Marrubiin Inhibits Peritoneal Inflammatory Response Induced by Carrageenan Application in C57 Mice.

Marrubiin is a diterpene with a long history of a wide range of biological activities. In this study, the anti-inflammatory effects of marrubiin were investigated using several in vitro and in vivo assays. Marrubiin inhibited carrageenan-induced peritoneal inflammation by preventing inflammatory cell infiltration and peritoneal mast cell degranulation. The anti-inflammatory activity was further demonstrated by monitoring a set of biochemical parameters, showing that the peritoneal fluid of animals treated with marrubiin had lower levels of proteins and lower myeloperoxidase activity compared with the fluid of animals that were not treated. Marrubiin exerted the most pronounced cytotoxic activity towards peripheral mononuclear cells, being the main contributors to peritoneal inflammation. Additionally, a moderate lipoxygenase inhibition activity of marrubiin was observed.

A Novel IRAK4 Inhibitor DW18134 Ameliorates Peritonitis and Inflammatory Bowel Disease.

IRAK4 is a critical mediator in NF-κB-regulated inflammatory signaling and has emerged as a promising therapeutic target for the treatment of autoimmune diseases; however, none of its inhibitors have received FDA approval. In this study, we identified a novel small-molecule IRAK4 kinase inhibitor, DW18134, with an IC50 value of 11.2 nM. DW18134 dose-dependently inhibited the phosphorylation of IRAK4 and IKK in primary peritoneal macrophages and RAW264.7 cells, inhibiting the secretion of TNF-α and IL-6 in both cell lines. The in vivo study demonstrated the efficacy of DW18134, significantly attenuating behavioral scores in an LPS-induced peritonitis model. Mechanistically, DW18134 reduced serum TNF-α and IL-6 levels and attenuated inflammatory tissue injury. By directly blocking IRAK4 activation, DW18134 diminished liver macrophage infiltration and the expression of related inflammatory cytokines in peritonitis mice. Additionally, in the DSS-induced colitis model, DW18134 significantly reduced the disease activity index (DAI) and normalized food and water intake and body weight. Furthermore, DW18134 restored intestinal damage and reduced inflammatory cytokine expression in mice by blocking the IRAK4 signaling pathway. Notably, DW18134 protected DSS-threatened intestinal barrier function by upregulating tight junction gene expression. In conclusion, our findings reported a novel IRAK4 inhibitor, DW18134, as a promising candidate for treating inflammatory diseases, including peritonitis and IBD.

Mycoplasma hominis peritonitis after oocyte donation.

We report the case of a young, immunocompetent, non-pregnant woman diagnosed with acute abdomen 3 weeks after an ultrasound-guided transvaginal oocyte retrieval (TVOR). Peritoneal fluid, obtained during exploratory laparoscopy, yielded Mycoplasma hominis as the sole pathogen. The patient's symptoms and signs improved after 24-hour treatment with intravenous clindamycin, ampicillin and gentamycin. Complete resolution was achieved with oral doxycycline for 14 days.

[Mechanism of Fushen Granules treat peritoneal dialysis-related peritonitis by regulating TLR4/NF-κB pathway:based on network pharmacology and animal experiments].

Network pharmacology was employed to probe into the mechanism of Fushen Granules in treating peritoneal dialysis-rela-ted peritonitis(PDRP) in rats. The main active components of Fushen Granules were searched against the Traditional Chinese Medicine Systems Pharmacology Database and Analysis Platform, and their targets were predicted. PDRP-related targets were retrieved from DisGeNET and other databases. The common targets shared by the drug and the disease were identified by the online tool, and protein-protein interaction(PPI) network of the common targets. The obtained 276 common targets were imported into DAVID for GO function enrichment and KEGG pathway enrichment. The main signaling pathway of Fushen Granules in the treatment of PDRP was predicted as Toll-like receptor 4(TLR4)/nuclear factor(NF)-κB. The rat model of uremia was induced by 5/6 nephrectomy. From two weeks after operation, the rat model of peritoneal dialysis(PD) was established by intraperitoneal injection of 20 mL dialysate with 1.25% glucose every day. The sham operation group and model group received 2 mL normal saline by gavage every day. The rats in Fushen Gra-nules groups were administrated with 2 mL solutions of low-(0.54 g·kg~(-1)), medium-(1.08 g·kg~(-1)) and high-dose(2.16 g·kg~(-1)) Fushen Granules every day. The bifico group received 2 mL(113.4 mg·kg~(-1)) of bifico solution every day. At the end of the 8th week, the levels of serum creatinine(Scr) and blood urea nitrogen(BUN) in each group were measured. The serum levels of hypersensitive C reactive protein(hs-CRP), tumor necrosis factor(TNF)-α, and interleukin(IL)-6 were measured, and the pathological changes in the colon tissue were observed by hematoxylin-eosin(HE) staining. The serum levels of lipopolysaccharide(LPS) and lipopolysaccharide-binding protein(LBP) of rats were measured, and the expression levels of LBP, TLR4, NF-κB p65, inhibitor of κB kinase α(IκBα), TNF-α, and IL-1ß in the colon tissue were determined. Compared with sham operation group, the model group had abnormal structure of all layers of colon tissue, sparse and shorter intestinal villi, visible edema in mucosal layer, wider gap, obvious local inflammatory cell infiltration, significantly decreased body weight(P<0.01), and significantly increased kidney function index(Scr, BUN) content(P<0.01). Serum levels of inflammatory cytokines(hs-CRP, TNF-α, IL-6), LPS and LBP were significantly increased(P<0.01), protein expressions of LBP, TLR4, NF-κB p65, TNF-α and IL-1ß were significantly increased(P<0.01), and protein expressions of IκBα were significantly decreased(P<0.01). Compared with model group, intestinal villi damage in colonic tissue of rats in low-, medium-and high-dose Fushen Granules groups and bifico group were alleviated to different degrees, edema in submucosa was alleviated, space was narrowed, and inflammatory cell infiltration in lamina propria was reduced. The contents of renal function index(Scr, BUN) and serum inflammatory factors(hs-CRP, TNF-α, IL-6) were significantly decreased(P<0.05 or P<0.01) in medium-and high-dose Fushen Granules groups and bifico group(P<0.05 or P<0.01). Serum LPS and LBP contents in Fushen Granules group and bifico group were significantly decreased(P<0.01), protein expressions of LBP, TLR4, NF-κB p65, TNF-α and IL-1ß in Fushen Granules group were significantly decreased(P<0.05 or P<0.01), and protein expressions of IκBα were significantly increased(P<0.01). The expression of LBP protein in bifico group was significantly decreased(P<0.01). The results suggest that Fushen Granules can protect the residual renal function of PD rats, reduce the inflammatory response, and protect the colon tissue. Based on network pharmacology, TLR4/NF-κB pathway may be the main signaling pathway of Fushen granule in the treatment of PDRP. The results showed that Fushen Granules could improve intestinal inflammation and protect intestinal barrier to prevent PDRP by regulating the expression of key factors in TLR4/NF-κB pathway in colon of PD rats.

Human Amniotic MSC Response in LPS-Stimulated Ascites from Patients with Cirrhosis: FOXO1 Gene and Th17 Activation in Enhanced Antibacterial Activation.

Spontaneous bacterial peritonitis (SBP) is a severe complication in patients with decompensated liver cirrhosis and is commonly treated with broad spectrum antibiotics. However, the rise of antibiotic resistance requires alternative therapeutic strategies. As recently shown, human amnion-derived mesenchymal stem cells (hA-MSCs) are able, in vitro, to promote bacterial clearance and modulate the immune and inflammatory response in SBP. Our results highlight the upregulation of FOXO1, CXCL5, CXCL6, CCL20, and MAPK13 in hA-MSCs as well as the promotion of bacterial clearance, prompting a shift in the immune response toward a Th17 lymphocyte phenotype after 72 h treatment. In this study, we used an in vitro SBP model and employed omics techniques (next-generation sequencing) to investigate the mechanisms by which hA-MSCs modify the crosstalk between immune cells in LPS-stimulated ascitic fluid. We also validated the data obtained via qRT-PCR, cytofluorimetric analysis, and Luminex assay. These findings provide further support to the hope of using hA-MSCs for the prevention and treatment of infective diseases, such as SBP, offering a viable alternative to antibiotic therapy.

The impact of icodextrin on the outcomes of incident peritoneal dialysis patients.

OBJECTIVE: The aim of the study is to investigate the effects of icodextrin on the risks of death, technique failure and the first episode of peritonitis in peritoneal dialysis (PD) patients. METHODS: From medical records of a medical center in Taiwan, a total of 725 newly diagnosed end-stage kidney disease patients receiving PD for at least 90 days from January 1, 2007 to December 31, 2018 were identified. These patients were grouped as 190 icodextrin users and 535 non-users. Users were defined as utilization of icodextrin for ≥ 50% of their PD duration. The use of icodextrin was considered a time-varying exposure in the Cox proportional hazard model. The risks of death, technique failure and the first episode of peritonitis were compared between two cohorts by the end of 2018. RESULTS: Compared to the non-users, the icodextrin users had significant lower risks of mortality (6.5 vs.7.2 per 100 person-years; adjusted HR = 0.62, 95% CI = 0.42-0.91) and technique failure (12.7 vs. 15.2 per 100 person-years; adjusted HR = 0.61, 95% CI = 0.47-0.81), and the first peritonitis episode (5.0 vs. 17.0 per 100 person-years; adjusted HR = 0.22, 95% CI = 0.14-0.35). The risk of peritonitis reduced further in icodextrin users with diabetes and with cardiovascular disease. CONCLUSION: Icodextrin was associated with lower risks of mortality, technique failure, and the first episode of peritonitis.

Impact of the phenotypic expression of temocillin resistance in Escherichia coli on temocillin efficacy in a murine peritonitis model.

BACKGROUND: Temocillin is a narrow spectrum ß-lactam active against MDR Enterobacterales. Mechanisms of acquired resistance to temocillin are poorly understood. We analysed resistance mechanisms in clinical isolates of Escherichia coli and evaluated their impact on temocillin efficacy in vitro and in a murine peritonitis model. METHODS: Two sets of isogenic clinical E. coli strains were studied: a susceptible isolate (MLTEM16S) and its resistant derivative, MLTEM16R (mutation in nmpC porin gene); and temocillin-resistant derivatives of E. coli CFT073: CFT-ΔnmpC (nmpC deletion), CFTbaeS-TP and CFTbaeS-AP (two different mutations in the baeS efflux-pump gene).Fitness cost, time-kill curves and phenotypic expression of resistance were determined. Temocillin efficacy was assessed in a murine peritonitis model. RESULTS: MICs of temocillin were 16 and 64 mg/L for MLTEM16S and MLTEM16R, respectively, and 8, 128, 256 and 256 mg/L for E. coli-CFT073, CFT-ΔnmpC, CFTbaeS-TP and CFTbaeS-AP, respectively. No fitness cost of resistance was evidenced. All resistant strains showed heteroresistant profiles, except for CFTbaeS-AP, which displayed a homogeneous pattern. In vitro, temocillin was bactericidal against MLTEM16R, CFT-ΔnmpC, CFTbaeS-TP and CFTbaeS-AP at 128, 256, 512 and 512 mg/L, respectively. In vivo, temocillin was as effective as cefotaxime against MLTEM16R, CFT-ΔnmpC and CFTbaeS-TP, but inefficient against CFTbaeS-AP (100% mortality). CONCLUSIONS: Heteroresistant NmpC porin alteration and active efflux modification do not influence temocillin efficacy despite high MIC values, unfavourable pharmacokinetic/pharmacodynamic conditions and the absence of fitness cost, whereas homogeneously expressed BaeS efflux pump alteration yielding similar MICs leads to temocillin inefficacy. MIC as sole predictor of temocillin efficacy should be used with caution.

Peritoneal dialysis-associated peritonitis caused by Neisseria.sicca: A case report and literature review.

Neisseria sicca, a Gram-negative diplococcus commonly found in the nasopharynx as part of normal bacterial flora, is typically non-pathogenic but has been associated with various diseases including endocarditis, conjunctivitis, pneumonia and meningitis (Jeurissen et al., 2006; Kozlova et al., 2020; Alcid, 1980; Carter et al., 2007). In this report, we present a case of peritonitis in a patient undergoing peritoneal dialysis caused by N. sicca and review the literature on Neisseria-associated peritonitis.

The antibacterial activity and mechanism of a novel peptide MR-22 against multidrug-resistant Escherichia coli.

Introduction: Bacterial infections have become serious threats to human health, and the excessive use of antibiotics has led to the emergence of multidrug-resistant (MDR) bacteria. E. coli is a human bacterial pathogen, which can cause severe infectious. Antimicrobial peptides are considered the most promising alternative to traditional antibiotics. Materials and methods: The minimum inhibitory concentration (MIC), minimum bactericidal concentration (MBC) and hemolytic activity were determined by the microdilution method. The antimicrobial kinetics of MR-22 against E. coli were studied by growth curves and time-killing curves. The cytotoxicity of MR-22 was detected by the CCK-8 assay. The antimicrobial activity of MR-22 in salt, serum, heat and trypsin was determined by the microdilution method. The antimicrobial mechanism of MR-22 against drug-resistant E. coli was studied by Scanning Electron Microscope, laser confocal microscopy, and Flow Cytometry. The in vivo antibacterial activity of MR-22 was evaluated by the mice model of peritonitis. Results and discussion: In this study, MR-22 is a new antimicrobial peptide with good activity that has demonstrated against MDR E. coli. The antimicrobial activity of MR-22 exhibited stability under conditions of high temperature, 10% FBS, and Ca2+. However, a decline of the activity was observed in the presence of Na+, serum, and trypsin. MR-22 had no significant cytotoxicity or hemolysis in vitro. SEM and fluorescent images revealed that MR-22 could disrupt the integrity of cell membrane. DCFH-DA indicated that MR-22 increased the content of reactive oxygen species, while it decreased the content of intracellular ATP. In mice model of peritonitis, MR-22 exhibited potent antibacterial activity in vivo. These results indicated that MR-22 is a potential drug candidate against drug-resistant E. coli.

Targeted macrophage phagocytosis by Irg1/itaconate axis improves the prognosis of intracerebral hemorrhagic stroke and peritonitis.

BACKGROUND: Macrophages are innate immune cells whose phagocytosis function is critical to the prognosis of stroke and peritonitis. cis-aconitic decarboxylase immune-responsive gene 1 (Irg1) and its metabolic product itaconate inhibit bacterial infection, intracellular viral replication, and inflammation in macrophages. Here we explore whether itaconate regulates phagocytosis. METHODS: Phagocytosis of macrophages was investigated by time-lapse video recording, flow cytometry, and immunofluorescence staining in macrophage/microglia cultures isolated from mouse tissue. Unbiased RNA-sequencing and ChIP-sequencing assays were used to explore the underlying mechanisms. The effects of Irg1/itaconate axis on the prognosis of intracerebral hemorrhagic stroke (ICH) and peritonitis was observed in transgenic (Irg1flox/flox; Cx3cr1creERT/+, cKO) mice or control mice in vivo. FINDINGS: In a mouse model of ICH, depletion of Irg1 in macrophage/microglia decreased its phagocytosis of erythrocytes, thereby exacerbating outcomes (n = 10 animals/group, p < 0.05). Administration of sodium itaconate/4-octyl itaconate (4-OI) promoted macrophage phagocytosis (n = 7 animals/group, p < 0.05). In addition, in a mouse model of peritonitis, Irg1 deficiency in macrophages also inhibited phagocytosis of Staphylococcus aureus (n = 5 animals/group, p < 0.05) and aggravated outcomes (n = 9 animals/group, p < 0.05). Mechanistically, 4-OI alkylated cysteine 155 on the Kelch-like ECH-associated protein 1 (Keap1), consequent in nuclear translocation of nuclear factor erythroid 2-related factor 2 (Nrf2) and transcriptional activation of Cd36 gene. Blocking the function of CD36 completely abolished the phagocytosis-promoting effects of Irg1/itaconate axis in vitro and in vivo. INTERPRETATION: Our findings provide a potential therapeutic target for phagocytosis-deficiency disorders, supporting further development towards clinical application for the benefit of stroke and peritonitis patients. FUNDING: The National Natural Science Foundation of China (32070735, 82371321 to Q. Li, 82271240 to F. Yang) and the Beijing Natural Science Foundation Program and Scientific Research Key Program of Beijing Municipal Commission of Education (KZ202010025033 to Q. Li).

Micrococcus Peritonitis Complicating Peritoneal Dialysis.

Peritonitis, a serious complication of peritoneal dialysis (PD), can be caused by opportunistic pathogens like Micrococcus species on rare occasions. We present a case of Micrococcus sp peritonitis in a 55-year-old female with end-stage kidney disease on continuous cycling peritoneal dialysis for one year who presented with cloudy effluent. Initial treatment against Micrococcus sp with vancomycin, gentamicin, and prophylactic oral nystatin was successful. However, one month later, the patient presented with abdominal pain and dialysate culture again grew Micrococcus sp. Treatment with vancomycin was unsuccessful in resolving culture positivity. The patient was transitioned to hemodialysis for non-medical reasons and then was later restarted on PD without further peritonitis episodes. Micrococcus sp peritonitis in PD poses treatment challenges due to limited guidelines. Intraperitoneal vancomycin is commonly used to target Micrococcus isolates although there is a high incidence of treatment failure. This case report highlights the need for continued reporting to enhance identification, prevention, and patient outcomes in Micrococcus sp peritonitis during PD.

Rapid and Effective Treatment of Peritonitis in Peritoneal Dialysis Patients with Intravenous Dalbavancin.

BACKGROUND Peritonitis is a complication associated with peritoneal dialysis (PD), which carries a significant morbidity and mortality risk. Empiric therapy must include coverage of gram-positive organisms; vancomycin is a recommended treatment option, particularly when MRSA infection is a risk. Vancomycin is cumbersome for patients, requiring therapeutic drug monitoring and re-administration by a healthcare provider. Dalbavancin, administered as a one-time intravenous dose, is a convenient potential treatment option for PD patients to cover gram-positive organisms without the need for routine drug monitoring. CASE REPORT We present 2 patients effectively treated with dalbavancin for infectious peritonitis. The first patient, a 73-year-old woman with end-stage renal disease (ESRD) on PD, presented to the hospital with fever, elevated white blood cells (WBCs), and cloudy peritoneal fluid with elevated nucleated cell counts (88% neutrophils). This patient was given 1 dose of 1500 mg IV dalbavancin. Within 3 days, her fever resolved, WBCs returned to normal, and peritoneal fluid results improved. The second patient was a 36-year-old woman presenting to an outpatient clinic with abdominal pain and cloudy peritoneal fluid with elevated nucleated cell counts (53% neutrophils) treated with dalbavancin 1500 mg IV once. Within 4 days, this patient's pain had resolved, and peritoneal fluid results returned to baseline. No adverse effects were noted for either patient. CONCLUSIONS These cases illustrate the potential of dalbavancin as a convenient option for patients with PD-associated peritonitis. Both patients demonstrated rapid and complete response to a single dose of dalbavancin without complications. Further prospective studies are needed to establish dalbavancin as an option for peritonitis.

Methylobacterium infection-induced peritonitis in a patient with renal insufficiency: A case report and literature review.

Clinical pharmacists participated in the drug therapy of peritonitis caused by Methylobacterium infection in a patient with renal insufficiency. Based on the knowledge of clinical pharmacy, the patient's condition and laboratory parameters, the literature, and the pharmacokinetic/pharmacodynamic characteristics of antibiotics, amikacin in combination with ciprofloxacin was suggested for anti-infection therapy. During the treatment, clinical pharmacists timely evaluated the efficacy of antibiotics, monitored the adverse reactions, and provided individualized pharmaceutical care in the patient.

The antioxidant, anti-inflammatory and analgesic activity effect of ethyl acetate extract from the flowers of Syringa pubescens Turcz.

ETHNOPHARMACOLOGICAL RELEVANCE: Syringa Pubescens Turcz. (SP), a member of the Oleaceae family, is a species of plant known as Syringa. Flowers, as the medicinal part, are commonly used in the treatment of hepatitis and tonsillitis. AIM OF THE STUDY: The research was the first to assess the antioxidant and anti-inflammatory potential of different parts of SP flowers (SPF) in vitro. The most promising fraction was ethyl acetate fraction of SP flower (SPFEA). The antioxidant, anti-inflammatory and analgesic activities of SPFEA were further studied, and the chemical components were identified. METHODS: HPLC was used to identify the major components in various fraction of SPF. DPPH and ABTS + radical scavenging assays as well as FRAP test and ß-carotene bleaching test were employed to assess the antioxidant potential of SPF fraction in vitro. The inhibitory effect on NO production in LPS-treated RAW264.7 cells and heat-induced protein denaturation test were used to evaluate the anti-inflammatory potential of SPF fraction. Further analysis of the biological activity of SPFEA was performed. Acute toxicity test was conducted to assess the toxicity of SPFEA. The anti-inflammatory effect was assessed by utilizing xylene induced ear edema model, carrageenan-induced foot edema model and peritonitis model in vivo. The analgesic effect of SPFEA was evaluated using hot plate test, tail immersion test, formaldehyde test as well as acetic acid-induced abdominal writhing pain experiment in vivo. In carrageenan induced foot edema model, ELISA kits were employed to measure levels of inflammation factors (NO, TNF-α, IL-6, COX-2, IL-1ß) in foot tissue as well as MDA, CAT, SOD, GSH-PX levels in liver tissue. RESULTS: HPLC results showed that there were significant differences in bioactive substances among different fractions of SPF, and SPFEA was rich in bioacitve components. Compared with other fractions of SPF, SPFEA exhibited better antioxidant and anti-inflammatory abilities. The 3000 mg/kg SPFEA group in mice had no obvious side effects. The xylene-induced ear edema model, carrageenan-induced foot edema and peritonitis models demonstrated that the SPFEA had significant anti-inflammatory effect. Moreover, inflammation factors including NO, TNF-α, IL-6, COX-2, IL-1ß were significantly reduced in SPFEA groups in foot tissue induced by carrageenan. Additionally, SPFEA effectively decreased liver tissue oxidative stress levels (MDA, SOD, GSH-PX and CAT). The bioactivities of SPFEA demonstrated a clear dose-dependent relationship. The results of the hot plate test, tail immersion test, formaldehyde test and acetic acid-induced abdominal writhing pain experiments indicated the SPFEA possessed an excellent analgesic effect, and this effect was in dose-dependent manner. CONCLUSION: The study provides a scientific foundation for understanding the pharmacological action of SPFEA. It has been indicated that SPFEA has excellent antioxidant, analgesic and anti-inflammatory effects.

Vancomycin flushing reaction after intraperitoneal vancomycin: A case report.

Vancomycin has been reported to cause vancomycin flushing reaction (VFR), a hypersensitivity reaction that mostly occurs after intravenous administration. The incidence of VFR in a patient receiving intraperitoneal vancomycin is rare. We report a case of a female peritoneal dialysis (PD) patient with a PD-related peritonitis who developed VFR after intraperitoneal administration of 2000 mg vancomycin. Seventy-five minutes after instillation, she developed flushing, a pruritic erythema on the upper body and swelling of the lips. Blood results revealed a vancomycin plasma concentration of 54.8 mg/L and a normal tryptase level. During a relapse of her PD-related peritonitis, vancomycin was successfully reintroduced in a 50% reduced dose. No symptoms of VFR developed, and the corresponding vancomycin plasma concentration was 33.6 mg/L. Intraperitoneal treatment was continued with 500 mg vancomycin every 2-3 days with frequently measured, adequate trough levels ranging from 15-22 mg/L. This case illustrates the risk factors for the development of VFR after intraperitoneal administration of vancomycin, namely a high and concentrated loading dose together with a low body weight, a fast peritoneal transport state and peritonitis. Reintroduction of vancomycin after occurrence of VFR is safe, but a lower loading dose or a slower instillation rate is recommended.

Sesquiterpene from Artemisia argyi seed extracts: A new anti-acute peritonitis agent that suppresses the MAPK pathway and promotes autophagy.

To find novel anti-inflammatory drugs, we screened anti-inflammatory compounds from 18 different types of Artemisia argyi seed extracts. The in vitro and in vivo anti-inflammatory activities of the screened compounds and their mechanisms were characterized. We first detected the cytotoxic effect of the compounds on RAW264.7 cells and the inhibitory effect on LPS-induced NO release. It was found that sesquiterpenoids CA-2 and CA-4 had low cytotoxic and strong NO inhibitory activity with an IC50 of 4.22 ± 0.61 µM and 2.98 ± 0.23 µM for NO inhibition, respectively. Therefore, compound CA-4 was studied in depth. We found that compound CA-4 inhibited LPS-induced pro-inflammatory factor production and M1 macrophage differentiation in RAW264.7 cells. Additionally, CA-4 inhibited the expression of p-ERK1/2, p-JNK, iNOS, and COX-2 by blocking the MAPK signaling pathway. CA-4 also promoted the expression of autophagy-related proteins such as LC3 II and Beclin-1 by inhibiting activation of the PI3K/AKT/mTOR signaling pathway, and promoted the generation of autophagosomes. Finally, CA-4 significantly inhibited the degree of inflammation in mice with acute peritonitis, showing good anti-inflammatory activity in vivo. Consequently, compound CA-4 may be a promising drug for the treatment of acute inflammatory diseases and provide new ideas for the synthesis of novel anti-inflammatory compounds.

Exploring immunoregulatory properties of a phenolic-enriched maple syrup extract through integrated proteomics and in vitro assays.

Our laboratory has established a comprehensive program to investigate the phytochemical composition and nutritional/medicinal properties of phenolic-enriched maple syrup extract (MSX). Previous studies support MSX's therapeutic potential in diverse disease models, primarily through its anti-inflammatory effects. We recently demonstrated MSX's ability to regulate inflammatory signaling pathways and modulate inflammatory markers and proteins in a lipopolysaccharide (LPS)-induced peritonitis mouse model. However, MSX's immunoregulatory properties remain unknown. Herein, we investigated MSX's immunoregulatory properties for the first time using an integrated approach, combining data-dependent acquisition (DDA) and data-independent acquisition (DIA) strategies in a proteomic analysis of spleen tissue collected from the aforementioned peritonitis mouse model. Additionally, we conducted immune cell activation assays using macrophages and T lymphocytes. The DIA analysis unveiled a distinctive expression pattern involving three proteins-Krt83, Thoc2, and Vps16-which were present in both the control and MSX-treated groups but absent in the LPS-induced model group. Furthermore, proteins Ppih and Dpp9 exhibited significant reductions in the MSX-treated group. Ingenuity pathway analysis indicated that MSX may modulate several critical signaling pathways, exerting a suppressive effect on immune responses in various cell types involved in both innate and adaptive immunity. Our in vitro cell assays supported findings from the proteomics, revealing that MSX significantly reduced the levels of interleukin-1 beta (IL-1ß) and tumor necrosis factor-alpha (TNF-α) in LPS-stimulated human macrophage cells, as well as the levels of IL-2 in anti-CD3/anti-CD28-induced Jurkat T cells. Taken together, our investigations provide evidence that MSX exerts immune regulatory effects that impact both innate and adaptive immunity, which adds to the data supporting MSX's development as a functional food.

Neutrophil Gelatinase-Associated Lipocalin in Peritoneal Dialysis-Related Peritonitis: Correlation with White Blood Cells over Time and a Possible Role as the Outcome Predictor.

INTRODUCTION: The present study aimed to monitor peritoneal neutrophil gelatinase-associated lipocalin (pNGAL) during peritonitis episodes and to enhance its diagnostic value by evaluating pNGAL at scheduled times in parallel with white blood cell (WBC) count. In addition, we investigated possible correlations between pNGAL and the etiology of peritonitis, evaluating it as a possible marker of the clinical outcome. METHODS: Twenty-two patients with peritoneal dialysis (PD)-related peritonitis were enrolled. Peritonitis was divided into Gram-positive, Gram-negative, polymicrobial, and sterile. WBC count and neutrophil gelatinase-associated lipocalin (NGAL) in PD effluent were measured at different times (days 0, 1, 5, 10, 15, and/or 20 and 10 days after antibiotic therapy discontinuation). NGAL was measured by standard quantitative laboratory-based immunoassay and by colorimetric NGAL dipstick (NGALds) (dipstick test). RESULTS: We found strong correlations between peritoneal WBC, laboratory-based NGAL, and NGALds values, both overall and separated at each time point. On day 1, we observed no significant difference in WBC, both NGALds (p = 0.3, 0.9, and 0.2) between Gram-positive, Gram-negative, polymicrobial, and sterile peritonitis. No significant difference has been found between de novo versus relapsing peritonitis for all markers (p > 0.05). We observed a parallel decrease of WBC and both NGAL in patients with favorable outcomes. WBC count and both pNGAL resulted higher in patients with negative outcomes (defined as relapsing peritonitis, peritonitis-associated catheter removal, peritonitis-associated hemodialysis transfer, peritonitis-associated death) at day 10 (p = 0.04, p = 0.03, and p = 0.05, respectively) and day 15 (p = 0.01, p = 0.04, and tendency for p = 0.005). There was a tendency toward higher levels of WBC and NGAL in patients with a negative outcome at day 5. No significant difference in all parameters was proven at day 1 (p = 0.3, p = 0.9, p = 0.2) between groups. CONCLUSION: This study confirms pNGAL as a valid and reliable biomarker for the diagnosis of PD-peritonitis and its monitoring. Its trend is parallel to WBC count during peritonitis episodes, in particular, patients with unfavorable outcomes.

Peritoneal dialysis-associated peritonitis with Elizabethkingia miricola.

Peritoneal dialysis (PD)-associated peritonitis is linked to increased mortality rates and transfer to haemodialysis or PD discontinuation. Rare and emerging pathogens can pose challenges in management. We present the first case of PD peritonitis caused by Elizabethkingia miricola through direct contamination, which was successfully treated with intraperitoneal and oral antibiotics.