Durvalumab plus carboplatin-etoposide treatment in a patient with small-cell lung cancer on hemodialysis: a case report and literature review.

Little is known about the efficacy and safety of durvalumab plus carboplatin-etoposide treatment in patients with extensive-disease (ED) small-cell lung cancer (SCLC) on hemodialysis. Here, we present a case of a 67-year-old man with pleuroperitoneal communication on continuous ambulatory peritoneal dialysis who was diagnosed with ED-SCLC based on a cytological analysis of the peritoneal fluid. He was switched from peritoneal dialysis to hemodialysis and received durvalumab (1500 mg/body on day 1) plus carboplatin (area under the concentration-time curve = 5, 125 mg on day 1) and etoposide (50 mg/m2 on days 1 and 3) as first-line therapy. During the first cycle, grade 2 anemia, grade 3 neutropenia, and grade 3 upper gastrointestinal bleeding occurred; therefore, durvalumab and reduced doses of carboplatin and etoposide were administered. No other severe adverse events occurred, and a partial response was observed after four cycles. Our findings indicate that durvalumab plus carboplatin-etoposide treatment is safe and effective even in patients on hemodialysis.

Crude Polysaccharides from Mushrooms Elicit an Anti-Allergic Effect Against Type 1 Allergy In Vitro.

Type 1 allergic disease is a global challenge, hence the search for alternative therapies. Mushrooms have several medicinal and health benefits. However, scant data exist on the anti-allergic properties of polysaccharides from fruiting bodies (FB) and mycelia of mushrooms. We used an in vitro co-culture system comprising Caco-2 cells (intestinal epithelial colorectal carcinoma cell line) and RBL-2H3 cells (cell line from rat basophilic leukemia cells). Reduction in degranulation of mast cells indicated anti-allergy properties. The inhibitory effect of crude polysaccharides from different mushroom FB and mycelia on ß-hexosaminidase release from RBL-2H3 cells was measured. Results showed that crude polysaccharides from the FB of Inonotus obliquus exhibited a significant inhibitory effect on ß-hexosaminidase release and lowered it by 16%. Polysaccharides from the FB of Lentinus squarrosulus, and Pleurotus ostreatus did not exhibit a significant reduction in ß-hexosaminidase. However, crude polysaccharides from their mycelia had a significant inhibitory effect, resulting in up to a 23% reduction in ß-hexosaminidase activity. Among fungi showing degranulation properties, crude polysaccharides from their mycelia showed more potent action against degranulation than their corresponding FB. Polysaccharides extracted from FB and or mycelia, of selected mushrooms, possess anti-allergic properties that could be harnessed for use in alternative allergy therapies.

Rationale and design of the Japanese Biomarkers in Nephrotic Syndrome (J-MARINE) study.

INTRODUCTION: Disease subtyping and monitoring are essential for the management of nephrotic syndrome (NS). Although various biomarkers for NS have been reported, their clinical efficacy has not been comprehensively validated in adult Japanese patients. METHODS: The Japanese Biomarkers in Nephrotic Syndrome (J-MARINE) study is a nationwide, multicenter, and prospective cohort study in Japan, enrolling adult (≥18 years) patients with minimal change disease (MCD), focal segmental glomerulosclerosis (FSGS), membranous nephropathy (MN), membranoproliferative glomerulonephritis (MPGN), C3 glomerulopathy (C3G), and lupus nephritis (LN). Baseline clinical information and plasma and urine samples will be collected at the time of immunosuppressive therapy initiation or biopsy. Follow-up data and plasma and urine samples will be collected longitudinally based on the designated protocols. Candidate biomarkers will be measured: CD80, cytotoxic T-lymphocyte antigen 4, and soluble urokinase plasminogen activator receptor for MCD and FSGS; anti-phospholipase A2 receptor and thrombospondin type-1 domain-containing protein 7A antibodies for MN; fragment Ba, C3a, factor I, and properdin for MPGN/C3G; and CD11b, CD16b, and CD163 for LN. Outcomes include complete and partial remission, relapse of proteinuria, a 30% reduction in estimated glomerular filtration rate (eGFR), eGFR decline, and initiation of renal replacement therapy. The diagnostic accuracy and predictive ability for clinical outcomes will be assessed for each biomarker. RESULTS: From April 2019 to April 2023, 365 patients were enrolled: 145, 21, 138, 10, and 51 cases of MCD, FSGS, MN, MPGN/C3G, and LN, respectively. CONCLUSION: This study will provide valuable insights into biomarkers for NS and serve as a biorepository for future studies.

Epidemiology and predictors of hyponatremia in a contemporary cohort of patients with malignancy: a retrospective cohort study.

Background: Hyponatremia is associated with worse outcomes among patients with malignancy. However, contemporary cohort data on epidemiology and risk factors are lacking. Methods: In this single-centre, retrospective cohort study, patients who received intravenous antineoplastic agents from 2018 to 2020 at Nagoya City University Hospital were enrolled. Associations of demographics, antineoplastic agents, types of malignancy and concomitant medications with hyponatremia, defined as serum sodium concentration ≤130 mmol/l, were analysed by mixed-effects logistic regression and the machine learning-based LightGBM model artificial intelligence technology. Results: Among 2644 patients, 657 (24.8%) developed at least one episode of hyponatremia. Approximately 80% of hyponatremia was due to sodium wasting from the kidneys. Variables associated with hyponatremia both by mixed-effects logistic regression and the LightGBM model were older age, hypoalbuminemia and higher estimated glomerular filtration rate. Among antineoplastic agents, cisplatin {odds ratio [OR] 1.52 [95% confidence interval (CI) 1.18-1.96]}, pembrolizumab [OR 1.42 (95% CI 1.02-1.97)] and bortezomib [OR 3.04 (95% CI 1.96-4.71)] were associated with hyponatremia and these variables also had a positive impact on predicted hyponatremia in the LightGBM model. Conclusions: Hyponatremia was common among patients with malignancy. In addition to older age and poor nutritional status, novel antineoplastic agents, including immune checkpoint inhibitors and bortezomib, should be recognized as risk factors for hyponatremia.

Peritoneal Expression of Membrane Complement Regulators Is Decreased in Peritoneal Dialysis Patients with Infected Peritonitis.

In peritoneal dialysis (PD) patients, fungi and Pseudomonas aeruginosa are considered important causative microorganisms for peritonitis with poor prognosis. Our objective was to explore expressions of membrane complement (C) regulators (CRegs) and tissue injuries in the peritoneum of patients with PD-related peritonitis, including fungal and Pseudomonas aeruginosa peritonitis. In peritoneal biopsy tissues obtained at PD catheter removal, we investigated the severity of peritonitis-associated peritoneal injuries and the expression of CRegs, CD46, CD55, and CD59 against peritoneal tissues without any episode of peritonitis. In addition, we evaluated peritoneal injuries among fungal and Pseudomonas aeruginosa-peritonitis (P1) and Gram-positive bacterial peritonitis (P2). We also observed deposition of C activation products such as activated C and C5b-9 and measured sC5b-9 in the PD fluid of patients. As a result, the severity of peritoneal injuries correlated inversely with the expression of peritoneal CRegs. Peritoneal CReg expression in peritonitis was significantly reduced compared to no peritonitis. Peritoneal injuries were more severe in P1 than in P2. CReg expression was further decreased and C5b-9 further increased in P1 than in P2. In conclusion, severe peritoneal injuries due to fungal and Pseudomonas aeruginosa-peritonitis decreased CReg expression and increased deposition of activated C3 and C5b-9 in the peritoneum, suggesting that peritonitis, particularly fungal and Pseudomonas aeruginosa-peritonitis, might induce susceptibility to further peritoneal injuries due to excessive C activation.

Inhibition of Transglutaminase 2 Reduces Peritoneal Injury in a Chlorhexidine-Induced Peritoneal Fibrosis Model.

Long-term peritoneal dialysis (PD) is often associated with peritoneal dysfunction leading to withdrawal from PD. The characteristic pathologic features of peritoneal dysfunction are widely attributed to peritoneal fibrosis and angiogenesis. The detailed mechanisms remain unclear, and treatment targets in clinical settings have yet to be identified. We investigated transglutaminase 2 (TG2) as a possible novel therapeutic target for peritoneal injury. TG2 and fibrosis, inflammation, and angiogenesis were investigated in a chlorhexidine gluconate (CG)-induced model of peritoneal inflammation and fibrosis, representing a noninfectious model of PD-related peritonitis. Transforming growth factor (TGF)-ß type I receptor (TGFßR-I) inhibitor and TG2-knockout mice were used for TGF-ß and TG2 inhibition studies, respectively. Double immunostaining was performed to identify cells expressing TG2 and endothelial-mesenchymal transition (EndMT). In the rat CG model of peritoneal fibrosis, in situ TG2 activity and protein expression increased during the development of peritoneal fibrosis, as well as increases in peritoneal thickness and numbers of blood vessels and macrophages. TGFßR-I inhibitor suppressed TG2 activity and protein expression, as well as peritoneal fibrosis and angiogenesis. TGF-ß1 expression, peritoneal fibrosis, and angiogenesis were suppressed in TG2-knockout mice. TG2 activity was detected by α-smooth muscle actin-positive myofibroblasts, CD31-positive endothelial cells, and ED-1-positive macrophages. CD31-positive endothelial cells in the CG model were α-smooth muscle actin-positive, vimentin-positive, and vascular endothelial-cadherin-negative, suggesting EndMT. In the CG model, EndMT was suppressed in TG2-knockout mice. TG2 was involved in the interactive regulation of TGF-ß. As inhibition of TG2 reduced peritoneal fibrosis, angiogenesis, and inflammation associated with TGF-ß and vascular endothelial growth factor-A suppression, TG2 may provide a new therapeutic target for ameliorating peritoneal injuries in PD.

The inhibitory effect of oral administration of lentinan on DSS-induced inflammation is exerted by the migration of T cells activated in the ileum to the colon.

Oral administration of lentinan ameliorated dextran sulfate sodium (DSS)-induced colitis through Dectin-1 receptor on intestinal epithelial cells. However, it is unclear where lentinan affects in the intestine to prevent the inflammation. We found that the administration of lentinan has induced migration of CD4+ cells from the ileum to the colon by using Kikume Green-Red (KikGR) mice in this study. This result suggests that the oral lentinan treatment could accelerate the migration of Th cells in lymphocyte from ileum into the colon during lentinan intake. Then, C57BL/6 mice were administered 2% DSS to induce colitis. The mice were administered lentinan daily via oral or rectal route before DSS administration. Its rectal administration also suppressed DSS-induced colitis, but its suppressive effects were lower compared to when orally administered, indicating that the biological responses to lentinan in the small intestine contributed to the anti-inflammatory effects. In normal mice (without DSS treatment), the expression of Il12b was significantly increased in the ileum by the oral administration of lentinan, but not by rectal one. On the other hand, no change was observed in the colon by either administration method. In addition, Tbx21 was significantly increased in the ileum. These suggested that IL-12 was increased in the ileum and Th1 cells differentiated in dependence on it. Therefore, Th1 predominant condition in the ileum could influence immunity in the colon and improve the colitis.

Serum and plasma levels of Ba, but not those of soluble C5b-9, might be affected by renal function in chronic kidney disease patients.

BACKGROUND: During the last few decades, pathogenic mechanisms associated with uncontrolled activation of the complement (C) system and development of anti-C agents have been closely investigated in the field of nephrology. The usefulness of some C products such as C5a and sC5b-9 for diagnostic and prognostic purposes remains controversial. On the other hand, decreased renal function is being observed in many patients with or without nephritis as a background factor in progressively aging societies. We therefore investigated whether renal function influenced the evaluation of various complement components and activation products. METHODS: To investigate the influence of renal function on evaluations of C3, C4, CH50, Ba, C5a and sC5b-9, 40 patients were retrospectively chosen from among 844 patients without active glomerulonephritis from 2009 to 2016. We measured plasma and serum levels of C3, C4, CH50, Ba, C5a and sC5b-9 using enzyme-linked immunosorbent assays and compared the findings with inulin clearance (Cin) as a marker of preserved renal function. RESULTS: Both plasma and serum levels of Ba correlated significantly with Cin, but other values did not. Compared with patients with Cin ≥ 60 or ≥ 30 mL/min/1.73 m2, plasma and serum levels of Ba were increased in patients with Cin decreased to < 60 or < 30 mL/min/1.73 m2, but levels of C5a and sC5b-9 were not. CONCLUSION: The influence of renal function might need to be considered when evaluating Ba, but not C5a and sC5b-9, in plasma and serum samples from chronic kidney disease patients.

Recurrent Cerebrovascular Complications under Enzyme Replacement Therapy in a Patient with Fabry Disease on Peritoneal Dialysis.

Fabry disease is an X-linked lysosomal storage disorder due to mutations in the alpha-galactosidase A gene, which leads to the accumulation of globotriaosylceramide in various organs. In Fabry disease with end-stage renal disease (ESRD), cerebrovascular events are lethal, even with enzyme replacement therapy (ERT). However, the utility of biomarkers to evaluate the ERT response is unclear. We herein report a case of recurrent cerebrovascular complications under ERT in a Fabry disease patient, progressing to ESRD on peritoneal dialysis. Further studies are warranted, but Fabry disease patients with ESRD receiving ERT might need careful long-term follow-up in cases with cerebrovascular manifestations.

Video-assisted thoracoscopic surgery for pleuroperitoneal communication.

Here we report the cases of five patients on continuous ambulatory peritoneal dialysis (CAPD) who developed hydrothorax because of pleuroperitoneal communication. Preoperative computed tomography (CT) peritoneography revealed penetrated sites on the diaphragm in all patients. All patients underwent video-assisted thoracoscopic surgery (VATS), and a dialysate containing indigo carmine was injected intraperitoneally through a CAPD catheter to confirm the fistula. In all patients, a thinned bleb was found at the center of the diaphragmatic tendon consistent with that noted on preoperative CT peritoneography. The bleb was resected using a surgical stapler in four patients, and the pleuroperitoneal communication did not recur. However, in one patient, the bleb was only covered with reinforcement agents and the hydrothorax recurred after CAPD. This study demonstrates that VATS treatment for pleuroperitoneal communication is safe and effective but that lesion resection would be more useful for preventing hydrothorax recurrence in patients undergoing CAPD.

Anti-Allergic Activity of Fucoidan Can Be Enhanced by Coexistence with Quercetin.

In recent years, the incidence of type I hypersensitivity including hay fever has been increasing year by year in Japan. Our previous study using mice showed that only oral, but not intraperitoneal, administration of fucoidan extracted from seaweed (Saccharina japonica) suppressed type I hypersensitivity by secretion of galectin-9, which has a high affinity for IgE in the blood. However, the amount of seaweed required to achieve this activity is quite high (12 g dry weight per person per day). Therefore, the purpose of this study was to search for food ingredients in vegetables that enhance type I hypersensitivity suppression effect when consumed together with fucoidan. As a result, the enhanced effect was observed in extracts from Welsh onions and onions among vegetables. When we compared the polyphenols in the vegetables that showed activity with those that did not, flavonols such as quercetin and kaempferol were found as candidates. When quercetin or kaempferol (100 µg each) were orally administered at the same time, even at amounts where fucoidan alone showed no anti-allergic activity, anti-allergic effects were observed. More interestingly, when both flavonols were combined and administered simultaneously at half the amount of each of the above flavonols (50 µg), while the fucoidan amount remained the same, a similar effect was observed as when each flavonol (100 µg) was administered alone. The simultaneous intake of fucoidan and vegetables containing high contents of quercetin or kaempferol may reduce fucoidan intake while maintaining the allergy suppression effect, suggesting the importance of food combination.

Interleukin-6 blockade reduces salt-induced cardiac inflammation and fibrosis in subtotal nephrectomized mice.

Cardiovascular disease is the most common comorbidity in patients with chronic kidney disease (CKD), affecting both their prognosis and quality of life. Cardiac fibrosis is common in patients with CKD with left ventricular diastolic dysfunction, and it is associated with increased risk of heart failure and mortality. Recent evidence suggests that high salt intake activates immune responses associated with local accumulation of sodium. We reported that high salt intake promotes cardiac inflammation in subtotal nephrectomized (Nx) mice. We investigated the effects of administration of MR16-1, a rat anti-mouse monoclonal interleukin (IL)-6 receptor antibody, in Nx mice with salt loading (Nx-salt). Expression of monocyte chemoattractant protein-1, tumor necrosis factor-α, IL-1ß, and IL-6 mRNAs and macrophage infiltration was significantly reduced in the heart of Nx-salt mice treated with MR16-1 (Nx-salt-MR16-1) compared with Nx-salt mice treated with control rat rat IgG1 (Nx-salt-rat IgG1). Correspondingly, cardiac fibrosis was significantly attenuated in Nx-salt-MR16-1 mice compared with Nx-salt-rat IgG1 mice. Furthermore, in the heart of Nx-salt-MR16-1 mice, expression of mRNA for nicotinamide adenine dinucleotide phosphate oxidase-2, an oxidative stress marker, was significantly downregulated compared with Nx-salt-rat IgG1 mice. Increases in cardiac metabolites, including histidine and γ-butyrobetaine, were also reversed by IL-6 blockade treatment. In conclusion, IL-6 blockade exerts anti-inflammatory, antifibrotic, and partial antioxidative effects in the heart of Nx-salt mice.NEW & NOTEWORTHY In the present study, IL-6 blockade exerted anti-inflammatory, antifibrotic, and partial antioxidative effects on the hearts of mice with CKD on a high-salt diet. Therefore, IL-6 potentially mediates cardiac fibrosis induced by high salt intake in patients with CKD, a finding with therapeutic implications. Of note, the next therapeutic implication may simply be the reinforcement of low-salt diets or diuretics and further research on the anti-inflammatory effects of these measures rather than IL-6 blockade with high-salt diet.

LENTINULA EDODES POLYSACCHARIDES SUPPRESSED PRO-INFLAMMATORY CYTOKINES EXPRESSION AND COLITIS IN MICE.

BACKGROUND: Polysaccharides from edible mushrooms possess immunomodulatory, anti-inflammatory, and anti-tumor activities. Recent studies indicated that necroptosis plays a role in the pathogenesis of inflammatory diseases and mediates increased expression of inflammatory cytokines. OBJECTIVE: Therefore, it is imperative to determine the impact of polysaccharide extract from Lentinula edodes (L. edodes) on inflammatory cytokines in experimental model of colitis in mice. METHODS: Female C57BL/6 mice divided into three or four mice per group were used for this study. Polysaccharide sample was orally administered to mice prior to (7 days) and during colitis induction with 2.5% dextran sodium sulfate (7 days), followed by additional 3 days of administration. Changes in body weight and colon length were used as markers for colitis, and pro-inflammatory cytokines and tumor necrosis factor receptor 1 (TNFR1) expressions, as well as necroptosis were analyzed in the colon of colitis mice. Data obtained were analysed by Tukey-Kramer and two-tailed standard t tests. RESULTS: The results indicated that the polysaccharide sample suppressed colitis in mice using effects on the body weight and colon length as markers. Also, it was demonstrated that necrostatin-1, a specific inhibitor of necroptosis, suppressed the expression of interleukin (IL)-8, a pro-inflammatory chemokine, in Caco-2 cells induced necroptosis induced by zVAD and TNF-α, an indication that necroptosis may be involved in the expression of pro-inflammatory cytokines. Moreover, the polysaccharide sample suppressed the expression of pro-inflammatory cytokines such as tumor necrosis factor (TNF)-α, IL-6, IL-1ß, and interferon (IFN)-γ in the colon of mice. CONCLUSION: These results suggested that the suppressive effects of the polysaccharide sample on inflammatory cytokines expression may contribute to its anti-colitis effect, and so may serve as a potent therapeutic agent against inflammatory bowel disease.

Polissacarídeos de Lentinula edodes suprimem a expressão de citocinas pró-inflamatórias e de colite em camundongos / Lentinula edodes polysaccharides suppressed pro-inflammatory cytokines expression and colitis in mice

ABSTRACT Background: Polysaccharides from edible mushrooms possess immunomodulatory, anti-inflammatory, and anti-tumor activities. Recent studies indicated that necroptosis plays a role in the pathogenesis of inflammatory diseases and mediates increased expression of inflammatory cytokines. Objective: Therefore, it is imperative to determine the impact of polysaccharide extract from Lentinula edodes (L. edodes) on inflammatory cytokines in experimental model of colitis in mice. Methods: Female C57BL/6 mice divided into three or four mice per group were used for this study. Polysaccharide sample was orally administered to mice prior to (7 days) and during colitis induction with 2.5% dextran sodium sulfate (7 days), followed by additional 3 days of administration. Changes in body weight and colon length were used as markers for colitis, and pro-inflammatory cytokines and tumor necrosis factor receptor 1 (TNFR1) expressions, as well as necroptosis were analyzed in the colon of colitis mice. Data obtained were analysed by Tukey-Kramer and two-tailed standard t tests. Results: The results indicated that the polysaccharide sample suppressed colitis in mice using effects on the body weight and colon length as markers. Also, it was demonstrated that necrostatin-1, a specific inhibitor of necroptosis, suppressed the expression of interleukin (IL)-8, a pro-inflammatory chemokine, in Caco-2 cells induced necroptosis induced by zVAD and TNF-α, an indication that necroptosis may be involved in the expression of pro-inflammatory cytokines. Moreover, the polysaccharide sample suppressed the expression of pro-inflammatory cytokines such as tumor necrosis factor (TNF)-α, IL-6, IL-1β, and interferon (IFN)-γ in the colon of mice. Conclusion: These results suggested that the suppressive effects of the polysaccharide sample on inflammatory cytokines expression may contribute to its anti-colitis effect, and so may serve as a potent therapeutic agent against inflammatory bowel disease.

RESUMO Contexto: Polissacarídeos de cogumelos comestíveis possuem atividades imunomodulatórias, anti-inflamatórias e anti-tumorais. Estudos recentes indicaram que a necroptose desempenha um papel na patogênese de doenças inflamatórias e regula o aumento da expressão de citocinas inflamatórias. Objetivo: Torna-se imprescindível determinar o impacto do extrato de polissacarídeo de Lentinula edodes (L. edodes) em citocinas inflamatórias em modelo experimental de colite em camundongos. Métodos: Foram utilizados para este estudo os camundongos C57BL/6 femininos divididos em três ou quatro camundongos por grupo. A amostra de polissacarídeo foi administrada oralmente em camundongos antes (7 dias) e durante a indução de colite com sulfato de dextran sulfato de sódio (7 dias), seguido por 3 dias adicionais de administração. Alterações no peso corporal e comprimento do cólon foram utilizadas como marcadores para colite, e citocinas pró-inflamatórias e tumores receptor fator 1 (TNFR1), bem como necroptose foram analisadas no cólon de camundongos colite. Os dados obtidos foram analisados por testes Tukey-Kramer e testes padrão t de duas caudas. Resultados: Os resultados indicaram que a amostra de polissacarídeo suprimiu colite em camundongos usando efeitos sobre o peso corporal e o comprimento do cólon como marcadores. Além disso, foi demonstrado que a necrostatina-1, inibidora específica da necroptose, suprimiu a expres são de interleucina (IL)-8, uma quimiocina pró-inflamatória, em células caco-2 induzidas necroptose induzidas por zVAD e TNF-α, uma indicação de que a necroptose pode estar envolvida na expressão de citocinas pro-inflamatórias. Além disso, a amostra de polissacarídeo suprimiu a expressão de citocinas pró-inflamatórias, como o fator de necrose tumoral (TNF)-α, IL-6, IL-1β e interferon (IFN)-γ no cólon dos camundongos. Conclusão: Esses resultados sugeriram que os efeitos supressivos da amostra de polissacarídeo na expressão de citocinas inflamatórias podem contribuir para o seu efeito anti-colite, podendo, portanto, servir como um potente agente terapêutico contra doença inflamatória intestinal.

Anti-allergic property of 4,8-sphingadienine stereoisomers in vivo and in vitro model.

4,8-Sphingadienines (SD), metabolites of glucosylceramides (GlcCer), are sometimes determined as key mediators of the biological activity of dietary GlcCer, and cis/trans geometries of 4,8-SD have been reported to affect its activity. Since regulating excessive activation of mast cells seems an important way to ameliorate allergic diseases, this study was focused on cis/trans stereoisomeric-dependent inhibitory effects of 4,8-SD on mast cell activation. Degranulation of RBL-2H3 was inhibited by treatment of 4-cis-8-trans- and 4-cis-8-cis-SD, and their intradermal administrations ameliorated ear edema in passive cutaneous anaphylaxis reaction, but 4-trans-8-trans- and 4-trans-8-cis-SD did not. Although the activation of mast cells depends on the bound IgE contents, those stereoisomers did not affect IgE contents on RBL-2H3 cells after the sensitization of anti-TNP IgE. These results indicated that 4-cis-8-trans- and 4-cis-8-cis-SD directly inhibit the activation of mast cells. In conclusion, it was assumed that 4,8-SD stereoisomers with cis double bond at C4-position shows anti-allergic activity by inhibiting downstream pathway after activation by the binding of IgE to mast cells.

Demographic, clinical characteristics and treatment outcomes of immune-complex membranoproliferative glomerulonephritis and C3 glomerulonephritis in Japan: A retrospective analysis of data from the Japan Renal Biopsy Registry.

The reclassification of membranoproliferative glomerulonephritis (MPGN) into immune-complex MPGN (IC-MPGN) and C3 glomerulopathy (C3G) based on immunofluorescence findings in kidney biopsies has provided insights into these two distinct diseases. C3G is further classified into dense deposit disease and C3 glomerulonephritis (C3GN) based on electron micrographic findings. Although these diseases have poor outcomes, limited Japanese literature confined to small, single-center cohorts exist on these diseases. We retrospectively analyzed 81 patients with MPGN type I and III from 15 hospitals in the Japan Renal Biopsy Registry to compare demographic, clinical characteristics and treatment outcomes of patients with IC-MPGN to those with C3GN. Of the 81 patients reviewed by immunofluorescence findings in kidney biopsies, 67 patients had IC-MPGN and 14 patients had C3GN. Age at diagnosis and systolic and diastolic pressure were higher and proteinuria and impaired renal function were significantly more prevalent in patients with IC-MPGN than those with C3GN. About 80% of the patients in both groups were treated with immunosuppressive therapy. At last follow-up (median 4.8 years), complete remission rate of proteinuria was significantly higher in patients with C3GN (64.3%) than in those with IC-MPGN (29.9%; P = 0.015). The renal survival rate was lower in patients with IC-MPGN when compared to C3GN (73.1% vs. 100%; log-rank, P = 0.031). Systolic blood pressure and renal function at baseline were independent predictors of progression to end-stage kidney disease. The overall prognosis of patients with C3GN is more favorable than for patients with IC-MPGN.

Lactiplantibacillus plantarum 22A-3-induced TGF-ß1 secretion from intestinal epithelial cells stimulated CD103+ DC and Foxp3+ Treg differentiation and amelioration of colitis in mice.

In the present study, we evaluated the anti-inflammatory properties of Lactiplantibacillus plantarum 22A-3 (LP22A3) and attempted to elucidate the underlying molecular mechanism. The oral administration of LP22A3 significantly inhibited body weight reduction and decreased colon shortening and colitis score in mice with dextran sulfate sodium (DSS)-induced colitis. It was demonstrated that the production of the active-form of TGF-ß tended to increase in both the intestinal epithelial cells (IECs) of the ileum and serum but not in the colon of non-DSS-treated mice by LP22A3. IL-10 level in serum was also elevated by LP22A3-treatment. The mRNA expression of TGF-ß, IL-10 and Foxp3 increased only in the small intestines of LP22A3-treated mice. Both the aldehyde dehydrogenase 1 family member A2 (Aldh1a2) mRNA expression and population of CD103+ dendritic cells (DCs) in the small intestine significantly increased in the LP22A3-treated group. LP22A3 induced TGF-ß secretion from the IECs of the small intestine with retinoic acid production probably through TLR2, resulting in an increase in CD103+ DCs and the Foxp3+ Treg population. Both cells secrete a high level of anti-inflammatory cytokines, TGF-ß and IL-10 contributing to the protective condition in the intestine and thus making it less susceptible to inflammation. This suggested that oral administration of LP22A-3 may be an alternative therapeutic strategy for IBD.

Low-GDP, pH-neutral solutions preserve peritoneal endothelial glycocalyx during long-term peritoneal dialysis.

BACKGROUND: During peritoneal dialysis (PD), solute transport and ultrafiltration are mainly achieved by the peritoneal blood vasculature. Glycocalyx lies on the surface of endothelial cells and plays a role in vascular permeability. Low-glucose degradation product (GDP), pH-neutral PD solutions reportedly offer higher biocompatibility and lead to less peritoneal injury. However, the effects on the vasculature have not been clarified. METHODS: Peritoneal tissues from 11 patients treated with conventional acidic solutions (acidic group) and 11 patients treated with low-GDP, pH-neutral solutions (neutral group) were examined. Control tissues were acquired from 5 healthy donors of kidney transplants (control group). CD31 and ratio of luminal diameter to vessel diameter (L/V ratio) were evaluated to identify endothelial cells and vasculopathy, respectively. Immunostaining for heparan sulfate (HS) domains and Ulex europaeus agglutinin-1 (UEA-1) binding was performed to assess sulfated glycosaminoglycans and the fucose-containing sugar chain of glycocalyx. RESULTS: Compared with the acidic group, the neutral group showed higher CD31 positivity. L/V ratio was significantly higher in the neutral group, suggesting less progression of vasculopathy. Both HS expression and UEA-1 binding were higher in the neutral group, whereas HS expression was markedly more preserved than UEA-1 binding in the acidic group. In vessels with low L/V ratio, which were found only in the acidic group, HS expression and UEA-1 binding were diminished, suggesting a loss of glycocalyx. CONCLUSION: Peritoneal endothelial glycocalyx was more preserved in patients treated with low-GDP, pH-neutral solution. The use of low-GDP, pH-neutral solutions could help to protect peritoneal vascular structures and functions.

C1 inhibitor mitigates peritoneal injury in zymosan-induced peritonitis.

Peritonitis, due to a fungal or bacterial infection, leads to injury of the peritoneal lining and thereby forms a hazard for the long-term success of peritoneal dialysis (PD) and remains a lethal complication in patients with PD. This study investigated whether C1 inhibitor (C1-INH) could protect against the progression of peritoneal injuries with five daily administrations of zymosan after mechanical scraping of the rat peritoneum to mimic fungal peritonitis. Severe peritoneal injuries were seen in this model, accompanied by fibrinogen/fibrin exudation and peritoneal deposition of complement activation products such as activated C3 and C5b-9. However, intraperitoneal injection of C1-INH decreased peritoneal depositions of activated C3 and C5b-9, ameliorated peritoneal thickening, reduced the influx of inflammatory cells, and prevented the production of peritoneal fibrous layers with both one and two doses of C1-INH each day. Our results suggest that C1-INH might be useful to protect against peritoneal injuries after causes of peritonitis such as fungal infection. This clinically available agent may thus help extend the duration of PD.NEW & NOTEWORTHY Peritoneal injuries associated with peritonitis comprise an important issue to prevent long-term peritoneal dialysis (PD) therapy. Here, we showed that C1 inhibitor (C1-INH), as an anticomplement agent, protected against peritoneal injuries in a peritonitis animal model related to fungal infection. Therefore, C1-INH might be useful to protect against peritoneal injuries after peritonitis due to fungal infection. This clinically available agent may thus help extend the duration of PD.

Oral Antibiotics are Effective for Preventing Colonoscopy-associated Peritonitis as a Preemptive Therapy in Patients on Peritoneal Dialysis.

Objective In patients on peritoneal dialysis (PD), it was reported that colonoscopy, but not upper gastrointestinal endoscopy, could cause peritonitis as a complication. A guideline of the International Society for Peritoneal Dialysis recommends preemptive intravenous antibiotics administration of ampicillin and aminoglycoside with or without metronidazole, to prevent colonoscopy-associated peritonitis. In this study, we retrospectively evaluated the effects of preemptive antibiotics therapy by oral administration instead of intravenous administration. Methods We investigated the incidence of colonoscopy-associated peritonitis in a single center. In 170 patients undergoing PD between January 2010 and December 2019, 50 colonoscopies were performed, including 49 with oral administration of amoxicillin and ciprofloxacin and/or metronidazole as preemptive therapy 1 hour before the colonoscopy procedure, and 1 without. Results We observed no incidence of colonoscopy-associated peritonitis. Conclusion Generally, oral administration of preemptive antibiotics is less painful and more convenient than intravenous administration, especially in outpatient procedures, such as a colonoscopy. Our results suggest that oral antibiotic administration might be effective for preventing colonoscopy-associated peritonitis in PD patients.