Total flavonoid in Epimedium koreanum Nakai alleviated chronic renal failure via promoting AMPK activation

Chronic renal failure (CRF) is a result of the progression of chronic kidney diseases (CKD), a global health problem with high cost of treatment and no ideal therapy. The aim...

Butyrate producing microbiota are reduced in chronic kidney diseases

Chronic kidney disease is a major public health concern that affects millions of people globally. Alterations in gut microbiota composition have been observed in patients with chronic kidney disease. Nevertheless, the correlation between the gut microbiota and disease severity has not been investigated. In this study, we performed shot-gun metagenomics sequencing and identified several taxonomic and functional signatures associated with disease severity in patients with chronic kidney disease. We noted that 19 microbial genera were significantly associated with the severity of chronic kidney disease. The butyrate-producing bacteria were reduced in patients with advanced stages of chronic kidney diseases. In addition, functional metagenomics showed that two-component systems, metabolic activity and regulation of co-factor were significantly associated with the disease severity. Our study provides valuable information for the development of microbiota-oriented therapeutic strategies for chronic kidney disease.

Nutritional and Health Potential of Probiotics: A Review

Several products consist of probiotics that are available in markets, and their potential uses are growing day by day, mainly because some strains of probiotics promote the health of gut microbiota, especially Furmicutes and Bacteroidetes, and may prevent certain gastrointestinal tract (GIT) problems. Some common diseases are inversely linked with the consumption of probiotics, i.e., obesity, type 2 diabetes, autism, osteoporosis, and some immunological disorders, for which the disease progression gets delayed. In addition to disease mitigating properties, these microbes also improve oral, nutritional, and intestinal health, followed by a robust defensive mechanism against particular gut pathogens, specifically by antimicrobial substances and peptides producing probiotics (AMPs). All these positive attributes of probiotics depend upon the type of microbial strains dispensed. Lactic acid bacteria (LAB) and Bifidobacteria are the most common microbes used, but many other microbes are available, and their use depends upon origin and health-promoting properties. This review article focuses on the most common probiotics, their health benefits, and the alleviating mechanisms against chronic kidney diseases (CKD), type 1 diabetes (T1D), type 2 diabetes (T2D), gestational diabetes mellitus (GDM), and obesity.

Renoprotective Role of Hypoxia-Inducible Factors and the Mechanism

<b><i>Background:</i></b> The kidney requires abundant blood supply, and oxygen is transmitted by diffusion through blood vessels. Most physiological metabolism of the kidney depends on oxygen, so it is very sensitive to oxygen. An increasing pool of evidence suggests that hypoxia is involved in almost all acute and chronic kidney diseases (CKDs). Vascular damage, tubular injury, and fibrosis are the main pathologies associated during hypoxia. Hypoxia-inducible factors (HIFs) are the main mediators during hypoxia, but their functions remain controversial. This article reviewed recent studies and described its mechanisms on renoprotection. <b><i>Summary:</i></b> HIF is degraded rapidly during under normal oxygen. But under hypoxia, HIFs accumulate and many target genes are regulated by HIFs. Homeostasis during injury is maintained through these genes. Pretreatment of HIF can protect the kidney from acute hypoxia and can improve repair, but HIF’s role in CKD and in renal tumor is still controversial. Due to its mechanism in kidney disease, many drugs toward HIFs are widely researched, even some of which have been used in clinical or in clinical research. <b><i>Key Messages:</i></b> In this review, we described the known physiological mechanisms, target genes, and renal protective roles of HIFs, and we discussed several drugs that are researched due to such renal protective roles.

Aristolochic Acid Induces Renal Fibrosis and Senescence in Mice

The kidney is one of the most susceptible organs to age-related impairments. Generally, renal aging is accompanied by renal fibrosis, which is the final common pathway of chronic kidney diseases. Aristolochic acid (AA), a nephrotoxic agent, causes AA nephropathy (AAN), which is characterized by progressive renal fibrosis and functional decline. Although renal fibrosis is associated with renal aging, whether AA induces renal aging remains unclear. The aim of the present study is to investigate the potential use of AAN as a model of renal aging. Here, we examined senescence-related factors in AAN models by chronically administering AA to C57BL/6 mice. Compared with controls, the AA group demonstrated aging kidney phenotypes, such as renal atrophy, renal functional decline, and tubulointerstitial fibrosis. Additionally, AA promoted cellular senescence specifically in the kidneys, and increased renal p16 mRNA expression and senescence-associated β-galactosidase activity. Furthermore, AA-treated mice exhibited proximal tubular mitochondrial abnormalities, as well as reactive oxygen species accumulation. Klotho, an antiaging gene, was also significantly decreased in the kidneys of AA-treated mice. Collectively, the results of the present study indicate that AA alters senescence-related factors, and that renal fibrosis is closely related to renal aging.

Uric Acid in Inflammation and the Pathogenesis of Atherosclerosis

Hyperuricemia is a common metabolic syndrome. Elevated uric acid levels are risk factors for gout, hypertension, and chronic kidney diseases. Furthermore, various epidemiological studies have also demonstrated an association between cardiovascular risks and hyperuricemia. In hyperuricemia, reactive oxygen species (ROS) are produced simultaneously with the formation of uric acid by xanthine oxidases. Intracellular uric acid has also been reported to promote the production of ROS. The ROS and the intracellular uric acid itself regulate several intracellular signaling pathways, and alterations in these pathways may result in the development of atherosclerotic lesions. In this review, we describe the effect of uric acid on various molecular signals and the potential mechanisms of atherosclerosis development in hyperuricemia. Furthermore, we discuss the efficacy of treatments for hyperuricemia to protect against the development of atherosclerosis.

Changes in the Expression of Renal Brush Border Membrane N-Glycome in Model Rats with Chronic Kidney Diseases

Chronic kidney disease (CKD) is defined by a reduced renal function i.e., glomerular filtration rate (GFR), and the presence of kidney damage is determined by measurement of proteinuria or albuminuria. Albuminuria increases with age and can result from glomerular and/or proximal tubule (PT) alterations. Brush-border membranes (BBMs) on PT cells play an important role in maintaining the stability of PT functions. The PT BBM, a highly dynamic, organized, specialized membrane, contains a variety of glycoproteins required for the functions of PT. Since protein glycosylation regulates many protein functions, the alteration of glycosylation due to the glycan changes has attracted more interests for a variety of disease studies recently. In this work, liquid chromatography-tandem mass spectrometry was utilized to analyze the abundances of permethylated glycans from rats under control to mild CKD, severe CKD, and diabetic conditions. The most significant differences were observed in sialylation level with the highest present in the severe CKD and diabetic groups. Moreover, high mannose N-glycans was enriched in the CKD BBMs. Characterization of all the BBM N-glycan changes supports that these changes are likely to impact the functional properties of the dynamic PT BBM. Further, these changes may lead to the potential discovery of glycan biomarkers for improved CKD diagnosis and new avenues for therapeutic treatments.

Diagnostic and prognostic value of peripheral blood leucocyte ratios in sick cats

The objective of this study was to assess the diagnostic and prognostic utility of feline neutrophil-to-lymphocyte (NLR) and lymphocyte-to-monocyte ratios (LMR) in a variety of underlying diseases. Five-year medical records from cats presenting to the internal medicine unit of a veterinary teaching hospital were retrospectively reviewed. Cats were considered for inclusion based on complete medical records. ADVIA 120 was used for the complete blood counts; the NLR and LMR were calculated by dividing the absolute numbers of the respective leucocytes. Two hundred and nineteen sick and 20 healthy cats were included in the study. The median NLR and LMR were significantly (P < 0.05) elevated and decreased, respectively, in cats with infectious, neoplastic and chronic kidney diseases compared to controls. Additionally, cats with neoplasia had significantly higher median NLR compared to cats with urinary tract and gastrointestinal diseases. Non-survivors had significantly higher NLR and lower LMR compared to survivors. Both ratios had suboptimal prognostic performance for the outcome of sick cats (NLR sensitivity: 37.9%, specificity: 86.4%; LMR sensitivity: 69.0%, specificity: 61.0%). Many different disease categories were associated with increased NLR and decreased LMR compared to controls, but the overall prognostic performance of the two leucocyte ratios was suboptimal.