scholarly journals Metals and molecular carcinogenesis

2020 ◽  
Vol 41 (9) ◽  
pp. 1161-1172 ◽  
Author(s):  
Yusha Zhu ◽  
Max Costa
Keyword(s):  
Molecular Mechanisms ◽  
Metal Exposure ◽  
Future Research ◽  
International Agency ◽  
Post Translational Modification ◽  
Microrna Regulation ◽  
Living Organisms ◽  
Occupational Settings ◽  
Higher Doses ◽  
Group 1

Abstract Many metals are essential for living organisms, but at higher doses they may be toxic and carcinogenic. Metal exposure occurs mainly in occupational settings and environmental contaminations in drinking water, air pollution and foods, which can result in serious health problems such as cancer. Arsenic (As), beryllium (Be), cadmium (Cd), chromium (Cr) and nickel (Ni) are classified as Group 1 carcinogens by the International Agency for Research on Cancer. This review provides a comprehensive summary of current concepts of the molecular mechanisms of metal-induced carcinogenesis and focusing on a variety of pathways, including genotoxicity, mutagenesis, oxidative stress, epigenetic modifications such as DNA methylation, histone post-translational modification and alteration in microRNA regulation, competition with essential metal ions and cancer-related signaling pathways. This review takes a broader perspective and aims to assist in guiding future research with respect to the prevention and therapy of metal exposure in human diseases including cancer.

scholarly journals Fifty Years of Research and One Conclusion: Opium Causes Cancer

2020 ◽  
Vol 23 (11) ◽  
pp. 757-760
Author(s):  
Mahdi Sheikh ◽  
Farin Kamangar ◽  
Reza Malekzadeh
Keyword(s):  
The Body ◽  
Future Research ◽  
International Agency ◽  
Short History ◽  
Important Public Health ◽  
The World ◽  
History Of ◽  
Opium Use ◽  
Group 1

In September 2020, the International Agency for Research on Cancer (IARC) announced that opium consumption causes cancer in humans – a conclusion drawn after reviewing data from five decades of research. Given the widespread use of opium and its derivatives by millions of people across the world, the classification of opium consumption as a "Group 1" carcinogen has important public health ramifications. In this mini-review, we offer a short history of opium use in humans and briefly review the body of research that led to the classification of opium consumption as carcinogenic. We also discuss possible mechanisms of opium’s carcinogenicity and potential avenues for future research.

Citrullination Site Prediction by Incorporating Sequence Coupled Effects into PseAAC and Resolving Data Imbalance Issue

2020 ◽  
Vol 15 (3) ◽  
pp. 235-245 ◽  
Author(s):  
Md. Al Mehedi Hasan ◽  
Md Khaled Ben Islam ◽  
Julia Rahman ◽  
Shamim Ahmad
Keyword(s):  
Molecular Mechanisms ◽  
Performance Metrics ◽  
Arginine Residue ◽  
Post Translational Modification ◽  
Cellular Processes ◽  
Arginine Residues ◽  
Living Organisms ◽  
Matthew’S Correlation Coefficient ◽  
User Friendly ◽  
Fold Cross Validation

Background: Post-translational modification is one of the bio-molecular mechanisms in living organisms, which incorporate functional diversity in proteins as well as regulate cellular processes. Transformation of arginine residue to citrulline in protein is such a modification. Objective: Our objective is to identify citrullinated arginine residue sites quickly and accurately. Methods: In this study, a novel computational tool, abbreviated as predCitru-Site, has been developed to predict citrullination sites. This technique effectively has incorporated the sequencecoupling effect of surrounding amino acids of arginine residues as well as optimizes skewed training citrullination dataset for prediction quality improvement. The performance of predCitru- Site has been measured from the average of 5 complete runs of the 10-fold cross-validation test to comply with existing tools. Results and Conclusion: predCitru-Site has achieved 97.6% sensitivity, 98.9% specificity, and overall accuracy of 98.5%. With Matthew’s correlation coefficient of 0.967, it has also shown an area under the receiver operator characteristics curve of 0.997. Compared with existing tools, predCitru-Site significantly outperforms on the same benchmark dataset. It also shows significant improvement in the case of independent tests in all performance metrics (around 50% higher in AUC). These results suggest that our method is promising and can be used as a complementary technique for fast exploration of citrullination in arginine residue. A user-friendly web server has also been deployed at http://research.ru.ac.bd/predCitru-Site/ for the convenience of experimental scientists.

Dicarbonyl derived post-translational modifications: chemistry bridging biology and aging-related disease

2020 ◽  
Vol 64 (1) ◽  
pp. 97-110
Author(s):  
Christian Sibbersen ◽  
Mogens Johannsen
Keyword(s):  
Mass Spectrometry ◽  
Future Research ◽  
Amino Acid Residues ◽  
Post Translational Modification ◽  
Dicarbonyl Compounds ◽  
Protein Targets ◽  
Post Translational Modifications ◽  
Reactive Protein ◽  
Glycation End Products ◽  
Direct Mass Spectrometry

Abstract In living systems, nucleophilic amino acid residues are prone to non-enzymatic post-translational modification by electrophiles. α-Dicarbonyl compounds are a special type of electrophiles that can react irreversibly with lysine, arginine, and cysteine residues via complex mechanisms to form post-translational modifications known as advanced glycation end-products (AGEs). Glyoxal, methylglyoxal, and 3-deoxyglucosone are the major endogenous dicarbonyls, with methylglyoxal being the most well-studied. There are several routes that lead to the formation of dicarbonyl compounds, most originating from glucose and glucose metabolism, such as the non-enzymatic decomposition of glycolytic intermediates and fructosyl amines. Although dicarbonyls are removed continuously mainly via the glyoxalase system, several conditions lead to an increase in dicarbonyl concentration and thereby AGE formation. AGEs have been implicated in diabetes and aging-related diseases, and for this reason the elucidation of their structure as well as protein targets is of great interest. Though the dicarbonyls and reactive protein side chains are of relatively simple nature, the structures of the adducts as well as their mechanism of formation are not that trivial. Furthermore, detection of sites of modification can be demanding and current best practices rely on either direct mass spectrometry or various methods of enrichment based on antibodies or click chemistry followed by mass spectrometry. Future research into the structure of these adducts and protein targets of dicarbonyl compounds may improve the understanding of how the mechanisms of diabetes and aging-related physiological damage occur.

scholarly journals Molecular Mechanisms of Insulin Resistance in Polycystic Ovary Syndrome: Unraveling the Conundrum in Skeletal Muscle?

2019 ◽  
Vol 104 (11) ◽  
pp. 5372-5381 ◽  
Author(s):  
Nigel K Stepto ◽  
Alba Moreno-Asso ◽  
Luke C McIlvenna ◽  
Kirsty A Walters ◽  
Raymond J Rodgers
Keyword(s):  
Insulin Resistance ◽  
Skeletal Muscle ◽  
Polycystic Ovary Syndrome ◽  
Molecular Mechanisms ◽  
Current Knowledge ◽  
Polycystic Ovary ◽  
Evidence Synthesis ◽  
Basic Research ◽  
Future Research ◽  
Ovary Syndrome

Abstract Context Polycystic ovary syndrome (PCOS) is a common endocrine condition affecting 8% to 13% of women across the lifespan. PCOS affects reproductive, metabolic, and mental health, generating a considerable health burden. Advances in treatment of women with PCOS has been hampered by evolving diagnostic criteria and poor recognition by clinicians. This has resulted in limited clinical and basic research. In this study, we provide insights into the current and future research on the metabolic features of PCOS, specifically as they relate to PCOS-specific insulin resistance (IR), that may affect the most metabolically active tissue, skeletal muscle. Current Knowledge PCOS is a highly heritable condition, yet it is phenotypically heterogeneous in both reproductive and metabolic features. Human studies thus far have not identified molecular mechanisms of PCOS-specific IR in skeletal muscle. However, recent research has provided new insights that implicate energy-sensing pathways regulated via epigenomic and resultant transcriptomic changes. Animal models, while in existence, have been underused in exploring molecular mechanisms of IR in PCOS and specifically in skeletal muscle. Future Directions Based on the latest evidence synthesis and technologies, researchers exploring molecular mechanisms of IR in PCOS, specifically in muscle, will likely need to generate new hypothesis to be tested in human and animal studies. Conclusion Investigations to elucidate the molecular mechanisms driving IR in PCOS are in their early stages, yet remarkable advances have been made in skeletal muscle. Overall, investigations have thus far created more questions than answers, which provide new opportunities to study complex endocrine conditions.

scholarly journals The Sex Determination Cascade in the Silkworm

Genes ◽  
2021 ◽  
Vol 12 (2) ◽  
pp. 315
Author(s):  
Xu Yang ◽  
Kai Chen ◽  
Yaohui Wang ◽  
Dehong Yang ◽  
Yongping Huang
Keyword(s):  
Sex Determination ◽  
Molecular Mechanisms ◽  
Future Research ◽  
Model Species ◽  
Male And Female ◽  
Master Regulators ◽  
Primary Signal ◽  
Basic Understanding ◽  
Female Specific ◽  
Working Mechanisms

In insects, sex determination pathways involve three levels of master regulators: primary signals, which determine the sex; executors, which control sex-specific differentiation of tissues and organs; and transducers, which link the primary signals to the executors. The primary signals differ widely among insect species. In Diptera alone, several unrelated primary sex determiners have been identified. However, the doublesex (dsx) gene is highly conserved as the executor component across multiple insect orders. The transducer level shows an intermediate level of conservation. In many, but not all examined insects, a key transducer role is performed by transformer (tra), which controls sex-specific splicing of dsx. In Lepidoptera, studies of sex determination have focused on the lepidopteran model species Bombyx mori (the silkworm). In B. mori, the primary signal of sex determination cascade starts from Fem, a female-specific PIWI-interacting RNA, and its targeting gene Masc, which is apparently specific to and conserved among Lepidoptera. Tra has not been found in Lepidoptera. Instead, the B. mori PSI protein binds directly to dsx pre-mRNA and regulates its alternative splicing to produce male- and female-specific transcripts. Despite this basic understanding of the molecular mechanisms underlying sex determination, the links among the primary signals, transducers and executors remain largely unknown in Lepidoptera. In this review, we focus on the latest findings regarding the functions and working mechanisms of genes involved in feminization and masculinization in Lepidoptera and discuss directions for future research of sex determination in the silkworm.

scholarly journals Molecular mechanisms underlying curcumin-mediated microRNA regulation in carcinogenesis; Focused on gastrointestinal cancers

2021 ◽  
Vol 141 ◽  
pp. 111849
Author(s):  
Abolfazl Akbari ◽  
Meghdad Sedaghat ◽  
Javad Heshmati ◽  
Seidamir Pasha Tabaeian ◽  
Sadegh Dehghani ◽  
...  
Keyword(s):  
Molecular Mechanisms ◽  
Gastrointestinal Cancers ◽  
Microrna Regulation

scholarly journals Adiponectin and its receptors in patients with cardiovascular disease

2021 ◽  
Vol 28 (Supplement_1) ◽  
Author(s):  
E Belik ◽  
OV Gruzdeva ◽  
YUA Dyleva ◽  
EG Uchasova ◽  
MYU Sinitsky ◽  
...  
Keyword(s):  
Heart Defects ◽  
Post Translational Modification ◽  
Fat Depots ◽  
Funding Sources ◽  
Adiponectin Mrna ◽  
Fat Stores ◽  
Group 2 ◽  
High Level ◽  
Group 1

Abstract Funding Acknowledgements Type of funding sources: None. Aim to determine the features of adiponectin expression, secretion of adiponectin and its receptors in local fat depots in CVD. Materials and methods The study included 90 patients with СAD (Group 1) and 60 patients with heart defects (Group 2). Adipocytes were isolated from samples of subcutaneous (SAT), epicardial (EAT) and perivascular (PVAT) adipose tissue obtained during CABG or heart valve replacement. The expression of adiponectin was determined by qPCR using TaqManTM Gene Expression Assays (Applied Biosystems, USA) in the ViiA 7 Real-Time PCR System (Applied Biosystems, USA), the levels of expression products was determined using enzyme immunoassay (Bender MedSystems GmbH, Vienna, Austria). The data were analyzed using the statistical software Statistica 9.0. Results EAT adipocytes were characterized by the lowest adiponectin expression relative to adipocytes of other localization both in Group 1 and Group 2. In patients Group 1 adiponectin expression in EAT was reduced relative in SAT and PVAT (by 1.2 and 1.5 times). In Group 2, the adiponectin mRNA in the EAT was lower than in the SAT and PVAT (1.4 and 1.5 times). The expression of adiponectin in EAT in Group 2 exceeded the same indicator in Group 1 by 1.2 times. The maximum expression of adiponectin was observed in the PVAT culture in patients of both groups. For Group 2, this indicator exceeded the values of Group 1 by 1.2 times. The content of adiponectin in the culture EAT was lower than in the SAT, both in Group 1 and Group 2 (by 1.3 and 1.13 times). The level of this indicator in Group 2 was 1.4 times higher than in Group 1. PVAT adipocytes of patients with CAD were characterized by the lowest level of adiponectin secretion in comparison with adipocytes of other localization. The adiponectin level in the PVAT of Group 2 exceeded that of fat stores of other localization and in Group 1 patients by 1.8 times. There were no statistically significant differences in the expression and concentration of adiponectin in the culture of adipocytes of the SAT between the groups of patients. In Group 1, the lowest level of AdipoR1 was found in the adipocyte culture of the PVAT. Noteworthy is the decrease in the level of AdipoR1 in Group 1 compared to the level of Group 2, observed in the SAT and PVAT: 1.3 and 1.5 times. There were no significant differences in the concentration of the AdipoR1 in the EAT, as well as AdipoR2 in all types of AT between the groups of patients. Conclusion: in CVD the EAT is characterized by minimal expression and secretion of adiponectin, regardless of nosology. In CAD despite the high level of expression of adiponectin, the adipocytes of the PVAT were found to have the lowest content in comparison with adipocytes of other localization. Dysregulation of the adiponectin/AdipoR axis is observed in PVAT, which may be due to low expression of adiponectin receptors and long-term processes of its post-translational modification and oligomerization in CAD.

scholarly journals Recent Advances in Nanotechnology with Nano-Phytochemicals: Molecular Mechanisms and Clinical Implications in Cancer Progression

2021 ◽  
Vol 22 (7) ◽  
pp. 3571
Author(s):  
Bonglee Kim ◽  
Ji-Eon Park ◽  
Eunji Im ◽  
Yongmin Cho ◽  
Jinjoo Lee ◽  
...  
Keyword(s):  
Cancer Progression ◽  
Animal Studies ◽  
Molecular Mechanisms ◽  
Future Research ◽  
Clinical Implications ◽  
Research Perspectives ◽  
Current Review ◽  
Gold Silver ◽  
Significant Efficacy ◽  
Rapid Clearance

Biocompatible nanoparticles (NPs) containing polymers, lipids (liposomes and micelles), dendrimers, ferritin, carbon nanotubes, quantum dots, ceramic, magnetic materials, and gold/silver have contributed to imaging diagnosis and targeted cancer therapy. However, only some NP drugs, including Doxil® (liposome-encapsulated doxorubicin), Abraxane® (albumin-bound paclitaxel), and Oncaspar® (PEG-Asparaginase), have emerged on the pharmaceutical market to date. By contrast, several phytochemicals that were found to be effective in cultured cancer cells and animal studies have not shown significant efficacy in humans due to poor bioavailability and absorption, rapid clearance, resistance, and toxicity. Research to overcome these drawbacks by using phytochemical NPs remains in the early stages of clinical translation. Thus, in the current review, we discuss the progress in nanotechnology, research milestones, the molecular mechanisms of phytochemicals encapsulated in NPs, and clinical implications. Several challenges that must be overcome and future research perspectives are also described.

scholarly journals Feedback Regulation of O-GlcNAc Transferase through Translation Control to Maintain Intracellular O-GlcNAc Homeostasis

2021 ◽  
Vol 22 (7) ◽  
pp. 3463
Author(s):  
Chia-Hung Lin ◽  
Chen-Chung Liao ◽  
Mei-Yu Chen ◽  
Teh-Ying Chou
Keyword(s):  
Molecular Mechanisms ◽  
Mrna Level ◽  
Feedback Regulation ◽  
Translation Initiation Factor ◽  
Initiation Factor ◽  
Cell Physiology ◽  
Hydroxyl Groups ◽  
Post Translational Modification ◽  
Translation Control ◽  
Glcnac Transferase

Protein O-GlcNAcylation is a dynamic post-translational modification involving the attachment of N-acetylglucosamine (GlcNAc) to the hydroxyl groups of Ser/Thr residues on numerous nucleocytoplasmic proteins. Two enzymes are responsible for O-GlcNAc cycling on substrate proteins: O-GlcNAc transferase (OGT) catalyzes the addition while O-GlcNAcase (OGA) helps the removal of GlcNAc. O-GlcNAcylation modifies protein functions; therefore, dysregulation of O-GlcNAcylation affects cell physiology and contributes to pathogenesis. To maintain homeostasis of cellular O-GlcNAcylation, there exists feedback regulation of OGT and OGA expression responding to fluctuations of O-GlcNAc levels; yet, little is known about the molecular mechanisms involved. In this study, we investigated the O-GlcNAc-feedback regulation of OGT and OGA expression in lung cancer cells. Results suggest that, upon alterations in O-GlcNAcylation, the regulation of OGA expression occurs at the mRNA level and likely involves epigenetic mechanisms, while modulation of OGT expression is through translation control. Further analyses revealed that the eukaryotic translation initiation factor 4E-binding protein 1 (4E-BP1) contributes to the downregulation of OGT induced by hyper-O-GlcNAcylation; the S5A/S6A O-GlcNAcylation-site mutant of 4E-BP1 cannot support this regulation, suggesting an important role of O-GlcNAcylation. The results provide additional insight into the molecular mechanisms through which cells may fine-tune intracellular O-GlcNAc levels to maintain homeostasis.

The role of heredity in cancer.

1989 ◽  
Vol 7 (4) ◽  
pp. 527-540 ◽  
Author(s):  
E G Levine ◽  
R A King ◽  
C D Bloomfield
Keyword(s):  
Molecular Mechanisms ◽  
Familial Cancer ◽  
Tumor Development ◽  
Future Research ◽  
Minor Role ◽  
Research Activity ◽  
Environmental Interactions ◽  
Future Research Directions ◽  
A Minor

Heredity is generally felt to play a minor role in the development of cancer. This review critically examines this assumption. Topics discussed include evidence for heritable predisposition in animals and humans; the potential importance of genetic-environmental interactions; approaches that are being used to successfully locate genes responsible for heritable predisposition; comparability of genetic findings among heritable and corresponding sporadic malignancies; and future research directions. Breast, colon, and lung cancer are used to exemplify clinical and research activity in familial cancer; clinical phenotypes, segregation and linkage analyses, models for environmental interactions with inherited traits, and molecular mechanisms of tumor development are discussed. We conclude that the contribution of heredity to the cancer burden is greater than generally accepted, and that study of heritable predisposition will continue to reveal carcinogenic mechanisms important to the development of all cancers.

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