes collectively impact the overall function of the immune system. This review summarizes the relationship between skin aging and immunity and explores the characteristics of skin aging, the composition and function of the skin immune system, the aging of immune cells, and the effects of these cells on immune function and skin aging. Immune dysfunction plays a significant role in skin aging, suggesting that immunoregulation may become one of the important strategies for the prevention and treatment of skin aging.
Topics: Skin Aging; Skin; Mast Cells; Cell Division
PubMed: 38612909
DOI: 10.3390/ijms25074101