Preventive Effects of Resveratrol-enriched Extract of Peanut Sprout on Bacteria- and Estradiol-induced Prostatitis in Mice

The present study investigated the effect of peanut sprout extract (PSE) as a natural resveratrol supplement on chronic bacterial prostatitis (CBP) and estradiol-induced benign prostatic hyperplasia (BPH). PSE contained a high level of resveratrol (148.51 ± 3.05 μg/g), and was tested on the mouse models of CBP (induced by Escherichia coli 292 infection) and BPH (induced by treatment with β-estradiol and dihydrotestosterone). PSE toxicity was assessed on the basis of changes in body weight, alanine aminotransferase activity (an indicator of hepatotoxicity), and expression of the kidney injury marker KIM-1. The effects of PSE on the histopathology of prostate tissue, the proportion of neutrophils, and immune cell profiles in the blood and spleen were examined. PSE administration did not result in any toxicity but reduced the bacterial burden and histopathological changes in the prostate. In addition, lymphocytes (CD4+, CD8+, and CD19+) in the spleen were significantly increased after PSE administration in CBP mice, suggesting immune enhancement. PSE treatment of bone marrow–derived macrophages increased the expression of CD40, which is related to the pro-inflammatory function and host defense against pathogens. It is concluded that PSE would be a good supplement for the mitigation of prostate hyperplasia and prostatitis.

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Stromal hyaluronan accumulation is associated with low immune response and poor prognosis in pancreatic cancer

Scientific Reports ◽

10.1038/s41598-021-91796-x ◽

2021 ◽

Vol 11 (1) ◽

Author(s):

Kyösti Tahkola ◽

Maarit Ahtiainen ◽

Jukka-Pekka Mecklin ◽

Ilmo Kellokumpu ◽

Johanna Laukkarinen ◽

...

Keyword(s):

Immune Response ◽

Immune Cell ◽

Geographical Area ◽

Prognostic Significance ◽

Staining Intensity ◽

Ductal Adenocarcinoma ◽

Poor Survival ◽

Negative Prognostic Factor ◽

High Level ◽

Immune Cell Score

AbstractHyaluronan (HA) accumulation has been associated with poor survival in various cancers, but the mechanisms for this phenomenon are still unclear. The aim of this study was to investigate the prognostic significance of stromal HA accumulation and its association with host immune response in pancreatic ductal adenocarcinoma (PDAC). The study material consisted of 101 radically treated patients for PDAC from a single geographical area. HA staining was evaluated using a HA-specific probe, and the patterns of CD3, CD8, CD73 and PD-L1 expression were evaluated using immunohistochemistry. HA staining intensity of tumour stromal areas was assessed digitally using QuPath. CD3- and CD8-based immune cell score (ICS) was determined. High-level stromal HA expression was significantly associated with poor disease-specific survival (p = 0.037) and overall survival (p = 0.013) In multivariate analysis, high-level stromal HA expression was an independent negative prognostic factor together with histopathological grade, TNM stage, CD73 positivity in tumour cells and low ICS. Moreover, high-level stromal HA expression was associated with low ICS (p = 0.017). In conclusion, stromal HA accumulation is associated with poor survival and low immune response in PDAC.

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Kahweol Ameliorates Cisplatin-Induced Acute Kidney Injury through Pleiotropic Effects in Mice

Biomedicines ◽

10.3390/biomedicines8120572 ◽

2020 ◽

Vol 8 (12) ◽

pp. 572

Author(s):

Jung-Yeon Kim ◽

Jungmin Jo ◽

Jaechan Leem ◽

Kwan-Kyu Park

Keyword(s):

Oxidative Stress ◽

Acute Kidney Injury ◽

Renal Injury ◽

Manganese Superoxide Dismutase ◽

Immune Cell ◽

Nicotinamide Adenine Dinucleotide Phosphate ◽

Kidney Injury ◽

Pleiotropic Effects ◽

Induced Apoptosis ◽

Vascular Adhesion

Cisplatin is an effective chemotherapeutic agent, but its clinical use is frequently limited by its nephrotoxicity. The pathogenesis of cisplatin-induced acute kidney injury (AKI) remains incompletely understood, but oxidative stress, tubular cell death, and inflammation are considered important contributors to cisplatin-induced renal injury. Kahweol is a natural diterpene extracted from coffee beans and has been shown to possess anti-oxidative and anti-inflammatory properties. However, its role in cisplatin-induced nephrotoxicity remains undetermined. Therefore, we investigated whether kahweol exerts a protective effect against cisplatin-induced renal injury. Additionally, its mechanisms were also examined. Administration of kahweol attenuated renal dysfunction and histopathological damage together with inhibition of oxidative stress in cisplatin-injected mice. Increased expression of nicotinamide adenine dinucleotide phosphate oxidase 4 and decreased expression of manganese superoxide dismutase and catalase after cisplatin treatment were significantly reversed by kahweol. Moreover, kahweol inhibited cisplatin-induced apoptosis and necroptosis in the kidneys. Finally, kahweol reduced inflammatory cytokine production and immune cell accumulation together with suppression of nuclear factor kappa-B pathway and downregulation of vascular adhesion molecules. Together, these results suggest that kahweol ameliorates cisplatin-induced renal injury via its pleiotropic effects and might be a potential preventive option against cisplatin-induced nephrotoxicity.

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B-cell lymphoma/leukaemia 10 and angiotensin II-induced kidney injury

Cardiovascular Research ◽

10.1093/cvr/cvz169 ◽

2019 ◽

Cited By ~ 1

Author(s):

Lajos Markó ◽

Joon-Keun Park ◽

Norbert Henke ◽

Song Rong ◽

András Balogh ◽

...

Keyword(s):

B Cell ◽

Renal Damage ◽

Cardiac Fibrosis ◽

Immune Cell ◽

Cell Lymphoma ◽

Kidney Injury ◽

B Cell Lymphoma ◽

Cell Infiltration ◽

Tubular Damage ◽

Ang Ii

Abstract Aims B-cell lymphoma/leukaemia 10 (Bcl10) is a member of the CARMA-Bcl10-MALT1 signalosome, linking angiotensin (Ang) II, and antigen-dependent immune-cell activation to nuclear factor kappa-B signalling. We showed earlier that Bcl10 plays a role in Ang II-induced cardiac fibrosis and remodelling, independent of blood pressure. We now investigated the role of Bcl10 in Ang II-induced renal damage. Methods and results Bcl10 knockout mice (Bcl10 KO) and wild-type (WT) controls were given 1% NaCl in the drinking water and Ang II (1.44 mg/kg/day) for 14 days. Additionally, Bcl10 KO or WT kidneys were transplanted onto WT mice that were challenged by the same protocol for 7 days. Kidneys of Ang II-treated Bcl10 KO mice developed less fibrosis and showed fewer infiltrating cells. Nevertheless, neutrophil gelatinase-associated lipocalin (Ngal) and kidney injury molecule (Kim)1 expression was higher in the kidneys of Ang II-treated Bcl10 KO mice, indicating exacerbated tubular damage. Furthermore, albuminuria was significantly higher in Ang II-treated Bcl10 KO mice accompanied by reduced glomerular nephrin expression and podocyte number. Ang II-treated WT mice transplanted with Bcl10 KO kidney showed more albuminuria and renal Ngal, compared to WT- > WT kidney-transplanted mice, as well as lower podocyte number but similar fibrosis and cell infiltration. Interestingly, mice lacking Bcl10 in the kidney exhibited less Ang II-induced cardiac hypertrophy than controls. Conclusion Bcl10 has multi-faceted actions in Ang II-induced renal damage. On the one hand, global Bcl10 deficiency ameliorates renal fibrosis and cell infiltration; on the other hand, lack of renal Bcl10 aggravates albuminuria and podocyte damage. These data suggest that Bcl10 maintains podocyte integrity and renal function.

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4-Hydroxychalcone Attenuates Hyperaldosteronism, Inflammation, and Renal Injury in Cryptochrome-Null Mice

BioMed Research International ◽

10.1155/2014/603415 ◽

2014 ◽

Vol 2014 ◽

pp. 1-5 ◽

Cited By ~ 1

Author(s):

Qi Qu ◽

Bingguang Dai ◽

Bo Yang ◽

Xuelian Li ◽

Yimin Liu ◽

...

Keyword(s):

Resistant Hypertension ◽

Renal Injury ◽

Systolic Pressure ◽

Kidney Injury ◽

High Plasma ◽

Salt Treatment ◽

Injury Treatment ◽

The Impact ◽

Preventive Effects ◽

Light Chain Enhancer

In the present study, we aimed to investigate the preventive effects of 4-hydroxychalcone (4HCH) on resistant hypertension. We used cryptochrome-null mice, which characteristically show high plasma aldosterone levels, inflammation, and renal injury. The cryptochrome-null mice received high-salt treatment and were treated orally with 4HCH 10 mg/kg, 4HCH 20 mg/kg, and 4HCH 40 mg/kg, respectively. The salt administration in cryptochrome-null mice is able to induce an increase in systolic pressure which is associated with hyperaldosteronism, inflammation, and kidney injury. Treatment with 40 mg/kg 4HCH reduced systolic hypertension, serum IL-1β, and TNF-αlevels and suppressed the activation of nuclear factor kappa-light-chain-enhancer of activated B cells (NF-κB) and renal injury. The impact of 4HCH on the hyperaldosteronism, inflammation, and kidney injury provides new insights for future development of therapeutic strategies in resistant hypertension.

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Given the importance of mTOR signaling in a number of illnesses, it looks suitable to use miR 99 family members as a therapeutic intervention to deal with these illnesses by using gene therapy tools

10.31219/osf.io/8cwgh ◽

2021 ◽

Author(s):

Moataz Dowaidar

Keyword(s):

Therapeutic Intervention ◽

Regulatory Network ◽

Immune Cell ◽

Family Members ◽

Cell Activity ◽

Mtor Signaling ◽

Critical Pathways ◽

Functional Roles ◽

Cell Life ◽

High Level

This review outlines the activities of mirR99 family members in different cancers. Though the functional roles of these miRs are well described in some malignancies, the functional functions of these family members in other forms of cancer remain uncertain. The development and use of engineered mouse models such as miR99a KO, miR100 KO, or miR99a/100 DKO mice challenged with the type or subtype of the cancer in question would be extremely beneficial in determining the physiological and pathological roles of members of this family in different types of cancer and immune cell subtypes.The miR99 family members, which include miR99a, miR99b, and miR100, are key components of a regulatory network that governs several aspects of the cell life cycle, including differentiation, metabolism, survival and death. They are involved in the deregulation of numerous critical pathways including growth factor receptors like FGFR and IGF1R, Notch, mTOR, TGFB and Wnt signaling pathways to alter cellular function. In addition, the typical miR99 target, mTOR, appears to be at the core of the regulatory network miR99, and is more commonly involved in miR99-mediated dysregulation of cell activity. Given the importance of mTOR signaling in a number of illnesses, it looks suitable to use miR99 family members as a therapeutic intervention to deal with these illnesses. mTOR depletion did not result in upregulating miR99a in OSCC cells. In addition, an aberrant activation of PI3K/AKT/mTOR signaling in AMLs, despite increased expression of miR99 family members in AMLs. All in all, this evidence alludes to the existence of an unknown mechanism that maintains mTOR activity running despite the presence in these cells of a high level of miR99 family members. Modulation of miR99 activity might be a viable method for changing the expression of Treg in autoimmune diseases.

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Neutrophils associate with Bowman’s capsule rupture specifically in PR3-ANCA glomerulonephritis

Journal of Nephrology ◽

10.1007/s40620-021-01208-6 ◽

2021 ◽

Author(s):

Samy Hakroush ◽

Björn Tampe

Keyword(s):

Plasma Cells ◽

Immune Cell ◽

Renal Involvement ◽

Kidney Injury ◽

Antineutrophil Cytoplasmic Antibody ◽

Stage Renal Disease ◽

End Stage ◽

Bowman's Capsule ◽

Tubulointerstitial Inflammation ◽

Capsule Rupture

Abstract Background Renal involvement is a common and severe complication of ANCA (antineutrophil cytoplasmic antibody) associated vasculitis (AAV) potentially resulting in a pauci-immune necrotizing and crescentic antineutrophil cytoplasmic antibody (ANCA) glomerulonephritis (GN) with acute kidney injury (AKI), end-stage renal disease (ESRD) or death. We recently described that Bowman’s capsule rupture links glomerular damage to tubulointerstitial inflammation in ANCA-associated glomerulonephritis. Herein we provide a comprehensive histological subtyping of immune cell infiltrates in association with Bowman’s capsule rupture in ANCA GN. Methods A total of 44 kidney biopsies with ANCA GN were retrospectively included in a single-center observational study. Within a renal biopsy specimen, each glomerulus was scored separately for the presence of extensive and focal Bowman’s capsule rupture in injured glomeruli. Infiltrates of neutrophils, eosinophils, plasma cells, and mononucleated cells (macrophages, lymphocytes) were quantified as a fraction of the area of total cortical inflammation. Results Extensive Bowman’s capsule rupture was associated with tubulointerstitial inflammation containing infiltrates of neutrophils, eosinophils and plasma cells. A similar association was observed for the presence of focal Bowman’s capsule rupture, correlating with tubulointerstitial inflammation containing neutrophils, eosinophils and plasma cells. Multiple logistic regression confirmed that extensive Bowman’s capsule rupture correlated with tubulointerstitial inflammation containing neutrophils, and focal Bowman’s capsule rupture correlated with neutrophil and plasma cell infiltration. Furthermore, this association was specifically observed in PR3-ANCA GN. Conclusion To our knowledge, this is the first report linking Bowman’s capsule rupture directly to tubulointerstitial inflammation by immune cell subtypes. This underscores a pathomechanistic link between tubulointerstitial and glomerular lesions in ANCA GN and needs further investigation. Graphical abstract

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Relationship between High Level of Estimated Glomerular Filtration Rate and Contrast-Induced Acute Kidney Injury in Patients who Underwent an Emergency Percutaneous Coronary Intervention

Chinese Medical Journal ◽

10.4103/0366-6999.239316 ◽

2018 ◽

Vol 131 (17) ◽

pp. 2041-2048 ◽

Cited By ~ 2

Author(s):

Ying Yuan ◽

Hong Qiu ◽

Xiao-Ying Hu ◽

Tong Luo ◽

Xiao-Jin Gao ◽

...

Keyword(s):

Acute Kidney Injury ◽

Percutaneous Coronary Intervention ◽

Glomerular Filtration Rate ◽

Filtration Rate ◽

Estimated Glomerular Filtration Rate ◽

Kidney Injury ◽

Coronary Intervention ◽

Percutaneous Coronary ◽

Emergency Percutaneous Coronary Intervention ◽

High Level

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Antioxidative, Antiapoptotic, and Anti-Inflammatory Effects of Apamin in a Murine Model of Lipopolysaccharide-Induced Acute Kidney Injury

Molecules ◽

10.3390/molecules25235717 ◽

2020 ◽

Vol 25 (23) ◽

pp. 5717 ◽

Cited By ~ 1

Author(s):

Jung-Yeon Kim ◽

Jaechan Leem ◽

Kwan-Kyu Park

Keyword(s):

Oxidative Stress ◽

Acute Kidney Injury ◽

Immune Cell ◽

Inflammatory Responses ◽

Tissue Injury ◽

Therapeutic Option ◽

Nicotinamide Adenine Dinucleotide Phosphate ◽

Kidney Injury ◽

Heme Oxygenase 1 ◽

Anti Inflammatory

Sepsis is the major cause of acute kidney injury (AKI) in severely ill patients, but only limited therapeutic options are available. During sepsis, lipopolysaccharide (LPS), an endotoxin derived from bacteria, activates signaling cascades involved in inflammatory responses and tissue injury. Apamin is a component of bee venom and has been shown to exert antioxidative, antiapoptotic, and anti-inflammatory activities. However, the effect of apamin on LPS-induced AKI has not been elucidated. Here, we show that apamin treatment significantly ameliorated renal dysfunction and histological injury, especially tubular injury, in LPS-injected mice. Apamin also suppressed LPS-induced oxidative stress through modulating the expression of nicotinamide adenine dinucleotide phosphate oxidase 4 and heme oxygenase-1. Moreover, tubular cell apoptosis with caspase-3 activation in LPS-injected mice was significantly attenuated by apamin. Apamin also inhibited cytokine production and immune cell accumulation, suppressed toll-like receptor 4 pathway, and downregulated vascular adhesion molecules. Taken together, these results suggest that apamin ameliorates LPS-induced renal injury through inhibiting oxidative stress, apoptosis of tubular epithelial cells, and inflammation. Apamin might be a potential therapeutic option for septic AKI.

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