scholarly journals Genetics and Epigenetics of Diabetic Nephropathy

2015 ◽  
Vol 1 (1) ◽  
pp. 42-51 ◽  
Author(s):  
Ruijie Liu ◽  
Kyung Lee ◽  
John Cijiang He
Keyword(s):  
Diabetic Nephropathy ◽  
Drug Targets ◽  
Rare Variants ◽  
Rapid Development ◽  
Strong Association ◽  
Kidney Tissue ◽  
Epigenetic Modifications ◽  
Diabetic Patients ◽  
Epigenetic Changes ◽  
Tissue Samples

Background: Diabetic nephropathy (DN) is the most common cause of end-stage renal disease (ESRD) in the USA and worldwide, contributing to significant morbidity and mortality in diabetic patients. A genetic factor for the development of DN is strongly implicated, as only one third of diabetic patients eventually develop kidney disease. Growing evidence also supports an important role of epigenetic modifications in DN. Summary: Multiple studies have been performed to identify risk genes and loci associated with DN. So far, only several genes and loci have been identified, none of which showed a strong association with DN. Therefore, a better study design with a larger sample size to identify rare variants and a clinically defined patient population to identify genes and loci associated with progressive DN are still needed. In addition to genetic factors, epigenetic modifications, such as DNA methylation, histone modifications and microRNAs, also play a major role in the pathogenesis of DN through a second layer of gene regulation. Although a major progress has been made in this field, epigenetic studies in DN are still in the early phase and have been limited mostly due to the heterogeneity of kidney tissue samples with multiple cells. However, rapid development of high-throughput genome-wide techniques will help us to better identify genetic variants and epigenetic changes in DN. Key Message: Understanding of genetic and epigenetic changes in DN is needed for the development of new biomarkers and better drug targets against DN. Summarized in this review are important recent findings on genetic and epigenetic studies in the field of DN.

scholarly journals Association of CCL2, CCR5, ELMO1, and IL8 Polymorphism with Diabetic Nephropathy in Malaysian Type 2 Diabetic Patients

2019 ◽  
Vol 2019 ◽  
pp. 1-13 ◽  
Author(s):  
Mohd Jokha Yahya ◽  
Patimah binti Ismail ◽  
Norshariza binti Nordin ◽  
Abdah binti Md Akim ◽  
Wan Shaariah binti Md. Yusuf ◽  
...  
Keyword(s):  
Diabetic Nephropathy ◽  
Strong Association ◽  
Additive Model ◽  
Diabetic Patients ◽  
Type 2 Diabetic Patients ◽  
Monocyte Chemoattractant Protein 1 ◽  
Cell Mortality ◽  
Type 2 Diabetic ◽  
Mode Of Inheritance

The unique variants or biomarkers of individuals help to understand the pathogenesis as well as the potential risk of individuals or patients to diabetic nephropathy (DN). The aim of this study was to investigate the association of a genetic polymorphism of monocyte chemoattractant protein-1 (CCL2-rs3917887), chemokine receptor 5 (CCR5-rs1799987), engulfment and cell mortality (ELMO1-rs74130), and interleukin-8 (IL8-rs4073) with the development of DN among Malaysian type 2 diabetes mellitus (T2DM) patients. More than one thousand diabetic patients were examined and a total of 652 T2DM patients were tested comprising 227 Malays (nonnephrotic=96 and nephrotic=131), 203 Chinese (nonnephrotic=95 and nephrotic=108), and 222 Indians (nonnephrotic=136 and nephrotic=86). DNA Sequenom mass ARRAY was employed to identify polymorphisms in CCL2, CCR5, ELMO1, and IL8 genes. DNA was extracted from the secondary blood samples taken from the T2DM patients. The alleles and genotypes were tested using four genetic models and the best mode of inheritance was chosen. CCR5 rs1799987 (G>A) showed strong association with the development of diabetic nephropathy only among the Chinese with OR=6.71 (2.55-17.68) 95% CI while IL8 rs4073 (T>A) showed association with nephropathy only among the Indians with OR=1.57 (0.66-3.71) 95% CI. The additive model was the best model for the mode of inheritance of all the genes. The contribution of genetic variants differs across ethnic groups or background. Further studies which involve environmental risk factors should be taken into consideration.

scholarly journals Establishment of a tissue microarray (TMA) platform as an efficient tool for soft tissue sarcoma (STS) research available for collaboration.

2019 ◽  
Vol 5 (suppl) ◽  
pp. 38-38
Author(s):  
Patrick Schoffski ◽  
Che-Jui Lee ◽  
Tom Van Cann ◽  
Jasmien Wellens ◽  
Inti Zlobec ◽  
...  
Keyword(s):  
Drug Targets ◽  
Rare Variants ◽  
Soft Part ◽  
Medical Center ◽  
Cost Effective ◽  
Clear Cell Sarcoma ◽  
University Hospital ◽  
Tumor Type ◽  
University Hospitals ◽  
Tissue Samples

38 Background: STS is a very heterogeneous family of orphan malignancies, characterized by morphological and genetic diversity. Tissue samples from individual STS patients are commonly used for routine diagnostic and research purposes. TMAs from multiple sarcoma tissue blocks have potential advantages over conventional tissue analysis in terms of efficiency and cost-effectiveness. We have established a comprehensive sarcoma TMA research platform. Methods: TMAs were constructed using left-over tissue from STS patients diagnosed at University Hospitals Leuven (B), Leiden University Medical Center (NL) and University Hospital Zürich (CH), and from patients with orphan sarcomas enrolled in EORTC trial 90101 “CREATE”. The clinical cases are well annotated in terms of diagnosis, treatment and follow-up. Each TMA block contains duplicate/triplicate 1.0-1.5 mm tissue cores from representative areas selected by sarcoma pathologists. The construction of TMAs was performed using TMA Grand Master (3DHistech) at University of Bern (CH) and in Leiden (NL). Results: The following subtype-specific TMAs have been created: clear cell sarcoma (CCSA, 54 cases), alveolar soft part sarcoma (ASPS, 59), inflammatory myofibroblastic tumor (IMFT, 33), alveolar rhabdomyo- (24) and leiomyosarcoma (55). For CCSA, ASPS and IMFT we have matching TMAs from clinical routine and patients entered in EORTC 90101. As a tool for broader drug- and target-screening purposes in STS we also produced a multi-sarcoma TMA combining multiple, more common subtypes on one block: angio-, dedifferentiated, pleomorphic and myxoid lipo-, leiomyo-, myxofibro-, rhabdomyo-, synovial and undifferentiated pleomorphic sarcoma, and MPNST, with 7-11 individual cases per tumor type. TMA construction is ongoing in other relevant sarcoma subtypes. Conclusions: We are currently expanding a very useful TMA platform representing the broad heterogeneity of STS, from more common to ultra-rare variants. TMAs are available for rapid, cost-effective morphological, histochemical and molecular characterization and identification of novel drug targets in collaboration with academic and commercial partners.

scholarly journals Diabetic nephropathy is a risk factor for audio-vestibular system

2019 ◽  
Vol 11 (1) ◽  
pp. 66-71
Author(s):  
Rafeek Mohamed ◽  
Hesham Mahmoud Samy ◽  
Mohamed Ahmed Shaarawy ◽  
Kholoud Nashaat Moustafa
Keyword(s):  
Diabetic Nephropathy ◽  
Auditory System ◽  
Vestibular System ◽  
Kidney Tissue ◽  
Rapid Test ◽  
Diabetic Patients ◽  
Distortion Product Otoacoustic Emission ◽  
Early Management ◽  
Distortion Product ◽  
Brainstem Response

Objective: There is evidence that both inner ear and kidney tissue are immunological, biochemically and functionally related. Accordingly, this study was conducted to explore, if there is possible damage of the ear associated with diabetic nephropathy. This may help in early diagnosis and early management of hearing problem and the vestibular problem which is a leading cause of fall and death especially in the geriatric population. Study design: Prospective study. Methods: All participants subjected to the following, thorough history of audio-vestibular symptoms, otoscopic examination, and basic audiological evaluation. Advanced audiological evaluation in the form of extended high frequency assessment. Distortion product otoacoustic emission (DPOAE) & auditory brainstem response (ABR). Vestibular assessment in the form of vestibular evoked myogenic potential (VEMP) and caloric test. Results: The vestibular system more resistant to diabetes than the auditory system as the only affected part in this research is the inferior vestibular division while the superior division was not affected. Conclusion: The audio-vestibular system was affected in patients with diabetic nephropathy more than the other diabetic patients and the vestibular system more resistant to diabetes than the auditory system. Screening of patients with diabetic nephropathy with a rapid test with minimal time consuming as OAE and cVEMP will help in early detection, early management of any affection of the audio-vestibular system and hence may aid in the prevention of imbalance, falls and death.

scholarly journals Down-regulation of Risa Improves Podocyte Injury by Enhancing Autophagy in Diabetic Nephropathy

2021 ◽  
Author(s):  
Peipei Su ◽  
Dongwei Liu ◽  
Sijie Zhou ◽  
Hang Chen ◽  
Xianming Wu ◽  
...  
Keyword(s):  
Diabetic Nephropathy ◽  
Poor Prognosis ◽  
Kidney Tissue ◽  
Podocyte Injury ◽  
Tissue Samples ◽  
Adeno Associated Virus ◽  
Qrt Pcr ◽  
Tail Vein Injection ◽  
Transmission Electron ◽  
Pas Staining

Abstract BackgroundLncRNA AK044604 (Risa), Sirt1 and GSK3β are autophagy related genes that can play important roles in diabetic nephropathy (DN). In this study, we sought to explore the effect of Risa on Sirt1/GSK3β-induced podocyte injury.MethodsTransgenic db/db mice were fed and injected with Risa inhibition of adeno-associated virus by tail vein injection, as well as intraperitoneally injected with LiCl. Blood, urine, kidney tissue samples, and clinical data were collected at different time points. Immortalized mouse podocyte cells (MPCs) were cultured and treated with Risa inhibition of lentivirus, EX-527, and LiCl. MPCs were collected under different stimulations. The effects of Risa on podocyte autophagy were examined by qRT-PCR, Western blot analysis, transmission electron microscope, PAS staining, and immunofluorescence staining. ResultsRisa and activated GSK3β were overexpressed, but Sirt1 decreased in Renal tissues of DN mice and high-glucose-treated MPCs and correlated with poor prognosis. Risa overexpression attenuated Sirt1-mediated downstream autophagy levels and aggravated the injury of podocytes by inhibiting the expression of Sirt1. In contrast, Risa inhibition enhanced Sirt1-induced autophagy and attenuated podocyte injury, but this effect could be abrogated by EX-527, suggesting that Risa overexpression aggravated podocyte injury by decreasing autophagy. ConclusionsRisa inhibits autophagy by regulating the Sirt1/GSK3β axis and thereby aggravates podocyte injury in DN. Risa may serve as a therapeutic target for the treatment of DN.

A Comparison Between Sterological Point Counting and Digitizing Tablets

1985 ◽  
Vol 43 ◽  
pp. 666-667
Author(s):  
John M. Basgen ◽  
Eileen N. Ellis ◽  
S. Michael Mauer ◽  
Michael W. Steffes
Keyword(s):  
Electron Microscopy ◽  
Kidney Tissue ◽  
Volume Density ◽  
Diabetic Patients ◽  
Normal Kidney ◽  
Point Counting ◽  
Normal Kidney Tissue ◽  
Biopsy Specimens ◽  
Mitochondrial Volume ◽  
Kidney Lesions

To determine the efficiency of methods of quantitation of the volume density of components within kidney biopsies, techniques involving a semi-automatic digitizing tablet and stereological point counting were compared.Volume density (Vv) is a parameter reflecting the volume of a component to the volume that contains the component, e.g., the fraction of cell volume that is made up of mitochondrial volume. The units of Vv are μm3 /μm3.Kidney biopsies from 15 patients were used. Five were donor biopsies performed at the time of kidney transplantation (patients 1-5, TABLE 1) and were considered normal kidney tissue. The remaining biopsies were obtained from diabetic patients with a spectrum of diabetic kidney lesions. The biopsy specimens were fixed and embedded according to routine electron microscogy protocols. Three glomeruli from each patient were selected randomly for electron microscopy. An average of 12 unbiased and systematic micrographs were obtained from each glomerulus and printed at a final magnification of x18,000.

Mycobacterial DNA Replication as a Target for Antituberculosis Drug Discovery

2017 ◽  
Vol 17 (19) ◽  
pp. 2129-2142 ◽  
Author(s):  
Renata Płocinska ◽  
Malgorzata Korycka-Machala ◽  
Przemyslaw Plocinski ◽  
Jaroslaw Dziadek
Keyword(s):  
Drug Resistance ◽  
Dna Replication ◽  
Drug Targets ◽  
Rapid Development ◽  
New Drugs ◽  
Drug Resistant ◽  
Antituberculosis Drug ◽  
Nucleotide Synthesis ◽  
Antituberculosis Therapy ◽  
Optimal Drug

Background: Mycobacterium tuberculosis (M. tuberculosis), the causative agent of tuberculosis, is a leading infectious disease organism, causing millions of deaths each year. This serious pathogen has been greatly spread worldwide and recent years have observed an increase in the number of multi-drug resistant and totally drug resistant M. tuberculosis strains (WHO report, 2014). The danger of tuberculosis becoming an incurable disease has emphasized the need for the discovery of a new generation of antimicrobial agents. The development of novel alternative medical strategies, new drugs and the search for optimal drug targets are top priority areas of tuberculosis research. Factors: Key characteristics of mycobacteria include: slow growth, the ability to transform into a metabolically silent - latent state, intrinsic drug resistance and the relatively rapid development of acquired drug resistance. These factors make finding an ideal antituberculosis drug enormously challenging, even if it is designed to treat drug sensitive tuberculosis strains. A vast majority of canonical antibiotics including antituberculosis agents target bacterial cell wall biosynthesis or DNA/RNA processing. Novel therapeutic approaches are being tested to target mycobacterial cell division, twocomponent regulatory factors, lipid synthesis and the transition between the latent and actively growing states. Discussion and Conclusion: This review discusses the choice of cellular targets for an antituberculosis therapy, describes putative drug targets evaluated in the recent literature and summarizes potential candidates under clinical and pre-clinical development. We focus on the key cellular process of DNA replication, as a prominent target for future antituberculosis therapy. We describe two main pathways: the biosynthesis of nucleic acids precursors – the nucleotides, and the synthesis of DNA molecules. We summarize data regarding replication associated proteins that are critical for nucleotide synthesis, initiation, unwinding and elongation of the DNA during the replication process. They are pivotal processes required for successful multiplication of the bacterial cells and hence they are extensively investigated for the development of antituberculosis drugs. Finally, we summarize the most potent inhibitors of DNA synthesis and provide an up to date report on their status in the clinical trials.

The Development of Epigenetics and Related Inhibitors for Targeted Drug Design in Cancer Therapy

2019 ◽  
Vol 18 (28) ◽  
pp. 2380-2394 ◽  
Author(s):  
Na Liu ◽  
Rongtong Zhao ◽  
Yue Ma ◽  
Dongyuan Wang ◽  
Chen Yan ◽  
...  
Keyword(s):  
Drug Design ◽  
Rapid Development ◽  
Epigenetic Changes ◽  
Disease Treatment ◽  
Nucleosome Remodeling ◽  
Epigenetic Modifiers ◽  
The Us ◽  
Targeted Drug ◽  
Heritable Change ◽  
Lymphoma Therapy

Epigenetics process is the heritable change in gene function that does not involve changes in the DNA sequence. Until now, several types of epigenetic mechanisms have been characterized, including DNA methylation, histone modification (acetylation, methylation, etc.), nucleosome remodeling, and noncoding RNAs. With the biological investigations of these modifiers, some of them are identified as promoters in the process of various diseases, such as cancer, cardiovascular disease and virus infection. Epigenetic changes may serve as potential “first hits” for tumorigenesis. Hence, targeting epigenetic modifiers is being considered as a promising way for disease treatment. To date, six agents in two epigenetic target classes (DNMT and HDAC) have been approved by the US Food and Drug Administration (FDA). Most of these drugs are applied in leukemia, lymphoma therapy, or are combined with other drugs for the treatment of solid tumor. Due to the rapid development of epigenetics and epigenetics targeted drugs, it is becoming an emerging area in targeted drug design.

Epigenetic Studies in Psychotherapy: A Systematic Review

2020 ◽  
Vol 16 (2) ◽  
pp. 86-92
Author(s):  
Rafael Penadés ◽  
Bárbara Arias ◽  
Mar Fatjó-Vilas ◽  
Laura González-Vallespí ◽  
Clemente García-Rizo ◽  
...  
Keyword(s):  
Systematic Review ◽  
Dna Methylation ◽  
Mental Disorders ◽  
Epigenetic Modifications ◽  
Symptom Improvement ◽  
Epigenetic Changes ◽  
Main Hypothesis ◽  
Psychological Treatments ◽  
Time Period ◽  
The Impact

Background: Epigenetic modifications appear to be dynamic and they might be affected by environmental factors. The possibility of influencing these processes through psychotherapy has been suggested. Objective: To analyse the impact of psychotherapy on epigenetics when applied to mental disorders. The main hypothesis is that psychological treatments will produce epigenetic modifications related to the improvement of treated symptoms. Methods: A computerised and systematic search was completed throughout the time period from 1990 to 2019 on the PubMed, ScienceDirect and Scopus databases. Results: In total, 11 studies were selected. The studies were evaluated for the theoretical framework, genes involved, type of psychotherapy and clinical challenges and perspectives. All studies showed detectable changes at the epigenetic level, like DNA methylation changes, associated with symptom improvement after psychotherapy. Conclusion: Methylation profiles could be moderating treatment effects of psychotherapy. Beyond the detected epigenetic changes after psychotherapy, the epigenetic status before the implementation could act as an effective predictor of response.

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