Causal association of plasma circulating metabolites with nephritis: a Mendelian randomization study

Frontiers in Nutrition, Journal Year: 2024, Volume and Issue: 11

Published: May 3, 2024

Nephritis is a pivotal catalyst in chronic kidney disease (CKD) progression. Although epidemiological studies have explored the impact of plasma circulating metabolites and drugs on nephritis, few harnessed genetic methodologies to establish causal relationships. Through Mendelian randomization (MR) two substantial cohorts, spanning large sample sizes, we evaluated over 100 263 discern their effects nephritis risk. The primary analytical tool was inverse variance weighted (IVW) analysis. Our bioinformatic scrutiny GSE115857 (IgA nephropathy, 86 samples) GSE72326 (lupus 238 unveiled anomalies lipid metabolism immunological characteristics nephritis. Thorough sensitivity analyses (MR-Egger, MR-PRESSO, leave-one-out analysis) were undertaken verify instrumental variables' (IVs) assumptions. Unique lipoprotein-related molecules established links with diverse subtypes. Notably, docosahexaenoic acid (DHA) emerged as protective factor for acute tubulointerstitial (ATIN) (OR1 = 0.84, [95% CI 0.78-0.90], p1 0.013; OR2 0.89, 0.82-0.97], p2 0.007). Conversely, multivitamin supplementation minus minerals notably increased risk ATIN (OR 31.25, 9.23-105.85], p 0.004). Reduced α-linolenic (ALA) levels due lipid-lowering linked both 4.88, 3.52-6.77], < 0.001) (TIN) 7.52, 2.78-20.30], 0.042). While non-renal drug indivina showed promise TIN treatment, use digoxin, hydroxocobalamin, liothyronine elevated (CTIN). Transcriptome analysis affirmed that anomalous immune infiltration are characteristic IgA nephropathy lupus robustness these reinforced by tests, indicating no signs pleiotropy. Dyslipidemia significantly contributes development. Strategies aimed at reducing low-density lipoprotein or ALA may enhance efficacy existing regimens treatment. Renal functional status should also be judiciously considered regard nonrenal medications.

Language: Английский

---

Lupus Nephritis from Pathogenesis to New Therapies: An Update

International Journal of Molecular Sciences, Journal Year: 2024, Volume and Issue: 25(16), P. 8981 - 8981

Published: Aug. 18, 2024

Lupus Nephritis (LN) still represents one of the most severe complications Systemic Erythematosus (SLE) and a major risk factor for morbidity mortality. However, over last few years, several studies have paved way deeper understanding its pathogenetic mechanisms more targeted treatments. This review aims to provide comprehensive update on progress key aspects in this setting: LN, including new insight into role autoantibodies, complement, vitamin D deficiency, interaction between infiltrating immune cells kidney resident ones; evolving renal biopsy biomarkers, which may integrate information from histology; newly approved drugs such as voclosporin (VOC) belimumab (BEL), allowing articulate strategy induction therapy, other promising phase III-immunosuppressive (IS) agents pipeline. Several adjunctive treatments aimed at reducing cardiovascular progression chronic damage, antiproteinuric agents, represent an important complement IS therapy. Furthermore, non-pharmacological measures concerning general lifestyle diet should also be adopted when managing LN. Integrating these therapeutic areas requires effort towards holistic multidisciplinary approach. At same time, availability increasingly wider armamentarium translate improvements patient’s outcomes next decades.

Language: Английский

---

Endoplasmic reticulum stress in the salivary glands of patients with primary Sjögren’s syndrome, associated Sjögren’s syndrome, and non-Sjögren’s sicca syndrome: a comparative analysis and the influence of chloroquine

Advances in Rheumatology, Journal Year: 2025, Volume and Issue: 65(1)

Published: Jan. 8, 2025

Abstract Background Endoplasmic reticulum stress (ERS) and the unfolded protein response (UPR) are adaptive mechanisms for conditions of high demand, marked by an accumulation misfolded proteins in endoplasmic (ER). Rheumatic autoimmune diseases (RAD) known to be associated with chronic inflammation ERS state. However, activation UPR signaling pathways is not completely understood Sjögren’s disease (SD). This study evaluated expression ERS-related genes glandular tissue patients primary SD (pSD), (aSD) other diseases, non-Sjögren sicca syndrome (NSS). Methods In a cross-sectional study, minor salivary gland biopsies were obtained from 44 suspected 13 healthy controls (HC). Patients classified as pSD, aSD, or NSS based on clinical, serological, histological assessment. Histopathological analysis mRNA (PERK, XBP1, ATF-6, ATF-4, CANX, CALR, CHOP, BIP) performed samples. Differences between groups (pSD, NSS, HC) assessed. The influence chloroquine (CQ) ER was also investigated. Results Twenty-eight showed increased PERK ( p = 0.0117) XBP1 0.0346), reduced ATF-6 0.0003) CHOP 0.0003), compared HC group. Increased BIP < 0.0001), CALR CANX 0.0111) observed group n 16). receiving CQ 16) significant increase 0.0317) taking medication 29). Conclusions Altogether, results suggest greater SD, especially pSD Antimalarial drugs, like CQ, used treat RAD, may affect function exocrine glands.

Language: Английский

---

Endoplasmic reticulum stress and unfolded protein response in renal lipid metabolism

Experimental Cell Research, Journal Year: 2025, Volume and Issue: unknown, P. 114463 - 114463

Published: Feb. 1, 2025

Language: Английский

---

Updating on the Dual Role of Salivary Gland Epithelial Cell (SGEC) in Sjögren’s Disease

Journal of Inflammation Research, Journal Year: 2025, Volume and Issue: Volume 18, P. 3039 - 3053

Published: Feb. 28, 2025

Sjögren's disease, an autoimmune inflammatory currently lacks effective treatment options. The salivary gland, a crucial exocrine organ responsible for saliva production and local immune responses on mucous membranes, is frequently impaired in individuals with disease. Restoring gland function poses significant challenge researchers. Salivary epithelial cells, recognized as pivotal components of the have been increasingly implicated key initiators inflammation exhibit innate cell-like properties. On whole, SGEC plays protective role physiological state, can also participate persistence initiating factor pathological state. In review, we explore interplay between Ca+, endoplasmic reticulum (ER), mitochondrial homeostasis imbalance cells. Additionally, provide overview current literature research advancements related to Pattern Recognition Receptors (PRRs), programmed cell death, posttranslational modification (PTM), oral microecology, etc. specifically focusing their implications Given cells onset based may potential alleviate condition by addressing response glands.

Language: Английский

---

Novel insights into immunopathogenesis and crucial biomarkers between primary open‐angle glaucoma and systemic lupus erythematosus

iMetaOmics., Journal Year: 2024, Volume and Issue: unknown

Published: Sept. 10, 2024

Abstract Glaucoma is the primary factor underlying irreversible blindness. Recent studies suggest that risk of glaucoma significantly increases in patients with systemic lupus erythematosus (SLE); however, mechanism this association remains unclear. Therefore, study aimed to identify novel common biomarkers and potential therapeutic drugs for SLE glaucoma. GSE27276, GSE50772, GSE148371 datasets were sourced from gene expression omnibus (GEO) database. An integrated analysis both diseases identified thoroughly examined their biological roles molecular mechanisms using differential (DEA), weighted co‐expression network (WGCNA), enrichment analysis, machine learning, microRNA (miRNA) transcription analyses, immune infiltration single‐cell transcriptome analysis. Concurrently, docking was used forecast targeting these biomarkers. Finally, reverse quantitative real‐time polymerase chain reaction (RT‐qPCR) performed human trabecular meshwork stem cells validate five The 10 key genes through DEA WGCNA predominantly involved immune, inflammatory, autophagy pathways. Additionally, learning biomarkers, we established associated factors miRNA regulatory networks. Immune indicated an elevated presence cells, including macrophages, T B conditions. Furthermore, DSigDB database yielded agents, three which showed strong binding via docking. RT‐qPCR results confirmed trend expression. This uncovered a new link between open‐angle glaucoma, identifying immunopathogenesis future research treatment strategies.

Language: Английский

---

New Insights into Decabromodiphenyl Ether-Induced Splenic Injury in Chickens: Involvement of ROS-Mediated Endoplasmic Reticulum Stress Pathway Triggering Autophagy and Apoptosis

Journal of Agricultural and Food Chemistry, Journal Year: 2024, Volume and Issue: 72(7), P. 3741 - 3754

Published: Feb. 10, 2024

Decabromodiphenyl ether (BDE-209) is a widely used brominated flame retardant that can easily detach from materials and enter into feed foodstuffs, posing serious risk to human animal health food safety of origin. However, the immunotoxic effects BDE-209 on avian spleen exact mechanism toxicity remain unknown. Therefore, we established an experimental model BDE-209-exposed chickens positive control cyclophosphamide-induced immunosuppression in vivo treated MDCC-MSB-1 cells chicken splenic primary lymphocytes with vitro. The results showed treatment caused morphological structural abnormalities spleens. Mechanistically, indicators related oxidative stress, endoplasmic reticulum stress (ERS), autophagy, apoptosis were significantly altered by exposure both lymphocytes, but use N-acetylcysteine or 4-phenylbutyric acid reversed these changes. In addition, decreased antimicrobial peptide immunoglobulin gene expression. conclusion, present research revealed enhanced lymphocyte autophagy via ROS-mediated ERS pathway. This signaling cascade regulatory relationship not only opens up new avenue for studying immunotoxicity also provides important insights preventing hazards health.

Language: Английский

---

H2S alleviate sepsis-induced acute kidney injury by inhibiting PERK/Bax-Bcl2 pathway

Nitric Oxide, Journal Year: 2024, Volume and Issue: 152, P. 11 - 18

Published: Sept. 11, 2024

Language: Английский

---

L-arginine, aminoguanidine and mesenchymal stem cells reduce the level of endoplasmic reticulum stress markers and D-dimer in the lungs of mice with antiphospholipid syndrome

The Ukrainian Biochemical Journal, Journal Year: 2024, Volume and Issue: 96(5), P. 21 - 30

Published: Oct. 23, 2024

Antiphospholipid syndrome (APS) is an autoimmune disease characterized by damage to the intima of microcirculatory blood vessels as a result formation antibodies phospholipids cell membranes. Recent data indicate possible link between occurrence diseases and endoplasmic reticulum stress, impaired nitric oxide availability, high plasma D-dimer level. The aim study was estimate effect synthesis modulators L-arginine aminoguanidine, mesenchymal stem cells on level inositol-requiring enzyme-1a (IRE-1a), glucose-regulated protein 78 (GRP-78) ER stress markers, in lung tissue female BALB/c line mice with experimental APS induced cardiolipin administration. 30 animals were divided into five groups: 1 – control animals; 2 APS; 3 APS, injected intraperitoneally hydrochloride (25 mg/kg) aminoguanidine (10 mg/kg); 4 (5×106/kg); 5 hydrochloride, combination. After 10 days post removed from experiment, proteins extracted their determined Western blotting. It established that group levels IRE-1, GRP-78 substantially increased compared group. separate administration both arginine MSC, well combined use, decreased indices APS. obtained indicated this probably due reduction through iNOS inhibition anti-inflammatory action MSCs. Keywords: antiphospholipid syndrome, D-dimer, reticulume GRP-78, L-arginine, lung,

Language: Английский

---

Mapping integral cell-type-specific interferon-induced gene regulatory networks (GRNs) involved in systemic lupus erythematosus using systems and computational analysis

Heliyon, Journal Year: 2024, Volume and Issue: 11(1), P. e41342 - e41342

Published: Dec. 19, 2024

Language: Английский

---