Rheumatoid arthritis (RA) is a progressive autoimmune disease. Due to local infiltration and damage to the joints, activated CD4+ T cells play a crucial role in the progression of RA. However, the exact regulatory mechanisms are perplexing, which makes the effective management of RA frustrating. This study aimed to investigate the effect of mitochondria fission on the polarization and migration of CD4+ T cells as well as the regulatory mechanism of NAR, so as to provide enlightenment on therapeutic targets and novel strategies for the treatment of RA. In this study, a collagen-induced arthritis (CIA) model was established, and rats were randomly given saline or naringenin (NAR, 10 mg/kg, 20 mg/kg, 50 mg/kg, i.p.) once a day, before being euthanized on the 42nd day of primary immunization. The pain-like behavior, articular index scores, account of synovial-infiltrated CD4+ T cells, and inflammatory factors were investigated in each group. In vitro, spleen CD4+ T lymphocytes were derived from each group. In addition, mitochondrial division inhibitor 1 (Mdivi-1) or NAR was added to the cell medium containing C-X-C motif chemokine ligand 12 (CXCL12) in order to induce CD4+ T lymphocytes, respectively. The polarization capacity of CD4+ T cells was evaluated through the immunofluorescence intensity of the F-actin and myosin light chain phosphorylated at Ser19 (pMLC S19), and the mitochondrial distribution was determined by co-localization analysis of the translocase of outer mitochondrial membrane 20 (TOM20, the mitochondrial marker) and intercellular adhesion molecule 1 (ICAM1, the uropod marker). The mitochondrial fission was investigated by detecting dynamin-related protein 1 (Drp1) and mitochondrial fission protein 1 (Fis1) using Western blot and immunofluorescence. This study revealed that high-dose NAR (50 mg/kg, i.p.) alleviated pain-like behavior and articular index scores, reduced the serum level of interleukin 6 (IL-6) and tumor necrosis factor α (TNF-α), and accounted for CD4+ T lymphocytes that infiltrated into the synovial membrane of the CIA group. Meanwhile, NAR (50 mg/kg, i.p.) suppressed the polarization of spleen CD4+ T lymphocytes, reduced the redistribution of mitochondria in the uropod, and inhibited the expression of Drp1 and Fis1 in the CIA model. Furthermore, the in vitro experiments confirmed that NAR reduced mitochondrial fission, which in turn inhibited the CXCL12-induced polarization and migration of CD4+ T lymphocytes. Our results demonstrated that the flavonoid NAR was a promising drug for the treatment of RA, which could effectively interfere with mitochondrial fission, thus inhibiting the polarization and migration of CD4+ T cells in the synovial membrane.

IntroductionMitochondria dysfunction is one of the primary causes of tubular injury in acute kidney injury (AKI). Notoginsenoside Fc (Fc), a new saponin isolated from Panax notoginseng, exhibited numerous pharmacological actions. However, the beneficial effects of Fc on renal tubular impairment and mitochondrial dysfunction in AKI have not been fully studied.MethodsIn this study, we established acetaminophen (APAP)-induced AKI model in mice to examine the therapeutic impacts of Fc on AKI.ResultsOur results showed that Fc could decrease the levels of the serum creatinine (Scr), blood urea nitrogen (BUN) and Cystatin C in mice with AKI. Fc also ameliorated renal histopathology, renal tubular cells apoptosis and restored expression of apoptosis-related proteins such as Bax, Bcl-2 and caspase3 (C-caspase3). Additionally, Fc increased the protein expression of SIRT3 and SOD2 in kidneys from mice with AKI. In vitro studies further showed Fc reduced the apoptosis of HK-2 cells exposure to APAP, attenuated the loss of mitochondrial membrane potential and decreased the formation of mitochondrial superoxide. Fc also partly restored the protein expression of Bax, Bcl-2, C-Caspase3, SIRT3, and SOD2 in HK-2 cells exposure to APAP.ConclusionIn summary, Fc might reduce renal tubular injury and mitochondrial dysfunction in AKI partly through the regulation of SIRT3/SOD2 pathway.

Background: Type 2 diabetic kidney disease (DKD) is one of the most common and harmful chronic complications in clinical practice, and there is no reliable and targeted treatment plan at present. As a classic complementary and alternative therapy, evidence have shown that warm acupuncture has advantages in the treatment of type 2 DKD. However, there is still a lack of high-quality and long-term follow-up randomized controlled trials of warm acupuncture in the treatment of type 2 DKD. Methods: This is a prospective randomized controlled trial to investigate the efficacy and safety of warm acupuncture in the treatment of type 2 DKD. Participants will be randomly assigned in a 1:1 ratio to either the treatment group (treated with conventional Western medicine) or the control group (treated with warm acupuncture added on the basis of the control group). Both groups will receive 12 weeks of treatment followed by 24 weeks of follow-up. Observation indicators include: 24-hour urinary protein quantification, kidney function, TCM syndrome score and adverse reactions. Finally, SPSS21.0 software will be used to analyze the data. Discussion: This study will evaluate the efficacy and safety of warm acupuncture in the treatment of DKD, and the results of this trial will provide clinical evidence for the treatment of type 2 DKD. Trial registration: The TCTR identification number is TCTR20221104004.

<b><i>Introduction:</i></b> Renal interstitial inflammation often presents in immunoglobulin A nephropathy (IgAN), but its predictive role in kidney disease progression remains controversial. <b><i>Methods:</i></b> This retrospective two-center cohort study included 1,420 adult IgAN patients between January 2003 and May 2018 followed for a median of approximately 7 years at two Chinese hospitals. The predictor was renal interstitial inflammation within the total cortical interstitium (none/mild [0–25%], moderate [26–50%], or severe [&#x3e;50%]). For the further propensity score matching analyses, the participants with moderate and severe level of interstitial inflammation were pooled to match those with none/mild level of interstitial inflammation. The outcomes included the rate of kidney function decline, and the composite kidney endpoint event defined as a &#x3e;40% reduction in the estimated glomerular filtration rate, end-stage kidney disease. Linear regression and Cox proportional hazards regression analyses were used to examine the association between interstitial inflammation and the outcomes. The predictive performance of the model also assessed using multivariate logistic regression analyses with the receiver operating characteristic curve analysis. Reclassification was assessed using the continuous net reclassification improvement and integrated discrimination improvement adapted for censoring for the assessment of the model with or without interstitial inflammation. <b><i>Results:</i></b> For the check of reproducibility, the kappa statistic was 0.71, and intraclass correlation coefficient was 0.77. After adjustment for relating covariates, a higher level of interstitial inflammation was associated with a faster rate of kidney function decline (eGFR slope [mL/min/1.73 m²] of 1.34 [95% CI: −2.56 to 5.23], 3.50 [95% CI: −0.40 to 7.40], and 7.52 [95% CI: 3.02 to 12.01]) in the patients with none/mild, moderate, and severe interstitial inflammation, respectively, in the multivariable linear regression models and with an increased risk of kidney disease progression (HR for moderate vs. none/mild, 1.85; 95% CI: 1.10–3.13; HR for severe vs. none/mild, 2.95; 95% CI: 1.52–5.73) in the multivariable Cox proportional hazards models. Analyses in the propensity score-matched cohort, subgroups, and the sensitive analyses yielded consistent results. The receiver operating curves indicated a higher area under the curve of 0.83 in the model with interstitial inflammation compared with 0.81 in that without interstitial inflammation. In addition, incorporating interstitial inflammation into the International IgAN Risk Prediction Tool improved the diagnostic power of the algorithm to predict risk of progression. <b><i>Conclusion:</i></b> Interstitial inflammation is a reproducible pathologic parameter that may be adopted as a predictor for kidney disease progression in patients with IgAN.