Investigation of preoperative physical activity level in kidney transplant recipients and its impact on early postoperative recovery: A retrospective cohort study.

Objective: To retrospectively investigate the preoperative physical activity (PA) level in kidney transplant recipients (KTRs) and its impact on early postoperative recovery. Methods: A total of 113 patients who received kidney transplantation at West China Hospital of Sichuan University were enrolled in this retrospective cohort study. According to the PA level measured by the Chinese version of the International Physical Activity Questionnaire-Long Version, the patients were allocated into the low PA level group (Group L, n = 55) and medium to high PA level group (Group MH, n = 58). The kidney function recovery indicators, including estimated glomerular filtration rate (eGFR), postoperative complications, postoperative length of stay (LOS), and unscheduled readmission within three months of discharge, were evaluated and documented. A association analysis was applied to analyze and compare the association between indicators. Results: The median PA levels of the KTRs were 1701.0 MTEs * min/week. Regarding the postoperative recovery indicators, the KTRs spent a mean time of 19.63 h to achieve transfer out of bed after the operation (Group L: 19.67 h; Group MH: 19.53 h; P = 0.952) and reached a mean distance of 183.10 m as the best ambulatory training score within two days after the operation (Group L: 134.91 m; Group MH: 228.79 m; P < 0.001). The preoperative PA level showed a moderate positive association with early postoperative ambulation distance (ρ = 0.497, P < 0.001). However, no significant between-group difference in eGFR on postoperative days 1, 3, and 5 (P = 0.913, 0.335, and 0.524) or postoperative complications, including DGF (P = 0.436), infection (P = 0.479), postoperative LOS (P = 0.103), and unscheduled readmission (P = 0.698), was found. Conclusions: The preoperative PA level of KTRs is lower than that of the general population. KTRs with moderate or high preoperative PA levels showed higher ambulatory function in the early postoperative period than those with low preoperative PA levels, but no between-group differences in other early recovery indicators were observed.

Naringin improves sepsis-induced intestinal injury by modulating macrophage polarization via PPARγ/miR-21 axis.

Naringin exhibited various pharmacological activities. However, its biological function and underlying mechanism in regulating macrophage polarization remain elusive. This study aimed to investigate the regulatory network between naringin and macrophage polarization in sepsis-induced intestinal injury. Cecal ligation and puncture (CLP) was used to establish the animal model of sepsis. Chromatin immunoprecipitation and a luciferase reporter assay were used to determine the interplay between peroxisome proliferator-activated receptor γ (PPARγ) and miR-21 promoter, as well as miR-21 and its target genes. Naringin enhanced the overall survival of septic mice and alleviated the CLP-induced inflammatory response and intestinal damage. This was accompanied by the increased expression of PPARγ in the intestines and the stimulation of ileal macrophages toward the M2 phenotype. Furthermore, in lipopolysaccharide-stimulated bone marrow-derived macrophages, naringin stimulated M2 polarization. Mechanistically, PPARγ inhibition attenuated the promotion of M2 polarization caused by naringin, and the naringin/PPARγ regulatory work was compromised by miR-21 inhibition. The present study suggested that naringin promoted M2 polarization via the PPARγ/miR-21 axis, thus relieving sepsis-induced intestinal injury. This study provides novel insights into the mechanism by which naringin alleviated sepsis-induced intestinal injury through regulation of macrophage polarization.

MiR-20b-5p modulates inflammation, apoptosis and angiogenesis in severe acute pancreatitis through autophagy by targeting AKT3.

BACKGROUND: Severe acute pancreatitis (SAP) is a common acute abdominal disease with high morbidity and mortality. However, the mechanism underlying SAP is still unclear. METHODS: Cerulean and LPS (Cer-LPS) was used to establish a rat model and an in vitro model of SAP. qRT-PCR, western blot and IHC were determined to analyse the expression of mRNA and proteins. IL-1ß, TNF-α and IL-6 levels were measured applying ELISA. H&E staining was determined to observe the pathological changes. Apoptosis was tested by AV-PI staining using flow cytometry. CCK8 assay was taken to detect cell viability. Cell migration was assessed by transwell assay. Tube formation assay was conducted to evaluate angiogenesis. Luciferase assay was used to detect relationship of miR-20b-5p and AKT3. RESULTS: MiR-20b-5p was lowly expressed in SAP models both in vivo and in vitro. Overexpression of miR-20b-5p restrained inflammation and apoptosis in Cer-LPS treated pancreatic acinar cells. Furthermore, miR-20b-5p promoted the angiogenesis of vascular endothelial cells, since the viability, migration and the capability of tube formation were increased by miR-20b-5p. Mechanically, miR-20b-5p directly targeted AKT3 to promote autophagy. Furthermore, miR-20b-5p could prevent the inflammation, apoptosis and enhance angiogenesis via enhancing autophagy, which was verified in vivo. CONCLUSION: This study demonstrated miR-20b-5p attenuates SAP through directly targeting AKT3 to regulate autophagy, subsequently inhibit inflammation and apoptosis, and promote angiogenesis. Our findings suggested a novel target of miR-20b-5p for the therapy of SAP.

Long Non-coding RNA FENDRR Modulates Autophagy Through Epigenetic Suppression of ATG7 via Binding PRC2 in Acute Pancreatitis.

Acute pancreatitis (AP) is an inflammatory, complicated pancreatic disease, carrying significant morbidity and mortality. However, the molecular and cellular mechanisms involved in AP pathogenesis remain to be elucidated. Here, we explore the role of FOXF1 adjacent non-coding developmental regulatory RNA (FENDRR) in AP progression. Caerulein with or without LPS- induced or taurolithocholic acid 3-sulfate (TLC-S)-induced AP mouse models and cell models were performed for the validation of FENDRR expression in vivo and in vitro, respectively. Histopathological examinations of pancreatic tissues were performed to evaluate the severity of AP. Transmission electron microscopy was utilized to visualize the autophagic vacuoles. siRNA specifically targeting FENDRR was further applied. Flow cytometry was employed to assess cell apoptosis. ELISA, immunoflureoscence, and western blotting analysis were also performed to determine the levels of inflammatory cytokines and autophagy activity. RNA immunoprecipitation (RIP) and chromatin immunoprecipitation (ChIP) assays were carried out to reveal the epigenetic regulation of FENDRR on ATG7. Additionally, silencing FENDRR was also verified in AP mouse models. Higher FENDRR and impaired autophagy were displayed in both AP mouse models and cell models. FENDRR knockdown dramatically attenuated caerulein- or TLC-S-induced AR42J cells apoptosis and autophagy suppression. Further mechanistic experiments implied that the action of FENDRR is moderately attributable to its repression of ATG7 via direct interaction with the epigenetic repressor PRC2. Moreover, the silencing of FENDRR significantly induced the promotion of ATG7, thus alleviating the development of AP in vivo. Our study highlights FENDRR as a novel target that may contribute to AP progression, suggesting a therapeutic target for AP treatment.

miR-375 Inhibits Autophagy and Further Promotes Inflammation and Apoptosis of Acinar Cells by Targeting ATG7.

OBJECTIVES: MicroRNAs have been considered to be closely related with the development of severe acute pancreatitis (SAP), and microRNA-375 (miR-375) was believed to be a marker of SAP. We aim to investigate the role of miR-375 in regulating SP. METHODS: Cerulein and lipopolysaccharide were used to establish the models of SAP. AR42J cell line was chosen for study in vitro. Flow cytometry was applied for assessing apoptosis. The contents of inflammatory factors were detected with related enzyme-linked immunosorbent assay and quantitative real-time polymerase chain reaction assays. Hematoxylin and eosin staining was applied to observe the pathological changes of pancreatic tissues. Immunohistochemistry analysis was conducted for investigating the expression of light chain 3. RESULTS: The level of miR-375 in pancreatitis tissues and cell lines was upregulated. Overexpression of miR-375 promoted inflammation and the apoptosis of acinar cells through inhibiting autophagy. The binding site between miR-375 and ATG7 was identified, and miR-375 could directly regulate the ATG7. microRNA-375 suppressed autophagy and promoted inflammation and the apoptosis of acinar cells via targeting ATG7. CONCLUSIONS: We proved that miR-375 could inhibit autophagy and promote inflammation and the apoptosis of acinar cells through regulating ATG7. This study first proves that miR-375 modulates the development of SAP through targeting ATG7.

The CD40 rs1883832 Polymorphism Affects Sepsis Susceptibility and sCD40L Levels.

Sepsis is a severe and progressive disease characterized by systemic inflammatory response syndrome (SIRS). CD40 serves as a vital link between immune response and inflammation. This study was designed to investigate the potential association between a functional single-nucleotide polymorphism (SNP) of CD40 (rs1883832) and susceptibility to sepsis. We first performed a case-control study to explore the relationship between the CD40 rs1883832 polymorphism and sepsis. CD40 mRNA expression and protein expression were determined by real-time PCR and western blotting, respectively, in peripheral blood mononuclear cells (PBMCs) from sepsis patients and healthy controls. The plasma sCD40L levels in the two groups were measured by ELISA. The results showed that the frequencies of the TT genotype and the CD40 rs1883832 T allele were significantly higher in sepsis patients than in healthy controls. Plasma sCD40L levels were also significantly increased in sepsis patients. In addition, TT genotype carriers among sepsis patients displayed the highest CD40 expression at both the mRNA and protein levels, accompanied by the highest plasma sCD40L concentrations. In conclusion, the CD40 rs1883832 T allele acts as a risk factor for increased susceptibility to sepsis and may be involved in the process of sepsis through regulation of CD40 expression and plasma sCD40L levels.

Protective mechanism of Panax notoginseng saponins on rat hemorrhagic shock model in recovery stage.

To explore protective mechanism of Panax notoginseng saponins (PNS) on rat hemorrhagic shock model in recovery stage. 72 Wistar rats were selected and divided into control group, model group and PNS group with 24 rats in each group. 200 mg/kg PNS was injected intravenously at 60 min of hemorrhagic shock stage in PNS groups. Changes of endotoxin, MPO, IL-6, SOD, MDA and TNF α were observed at 30 and 120 min of recovery stage by ELISA; water content of lung and intestine was detected; HE staining was applied to observe morphological change of intestinal mucosa, kidney, liver and lung; western blot was used to detect intercellular adhesion molecule-1 (ICAM-1) level in lung tissue and intestine tissue. At 30 min and 120 min of recovery stage, MDA, MPO, endotoxin, TNF α and IL-6 levels significantly increased in model group compared with control group, however SOD level significantly decreased, the difference was statistically significant (P < 0.05); PNS dose-dependently decreased MDA, MPO, endotoxin, TNF α and IL-6 levels, and increased SOD level, which was statistically significant (P < 0.05); In results of water content detection, water content in lung tissue and intestine tissue was significantly higher than in control group, however, after being treated with PNS, the water content was significantly decreased; HE staining showed the morphologic change of lung tissue cells; Western blot showed that in lung tissue and intestine tissue, ICAM-1 level in model group was significantly higher than in control group, and it was lower in PNS group than in model group. PNS can increase SOD activity, decrease levels of MDA, endotoxin and MPO, decrease expression of TNF α and IL-6, and decrease water content in lung tissue and intestine tissue. Thus, PNS is protective to rat hemorrhagic shock model by anti oxidative stress and anti-inflammatory pathways, and ICAM-1 may play an important role in the mechanism.