Background Diabetic nephropathy (DN) is the leading cause of end-stage renal disease. Mesenchymal stem cells (MSCs) treatment has been proved to be effective in DN models by protecting renal function and preventing fibrosis. However, the underlying mechanism is unclear. Previous research indicated diabetes and associated complications may be attributed to failed resolution of inflammation, which is deliberately regulated by pro-resolving lipids, including lipoxins (LXs), resolvins (Rv) D and E series, protectins, and maresins. In this study, we monitored pro-resolving mediators in a DN model to explore the mechanism of MSCs treatment. Material/Methods The DN model was induced by STZ injection in SD rats. UPLC-MS/MS was performed to determine pro-resolving lipids in kidney tissue and serum of DN model before and after MSCs treatment, as well as in supernatants of HBZY-1-MSCs co-culture. Results LXA4 was highly accumulated in renal tissue of DN rats with MSCs treatment; ex vivo , LXA4 was significantly increased in the supernatants of HBZY-1 cells co-cultured with MSCs in a high-glucose (HG) medium. Western blot analysis indicated that ALX/FPR2, the receptor of LXA4, was markedly expressed in renal tissue of the DN-MSC group and HBZY-1 after incubating with MSCs in HG. Intraperitoneal injection of LXA4 inhibited renal fibrosis by targeting TGF-β/Smad signaling and downregulated serum TNF-α, IL-6, IL-8, and IFN-γ in DN rats. Notably, all the protective effects induced by MSCs or LXA4 were abolished by ALX/FRP2 blocking. Conclusions Our results demonstrate that MSCs intervention prevented DN procession via the LXA4-ALX/FPR2 axis, which inhibited glomerulosclerosis and pro-inflammatory cytokines, eventually contributing to kidney homeostasis.
Objectives. Interactions between the host and gut microbial community contribute to the pathogenesis of Crohn's disease (CD). In this study, we aimed to detect lipopolysaccharide (LPS) and 1,3-β-D-glucan (BG) in the sera of CD patients and clarify the potential role in the diagnosis and therapeutic approaches. Materials and Methods. Serum samples were collected from 46 patients with active CD (A-CD), 22 CD patients at remission stage (R-CD), and 20 healthy controls, and the levels of LPS, BG, and TNF in sera were determined by ELISA. Moreover, sixteen patients with A-CD received anti-TNF monoclonal antibody therapy (infliximab, IFX) at a dose of 5 mg/kg body weight at weeks 0, 2, and 6, and the levels of LPS and BG were also tested at week 12 after the first intravenous infusion. Results. Serum levels of LPS and BG were found to be markedly increased in A-CD patients compared with R-CD patients and healthy controls (P < 0.05). They were also observed to be positively correlated with CDAI, ESR, and SES-CD, respectively (P < 0.05). Furthermore, the levels of TNF in sera had a significant correlation with LPS and BG, respectively. The concentrations of LPS and BG were demonstrated to be significantly downregulated in the sera of A-CD patients 12 weeks after IFX treatment (P < 0.05), suggesting that blockade of TNF could inhibit bacterial endotoxin absorption, partially through improving intestinal mucosal barrier. Conclusions. Serum levels of LPS and BG are significantly increased in A-CD patients and positively correlated with the severity of the disease. Blockade of intestinal mucosal inflammation with IFX could reduce the levels of LPS and BG in sera. Therefore, this study has shed some light on measurement of serum LPS and BG in the diagnosis and treatment of CD patients.
PurposeHepatitis C virus (HCV) infection is a major cause of liver disease. Several miRNAs have been found to be associated with HCV infection. This study aimed to investigate the functional roles and possible molecular mechanisms of miR-215 in HCV replication.Materials and MethodsThe expression levels of miR-215 and TRIM22 were detected by quantitative real-time PCR (qRT-PCR) and western blot analysis in Con1b subgenomic genotype 1b HCV replicon cells (Con1b cells) and JFH1 full genome infecting Huh7.5.1 cells (Huh7.5.1 cells). HCV RNA levels were measured by qRT-PCR. The protein levels of NS3, NS5A, p65 subunit of NF-κB (p65), and phosphorylated p65 (p-p65) were determined by western blot analysis. The relationship between miR-215 and TRIM22 were explored by target prediction and luciferase reporter analysis.ResultsmiR-215 overexpression enhanced HCV replication in Con1b cells, while miR-215 knockdown suppressed HCV replication in Huh7.5.1 cells. TRIM22 was confirmed to be a direct target of miR-215. TRIM22 upregulation resulted in a decline in HCV replication, while TRIM22 inhibition led to enhancement of HCV replication. Additionally, exogenous expression of TRIM22 reversed the facilitating effect of miR-215 on HCV replication, while TRIM22 downregulation counteracted the inhibitory effect of miR-215 knockdown on HCV replication. Furthermore, miR-215 targeted TRIM22 to block the NF-κB pathway, and exerted a positively regulatory role on HCV replication.ConclusionmiR-215 facilitated HCV replication via inactivation of the NF-κB pathway by inhibiting TRIM22, providing a novel potential target for HCV infection.
As a biomarker of periodontitis, sensitive and timely monitoring of hydrogen sulfide (H2S) in exhaled breath at room temperature (RT) is important for the early intervention of oral diseases. However, the required high operation temperature to achieve high sensitivity is still a technical challenge for directly monitoring exhaled breath. In this study, by integrating metal–organic frameworks (MOFs) into self-aligned TiO2 nanotube arrays (NTs), a chemiresistor gas sensor with outstanding sensitivity and selectivity was constructed for the detection of H2S at RT. The precise regulation of a Co(III)-based MOF CoBDC-NH2 (BDC-NH2 = 2-aminoterephthalic acid) not only induced more active surface for the preconcentration of the target gas but also caused a buildup of Z-scheme heterojunctions in the H2S atmosphere that induced an ultrahigh sensitivity at RT via 365 nm light-emitting diode irradiation. The response and recovery times decreased to ∼50 and ∼28%, respectively, when this system was exposed to UV light. The sensing chips based on the as-prepared TiO2/CoBDC-NH2 NTs exhibited the highest-ranking H2S sensing performance, i.e., a limit of detection of 1.3 ppb and excellent selectivity even to 100 times high concentration of interference gases, owing to the synergistic chemical environment provided by NH2-functionalized Co-MOFs and abundant photogenerated electrons provided by Z-scheme heterojunctions. This sensing chip was also used in a practical application for the timely monitoring of halitosis from direct exhaled breath. This study provides a reliable and sensitive design for clinically aiding the timely detection of H2S in a complex oral environment.
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