Self-expanding cellulose sponge with enhanced hemostatic ability by tannic acid/metal ion composite coating for highly effective hemostasis of difficult-to-control bleeding wounds.

Refractory bleeding presents a critical, life-threatening challenge, and the goal of medical professionals and researchers has always been to achieve safe and effective hemostasis for bleeding wounds. In this study, we utilized the benefits of a self-expanding cellulose sponge to control incompressible bleeding, which is achieved this by creating a tannic acid/metal ion coating on the surface and within the pores of the sponge to improve its hemostatic effectiveness. The effects of various types and concentrations of metal ions (calcium, magnesium, iron, and zinc) on hemostatic efficiency and biosafety is systematically investigated. The results from bacteriostasis and in vitro coagulation experiments identified 0.3 wt% Fe3+ as the optimal metal ion coating. Scanning electron microscope energy spectrum analysis confirmed the uniform distribution of Fe3+ within the cellulose sponge. Furthermore, the in vivo and in vitro results demonstrated that the prepared tannic acid/Fe3+ coated composite hemostatic sponge exhibits excellent coagulation ability and biocompatibility. Both the bleeding time and theblood loss in two bleeding models are significantly reduced, showing promising potential for treating extensive surface bleeding and deep penetrating wounds. Furthermore, the straightforward preparation method for this composite hemostatic sponge facilitates additional research towards market application.

Popcorn-Inspired Expanded Graphite Microspheres with Controlled Morphology and Considerable Conductivity.

The structured processing of graphite is complex and challenging, in which expanded graphite plays a crucial role. Given its superior physical and chemical properties, expanded graphite finds extensive application in diverse domains such as electrochemistry and thermal management. However, the traditional preparation process is inconvenient in effectively meeting the design requirements on the macro and micro scales, which presents a challenge for the structured processing of expanded graphite materials. Here, an innovative method is first proposed for the controllable preparation of expanded graphite microspheres. Inspired by the explosion process of popcorn, the controlled gas release inside the natural flake graphite during chemical expansion is regulated by fuming sulfuric acid, realizing the controllable preparation of expanded graphite microspheres. Subsequently, sulfur trioxide can also intensify the degree of oxidation on the surface of the microspheres. The controllable microsphere morphology endows the composite with good isotropic network bonding, with considerable thermal conductivity of 1.703 W m-1 K-1 at low loading of 10 wt.% and reliable cyclic stability. This work opens up a new way for the morphology control of expanded graphite and provides a novel design thought for the physical and chemical structure control of carbon materials in the future.

Effects of fasudil on glial cell activation induced by tooth movement.

BACKGROUND: Orthodontic pain affects the physical and mental health of patients. The spinal trigeminal subnucleus caudalis (SPVC) contributes to the transmission of pain information and serves as a relay station for integrating orofacial damage information. Recently, glial cells have been found to be crucial for both acute and maintenance phases of pain. It has also been demonstrated that rho kinase (ROCK) inhibitors can manage different pain models by inhibiting glial cell activation. Here, we hypothesized that orthodontic pain is related to glial cells in the SPVC, and Fasudil, a representative rho/rock kinase inhibitor, can relieve orthodontic pain by regulating the function of glial cells and the related inflammatory factors. In this study, we constructed a rat model of tooth movement pain and used immunofluorescence staining to evaluate the activation of microglia and astrocytes. Quantitative real-time PCR was used to detect the release of related cytokines and the expression of pain-related genes in the SPVC. Simultaneously, we investigated the effect of Fasudil on the aforementioned indicators. RESULTS: In the SPVC, the expression of c-Fos peaked on day 1 along with the expression of OX42 (related to microglial activation), CD16 (a pro-inflammatory factor), and CD206 (an anti-inflammatory factor) on day 3 after tooth movement, followed by a gradual decrease. GFAP-staining showed that the number of activated astrocytes was the highest on day 5 and that cell morphology became complex. After Fasudil treatment, the expression of these proteins showed a downward trend. The mRNA levels of pro-inflammatory factors (IL-1ß and TNF-α) peaked on day 3, and the mRNA expression of the anti-inflammatory factor TGF-ß was the lowest 3 days after tooth movement. Fasudil inhibited the mRNA expression of pain-related genes encoding CSF-1, t-PA, CTSS, and BDNF. CONCLUSION: This study shows that tooth movement can cause the activation of glial cells in SPVC, and ROCK inhibitor Fasudil can inhibit the activation of glial cells and reduce the expression of the related inflammatory factors. This study presents for the first time the potential application of Fasudil in othodontic pain.

Mechanically Stable and Biocompatible Polymer Brush Coated Dental Materials with Lubricious and Antifouling Properties.

Surface modification plays a crucial role in enhancing the functionality of implanted interventional medical devices, offering added advantages to patients, particularly in terms of lubrication and prevention of undesired adsorption of biomolecules and microorganisms, such as proteins and bacteria, on the material surfaces. Utilizing polymer brushes for surface modification is currently a promising approach to maintaining the inherent properties of materials while introducing new functionalities to surfaces. Here, surface-initiated atom transfer radical polymerization (SI-ATRP) technology to effectively graft anionic, cationic, and neutral polymer brushes from a mixed silane initiating layer is employed. The presence of a polymer brush layer significantly enhances the lubrication performance of the substrates and ensures a consistently low coefficient of friction over thousands of friction cycles in aqueous environments. The antimicrobial efficacy of polymer brushes is evaluated against gram-positive Staphylococcus aureus (S. aureus) and gram-negative Escherichia coli (E. coli). It is observed that polym er brushes grafted to diverse substrate surfaces displays notable antibacterial properties, effectively inhibiting bacterial attachment. Furthermore, the polymer brush layer shows favorable biocompatibility and anti-inflammatory characteristics, which shows potential applications in dental materials, and other fields such as catheters and food packaging.

Effects of polypropylene micro(nano)plastics on soil bacterial and fungal community assembly in saline-alkaline wetlands.

Microplastic pollution is a major environmental threat, especially to terrestrial ecosystems. To better understand the effects of microplastics on soil microbiota, the influence of micro- to nano-scale polypropylene plastics was investigated on microbial community diversity, functionality, co-occurrence, assembly, and their interaction with soil-plant using high-throughput sequencing approaches and multivariate analyses. The results showed that polypropylene micro/nano-plastics mainly reduced bacterial diversity, not fungal, and that plastic size had a stronger effect than concentration on the assembly of microbial communities. Nano-plastics decreased the complexity and connectivity of both bacterial and fungal networks compared to micro-plastics. Moreover, bacteria were more sensitive and deterministic to polypropylene micro/nano-plastic stress than fungi, as shown by their different growth rates, guanine-cytosine content, and cell structure. Interestingly, the dominant ecological process for bacteria shifted from stochastic drift to deterministic selection with polypropylene micro/nano-plastic exposure. Furthermore, nano-plastics directly or indirectly disrupted the interactions within intra-microbes and between soil-bacteria-plant by altering soil nutrients and stoichiometry (C:N:P) or plant diversity. Collectively, the results indicate that polypropylene nano-plastics pose more ecological risks to soil microbes and their plant-soil interactions. This study sheds light on the potential ecological consequences of polypropylene micro/nano-plastic pollution in terrestrial ecosystems.

Association between circulatory complement activation and hypertensive renal damage: a case-control study.

OBJECTIVE: The aim of this study was to investigate the potential importance of complement system activation, with particular emphasis on the complement alternative pathway (AP), in the pathogenesis of hypertensive renal damage. METHODS: Serum complement C3, complement Factor H (CFH) and AP activation were assessed in 66 participants with established essential hypertension with renal damage (RD). Fifty-nine patients with age- and sex-matched essential hypertension without renal damage (NRD) and 58 healthy participants (normal) were selected. RESULTS: Our study revealed that C3 and AP50 continuously increased from normal to NRD to RD (p < 0.05, respectively), while CFH was significantly lower than that in NRD and healthy participants (p < 0.05, respectively). After multifactorial logistic regression analysis corrected for confounders, elevated serum C3 (p = 0.001) and decreased CFH (p < 0.001) were found to be independent risk factors for hypertension in healthy participants; elevated serum C3 (p = 0.034), elevated AP50 (p < 0.001), decreased CFH (p < 0.001), increased age (p = 0.011) and increased BMI (p = 0.013) were found to be independent risk factors for the progression of hypertension to hypertensive renal damage; elevated serum C3 (p = 0.017), elevated AP50 (p = 0.023), decreased CFH (p = 0.005) and increased age (p = 0.041) were found to be independent risk factors for the development of hypertensive renal damage in healthy participants. CONCLUSION: Abnormal activation of complement, particularly complement AP, may be a risk factor for the development and progression of hypertensive renal damage.

Occurrence, fate, and risk assessment of antibiotics in conventional and advanced drinking water treatment systems: From source to tap.

The occurrence and removal of 38 antibiotics from nine classes in two drinking water treatment plants (WTPs) were monitored monthly over one year to evaluate the efficiency of typical treatment processes, track the source of antibiotics in tap water and assess their potential risks to ecosystem and human health. In both source waters, 18 antibiotics were detected at least once, with average total antibiotic concentrations of 538.5 ng/L in WTP1 and 569.3 ng/L in WTP2. The coagulation/flocculation and sedimentation, sand filtration and granular activated carbon processes demonstrated limited removal efficiencies. Chlorination, on the other hand, effectively eliminated antibiotics by 48.7 ± 11.9%. Interestingly, negative removal was observed along the distribution system, resulting in a significant antibiotic presence in tap water, with average concentrations of 131.5 ng/L in WTP1 and 362.8 ng/L in WTP2. Source tracking analysis indicates that most antibiotics in tap water may originate from distribution system. The presence of antibiotics in raw water and tap water posed risks to the aquatic ecosystem. Untreated or partially treated raw water could pose a medium risk to infants under six months. Water parameters, for example, temperature, total nitrogen and total organic carbon, can serve as indicators to estimate antibiotic occurrence and associated risks. Furthermore, machine learning models were developed that successfully predicted risk levels using water quality parameters. Our study provides valuable insights into the occurrence, removal and risk of antibiotics in urban WTPs, contributing to the broader understanding of antibiotic pollution in water treatment systems.

Safety and efficacy of sirolimus in recurrent intravenous leiomyomatosis, pulmonary benign metastatic leiomyomatosis, and leiomyomatosis peritonealis disseminata: a pilot study.

BACKGROUND: Intravenous leiomyomatosis (IVL), pulmonary benign metastatic leiomyomatosis (PBML), and leiomyomatosis peritonealis disseminata (LPD) are leiomyomas with special growth patterns and high postoperative recurrence rates. We report the safety and efficacy of a pilot study of sirolimus in the treatment of recurrent IVL, PBML, and recurrent LPD. METHODS: This was a pilot study to evaluate the safety and efficacy of sirolimus in the treatment of leiomyomatosis (ClinicalTrials.gov identifier NCT03500367) conducted in China. Patients received oral sirolimus 2 mg once a day for a maximum of 60 months or until disease progression, intolerable toxicity, withdrawal of consent, or investigator decision to stop. The primary end point of this study was the objective response rate. Secondary end points included safety and tolerability, disease control rate, and progression-free survival. RESULTS: A total of 15 patients with leiomyomatosis were included in the study, including five with recurrent IVL, eight with PBML and two with recurrent LPD. The median follow-up time was 15 months (range 6-54 months), nine patients (60%) had treatment-related adverse events (including all levels), and two patients had treatment-related grade 3 or 4 adverse events. The objective response rate was 20.0% (95% CI, 7.1-45.2%), and the disease control rate was 86.7% (95% CI, 62.1-96.3%). Partial response was achieved in three patients. The median response time in the three partial response patients was 33 months (range 29-36 months), and the sustained remission time of these three patients reached 0, 18, and 25 months, respectively. CONCLUSIONS: Sirolimus was safe and effective in the treatment of recurrent IVL, PBML, and recurrent LPD. TRIAL REGISTRATION: ClinicalTrials.gov identifier NCT03500367. Registered on 18 April 2018.

Analysis of risk factors for post-operative recurrence or progression of intravenous leiomyomatosis.

OBJECTIVE: To analyse the risk factors for post-operative recurrence or progression of intravenous leiomyomatosis and explore the impact of different treatment strategies on patient prognosis. METHODS: Patients with intravenous leiomyomatosis who underwent surgery from January 2011 to December 2020 and who were followed for ≥3 months were included. The primary endpoint was recurrence (for patients with complete resection) or progression (for patients with incomplete resection). Kaplan-Meier survival analysis was used to analyse the factors affecting recurrence. RESULTS: A total of 114 patients were included. The median age was 45 years old (range 24-58). The tumors were confined to the uterus and para-uterine vessels in 48 cases (42.1%), while in 66 cases (57.9%) it involved large vessels (iliac vein or genital vein and/or proximal large veins). The median follow-up time was 24 months (range 3-132). Twenty-nine patients (25.4%) had recurrence or progression. The median recurrence or progression time was 16 months (range 3-60). Incomplete tumor resection (p=0.019), involvement of the iliac vein or genital vein (p=0.042), involvement of the inferior vena cava (p=0.025), and size of the pelvic tumor ≥15 cm (p=0.034) were risk factors for recurrence and progression. For intravenous leiomyomatosis confined to the uterus or para-uterine vessels, no post-operative recurrence after hysterectomy and bilateral oophorectomy occurred in this cohort. Compared with hysterectomy and bilateral oophorectomy, the risk of recurrence after tumorectomy (with the uterus and ovaries retained) was significantly greater (p=0.009), while the risk of recurrence after hysterectomy was not significantly increased (p=0.058). For intravenous leiomyomatosis involving the iliac vein/genital vein and the proximal veins, post-operative aromatase inhibitor treatment (p=0.89) and two-stage surgery (p=0.86) were not related to recurrence in patients with complete tumor resection. CONCLUSION: Incomplete tumor resection, extent of tumor lesions and size of the pelvic tumor were risk factors for post-operative recurrence and progression of intravenous leiomyomatosis.

Corrigendum: Preliminary study on mesenchymal stem cells in repairing nerve injury in pelvic floor denervation.

[This corrects the article DOI: 10.3389/fbioe.2023.1190068.].

Canagliflozin attenuates kidney injury, gut-derived toxins, and gut microbiota imbalance in high-salt diet-fed Dahl salt-sensitive rats.

PURPOSE: To investigate the effects of canagliflozin (20 mg/kg) on Dahl salt-sensitive (DSS) rat gut microbiota and salt-sensitive hypertension-induced kidney injury and further explore its possible mechanism. METHODS: Rats were fed a high-salt diet to induce hypertension and kidney injury, and physical and physiological indicators were measured afterwards. This study employed 16S rRNA sequencing technology and liquid chromatography-tandem mass spectrometry (LC-MS/MS)-based metabolic profiling combined with advanced differential and association analyses to investigate the correlation between the microbiome and the metabolome in male DSS rats. RESULTS: A high-salt diet disrupted the balance of the intestinal flora and increased toxic metabolites (methyhistidines, creatinine, homocitrulline, and indoxyl sulfate), resulting in severe kidney damage. Canagliflozin contributed to reconstructing the intestinal flora of DSS rats by significantly increasing the abundance of Corynebacterium spp., Bifidobacterium spp., Facklamia spp., Lactobacillus spp., Ruminococcus spp., Blautia spp., Coprococcus spp., and Allobaculum spp. Moreover, the reconstruction of the intestinal microbiota led to significant changes in host amino acid metabolite concentrations. The concentration of uremic toxins, such as methyhistidines, creatinine, and homocitrulline, in the serum of rats was decreased by canagliflozin, which resulted in oxidative stress and renal injury alleviation. CONCLUSION: Canagliflozin may change the production of metabolites and reduce the level of uremic toxins in the blood circulation by reconstructing the intestinal flora of DSS rats fed a high-salt diet, ultimately alleviating oxidative stress and renal injury.

Electrochemically Mediated Surface-Initiated Atom Transfer Radical Polymerization by ppm of CuII/Tris(2-pyridylmethyl)amine.

Atom transfer radical polymerization (ATRP) is one of the most widely used methods for modifying surfaces with functional polymer films and has received considerable attention in recent years. Here, we report an electrochemically mediated surface-initiated ATRP to graft polymer brushes onto solid substrates catalyzed by ppm amounts of CuII/TPMA in water/MeOH solution. We systematically investigated the type and concentrations of copper/ligand and applied potentials correlated to the polymerization kinetics and polymer brush thickness. Gradient polymer brushes and various types of polymer brushes are prepared. Block copolymerization of 2-hydroxyethyl methacrylate (HEMA) and 3-sulfopropyl methacrylate potassium salt (PSPMA) (poly(HEMA-b-SPMA)) with ultralow ppm eATRP indicates the remarkable preservation of chain end functionality and a pronounced "living" characteristic feature of ppm-level eATRP in aqueous solution for surface polymerization.

scGRN: a comprehensive single-cell gene regulatory network platform of human and mouse.

Gene regulatory networks (GRNs) are interpretable graph models encompassing the regulatory interactions between transcription factors (TFs) and their downstream target genes. Making sense of the topology and dynamics of GRNs is fundamental to interpreting the mechanisms of disease etiology and translating corresponding findings into novel therapies. Recent advances in single-cell multi-omics techniques have prompted the computational inference of GRNs from single-cell transcriptomic and epigenomic data at an unprecedented resolution. Here, we present scGRN (https://bio.liclab.net/scGRN/), a comprehensive single-cell multi-omics gene regulatory network platform of human and mouse. The current version of scGRN catalogs 237 051 cell type-specific GRNs (62 999 692 TF-target gene pairs), covering 160 tissues/cell lines and 1324 single-cell samples. scGRN is the first resource documenting large-scale cell type-specific GRN information of diverse human and mouse conditions inferred from single-cell multi-omics data. We have implemented multiple online tools for effective GRN analysis, including differential TF-target network analysis, TF enrichment analysis, and pathway downstream analysis. We also provided details about TF binding to promoters, super-enhancers and typical enhancers of target genes in GRNs. Taken together, scGRN is an integrative and useful platform for searching, browsing, analyzing, visualizing and downloading GRNs of interest, enabling insight into the differences in regulatory mechanisms across diverse conditions.

eRNAbase: a comprehensive database for decoding the regulatory eRNAs in human and mouse.

Enhancer RNAs (eRNAs) transcribed from distal active enhancers serve as key regulators in gene transcriptional regulation. The accumulation of eRNAs from multiple sequencing assays has led to an urgent need to comprehensively collect and process these data to illustrate the regulatory landscape of eRNAs. To address this need, we developed the eRNAbase (http://bio.liclab.net/eRNAbase/index.php) to store the massive available resources of human and mouse eRNAs and provide comprehensive annotation and analyses for eRNAs. The current version of eRNAbase cataloged 10 399 928 eRNAs from 1012 samples, including 858 human samples and 154 mouse samples. These eRNAs were first identified and uniformly processed from 14 eRNA-related experiment types manually collected from GEO/SRA and ENCODE. Importantly, the eRNAbase provides detailed and abundant (epi)genetic annotations in eRNA regions, such as super enhancers, enhancers, common single nucleotide polymorphisms, expression quantitative trait loci, transcription factor binding sites, CRISPR/Cas9 target sites, DNase I hypersensitivity sites, chromatin accessibility regions, methylation sites, chromatin interactions regions, topologically associating domains and RNA spatial interactions. Furthermore, the eRNAbase provides users with three novel analyses including eRNA-mediated pathway regulatory analysis, eRNA-based variation interpretation analysis and eRNA-mediated TF-target gene analysis. Hence, eRNAbase is a powerful platform to query, browse and visualize regulatory cues associated with eRNAs.

KnockTF 2.0: a comprehensive gene expression profile database with knockdown/knockout of transcription (co-)factors in multiple species.

Transcription factors (TFs), transcription co-factors (TcoFs) and their target genes perform essential functions in diseases and biological processes. KnockTF 2.0 (http://www.licpathway.net/KnockTF/index.html) aims to provide comprehensive gene expression profile datasets before/after T(co)F knockdown/knockout across multiple tissue/cell types of different species. Compared with KnockTF 1.0, KnockTF 2.0 has the following improvements: (i) Newly added T(co)F knockdown/knockout datasets in mice, Arabidopsis thaliana and Zea mays and also an expanded scale of datasets in humans. Currently, KnockTF 2.0 stores 1468 manually curated RNA-seq and microarray datasets associated with 612 TFs and 172 TcoFs disrupted by different knockdown/knockout techniques, which are 2.5 times larger than those of KnockTF 1.0. (ii) Newly added (epi)genetic annotations for T(co)F target genes in humans and mice, such as super-enhancers, common SNPs, methylation sites and chromatin interactions. (iii) Newly embedded and updated search and analysis tools, including T(co)F Enrichment (GSEA), Pathway Downstream Analysis and Search by Target Gene (BLAST). KnockTF 2.0 is a comprehensive update of KnockTF 1.0, which provides more T(co)F knockdown/knockout datasets and (epi)genetic annotations across multiple species than KnockTF 1.0. KnockTF 2.0 facilitates not only the identification of functional T(co)Fs and target genes but also the investigation of their roles in the physiological and pathological processes.

LncSEA 2.0: an updated platform for long non-coding RNA related sets and enrichment analysis.

Long non-coding RNAs (lncRNAs) possess a wide range of biological functions, and research has demonstrated their significance in regulating major biological processes such as development, differentiation, and immune response. The accelerating accumulation of lncRNA research has greatly expanded our understanding of lncRNA functions. Here, we introduce LncSEA 2.0 (http://bio.liclab.net/LncSEA/index.php), aiming to provide a more comprehensive set of functional lncRNAs and enhanced enrichment analysis capabilities. Compared with LncSEA 1.0, we have made the following improvements: (i) We updated the lncRNA sets for 11 categories and extremely expanded the lncRNA scopes for each set. (ii) We newly introduced 15 functional lncRNA categories from multiple resources. This update not only included a significant amount of downstream regulatory data for lncRNAs, but also covered numerous epigenetic regulatory data sets, including lncRNA-related transcription co-factor binding, chromatin regulator binding, and chromatin interaction data. (iii) We incorporated two new lncRNA set enrichment analysis functions based on GSEA and GSVA. (iv) We adopted the snakemake analysis pipeline to track data processing and analysis. In summary, LncSEA 2.0 offers a more comprehensive collection of lncRNA sets and a greater variety of enrichment analysis modules, assisting researchers in a more comprehensive study of the functional mechanisms of lncRNAs.

Tailored Water-Soluble Covalent Organic Cages for Encapsulation of Pyrene and Information Encryption.

Forming pyridine salts to construct covalent organic cages is an effective strategy for constructing covalent cage compounds. Covalent organic cages based on pyridine salt structures are prone to form water-soluble supramolecular compounds. Herein, we designed and synthesized a triangular prism-shaped hexagonal cage with a larger cavity and relatively flexible conformation. The supramolecular cage structure was also applied to the encapsulation of pyrene and information encryption.

FoxO1 knockdown inhibits RANKL-induced osteoclastogenesis by blocking NLRP3 inflammasome activation.

OBJECTIVES: This study aimed to elucidate the connection between osteoclastic forkhead transcription factor O1 (FoxO1) and periodontitis and explore the underlying mechanism by which FoxO1 knockdown regulates osteoclast formation. MATERIALS AND METHODS: A conventional ligature-induced periodontitis model was constructed to reveal the alterations in the proportion of osteoclastic FoxO1 in periodontitis via immunofluorescence staining. Additionally, RNA sequencing (RNA-seq) was performed to explore the underlying mechanisms of FoxO1 knockdown-mediated osteoclastogenesis, followed by western blotting, quantitative polymerase chain reaction, and enzyme-linked immunosorbent assay. RESULTS: FoxO1+ osteoclasts were enriched in the alveolar bone in experimental periodontitis. Moreover, FoxO1 knockdown led to impaired osteoclastogenesis with low expression of osteoclast differentiation-related genes, accompanied by an insufficient osteoclast maturation phenotype. Mechanistically, RNA-seq revealed that the nuclear factor kappa B (NF-κB) and nucleotide-binding oligomerization domain-like receptor family pyrin domain containing 3 (NLRP3) inflammasome signaling pathways were inhibited in FoxO1-knockdown osteoclasts. Consistent with this, MCC950, an effective inhibitor of the NLRP3 inflammasome, substantially attenuated osteoclast formation. CONCLUSIONS: FoxO1 knockdown contributed to the inhibition of osteoclastogenesis by effectively suppressing NF-κB signaling and NLRP3 inflammasome activation. This prospective study reveals the role of FoxO1 in mediating osteoclastogenesis and provides a viable therapeutic target for periodontitis treatment.

Canagliflozin and irbesartan ameliorate renal fibrosis via the TGF-ß1/Smad signaling pathway in Dahl salt-sensitive rats.

OBJECTIVES: This study assessed the antifibrotic effects of canagliflozin, with or without irbesartan, on renal injury in Dahl salt-sensitive (SS) rats fed a high-salt (HS) diet. METHODS: After the preconditioning stage, Dahl SS rats (n = 47) were divided into five experimental groups as follows: low-salt (LS, n = 7), HS (n = 10), HS with canagliflozin (n = 10), HS with irbesartan (n = 10), and HS with canagliflozin and irbesartan (n = 10). RESULTS: The HS diet increased systolic blood pressure (SBP), renal fibrosis, fibrotic protein expression, and transforming growth factor-ß1 (TGF-ß1)/Smad2/3 pathway protein expression compared with the findings in the LS group. Irbesartan reduced SBP and slowed the loss of renal function. Canagliflozin significantly reduced body weight and renal fibrosis and suppressed the TGF-ß1/Smad2/3 pathway. The combined therapy exerted better renoprotective effects on all outcome parameters. CONCLUSIONS: These results indicate that canagliflozin and irbesartan exert different effects on renal injury in SS hypertensive rats, and the combined regimen could have stronger effects than either monotherapy.