Proteinuria is a risk factor for chronic kidney disease (CKD) progression and associated complications. However, there is insufficient information on individual protein components in urine and the severity of CKD. We aimed to investigate urinary proteomics and its association with proteinuria and kidney function in early-stage CKD and in healthy individuals. A 24 h urine sample of 42 individuals (21-CKD and 21-healthy individuals) was used for mass spectrometry-based proteomics analysis. An exponentially modified protein abundance index (emPAI) was calculated for each protein. Data were analyzed by Mascot software using the SwissProt database and bioinformatics tools. Overall, 298 unique proteins were identified in the cohort; of them, 250 proteins belong to the control group with median (IQR) emPAI 39.1 (19–53) and 142 proteins belong to the CKD group with median (IQR) emPAI 67.8 (49–117). The level of 24 h proteinuria positively correlated with emPAI (r = 0.390, p = 0.011). The emPAI of some urinary proteomics had close positive (ALBU, ZA2G, IGKC) and negative (OSTP, CD59, UROM, KNG1, RNAS1, CD44, AMBP) correlations (r < 0.419, p < 0.001) with 24 h proteinuria levels. Additionally, a few proteins (VTDB, AACT, A1AG2, VTNC, and CD44) significantly correlated with kidney function. In this proteomics study, several urinary proteins correlated with proteinuria and kidney function. Pathway analysis identified subpathways potentially related to early proteinuric CKD, allowing the design of prospective studies that explore their response to therapy and their relationship to long-term outcomes.
Kazakhstan covers a vast territory, and it has always been a land of nomadic pastoralism, where domesticated horses and sheep were moved by nomadic people across the steppe. Previous reports suggest that sheep breeds from Kazakhstan have an intermediate genetic composition between Asian and European breeds; however, this data appears to be limited. Therefore, we studied the genetic diversity of ancient domestic sheep from two Late Bronze Age settlements, Toksanbai and Kent, located in the Pre-Caspian region of Kazakhstan and central Kazakhstan, respectively. We have applied ZooMS analysis for taxonomic identification of small ruminant remains to select ancient specimens of domestic sheep ( Ovis aries ). To assign sheep mitochondrial DNA (mtDNA) haplogroups, the single nucleotide polymorphisms (SNPs) from the control region were analyzed by real-time PCR and direct sequencing. Identical distribution of mtDNA haplogroups A (8/14; 57%), B (5/14; 36%), and C (1/14; 7%) was observed in the specimens from Toksanbai (n = 14) and Kent (n = 14). Ovine haplogroup A was predominant in both settlements. Both archeological sites had similar patterns of haplogroup distribution, indicating early sheep introduction into the region. These results are important to gain a better understanding of sheep migrations in the Eurasian steppe and highlight the importance of genomic analysis of earlier local lineages.
Gram-positive bacteria of Mycobacterium tuberculosis complex (MTBC) are causative agents of tuberculosis disease. According to the report of the World Health Organization, tuberculosis is one of the leading causes of mortality worldwide. Moreover, epidemiological data shows that due to the COVID-19 pandemic tuberculosis mortality has risen in comparison with previous years. Drug resistance is another threatening issue when the resistance to antitubercular (anti-TB) drugs makes therapy less effective. Furthermore, drug resistance is often burdened with compensatory mechanisms that overcome fitness defects related to drug-resistant mutations. This review discusses the drug resistance and compensatory mutations in Mycobacterium tuberculosis and the current situation with anti-TB drug resistance in the Republic of Kazakhstan.
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