A Glimpse of Inflammation and Anti-Inflammation Therapy in Diabetic Kidney Disease.

Diabetic kidney disease (DKD) is a common complication of diabetes mellitus and a major cause of end-stage kidney disease (ESKD). The pathogenesis of DKD is very complex and not completely understood. Recently, accumulated evidence from in vitro and in vivo studies has demonstrated that inflammation plays an important role in the pathogenesis and the development of DKD. It has been well known that a variety of pro-inflammatory cytokines and related signaling pathways are involved in the procession of DKD. Additionally, some anti-hyperglycemic agents and mineralocorticoid receptor antagonists (MRAs) that are effective in alleviating the progression of DKD have anti-inflammatory properties, which might have beneficial effects on delaying the progression of DKD. However, there is currently a lack of systematic overviews. In this review, we focus on the novel pro-inflammatory signaling pathways in the development of DKD, including the nuclear factor kappa B (NF-κB) signaling pathway, toll-like receptors (TLRs) and myeloid differentiation primary response 88 (TLRs/MyD88) signaling pathway, adenosine 5'-monophosphate-activated protein kinase (AMPK) signaling pathways, inflammasome activation, mitochondrial DNA (mtDNA) release as well as hypoxia-inducible factor-1(HIF-1) signaling pathway. We also discuss the related anti-inflammation mechanisms of metformin, finerenone, sodium-dependent glucose transporters 2 (SGLT2) inhibitors, Dipeptidyl peptidase-4 (DPP-4) inhibitors, Glucagon-like peptide-1 (GLP-1) receptor agonist and traditional Chinese medicines (TCM).

The Effect of Antioxidant Vitamins on Patients With Diabetes and Albuminuria: A Meta-Analysis of Randomized Controlled Trials.

OBJECTIVE: This study aimed to investigate the effect of antioxidant vitamins, including vitamins E and C, on patients with diabetes and albuminuria by conducting a meta-analysis of randomized controlled trials. DESIGN: The PubMed, Embase, CENTRAL (the Cochrane Central Register of Controlled Trials at the Cochrane Library), Web of Science, OVID, and www.clinicaltrials.gov (latest search: December 10, 2018) databases were searched. This study was limited to randomized controlled trials. Patients with diabetes and albuminuria were included regardless of diabetic type, and patients must have received treatment with vitamins C or E. RESULTS: Ten studies, representing 445 participants, were identified for analysis. Antioxidant vitamins had significant effects on serum creatinine levels (mean difference = -0.11 mg/dL, 95% confidence interval -0.19 to -0.03, P = .007) and systolic pressure (mean difference = -6.02 mm Hg, 95% confidence interval -9.65 to -2.40, P = .001) with low heterogeneity. Antioxidant vitamins had no effect on albuminuria or proteinuria, diastolic blood pressure, glucose, or lipid metabolism. CONCLUSION: This meta-analysis indicated that antioxidant vitamins can benefit kidney function and systolic blood pressure in patients with diabetes and albuminuria. Further studies with larger sample sizes and longer follow-up are needed to completely understand the effect of antioxidant vitamins in these patients.

Asiatic acid protects against cisplatin-induced acute kidney injury via anti-apoptosis and anti-inflammation.

Cisplatin is a well-known chemotherapeutic drug applied for the treatment of numerous human cancers. However, the use of cisplatin in clinic is limited by certain serious side effects, such as nephrotoxicity. Unfortunately, there is currently no effective therapeutic approach to prevent cisplatin-induced AKI. Increasing evidence suggests that apoptosis of tubular epithelial cells and renal inflammation mainly determine the progression and outcome of cisplatin-induced AKI. Asiatic acid (AA) has been reported have the functions of anti-inflammation and anti-apoptosis, etc. But the effects of AA on kidney injury induced by cisplatin are still not known. The current study aimed to determine the potential renoprotective effects of AA on kidney injury induced by cisplatin. Twenty-four C57BL/6 male mice were randomly divided into four groups: normal control (CON), cisplatin-induced AKI (CIS), AKI with 50 mg/kg AA pretreatment (CIS + AA50), and AKI with 100 mg/kg AA pretreatment (CIS + AA100). Mice were anesthetized and sacrificed at 72 h after the cisplatin injection. Blood and kidney samples were collected for analyses. Compared with CON mice, cisplatin-treated mice exhibited severe tubular necrosis and elevated serum creatinine level. However, AA pretreatment (50 mg/kg or 100 mg/kg) markedly suppressed the elevated serum creatinine, blood urea nitrogen and histological changes. Moreover, AA pretreatment notably downregulated tubular expression of kidney injury molecule-1 (KIM-1) and the number of apoptotic cells, and upregulated the expression of the apoptosis inhibitor survivin and promoted tubular proliferation as evidenced by an increase in the number of proliferating cell nuclear antigen-positive cells. In addition, AA suppressed the enhanced mRNA expression of proinflammatory cytokines IL-1ß, TNF-α, MCP-1 and caspase-1 in the kidneys. Furthermore, AA pretreatment inhibited NF-κB activation and the inflammatory response, which may result from Smad7 up-regulation. In conclusion, AA protects against cisplatin-induced AKI via anti-apoptosis and anti-inflammation.

Using microPET imaging in quantitative verification of the acupuncture effect in ischemia stroke treatment.

Acupuncture has been indispensable in Chinese medicine. However, its function still remains elusive. This paper studies the effect of acupuncture in ischemia stroke treatment using the Sprague Dawley rat animal model. We induced focal cerebral ischemia in rats using the middle cerebral artery occlusion (MCAO) procedure. For each rat in the real acupuncture group (n = 63), the sham acupoint treatment group (n = 62), and the blank control group (n = 30), we acquired 3-D fluorodeoxyglucose-microPET images at baseline, after MCAO, and after treatment, respectively. Then, we measured the changes of the injury-volume in the right hemisphere of these rats. The measurements showed that real acupuncture slightly reduced the injury-volume, sham acupoint treatment increased the injury-volume, and blank control had no obvious effect in reducing the injury-volume. Statistical tests also confirmed that acupuncture was more effective than random stimulus in improving the metabolic recovery after stroke.

Transmural imaging of ventricular action potentials and post-infarction scars in swine hearts.

The problem of using surface data to reconstruct transmural electrophysiological (EP) signals is intrinsically ill-posed without a unique solution in its unconstrained form. Incorporating physiological spatiotemporal priors through probabilistic integration of dynamic EP models, we have previously developed a Bayesian approach to transmural electrophysiological imaging (TEPI) using body-surface electrocardiograms. In this study, we generalize TEPI to using electrical signals collected from heart surfaces, and we test its feasibility on two pre-clinical swine models provided through the STACOM 2011 EP simulation Challenge. Since this new application of TEPI does not require whole-body imaging, there may be more immediate potential in EP laboratories where it could utilize catheter mapping data and produce transmural information for therapy guidance. Another focus of this study is to investigate the consistency among three modalities in delineating scar after myocardial infarction: TEPI, electroanatomical voltage mapping (EAVM), and magnetic resonance imaging (MRI). Our preliminary data demonstrate that, compared to the low-voltage scar area in EAVM, the 3-D electrical scar volume detected by TEPI is more consistent with anatomical scar volume delineated in MRI. Furthermore, TEPI could complement anatomical imaging by providing EP functional features related to both scar and healthy tissue.

[Effect of bone morphogenetic protein-7 on aristolochic acid induced renal tubular epithelial cells transdifferentiation].

OBJECTIVE: To observe the effect of bone morphogenetic protein-7 (BMP-7) on aristolchic acid induced renal tubular epithelial cell trans-differentiation to look for new therapeutic approach for aristolchic acid nephropathy (AAN). METHODS: In vitro cultured human proximal renal tubular epithelial cell line HK-2 cells were treated with different concentrations of BMP-7 (75 ng/mL, 150 ng/mL and 300 ng/mL) after trans-differentiation of the cells was induced by AA (10 microg/mL). Levels of alpha-SMA mRNA and protein expressions were detected by semi-quantitative reverse transcription polymerase chain reaction (RT-PCR) and Western blotting respectively. RESULTS: BMP-7 reversed the AA inducing alpha-SMA expressions in HK-2 cells in a dose-dependent manner. CONCLUSION: BMP-7 can inhibit the trans-differentiation of human renal tubular epithelial cell induced by AA, thereby might be a new potential drug for AAN prevention and treatment.

[Comparison of in vitro release behavior of proanthocyanidins flexible nanoliposomes and general nanoliposomes].

OBJECTIVE: To prepare flexible proanthocyanidins nanoliposomes, and explore the in vitro release behavior of proanthocyanidins flexible nanoliposomes and general nanoliposomes. METHOD: Flexible proanthoeyanidins nanoliposomes were prepared proanthocyanidins using a film dispersion method, characterized by transmission electron microscope, and the in vitro release action was studied in different dissolution mediums using dynamic dialyse method with the content of total phenol as index. RESULT: The in vitro release of both proanthocyanidins flexible nanoliposomes and general nanoliposomes were in accordance with Weibull distribution. CONCLUSION: Proanthocyanidins flexible nanoliposomes without pressure had similar in vitro release behavior with general nanoliposomes.

[Preparation and release in vitro of injectable thermosensitive in situ gel of Glabrous Sarcandra herb extract].

OBJECTIVE: To prepare and evaluate the injectable temperature responsive in situ gel for sustained release of Glabrous Sarcandra Herb extract in vitro. METHOD: The novel temperature responsive poloxamer 407 was used as the carrier material of Glabrous Sarcandra Herb extract sustained release injection. The release of Glabrous Sarcandra Herb extract from poloxamer 407 based in situ gel in the phosphate buffer (pH 7. 6) was studied at 37 degrees C under agitation. HPLC method was used for the determination of Glabrous Sarcandra Herb extract. RESULT: The best prescription was composed of by 16% P-407, 6% P-188, 0.2% HPMC, 0.5% benzil alcohol and 4% (g mL(-1)) Glabrous Sarcandra Herb extract. The optimal gelation temperature was around 33 degrees C. The data of release in vitro were analyzed according to the theoretical model of Korsmeyer-Peppas. CONCLUSION: The preparation method of the injectable thermosensitive in situ gel of Glabrous Sarcandra Herb extract is appropriate. The release in vitro can reach the expecting request.