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Rhein (RH), a natural anthraquinone compound, is considered an effective treatment candidate for ulcerative colitis (UC), whose multiple biological activities contribute to UC, including anti-inflammation, antioxidation, intestinal barrier repair, and microflora regulation. However, the application of RH is severely limited by its low water solubility, low bioavailability, and poor colonic targeting. Although some nanoparticles have been developed for the oral delivery of RH, most of them mainly highlighted only one effect of some drug delivery strategies but the above multiple biological activities. Therefore, a multiple polysaccharide-based nanodelivery system, comprising chitosan (CS) and fucoidan (FU), with pH/reactive oxygen species (ROS) sensitivity and mucosal adhesion, was developed and first used to load RH as a comprehensive treatment for UC. Briefly, RH-F/C-NPs were prepared using the polyelectrolyte self-assembly method; the average size of RH-F/C-NPs was 233.1 ± 5.7 nm, and the encapsulation rate of RH was 93.67 ± 1.60%. And it could maintain gastric stability and release RH in the colon with the designed pH/ROS sensitivity contributed by the polysaccharide-based structures. Cellular uptake experiments showed that both NCM 460 cells and RAW 264.7 cells had a good uptake of RH-F/C-NPs. Importantly, the effects of RH were highlighted in

β-Glucan, an essential natural polysaccharide widely distributed in cereals and microorganisms, exhibits extensive biological activities, including immunoregulation, anti-inflammatory, antioxidant, antitumor properties, and flora regulation. Recently, increasing evidence has shown that β-glucan has activities that may be useful for treating intestinal diseases, such as inflammatory bowel disease (IBD), and colorectal cancer. The advantages of β-glucan, which include its multiple roles, safety, abundant sources, good encapsulation capacity, economic development costs, and clinical evidence, indicate that β-glucan is a promising polysaccharide that could be developed as a health product or medicine for the treatment of intestinal disease. Unfortunately, few reports have summarized the progress of studies investigating natural β-glucan in intestinal diseases. This review comprehensively summarizes the structure-activity relationship of β-glucan, its pharmacological mechanism in IBD and colorectal cancer, its absorption and transportation mechanisms, and its application in food, medicine, and drug delivery, which will be beneficial to further understand the role of β-glucan in intestinal diseases.

Acute kidney injury (AKI), a common condition associated with a high mortality rate, is characterized by declined glomerular filtration rate, retention of nitrogen products, and disturbances in balance of water, electrolyte, and acid-base. Up to date, there is no effective treatment for AKI. Despite the continuous improvement in blood purification techniques, a considerable proportion of patients with AKI still progress to end-stage renal disease. These patients with advanced stage of end-stage renal disease will require long-term renal replacement therapy, which places a heavy burden on the family and the society. In recent years, the use of traditional Chinese medicine (TCM) in AKI management has been gradually increasing. Clinical evidence has demonstrated that three-month treatment with TCM produced better clinical outcomes in terms of clinical effectiveness rate and improvement in renal function (serum creatinine, neutrophil gelatinase-associated lipocalin, and cystatin C) compared with Western medicine. Rhubarb is a commonly used herb in TCM for the treatment of AKI. The main active component of rhubarb is emodin, which was first recorded in Shennong’s Classic of Materia Medica. It has been shown that emodin has a variety of pharmacological activities including antibacterial, anti-inflammatory, antiulcer, and immunosuppressive effects. Emodin has been found to be effective against renal fibrosis and has been widely studied for its effects on kidney diseases such as diabetic nephropathy, renal fibrosis, and AKI. Moreover, promising results have been obtained from these studies. In this study, the results obtained from research on the use of emodin for AKI treatment has been reviewed.

An oral nanoparticle (NPs) encapsulated in chitosan/alginate hydrogel (CA-Gel) with dual-sensitive in pH and reactive oxygen species (ROS) was developed to load curcumin (CUR) based on the intracellular-specific characteristics of macrophages. Chondroitin sulfate (CS) wrapped PBAE-SA-PAPE with intracellular pH/ROS dual-sensitive characteristics and CUR via a simple nanoprecipitation method to form NPs (CS-CUR-NPs), and mixed CA-Gel to acquire the final preparation (CS-CUR-NPs-Gel). CS-CUR-NPs displayed an ideal average particle size (179.19±5.61nm) and high encapsulating efficiency (94.74±1.15%). CS showed a good targeting ability on macrophages and the CA-Gel contribution in protecting NPs from being destroyed in the upper gastrointestinal tract. As expected, CS-CUR-NPs-Gel could significantly alleviate inflammation in DSS-induced UC mice via TLR4-MAPK/NF-κB pathway. This study is the first to attempt to design a novel pH/ROS dual-stimulated release strategy in helping intracellular CUR delivery and anticipated for efficient anti-UC therapy.

Background: Renal cell carcinoma (RCC) is a common malignant tumor of the urinary system.The incidence rate was increasing year by year, which has become a worldwide health problem. Achyranthis bidentate radix（ABR) is a traditional Chinese medicine that has been commonly reported on the prevention and treatment of RCC. However, the detailed mechanism of ABR is unclear. Therefore, this study aims to explore the possible molecular mechanism of ABR in the treatment of RCC based on network pharmacology and molecular docking.Methods: The main active compounds of ABR were obtained from pharmacology analysis platform of the Chinese Medicine System (TCMSP). The targets of ABR active compounds were obtained from TCMSP and Swiss Target Prediction. The targets of RCC were then screened in the Gene Cards and Online Mendelian Inheritance in Man (OMIM). The network of “medicine-ingredients-disease-targets” was established employing network pharmacology, and the key targets and core pathways were determined by R analysis. The molecular docking method was used to evaluate the binding activity between the target and the active compounds of ABR.Results: Twenty active compounds were found from ABR and are involving in 164 targets. The results of network analysis indicated that the targets mainly involve biological processes such as active oxygen metabolism, oxidative stress, cell proliferation, and apoptosis. ABR was able to treat RCC through regulating AGE-RAGE, PI3K-Akt, MAPK, JAK-STAT, NF-KB, and other major signaling pathways. Quercetin, baicalein, kaempferol had a strong binding to the target proteins of and MAPK1, AKT1, HSP90AA1.Conclusion: Flavonoids in ABR may be the material basis for its treatment of RCC. The mechanisms of action were through regulating active oxygen metabolism, inhibiting oxidative stress, cell proliferation, activating tumor cell apoptosis pathway, regulating protein kinase activity and nuclear receptor Activity, etc.

Objective: To explore the mechanism of Bazhen Decoction in the treatment of Clear-cell renal cell carcinomaCRCC）through the methods of network pharmacology and bioinformatics.Methods: The active ingredients of Bazhen decoction were identified through TCMSP, Targets of each active ingredients were accessed through TCMSP and Swiss Target Prediction. The target gene by CRCC was obtained from GEO database and interlinked of both active ingredient and cancer gene was performed to obtain drug-disease protein target gene. Cytoscape 3.7.1 software was used to draw the active ingredient-target network. The protein interaction network was drawn using the String database and Cytoscape 3.7.1 software. Gene Ontology (GO) and KEGG pathway analysis on the target were performed using R language.Results: From analysis, 160 of active ingredients were found from Bazhen Decoction with 5002 of predicted targets; 544 of disease targets and 39 drug-disease protein target genes.Network analysis on drug-disease protein interaction found out the targets were mainly involve mechanisms such as positive regulation of angiogenesis, positive regulation of vasculature development, epithelial cell proliferation,growth factor receptor and growth factor binding activity, as well as prostanoid receptor binding activity. Treatment of clear-cell renal cell carcinoma can be controlled through regulating the signaling pathways in relation to bladder cancer, MicroRNAs in cancer, focal adhesion, Human cytomegalovirus infection, Ovarian steroidogenesis and HIF-1 signaling pathway.Conclusion: The mechanism of Bazhen Decoction in the treatment of CRCC reflects the characteristics of multiple ingredients, multiple targets, and multiple pathways of traditional Chinese medicine. The findings from this study able to provide a theoretical basis on anti-cancer mechanism.

Background. Acute kidney injury is a global problem, which brings a great burden to the society and family. The component of rhubarb, Salvia miltiorrhiza, Astragalus membranaceus, and safflower (CRSAS) has been proved as an useful agent to treat acute kidney injury (AKI) patients in China. Objective. To assess the effect of CRSAS on human renal tubular epithelial cells (HK-2) after the hypoxia/reoxygenation (H/R) and investigate the potential mechanisms. Methods. Network pharmacology was used to predict the potential pathways shared by CRSAS and AKI. Cell counting kit-8 (CCK-8) was used to assess the HK-2 vitality. Apoptosis of HK-2 cells was detected by carboxyfluorescein succinimidyl ester/propidium iodide (CFSF/PI) staining. Expression of GRP78, CHOP, caspase-3, and Bax was detected by western blot and quantitative real-time RT-PCR. Result. CRSAS and AKI shared the endoplasmic reticulum stress (ERS) pathway based on network pharmacology analysis. CRSAS increases the vitality of HK-2 cells and reduces the apoptosis of HK-2 cells induced by H/R injury. The expression of GRP78 and CHOP in CRSAS groups was lower than that of control groups. Conclusions. H/R can induce HK-2 cell apoptosis and ERS. CRSAS can reduce HK-2 cell apoptosis by inhibiting the ERS. Therefore, CRSAS might be able to treat kidney disease due to I/R injury. Animal experiment should be done to further prove our finding.

Herein, a β-1,3-d-glucan based microcarrier, yeast cell wall microparticles (YPs), was used to develop a food-source-based nano-in-micro oral delivery system for ulcerative colitis (UC) treatment. Briefly, lactoferrin (Lf), which targets intestinal epithelial cells, was used to encapsulate emodin (EMO) to form nanoparticles (EMO-NPs), and then loaded into YPs with the natural macrophages targeting ability, forming a final formula with two outer-inner targeting layers (EMO-NYPs). These dual-targeting strategy could enhance the dual-effects of EMO in anti-inflammatory and mucosal repair effects respectively. As expected, cell uptake assessment confirmed that EMO-NPs and EMO-NYPs could target on the Lf and dection-1 receptors on the membranes of Caco-2 cells and macrophages, respectively. Importantly, EMO-NYPs showed the best anti-UC effects compared to EMO-NPs and free EMO, by inhibiting NF-κB pathway to anti-inflammation and promoting intestinal mucosa repair via MLCK/pMLC2 pathway. The results show that EMO-NYPs are a promising food-based oral delivery system in anti-UC.

Herein, dual-bioresponsive of Rhein (RH) in promoting colonic mucous damage repair and controlling inflammatory reactions were combined by the dual-targeting (intestinal epithelial cells and macrophages) oral nano delivery strategy for effective therapy of ulcerative colitis (UC). Briefly, two carbohydrates, calcium pectinate (CP) and hyaluronic acid (HA) were used to modify lactoferrin (LF) nanoparticles (NPs) to encapsulate RH (CP/HA/RH-NPs). CP layer make CP/HA/RH-NPs more stable and protect against the destructive effects of the gastrointestinal environment and then release HA/RH-NPs to colon lesion site. Cellular uptake evaluation confirmed that NPs could specifically target and enhance the uptake rate via LF and HA ligands. in vivo experiments revealed that CP/HA/RH-NPs significantly alleviated inflammation by inhibiting the TLR4/MyD88/NF-κB signaling pathway and accelerated colonic healing. Importantly, with the help of CP, this study was the first to attempt for LF as a targeting nanomaterial in UC treatment and offers a promising food-based nanodrug in anti-UC.

The efficacy of vitamin D on vascular function remains controversial in chronic kidney disease (CKD) patients. The aim of the present work was to perform a meta-analysis of randomized controlled trials to evaluate the efficacy of vitamin D on vascular function in CKD patients. We searched Medline, the Cochrane Central Register of Controlled Trials, Embase, the Science Citation Index, and clinical trial registries for randomized controlled trials comparing vitamin D with a placebo in CKD patients. We included seven trials. For flow-mediated dilation (FMD), there was no significant difference between the two groups (WMD 1.66%; 95% CI − 0.2 to 3.51, p = 0.08; with significant heterogeneity, p

To evaluate the efficacy and safety of PA21 versus sevelamer in dialysis patients. We searched Medline, Embase, Science Citation Index, Cochrane Central Register of Controlled Trials, and Clinical Trial Registries for randomized controlled trials comparing PA21 and sevelamer in dialysis patients. Four studies were included. Compared with sevelamer group, PA21 needed fewer mean daily number of tablets (WMD, − 7.97 pill; 95% CI, − 11.28 to − 4.65, p