Natural polysaccharides as promising reno-protective agents for the treatment of various kidney injury.

Renal injury, a prevalent clinical outcome with multifactorial etiology, imposes a substantial burden on society. Currently, there remains a lack of effective management and treatments. Extensive research has emphasized the diverse biological effects of natural polysaccharides, which exhibit promising potential for mitigating renal damage. This review commences with the pathogenesis of four common renal diseases and the shared mechanisms underlying renal injury. The renoprotective roles of polysaccharides in vivo and in vitro are summarized in the following five aspects: antioxidative stress effects, antiapoptotic effects, antiinflammatory effects, antifibrotic effects, and gut modulatory effects. Furthermore, we explore the structure-activity relationship and bioavailability of polysaccharides in relation to renal injury, as well as investigate their utility as biomaterials for alleviating renal injury. The clinical experiments of polysaccharides applied to patients with chronic kidney disease are also reviewed. Broadly, this review provides a comprehensive perspective on the research direction of natural polysaccharides in the context of renal injury, with the primary aim to serve as a reference for the clinical development of polysaccharides as pharmaceuticals and prebiotics for the treatment of kidney diseases.

Study on Fu-Fang-Jin-Qian-Cao Inhibiting Autophagy in Calcium Oxalate-induced Renal Injury by UHPLC/Q-TOF-MS-based Metabonomics and Network Pharmacology Approaches.

INTRODUCTION: Fu-Fang-Jin-Qian-Cao is a Chinese herbal preparation used to treat urinary calculi. Fu-Fang-Jin-Qian-Cao can protect renal tubular epithelial cells from calcium oxalateinduced renal injury by inhibiting ROS-mediated autopathy. The mechanism still needs further exploration. Metabonomics is a new subject; the combination of metabolomics and network pharmacology can find pathways for drugs to act on targets more efficiently. METHODS: Comprehensive metabolomics and network pharmacology to study the mechanism of Fu-Fang-Jin-Qian-Cao inhibiting autophagy in calcium oxalate-induced renal injury. Based on UHPLC-Q-TOF-MS, combined with biochemical analysis, a mice model of Calcium oxalateinduced renal injury was established to study the therapeutic effect of Fu-Fang-Jin-Qian-Cao. Based on the network pharmacology, the target signaling pathway and the protective effect of Fu- Fang-Jin-Qian-Cao on Calcium oxalate-induced renal injury by inhibiting autophagy were explored. Autophagy-related proteins LC3-II, BECN1, ATG5, and ATG7 were studied by immunohistochemistry. RESULTS: Combining network pharmacology and metabolomics, 50 differential metabolites and 2482 targets related to these metabolites were found. Subsequently, the targets enriched in PI3KAkt, MAPK and Ras signaling pathways. LC3-II, BECN1, ATG5 and ATG7 were up-regulated in Calcium oxalate-induced renal injury. All of them could be reversed after the Fu-Fang-Jin-Qian- Cao treatment. CONCLUSIONS: Fu-Fang-Jin-Qian-Cao can reverse ROS-induced activation of the MAPK signaling pathway and inhibition of the PI3K-Akt signaling pathway, thereby reducing autophagy damage of renal tubular epithelial cells in Calcium oxalate-induced renal injury.

Corrigendum: Phyllanthus niruri L. exerts protective effects against the calcium oxalate-induced renal injury via ellgic acid.

[This corrects the article DOI: 10.3389/fphar.2022.891788.].

Bone Marrow-Derived Mesenchymal Stem Cells Transplantation Attenuates Renal Fibrosis Following Acute Kidney Injury in Rats by Diminishing Pericyte-Myofibroblast Transition and Extracellular Matrix Augment.

BACKGROUND: Renal fibrosis is a common chronic outcome of acute kidney injury (AKI). Pericyte-myofibroblasts transition and production of abundant extracellular matrix are the important pathologic basis. This study investigated the effect of bone marrow-derived mesenchymal stem cells (BMSCs) transplantation on the AKI kidney fibrosis and the possible mechanisms. METHODS: By constructing the animal and cell model of AKI pericyte injury, the therapeutic effect of BMSCs on pericyte-myofibroblasts transition was detected. The production and accumulation of extracellular matrix, including collagen I, collagen III, and fibronectin were also tested. The mechanism was revealed by means of analysis of signal pathway. RESULTS: After AKI insult, many myofibroblasts emerged in the renal interstitium together with a large amount of extracellular matrix components. The BMSCs transplantation significantly decreased the number of myofibroblasts trans-differentiated from pericytes in the AKI model. The changes of vascular endothelial growth factor subtypes and Ang-I/AngII secreted by pericytes were also significantly reduced after BMSCs co-culture. At the same time, extracellular matrix components, including collagen I, collagen III, and fibronectin, decreased significantly. Transplantation treatment alleviated the fibrosis score. The transforming growth factor ß (TGF-ß) concentration decreased as well as the levels of Smad2/3 and p-Smad2/3 with the presence of BMSCs therapy. CONCLUSIONS: Bone marrow-derived mesenchymal stem cells transplantation diminished pericyte-myofibroblast transition and extracellular matrix augment after AKI by regulating the TGF-ß/Smad2/3 signaling pathway. It may be used as a novel therapeutic method for retarding renal fibrosis, which is worthy of further study.

Current status and temporal trend of disease burden of thyroid cancer in China from 1990 to 2019.

OBJECTIVE: Thyroid cancer has been an increasingly high-profile public health issue. Comprehensive assessment for its disease burden seems particularly important for understanding health priorities and hinting high-risk populations. METHODS: We estimated the age-sex-specific thyroid cancer burden and its temporal trend in China from 1990 to 2019 by following the general methods from the global burden of disease (GBDs) 2019 Study. And Joinpoint regression model, the Cox-Stuart trend test, and Cochran-Armitage test were applied for the analysis of temporal and age trend. The Mantel-Haenszel statistical method was used to compare the gender difference. RESULTS: From 1990 to 2019, the age-standardized incidence rate of thyroid cancer in China has almost doubled to 2.05 per 100,000. Although the mortality rate and DALY rate kept leveling off, they presented a downtrend among females, while an upward trend in males. While the average annual percentage changes of those metrics all became deline since 2010 than the previous years. With age advancing, the rates of incidence, mortality, and DALYs for both sexes all presented linear fashion increases, which was particularly typical among males. CONCLUSION: Given the serious trend and gender-age heterogeneity of Chinese thyroid cancer burden, male gender and advanced age may be related to poor prognosis of thyroid cancer, and strengthening primary prevention and exploring the underlying risk factors should be among the top priorities.

Phyllanthus Niruri L. Exerts Protective Effects Against the Calcium Oxalate-Induced Renal Injury via Ellgic Acid.

Background: Urolithiasis or kidney stones is a common and frequently occurring renal disease; calcium oxalate (CaOx) crystals are responsible for 80% of urolithiasis cases. Phyllanthus niruri L. (PN) has been used to treat urolithiasis. This study aimed to determine the potential protective effects and molecular mechanism of PN on calcium oxalate-induced renal injury. Methods: Microarray data sets were generated from the calcium oxalate-induced renal injury model of HK-2 cells and potential disease-related targets were identified. Network pharmacology was employed to identify drug-related targets of PN and construct the active ingredient-target network. Finally, the putative therapeutic targets and active ingredients of PN were verified in vitro and in vivo. Results: A total of 20 active ingredients in PN, 2,428 drug-related targets, and 127 disease-related targets were identified. According to network pharmacology analysis, HMGCS1, SQLE, and SCD were identified as predicted therapeutic target and ellagic acid (EA) was identified as the active ingredient by molecular docking analysis. The increased expression of SQLE, SCD, and HMGCS1 due to calcium oxalate-induced renal injury in HK-2 cells was found to be significantly inhibited by EA. Immunohistochemical in mice also showed that the levels of SQLE, SCD, and HMGCS1 were remarkably restored after EA treatment. Conclusion: EA is the active ingredient in PN responsible for its protective effects against CaOx-induced renal injury. SQLE, SCD, and HMGCS1 are putative therapeutic targets of EA.

The Spatial Distribution of Renal Fibrosis Investigated by Micro-probe Terahertz Spectroscopy System.

Renal fibrosis, which is characterized as progressive extracellular matrix accumulation, is a common feature of different stages of chronic kidney disease, and the degree of fibrosis is strongly associated with renal function. In clinical practice, precise understanding of the space distribution of fibrosis is extremely important for the diagnosis and prognosis of renal disease. Rapid advances in terahertz (THz) technology have been made, and this technology has a broad application in bio-detection, as it can interact and measure the collective vibrations and rotations of molecular groups. It is well known that hydroxyproline (HYP) is the key component of collagen, which is synthesized by fibroblasts to maintain the extracellular matrix, and HYP content detection in tissue homogenate can be achieved by classical biochemistry method. In this study, a THz microprobe system was employed to conduct THz microspatial scanning with a resolution of 20 µm. Both the content and distribution of HYP were directly characterized by the THz absorption spectrum. The absorption intensity in the THz spectrum was used to determine HYP density in renal tissues; therefore, the fibrosis change in the kidneys can be determined using THz scanning at micrometer resolution, which provides more possibilities for precise diagnosis of renal fibrosis.

Bioaugmentation with syntrophic volatile fatty acids-oxidizing consortia to alleviate the ammonia inhibition in continuously anaerobic digestion of municipal sludge.

Ammonia inhibition easily affects the performance of anaerobic digestion (AD) for municipal sludge and the oxidization of volatile fatty acids (VFAs) is the rate-limiting step of this process. Bioaugmentation is considered to be an effective method to alleviate ammonia inhibition of AD, but most study used the hydrogenotrophic methanogens as the bioaugmentation culture. In this study, bioaugmentation of mesophilic AD (MAD) and thermophilic AD (TAD) under ammonia inhibition with syntrophic acetate and propionate oxidizing consortia was investigated. The results showed that the bioaugmented reactors recovered earlier than control reactors with 20 (MAD) and 8 (TAD) days, respectively. The high-throughput 16S rRNA gene sequencing indicated that the relative abundance of carbohydrates fermenter (Lentimicrobium), syntrophic VFAs-oxidizing bacteria (Rikenellaceae_DMER64, Smithella and Syntrophobacter) and acetoclastic and hydrogenotrophic methanogens (Methanosaeta, Methanolinea and Methanospirillum) increased in MAD after bioaugmentation. However, part of the bioaugmentation culture could not adapt to the high free ammonia (FAN) concentration in MAD and the effect was weakened. In TAD, proteolytic bacteria (Keratinibaculum and Tepidimicrobium), syntrophic VFAs-oxidizing bacteria (Syntrophomonas) and hydrogenotrophic methanogen (Methanosarcina) were strengthened. The effect of bioaugmentation in TAD was durable even at higher organic loading rate (OLR), due to its positive influence on microbial community. These results suggested that the different bioaugmentation mechanism occurred in MAD and TAD, which are derived from the synergetic effects of ammonia tolerance and microbial interactions. Our study revealed the VFAs-oxidizing consortia as bioaugmented culture could be the potential strategy to alleviate the ammonia stress of AD.

Network Pharmacology-Based Approach to Investigate the Molecular Targets of Sinomenine for Treating Breast Cancer.

PURPOSE: Sinomenine has been known to inhibit the proliferation of breast cancer cells. However, its targets have not been found yet. This study aimed to search for molecular targets of sinomenine for treating breast cancer via network pharmacology. METHODS: Potential targets of sinomenine or breast cancer were separately screened from indicated databases. The common targets of both sinomenine and breast cancer were considered as the targets of sinomenine for treating breast cancer. A sinomenine-target-pathway network was constructed based on the obtained results from Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway enrichment analysis. The putative targets of sinomenine were further determined by using protein-protein interaction (PPI) analysis and molecular docking. Finally, the putative targets were verified in vitro and in vivo. RESULTS: Twenty predicted targets were identified through network pharmacological analysis. Gene Ontology (GO) and KEGG pathway enrichment indicated that these predicted targets enriched in the process of MAP kinase activity, VEGF signaling pathway, Relaxin signaling pathway, Growth hormone synthesis, secretion and action. MAPK1, NOS3, NR3C1, NOS1 and NOS2 were further identified as the putative targets by using PPI and molecular docking analysis. Expression of MAPK1, NR3C1, NOS1, NOS2 and NOS3 genes were significantly regulated by sinomenine in both MCF-7 cells and MDA-MB-231 cells. Furthermore, the expression of NR3C1 in human breast cancer specimens was lower than that in para-tumor normal tissues. Meanwhile, the expression of NR3C1 in xenograft tumors was up-regulated after sinomenine treatment. CONCLUSION: MAPK1, NR3C1, NOS1, NOS2 and NOS3 were identified as the putative targets of sinomenine for treating breast cancer. NR3C1 was preliminarily confirmed as a target of sinomenine in two breast cancer cell lines, xenograft tumor models and human breast cancer specimens. These data indicated that the network pharmacology-based prediction of sinomenine targets for treating breast cancer could be reliable.