Autoimmune nephrological and rheumatological diseases involve macrophage-driven inflammation, yet disease activity is often assessed using invasive or non-specific measures. Soluble CD163 (sCD163), released from activated monocytes and macrophages, is emerging as a biomarker of macrophage-mediated inflammation in these conditions. This narrative review summarizes current evidence on the diagnostic, prognostic, and disease-monitoring potential of sCD163 measured in blood, urine, and synovial fluid in autoimmune nephrological and rheumatological diseases. This review is based on a narrative analysis of selected publications investigating the clinical utility of sCD163 in autoimmune kidney and rheumatic diseases, with emphasis on correlations with disease activity, histopathological findings, and clinical outcomes. Urinary sCD163 shows excellent diagnostic accuracy for active lupus nephritis (area under the receiver operating characteristic [AUROC] 0.89-0.998), correlates with histological activity index (but not chronicity), and distinguishes ongoing inflammation from chronic damage during treatment. In IgA nephropathy, it predicts remission failure and greater benefit from corticosteroids. In ANCA-associated vasculitis, it identifies active renal involvement (AUROC 0.95 in multicenter cohorts). In rheumatoid arthritis (RA), serum sCD163 correlates with early disease activity, predicts radiographic progression, and detects subclinical macrophage activation in remission. In spondylarthritis, synovial fluid sCD163 reflects a disease-specific M2-polarized macrophage phenotype distinct from RA. Utility is compartmentalized: urinary levels indicate intrarenal macrophage activation, synovial fluid local joint inflammation, and serum systemic activation. sCD163 is a promising macrophage-specific biomarker across autoimmune diseases, but its compartmentalized nature requires context-specific measurement. Before clinical implementation, assay standardization, multicenter validation, and interventional trials showing the benefit of sCD163-guided management are needed.
Fracture-related infection is a challenging aspect of orthopedic care, as it leads to prolonged inflammation and impaired bone healing. Although isovitexin is a naturally occurring flavonoid with anti-inflammatory properties, its effects on fracture-related infection remain unclear. A rat fracture infection model was established and randomly divided into four groups: control, model, Vancomycin, and isovitexin. Tissue staining was used to assess bone healing. In contrast, enzyme-linked immunosorbent assay and biochemical kits were used to measure the levels of inflammatory factors and bone metabolism-related indicators. The expression of proteins associated with osteogenesis and the Nuclear Factor kappa-light-chain-enhancer of activated B cells (NF-κB) signaling pathway was examined using Western blot. When compared to the model group, isovitexin treatment more effectively reduced inflammatory cell infiltration in bone tissue and promoted callus formation than the Vancomycin group. In addition, isovitexin improved the imbalance of bone metabolism and promoted the expression of osteogenesis-related proteins Bone Morphogenetic Protein 2 (BMP2), Osteopontin (OPN), and Runt-related Transcription Factor 2 (RUNX2). It also decreased the levels of pro-inflammatory factors tumor necrosis factor (TNF)-α and interleukin (IL)-6, and increased the level of the anti-inflammatory factor IL-10. Mechanistic studies showed that isovitexin significantly inhibited the activation of the NF-κB signaling pathway. Isovitexin can promote bone metabolism and healing, suppress the NF-κB signaling pathway, and reduce the inflammatory response associated with fracture-related infection. This study suggests that isovitexin may be a viable therapy option for fracture-related infections.
Oral squamous cell carcinoma (OSCC) ranks 16th worldwide as the most common type of malignancy in head and neck cancer globally, and addressing it has been an ongoing but difficult pursuit, as treatment resistance is commonly reported. Hence, employing multiple cell death pathways is an emerging strategy in overcoming treatment resistance in OSCC. We investigate here the effect of heteronemin, a marine sesterterpenoid isolated from sponges, for its anti-cancer potential, hypothesizing that it can induce non-apoptotic cell death pathways to overcome apoptosis-resistant cells and elucidate the underlying mechanisms involved. Our results show that heteronemin significantly kills cancer cells via the induction of the intrinsic apoptotic pathway. It also triggers ferroptosis, down-regulating glutathione peroxidase 4 (GPX4) and upregulating markers of lipid peroxidation such as 4-hydroxynonenal and malondialdehyde. We demonstrate that increasing reactive oxygen species generation plays a central role in triggering these pathways. ensuring the death of the cancer cells despite a compensation attempt via inducing autophagy and modulating Nrf2. Our study is the first to demonstrate the complex but interesting role of heteronemin in killing OSCC cells: inducing apoptosis and switching to ferroptosis as the cells attempt to survive. It also inhibits protective autophagy, leaving OSCC cells incapable of protecting themselves from imminent death. This complex mechanism adds to the existing knowledge on the mechanism of heteronemin as a strong therapeutic compound to treat OSCC cells.
Cytomegalovirus (CMV) infection remains a significant cause of morbidity and mortality due to the compromised immune system after hematopoietic stem cell transplantation (HSCT). Natural killer (NK) cells are pivotal in the immune response following HSCT, as these cells regenerate early and play a crucial role in detecting and eliminating infections. In the present study, we analyzed expression and single nucleotide polymorphisms (SNPs) of genes coding for NK cell Natural Cytotoxicity Receptors (NCRs). Expression was studied on the mRNA level and on the protein level, using flow cytometry to examine NCR-positive NK cell populations. Our study revealed significant higher expression of NCR1 and NCR3 in HSCT recipients with CMV infection compared to those without complications. Additionally, expression of both receptors correlated with expression of IFN-γ. Changes over time after HSCT were observed in the proportion of NCR1+ NK cells. SNPs genotyping identified associations of NCR1 rs1433097 and NCR3 rs11575836 genotypes with increased risk of CMV infection, as well as of NCR3 rs11575836 with post-HSCT overall survival. These results underscore the crucial role of NCRs in the prevention of infection and the development of post-HSCT complications, highlighting their potential as therapeutic targets to improve transplant outcomes.
Acute pancreatitis (AP) frequently triggers intestinal barrier dysfunction, yet the underlying molecular mechanisms remain poorly understood. This study investigated whether small extracellular vesicle (sEV)-enriched serum preparations from healthy individuals protect against AP-induced intestinal barrier dysfunction through microRNA-mediated regulation of pyroptosis. sEV-enriched preparations were isolated from 10 AP patients (AP-sEV) and 10 healthy controls (HC-sEV) using ExoQuick precipitation followed by ultracentrifugation. A murine AP model was established using cerulein and lipopolysaccharide, and human intestinal epithelial cells were stimulated with lipopolysaccharide for in vitro studies. HC-sEV preparations significantly ameliorated AP-induced tissue damage, restored tight junction proteins (claudin-1, occludin, ZO-1), reduced intestinal permeability, and suppressed inflammatory cytokines (TNF-α, IL-6, IL-1β) and pyroptosis-related proteins including NLRP3, gasdermin D, and cleaved caspase-1. Conversely, AP-sEV preparations exacerbated barrier dysfunction. Bioinformatics analysis identified miR-579-3p as significantly downregulated in AP-sEV. Inhibition of miR-579-3p reversed HC-sEV protective effects. ANXA3 was validated as a direct miR-579-3p target, and ANXA3 overexpression counteracted miR-579-3p-mediated protection. These findings demonstrate that HC-sEV preparations protect against AP-induced intestinal barrier dysfunction through miR-579-3p delivery targeting ANXA3 to suppress NLRP3 inflammasome-mediated pyroptosis. The miR-579-3p/ANXA3/NLRP3 axis represents a novel therapeutic target for preserving intestinal barrier integrity during acute pancreatitis.
Acute myeloid leukemia (AML) is an incursionary hematopoietic tumor with frequent relapses and an unfavorable prognosis. Ubiquitin-specific peptidase 25 (USP25) mediates the progression of various cancers, but its role in AML remains uncharted. The expression of USP25 in AML was analyzed in silico, in vitro, and in vivo through real-time quantitative polymerase chain reaction (RT-qPCR) and Western blot. The function of USP25 in proliferation, apoptosis, glycolysis, and immunity in AML was addressed through cell counting kit-8 (CCK-8), flow cytometry, detection of glucose consumption, lactate production, extracellular acidification rate (ECAR), and oxygen consumption rate (OCR), immunohistochemistry, immunofluorescence, and Western blot. The mechanism of USP25 in AML was explored via co-immunoprecipitation (Co-IP), ubiquitination, cycloheximide, and Western blot. Upregulation of USP25 indicated a poor overall survival in AML patients. Knock-in and knock-down results revealed that USP25 enhanced viability, the level of glucose consumption, lactate production, ECAR, and the level of anti-glucose transporter type 1 (GLUT1) and hexokinase-2 (HK2), but reduced the apoptosis rate and the OCR level. Mechanically, USP25 directly bound and deubiquitinated c-Myc. An upregulation of c-Myc and programmed cell death ligand 1 (PD-L1) was found in AML. Knockdown of c-Myc decreased USP25-induced cell viability, glucose consumption, and lactate production level. In vivo, knockdown of USP25 decreased tumor volume and weight, the ki-67 expression, and the levels of c-Myc and PD-L1, but elevated the levels of cluster of differentiation 4 (CD4) and cluster of differentiation 8 (CD8). USP25 facilitated proliferation, glycolysis, and immunity through deubiquitinating c-Myc in AML. The results identified USP25 as a possible target for AML treatment.
Exopolysaccharide (EPS), a major constituent of Pseudomonas aeruginosa biofilms, protects bacteria from M1-macrophage-mediated clearance while promoting chronic inflammation. This study investigated how Saccharomyces cerevisiae β-glucan (BG)-induced macrophage training reshapes subsequent inflammatory and antimicrobial responses to EPS. Peritoneal macrophages from C57BL/6 mice were trained in vitro with BG and subsequently stimulated with EPS purified from a clinical P. aeruginosa isolate obtained from a patient with severe cystic fibrosis. Cytokines, prostaglandin E2 (PGE2), and nitric oxide (NO) were quantified, and global proteomic profiling was performed. BG training amplified EPS-induced secretion of TNF-α, IL-6, and additional pro-inflammatory mediators. Trained macrophages also showed markedly increased PGE2 production, minimal NO release, and reduced phagocytic activity. Proteomic analyzes confirmed upregulation of PGE2-biosynthetic enzymes and suppression of inducible NO synthase, along with enhanced expression of antimicrobial and immunoregulatory factors, including platelet factor 4, antileucoproteinase, C1q components, and selected chemokines. These data reveal a previously uncharacterized macrophage state-neither M1 nor M2-emerging specifically from BG training and defined by high PGE2 and low NO production in response to EPS. S. cerevisiae BG training reprograms EPS-stimulated macrophages toward a distinct, non-classical trained-immunity phenotype characterized by elevated PGE2 and suppressed NO production. This newly defined phenotype represents a novel form of trained immunity and highlights the dual proinflammatory and immunoregulatory roles of macrophage-derived PGE2. These findings suggest that targeted macrophage reprogramming may offer a promising therapeutic strategy for mitigating P. aeruginosa biofilm-driven chronic inflammation, including in cystic fibrosis.
Myocardial infarction (MI) is one of the leading causes of death worldwide and results in substantial harm to human health and family well-being. Salvianolic acid C (SAC), a bioactive compound isolated from Salvia miltiorrhiza Bge., exhibits anti-oxidant, anti-inflammatory, and anti-apoptotic capacities. However, the protective effects of SAC against MI-induced cardiomyocyte injury and the underlying molecular mechanisms, particularly its role in ferroptosis and AMPK signaling, remain unclear. Infarct size in rat hearts was assessed through triphenyltetrazolium chloride (TTC) staining. Myocardial tissue damage was examined through hematoxylin-eosin (HE) staining. The mRNA and protein levels of inflammatory cytokines, including Interleukin (IL)-1β, IL-6, and tumor necrosis factor (TNF)-α, were measured by reverse transcription quantitative polymerase chain reaction (RT-qPCR) and enzyme-linked immunosorbent assay (ELISA), respectively. Apoptosis in myocardial tissues was evaluated through the terminal deoxynucleotide transferase-mediated dUTP nick end-labeling (TUNEL) assay. Protein expression levels were determined by Western blot. The results demonstrated that SAC significantly reduced infarct size in MI rats. Inflammation and cardiomyocyte apoptosis were markedly increased in the MI group, but these impacts were neutralized after SAC treatment. In addition, SAC effectively suppressed ferroptosis in MI rats. Mechanistically, SAC activates the AMPK pathway. Finally, SAC was shown to alleviate oxygen-glucose deprivation (OGD)-induced cardiomyocyte injury by activating the AMPK pathway. This study is the first to demonstrate that SAC activates the AMPK pathway to inhibit ferroptosis and alleviate cardiomyocyte injury after acute MI. These findings suggest that SAC may present a promising therapeutic candidate for the treatment of MI.
Bladder cancer is a prevalent malignancy with a high recurrence rate, necessitating the identification of novel molecular targets for diagnosis and therapy. Recent studies have highlighted the role of long noncoding RNAs (lncRNAs) in cancer progression. This study aims to investigate the role of the lncRNA IDH1-AS1 in bladder cancer, focusing on its effects on tumor growth, cell proliferation, and autophagy-related protein expression. We utilized both in vivo and in vitro models to assess the impact of IDH1-AS1 overexpression and knockdown. Tumor growth was evaluated in nude mice model of bladder cancer, while cell proliferation was measured using the EDU assay. Protein expression levels of Beclin1, P62, and LC3 were determined by Western Blot analysis. Gene expression of IDH1-AS1 was quantified using quantitative polymerase chain reaction (qPCR). Overexpression of IDH1-AS1 in nude mice model of bladder cancer led to a significant increase in tumor volume and weight, whereas knockdown of IDH1-AS1 resulted in a substantial decrease in tumor size. In vitro, IDH1-AS1 overexpression significantly enhanced cell proliferation, while its knockdown reduced proliferation. Western Blot analysis revealed that IDH1-AS1 overexpression increased the levels of autophagy-related proteins Beclin1 and LC3, and decreased P62 protein levels, with contrary effects observed upon IDH1-AS1 knockdown. qPCR confirmed successful modulation of IDH1-AS1 expression in experimental groups. Our findings indicate that IDH1-AS1 promotes tumor growth and cell proliferation in bladder cancer, potentially through the regulation of autophagy-related proteins. These results suggest that IDH1-AS1 could serve as a novel biomarker and therapeutic target for bladder cancer.
Chimerism-based strategies remain promising for tolerance induction in solid organ and vascularized composite allograft (VCA) transplantation. This study aimed to develop a novel, less toxic chimeric cell therapy to prolong allograft survival and reduce the need for lifelong immunosuppression. Di-chimeric cells (DCC) were created via polyethylene glycol (PEG)-mediated ex vivo fusion of allogeneic hematopoietic stem cells (HSC) and mesenchymal stem cells (MSC) derived from August Copenhagen Irish (ACI) and Lewis rats. Twenty-four fully major histocompatibility complex (MHC)-mismatched groin flap VCAs were transplanted from ACI rat major histocompatibility complex (rat MHC) (RT1a) donors to Lewis (RT11) recipients under a 7-day immunosuppressive protocol of anti-αβTCR antibody and tacrolimus, combined with four different cell therapies of n = 6/group: Group 1, saline control; Group 2, MSC; Group 3, HSC/HSC DCC; and Group 4, HSC/MSC DCC. DCC were delivered via the intraosseous injection. DCC phenotype was confirmed by flow cytometry (FC). Graft rejection was evaluated macroscopically. A single DCC dose significantly prolonged VCA survival, with the best results in Group 4 (94 ± 1.65 days), followed by Group 3 (66 ± 1.24 days), Group 2 (45.5 ± 4.08 days), and Group 1 (38 ± 4.29 days). This study confirmed immunomodulatory and tolerogenic properties of DCC, supporting VCA transplantation.
To investigate the role of 3-hydroxybutyrate dehydrogenase 2 (BDH2) in regulating ferroptosis and its impact on the metastasis of lung adenocarcinoma (LUAD). Expression levels of BDH2 were modulated in LUAD cell lines (A549, PC9) using pcDNA-BDH2 plasmid transfection. Cell motility was assessed by Transwell assays, while ferroptosis-associated markers, including Fe2+, malondialdehyde (MDA), lipid reactive oxygen species (ROS), ACSL4, and GPX4, were evaluated by biochemical assays, flow cytometry, and Western blotting. The involvement of the Nrf2/HO-1 signaling axis was analyzed by Western blotting and RT-qPCR. Furthermore, a xenograft mouse model was established to confirm the effect of BDH2 on tumor progression and metastasis in vivo. Overexpression of BDH2 significantly inhibited LUAD cell migration and invasion. BDH2 upregulation enhanced ferroptosis, effects that were reversed by the ferroptosis inhibitor Fer-1. Mechanistically, BDH2 suppressed the activation of the Nrf2/HO-1 pathway, thereby enhancing sensitivity to ferroptosis. In vivo, BDH2 overexpression markedly reduced tumor growth and metastasis in nude mice, while inhibition of ferroptosis attenuated these effects. BDH2 suppresses metastasis in LAUD by promoting ferroptosis via suppression of the Nrf2/HO-1 pathway, highlighting BDH2 as a potential therapeutic target for LUAD.
This paper elucidates the role of RNA-binding motif protein 15 (RBM15) in programmed death-ligand 1 (PD-L1)-mediated immune escape in ovarian cancer (OC), providing a novel immunotherapeutic strategy. RBM15/circFGFR3/JAK2/STAT3/STAT5 expression was assessed. OC cell progression was analyzed. OC cells were co-cultured with CD8+ T cells. The m6A enrichment on circRNA fibroblast growth factor receptor 3 (circFGFR3) was determined. The expression of p-JAK2, p-STAT3, and p-STAT5 was investigated. The bindings of circFGFR3 to EIF4A3 and EIF4A3 to JAK2, STAT3, or STAT5 were analyzed. In conclusion, RBM15 promotes PD-L1-mediated immune escape and accelerates OC progression by upregulating circFGFR3 expression through m6A modification and activating the Janus kinase-signal transducer and activator of transcription (JAK/STAT) pathway.
Neurodegenerative diseases, such as Parkinson's, Alzheimer's, and Huntington's, are major causes of disability. Current treatments are mostly symptomatic, due to a limited understanding of the disease mechanisms and the brain's poor regenerative capacity. Neuronal transdifferentiation offers a promising solution. Existing protocols are often inefficient, invasive, or time-consuming, and expensive. Furthermore, they mostly rely on nucleic acids as transdifferentiation-inducers, hence this carries risks of insertion mutagenesis. In this study, monocytes were isolated from buffy coats and cultured under four protocols using different small-molecule combinations. Two protocols successfully generated TUJ1+ MAP2+ SYP+ cells. Transdifferentiation is achievable through cheap and efficient chemical induction.
This study evaluated the immune surveillance function in chronic myeloid leukemia (CML) through tumor antigen gene expression analysis, in vitro mixed lymphocyte cultures with peptides, and immunological analysis of patients after imatinib withdrawal to investigate factors affecting treatment-free remission (TFR). Specific immune responses were demonstrated in T lymphocytes against SPAG9 and NY-REN-60 peptides, highlighting their potential in immunotherapy. Immune profiling identified that CD8+PD1+, CD56dimCD16+PD1+, and iNKT+CD161+ cells contribute to recurrence-free survival. A Cox model confirmed the prognostic value of immune markers. These results emphasize the critical role of the immune system in CML and indicate novel targets for sustaining TFR.
Melanoma is a highly aggressive and heterogeneous form of skin cancer with limited effective treatment options. Although substantial progress has been made in immunotherapy, chemotherapy still serves as an essential alternative therapeutic strategy for many patients. Diphenyl disulfide (DPDS), a small molecule composed of two phenyl groups linked by a disulfide bond, has been reported to exert antioxidant and anticancer activities across several types of malignancies. In this study, we examined the cytotoxic effects of DPDS on melanoma cells and investigated the underlying mechanisms responsible for its antitumor activity. Our results showed that DPDS induces both ferroptosis and apoptosis in melanoma cells in a time-dependent manner. At 24 h, DPDS promoted lipid peroxidation, enhanced xCT ubiquitination, and reduced GPX4 expression, all of which are characteristic hallmarks of ferroptosis. Whereas at 48 h, apoptosis occurred, likely because of NRF2 phosphorylation inhibition, which initially protected against cell death. Additionally, DPDS inhibited the PI3K/AKT/mTOR pathway, leading to decreased mTOR expression and increased autophagy levels. Furthermore, the inhibition of ferroptosis or autophagy partially restored cell viability, suggesting a complex interplay between these pathways in DPDS-induced cytotoxicity. These findings highlight that DPDS may be a potential therapeutic agent for melanoma that functions by leveraging dual programmed cell death mechanisms and targeting the PI3K/AKT/mTOR signaling pathway.
Vascular endothelial cells (ECs) are pivotal in maintaining vascular homeostasis. Liraglutide (LIR) can prevent and reverse hyperglycemia-induced cell dysfunction. However, the mechanism by which it improves hyperglycemia-induced EC senescence remains unclear. This study investigates whether the La Ribonucleoprotein 7/Sirutin 1 (LARP7/SIRT1) signaling axis is essential for LIR efficacy in mitigating EC senescence and dysfunction. We treated senescent human umbilical vein ECs induced by high glucose levels with LIR and evaluated cell viability cell counting kit-8 (CCK-8 assay), senescence (SA-β-gal staining), and SASP alterations (qPCR). We also investigated the expression of senescence-related proteins and changes in the LARP7/SIRT1 signaling pathway using Western blot analysis. Additionally, reactive oxygen species levels were measured with 2′,7′-Dichlorodihydrofluorescein diacetate (DCFH-DA), and changes in oxidative stress-related factors were assessed using specific assay kits. The effect of LIR on endothelial dysfunction was examined by cellular tube-forming assay and transwell assay after LARP7 knockdown/overexpression. LIR markedly improved cell vitality and the senescence phenotype while reducing oxidative stress. The LARP7/SIRT1 pathway emerged as crucial for its effectiveness. Following LARP7 knockdown, the therapeutic efficacy of LIR was notably attenuated. The overexpression of LARP7 enhanced the therapeutic efficacy of LIR. The tube formation and transwell assays further supported the hypothesis that LIR's beneficial impact on endothelial dysfunction depends on the LARP7/SIRT1 signaling axis. Our study reveals a novel aspect of LIR as an antidiabetic agent in delaying vascular aging driven by high glucose through targeting the LARP7/SIRT1 pathway. This discovery enhances the therapeutic value of LIR and proposes a new strategy for addressing vascular aging in treatments for elderly patients with diabetes.
In light of the increasing incidence of head and neck cancer and the widespread occurrence of methylparabens (MeP) in the human environment, which mimic the action of endogenous estrogens, we investigated the effect of this compound on head and neck squamous cell carcinoma (HNSCC) cells. We took into account autophagy and apoptosis, as well as the ability of HNSCC cell lines FaDu and Detroit 562 to proliferate, and the effect of flavonoids on the determined parameters. The obtained results revealed that MeP inhibits autophagy, indicated by downregulation of autophagy-related proteins such as beclin-1, LC3β, and APG5 expression in both cancer cell lines. Moreover, MeP, by changing the expression of mitochondrial proteins Bcl-2 and Bax, may be responsible for the reduction of apoptosis and the increased proliferation of cancer cells associated with high expression of caspase-3. The applied flavonoids restored the values of the tested parameters to the level observed in cells not exposed to MeP. In conclusion, our studies have shown for the first time that MeP, in addition to well-documented exposure factors, may facilitate the development of HNSCCs. We suggest that the adverse effects of MeP can be reduced by the use of flavonoids, which may lead to the inhibition of HNSCC cells growth.
Skin cutaneous melanoma (SKCM) is a highly aggressive skin cancer with poor prognosis in advanced stages, despite recent advances in immunotherapy and targeted treatments. Novel therapeutic targets are urgently needed to improve the patient outcomes. Scavenger receptor class A member 5 (SCARA5), a scavenger receptor widely expressed in various human tissues, has been reported to act as a tumor suppressor in multiple cancers. The expression level of SCARA5 in SKCM tissues and cell lines was analyzed using the Gene Expression Profiling Interactive Analysis (GEPIA) database and validated by Western blotting. SKCM cells were transfected with SCARA5 overexpression plasmids, and cell proliferation, migration, and apoptosis were assessed using Cell Counting Kit-8 (CCK-8), colony formation, flow cytometry, and Transwell assays. Ferroptosis-related changes were examined by detecting intracellular Fe2, lipid Reactive Oxygen Species (ROS), and malondialdehyde (MDA) levels. Additionally, the expression of ferroptosis-associated proteins glutathione peroxidase 4 (GPX4), acyl-CoA synthetase long-chain family member 4 (ACSL4), and SLC7A11 was analyzed by Western blotting. SCARA5 expression was markedly downregulated in SKCM cells compared with normal skin cells. Restoration of SCARA5 expression significantly suppressed the proliferation and migration of SKCM cells. Further analysis revealed that SCARA5 overexpression induced ferroptosis, as evidenced by increased levels of Fe2, lipid ROS, and MDA. Mechanistically, SCARA5 regulated the ferroptosis process through modulation of the GPX4/ACSL4 pathway. CARA5 inhibits SKCM progression by promoting ferroptosis and disrupting the GPX4/ACSL4 axis.
Sepsis-related acute kidney injury (S-AKI) is a severe condition characterized by rapid onset and high mortality. Thus, identifying effective treatments for S-AKI is of critical importance. Lipopolysaccharide (LPS) was used to activate HK-2 cells to mimic S-AKI in vitro. Lentiviral transfection was performed to knock down C-type lectin domain family 5 member A (CLEC5A) expression, and protein immunoblotting was used to detect changes in CLEC5A expression. Cell damage was evaluated using the cell counting kit-8 (CCK-8) and lactate dehydrogenase (LDH) kit, cellular inflammatory factor levels were determined using the enzyme-linked immunosorbent assay (ELISA), and oxidative stress signs were detected using the kit. Western blotting was used to detect the expression of NF-κB/NLRP3 (NLR family, pyrin domain-containing protein 3) pathway, and NF-κB activator was used to detect whether knockdown of CLEC5A acts through the NF-κB/NLRP3 pathway. LPS stimulated the expression of CLEC5A in HK-2 cells. Knockdown of CLEC5A could inhibit the LPS-induced decrease in HK-2 cell viability and increased LDH release. Knockdown of CLEC5A could inhibit the LPS-induced increase in HK-2 cell release of inflammatory factors. Knockdown of CLEC5A could inhibit LPS-induced oxidative stress. CLEC5A knockdown can prevent the NF-κB/NLRP3 signaling pathway from being activated, and NF-κB activation can undo the effects of CLEC5A knockdown. Knockdown of CLEC5A can ameliorate renal tubular damage and lessen inflammation and oxidative stress via reducing NF-κB/NLRP3 activation.
