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Age-related structural and functional deterioration of the kidneys is common among elderly individuals and contributes to increased mortality and morbidity. Mitochondrial dysfunction and cellular senescence are two hallmarks of aging that drive a progressional renal decline; however, the underlying molecular mechanisms and endogenous regulators behind these processes remain incompletely understood. The metabolism of polyunsaturated fatty acids by CYP450 enzymes produces numerous bioactive lipid mediators that can be further metabolized by soluble epoxide hydrolase (sEH) and microsomal epoxide hydrolase (mEH) into diol metabolites, often with reduced biological effects. The objective of this study was to assess renal mitochondrial alterations and cellular senescence in young and aged wild-type (WT) and sEH-deficient (sEH null) female mice. We found aged sEH null mice exhibited better physiological health, as reflected by lower frailty index scores and reduced circulating levels of GDF-15 levels, creatinine, an

Acid soaking with hydrochloric acid (HCl) is a common method used to prevent or break diapause in silkworm eggs and has been widely applied in production. However, its underlying mechanism remains to be explored. Few studies have reported on the metabolism of mono‐ or disaccharides, and the differential expression patterns of genes and proteins related to the phosphatidyl inositol 3‐kinase (PI3K/)Akt signaling pathway across the stages of silkworm diapause eggs, non‐diapause eggs, instant acid‐soaked eggs, and red bean color acid‐soaked (RBCAS) eggs. In this study, eggs from the silkworm 932 strain at different stages were used to explore the content of several saccharides and analyze the expression profiles of 4 diapause‐related genes in the PI3K/Akt signaling pathway via qPCR. Results revealed that in addition to monosaccharides such as glucose and fructose, the contents of polysaccharides, maltose, trehalose, and sorbitol varied significantly at different stages and states of the eggs. The expression profi

Intestinal ischemia/reperfusion (IIR) is a substantial cause of mortality and morbidity worldwide. Octreotide (OCT) has been proven to be effective against various organ insults. However, the exact mechanism by which it exerts protective effect against IIR is still obscure. Thus, the aim was to unveil the potential role of octreotide in an IIR model and decipher its mechanism of action. The rats were allocated into sham-operated, IIR, and OCT groups. Histopathological changes were performed to assess the intestinal injury. Immunohistochemical analysis was used to estimate the NF-κB, Bcl2, caspase-3, IL-17, LC3B, and beclin-1. The mRNA of TNF-α and IL-17 were examined using real time PCR. The levels of p-Nrf2, PRX2, p-JNK, ASK1, and LC3 were assessed using western blot technique. The levels of total antioxidant capacity and SOD were measured using appropriate kits. Furthermore, the protein expressions of Bax, caspase-3, ASK1, and Nrf2 were assessed using proper ELISA kits. Additionally, the comet assay was det

Osteoarthritis (OA) is a common chronic inflammatory joint disease, in which innate immunity plays a pivotal role in pathogenesis. Anti-interleukin-1(IL-1) therapies have shown inconsistent results in clinical trials, potentially due to a mismatch in the spatial and temporal dynamics of interleukin-1beta (IL-1β) production and therapeutic interventions. To address this issue, we developed a novel IL-1β “sticky-trap” utilizing cell and gene-based technologies from our lab and evaluated its efficacy in reducing osteoarthritis progression using a murine destabilization of the medial meniscus (DMM) OA model and a compact bone-derived mesenchymal stromal cell (MSC)-based gene expression system. The extracellular domain of interleukin-1 receptor 2 (IL1R2) was employed to design the sticky IL1R2 trap (stkIL1R2). A murine compact bone-derived MSC line was engineered for gene delivery. Although stkIL1R2 was undetectable in the engineered MSC supernatants by enzyme-linked immunosorbent assay (ELISA) and Western blot, i

Introduction Nephrotoxicity and hepatotoxicity are substantial side effects triggered in individuals injected with 5-fluorouracil (5-FU), an anticancer drug. This study aimed to investigate the impact of the natural antioxidant and anti-inflammatory phenolic compound; protocatechuic acid (PCA) on 5-FU-provoked renal and hepatic injury in rats. Methods Rats were allocated to 4 groups: control, 5-FU, 5-FU + PCA (50 mg/kg), and 5-FU + PCA (100 mg/kg). Rats were intraperitoneally injected 5-FU (75 mg/kg; once a week for 21 days. Protocatechuic acid (50 and 100 mg/kg/day; orally) was administered for 3 weeks. Results Rats co-treated with PCA had lower serum kidney and liver function markers than those receiving 5-FU alone. Furthermore, co-treatment with PCA successfully modulated kidney and liver contents of TNF-α, NF-κB p65, active caspase-1, IL-1β, p-p38 MAPK, SOD, GSH, Nrf-2, HO-1 and MDA. Moreover, PCA impro

Real-time breath analysis has shown potential as a non-invasive method for detecting oxidative stress and airway inflammation. However, there is a lack of data on the association of full-breath profiles with established urinary biomarkers of oxidative stress and respiratory inflammation, which could help advance the implementation of this method in clinical practice. We analyzed breath profiles of 25 tobacco smoke-exposed and 103 non-exposed children via real-time secondary electrospray ionization high-resolution mass spectrometry (SESI-HRMS) and determined in parallel the urinary concentrations of biomarkers of oxidative stress and respiratory inflammation. We evaluated the correlation between breath features and urinary biomarkers and tested the prediction of these biomarkers by exhaled breath. We found 71 breath features that correlated significantly with the urinary oxidative stress marker 8-iso-prostaglandin F2α (8-iso-PGF2α). The agreement (mean ± standard deviation) (Lin’s concordance correlation) betw

Background/Objectives: Methotrexate is a folate antagonist that has proven efficacy as an anticancer and immunomodulatory agent. However, the possible incidence of overt hepatotoxicity represents a challenge for its clinical use. Up till now, no single remedy has been considered an effective solution to this important adverse effect. Perindopril is an angiotensin-converting enzyme inhibitor that is widely used for the treatment of hypertension. Due to the involvement of the renin–angiotensin system in the pathogenesis of methotrexate-elicited hepatotoxicity, investigating the efficacy of perindopril in this condition may be of particular interest. The current work aimed at an evaluation of the potential effects of perindopril in a rat model of methotrexate-induced hepatotoxicity and tried to precisely determine the molecular mechanisms that may represent the basis of these effects. Methods: In a model of methotrexate-elicited hepatotoxicity in male Wistar rats, the effects of different doses of perindopril we

Herbicides such as paraquat (PQ) are frequently utilized particularly in developing nations. The present research concentrated on the pulmonary lesions triggered by PQ and the beneficial effect of the angiotensin receptor neprilysin inhibitor (ARNI), sacubitril/valsartan, against such pulmonary damage. Five groups of rats were established: control, ARNI, PQ (10 mg/kg), ARNI 68 + PQ, and ARNI 34 + PQ. Following euthanasia, lungs were isolated and subjected to a histopathological test, and the ELISA technique was used to evaluate oxidative stress biomarkers, toll-like receptor 4 (TLR4), nuclear factor erythroid 2–related factor 2 (Nrf2), phosphatidylinositol-3-kinase (PI3K), phosphorylated protein kinase B (p-AKT), and inflammatory markers: nuclear factor kappa B p65 subunit (NF-κB p65), tumor necrosis factor α (TNFα), and interleukin 1beta (IL-1β). In conjunction with abnormally high levels of malondialdehyde (MDA) and inducible nitric oxide synthase (iNOS), the PQ group also displayed low levels of reduced gl

Background The benefit of universal CAR-T cells over autologous CAR-T cell therapy is that they are a treatment that is ready to use. However, the prevention of graft-versus-host disease (GVHD) and host-versus-graft reaction (HVGR) remains challenging. Deleting class I of human leukocyte antigen (HLA-I) and class II of human leukocyte antigen (HLA-II) can prevent rejection by allogeneic T cells; however, natural killer (NK) cell rejection due to the loss of self-recognition remains unresolved. This study tested whether the overexpression of Lectin-like transcript 1 (LLT1), an NK cell inhibitory ligand, in T cell receptor (TCR) and HLA-I/II disrupted universal CD38-targeting CAR-T cells could prevent rejection by allogeneic NK cells. Methods We generated CD38-targeting universal CAR-T cells by transducing T cells with lentiviruses encoding the CD38 CAR and LLT1 constructs. T cells were subjected to CD38, TCR, HLA-I, and HLA-II gene knockdown using CRISP

In this study, we investigated the therapeutic effects and mechanisms of umbilical cord mesenchymal stem cells (UCMSCs) in diabetic nephropathy (DN) ZDF (FA/FA) rats. The therapeutic effects were assessed by renal function tests, the urinary albumin–creatinine ratio, PAS staining, electron microscopy, and TGF‐β1 expression in renal tissue. Subsequently, podocyte injury in renal tissue was detected by immunofluorescence staining for podocin. To further explore the underlying mechanism, serum Angptl4 levels were measured, and Angptl4, integrin β3, fibronectin, and podocin levels in renal tissue were analysed by Western blotting. In vitro, podocytes are stimulated with high glucose and then treated with UCMSCs, and podocyte activity and the expression of synaptopodin, Angptl4, and integrin β3 were observed. UCMSC significantly improve renal function, pathological injury, and podocyte injury in the ZDF (FA/FA) rats. Western blot revealed increased expression of Angptl4, integrin β3, and fibronectin in renal tissu