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Biomedical Journal Jun 2024The incidence of autoimmune diseases is increasing in developed countries, possibly due to the modern Western diet and lifestyle. We showed earlier that polysaccharides...
BACKGROUND
The incidence of autoimmune diseases is increasing in developed countries, possibly due to the modern Western diet and lifestyle. We showed earlier that polysaccharides derived from the medicinal fungus Hirsutella sinensis produced anti-inflammatory, anti-diabetic and anti-obesity effects by modulating the gut microbiota and increasing the abundance of the commensal Parabacteroides goldsteinii in mice fed with a high-fat diet.
METHODS
We examined the effects of the prebiotics, H. sinensis polysaccharides, and probiotic, P. goldsteinii, in a mouse model of imiquimod-induced systemic lupus erythematosus.
RESULTS
The fungal polysaccharides and P. goldsteinii reduced markers of lupus severity, including the increase of spleen weight, proteinuria, and serum levels of anti-DNA auto-antibodies and signal transducer and activator of transcription 4 (STAT4). Moreover, the polysaccharides and P. goldsteinii improved markers of kidney and liver functions such as creatinine, blood urea nitrogen, glomerulus damage and fibrosis, and serum liver enzymes. However, the prebiotics and probiotics did not influence gut microbiota composition, colonic histology, or expression of tight junction proteins in colon tissues.
CONCLUSIONS
Our results indicate that H. sinensis polysaccharides and the probiotic P. goldsteinii can reduce lupus markers in imiquimod-treated mice. These prebiotics and probiotics may therefore be added to other interventions conducive of a healthy lifestyle in order to counter autoimmune diseases.
PubMed: 38901796
DOI: 10.1016/j.bj.2024.100754 -
Kidney & Blood Pressure Research Jun 2024The early diagnosis of kidney injury in type 2 diabetes (T2DM) is important to prevent the long-term damaging effects of kidney loss and is decisive for patient...
INTRODUCTION
The early diagnosis of kidney injury in type 2 diabetes (T2DM) is important to prevent the long-term damaging effects of kidney loss and is decisive for patient outcomes. While SIRT2 is implicated in diabetes pathogenesis, its correlation with diabetic nephropathy remains unexplored. This study was designed to evaluate the association of circulating and urine SIRT2 levels with diabetic kidney injury, as well as potential underlying mechanisms.
METHODS
In T2DM patients, db/db mice, and high-glucose plus palmitic acid treated HK-2 cell models, ELISA, immunoturbidimetry, immunohistochemistry, western blot and RT-qPCR were used to detect SIRT2 levels and kidneys damage. According to urinary albumin/creatinine ratio (UACR), 163 T2DM patients were divided into three groups. Spearman correlation analysis was used to investigate the relationship between urinary sirtuin2/creatinine ratio (USCR) and biomarkers of kidney injury. The influencing factors of proteinuria in T2DM patients were analyzed by Logistic regression model.
RESULTS
In our findings, the Macro group exhibited the highest USCR levels as UACR increased. There was a positive association between USCR and UACR, α1-microglobulin/creatinine ratio (UαCR), β2-microglobulin/creatinine ratio (UβCR), and retinol-binding protein/creatinine ratio (URCR), with a negative correlation observed with eGFR. Logistic ordered multiclassification regression analysis, adjusting for confounding variables, confirmed that USCR remained a significant risk factor for the severity of proteinuria in T2DM patients. In the kidney tissue of db/db mice, increased KIM-1 levels were associated with increased SIRT2 levels. Increased SIRT2 protein levels were also observed in renal tubular epithelial cells treated with high-glucose plus palmitic acid. Moreover, SIRT2 promotes the expression of pro-inflammatory factors TNF-α and IL-6 by modulating the phosphorylation of p38 MAPK and pJNK in renal tubular cells induced by high glucose and palmitic acid.
CONCLUSION
Urinary SIRT2 is closely related to eGFR, renal tubule injury and urinary albumin excretion in T2DM patients, which is expected to be an important indicator to comprehensively reflect renal injury.
PubMed: 38901411
DOI: 10.1159/000539886 -
Biomedicine & Pharmacotherapy =... Jun 2024Astragaloside IV (AS-IV) exhibits diverse biological activities. Despite this, the detailed molecular mechanisms by which AS-IV ameliorates diabetic nephropathy (DN) and...
Phenylsulfate-induced oxidative stress and mitochondrial dysfunction in podocytes are ameliorated by Astragaloside IV activation of the SIRT1/PGC1α /Nrf1 signaling pathway.
Astragaloside IV (AS-IV) exhibits diverse biological activities. Despite this, the detailed molecular mechanisms by which AS-IV ameliorates diabetic nephropathy (DN) and shields podocytes from oxidative stress (OS) and mitochondrial dysfunction remain poorly understood. In this study, we used biochemical assays, histopathological analysis, Doppler ultrasound, transmission electron microscopy,flow cytometry, fluorescence staining, and Western blotting and other methods. AS-IV was administered to db/db mice for in vivo experimentation. Our findings indicated that AS-IV treatment significantly reduced diabetes-associated markers, proteinuria, and kidney damage. It also diminished ROS levels in the kidney, enhanced the expression of endogenous antioxidant enzymes, and improved mitochondrial health. Phenyl sulfate (PS), a protein-bound uremic solute of enteric origin, has been closely linked with DN and represents a promising avenue for further research. In vitro, PS exposure induced OS and mitochondrial dysfunction in podocytes, increasing ROS levels while decreasing antioxidant enzyme activity (Catalase, Heme Oxygenase-1, Superoxide Dismutase, and Glutathione Peroxidase). ROS inhibitors (N-acetyl-L-cysteine, NAC) as the positive control group can significantly reduce the levels of ROS and restore antioxidant enzymes protein levels. Additionally, PS reduced markers associated with mitochondrial biosynthesis and function (SIRT1, PGC1α, Nrf1, and TFAM). These adverse effects were partially reversed by AS-IV treatment. However, co-treatment with AS-IV and the SIRT1 inhibitor EX527 failed to restore these indicators. Overall, our study demonstrates that AS-IV effectively attenuates DN and mitigates PS-induced OS and mitochondrial dysfunction in podocytes via the SIRT1/PGC1α/Nrf1 pathway.
PubMed: 38901196
DOI: 10.1016/j.biopha.2024.117008 -
Journal of Reproductive Immunology Jun 2024Maternal immunologic mechanisms for tolerance are essential for a successful pregnancy because they prevent maladaptive immune responses to the placenta and... (Review)
Review
Maternal immunologic mechanisms for tolerance are essential for a successful pregnancy because they prevent maladaptive immune responses to the placenta and semi-allogeneic fetus and promote fetal growth. Preeclampsia is a major global cause of fetal mortality and morbidity. It is characterized by new-onset hypertension and proteinuria that occurs at twenty weeks of pregnancy or later. Preeclampsia is defined by a rise in cytokines that are pro-inflammatory and antiangiogenic components in the fetoplacental unit and the vascular endothelium of pregnant women, as well as an excessive and increasing stimulation of the immune system. Crucially, inflammation can result in low birth weight and inadequate placental perfusion in neonates. Preeclampsia, which is ultimately connected to inflammatory responses, can be impacted by several immunological mechanisms. Our goal in this work was to compile the most recent research on the pathoimmunology of preeclampsia, including studies on angiogenic variables and, in particular, immunological components.
PubMed: 38901108
DOI: 10.1016/j.jri.2024.104282 -
World Journal of Urology Jun 2024Preoperative proteinuria is a prognostic factor of chronic kidney disease (CKD). We assessed the association between preoperative proteinuria and postoperative renal...
PURPOSE
Preoperative proteinuria is a prognostic factor of chronic kidney disease (CKD). We assessed the association between preoperative proteinuria and postoperative renal function after partial nephrectomy (PN).
METHODS
We retrospectively reviewed our records of patients with a single malignant renal mass who underwent PN between 2000 and 2021. Patients with data on preoperative proteinuria were included. Baseline characteristics and eGFR differences over time between patients with and without proteinuria were evaluated. Univariate and multivariable logistic regression models (LRM) tested for presence of CKDIII or higher at 12-month and at last follow-up.
RESULTS
Two hundred ninety-five patients were included. Twenty-two of them had preoperative proteinuria. No differences of age, smoking status, hypertension or diabetes, tumor size and use of ischemia were observed. Patients with proteinuria had a higher rate of CKD-III at baseline. At a median follow-up of 46.5 months (IQR 19-82), 117 patients developed de novo CKD-III, without differences in the two groups. No differences in decline in eGFR were observed. At univariate LRM, predictors of CKD-III at 12 months after PN were preoperative proteinuria (OR 3.2, 95%CI 1.4-7.8, p = 0.005), age and baseline eGFR, while predictors of CKD-III at last follow-up were age and baseline eGFR. At multivariable LRM, only baseline eGFR predicted CKD-III at 12-month and at last-follow-up.
CONCLUSIONS
Preoperative eGFR is the only independent predictor of long-term renal function after PN. Preoperative proteinuria correlates with renal function at 12 months. Proteinuria should be assessed before PN to identify patients at higher risk of renal functional deterioration in the 12 months following PN.
Topics: Humans; Nephrectomy; Kidney Neoplasms; Male; Proteinuria; Female; Middle Aged; Retrospective Studies; Carcinoma, Renal Cell; Preoperative Period; Aged; Glomerular Filtration Rate; Renal Insufficiency, Chronic; Correlation of Data; Kidney
PubMed: 38900287
DOI: 10.1007/s00345-024-05042-w -
Indian Journal of Dermatology,... Jun 2024Background Several studies have reported that psoriasis has a positive correlation with type 2 diabetes mellitus (DM). Understanding the risk of psoriasis in diabetic...
Background Several studies have reported that psoriasis has a positive correlation with type 2 diabetes mellitus (DM). Understanding the risk of psoriasis in diabetic patients is significant because it allows for early intervention and potential insights into the common pathways between the two conditions. Objectives We analysed the risk of psoriasis according to the estimated glomerular filtration rate (eGFR) and proteinuria level in DM patients using Korean population-based data. Methods This study was a retrospective cohort study using data collected from the country in the form of exploratory data analysis. A total of 927,234 participants diagnosed with DM were enrolled. Patients under the age of 20 with existing psoriasis or psoriasis developed within 1 year and missing data were excluded. The development of psoriasis was the primary outcome within a follow-up period of 7.83 ± 1.68 years. Results Of the 840,395 final participants, 28,010 (3.33%) patients developed psoriasis. In multivariate-adjusted Cox proportional hazards regression models, the DM patients with eGFR < 30 had a higher risk of psoriasis after adjustment (eGFR 60-90, hazard ratio [HR] 1 (Ref.); eGFR < 30, HR 1.173, 95% CI 1.089-1.264). In addition, there was an increased psoriatic risk of patients with DM and proteinuria after adjustment (negative, HR 1 (Ref.); 2+, HR 1.164, 95% CI 1.080-1.254; 3+, HR 1.433, 95% CI 1.273-1.613; 4+, HR 1.508, 95% CI 1.177-1.931). Limitations The severity of psoriasis was not measured since the occurrence of psoriasis was the outcome. Details of oral hypoglycaemic agents such as type and dose were not investigated. Conclusion This study showed that a decrease in eGFR and aggravation of proteinuria increase the risk of psoriasis in diabetic patients. Therefore, by using eGFR and proteinuria as predictive risk factors of psoriasis in DM patients, early and proactive treatment may play a vital role in managing diabetic patients.
PubMed: 38899413
DOI: 10.25259/IJDVL_669_2023 -
Journal of Medical Virology Jun 2024Pathogenic Eurasian hantaviruses cause hemorrhagic fever with renal syndrome (HFRS), which is characterized by acute kidney injury. The clinical course shows a broad...
Pathogenic Eurasian hantaviruses cause hemorrhagic fever with renal syndrome (HFRS), which is characterized by acute kidney injury. The clinical course shows a broad range of severity and is influenced by direct and immune-mediated effects. The neutrophil-to-lymphocyte ratio (NLR) is a marker of systemic inflammation and predicts severity and outcome in various diseases. Therefore, we examined the role of NLR in HFRS caused by hantavirus Puumala (PUUV) and its association with disease severity and kidney injury. We detected elevated NLR levels on admission (NLR: median 3.82, range 1.75-7.59), which increased during acute HFRS. Maximum NLR levels (NLR: median 4.19, range 1.75-13.16) were 2.38-fold higher compared to the reference NLR level of 1.76 in the general population. NLR levels on admission correlate with markers of severity (length of hospital stay, serum creatinine) but not with other markers of severity (leukocytes, platelets, C-reactive protein, lactate dehydrogenase, serum albumin, proteinuria). Interestingly, levels of nephrin, which is a specific marker of podocyte damage in kidney injury, are highest on admission and correlate with NLR, but not with NLR. Together, we observed a correlation between systemic inflammation and the severity of HFRS, but our results also revealed that podocyte damage precedes these inflammatory processes.
Topics: Humans; Neutrophils; Hemorrhagic Fever with Renal Syndrome; Male; Adult; Biomarkers; Lymphocytes; Middle Aged; Female; Severity of Illness Index; Puumala virus; Aged; Young Adult; Acute Kidney Injury
PubMed: 38899399
DOI: 10.1002/jmv.29759 -
Kidney International Reports Jun 2024
PubMed: 38899179
DOI: 10.1016/j.ekir.2024.03.005 -
World Journal of Clinical Cases Jun 2024Glomerulopathy with fibrillary deposits is not uncommon in routine nephropathology practice, with amyloidosis and fibrillary glomerulonephritis being the two most...
BACKGROUND
Glomerulopathy with fibrillary deposits is not uncommon in routine nephropathology practice, with amyloidosis and fibrillary glomerulonephritis being the two most frequently encountered entities. Renal amyloid heavy and light chain (AHL) is relatively uncommon and its biopsy diagnosis is usually limited to cases that show strong equivalent staining for a single immunoglobulin (Ig) heavy chain and a single light chain, further supported by mass spectrometry (MS) and serum studies for monoclonal protein. But polyclonal light chain staining can pose a challenge.
CASE SUMMARY
Herein we present a challenging case of renal AHL with polyclonal and polytypic Ig gamma (IgG) staining pattern by immunofluorescence. The patient is a 62-year-old Caucasian male who presented to an outside institution with a serum creatinine of up to 8.1 mg/dL and nephrotic range proteinuria. Despite the finding of a polyclonal and polytypic staining pattern on immunofluorescence, ultrastructural study of the renal biopsy demonstrated the presence of fibrils with a mean diameter of 10 nm. Congo red was positive while DNAJB9 was negative. MS suggested a diagnosis of amyloid AHL type with IgG and lambda, but kappa light chains were also present supporting the immunofluorescence staining results. Serum immunofixation studies demonstrated IgG lambda monoclonal spike. The patient was started on chemotherapy. The chronic renal injury however was quite advanced and he ended up needing dialysis shortly after.
CONCLUSION
Tissue diagnosis of AHL amyloid can be tricky. Thorough confirmation using other available diagnostic techniques is recommended in such cases.
PubMed: 38898862
DOI: 10.12998/wjcc.v12.i17.3200 -
World Journal of Clinical Cases Jun 2024Many guidelines have recommended renin-angiotensin system inhibitors (RASI) as the first-line treatment for patients with chronic kidney disease (CKD). We studied RASI...
BACKGROUND
Many guidelines have recommended renin-angiotensin system inhibitors (RASI) as the first-line treatment for patients with chronic kidney disease (CKD). We studied RASI prescription trends from 2010 to 2019, and analyzed the characteristics associated with RASI prescription in Chinese hospitalized CKD patients.
AIM
To study the prescription of renin angiotensin system inhibitors in hospitalized patients with CKD in China.
METHODS
It was retrospectively, cross-sectional reviewed RASI prescriptions in hospitalized CKD patients in China from 2010 to 2019. RASI prescribing trends were analyzed from 2010 to 2019, and bivariate and multivariate logistic regression analyses were conducted to identify characteristics associated with RASI prescription.
RESULTS
A total of 35090 CKD patients were included, with 10043 (28.6%) RASI prescriptions. Among these patients, 18919 (53.9%) met the criteria for RASI treatments based on the 2012 kidney disease: Improving global outcomes guidelines. Of these, 7246 (38.3%) patients received RASI prescriptions. RASI prescriptions showed an initial rapid increase from 2011 to 2012, reached its peak around 2015 and 2016, and then exhibited a subsequent slight decreasing trend. Both bivariate and multivariate analyses showed that several characteristics, including the male gender, age less than 60-year-old, nephrology department admission, lower CKD stage, history of hypertension or diabetes, proteinuria, glomerulonephritis as the CKD etiology, and non-acute kidney injury were associated with RASI prescriptions.
CONCLUSION
The frequency of RASI prescriptions showed an initial increase but a slight decreasing trend in more recent years. CKD patients with certain characteristics such as elderly age, advanced disease stage, surgery department admission, or acute kidney injury were less likely to receive RASI prescriptions. In the application of RASI in hospitalized CKD patients is insufficient. The actual clinical practice needs to be improved. The development of related research is helpful to guide the correct choice of clinical treatment strategy.
PubMed: 38898860
DOI: 10.12998/wjcc.v12.i17.3061