Niaodukang mixture inhibits micro-inflammation in CKD rats by enhancing MiR-146a levels in enterogenous exosomes.

ETHNOPHARMACOLOGICAL RELEVANCE: The Niaodukang mixture (NDK) is a preparation known for its ability to lower serum creatine levels in individuals with chronic kidney disease (CKD) and is commonly administered at medical facilities like the Zhongshan Hospital of Traditional Chinese Medicine. The initial use of NDK was mainly to treat CKD. Our hospital frequently utilizes NDK, which consists of Rheum officinaleBaill., Salvia miltiorrhiza Bunge., Astragalus aaronii (Eig) Zohary., Carthamus tinctorius L., and Sanguisorba officinalis L., for treating patients with CKD-MBD. It has the effects of eliminating dampness and turbidity and dredging kidney collaterals. However, The impact and process of NDK in chronic kidney disease remain unknown. AIM OF THE STUDY: To determine whether microRNA-146a (miR-146a) is associated with CKD micro-inflammationand whether NDK protects against CKD micro-inflammation by modulating the miR-146a/nuclear factor kappa-B (NF-κB) signaling pathway. MATERIALS AND METHODS: (1) An adenine-induced rat model of chronic kidney disease was created through the use of materials and methods. The levels of miR-146a in exosomes from plasma and ileum were determined by RT-PCR. (2) Human cloned colon adenocarcinoma (Caco-2)cellswere stimulated with lipopolysaccharide (LPS)and transfected with miR-146a mimic and inhibitor. Following that, the Western blot and RT-PCR techniques were used to measure the protein and mRNA quantities of Toll-like receptor 4 (TLR4), NF-κB, and TNF receptor-associated factor 6 (TRAF6). (3) Enzyme-linked immunosorbent assay (ELISA) was used to identify serum levels of interleukin-1ß (IL-1ß), interleukin-6 (IL-6), and tumor necrosis factor α (TNF-α). (4) Plasma exosomes were extracted, and the exosomes in intestinal tissues were extracted via ultrahigh-speed centrifugation.Negative staining electron microscopy was used to analyze the morphology of exosomes and the ultrastructure of intestinal tissue and exosomes. The particle size of the exosomes was measured using nanoparticle tracking analysis. RESULTS: The pathological characteristics of CKD rats included those associated with systemic micro-inflammation, which may be associated with the release of exosomes in intestinal tissue. NDK suppressed the inflammatory response in Caco-2 cells and decreased the levels of IL-1ß, IL-6, and TNF-α in rats with CKD. The expression of miR-146a, which regulates inflammation, differed between plasma-derived and enterogenous exosomes in CKD rats, which may be due to stimulation of ileal exosome release into the blood. NDK effectively reduced the levels of TRAF6, NF-κB, and TLR4 in the ileum tissue of CKD rats. CONCLUSION: NDK can effectively improve micro-inflammation in CKD ratsby enhancing the release of enterogenous exosomes, thereby enhancing the release of exosome-associated miR-146a and inhibiting micro-inflammation.

New Mechanisms to Prevent Heart Failure with Preserved Ejection Fraction Using Glucagon-like Peptide-1 Receptor Agonism (GLP-1 RA) in Metabolic Syndrome and in Type 2 Diabetes: A Review.

This review examines the impact of obesity on the pathophysiology of heart failure with preserved ejection fraction (HFpEF) and focuses on novel mechanisms for HFpEF prevention using a glucagon-like peptide-1 receptor agonism (GLP-1 RA). Obesity can lead to HFpEF through various mechanisms, including low-grade systemic inflammation, adipocyte dysfunction, accumulation of visceral adipose tissue, and increased pericardial/epicardial adipose tissue (contributing to an increase in myocardial fat content and interstitial fibrosis). Glucagon-like peptide 1 (GLP-1) is an incretin hormone that is released from the enteroendocrine L-cells in the gut. GLP-1 reduces blood glucose levels by stimulating insulin synthesis, suppressing islet α-cell function, and promoting the proliferation and differentiation of ß-cells. GLP-1 regulates gastric emptying and appetite, and GLP-1 RA is currently indicated for treating type 2 diabetes (T2D), obesity, and metabolic syndrome (MS). Recent evidence indicates that GLP-1 RA may play a significant role in preventing HFpEF in patients with obesity, MS, or obese T2D. This effect may be due to activating cardioprotective mechanisms (the endogenous counter-regulatory renin angiotensin system and the AMPK/mTOR pathway) and by inhibiting deleterious remodeling mechanisms (the PKA/RhoA/ROCK pathway, aldosterone levels, and microinflammation). However, there is still a need for further research to validate the impact of these mechanisms on humans.

Functional Dyspepsia: Current Understanding and Future Perspective.

BACKGROUND: Functional dyspepsia (FD) is a common disorder characterized by chronic or recurrent upper abdominal pain or discomfort without any structural abnormalities in the gastrointestinal tract. FD is categorized into two subgroups based on symptoms: postprandial distress syndrome (PDS) and epigastric pain syndrome. SUMMARY: The pathophysiology of FD involves several mechanisms. Delayed gastric emptying is observed in approximately 30% of FD patients but does not correlate with symptom patterns or severity. Impaired gastric accommodation is important in the pathophysiology, particularly for PDS. Visceral hypersensitivity, characterized by heightened sensitivity to normal activities, contributes to the perception of discomfort or pain in FD. Alterations to the duodenal mucosa, including impaired mucosal barrier function and low-grade inflammation, are also implicated in the pathogenesis of FD. Microbial dysbiosis and psychological factors such as stress can further exacerbate symptoms. Treatment options include dietary modifications, establishing a physician-patient relationship, acid suppressants, prokinetics, neuromodulators, and behavioral therapies. Dietary recommendations include eating smaller, more frequent meals, and avoiding trigger foods. Acid suppressants are used as the first-line treatment. Prokinetics and neuromodulators aim to improve gastric motility and central pain processing, respectively. Behavioral therapies, including cognitive behavioral therapy and hypnotherapy, have shown benefits for refractory FD. Severe and refractory cases may require combination therapies or experimental treatments. KEY MESSAGES: FD is a disorder of gut-brain interaction involving diverse pathophysiological mechanisms. Individualized treatment based on symptoms and responses to interventions is crucial. Further research is needed to improve the understanding of FD and advance the development of effective therapies.

The bidirectional association between diabetes and periodontitis, from basic to clinical.

The prevalence and severity of periodontitis are increased and advanced in diabetes. Severe periodontitis elicits adverse effects on diabetes by impairing insulin actions due to systemic microinflammation. Recent studies unveil the emerging findings and molecular basis of the bidirectional relationship between periodontitis and diabetes. In addition to conventional mechanisms such as hyperglycemia, hyperlipidemia, and chronic inflammation, deficient insulin action may play a pathogenic role in the progression of periodontitis under diabetes. Epidemiologically, from the viewpoint of the adverse effect of periodontitis on diabetes, recent studies have suggested that Asians including Japanese and Asian Americans with diabetes and mild obesity (BMI <25 kg/m2) should pay more attention to their increased risk for cardiovascular diseases. In this review, we summarize recent findings on the effect of diabetes on periodontitis from the viewpoint of abnormalities in metabolism and insulin resistance with novel mechanisms, and the influence of periodontitis on diabetes mainly focused on micro-inflammation related to mature adipose tissue and discuss future perspectives about novel approaches to interrupt the adverse interrelationship.

Association of long-term aspirin use with kidney disease progression.

Background: Chronic microinflammation contributes to the progression of chronic kidney disease (CKD). Aspirin (ASA) has been used to treat inflammation for centuries. The effects of long-term low-dose ASA on CKD progression are unclear. Methods: We examined the association of long-term use of newly initiated low-dose ASA (50-200 mg/day) with all-cause mortality using Cox proportional hazard models; with cardiovascular/cerebrovascular (CV) mortality and with end stage kidney disease (ESKD) using Fine and Gray competing risk regression models; with progression of CKD defined as patients' eGFR slopes steeper than -5 mL/min/1.73m2/year using logistic regression models in a nationwide cohort of US Veterans with incident CKD. Among 831,963 patients, we identified 385,457 who either initiated ASA (N = 21,228) within 1 year of CKD diagnosis or never received ASA (N = 364,229). We used propensity score matching to account for differences in key characteristics, yielding 29,480 patients (14,740 in each group). Results: In the matched cohort, over a 4.9-year median follow-up period, 11,846 (40.2%) patients (6,017 vs. 5,829 ASA users vs. non-users) died with 25.8% CV deaths, and 934 (3.2%) patients (476 vs. 458) reached ESKD. ASA users had a higher risk of faster decline of kidney functions, i.e., steeper slopes (OR 1.30 [95%CI: 1.18, 1.44], p < 0.01), but did not have apparent benefits on mortality (HR 0.97 [95%CI: 0.94, 1.01], p = 0.17), CV mortality (Sub-Hazard Ratio [SHR]1.06 [95%CI: 0.99-1.14], p = 0.11), or ESKD (SHR1.00 [95%CI: 0.88, 1.13], p = 0.95). Conclusion: Chronic low-dose ASA use was associated with faster kidney function deterioration, and no association was observed with mortality or risk of ESKD.

Micro-inflammation related gene signatures are associated with clinical features and immune status of fibromyalgia.

BACKGROUND: Fibromyalgia (FM) is a multifaceted disease. Along with the genetic, environmental and neuro-hormonal factors, inflammation has been assumed to have role in the pathogenesis of FM. The aim of the present study was to explore the differences in clinical features and pathophysiology of FM patients under different inflammatory status. METHODS: The peripheral blood gene expression profile of FM patients in the Gene Expression Omnibus database was downloaded. Differentially expressed inflammatory genes were identified, and two molecular subtypes were constructed according to these genes used unsupervised clustering analysis. The clinical characteristics, immune features and pathways activities were compared further between the two subtypes. Then machine learning was used to perform the feature selection and construct a classification model. RESULTS: The patients with FM were divided into micro-inflammation and non-inflammation subtypes according to 54 differentially expressed inflammatory genes. The micro-inflammation group was characterized by more major depression (p = 0.049), higher BMI (p = 0.021), more active dendritic cells (p = 0.010) and neutrophils. Functional enrichment analysis showed that innate immune response and antibacterial response were significantly enriched in micro-inflammation subtype (p < 0.050). Then 5 hub genes (MMP8, ENPP3, MAP2K3, HGF, YES1) were screened thought three feature selection algorithms, an accurate classifier based on the 5 hub DEIGs and 2 clinical parameters were constructed using support vector machine model. Model scoring indicators such as AUC (0.945), accuracy (0.936), F1 score (0.941), Brier score (0.079) and Hosmer-Lemeshow goodness-of-fit test (χ2 = 4.274, p = 0.832) proved that this SVM-based classifier was highly reliable. CONCLUSION: Micro-inflammation status in FM was significantly associated with the occurrence of depression and activated innate immune response. Our study calls attention to the pathogenesis of different subtypes of FM.

In situ Microinflammation Detection Using Gold Nanoclusters and a Tissue-clearing Method.

Microinflammation enhances the permeability of specific blood vessel sites through an elevation of local inflammatory mediators, such as interleukin (IL)-6 and tumor necrosis factor (TNF)-α. By a two-dimensional immunohistochemistry analysis of tissue sections from mice with experimental autoimmune encephalomyelitis (EAE), an animal model for multiple sclerosis (MS), we previously showed that pathogenic immune cells, including CD4+ T cells, specifically accumulate and cause microinflammation at the dorsal vessels of the fifth lumbar cord (L5), resulting in the onset of disease. However, usual pathological analyses by using immunohistochemistry on sections are not effective at identifying the microinflammation sites in organs. Here, we developed a new three-dimensional visualization method of microinflammation using luminescent gold nanoclusters (AuNCs) and the clear, unobstructed brain/body imaging cocktails and computational analysis (CUBIC) tissue-clearing method. Our protocol is based on the detection of leaked AuNCs from the blood vessels due to an enhanced vascular permeability caused by the microinflammation. When we injected ultrasmall coordinated Au13 nanoclusters intravenously (i.v.) to EAE mice, and then subjected the spinal cords to tissue clearing, we detected Au signals leaked from the blood vessels at L5 by light sheet microscopy, which enabled the visualization of complex tissue structures at the whole organ level, consistent with our previous report that microinflammation occurs specifically at this site. Our method will be useful to specify and track the stepwise development of microinflammation in whole organs that is triggered by the recruitment of pathogenic immune cells at specific blood vessels in various inflammatory diseases.

The mechanism of macrophage-inducible C-type lectin involved in uremic microinflammatory state / 西安交通大学学报(医学版)

【Objective】 To explore the mechanism of macrophage-inducible C-type lectin (Mincle) and microinflammatory state in uremia. 【Methods】 SD rats were randomly divided into uremia group and sham operation group. The morphology and permeability of intestinal tissue, the morphology of intestinal tissue and macrophages were observed by transmission electron microscope, the expression of Mincle was detected in intestinal tissue sections, and the expressions of Toll-like receptor 4 (TLR-4) and NF-kappa B (NF-κB) protein on the surface of macrophages were detected by Western blotting. After the plasma was separated, the levels of endotoxin, C-reactive protein (CRP), interleulin-6 (IL-6) and tumor necrosis factor-α (TNF-α) were detected by Limulus lysate dynamic turbidimetric assay, and enzyme-linked immunosorbent assay (ELISA). The data were analyzed with IBM SPSS19.0 software. 【Results】 The expression of Mincle in the jejunum, ileum, and colon in uremia group was higher than that in sham-operation group (P<0.05). The expressions of TLR4 and NF-κB protein significantly differed in the ileum, jejunum and colon in uremia group (P<0.001). The levels of endotoxin, CRP, IL-6, and TNF-α were significantly increased in uremia group compared with sham-operation group (P<0.05). 【Conclusion】 In uremia, Mincle on the surface of intestinal macrophages increases and further through TLR4/NF-κB pathway mediates the transformation of intestinal macrophages to M1 type, releasing inflammatory products and causing systemic microinflammation.

Use of the systemic inflammation response index (SIRI) as a novel prognostic marker for patients on peritoneal dialysis.

BACKGROUND: The systemic inflammatory response index (SIRI), a novel inflammation maker, has proven to be associated with prognostic outcomes in various diseases. However, few studies have been conducted assessing how SIRI may influence outcomes of patients on peritoneal dialysis (PD). Herein, we assessed the predictive value of SIRI on mortality all-cause mortality, including cardiovascular disease (CVD) in PD patients. METHODS: A total of 646 PD patients were enrolled in this study. PD patients received regular PD treatments at the Zhujiang Hospital from 1 January 2011 to 31 December 2018. SIRI values could be computed as follows: neutrophil count × monocyte count/lymphocyte count. Patients were divided into two groups according to the median level of SIRI. Cox regression analysis and Kaplan-Meier methods were applied to analyze the relationship between SIRI and mortality outcomes in PD patients. RESULTS: During the median 31-month follow-up period, 97 (15.0%) PD patients died from all-causes, and 47 (49.0%) died of CVD. Kaplan-Meier analyses revealed that a high SIRI corresponded to the high mortality of all-cause deaths, including CVD (both p < 0.001) in patients on PD. After adjusting for potential confounders, the higher SIRI level was significantly associated with an increased all-cause mortality (HR: 2.007, 95% CI: 1.304-3.088, p = 0.002) and cardiovascular mortality (HR: 2.847, 95% CI: 1.445-5.608, p = 0.002). CONCLUSIONS: SIRI was a promising predictor of mortality in PD patients, with a higher SIRI corresponding to increased risk of mortality.

The central nervous system control of energy homeostasis: High fat diet induced hypothalamic microinflammation and obesity.

Obesity is believed to arise through the imbalance of energy homeostasis controlled by the central nervous system, where the hypothalamus plays the fundamental role in energy metabolism. In this review, we will provide an overview regarding the functions of POMC neurons and AgRP neurons in acute nucleus of the hypothalamus which mediated the energy metabolism, highlighting their interactions with peripheral organs derived hormones in control of energy homeostasis. Furthermore, the role of high fat diet induced hypothalamic microinflammation in the pathogenesis of obesity will be discussed. We hope this review could help researchers to understand the mechanism of hypothalamus in control of energy metabolism, and design related drugs to block the pathways involving in the impaired metabolism in obese patients.

[Meta-analysis of Bailing Capsules in improvement of microinflammation and nutritional status among maintenance hemodialysis patients].

This Meta-analysis was designed to evaluate the effects of Bailing Capsules on microinflammation and nutritional status of maintenance hemodialysis patients, and to determine its efficacy and safety. The randomized controlled trials concerning the intervention of microinflammation and nutritional status in maintenance hemodialysis patients with Bailing Capsules were searched from Chinese and English databases including CNKI, Wanfang, VIP, PubMed, EMbase, and Cochrane Library. A total of 16 articles were obtained, involving 1 095 cases. As revealed by Meta-analysis,(1)Bailing Capsules lowered the levels of serum high sensitivity C-reactive protein(SMD=-0.92, 95%CI[-1.05,-0.80], P<0.000 01), interleukin-6(SMD=-1.49, 95%CI[-1.96,-1.02], P<0.000 01), and tumor necrosis factor-α(SMD=-1.48, 95%CI[-1.68,-1.28], P<0.000 01) in patients with maintenance hemodialysis, thus alleviating microinflammation.(2)Bailing Capsules elevated the levels of serum hemoglobin(SMD=1.37, 95%CI[1.21, 1.54], P<0.000 01), albumin(SMD=0.78, 95%CI[0.57, 0.98], P<0.000 01), and triglyceride(SMD=0.29, 95%CI[0.07, 0.50], P=0.01) in patients with hemodialysis to improve their nutritional status.(3)Bailing Capsules reduced the incidence of cardiovascular events(RR=0.45, 95%CI[0.34, 0.59], P<0.000 01).(4)A total of six patients presented with mild gastrointestinal discomfort after receiving Bailing Capsules, and no serious adverse reactions were observed. The sequential analysis showed that the sample size of this Meta-analysis had reached the expected value. Meanwhile, the grade of evidence quality suggested that the outcome indicators were mainly low or extremely low in quality. In conclusion, Bailing Capsules might have potential advantages in alleviating microinflammation, improving nutritional status, and reducing the incidence of cardiovascular events. However, in view of the low quality and evidence of the included literature, high-quality clinical trials are needed to further confirm the efficacy and safety of Bailing Capsules.

Safflower oil body nanoparticles deliver hFGF10 to hair follicles and reduce microinflammation to accelerate hair regeneration in androgenetic alopecia.

Androgenetic alopecia (AGA) affects physical and mental health with limited therapeutic options. Novel materials and delivery methods have considerable potential to improve the current paradigm of treatment. In this study, we used a novel plant nanoparticle of safflower oil body (SOB) loaded with human fibroblast growth factor 10 (hFGF10) to target hair follicles and accelerate hair regeneration in AGA mice with few adverse effects. Our data revealed that the average particle size of SOB-hFGF10 was 226.73 ± 9.98 nm, with a spherical and uniform structure, and that SOB-hFGF10 was quicker to preferentially penetrate into hair follicles than hFGF2 alone. Using a mouse model of AGA, SOB-hFGF10 was found to significantly improve hair regeneration without any significant toxicity. Furthermore, SOB-hFGF10 inhibited dihydrotestosterone (DHT)-induced TNF-α, IL-1ß, and IL-6 overproduction in macrophages in relation to hair follicle microinflammation, thereby enhancing the proliferation of dermal papilla cells. Overall, this study provides an applicable therapeutic method through targeting hair follicles and reducing microinflammation to accelerate hair regeneration in AGA.

The Usefulness of the Erythrocyte Sedimentation Rate and C-reactive Protein for the Differential Diagnosis of Non-Arteritic Anterior Ischemic Optic Neuropathy in the Era of Microinflammation.

PURPOSE: The presence of a microinflammatory response is one of the possible pathological mechanisms related to the development of nonarteritic anterior ischemic optic neuropathy (NAAION), a common cause of optic neuropathy in old age.We tested whether individuals with NAAION harbor a heightened microinflammatory response compared to controls. METHODS: We measured the erythrocyte sedimentation rate (ESR) and high sensitivity C-reactive protein (hs-CRP) in NAAION patients during hospital admission and in four matched controls for each patient, retrieved from a large cohort of 20,000 apparently healthy individuals. RESULTS: We included 128 NAAION patients and 512 controls. No significant differences were found between patients and controls regarding the inflammatory biomarkers. CONCLUSIONS: This is the first report showing a lack of difference in ESR and hs-CRP levels between NAAION patients and matched controls, suggesting NAAION is not associated with a heightened inflammatory response, such as the one associated with multiple atherothrombotic risk factors.

Meta-analysis of Bailing Capsules in improvement of microinflammation and nutritional status among maintenance hemodialysis patients / 中国中药杂志

This Meta-analysis was designed to evaluate the effects of Bailing Capsules on microinflammation and nutritional status of maintenance hemodialysis patients, and to determine its efficacy and safety. The randomized controlled trials concerning the intervention of microinflammation and nutritional status in maintenance hemodialysis patients with Bailing Capsules were searched from Chinese and English databases including CNKI, Wanfang, VIP, PubMed, EMbase, and Cochrane Library. A total of 16 articles were obtained, involving 1 095 cases. As revealed by Meta-analysis,(1)Bailing Capsules lowered the levels of serum high sensitivity C-reactive protein(SMD=-0.92, 95%CI[-1.05,-0.80], P<0.000 01), interleukin-6(SMD=-1.49, 95%CI[-1.96,-1.02], P<0.000 01), and tumor necrosis factor-α(SMD=-1.48, 95%CI[-1.68,-1.28], P<0.000 01) in patients with maintenance hemodialysis, thus alleviating microinflammation.(2)Bailing Capsules elevated the levels of serum hemoglobin(SMD=1.37, 95%CI[1.21, 1.54], P<0.000 01), albumin(SMD=0.78, 95%CI[0.57, 0.98], P<0.000 01), and triglyceride(SMD=0.29, 95%CI[0.07, 0.50], P=0.01) in patients with hemodialysis to improve their nutritional status.(3)Bailing Capsules reduced the incidence of cardiovascular events(RR=0.45, 95%CI[0.34, 0.59], P<0.000 01).(4)A total of six patients presented with mild gastrointestinal discomfort after receiving Bailing Capsules, and no serious adverse reactions were observed. The sequential analysis showed that the sample size of this Meta-analysis had reached the expected value. Meanwhile, the grade of evidence quality suggested that the outcome indicators were mainly low or extremely low in quality. In conclusion, Bailing Capsules might have potential advantages in alleviating microinflammation, improving nutritional status, and reducing the incidence of cardiovascular events. However, in view of the low quality and evidence of the included literature, high-quality clinical trials are needed to further confirm the efficacy and safety of Bailing Capsules.

Effect of Rehmanniae Radix combined with Scrophulariae Radix on renal microinflammation in diabetic nephropathy rats based on NF-κB pathway / 国际中医中药杂志

Objective:To explore the effect of Rehmanniae Radix combined with Scrophulariae Radix on renal microinflammation in diabetic nephropathy (DN) rats. Methods:50 Sprague Dawley (SD) rats were adaptively fed for 1 week, and then 10 rats were randomly selected as the blank control group, and the rest were treated with STZ intraperitoneal injection combined with high-fat diet to induce DN model. After 4 weeks, the successful modeled rats were randomly divided into model group, Rehmannia glutinosa Scrophularia group (5.25 g/kg) and metformin group (200 mg/kg), with 10 rats in each group. After 8 weeks of administration, fasting blood glucose was measured by blood glucose meter; microalbuminuria was measured by benzalkonium chloride turbidimetry; serum cystatin, TNF-α, IL-6 and hs-CRP levels were measured by ELISA kit; renal pathological changes were detected by HE staining, Masson staining and PAS staining; the expression of MCP-1, NF-κB (total) and p-NF-κB protein in renal tissue was detected by Western blot.Results:Compared with the model group, the body weight of rats in DHXS group was significantly decreased ( P<0.05). The content of fasting blood glucose[(18.06 ± 5.69) mmol/L vs. (29.42 ± 0.63)mmol/L], 24-hour urine protein [(11.02 ± 1.77)mg/d vs. (31.61 ± 0.65)mg/d], serum cystatin [(208.16 ± 12.07)ng/ml vs. (278.05 ± 19.33)ng/ml], TNF-α [(9.13 ± 1.46)pg/ml vs. (73.16 ± 8.30)pg/ml], IL-6[(4.27 ± 1.07)pg/ml], hs-CRP[(219.36 ± 22.02)ng/ml vs. (266.97 ± 15.80)ng/ml] in DHXS group were significantly decreased ( P<0.05), and the expression level of p-NF-κB (0.49 ± 0.07 vs. 0.84 ± 0.12) and MCP-1 (0.44 ± 0.02 vs. 0.64 ± 0.11) in renal tissue of rats in DHXS group were significantly reduced ( P<0.05). Conclusion:Rehmanniae Radix combined with Scrophulariae Radix can protect kidney by inhibiting the over activation of NF-κB, and reducing the expression of MCP-1 related protein to reduce renal micro inflammation.

Expanded Hemodialysis Therapy Ameliorates Uremia-Induced Systemic Microinflammation and Endothelial Dysfunction by Modulating VEGF, TNF-α and AP-1 Signaling.

Abstract: Systemic chronic microinflammation and altered cytokine signaling, with adjunct cardiovascular disease (CVD), endothelial maladaptation and dysfunction is common in dialysis patients suffering from end-stage renal disease and associated with increased morbidity and mortality. New hemodialysis filters might offer improvements. We here studied the impact of novel improved molecular cut-off hemodialysis filters on systemic microinflammation, uremia and endothelial dysfunction. Human endothelial cells (ECs) were incubated with uremic serum obtained from patients treated with two different hemodialysis regimens in the Permeability Enhancement to Reduce Chronic Inflammation (PERCI-II) crossover clinical trial, comparing High-Flux (HF) and Medium Cut-Off (MCO) membranes, and then assessed for their vascular endothelial growth factor (VEGF) production and angiogenesis. Compared to HF membranes, dialysis with MCO membranes lead to a reduction in proinflammatory mediators and reduced endothelial VEGF production and angiogenesis. Cytokine multiplex screening identified tumor necrosis factor (TNF) superfamily members as promising targets. The influence of TNF-α and its soluble receptors (sTNF-R1 and sTNF-R2) on endothelial VEGF promoter activation, protein release, and the involved signaling pathways was analyzed, revealing that this detrimental signaling was indeed induced by TNF-α and mediated by AP-1/c-FOS signaling. In conclusion, uremic toxins, in particular TNF-signaling, promote endothelial maladaptation, VEGF expression and aberrant angiogenesis, which can be positively modulated by dialysis with novel MCO membranes. Translational Perspective and Graphical Abstract: Systemic microinflammation, altered cytokine signaling, cardiovascular disease, and endothelial maladaptation/dysfunction are common clinical complications in dialysis patients suffering from end-stage renal disease. We studied the impact of novel improved medium-cut-off hemodialysis filters on uremia and endothelial dysfunction. We can show that uremic toxins, especially TNF-signaling, promote endothelial maladaptation, VEGF expression and aberrant angiogenesis, which can be positively modulated by dialysis with novel improved medium-cut-off membranes.

Low serum vitamin D concentration is correlated with anemia, microinflammation, and oxidative stress in patients with peritoneal dialysis.

BACKGROUND: Peritoneal dialysis (PD) is a form of dialysis to replace the function of kidney, that uses the peritoneum as a dialysis membrane to remove metabolites and water retained in the body. Vitamin D deficiency is prevalent in patients treated with PD. This research investigated the correlation between serum 25-hydroxyvitamin D [25(OH)D] concentration and anemia, microinflammation, and oxidative stress in PD patients. METHODS: 62 PD patients and 56 healthy volunteers were recruited in this research. Serum concentrations of 25(OH)D and basic parameters of anemia were detected. The correlation between serum 25(OH)D concentration with anemia, oxidative stress, and microinflammatory state were analyzed. RESULTS: In the PD group, the concentration of 25(OH)D was lower than the healthy control (HC) group (p < 0.001). Hemoglobin, red blood cell count (RBC), and total iron binding capacity (TIBC) in the PD group was significantly lower (all p < 0.001), while high-sensitivity C-reactive protein (hs-CRP), interleukin-6 (IL-6), and tumor necrosis factor α (TNF-α) concentrations were significantly higher, than the HC group (all p < 0.001). In the PD group, malondialdehyde (MDA) concentration was higher than in the HC group (p < 0.001), while superoxide dismutase (SOD) and glutathione peroxidase (GSH-Px) were lower (both p < 0.001). Serum 25(OH)D exhibited positive correlation with hemoglobin (r = 0.4509, p = 0.0002), RBC (r = 0.3712, p = 0.0030), TIBC (r = 0.4700, p = 0.0001), SOD (r = 0.4992, p < 0.0001) and GSH-Px (r = 0.4312, p = 0.0005), and negative correlation with hs-CRP (r = - 0.4040, p = 0.0011), TNF-α (r = - 0.4721, p = 0.0001), IL-6 (r = - 0.5378, p < 0.0001) and MDA (r = - 0.3056, p = 0.0157). CONCLUSION: In conclusion, reduced serum 25(OH)D concentrations in PD patients contribute to anemia, oxidative stress and microinflammatory state.

Circulating extracellular DNA is in association with continuous metabolic syndrome score in healthy adolescents.

Obesity is associated with chronic low-grade inflammation that eventually leads to metabolic complications. Extracellular DNA (ecDNA) is a damage-associated molecular pattern. Extracellular mitochondrial DNA can activate innate immunity. We hypothesized that ecDNA, especially of mitochondrial origin, could be associated with components of the metabolic syndrome in young healthy probands. In a cross-sectional study, healthy adolescents (n = 1,249) provided blood samples. Anthropometric data, blood pressure, and blood counts were assessed. In addition, biochemical analysis of sera or plasma was conducted, including the quantification of advanced oxidation protein products (AOPPs) as a marker of oxidative stress induced by neutrophil or monocyte activation. Plasma ecDNA was isolated and measured by fluorometry. Nuclear and mitochondrial DNA were quantified by real-time PCR. Males had higher total plasma ecDNA [15 (11-21) vs. 11 (8-17) ng/mL; median (interquartile range)], nuclear [1,760 (956-3,273) vs. 1,153 (600-2,292) genome equivalents (GE)/mL], and mitochondrial [37,181 (14,836-90,896) vs. 30,089 (12,587-72,286) GE/mL] DNA. ecDNA correlated positively with the continuous metabolic syndrome score (r = 0.158 for males and r = 0.134 for females). Stronger correlations were found between ecDNA of mitochondrial origin and AOPP (r = 0.202 and 0.186 for males and females, respectively). Multivariate regression analysis revealed associations of nuclear DNA with leukocyte and erythrocyte counts. The results of this study of healthy adolescents show that circulating ecDNA is associated with the risk of metabolic syndrome, not with obesity per se. The association between mitochondrial ecDNA and AOPP requires further attention as it supports a potential role of mitochondria-induced sterile inflammation in the pathogenesis of the metabolic syndrome.

The Relationship between Serum Procalcitonin and Dialysis Adequacy in Peritoneal Dialysis Patients.

BACKGROUND: To detect the serum procalcitonin (PCT) levels of peritoneal dialysis (PD) patients. METHODS: We analyzed the relationship between the PCT Level and dialysis adequacy. We studied 120 peritoneal dialysis patients without signs of infection in Affiliated Hangzhou First People's Hospital and 120 controls from Jan 2014 to Apr 2016. PCT and high sensitivity C-reactive protein (hs-CRP) were detected. 120 PD patients were divided into two groups according to the dialysis adequacy. A correlation analysis was processed between the PCT level and the total solute clearance (Kt/V). The value of PCT for identifying the dialysis adequacy in PD patients was assessed by ROC curve analysis. RESULTS: PCT level in serum of PD group (0.29±0.24 ng/ml) was higher than that of the control group (0.02±0.01 ng/ml) (P<0.01). Compared with the inadequate dialysis group (0.5±0.37 ng/ml), the PCT Level of the adequate dialysis group (0.23±0.15 ng/ml) was lower (P<0.01). There were negative correlations between PCT and Kt/v(r=-0.451), Prealbumin (PA) (r=-0.258), Glomerular Filtration Rate (eGFR; r=-0.280), while there was positive correlation between PCT and Hypersensitive c-reactive protein (r=0.458) (P<0.01). At a serum PCT cut-off value of 0.283 ng/ml, the sensitivity and specificity for identifying the dialysis adequacy in PD patients were 0.913 and 0.805 respectively. The serum levels of PCT in peritoneal dialysis patients were significantly higher than the levels in healthy controls. CONCLUSION: The serum level of PCT can be used as an indirect maker to evaluate the adequacy of dialysis.