Retinoblastoma is one of the most common primary intraocular malignancies in young children. Traditional treatment methods such as chemotherapy often come with significant adverse effects, such as hearing loss, cognitive impairment, and vision loss. Therefore, there is an urgent need to explore a novel therapeutic drug that is both effective and safe. S-adenosylmethionine (SAM) is a natural compound known to exhibit anti-proliferative effects in various cancer cell lines. However, to date, no studies investigated the effects of SAM on retinoblastoma cells and its potential mechanisms of action. Therefore, this study aims to investigate the impact of SAM on retinoblastoma cells and explore its possible mechanisms of action, with the hope of providing new insights into the treatment of this disease. The optimal concentration of SAM was determined using the Cell Counting Kit-8 assay. The effect of SAM on retinoblastoma proliferation was assessed using the 5-ethynyl-2'-deoxyuridine cell proliferation assay. Y79 cells were subjected to hematoxylin and eosin stain and electron microscopy to observe any morphological changes induced by SAM. The stages of SAM's action on the retinoblastoma cell cycle and its apoptotic effects were measured using flow cytometry. The apoptotic effect of SAM on retinoblastoma was further confirmed using the TUNEL assay. Differential expression of related genes was detected through RT-PCR. In vivo subcutaneous tumor formation in nude mice and immunohistochemistry were employed to validate the effect of SAM on retinoblastoma-related phenotypes. Western blotting was conducted to investigate whether SAM modulated retinoblastoma-related phenotypes via the Wnt2/β-catenin pathway. SAM arrested the cell cycle of retinoblastoma at the G1 phase, induced apoptosis of retinoblastoma cells through the Wnt2/β-catenin pathway, and affected their morphology and even ultrastructure. In addition, in vitro and in vivo experiments demonstrated that SAM had an oncogenic effect on retinoblastoma. In this study, we verify in vitro and in vivo whether SAM inhibits the proliferation of retinoblastoma cell Y7, induces apoptosis and cell cycle arrest of Y79 cells by inhibiting the Wnt2/β-catenin pathway, and affects the morphology and structure of retinoblastoma cell Y79.
Endometriosis is a debilitating gynecological disease defined as the presence of endometrium-like epithelium and/or stroma outside the uterine cavity. The most commonly affected sites are the pelvic peritoneum, ovaries, uterosacral ligaments, and the rectovaginal septum. The aberrant tissue responds to hormonal stimulation, undergoing cyclical growth and shedding similar to appropriately located endometrial tissue in the uterus. Common symptoms of endometriosis are painful periods and ovulation, severe pelvic cramping, heavy bleeding, pain during sex, urination and bowel pain, bleeding, and pain between periods. Numerous theories have been proposed to explain the pathogenesis of endometriosis. Sampson's theory of retrograde menstruation is considered to be the most accepted. This theory assumes that endometriosis occurs due to the retrograde flow of endometrial cells through the fallopian tubes during menstruation. However, it has been shown that this process takes place in 90% of women, while endometriosis is diagnosed in only 10% of them. This means that there must be a mechanism that blocks the immune system from removing endometrial cells and interferes with its function, leading to implantation of the ectopic endometrium and the formation of lesions. In this review, we consider the contribution of components of the Major Histocompatibility Complex (MHC)-I-mediated antigen-processing pathway, such as the ERAP, TAP, LMP, LNPEP, and tapasin, to the susceptibility, onset, and severity of endometriosis. These elements can induce significant changes in MHC-I-bound peptidomes that may influence the response of immune cells to ectopic endometrial cells.
Parkinson's disease (PD) affects millions of people globally. Accurate early diagnosis remains a challenge due to the lack of specific biomarkers. This systematic review explores the potential of 1H-NMR metabolomics in identifying diagnostic markers and therapeutic targets for PD. A comprehensive analysis was conducted across databases such as Scopus, Web of Science, PubMed, and Embase, focusing on studies that utilized 1H-NMR spectroscopy to profile metabolites associated with PD progression. The review identifies key metabolites-glutamate, taurine, myo-inositol, glutamine, and creatine-that play critical roles in the pathophysiology of PD. Glutamate, linked to excitotoxicity and neuronal degeneration, emerges as a prominent target for therapeutic intervention, while taurine is associated with oxidative stress. Myo-inositol, a key regulator of autophagy, underscores the biochemical dysregulation associated with PD, similar to glutamine and glutamate. Creatine's role in neuronal energy metabolism suggests potential avenues for treatment focused on energy supplementation. The reproducibility of metabolite findings varied, indicating the complexity of PD's metabolomic landscape. Despite challenges in consistency, these metabolites hold promise as biomarkers for diagnosing PD and tracking disease progression. The review underscores the need for further validation of these markers and their integration with other omics technologies to enhance PD management. By identifying key metabolic pathways, this study opens new directions for personalized medicine, offering potential therapeutic targets to slow disease progression and improve patient outcomes.
Studies on the bacillus Calmette-Guérin (BCG) vaccine, traditionally used against tuberculosis, indicate its potential benefit in protecting against infections. The vaccine's ability to broadly activate the immune system suggests its potential to bolster non-specific immunity, which could be crucial for combating respiratory pathogens. This study aimed to evaluate the messenger RNA (mRNA) expression of interferon (IFN)-α, IFN-β, and IFN-γ as well as the secretion of these cytokines in whole blood co-stimulated cultures with BCG and antigens of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) or respiratory syncytial virus (RSV) from BCG-vaccinated Polish children who have been infected or uninfected with RSV and/or SARS-CoV-2. Significant differences were observed in the secretion and mRNA expression of IFN-α and IFN-γ in response to RSV antigens in all groups of children studied. When cultures were conducted in the presence of SARS-CoV-2 antigens, live BCG did not induce increased IFN-α secretion compared with cultures stimulated with these antigens alone. However, enhanced secretion was observed for IFN-γ, and no such relationship was observed for mRNA expression. Furthermore, discrepancies between IFN-β secretion and mRNA expression were observed, suggesting that IFN protein secretion can also be controlled at the translational or posttranslational level. The data from our studies indicate that BCG vaccination may modulate the IFN response to viral challenges with SARS-CoV-2 and RSV, suggesting a potential immunoregulatory role.
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.
Pregnancy is a remarkable event where the semi-allogeneic fetus develops in the mother's uterus, despite genetic and immunological differences. The antigen handling and processing at the maternal-fetal interface during pregnancy appear to be crucial for the adaptation of the maternal immune system and for tolerance to the developing fetus and placenta. Maternal antigen-presenting cells (APCs), such as macrophages (Mφs) and dendritic cells (DCs), are present at the maternal-fetal interface throughout pregnancy and are believed to play a crucial role in this process. Despite numerous studies focusing on the significance of Mφs, there is limited knowledge regarding the contribution of DCs in fetomaternal tolerance during pregnancy, making it a relatively new and growing field of research. This review focuses on how the behavior of DCs at the maternal-fetal interface adapts to pregnancy's unique demands. Moreover, it discusses how DCs interact with other cells in the decidual leukocyte network to regulate uterine and placental homeostasis and the local maternal immune responses to the fetus. The review particularly examines the different cell lineages of DCs with specific surface markers, which have not been critically reviewed in previous publications. Additionally, it emphasizes the impact that even minor disruptions in DC functions can have on pregnancy-related complications and proposes further research into the potential therapeutic benefits of targeting DCs to manage these complications.
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.
AdoMet (S-adenosylmethionine) inhibits cancer cell proliferation and migration via epigenetic alterations. This study aimed to investigate whether AdoMet may cause alterations in microRNA (miRNA) expression profiles that are important for the initiation and progression of prostate cancer. PC-3 cells were treated with AdoMet before miRNA sequencing. A total of 17 differentially expressed miRNAs were detected. Target gene prediction was performed by means of databases. Results were aligned to transcriptomic data. The bioinformatic analysis revealed upregulation of anticancerogenic genes, downregulation of cancerogenic-related processes and pathways. Knocking down hsa-miR-192-5p in PC-3 cells resulted in downregulation of cancer cell proliferation, thus confirming these results.
The aim of the present study was to determine the associations between the MICB genetic variability and the expression and the risk of development of post-transplant complications after allogeneic hematopoietic stem cell transplantation (HSCT). HSCT recipients and their donors were genotyped for two MICB polymorphisms (rs1065075, rs3828903). Moreover, the expression of a soluble form of MICB was determined in the recipients' serum samples after transplantation using the Luminex assay. Our results revealed a favorable role of the MICB rs1065075 G allele. Recipients with donors carrying this genetic variant were less prone to developing chronic graft-versus-host disease (cGvHD) when compared to recipients without any symptoms of this disease (41.41% vs. 65.38%, p = 0.046). Moreover, the MICB rs1065075 G allele was associated with a lower incidence of cytomegalovirus (CMV) reactivation, both as a donor (p = 0.015) and as a recipient allele (p = 0.039). The MICB rs1065075 G variant was also found to be associated with decreased serum soluble MICB (sMICB) levels, whereas serum sMICB levels were significantly higher in recipients diagnosed with CMV infection (p = 0.0386) and cGvHD (p = 0.0008) compared to recipients without those complications. A protective role of the G allele was also observed for the rs3828903 polymorphism, as it was more frequently detected among donors of recipients without cGvHD (89.90% vs. 69.23%; p = 0.013). MICB genetic variants, as well as serum levels of sMICB, may serve as prognostic factors for the risk of developing cGvHD and CMV infection after allogeneic HSCT.
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.
This study aims to investigate the effects and underlying mechanisms of isorhynchophylline (IRN) on gestational diabetes mellitus (GDM). The db/+ mice were randomly divided into four groups: GDM, GDM + IRN (20 mg/kg), and GDM + IRN (40 mg/kg). Blood glucose and insulin tolerance were assessed using intraperitoneal glucose tolerance tests (IPGTTs) and intraperitoneal insulin tolerance tests (IPITTs) on gestational day 10. On gestational day 20, placental inflammation (tumor necrosis factor [TNF]-α, interleukin [IL]-6, IL-1β), oxidative stress markers (malondialdehyde [MDA], SOD, glutathione peroxidase [GPx], and glutathione [GSH]), and nuclear factor-κB/NOD-like receptor protein 3 [NLRP3] inflammasome activity were measured using enzyme-linked immunosorbent assay (ELISA), immunoblotting, and biochemical assays. IRN significantly improved blood glucose levels and insulin tolerance in GDM mice. IRN treatment reduced placental inflammation. In addition, oxidative stress in the placenta was alleviated in the IRN-treated groups, leading to improved placental function and healthier fetal development. The birth weight of offspring was higher in the IRN-treated groups compared with untreated GDM mice. Furthermore, IRN inhibited the activation of the NLRP3 pathway. IRN significantly improves metabolic and inflammatory parameters in GDM through the NF-κB/NLRP3 pathway, highlighting its potential therapeutic benefits for managing GDM and improving maternal and fetal outcomes.
The rapid development of nanotechnology has led to the use of silver nanoparticles (Ag-NPs) in various biomedical fields. However, the effect of Ag-NPs on human mesenchymal stem cells (hMSCs) is not fully understood. Moreover, too frequent an exposure to products containing nanosilver in sublethal amounts raises widespread concerns that it will lead to the development of silver-resistant microorganisms. Therefore, this study aimed to evaluate the mechanism of action of Ag-NPs on hMSCs by analyzing the cellular uptake of Ag-NPs by the cells and its effect on their viability and to assess antimicrobial activity of Ag-NPs against emerging bacterial strains, including multidrug-resistant pathogens. For metabolic activity and viability evaluation, hMSCs were incubated with different concentrations of Ag-NPs (14 μg/mL, 7 μg/mL, and 3.5 μg/mL) for 10 min., 1 h and 24 h and subsequently analyzed for their viability by live-dead staining and metabolic activity by the MTS assay. The effect of Ag-NPs on bacterial pathogens was studied by determining their minimum inhibitory concentration (MIC) and minimum bactericidal concentration (MBC). In conclusion, it was observed that exposure of hMSCs to Ag-NPs of size <10 nm has no cytotoxic effect on the metabolic activity of the cells at the concentration of 3.5 μg/mL, with minimal cytotoxic effect being observed at the concentration of 14 μg/mL after 24 h of incubation. Our findings also confirmed that Ag-NPs at the concentration of 4 μg/mL are effective broad-spectrum bactericidal agents, regardless of the antibiotic-resistance mechanism present in bacteria.
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.
This is an animal model study to investigate changes in hemostasis during endotoxemic shock and to determine whether the combination of inhaled nitric oxide (iNO) + intravenous hydrocortisone had an effect on clot formation and fibrinolysis. iNO selectively decreases pulmonary artery pressure, without affecting cardiac index or systemic vascular resistance; however, the results of studies on the possible consequences of iNO administration on coagulation are inconsistent and require further research. Thirty-four piglets were included. Administering endotoxin caused severe hypodynamic shock. Half of the animals received iNO (30 ppm) + hydrocortisone, starting 3 h after endotoxin infusion and continuing to the end of the study. All animals developed coagulation disorders, manifested by a tendency to hypocoagulation; at the same time, fibrinolysis was impaired. Coagulation and fibrinolysis disorders persisted after endotoxin infusion was discontinued, with worse severity in the animals that died before the study was terminated. Administering iNO + hydrocortisone did not cause further changes in coagulation and fibrinolysis parameters, either during or after the endotoxin challenge, suggesting that potential therapeutic interventions with iNO to lower pulmonary arterial pressure will not affect hemostasis.
Vitamin D levels have been related to the severity and progression of various autoimmune disorders. In this study, we aimed to investigate the impact of genetic variability in the vitamin D receptor (VDR) gene on disease susceptibility and progression in patients with rheumatoid arthritis (RA) treated with tumor necrosis factor (TNF) inhibitors. The study comprises 121 RA patients subjected to anti-TNF therapy genotyped for four VDR polymorphic variants: rs1544410 (BsmI), rs2228570 (FokI), rs731236 (TaqI), and rs7975232 (ApaI). There was no significant association between RA susceptibility and VDR genetic variants. The study results revealed that patients with the rs2228570 CC genotype were characterized by lower vitamin D3 levels (p = 0.028) than those with the T allele. Also, the vitamin D3 levels (p = 0.029) and age at diagnosis (p = 0.017) were significantly lower in rs7975232 A allele carriers compared to CC homozygotes. However, after 6 months of therapy, the A allele seemed to be related to lower disease activity score 28 (DAS28) values (p = 0.030) and more common in patients who achieved remission (p = 0.004) compared to the CC genotype. Concerning other investigated polymorphisms, patients carrying rs1544410 AA and rs731236 CC homozygosity had lower C-reactive protein (CRP) levels before therapy (p = 0.009). In conclusion, VDR rs2228570 and rs7975232 polymorphic variants were found to be related to vitamin D3 levels. Moreover, the genotyping of rs7975232 was also useful in evaluating disease onset and disease activity after 6 months of therapy with TNF inhibitors in RA patients.
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.
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.
The immune system is regulated by a complex set of genetic, molecular, and cellular interactions. Rapid advances in the study of immunity and its network of interactions have been boosted by a spectrum of "omics" technologies that have generated huge amounts of data that have reached the status of big data (BD). With recent developments in artificial intelligence (AI), theoretical and clinical breakthroughs could emerge. Analyses of large data sets with AI tools will allow the formulation of new testable hypotheses open new research avenues and provide innovative strategies for regulating immunity and treating immunological diseases. This includes diagnosis and identification of rare diseases, prevention and treatment of autoimmune diseases, allergic disorders, infectious diseases, metabolomic disorders, cancer, and organ transplantation. However, ethical and regulatory challenges remain as to how these studies will be used to advance our understanding of basic immunology and how immunity might be regulated in health and disease. This will be particularly important for entities in which the complexity of interactions occurring at the same time and multiple cellular pathways have eluded conventional approaches to understanding and treatment. The analyses of BD by AI are likely to be complicated as both positive and negative outcomes of regulating immunity may have important ethical ramifications that need to be considered. We suggest there is an immediate need to develop guidelines as to how the analyses of immunological BD by AI tools should guide immune-based interventions to treat various diseases, prevent infections, and maintain health within an ethical framework.
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.
Antinuclear antibodies (ANAs) are critical immunological markers commonly associated with various connective tissue diseases (CTDs). However, these autoantibodies are also detectable in healthy individuals, patients with non-rheumatic autoimmune diseases, those with viral infections, and subjects using specific medications (such as procainamide, hydralazine, and minocycline) that can lead to drug-induced ANA elevation. The standard method for ANA detection is indirect immunofluorescence, a process that requires precision and thoroughness as it assesses both titer and fluorescence patterns. Additionally, immunoblotting and enzyme-linked immunosorbent assay (ELISA) are recommended to identify specific ANAs precisely, highlighting the importance of precision in ANA detection. This review explores the advantages and limitations of current ANA detection methods. It also describes the clinical implications of ANA presence in non-rheumatic diseases, including autoimmune disorders, infectious conditions, non-autoimmune and non-infectious diseases, and autoimmune cutaneous diseases. The presence of elevated ANA titers in these contexts can complicate clinical decision-making, as the diagnostic value of ANA testing alone is limited in non-rheumatic conditions. However, despite these limitations, ANA remains a key component in diagnosing and prognosis systemic CTDs, as it can indicate disease activity, severity, and response to treatment, which is of utmost importance in rheumatology and internal medicine. This paper provides a comprehensive review of the role of ANA in non-rheumatic diseases. It focuses on ANA diagnostic and prognostic significance and offers valuable insights for clinical practice.