Recent research has greatly increased our knowledge regarding the molecular mechanisms of collagen synthesis and processing. Heat specific shock protein (HSP47) is a collagen-specific molecular chaperone, and helps in post-translational modifications of procollagens, during biosynthesis of collagen. Both in vivo and in vitro studies have convincingly demonstrated that HSP47 is localized in the endoplasmic reticulum of collagen-producing cells, and that its synthesis is closely associated with the rate of procollagen assembly. Recent studies are directed towards the pathological relevance of HSP47 in tissue scarring, a process that is characterized by excessive accumulation of collagens. It appears likely that increased levels of HSP47 in fibrotic diseases assist in increased assembly of procollagen, and thereby help in excessive accumulation of collagens in the fibrotic mass. Such profibrotic effects of HSP47 suggest that modulation of HSP47 expression in scarring diseases might alter the course of fibrotic diseases. In this brief article, we review the role of HSP47 in renal fibrotic diseases and its relevance to other scarring diseases.

To determine whether life-long reduction in the GH/IGF-I activity could be renoprotective and attenuate renal damage, we examined the kidneys of transgenic strain of rats whose GH gene was suppressed by an antisense GH transgene. Male rats homozygote for the transgene (tg/tg) had a reduced number of pituitary GH-secreting cells, and 53% less plasma concentration of IGF-I, compared with wild-type (wt/wt) rats at 6 months of age. We compared the kidneys obtained from male wild-type young (6 months) and old (24 months) rats with male homozygote transgenic young (6 months) and old (24 months) rats. The wild-type rats showed features of renal damage as they grew older, including glomerulosclerosis (higher sclerosis index at 24 months; P<0.0001), tubulointerstitial widening (increased interstitial volume at 24 months; P<0.0001), and presence of phenotypically altered myofibroblasts and increased accumulation of collagens. Life-long suppression of GH/IGF-I activity resulted in prevention of age-associated renal diseases in homozygote transgenic rats at 24 months (sclerosis index: 1.65+/-0.11 in wild-type vs. 0.463+/-0.061 in transgenic rats; interstitial volume: 34.2+/-0.82 in wild-type vs. 12.8+/-0.32 in homozygote transgenic rats at 24 months; P<0.0001). Such reno-protective effects in transgenic rats were associated with decreased renal accumulation of ED-1-positive macrophages, and less renal expression of pro-fibrogenic factors, including connective tissue growth factor and heat shock protein 47. Our in vivo genetic manipulation study provides direct evidence of reno-protective effects of life-long suppression of GH/IGF-I system, by reducing renal infiltration of inflammatory cells, and by suppressing the synthesis of profibrogenic factors and accumulation of extracellular matrix protein.

A 57-year-old Japanese female was admitted because of edema, hypoproteinemia and proteinuria. Her histopathological findings of renal biopsy specimen were quite unique. Light microscopic findings suggested membranous glomerulonephritis, but no significant deposition of immunoglobulins or complements was detected in glomeruli by immunofluorescence. Electron microscopic examination revealed irregular thickening of the glomerular basement membrane (GBM). The GBM had no electron-dense deposits, but numerous microparticles varying in shape and size were present in all the thickened GBM and occasionally in the mesangium. The microparticles were round or oval in shape, and the size varied widely, measuring 25-290 nm (mostly 40-120 nm). The cytoplasmic infolding into the GBM by podocytes was seen. The large-sized particles had microgranules, mimicking free ribosomes seen in podocytes or endothelial cells. We conclude that cytoplasmic infolding and subsequent degradation may, partly, contribute to the formation of microparticles in the GBM.

Background Tacrolimus trough levels (C0) are used in most transplant centres for therapeutic drug monitoring (TDM) of tacrolimus (Tac). The target range of Tac C0 has been remarkably changed, with a target as low as 3–7 ng/ml in the 2009 European consensus conference and a target of 4–12 ng/ml (preferably to 7–12 ng/ml) following the second consensus report in 2019. Our aim was to investigate whether reaching early Tac therapeutic targets and maintaining time in the therapeutic range (TTR) according to the new recommendations may be necessary for preventing acute rejection (AR) during the first month after transplantation. Methods A retrospective study including 160 adult renal transplant patients (113 men and 47 women) with a median age of 36.3 (20–44) years was conducted between January 2018 and December 2019 at 103 Military Hospital (Vietnam). Tac trough levels were recorded in the first month, and episodes of AR were confirmed by kidney biopsy. Tac TTR was calculated as the percentage of time within the target range of 7–12 ng/ml, according to the 2019 second consensus report. Multivariate Cox analysis was performed to identify the correlation between the Tac target range and TTR with AR. Results In the first month after RT, 14 (8.8%) patients experienced AR. There was a significant difference in the incidence of AR between the Tac level groups of < 4, 4–7 and > 7 ng/ml (p = 0.0096). In the multivariate Cox analysis, after adjusting for related factors, a mean Tac level > 7 ng/ml was associated with an 86% decreased risk of AR compared with that of 4–7 ng/ml in the first month (HR, 0.14; 95% CI, 0.03–0.66; p = 0.0131). Every 10% increase in TTR was associated with a 28% lower risk of AR (HR, 0.72; 95% CI, 0.55–0.94; p = 0.014). Conclusion Gaining and maintaining Tac C0 according to the 2019 second consensus report might reduce the risk of AR in the first month following transplantation.

The primary goal of this study is to investigate the classification capability of several artificial intelligence techniques, including the decision tree (DT), multilayer perceptron (MLP) network, Naïve Bayes, radial basis function (RBF) network, and support vector machine (SVM) for evaluating spatial and temporal variations in water quality. The application case is the Song Quao-Ca Giang (SQ-CG) water system, a main domestic water supply source of the city of Phan Thiet in Binh Thuan province, Vietnam. To evaluate the water quality condition of the source, the government agency has initiated an extensive sampling project, collecting samples from 43 locations covering the SQ reservoir, the main canals, and the surrounding areas during 2015–2016. Different classifying models based on artificial intelligence techniques were developed to analyze the sampling data after the performances of the models were evaluated and compared using the confusion matrix, accuracy rate, and several error indexes. The results show that machine-learning techniques can be used to explicitly evaluate spatial and temporal variations in water quality.