scholarly journals Epigenetic modification and a role for the E3 ligase RNF40 in cancer development and metastasis

Oncogene ◽  
2020 ◽  
Author(s):  
Junjiang Fu ◽  
Li Liao ◽  
Kyathegowdanadoddi Srinivasa Balaji ◽  
Chunli Wei ◽  
Jaehoon Kim ◽  
...  
Keyword(s):  
Current Knowledge ◽  
Epigenetic Modification ◽  
Ring Finger ◽  
Public Health Problem ◽  
Cancer Therapeutics ◽  
Cancer Prognosis ◽  
Cancer Development ◽  
Major Public Health Problem ◽  
Histone H2b ◽  
Nonhistone Proteins

AbstractRNF40 (OMIM: 607700) is a really interesting new gene (RING) finger E3 ubiquitin ligase containing multiple coiled-coil domains and a C-terminal RING finger motif, which engage in protein–DNA and protein–protein interactions. RNF40 encodes a polypeptide of 1001 amino acids with a predicted molecular mass of 113,678 Da. RNF40 and its paralog RNF20 form a stable heterodimer complex that can monoubiquitylate histone H2B at lysine 120 as well as other nonhistone proteins. Cancer is a major public health problem and the second leading cause of death. Through its protein ubiquitylation activity, RNF40 acts as a tumor suppressor or oncogene to play major epigenetic roles in cancer development, progression, and metastasis, highlighting the essential function of RNF40 and the importance of studying it. In this review, we summarize current knowledge about RNF40 gene structure and the role of RNF40 in histone H2B monoubiquitylation, DNA damage repair, apoptosis, cancer development, and metastasis. We also underscore challenges in applying this information to cancer prognosis and prevention and highlight the urgent need for additional investigations of RNF40 as a potential target for cancer therapeutics.

scholarly journals A Review of Cardiovascular Toxicity of Microcystins

Toxins ◽  
2019 ◽  
Vol 11 (9) ◽  
pp. 507 ◽  
Author(s):  
Linghui Cao ◽  
Isaac Yaw Massey ◽  
Hai Feng ◽  
Fei Yang
Keyword(s):  
Cardiovascular Health ◽  
Environmental Concern ◽  
Current Knowledge ◽  
Public Health Problem ◽  
Cyanobacterial Blooms ◽  
Major Public Health Problem ◽  
Cardiovascular Toxicity ◽  
Secondary Products ◽  
Global Environmental ◽  
Global Environmental Concern

The mortality rate of cardiovascular diseases (CVD) in China is on the rise. The increasing burden of CVD in China has become a major public health problem. Cyanobacterial blooms have been recently considered a global environmental concern. Microcystins (MCs) are the secondary products of cyanobacteria metabolism and the most harmful cyanotoxin found in water bodies. Recent studies provide strong evidence of positive associations between MC exposure and cardiotoxicity, representing a threat to human cardiovascular health. This review focuses on the effects of MCs on the cardiovascular system and provides some evidence that CVD could be induced by MCs. We summarized the current knowledge of the cardiovascular toxicity of MCs, with regard to direct cardiovascular toxicity and indirect cardiovascular toxicity. Toxicity of MCs is mainly governed by the increasing level of reactive oxygen species (ROS), oxidative stress in mitochondria and endoplasmic reticulum, the inhibition activities of serine/threonine protein phosphatase 1 (PP1) and 2A (PP2A) and the destruction of cytoskeletons, which finally induce the occurrence of CVD. To protect human health from the threat of MCs, this paper also puts forward some directions for further research.

scholarly journals Histone H2B monoubiquitination: roles to play in human malignancy

2014 ◽  
Vol 22 (1) ◽  
pp. T19-T33 ◽  
Author(s):  
Alexander J Cole ◽  
Roderick Clifton-Bligh ◽  
Deborah J Marsh
Keyword(s):  
Dna Damage ◽  
Current Knowledge ◽  
Ring Finger ◽  
Stem Cell Differentiation ◽  
Open Chromatin ◽  
Post Translational Modification ◽  
Histone H2b ◽  
Human Malignancy ◽  
Damage Response ◽  
Specific Protease

Ubiquitination has traditionally been viewed in the context of polyubiquitination that is essential for marking proteins for degradation via the proteasome. Recent discoveries have shed light on key cellular roles for monoubiquitination, including as a post-translational modification (PTM) of histones such as histone H2B. Monoubiquitination plays a significant role as one of the largest histone PTMs, alongside smaller, better-studied modifications such as methylation, acetylation and phosphorylation. Monoubiquitination of histone H2B at lysine 120 (H2Bub1) has been shown to have key roles in transcription, the DNA damage response and stem cell differentiation. The H2Bub1 enzymatic cascade involves E3 RING finger ubiquitin ligases, with the main E3 generally accepted to be the RNF20–RNF40 complex, and deubiquitinases including ubiquitin-specific protease 7 (USP7), USP22 and USP44. H2Bub1 has been shown to physically disrupt chromatin strands, fostering a more open chromatin structure accessible to transcription factors and DNA repair proteins. It also acts as a recruiting signal, actively attracting proteins with roles in transcription and DNA damage. H2Bub1 also appears to play central roles in histone cross-talk, influencing methylation events on histone H3, including H3K4 and H3K79. Most significantly, global levels of H2Bub1 are low to absent in advanced cancers including breast, colorectal, lung and parathyroid, marking H2Bub1 and the enzymes that regulate it as key molecules of interest as possible new therapeutic targets for the treatment of cancer. This review offers an overview of current knowledge regarding H2Bub1 and highlights links between dysregulation of H2Bub1-associated enzymes, stem cells and malignancy.

scholarly journals The Relevance of MicroRNAs in the Pathogenesis and Prognosis of HCV-Disease: The Emergent Role of miR-17-92 in Cryoglobulinemic Vasculitis

Viruses ◽  
2020 ◽  
Vol 12 (12) ◽  
pp. 1364
Author(s):  
Serena Lorini ◽  
Laura Gragnani ◽  
Anna Linda Zignego
Keyword(s):  
Gene Expression ◽  
Molecular Mechanisms ◽  
Current Knowledge ◽  
Public Health Problem ◽  
Lymphoproliferative Disorders ◽  
Major Public Health Problem ◽  
Cryoglobulinemic Vasculitis ◽  
Association Analyses ◽  
Non Invasive

Hepatitis C virus (HCV) is a major public health problem. HCV is a hepatotropic and lymphotropic virus that leads to hepatocellular carcinoma (HCC) and lymphoproliferative disorders such as cryoglobulinemic vasculitis (CV) and non-Hodgkin’s lymphoma (NHL). The molecular mechanisms by which HCV induces these diseases are not fully understood. MicroRNAs (miRNAs) are small non-coding molecules that negatively regulate post-transcriptional gene expression by decreasing their target gene expression. We will attempt to summarize the current knowledge on the role of miRNAs in the HCV life cycle, HCV-related HCC, and lymphoproliferative disorders, focusing on both the functional effects of their deregulation as well as on their putative role as biomarkers, based on association analyses. We will also provide original new data regarding the miR 17-92 cluster in chronically infected HCV patients with and without lymphoproliferative disorders who underwent antiviral therapy. All of the cluster members were significantly upregulated in CV patients compared to patients without CV and significantly decreased in those who achieved vasculitis clinical remission after viral eradication. To conclude, miRNAs play an important role in HCV infection and related oncogenic processes, but their molecular pathways are not completely clear. In some cases, they may be potential therapeutic targets or non-invasive biomarkers of tumor progression.

scholarly journals Physical inactivity, and its association with hypertension among employees in the district of Colombo

2021 ◽  
Vol 21 (1) ◽  
Author(s):  
A. U. Gamage ◽  
R. de A. Seneviratne
Keyword(s):  
Physical Activity ◽  
Sri Lanka ◽  
Physical Inactivity ◽  
Current Knowledge ◽  
Public Health Problem ◽  
Energy Utilization ◽  
Major Public Health Problem ◽  
Total Transport ◽  
Commuting Distance ◽  
Physically Inactive

Abstract Background Physical inactivity is a leading cause of morbidity and mortality and is a major public health problem. Insufficient activity is responsible for a large proportion of non-communicable diseases such as hypertension. Objectives The purpose of this study was to assess socioeconomic variations in physical activity and to measure the association between physical inactivity and hypertension among government officials in Sri Lanka. Methods A cross-sectional study was carried out among 275 senior-officers(SOs) and 760 managerial-assistants(MAs) aged 30–60 years and attached to Public Administration institutions in Colombo District in Sri Lanka. Physical-activity(PA) was gathered using the International Physical Activity Questionnaire(IPAQ) adopted and validated to the Sri Lankan context. Blood pressure(measured and classified using JNC-7 guidelines) and anthropometric indices were recorded. Energy utilization of all vigorous and moderated PA and walking was expressed as metabolic-equivalent-of-task(MET) min per week. A total-MET-score was calculated and categorized based on IPAQ guidelines. Results Socioeconomic variations in PA levels were observed as 58.1%(n = 158) SOs and 30.6%(n = 226) MAs were involved in inadequate PA. Among the SOs diagnosed with hypertension, more half(59.1%; n = 52) were physically inactive, while among MAs, 65.9%(n = 143) with hypertension were physically inactive. After adjusting for potential confounding factors being physically inactive was associated with a higher risk of hypertension among SOs[OR 2.08 [95% CI 1.07, 4.6] and MAs[OR 2.8 [95% CI 1.8, 4.6]. The main modality of commuting to work for SOs(59%) was private transport, and MAs(64%) public transport Commuting distance was positively correlated(p < 0.05) with total transport MET among SOs and MAs. After adjusting for confounders, commuting distance of > 20 km was found to lower the odds of hypertension among SOs and MAs(OR = 0.713; 95% CI 0.4 to1.3; and OR = 0.63; 95% CI 0.46 to 0.87). Conclusion Despite the current knowledge that being physically active promotes health, the practice was different. Physical inactivity was associated with hypertension and prevalent among both SOs and MAs. Higher commuting distance is positively correlated with total transport MET and associated with lower odds of hypertension among SOs and MAs. Longitudinal studies are required to provide a causative association between physical inactivity and hypertension among these employees.

scholarly journals The Arcuate Nucleus of the Hypothalamus and Metabolic Regulation: An Emerging Role for Renin–Angiotensin Pathways

2021 ◽  
Vol 22 (13) ◽  
pp. 7050
Author(s):  
Darren Mehay ◽  
Yuval Silberman ◽  
Amy C. Arnold
Keyword(s):  
Blood Pressure ◽  
Energy Balance ◽  
Arcuate Nucleus ◽  
Current Knowledge ◽  
Public Health Problem ◽  
Renin Angiotensin System ◽  
Major Public Health Problem ◽  
Angiotensin System ◽  
Renin Angiotensin ◽  
The Metabolic Syndrome

Obesity is a chronic state of energy imbalance that represents a major public health problem and greatly increases the risk for developing hypertension, hyperglycemia, and a multitude of related pathologies that encompass the metabolic syndrome. The underlying mechanisms and optimal treatment strategies for obesity, however, are still not fully understood. The control of energy balance involves the actions of circulating hormones on a widely distributed network of brain regions involved in the regulation of food intake and energy expenditure, including the arcuate nucleus of the hypothalamus. While obesity is known to disrupt neurocircuits controlling energy balance, including those in the hypothalamic arcuate nucleus, the pharmacological targeting of these central mechanisms often produces adverse cardiovascular and other off-target effects. This highlights the critical need to identify new anti-obesity drugs that can activate central neurocircuits to induce weight loss without negatively impacting blood pressure control. The renin–angiotensin system may provide this ideal target, as recent studies show this hormonal system can engage neurocircuits originating in the arcuate nucleus to improve energy balance without elevating blood pressure in animal models. This review will summarize the current knowledge of renin–angiotensin system actions within the arcuate nucleus for control of energy balance, with a focus on emerging roles for angiotensin II, prorenin, and angiotensin-(1–7) pathways.

Knowledge of emergency management of avulsed tooth among intern dental students: a questionnaire based study

2018 ◽  
Vol 0 (0) ◽  
Author(s):  
Neha Jain ◽  
Adepu Srilatha ◽  
Dolar Doshi ◽  
Abhilasha Nellutla ◽  
Khwaja Shoeb Alam
Keyword(s):  
Current Knowledge ◽  
Public Health Problem ◽  
Knowledge Score ◽  
Dental Students ◽  
Research Centre ◽  
Dental Student ◽  
Major Public Health Problem ◽  
Chi Squared ◽  
Student Interns ◽  
Dental Injuries

Abstract Background Traumatic dental injuries (TDIs) represent a major public health problem because of their increasing prevalence and psychosocial impact. Avulsion, one of the most complicated TDIs comprising of 1–16% of all injuries. The present study aimed to assess the current knowledge regarding management of avulsed teeth among dental interns in the city of Hyderabad. Subjects Dental interns of the Panineeya Institute of Dental Sciences and Research Centre, Hyderabad. Method A validated, self-administered 23-item questionnaire was used to obtain demographic details and data on dental avulsion management. Descriptive analyses were carried out on frequency, and a comparison of knowledge score was carried out using a chi-squared test and an independent t-test. Results More than half of the study subjects gave correct responses for most of the items on knowledge regarding avulsion. Around 45.4% of the study populations were categorized with low levels of correct knowledge, with more females (46.6%) having significantly lower levels compared to males (p = 0.03). However, the mean knowledge scores between males (15.5 ± 4.74) and females (16.5 ± 1.68) were comparable (p = 0.15). Conclusion Based on the findings of the study, a majority of dental student interns were aware of the basic procedures to be followed in cases of avulsion.

scholarly journals Leishmania, microbiota and sand fly immunity

Parasitology ◽  
2018 ◽  
Vol 145 (10) ◽  
pp. 1336-1353 ◽  
Author(s):  
Erich Loza Telleria ◽  
Andrea Martins-da-Silva ◽  
Antonio Jorge Tempone ◽  
Yara Maria Traub-Csekö
Keyword(s):  
Public Health ◽  
Immune Responses ◽  
Current Knowledge ◽  
Public Health Problem ◽  
Sand Fly ◽  
Gut Contents ◽  
Host Immune System ◽  
Major Public Health Problem ◽  
Sand Flies ◽  
Public Health Importance

AbstractIn this review, we explore the state-of-the-art of sand fly relationships with microbiota, viruses and Leishmania, with particular emphasis on the vector immune responses. Insect-borne diseases are a major public health problem in the world. Phlebotomine sand flies are proven vectors of several aetiological agents including viruses, bacteria and the trypanosomatid Leishmania, which are responsible for diseases such as viral encephalitis, bartonellosis and leishmaniasis, respectively. All metazoans in nature coexist intimately with a community of commensal microorganisms known as microbiota. The microbiota has a fundamental role in the induction, maturation and function of the host immune system, which can modulate host protection from pathogens and infectious diseases. We briefly review viruses of public health importance present in sand flies and revisit studies done on bacterial and fungal gut contents of these vectors. We bring this information into the context of sand fly development and immune responses. We highlight the immunity mechanisms that the insect utilizes to survive the potential threats involved in these interactions and discuss the recently discovered complex interactions among microbiota, sand fly, Leishmania and virus. Additionally, some of the alternative control strategies that could benefit from the current knowledge are considered.

scholarly journals Pathway-Based Drug-Repurposing Schemes in Cancer: The Role of Translational Bioinformatics

2021 ◽  
Vol 10 ◽  
Author(s):  
Enrique Hernández-Lemus ◽  
Mireya Martínez-García
Keyword(s):  
Public Health Problem ◽  
Cancer Therapeutics ◽  
Response To Therapy ◽  
Driver Mutations ◽  
Multi Drug Resistance ◽  
Multidisciplinary Teams ◽  
Major Public Health Problem ◽  
Translational Bioinformatics ◽  
Driver Genes ◽  
Silver Bullet

Cancer is a set of complex pathologies that has been recognized as a major public health problem worldwide for decades. A myriad of therapeutic strategies is indeed available. However, the wide variability in tumor physiology, response to therapy, added to multi-drug resistance poses enormous challenges in clinical oncology. The last years have witnessed a fast-paced development of novel experimental and translational approaches to therapeutics, that supplemented with computational and theoretical advances are opening promising avenues to cope with cancer defiances. At the core of these advances, there is a strong conceptual shift from gene-centric emphasis on driver mutations in specific oncogenes and tumor suppressors—let us call that the silver bullet approach to cancer therapeutics—to a systemic, semi-mechanistic approach based on pathway perturbations and global molecular and physiological regulatory patterns—we will call this the shrapnel approach. The silver bullet approach is still the best one to follow when clonal mutations in driver genes are present in the patient, and when there are targeted therapies to tackle those. Unfortunately, due to the heterogeneous nature of tumors this is not the common case. The wide molecular variability in the mutational level often is reduced to a much smaller set of pathway-based dysfunctions as evidenced by the well-known hallmarks of cancer. In such cases “shrapnel gunshots” may become more effective than “silver bullets”. Here, we will briefly present both approaches and will abound on the discussion on the state of the art of pathway-based therapeutic designs from a translational bioinformatics and computational oncology perspective. Further development of these approaches depends on building collaborative, multidisciplinary teams to resort to the expertise of clinical oncologists, oncological surgeons, and molecular oncologists, but also of cancer cell biologists and pharmacologists, as well as bioinformaticians, computational biologists and data scientists. These teams will be capable of engaging on a cycle of analyzing high-throughput experiments, mining databases, researching on clinical data, validating the findings, and improving clinical outcomes for the benefits of the oncological patients.

scholarly journals The Interactions Between HBV and the Innate Immunity of Hepatocytes

Viruses ◽  
2020 ◽  
Vol 12 (3) ◽  
pp. 285 ◽  
Author(s):  
Fayed Attia Koutb Megahed ◽  
Xiaoling Zhou ◽  
Pingnan Sun
Keyword(s):  
Innate Immunity ◽  
Hepatitis B ◽  
Current Knowledge ◽  
Hepatitis B Surface Antigen ◽  
Deep Understanding ◽  
Public Health Problem ◽  
Hbv Infection ◽  
Major Public Health Problem ◽  
Immune Recognition

Hepatitis B virus (HBV) infection affects ~350 million people and poses a major public health problem worldwide. HBV is a major cause of cirrhosis and hepatocellular carcinoma. Fewer than 5% of HBV-infected adults (but up to 90% of HBV-infected infants and children) develop chronic HBV infection as indicated by continued, detectable expression of hepatitis B surface antigen (HBsAg) for at least 6 months after the initial infection. Increasing evidence indicates that HBV interacts with innate immunity signaling pathways of hepatocytes to suppress innate immunity. However, it is still not clear how HBV avoids monitoring by the innate immunity of hepatocytes and whether the innate immunity of hepatocytes can be effective against HBV if re-triggered. Moreover, a deep understanding of virus–host interactions is important in developing new therapeutic strategies for the treatment of HBV infection. In this review, we summarize the current knowledge regarding how HBV represses innate immune recognition, as well as recent progress with respect to in vitro models for studying HBV infection and innate immunity.

Substance Abuse and Drug-Related Death, Suicidal Ideation, and Suicide: A Review

Crisis ◽  
1999 ◽  
Vol 20 (1) ◽  
pp. 28-35 ◽  
Author(s):  
Annie Mino ◽  
Arnaud Bousquet ◽  
Barbara Broers
Keyword(s):  
Public Health ◽  
Risk Factors ◽  
Substance Abuse ◽  
Suicidal Ideation ◽  
Family Support ◽  
Drug Users ◽  
Suicide Attempts ◽  
Public Health Problem ◽  
Major Public Health Problem ◽  
Hiv Epidemic

The high mortality rate among drug users, which is partly due to the HIV epidemic and partly due to drug-related accidental deaths and suicides, presents a major public health problem. Knowing more about prevalence, incidence, and risk factors is important for the development of rational preventive and therapeutic programs. This article attempts to give an overview of studies of the relations between substance abuse, suicidal ideation, suicide, and drug-related death. Research in this field is hampered by the absence of clear definitions, and results of studies are rarely comparable. There is, however, consensus about suicidal ideation being a risk factor for suicide attempts and suicide. Suicidal ideation is also a predictor of suicide, especially among drug users. It is correlated with an absence of family support, with the severity of the psychosocial dysfunctioning, and with multi-drug abuse, but also with requests for treatment. Every clinical examination of a drug user, not only of those who are depressed, should address the possible presence of suicidal ideation, as well as its intensity and duration.

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