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Optical Angiography at Diabetes
Published in Andrey V. Dunaev, Valery V. Tuchin, Biomedical Photonics for Diabetes Research, 2023
Dan Zhu, Jingtan Zhu, Dongyu Li, Tingting Yu, Wei Feng, Rui Shi
There are now many tissue clearing methods proved to be available for 3D imaging of neural and vascular structures in kidneys. For example, 3DISCO, the typical solvent-based clearing method [49], was confirmed to be useful for imaging the vasculature of mouse kidneys labeled by lectin [50]. Qi et al. developed FDISCO method and applied it in 3D imaging and reconstruction of mouse kidneys; quantification of glomeruli was also performed [51] (Figure 6.2a). iDISCO method, recognized as a powerful whole-mount immunolabeling protocol, was also used to image the entire kidneys labeled by anti-Aquaporin2 for labeling collecting ducts and anti-Nephrin for labeling glomeruli, respectively [52]. Ethanol-ECi was developed for 3D imaging and evaluation of total glomerular number and capillary tuft size of kidneys with nephrotoxic nephritis [53]. The latest SHANEL protocol developed by Zhao et al. rendered the intact adult human kidney transparent, and 3D histology was performed with antibodies and dyes in centimeters depth [54].
Potential of Fenugreek in Management of Kidney and Lung Disorders
Published in Dilip Ghosh, Prasad Thakurdesai, Fenugreek, 2022
Amit D. Kandhare, Anwesha A. Mukherjee-Kandhare, Subhash L. Bodhankar
A study demonstrated the potential of dietary fenugreek seed (3%) administration against renin-angiotensin system-mediated renal damage in diabetic rats (Pradeep, Barman, and Srinivasan 2019). Fenugreek seed administration showed profound down-regulation in renal glucose transporters (GLUT-1 and GLUT-2), renal angiotensin-converting enzyme (ACE activity) and AT1 receptor expression, metabolites of the polyol pathway, and N-acetyl-β-d-glycosaminidase activity. The upregulated expression of kidney injury molecule-1, inducible nitric oxide, and type I collagen were markedly ameliorated by dietary fenugreek. Furthermore, podocyte damage was partially restored by fenugreek administration reflected by a correction in urinary nephrin, podocin, and podocalyxin markers. Diabetes-induced renal aberrations were also reduced by dietary fenugreek intake. The researcher concluded that dietary intake of fiber-rich fenugreek seeds was associated with inhibition of glucose translocation and renin-angiotensin system, which halted the development of diabetic nephropathy (Pradeep, Barman, and Srinivasan 2019).
The Nature of Renal Function
Published in Anthony R. Mundy, John M. Fitzpatrick, David E. Neal, Nicholas J. R. George, The Scientific Basis of Urology, 2010
All three layers of the glomerular capillary wall probably contribute to the retention of macromolecules in the capillary lumen. Ultrastructural studies using macromolecular tracers of different sizes and electrical charge suggest that very large molecules are completely excluded from the basement membrane, while smaller ones penetrate it to varying degrees (12). Small quantities of molecules of approximately the size of albumin appear to traverse the basement membrane but are retained at the filtration slits between the epithelial foot processes (13). The electrical charge, as well as the size, of molecules is an important determinant of their ability to cross the capillary wall into Bowman’s space (14). Proteinuric states are associated with loss of negative charge from one or more layers of the capillary wall. The passage of large amounts of protein from the plasma into the glomerular filtrate is prevented partly by the physical structure of the proteoglycan mesh of the basement membrane and partly by its electronegativity. The small amount of albumin that crosses the basement membrane is further contained by the polyanionic coat surrounding the epithelial cells and extending to the filtration slits between them. The relative importance of charge and size selectivity is still controversial. The filtration slits between foot processes are bridged by a fine membrane, the slit diaphragm, which consists mainly of a specialized membrane protein, nephrin (15). Nephrin molecules from adjacent foot processes interdigitate to form a zipper-like structure, which is thought to be the limiting part of the filtration complex for albumin. Mutations in the gene for nephrin cause a severe form of recessively inherited congenital nephrotic syndrome (CNS), known as CNS of the Finnish type (16). Other specialized proteins expressed in the foot processes are also essential to the proper formation of the filtration barrier, and mutations in the genes that code for them cause other, even rarer, forms of CNS. The role of these proteins, if any, in the pathogenesis of acquired forms of nephrotic syndrome is unknown.
TNF-α-mediated podocyte injury via the apoptotic death receptor pathway in a mouse model of IgA nephropathy
Published in Renal Failure, 2022
Qiang Wan, Jiabao Zhou, Yansheng Wu, Liqiang Shi, Weiwei Liu, Jiaoying Ou, Jiandong Gao
Podocytes, the GBM and endothelial cells constitute the glomerular filtration membrane, and the foot processes of neighboring podocytes are interdigitated, forming a complex modified adherens junction, known as the slit diaphragm [6]. Podocyte injury involves apoptosis, necrosis, detachment from the GBM and defective autophagy, ultimately leading to proteinuria [25]. The reduction in the number of podocytes in IgAN is closely associated with disease severity [26]. In vitro experiments have revealed that the mesangial cell-derived humoral factor TNF-α can alter glomerular permeability and cause podocyte apoptosis in the event of proteinuria in IgAN [7]. Nephrin is an important podocyte-specific protein and it is involved in signaling pathways regulating actin dynamics and cell survival [27]. Podocin is a structural molecule that interacts with nephrin and they both play an important role in supporting the slit diaphragm [28,29]. However, the pathway and underlying mechanisms through which TNF-α leads to podocyte apoptosis in IgAN have yet to be fully elucidated.
Gastric duplication cyst in an infant with Finnish-type congenital nephrotic syndrome: concurrence or coincidence?
Published in Acta Clinica Belgica, 2021
Tülin Güngör, Fehime Kara Eroğlu, Evrim Kargın Çakıcı, Fatma Yazılıtaş, Gökçe Can, Evra Çelikkaya, Deniz Karakaya, Eda Didem Kurt Şükür, Fatih Özaltın, Beytullah Yağız, Mehmet Bülbül
Most infants with CNS exhibit a failure to thrive due to insufficient oral intake and frequent vomiting. Any evaluation of vomiting by CNS infants should take into consideration the potential causes, such as increased nutritional requirement compared to healthy infants, hypo-peristalsis, edema of the gastrointestinal tract and uremia associated with chronic kidney failure [9]. Structural digestive disorders, such as hypertrophic pyloric stenosis, gastroesophagal reflux and intestinal malrotation, have to be considered. The etiology of hypertrophic pyloric stenosis is unknown but it is likely to be multifactorial, involving genetic predisposition and environmental factors. Pyloric stenosis appears to be associated with CNS. In one series, 12% of 41 infants with CNS presented pyloric stenosis. The reason for this association is not known [10]. A novel mutation in the nephrin gene was detected in our patient. Nephrin is expressed in the testis, central nervous system, pancreas, placenta, heart and lymphoid tissue; however, its expression in the digestive tract has not been clarified [11]. Perhaps the effects of the neprin gene on the gastrointestinal tract will be demonstrated as similar case samples increase in following years.
Physiological role of adiponectin in different tissues: a review
Published in Archives of Physiology and Biochemistry, 2020
S. Esmaili, M. Hemmati, M. Karamian
Transforming growth factor beta 1 (TGF-β1) is involved in pathogenesis of diabetic nephropathy through cellular hypertrophy and increased collagen synthesis. Adiponectin may inhibit changes made by TGF-β1 and improve diabetic complications. In this regard, rats that received injections of an adenovirus to cause overexpression of adiponectin (Ad-Adiop) had increased levels of nephrin mRNA in the renal cortex. Nephrin is a protein that is found in podocytes and is necessary for glomerular filtration. Down regulation of nephrin is involved in the development of proteinuria in diabetic nephropathy. Therefore, increasing levels of nephrin through adiponectin can lead to reduced albuminuria in diabetic nephropathy (Nakamaki et al. 2011). Adiponectin undermines the harmful effects of angiotensin ІІ (Fang et al. 2013), and decreases oxidative stress particularly induced by angiotensin ІІ like the activation of NADPH oxidase, inflammation (through the activation of NF-κB) and fibrosis (expression of fibronectin) in human renal tubular cells. Also, adiponectin inhibits angiotensin ІІ as the inducer of NADPH oxidase by AdiporR1 through the activation of AMPK pathways and cAMP-Epac (Cheng et al. 2012). Role of adiponectin in kidney pathophysiology is summarized in Figure 1.