Scavenger Receptor Class Research Articles

SR-B1 deficiency suppresses progression in acute myeloid leukemia via ferroptosis and reverses resistance to venetoclax.

SR-B1 deficiency suppresses progression in acute myeloid leukemia via ferroptosis and reverses resistance to venetoclax.

Characteristics and preliminary immune function of SRA5 in Lateolabrax maculatus.

Characteristics and preliminary immune function of SRA5 in Lateolabrax maculatus.

Flavivirus-NS1 triggers the Type-I interferon response through miR-145-5p mediated regulation of scavenger receptor class B1 in human cerebral microvascular endothelial cells.

Flavivirus-NS1 triggers the Type-I interferon response through miR-145-5p mediated regulation of scavenger receptor class B1 in human cerebral microvascular endothelial cells.

Expression of the cholesterol transporter SR-B1 in melanoma cells facilitates inflammatory signaling leading to reduced cholesterol synthesis.

Expression of the cholesterol transporter SR-B1 in melanoma cells facilitates inflammatory signaling leading to reduced cholesterol synthesis.

SCARA5 deficiency inhibits ferroptosis via regulating iron homeostasis and results in sorafenib resistance in hepatocellular carcinoma.

SCARA5 deficiency inhibits ferroptosis via regulating iron homeostasis and results in sorafenib resistance in hepatocellular carcinoma.

Role of Scavenger Receptor B1 (SR-B1) in Improving Food Benefits for Human Health.

Scavenger receptor class B member 1 (SR-B1) is a multiligand receptor with a broad range of functions spanning from the uptake of cholesteryl esters from high-density lipoproteins (HDLs) and transport of micronutrients such as fat-soluble vitamins and carotenoids across cell membranes to roles in tumor progression, pathogen recognition, and inflammatory responses. As a target of exposome factors such as environmental stressors and unhealthy lifestyle choices, as well as aging, dysregulated expression and activity of SR-B1 can negatively impact human health. Intriguingly, not only is SR-B1 a major determinant of nutrient homeostasis and, hence, metabolic health status, but these same nutrients and some phytochemicals have also demonstrated their ability to modulate SR-B1. Therefore, an integrated approach that, taking into account human health, nutrition, and food technology sciences, aims to produce foods with health-promoting effects should take advantage of the multifaceted properties of SR-B1. Improved functional foods and novel nanoparticle-based delivery systems, rich in nutrients and phytochemicals, with precise targeting to SR-B1 in specific tissues or structures could represent a strategic advance to improve human health and promote well-being.

Abstract 2824: Physiologic regulation of lipid oxidation and ferroptosis by vitamin E, high-density lipoprotein and scavenger receptor class B type 1

Abstract Introduction: Ferroptosis is a form of cell death caused by oxidative (-OOH) damage to phospholipids (PL) in the cell membrane. Understanding mechanisms of ferroptosis is important because of the role it plays in cancer. Previous work has focused on the intracellular antioxidant enzyme glutathione peroxidase 4 (GPx4), which detoxifies PL-peroxides (PL-OOH) and prevents ferroptosis. Studies show that alpha-tocopherol (α-toc), the active form of Vitamin E, is an exogenous lipophilic antioxidant that inhibits ferroptosis in cancer cells in vitro. The mechanisms by which α-toc engages cells to manipulate PL redox balance and ferroptosis are unknown. Lipoproteins, like high- and low-density lipoproteins (HDL and LDL), carry α-toc in the circulation. Using diffuse large B cell lymphoma (DLBCL) and clear cell renal cell carcinoma (ccRCC) models, two malignancies sensitive to ferroptosis, we show that lipoproteins, particularly HDL, deliver α-toc by binding the cell membrane receptor scavenger receptor class B type 1 (SR-B1) to prevent ferroptosis. Methods: Ramos (lymphoma), SUDHL4 (lymphoma) and 786-O (ccRCC) cell lines were used in these experiments. Ferroptosis was induced using ML210 and erastin. α-toc loading of native HDL and LDL was increased by incubation with free α-toc and spin filter purification. To isolate α-toc as the component responsible for modulating ferroptosis, we developed synthetic α-toc-loaded HDLs (sHDL). siRNAs were used to reduce SR-B1 and LDL Receptor (LDLR) expression. Blocker of lipid transport-1 (BLT-1) was used to inhibit uptake of lipoprotein cargo via SR-B1. Cell viability was measured by MTS assay and lipid peroxidation was measured by C11-BODIPY. Results: The α-toc level was higher in LDLs compared to HDLs (6.0 ± 0.1 α-toc/ apoB-100 vs. 1.0 ± 0.1 α-toc/ apoA-I) and increased in both HDL and LDL following incubation with free α-toc (α-toc LDL, 10.1 ± 0.1; α-toc HDL, 1.6 ± 0.3). HDL, α-toc HDL and α-toc LDL, but not LDL, rescued DLBCL and ccRCC cells from ferroptosis induced by the addition of ML210 and erastin, with a corresponding decrease in PL-OOH accumulation. Similarly, α-toc sHDLs, but not empty sHDLs, prevented ferroptosis in DLBCL and ccRCC. Knockdown of SR-B1 resulted in down-regulation of GPx4 expression and ferroptosis in ccRCC cells, requiring the use of BLT-1 to investigate SR-B1’s role in α-toc delivery. Addition of BLT-1 prevented α-toc lipoprotein rescue from ferroptosis. Knockdown of LDLR expression did not alter the ability of HDL and α-toc HDL to prevent ferroptosis and enhanced the ability of α-toc LDL to prevent ferroptosis. Conclusion: We reveal a tunable cellular redox axis whereby HDLs containing α-toc target SR-B1 to reduce PL-OOH and prevent ferroptosis. Accordingly, this work reveals that the α-toc / HDL/ SR-B1 axis of ferroptosis prevention must be accounted for when targeting ferroptosis in vivo. Citation Format: Jonathan S. Rink, Andrea E. Calvert, Adam Y. Lin, SonBihn T. Nguyen, Leo I. Gordon, C Shad Thaxton. Physiologic regulation of lipid oxidation and ferroptosis by vitamin E, high-density lipoprotein and scavenger receptor class B type 1 [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2025; Part 1 (Regular Abstracts); 2025 Apr 25-30; Chicago, IL. Philadelphia (PA): AACR; Cancer Res 2025;85(8_Suppl_1):Abstract nr 2824.

Abstract 4467: Receptor targeted delivery of the multi-kinase inhibitor F7/PIK-75 by organic-core templated lipid nanoparticles as cancer therapy

Abstract Introduction: PIK-75 is a potent multi-kinase inhibitor, targeting p110α, p38γ and DNA-PKs. We and others have demonstrated that PIK-75 is effective against a diverse range of malignancies, including prostate cancer, cutaneous T-cell lymphomas, acute myeloid leukemia (AML) and pancreatic cancer, among others. However, PIK-75 is hydrophobic and difficult to deliver to target tissues, which has limited clinical development. To address these limitations, we developed a bio-inspired delivery platform for PIK-75 that has some features of natural high-density lipoproteins (HDL). We employed an organic core (oc) template to synthesize HDL-like nanoparticles (ocHDL NP) with size, shape, surface composition and targeting functions similar to mature, spherical, naturally occurring HDLs. The ocHDL NPs target and bind to the high-affinity HDL receptor scavenger receptor class B type 1 (SR-B1). SR-B1 is often over-expressed in cancer, making it an ideal target for drug delivery. Therefore, we hypothesized that ocHDL NPs can deliver PIK-75 via SR-B1 to cancer cells to induce cell death in vitro and in vivo. Methods: PIK-75 ocHDL NPs were synthesized by combining an oc with PIK-75, phospholipids and the HDL-defining apolipoprotein A-I. Following spontaneous self-assembly the PIK-75 ocHDL NP were purified by dialysis. PIK-75 ocHDL NPs were characterized for size, surface charge and drug loading. In vitro efficacy was assessed in prostate cancer cell lines (CWRR1, LnCaP), AML cell lines (HEL, KASUMI-1, BDCM, KG1a), and the NCI-60 panel + 6 pancreatic cancer cell lines. An SR-B1 blocking antibody and small molecule inhibitor of SR-B1 were used to demonstrate SR-B1-mediated delivery of PIK-75 by ocHDL NPs. In vivo efficacy was assessed in a prostate cancer tumor xenograft model. Results: PIK-75 was successfully incorporated into the ocHDL NP platform. Data demonstrate PIK-75 ocHDL NP had 20 ± 1 PIK-75/ NP. PIK-75 ocHDL NPs specifically target SR-B1 and deliver PIK-75 to inhibit its kinase targets, as measured by flow cytometry and western blotting. PIK-75 ocHDL NPs potently induced cell death in all cell lines tested, with average IC50s for prostate cancer (1.58 nM), AML (2.50 nM), pancreatic cancer (10.56 nM) and NCI60 panel (3.09 nM) in the low nanomolar range. PIK-75 ocHDL NPs significantly reduced tumor growth in a murine model of castrate resistant prostate cancer and there were no obvious untoward side effects. Conclusions: ocHDL NPs can be successfully loaded with hydrophobic drug cargo, such as PIK-75, to enable SR-B1 targeting and delivery of PIK-75 to cancer cells. PIK-75 ocHDL NPs potently induced cell death across a wide array of malignancies in vitro, and in an in vivo prostate cancer xenograft model. These results provide proof-of-principle that ocHDL NPs can be successfully leveraged to deliver hydrophobic small molecule drugs in a receptor targeted manner. Citation Format: Jonathan S. Rink, Andrea E. Calvert, David Kwon, Xu Hannah Zhang, Hongwei H. Yin, David Horne, SonBinh T. Nguyen, Adam Y. Lin, Steven T. Rosen, Leo I. Gordon, C Shad Thaxton. Receptor targeted delivery of the multi-kinase inhibitor F7/PIK-75 by organic-core templated lipid nanoparticles as cancer therapy [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2025; Part 1 (Regular Abstracts); 2025 Apr 25-30; Chicago, IL. Philadelphia (PA): AACR; Cancer Res 2025;85(8_Suppl_1):Abstract nr 4467.

Biodistribution of Reconstituted High-Density Lipoprotein Nanoparticles for Targeted Delivery to Retinal Ganglion Cells.

Purpose: Nanoparticle-based drug delivery systems offer a promising approach for overcoming the challenges of ocular drug delivery. Our study evaluated the biodistribution and potential targeting of reconstituted high-density lipoprotein nanoparticles (rHDL NPs) loaded with near-infrared dye IR780 to retinal ganglion cells (RGCs) and optic nerve head astrocytes (ONHAs) as a model for neuroprotective drug delivery in glaucoma. Methods: A stable rHDL-payload complex was formulated using IR780, phosphatidylcholine, and apolipoprotein A-I (Apo A-I) by using a novel preparation method. Fluorescent rHDL (rHDL-IR780) was assessed for cellular uptake in primary human ONHAs in vitro, whereas scavenger receptor class B1 (SR-B1) expression was confirmed by Western blot. Receptor-mediated uptake was examined by SR-B1 receptor blocking. Ex vivo biodistribution was evaluated by intravitreal injection of rHDL into postmortem human donor eyes. Results: Spectroscopic analysis confirmed IR780 encapsulation in rHDL NPs. Blocking SR-B1 receptors significantly reduced IR780 uptake by ONHAs, supporting an SR-B1-mediated delivery mechanism, in addition to confirming SR-B1 expression in human retinal lysates. In ex vivo experiments, 4 h postinjection, IR780 localized in the retinal nerve fiber and ganglion cell layers. By 24 h, IR780 penetrated deeper retinal layers, achieving RGC uptake. Conclusions: Our findings demonstrate that rHDL NPs facilitate targeted delivery to retinal tissues through an Apo A-I/SR-B1 pathway, overcoming ocular barriers to reach RGCs. This study supports the potential of rHDL NPs as a platform for neuroprotective drug delivery to treat glaucoma, enhancing both pharmacokinetics and targeted cellular uptake.

Toxicological impacts of neoteric Vip3A toxins from Bacillus thuringiensis on survival and development of Spodoptera frugiperda and S. litura

ABSTRACT The toxicity of Vip3A proteins encoded by vip3Aa44, vip3Aa67, vip3Aa68, vip3Aa69 and vip3Aa72 genes previously cloned from Indian Bacillus thuringiensis isolates and BGSC strains in our laboratory was investigated toward Spodoptera frugiperda (Fall army worm, Lepidoptera: Noctuidae) and S. litura (tobacco cutworm/ cotton leaf worm, Lepidoptera: Noctuidae). Diet incorporation bioassays were performed using five toxins for S. frugiperda and three toxins for S. litura neonates. The LC50 values for S. frugiperda and S. litura ranged from 1.381 to 13.509 ppm and 3.538 to 13.233 ppm, respectively, indicating higher susceptibility of S. frugiperda towards these toxins as compared with S. litura. Investigation of the impact of expressed Vip3A proteins on the development of S. frugiperda and S. litura revealed considerable post-larval mortality along with various sub-lethal effects on growth and fecundity. These sub-lethal effects encompassed reductions in larval and pupal weights across the concentration spectrum, prolonged generation period, and malformations in pupae and adults. Vip3Aa69 protein was found to be the most toxic among all proteins tested for both insects. Together with our previous study, in which Vip3Aa69 was found to be most toxic to Helicoverpa armigera, this toxin has the potential for biocontrol of multiple agriculturally important lepidopteran pests. Preliminary molecular docking of Vip3Aa44 and Vip3Aa69 proteins to Fibroblast growth factor receptor-like protein (Sf-FGFR) and Scavenger Receptor Class C like Protein (Sf-SR-C), the reported receptors in S. frugiperda, showed similar binding interactions for these toxins.

Intestinal Activation of LXRα Counteracts Metabolic-Associated Steatohepatitis Features in Mice.

Background/Objectives: Metabolic dysfunction-associated steatotic liver disease (MASLD) is a growing global health problem and the discovery of drugs is challenging. In this study, we aimed to investigate the effects of intestinal activation of the liver X receptor (LXR)α on MASH. Methods: An intestinal-specific LXRα activation model in mice was established and subjected to MASH development by combining a Western diet and carbon tetrachloride. Lipid metabolism, reverse cholesterol transport (RCT), steatosis, inflammation, and fibrosis were evaluated. In vitro models of steatosis and fibrosis were used to explore the role of scavenger receptor class B type 1 (SRB1). Results: We found that the intestinal activation of LXRα improved several MASLD features, including levels of triglycerides, RCT, steatosis, systemic and hepatic inflammatory profiles, and liver fibrosis. These effects were associated with increased high-density lipoprotein (HDL) levels and hepatic SRB1 expression. In vitro depletion of SRB1 hampered the beneficial effects of HDL on steatosis and fibrogenesis in liver cells by altering the activation of both peroxisome proliferator-activated receptors γ and small mothers against decapentaplegic homolog protein (SMAD)2/3 proteins. Conclusions: Our findings showed that the intestinal activation of LXRα and a parallel induction of hepatic SRB1 are protective against inflammation, steatosis, and advanced liver fibrosis in MASLD.

Keratinocyte SR-B1 expression and targeting in cytokine-driven skin inflammation

BackgroundStrategies to treat inflammatory skin conditions require identifying new targets involved in interactions between overlying epithelial and underlying dermal immune cells. Scavenger receptor class B type 1 (SR-B1) is a cell surface receptor that binds high-density lipoproteins (HDL) and mediates inflammatory responses in immune and endothelial cells. The SR-B1 receptor is also expressed in keratinocytes, but its role in inflammatory skin diseases remains unexplored.MethodsTo investigate keratinocyte SR-B1 in the setting of inflammation, we measured its expression in skin biopsy samples obtained from patients with psoriasis; human skin explants exposed to the inflammatory cytokine, interleukin-17A (IL-17A); and mouse skin exposed to the pro-inflammatory agent, imiquimod (IMQ). We also evaluated the effects of SR-B1 knockdown on primary keratinocyte responses to IL-17A. Finally, we employed a synthetic HDL-nanoparticle (HDL NP) to investigate the therapeutic potential of targeting SR-B1 in IL-17A-stimulated keratinocytes and in male C57BL/6 mice with IMQ-induced skin inflammation.ResultsOur data show SR-B1 expression is increased in diseased human skin and in both human and mouse models of skin inflammation. SR-B1 knockdown in keratinocytes exacerbates the inflammatory response to IL-17A, whereas targeting SR-B1 with HDL NP attenuates this response. In the IMQ murine model, topical application of HDL NPs improves the skin phenotype, normalizes SR-B1 expression, and reduces molecular and cellular markers of inflammation.ConclusionsOverall, SR-B1 plays a role in skin inflammation and HDL NP-mediated targeting of SR-B1 in keratinocytes may offer a targeted new therapy for inflammatory skin disease.

Transcytosis of LDL Across Arterial Endothelium: Mechanisms and Therapeutic Targets.

Transport of LDL (low-density lipoprotein) from plasma to arterial intima is thought to be rate limiting in the development of atherosclerosis. Its variation likely determines where lesions develop within arteries and might account for some of the currently unexplained difference in disease susceptibility between individuals. It may also be critical in the development of lipid-rich, unstable plaques. Mechanisms have been controversial but recent evidence suggests that caveolar transcytosis across endothelial cells is the dominant pathway. Receptors involved are LDLR (LDL receptor), SR-B1 (scavenger receptor class B type 1), and ALK1 (activin receptor-like kinase 1). The role of LDLR is influenced by IL-1β (interleukin-1β); the role of SR-B1 by HDL (high-density lipoprotein), DOCK4 (dedicator of cytokinesis 4), GPER (G-protein-coupled estrogen receptor), and HMGB1 (high mobility group box 1); and the role of ALK1 by BMP (bone morphogenetic protein) 9. Additionally, BMP4 stimulates transcytosis and FSTL1 (follistatin-like 1 protein) inhibits it. Fundamental transcytotic mechanisms include caveola formation, undocking, trafficking, and docking; they are influenced by cholesterol-lowering agents, MYDGF (myeloid-derived growth factor), MFSD2a (major facilitator superfamily domain containing 2a) in the blood-brain barrier, and inhibitors of dynamin-2 and tubulin polymerization. The relative merits of different therapeutic approaches are discussed, with statins, colchicine, benzimidazoles, and metformin being existing drugs that might be repurposed and salidroside and glycyrrhizic acid being nutraceuticals worth investigating. Finally, we discuss evidence against the ferry-boat model of transcytosis, the contributions of receptor-mediated, fluid-phase, and active transcytosis, and where inhibition of transcytosis might be most beneficial.

Effect of metformin on the endometrial proteome of diet-induced obese mice.

Obesity is known to have detrimental effects on female fertility, influencing both ovarian and endometrial functions. There is evidence that endometrial function is altered in obese and/or insulin-resistant women. Metformin, an insulin-sensitizing drug, has shown potential in treating metabolic and reproductive disorders, including polycystic ovary syndrome (PCOS) and may enhance fertility outcomes by improving endometrial dysfunction. Using a mouse model, this study aimed to investigate how a high-fat diet impacts endometrial-specific protein expression and whether metformin can mitigate these effects. C57BL/6N mice were fed a standard or high-fat diet and either received metformin treatment or did not. Proteomic analyses revealed significant alterations in endometrial protein expression due to the high-fat diet, while metformin administration appeared to restore many of these changes to normal levels. Metformin's impact was evident through alterations in specific proteins associated with reproductive health and metabolic functions, such calcium-independent phospholipase A2-gamma, ATP-binding cassette sub-family D member 1, RAC-beta serine/threonine-protein kinase, acyl-CoA:lysophosphatidylglycerol acyltransferase 1, O-GlcNAcase, scavenger receptor class A member 3, protein kinase C beta type, sortilin, beta-2-microglobulin and apolipoprotein C-III. These results suggest a potential therapeutic role for metformin in normalizing endometrial protein expression, providing insights into how this drug could improve fertility outcomes in obese or insulin-resistant females, besides normalizing ovulation patterns. Overall, this study enhances our understanding of the relationship among obesity, endometrial function and metformin's therapeutic potential, offering a foundation for further research into reproductive health and metabolic disorders.

Integrative proteomic and lipidomic analysis of GNB1 and SCARB2 knockdown in human subcutaneous adipocytes.

Obesity, a global public health concern, is influenced by various factors, including genetic predispositions. Although many obesity-associated genes have been identified through genome-wide association studies (GWAS), the molecular mechanisms linking these genes to adipose tissue function remain largely unexplored. This study integrates proteomic data on adipocyte fat accumulation with GWAS data on obesity to unravel the roles of the identified key candidate genes - G protein subunit beta 1 (GNB1) and scavenger receptor class B member 2 (SCARB2) - involved in fat accumulation. We utilized RNA interference to knock down GNB1 and SCARB2 in human subcutaneous adipocytes, followed by lipidome and proteome analyses using mass spectrometry. Knockdown of these genes resulted in a reduction in lipid droplet accumulation, indicating their role in adipocyte lipid storage. Digital PCR confirmed effective gene knockdown, with GNB1 and SCARB2 mRNA levels significantly reduced. In total, the lipidomic analysis identified 96 lipid species with significant alterations. GNB1 knockdown resulted in a decrease in cholesterol esters and an increase in phosphatidylcholines, phosphatidylinositols, and ceramides. SCARB2 knockdown also led to an increase in phosphatidylcholines, with a trend towards decreased triacylglycerols. Proteomic analysis revealed significant changes in proteins involved in lipid metabolism and adipocyte function, including PLPP1 and CDH13, which were upregulated following GNB1 knockdown, and HSPA8, which was downregulated. Conversely, SCARB2 knockdown resulted in the downregulation of PLPP1 and METTL7A, and the upregulation of PLIN2, HSPA8, NPC2, and SQSTM1. Our findings highlight the significant roles of GNB1 and SCARB2 in lipid metabolism and adipocyte function, providing insights that could inform therapeutic strategies targeting these regulatory genes in obesity.

The role and mechanism of quercetin in improving late-onset hypogonadism through network analysis and experimental validation.

The rising incidence of late-onset hypogonadism (LOH) profoundly diminishes the quality of life in men due to declining testosterone levels. Quercetin is an important active metabolite in various traditional botanical drugs that enhance male fertility, yet its mechanisms of action remain unclear. This study delves into the therapeutic potential and underlying mechanisms of quercetin in LOH management, proposing novel treatment strategies. An aging murine model was created and treated with quercetin starting at 12weeks of age. Sperm parameters were evaluated, and serum and testicular testosterone and inflammatory cytokines were quantified via ELISA. Histological analyses of testicular tissue were performed. Network analysis and molecular docking studies predicted quercetin's therapeutic pathways in LOH. Key proteins involved in testosterone synthesis and testicular aging were verified using western blotting and immunofluorescence. Aged TM3 cells were treated with quercetin to corroborate the effects on testicular Leydig cells. In the murine model, the quercetin treatment group showed an increase in sperm average path velocity (VAP) by 1.21 ± 0.087-fold (p < 0.01), an increase in straight-line velocity (VCL) by 1.12 ± 0.18-fold (p < 0.01), a rise in serum testosterone levels by 0.27 ± 0.48-fold (p < 0.05), and an increase in testosterone levels in testicular tissue by 0.30 ± 0.20-fold (p < 0.05), while IL-1β levels decreased to 0.61 ± 0.13-fold (p < 0.01) compared to the aging group. Network analysis suggested quercetin's efficacy in LOH may be mediated through the AR and PI3K/AKT pathways. In quercetin-treated aged mice, a reduction in γH2AX and an increase in Ki67 expression were observed in testicular tissue, alongside upregulated expression of key testosterone synthesis proteins-steroidogenic acute regulatory (STAR) and scavenger receptor class B type 1 (SRB1), accompanied with enhanced AR expression and AKT1 phosphorylation. Similar results were confirmed in testicular Leydig cells. Compared to the group treated with bleomycin alone, the bleomycin plus quercetin treatment group showed a reduced positive area in β-gal staining, downregulation of the senescence-associated marker γH2AX, increased expression of the key testosterone synthesis protein SRB1, and elevated levels of expression of quercetin's potential target AR as well as phosphorylation of AKT1. Quercetin ameliorates the aging of testicular Leydig cells and promotes testosterone synthesis through modulation of the AR/PI3K/AKT signaling pathway, presenting a promising therapeutic approach for LOH.

SR-A3 suppresses AKT activation to protect against MAFLD by inhibiting XIAP-mediated PTEN degradation

Scavenger receptor class A member 3 (SR-A3) is implicated in metabolic diseases; however, the relationship between SR-A3 and metabolic dysfunction-associated fatty liver disease (MAFLD) has not been documented. Here, we show that hepatic SR-A3 expression is significantly reduced in human and animal models in the context of MAFLD. Genetic inhibition of SR-A3 in hamsters elicits hyperlipidemia, hyperglycemia, insulin resistance, and hepatic steatosis under chow-diet condition, yet escalates in diet-induced MAFLD. Mechanistically, SR-A3 ablation enhances E3 ligase XIAP-mediated proteasomal ubiquitination of PTEN, leading to AKT hyperactivation. By contrast, hepatic overexpression of human SR-A3 is sufficient to attenuate metabolic disorders in WT hamsters fed a high-fat-high-cholesterol diet and ob/ob mice via suppressing the XIAP/PTEN/AKT axis. In parallel, pharmacological intervention by PTEN agonist oroxin B or lipid lowering agent ezetimibe differentially corrects MAFLD in hamsters.

Transporters in vitamin uptake and cellular metabolism: impacts on health and disease

Abstract Vitamins are vital nutrients essential for metabolism, functioning as coenzymes, antioxidants, and regulators of gene expression. Their absorption and metabolism rely on specialized transport proteins that ensure bioavailability and cellular utilization. Water-soluble vitamins, including B-complex and vitamin C, are transported by solute carrier (SLC) family proteins and ATP-binding cassette (ABC) transporters for efficient uptake and cellular distribution. Fat-soluble vitamins (A, D, E, and K) rely on lipid-mediated pathways through proteins like scavenger receptor class B type I (SR-BI), CD36, and Niemann-Pick C1-like 1 (NPC1L1), integrating their absorption with lipid metabolism. Defective vitamin transporters are associated with diverse metabolic disorders, including neurological, hematological, and mitochondrial diseases. Advances in structural and functional studies of transport proteins highlight their tissue-specific roles and regulatory mechanisms, shedding light on their impact on health and disease. This review emphasizes the significance of vitamin transporters and their potential as therapeutic targets for deficiencies and related chronic conditions.

Scavenger receptor class B member 1 promotes lung cancer growth and metastasis through enhanced twist family BHLH transcription factor 1 signaling in vitro and in vivo: Exploration of RPPNs as a therapeutic Strategy.

Lung cancer remains a leading cause of cancer-related mortality worldwide. Although scavenger receptor class B member 1 (SCARB1), a crucial cell surface receptor, plays a vital role in various cancers, its function in lung cancer remains incompletely elucidated. This study aims to investigate the role and molecular mechanisms of SCARB1 in lung cancer progression and develop a novel SCARB1-targeted nanoparticle drug delivery system. We analyzed SCARB1 expression levels in lung cancer tissues and their correlation with patient prognosis using the Cancer Genome Atlas database. In vitro experiments, including quantitative real-time polymerase chain reaction, Western blot, 5-ethynyl-2'-deoxyuridine, colony formation, and Transwell analyses, were conducted to study the effects of SCARB1 on lung cancer cell proliferation, invasion, and migration. A lung metastasis model was established through tail vein injection to evaluate the role of SCARB1 in promoting lung cancer metastasis in vivo. We also developed red blood cell membrane-coated poly (lactic-co-glycolic acid) nanocarriers loaded with paclitaxel (RPPNs) and assessed their effect on SCARB1 expression and lung cancer progression. SCARB1 was overexpressed in human lung cancer tissues and significantly associated with poor patient prognosis. In vitro experiments confirmed that silencing SCARB1 inhibited lung cancer cell growth, invasion, and migration. SCARB1 overexpression promoted lung cancer cell proliferation, migration, and epithelial-mesenchymal transition through twist family BHLH transcription factor 1 (Twist1) activation. In vivo experiments further validated the crucial role of SCARB1 in promoting lung cancer metastasis. The developed RPPNs effectively suppressed SCARB1 expression in lung cancer and demonstrated superior inhibitory effects compared with traditional RPPNs. However, SCARB1 overexpression partially antagonized the antimetastatic effects of RPPNs. This work elucidates, for the 1st time, the molecular mechanism by which SCARB1 promotes lung cancer growth and metastasis through the activation of the Twist1 signaling pathway and develops a novel SCARB1-targeted nanoparticle drug delivery system, namely RPPNs. The findings of this work not only deepen our understanding of the molecular mechanisms underlying lung cancer progression but also provide new strategies for lung cancer diagnosis and treatment.

Adipocyte-derived glutathione promotes obesity-related breast cancer by regulating the SCARB2-ARF1-mTORC1 complex.

Adipocyte-derived glutathione promotes obesity-related breast cancer by regulating the SCARB2-ARF1-mTORC1 complex.