scholarly journals Ethionine-mediated reduction of S-adenosylmethionine is responsible for the neural tube defects in the developing mouse embryo-mediated m6A modification and is involved in neural tube defects via modulating Wnt/β-catenin signaling pathway

2021 ◽  
Vol 14 (1) ◽  
Author(s):  
Li Zhang ◽  
Rui Cao ◽  
Dandan Li ◽  
Yuqing Sun ◽  
Juan Zhang ◽  
...  
Keyword(s):  
Cell Proliferation ◽  
Signaling Pathway ◽  
Neural Tube ◽  
Neural Tube Defects ◽  
Epigenetic Mechanism ◽  
Proliferation And Apoptosis ◽  
Life Threatening ◽  
Neural Tube Development

AbstractNeural tube defects (NTDs) remain one of the most life-threatening birth defects affecting infants. Most patients with NTDs eventually develop lifelong disability, which cause significant morbidity and mortality and seriously reduce the quality of life. Our previous study has found that ethionine inhibits cell viability by disrupting the balance between proliferation and apoptosis, and preventing neural stem cells from differentiating into neurons and astrocytes. However, how ethionine participates in the pathogenesis of neural tube development through N6-methyladenosine (m6A) modification remains unknown. This study aims to investigate METTL3- and ALKBH5-mediated m6A modification function and mechanism in NTDs. Herein, our results demonstrate that SAM play not only a compensatory role, it also leads to changes of m6A modification in neural tube development and regulation. Additionally, these data implicate that METTL3 is enriched in HT-22 cells, and METTL3 knockdown reduces cell proliferation and increases apoptosis through suppressing Wnt/β-catenin signaling pathway. Significantly, overexpression of ALKBH5 can only inhibit cell proliferation, but cannot promote cell apoptosis. This research reveals an important role of SAM in development of NTDs, providing a good theoretical basis for further research on NTDs. This finding represents a novel epigenetic mechanism underlying that the m6A modification has profound and lasting implications for neural tube development.

scholarly journals METTL3-Mediated m6A Modification is Involved in Neural Tube Defects via Modulating Wnt/β-Catenin Signaling Pathway

2021 ◽  
Author(s):  
Li Zhang ◽  
Rui Cao ◽  
Dandan Li ◽  
Yuqing Sun ◽  
Juan Zhang ◽  
...  
Keyword(s):  
Neural Tube ◽  
Neural Tube Defects ◽  
Theoretical Basis ◽  
Clinical Work ◽  
Folic Acid Deficiency ◽  
Acid Deficiency ◽  
Life Threatening ◽  
Neural Tube Development

Abstract Neural tube defects (NTDs) remain one of the most life-threatening birth defects affecting infants. Most patients with a NTDs eventually develop lifelong disability, which cause significant morbidity and mortality and seriously reduce the quality of life. Therefore, identifiable of novel pathogenic strategies for NTDs patients is urgently required. Increasing evidence indicates that METTL3-mediated m6A modification is present in many physiopathological processes of cell apoptosis and survival. Our results demonstrate that SAM play not only a compensatory role, SAM can also lead to m6A modification changes in neural tube development and regulation. This research provides a good theoretical basis for further research on folic acid deficiency leading to NTDs, reveals the important role of SAM in the development of NTDs, and provides new clue for clinical researchers and clinical work.

Neural tube defects, their implications and solutions in Muslim society

2020 ◽  
pp. 1-8
Author(s):  
Muhammad Fayyaz ◽  
Arshad Khushdil ◽  
Shehla Baqai
Keyword(s):  
Folic Acid ◽  
Neural Tube ◽  
Neural Tube Defects ◽  
Time Frame ◽  
Value Systems ◽  
Complex Issue ◽  
Empathic Understanding ◽  
The Given

Abstract Neural Tube Defects (NTDs) are serious congenital abnormalities and most of them are incompatible with life. The extremely debilitating quality of life, if one survives, calls for actions to prevent such sufferings.  Experts agree on the role of Folic Acid in primary prevention of NTDs, yet, despite best efforts, the use of Folic Acid has reduced NTDs by only 50%. These cases too can be prevented by employing secondary preventive measures. These involve timely interruption of pregnancy -- a decision which, in addition to a medical judgment, is based on ethics, social, cultural and Muslim religious value systems in Pakistan. Indeed, it is a complex issue but empathic understanding and strong co-ordination, once established between different disciplines, can help parents to decide and opt for necessary secondary prevention by interruption of malformed foetus within the given time frame mandated by medical and religious authorities. Continuous....

scholarly journals Reducing inequities in preventable neural tube defects: the critical and underutilized role of neurosurgical advocacy for folate fortification

2018 ◽  
Vol 45 (4) ◽  
pp. E20 ◽  
Author(s):  
Dagoberto Estevez-Ordonez ◽  
Matthew C. Davis ◽  
Betsy Hopson ◽  
Anastasia Arynchyna ◽  
Brandon G. Rocque ◽  
...  
Keyword(s):  
Neural Tube ◽  
Neural Tube Defects ◽  
Implementation Strategies ◽  
Indirect Costs ◽  
Childhood Mortality ◽  
High Morbidity ◽  
Disability Adjusted Life ◽  
Life Years

Neural tube defects (NTDs) are one of the greatest causes of childhood mortality and disability-adjusted life years worldwide. Global prevalence at birth is approximately 18.6 per 10,000 live births, with more than 300,000 infants with NTDs born every year. Substantial strides have been made in understanding the genetics, pathophysiology, and surgical treatment of NTDs, yet the natural history remains one of high morbidity and profound impairment of quality of life. Direct and indirect costs of care are enormous, which ensures profound inequities and disparities in the burden of disease in countries of low and moderate resources. All indices of disease burden are higher for NTDs in developing countries. The great tragedy is that the majority of NTDs can be prevented with folate fortification of commercially produced food. Unequivocal evidence of the effectiveness of folate to reduce the incidence of NTDs has existed for more than 25 years. Yet, the most comprehensive surveys of effectiveness of implementation strategies show that more than 100 countries fail to fortify, and consequently only 13% of folate-preventable spina bifida is actually prevented. Neurosurgeons harbor a disproportionate, central, and fundamental role in the management of NTDs and enjoy high standing in society. No organized group in medicine can speak as authoritatively or convincingly. As a result, neurosurgeons and organized neurosurgery harbor disproportionate potential to advocate for more comprehensive folate fortification, and thereby prevent the most common and severe birth defect to impact the human nervous system. Assertive, proactive, informed advocacy for folate fortification should be a central and integral part of the neurosurgical approach to NTDs. Only by making the prevention of dysraphism a priority can we best address the inequities often observed worldwide.

scholarly journals The role of primary cilia in the pathophysiology of neural tube defects

2012 ◽  
Vol 33 (4) ◽  
pp. E2 ◽  
Author(s):  
Timothy W. Vogel ◽  
Calvin S. Carter ◽  
Kingsley Abode-Iyamah ◽  
Qihong Zhang ◽  
Shenandoah Robinson
Keyword(s):  
Neural Tube ◽  
Neural Tube Defects ◽  
Neural Development ◽  
Planar Cell Polarity ◽  
Primary Cilia ◽  
Integration Site ◽  
Genetics Research ◽  
Neural Tube Development ◽  
Insight Into

Neural tube defects (NTDs) are a set of disorders that occur from perturbation of normal neural development. They occur in open or closed forms anywhere along the craniospinal axis and often result from a complex interaction between environmental and genetic factors. One burgeoning area of genetics research is the effect of cilia signaling on the developing neural tube and how the disruption of primary cilia leads to the development of NTDs. Recent progress has implicated the hedgehog (Hh), wingless-type integration site family (Wnt), and planar cell polarity (PCP) pathways in primary cilia as involved in normal neural tube patterning. A set of disorders involving cilia function, known as ciliopathies, offers insight into abnormal neural development. In this article, the authors discuss the common ciliopathies, such as Meckel-Gruber and Joubert syndromes, that are associated with NTDs, and review cilia-related signaling cascades responsible for mammalian neural tube development. Understanding the contribution of cilia in the formation of NTDs may provide greater insight into this common set of pediatric neurological disorders.

Resveratrol: A new potential therapeutic agent for melanoma?

2019 ◽  
Vol 26 ◽  
Author(s):  
Mohamad Hossein Pourhanifeh ◽  
Kazem Abbaszadeh-Goudarzi ◽  
Mohammad Goodarzi ◽  
Sara G.M. Piccirillo ◽  
Alimohammad Shafiee ◽  
...  
Keyword(s):  
Quality Of Life ◽  
Therapeutic Agent ◽  
Current Knowledge ◽  
Treatment Resistance ◽  
Anti Cancer ◽  
Apoptosis Inducer ◽  
Life Threatening ◽  
First Time

: Melanoma is the most life-threatening and aggressive class of skin malignancies. The incidence of melanoma has steadily increased. Metastatic melanoma is greatly resistant to standard anti-melanomatreatments such as chemotherapy, and 5-year survival rate of cases with melanoma who have metastatic form of disease is less than 10%. The contributing role of apoptosis, angiogenesis and autophagy in the pathophysiology of melanoma has been previously demonstrated. Thus, it is extremely urgent to search for complementary therapeutic approachesthat couldenhance the quality of life of subjects and reduce treatment resistance and adverse effects. Resveratrol, known as a polyphenol component present in grapes and some plants, has anti-cancer properties due to its function as an apoptosis inducer in tumor cells, and anti-angiogenic agent to prevent metastasis. However, more clinical trials should be conducted to prove resveratrol efficacy. : Herein, for first time, we summarize current knowledge of anti-cancerous activities of resveratrol in melanoma.

scholarly journals Therapy for myeloproliferative neoplasms: when, which agent, and how?

Hematology ◽  
2014 ◽  
Vol 2014 (1) ◽  
pp. 277-286 ◽  
Author(s):  
Holly L. Geyer ◽  
Ruben A. Mesa
Keyword(s):  
Quality Of Life ◽  
Disease Burden ◽  
Myeloproliferative Neoplasms ◽  
Jak Inhibitors ◽  
Symptom Profiles ◽  
Risk Of Progression ◽  
Life Threatening ◽  
Jak2 Inhibition

Abstract Myeloproliferative neoplasms, including polycythemia vera (PV), essential thrombocythemia, and myelofibrosis (MF) (both primary and secondary), are recognized for their burdensome symptom profiles, life-threatening complications, and risk of progression to acute leukemia. Recent advancements in our ability to diagnose and prognosticate these clonal malignancies have paralleled the development of MPN-targeted therapies that have had a significant impact on disease burden and quality of life. Ruxolitinib has shown success in alleviating the symptomatic burden, reducing splenomegaly and improving quality of life in patients with MF. The role and clinical expectations of JAK2 inhibition continues to expand to a variety of investigational arenas. Clinical trials for patients with MF focus on new JAK inhibitors with potentially less myelosuppression (pacritinib) or even activity for anemia (momelotinib). Further efforts focus on combination trials (including a JAK inhibitor base) or targeting new pathways (ie, telomerase). Similarly, therapy for PV continues to evolve with phase 3 trials investigating optimal frontline therapy (hydroxyurea or IFN) and second-line therapy for hydroxyurea-refractory or intolerant PV with JAK inhibitors. In this chapter, we review the evolving data and role of JAK inhibition (alone or in combination) in the management of patients with MPNs.

scholarly journals Neuropeptide Y (NPY) promotes inflammation-induced tumorigenesis by enhancing epithelial cell proliferation

2017 ◽  
Vol 312 (2) ◽  
pp. G103-G111 ◽  
Author(s):  
Sabrina Jeppsson ◽  
Shanthi Srinivasan ◽  
Bindu Chandrasekharan
Keyword(s):  
Cell Proliferation ◽  
Epithelial Cell ◽  
Neuropeptide Y ◽  
Intestinal Inflammation ◽  
Enteric Neurons ◽  
Intestinal Epithelial ◽  
Epithelial Proliferation ◽  
Proliferation And Apoptosis

We have demonstrated that neuropeptide Y (NPY), abundantly produced by enteric neurons, is an important regulator of intestinal inflammation. However, the role of NPY in the progression of chronic inflammation to tumorigenesis is unknown. We investigated whether NPY could modulate epithelial cell proliferation and apoptosis, and thus regulate tumorigenesis. Repeated cycles of dextran sodium sulfate (DSS) were used to model inflammation-induced tumorigenesis in wild-type (WT) and NPY knockout ( NPY−/−) mice. Intestinal epithelial cell lines (T84) were used to assess the effects of NPY (0.1 µM) on epithelial proliferation and apoptosis in vitro. DSS-WT mice exhibited enhanced intestinal inflammation, polyp size, and polyp number (7.5 ± 0.8) compared with DSS- NPY−/− mice (4 ± 0.5, P < 0.01). Accordingly, DSS-WT mice also showed increased colonic epithelial proliferation (PCNA, Ki67) and reduced apoptosis (TUNEL) compared with DSS- NPY−/− mice. The apoptosis regulating microRNA, miR-375, was significantly downregulated in the colon of DSS-WT (2-fold, P < 0.01) compared with DSS- NPY−/−-mice. In vitro studies indicated that NPY promotes cell proliferation (increase in PCNA and β-catenin, P < 0.05) via phosphatidyl-inositol-3-kinase (PI3-K)-β-catenin signaling, suppressed miR-375 expression, and reduced apoptosis (increase in phospho-Bad). NPY-treated cells also displayed increased c-Myc and cyclin D1, and reduction in p21 ( P < 0.05). Addition of miR-375 inhibitor to cells already treated with NPY did not further enhance the effects induced by NPY alone. Our findings demonstrate a novel regulation of inflammation-induced tumorigenesis by NPY-epithelial cross talk as mediated by activation of PI3-K signaling and downregulation of miR-375. NEW & NOTEWORTHY Our work exemplifies a novel role of neuropeptide Y (NPY) in regulating inflammation-induced tumorigenesis via two modalities: first by enhanced proliferation (PI3-K/pAkt), and second by downregulation of microRNA-375 (miR-375)-dependent apoptosis in intestinal epithelial cells. Our data establish the existence of a microRNA-mediated cross talk between enteric neurons producing NPY and intestinal epithelial cells, and the potential of neuropeptide-regulated miRNAs as potential therapeutic molecules for the management of inflammation-associated tumors in the gut.

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