scholarly journals Epigenetics and Signaling Pathways in Glaucoma

2017 ◽  
Vol 2017 ◽  
pp. 1-12 ◽  
Author(s):  
Angela C. Gauthier ◽  
Ji Liu
Keyword(s):  
Gene Expression ◽  
Animal Models ◽  
Rho Kinase ◽  
Therapeutic Agents ◽  
Retinal Neurons ◽  
Common Cause ◽  
Increased Risk ◽  
Genetic And Environmental Factors ◽  
Proapoptotic Gene ◽  
Novel Therapeutic

Glaucoma is the most common cause of irreversible blindness worldwide. This neurodegenerative disease becomes more prevalent with aging, but predisposing genetic and environmental factors also contribute to increased risk. Emerging evidence now suggests that epigenetics may also be involved, which provides potential new therapeutic targets. These three factors work through several pathways, including TGF-β, MAP kinase, Rho kinase, BDNF, JNK, PI-3/Akt, PTEN, Bcl-2, Caspase, and Calcium-Calpain signaling. Together, these pathways result in the upregulation of proapoptotic gene expression, the downregulation of neuroprotective and prosurvival factors, and the generation of fibrosis at the trabecular meshwork, which may block aqueous humor drainage. Novel therapeutic agents targeting these pathway members have shown preliminary success in animal models and even human trials, demonstrating that they may eventually be used to preserve retinal neurons and vision.

scholarly journals Prognostic molecular biomarkers in diffuse large B-cell lymphoma in the rituximab era and their therapeutic implications

2021 ◽  
Vol 12 ◽  
pp. 204062072110139
Author(s):  
Sotirios G. Papageorgiou ◽  
Thomas P. Thomopoulos ◽  
Ioannis Katagas ◽  
Anthi Bouchla ◽  
Vassiliki Pappa
Keyword(s):  
Gene Expression ◽  
Clinical Practice ◽  
B Cell ◽  
Cell Lymphoma ◽  
Expression Profiles ◽  
B Cell Lymphoma ◽  
Therapeutic Agents ◽  
Large B Cell Lymphoma ◽  
Large B Cell ◽  
Novel Therapeutic

Diffuse large B-cell lymphoma (DLBCL) represents a group of tumors characterized by substantial heterogeneity in terms of their pathological and biological features, a causal factor of their varied clinical outcome. This variation has persisted despite the implementation of rituximab in treatment regimens over the last 20 years. In this context, prognostic biomarkers are of great importance in order to identify high-risk patients that might benefit from treatment intensification or the introduction of novel therapeutic agents. Herein, we review current knowledge on specific immunohistochemical or genetic biomarkers that might be useful in clinical practice. Gene-expression profiling is a tool of special consideration in this effort, as it has enriched our understanding of DLBCL biology and has allowed for the classification of DLBCL by cell-of-origin as well as by more elaborate molecular signatures based on distinct gene-expression profiles. These subgroups might outperform individual biomarkers in terms of prognostication; however, their use in clinical practice is still limited. Moreover, the underappreciated role of the tumor microenvironment in DLBCL prognosis is discussed in terms of prognostic gene-expression signatures, as well as in terms of individual biomarkers of prognostic significance. Finally, the efficacy of novel therapeutic agents for the treatment of DLBCL patients are discussed and an evidence-based therapeutic approach by specific genetic subgroup is suggested.

scholarly journals Febrile Seizures: Current Views and Investigations

2009 ◽  
Vol 36 (6) ◽  
pp. 679-686 ◽  
Author(s):  
Aylin Y. Reid ◽  
Michael A. Galic ◽  
G. Campbell Teskey ◽  
Quentin J. Pittman
Keyword(s):  
Animal Models ◽  
Current Literature ◽  
Growth And Development ◽  
Animal Studies ◽  
Pediatric Population ◽  
Febrile Seizures ◽  
Long Term Effects ◽  
Common Cause ◽  
Increased Risk

Febrile seizures (FSs) are seizures that occur during fever, usually at the time of a cold or flu, and represent the most common cause of seizures in the pediatric population. Up to 5% of children between the ages of six months and five years-of-age will experience a FS. Clinically these seizures are categorized as benign events with little impact on the growth and development of the child. However, studies have linked the occurrence of FSs to an increased risk of developing adult epileptic disorders. There are many unanswered questions about FSs, such as the mechanism of their generation, the long-term effects of these seizures, and their role in epileptogenesis. Answers are beginning to emerge based on results from animal studies. This review summarizes the current literature on animal models of FSs, mechanisms underlying the seizures, and functional, structural, and molecular changes that may result from them.

Animal models in antihypertensive drug development research

2020 ◽  
Vol 1 (2) ◽  
Author(s):  
Dwi Aris Agung Nugrahaningsih ◽  
Mia Munawarroh Yuniyanti ◽  
Rahmi Ayu Wijayaningsih ◽  
Mosa Rini Nurul Hidayati ◽  
Setyo Purwono
Keyword(s):  
Animal Model ◽  
Animal Models ◽  
Drug Development ◽  
Antihypertensive Drug ◽  
Therapeutic Agents ◽  
Development Research ◽  
The World ◽  
Drug Development Research ◽  
Different Characteristics ◽  
Novel Therapeutic

Hypertension is one of the most common diseases in the world. However, its pathogenesis is not fully understood and its treatment is not yet satisfying. Animal models of hypertension have been useful to understand the pathogenesis of hypertension and to test novel therapeutic agents. There are several kinds of hypertension animal models. Each model has different characteristics. Knowing the characteristic of each model is important to obtain valid research. This review will describe several available methods to develop animal model for hypertension.

Reductionist thinking and animal models in neuropsychiatric research

2019 ◽  
Vol 42 ◽  
Author(s):  
Nicole M. Baran
Keyword(s):  
Animal Models ◽  
Mental Disorders ◽  
Environmental Factors ◽  
Neuropsychiatric Disorders ◽  
Model Organisms ◽  
Developmental Genetic ◽  
Term Study ◽  
Genetic And Environmental Factors ◽  
Mechanisms Of Plasticity

AbstractReductionist thinking in neuroscience is manifest in the widespread use of animal models of neuropsychiatric disorders. Broader investigations of diverse behaviors in non-model organisms and longer-term study of the mechanisms of plasticity will yield fundamental insights into the neurobiological, developmental, genetic, and environmental factors contributing to the “massively multifactorial system networks” which go awry in mental disorders.

Male Osteoporosis

2013 ◽  
Vol 22 (04) ◽  
pp. 260-266 ◽  
Author(s):  
S. P. Tuck ◽  
R. M. Francis ◽  
B. C. Hanusch
Keyword(s):  
Prostate Cancer ◽  
Older Men ◽  
Good Evidence ◽  
Male Osteoporosis ◽  
Fracture Rate ◽  
Common Cause ◽  
Increased Risk ◽  
Osteoporosis In Men ◽  
Considerable Morbidity ◽  
Secondary Causes

SummaryMale osteoporosis is common and results in considerable morbidity and mortality. There are distinct differences in the normal aging of bone between the genders, which result in a lower fracture rate in men. Men who suffer from osteoporosis are much more likely than women to have secondary causes. The identification and treatment of these secondary causes, wherever possible, will result in substantial improvements in BMD. There is now evidence for use of many of the existing agents to treat osteoporosis in men. In younger hypogonadal men testosterone replacement is worth considering, but in older men especially the over sixties this is less effective and there is an increased risk of adverse cardiovascular and prostatic outcomes. Prostate cancer is an increasingly common cause, which is partially the result of the success of ADT. There is now good evidence for the use of bisphosphonates and denosumab in this group of patients. HIV, whilst not being specific to men, is an increasingly recognised cause of male osteoporosis. The reasons for this are multifactorial and some may well be attributable to the anti-retroviral therapy itself. There is emerging evidence of an increased fracture risk in HIV infected individuals. The bone loss can be prevented by the use of bisphosphonates.

scholarly journals Candidate therapeutic agents for hepatocellular cancer can be identified from phenotype-associated gene expression signatures

Cancer ◽  
2009 ◽  
Vol 115 (16) ◽  
pp. 3738-3748 ◽  
Author(s):  
Chiara Braconi ◽  
Fanyin Meng ◽  
Erica Swenson ◽  
Lyudmyla Khrapenko ◽  
Nianyuan Huang ◽  
...  
Keyword(s):  
Gene Expression ◽  
Hepatocellular Cancer ◽  
Therapeutic Agents ◽  
Gene Expression Signatures

37 Monitoring the evolution of inflammatory bowel disease (IBD) in pediatric and adult cohorts of patients to identify biomarkers to predict cancer risk

2020 ◽  
Vol 8 (Suppl 3) ◽  
pp. A38-A38
Author(s):  
Shilpa Ravindran ◽  
Heba Sidahmed ◽  
Harshitha Manjunath ◽  
Rebecca Mathew ◽  
Tanwir Habib ◽  
...  
Keyword(s):  
Oxidative Stress ◽  
Gene Expression ◽  
Colorectal Cancer ◽  
Inflammatory Bowel Disease ◽  
Bowel Disease ◽  
Mesenchymal Transition ◽  
Increased Risk ◽  
Hamad Medical Corporation ◽  
Inflammatory Bowel ◽  
Left And Right

BackgroundPatients with inflammatory bowel disease (IBD) have increased risk of developing colorectal cancer (CRC), depending on the duration and severity of the disease. The evolutionary process in IBD is driven by chronic inflammation leading to epithelial-to-mesenchymal transition (EMT) events in colonic fibrotic areas. EMT plays a determinant role in tumor formation and progression, through the acquisition of ‘stemness’ properties and the generation of neoplastic cells. The aim of this study is to monitor EMT/cancer initiating tracts in IBD in association with the deep characterization of inflammation in order to assess the mechanisms of IBD severity and progression towards malignancy.Methods10 pediatric and 20 adult IBD patients, admitted at Sidra Medicine (SM) and Hamad Medical Corporation (HMC) respectively, have been enrolled in this study, from whom gut tissue biopsies (from both left and right side) were collected. Retrospectively collected tissues (N=10) from patients with malignancy and history of IBD were included in the study. DNA and RNA were extracted from fresh small size (2–4 mm in diameter) gut tissues using the BioMasher II (Kimble) and All Prep DNA/RNA kits (Qiagen). MicroRNA (miRNA; N=700) and gene expression (N=800) profiling have been performed (cCounter platform; Nanostring) as well as the methylation profiling microarray (Infinium Methylation Epic Bead Chip kit, Illumina) to interrogate up to 850,000 methylation sites across the genome.ResultsDifferential miRNA profile (N=27 miRNA; p<0.05) was found by the comparison of tissues from pediatric and adult patients. These miRNAs regulate: i. oxidative stress damage (e.g., miR 99b), ii. hypoxia induced autophagy; iii. genes associated with the susceptibility to IBD (ATG16L1, NOD2, IRGM), iv. immune responses, such as TH17 T cell subset (miR 29). N=6 miRNAs (miR135b, 10a196b, 125b, let7c, 375) linked with the regulation of Wnt/b-catenin, EM-transaction, autophagy, oxidative stress and play role also in cell proliferation and mobilization and colorectal cancer development were differentially expressed (p<0.05) in tissues from left and right sides of gut. Gene expression signature, including genes associated with inflammation, stemness and fibrosis, has also been performed for the IBD tissues mentioned above. Methylation sites at single nucleotide resolution have been analyzed.ConclusionsAlthough the results warrant further investigation, differential genomic profiling suggestive of altered pathways involved in oxidative stress, EMT, and of the possible stemness signature was found. The integration of data from multiple platforms will provide insights of the overall molecular determinants in IBD patients along with the evolution of the disease.Ethics ApprovalThis study was approved by Sidra Medicine and Hamad Medical Corporation Ethics Boards; approval number 180402817 and MRC-02-18-096, respectively.

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