Uromodulin as a potential candidate marker for predicting the course of chronic kidney disease

Uromodulin is a nephrospecific protein that is most common in normal urine. And although it has been known for more than 70 years, the function of uromodulin remains unclear. Uromodulin is involved in regulating the transport of salts, protects against urinary tract infections, namely, the mucous membrane of the bladder, and prevents the formation of kidney stones, as well as plays a role in kidney damage and innate immunity. Serum uromodulin and uromodulin of urine, daily excretion and excretion of uromodulin per 1 milliliter of creatinine clearance are actively studied. Complete genome studies of the association have established a correlation between uromodulin gene mutations and autosomal dominant tubulointerstitial kidney disease.

Polymorphism of CAST gene in five sheep breeds in Bulgaria

CAST gene is a candidate marker that influences the intensity of growth and meat quality. The aim of this study was to investigate the genetic variability of CAST gene in five Bulgarian sheep breeds – two merino, two local and one for milk. A total of 150 ewes, belonging to these breeds were investigated for polymorphisms of CAST gene by using PCR-RFLP method. A 622 bp fragment of Ovis aries CAST gene was amplified using PCR. After restriction with endonuclease MspI two alleles were observed in Ascanian, Caucasian, Breznik and Pleven Blackhead breeds. One allele (M) and one genotype (MM) were detected in Cooper-Red Shumen breed. The highest frequency of the allele N was established in the Ascanian merino breed (0.27) followed by Caucasian merino (0.13), Breznik (0.12) and Pleven Blackhead (0.07). Two genotypes - MM and MN, were observed in Caucasian, Breznik and Pleven Blackhead breeds. The three possible genotypes were found only in Ascanian merino ewes - MM, MN and NN. The lowest frequency of the homozygous genotype MM (0.50) and the highest frequency of the heterozygous genotype MN was established in the Ascanian merino breed (0.47). The obtained results confirm that the PCR-RFLP method can be used to identify different genotypic variation of CAST gene in Bulgarian sheep breeds. The established genetic diversity in the calpastatin gene indicates that, after further associative studies, this gene may be included in the breeding programs of certain sheep breeds.

HP1γ sets the biological age of the intestinal epithelium

ABSTRACTAltered RNA maturation and decay have well-documented effects on tissue longevity. Yet, RNA metabolism is poorly investigated in the gut epithelium, a constantly renewing tissue particularly challenged by ageing. We found that inactivation of the epigenetic regulator HP1γ in the mouse gut epithelium results in accelerated ageing associated with both ectopic expression of ribosomal RNAs and accumulation of miss-spliced messenger RNAs. A consequence of the latter is the production of progerin, a spliced product of the LMNA gene associated with the Hutchinson Gilford Syndrome. Production of progerin transcript increased naturally in the mouse ageing gut, in correlation with a reduced HP1γ expression. Thus, progerin is a candidate marker of aging of the gut epithelium, while HP1γ inactivation emerges as a new model for accelerated aging in this tissue.

Digitally quantified CD8+ cells: the best candidate marker for an immune cell score in non-small cell lung cancer?

The TNM classification is well established as a state-of-the-art prognostic and treatment-decision-making tool for non-small cell lung cancer (NSCLC) patients. However, incorporation of biological data may hone the TNM system. This article focuses on choosing and incorporating subsets of tissue-infiltrating lymphocyte (TIL), detected by specific immunohistochemistry and automatically quantified by open source software, into a TNM-Immune cell score (TNM-I) for NSCLC. We use common markers (CD3, CD4, CD8, CD20 and CD45RO) of TILs to identify TIL subsets in tissue micro-arrays comprising tumor tissue from 553 patients resected for primary NSCLC. The number of TILs is automatically quantified using open source software (QuPath). Their prognostic efficacy, alone and within a TNM-I model, is evaluated in all patients and histological subgroups. Compared with previous manual semi-quantitative scoring of TILs in the same cohort, the present digital quantification proved superior. As a proof-of-concept, we construct a TNM-I, using TNM categories and the CD8+ TIL density. The TNM-I is an independent prognosticator of favorable diagnosis in both the overall cohort and in the main histological subgroups. In conclusion, CD8+ TIL density is the most promising candidate marker for a TNM-I in NSCLC. The prognostic efficacy of the CD8+ TIL density is strongest in lung squamous cell carcinomas, whereas both CD8+ TILs and CD20+ TILs, or a combination of these, may be candidates for a TNM-I in lung adenocarcinoma. Furthermore, based on the presented results, digital quantification is the preferred method for scoring TILs in the future.