Immunomodulatory Properties Research Articles

Abstract 6571: Natural killer cell-derived exosomes encapsulated with IL-12 as nanocarriers for cancer immunotherapy

Abstract Cold tumors, owing to poor immune cell infiltration, immunosuppressive tumor microenvironment (TME) and low immunogenicity, are marked as a therapeutic challenge in cancer. Immunomodulatory cytokines showed encouraging outcomes in clinical settings by converting TME more immunoresponsive. Among the cytokines, IL-12 has drawn attention for its role in bridging innate and adaptive immunity, by inducing the proliferation and activation of NK and T cells. IL-12 enhances antigen-specific cell-mediated immunity by promoting Th1 immunity that in turn boosts IFN-γ production and inhibits angiogenesis. It also drives M2 to M1 macrophage polarization, enhances the infiltration of tumor-targeting immune cells, and depletes immunosuppressive cells. This action is critical in converting "cold" into "hot" tumors, making them more susceptible to immunotherapy. Additionally, IL-12 has a short plasma half-life and shows systemic toxicity which limits its use in clinical settings. We aim to deliver IL-12 encapsulating inside NK cell derived nanovesicle (NKnvs) which will bring many attributes- small size of NKnvs will facilitate better tumor accumulation, encapsulation will enhance the plasma half-life of IL-12, slow release of payload will-lower the dose-limiting systemic toxicity, NKnvs will carry cytotoxic proteins, miRNAs, and cytokines with tumor-killing and immunomodulatory properties. NKnvs was isolated by differential ultracentrifugation method, the purity of the isolated NKnvs was determined by Western blot. NTA, DLS and SEM was performed to determine the concentration, size and morphology of NKnvs. Next, IL-12 was encapsulated inside NKnvs by probe sonication method and the loading percentage was quantified by ELISA. To visualise the accumulation of NKnvs in different tissues and to determine the plasma half-life, NKnvs was labelled with DiI dye and purified by size exclusion chromatography. NKnvs showed the hydrodynamic radius and zeta potential of 189±20.61 nm and -10.5±10.1 mV respectively. SEM confirmed the spherical morphology of NKnvs. Loading percentage of IL-12 inside NKnvs was found 20.5±0.5 %. NKnvs induced activation and polarization of immune cells, enhancing tumor cell killing. Pharmacokinetic analysis indicated that NKnvs extended the half-life of the payload. The biodistribution study revealed that DiI labelled NKnvs showed enhanced tumor accumulation which also increased till 48 hrs. In conclusion, the developed nanoformulation offers a promising strategy to target the tumor microenvironment, improving therapeutic efficacy and reducing systemic toxicity. Further, the efficacy of immunovesicle (IL-12 NKnvs) can be explored in-vivo to determine the further therapeutic benefits associated with the developed nanoformulation. Citation Format: Monu Pandey, Vidit Gaur, Jayanta Bhattacharyya. Natural killer cell-derived exosomes encapsulated with IL-12 as nanocarriers for cancer immunotherapy [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 6571.

Abstract 3819: Modeling T cell and cancer cell interactions to examine immune checkpoint inhibition resistance in pancreatic cancer

Abstract Pancreatic cancer (PC) is a lethal cancer, with ∼90% of patients dying within 5 years. This dire statistic underscores the limitations of current treatments and the need for improved therapeutic approaches. Immune checkpoint inhibition (ICI) has shown promise in promoting long-term progression-free survival across various cancers by reactivating a patients’ latent anti-cancer immune response. However, PC is almost completely resistant to ICI, highlighting the incomplete understanding of immune-cancer interactions in this disease. The tumor microenvironment is a key factor in immunotherapy resistance in PC, where immunosuppressive immune cells and cancer-associated fibroblasts (CAFs) act to inhibit T cell function. Additionally, the extracellular matrix (ECM) landscape of PC presents a physical barrier to T cell infiltration and motility within the tumor. Developing strategies to overcome these barriers has been challenging, partly due to the difficulty in replicating the complex PC tumor microenvironment in experimental models. The use of 3D cancer tumoroid cultures enables modeling of cancer and stromal cells spatial arrangements, mimicking native tumor microenvironments and facilitating high resolution examination of cell-to-cell and cell-to-environment interactions. However, most tumoroid cultures often use commercial matrix products like basement membrane extracts (BME), which poorly recapitulate the distinct biochemical and mechanical properties inherent to PC tumors. Here, we utilize the Inventia RASTRUMTM platform to create 3D cancer/CAF/T cell co-cultures based on synthetic PEG-based hydrogel matrices, which were tuned to mimic the stiffness and ECM composition of PC tumors. Using real-time longitudinal imaging and 3D image analysis pipelines, we visualize cancer-stromal cell interactions, which are obscured in conventional BME-based models. We also investigate the role of CAFs in supporting immune evasion and highlight the effect of multiple immunomodulators on cancer/T cell behavioral dynamics. Overall, our approach provides a scalable in vitro framework to dissect cell-to-cell interactions and offers a platform to the profile immunomodulatory properties of drugs. Future work using this platform will focus on molecular profiling of cancer-CAF-T cell interactions to provide predictive data aiding the rational design and evaluation of ICI combination therapies prior to pre-clinical in vivo work and clinical translation. Citation Format: Aji Istadi, Inna Navarro, Silvia Lombardi, Dannielle Upton, Mezzalina Vankan, Cesar Moreno, Michael Trpceski, Cecilia Chambers, David Hermann, Marco Herold, Paul Timpson, Sean Porazinski, Greg Neely, Marina Pajic. Modeling T cell and cancer cell interactions to examine immune checkpoint inhibition resistance in pancreatic cancer [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 3819.

Effects of Vitamin D, Melatonin, and Omega-3 Fatty Acids on Periodontal Health: A Narrative Review

Periodontitis is a chronic inflammatory disease characterized by the destruction of tooth-supporting structures, influenced by immune system dysregulation, oxidative stress, and imbalances in bone metabolism. Given its multifactorial pathogenesis, bioactive compounds such as vitamin D, melatonin, and omega-3 fatty acids have emerged as potential adjuncts to periodontal therapy due to their immunomodulatory, anti-inflammatory, and antioxidative properties. This narrative review explores the role of these three supplements in periodontal health, their potential in synergistic effects, and existing research gaps, providing a foundation for future studies on their clinical applications. Vitamin D is essential for calcium homeostasis, bone remodeling, and immune function. It modulates both innate and adaptive immune responses, enhancing antimicrobial peptide production and reducing inflammatory cytokine expression. Omega-3 fatty acids reduce the production of pro-inflammatory eicosanoids while promoting the synthesis of pro-resolving lipid mediators, contributing to bone preservation and immune balance. Melatonin, known for its antioxidant and osteogenic properties, supports bone remodeling by stimulating osteoblast proliferation and inhibiting osteoclast activity, while also regulating circadian rhythms, which may influence oral health. Although these bioactive compounds show promising effects in preclinical and clinical studies, significant knowledge gaps remain regarding optimal dosages, long-term efficacy, combined use, and standardized treatment protocols. Further clinical trials are necessary to elucidate their therapeutic value in periodontal disease management, especially those focused on their potential synergistic mechanisms. Understanding their synergistic mechanisms may open new avenues for adjunctive strategies in periodontal therapy.

Mesenchymal Stem Cells in Veterinary Medicine—Still Untapped Potential

Mesenchymal stem cells (MSCs) hold significant therapeutic potential in veterinary medicine due to their regenerative and immunomodulatory properties. This review examines the clinical applications of MSCs across multiple animal species, including equine, canine, feline, and bovine medicine. MSC therapies have demonstrated promising outcomes in treating musculoskeletal disorders, osteoarthritis, inflammatory diseases, and tissue injuries, particularly in horses and dogs. In cats, MSCs show potential for managing chronic kidney disease, inflammatory bowel disease, and asthma, while in bovine medicine, they offer alternative treatment approaches for mastitis and orthopedic injuries. Despite these advancements, challenges such as treatment standardization, cell sourcing, and potential adverse effects, including tumorigenicity, remain under investigation. The emerging field of MSC-based veterinary medicine highlights its capacity to enhance healing, reduce inflammation, and improve clinical outcomes. However, further research is necessary to optimize treatment protocols and address safety concerns, ensuring the widespread adoption of MSC therapies in veterinary practice.

Therapeutic potential of ADSC-derived exosomes in acute lung injury by regulating macrophage polarization through IRF7/NLRP3 signaling.

Therapeutic potential of ADSC-derived exosomes in acute lung injury by regulating macrophage polarization through IRF7/NLRP3 signaling.

Imine Crosslinked, Injectable, and Self-Healing Fucoidan Hydrogel with Immunomodulatory Properties.

Biomaterials with inherent anti-inflammatory properties and the ability to foster a pro-regenerative environment hold significant promise for enhancing cell transplantation and tissue regeneration. Fucoidan, a sulfated polysaccharide with well-documented immune-regulatory and antioxidant capabilities, offers strong potential for creating such biomaterials. Yet, there is a lack of engineered fucoidan hydrogels that are injectable and provide tunable physicochemical properties. In this study, the ability of fucoidan to undergo periodate-mediated oxidation is leveraged to introduce aldehydes into backbone (oxidized fucoidan, OFu), enabling the formation of reversible, imine-crosslinks with amine-containing molecules such as gelatin. The imine-crosslinked OFu-gelatin hydrogel provided excellent control over gelation rate and mechanical properties. Counter-intuitively, OFu-gelatin hydrogel exhibited excellent long-term stability (≥28 days), even though imine crosslinks are known to be relatively less stable. Moreover, the OFu-gelatin hydrogels are self-healing, injectable, and biocompatible, supporting cell culture and encapsulation. Furthermore, fucoidan hydrogels displayed immune-modulatory properties both in vitro and in vivo. This innovative injectable fucoidan hydrogel presents a versatile platform for applications in tissue engineering and regenerative medicine.

Can pyridoxine function as an anti-pyroptosis agent? A narrative review.

Pyroptosis, a highly inflammatory form of programmed cell death, plays a key role in diseases such as sepsis, rheumatoid arthritis, Alzheimer's disease, and COPD. It is driven by inflammasome activation, leading to the release of pro-inflammatory cytokines. Pyridoxine (Vitamin B6), an essential micronutrient with known anti-inflammatory effects, has been suggested as a potential regulator of inflammasome activation and pyroptosis. This review examines current evidence on pyridoxine's role in modulating pyroptosis. A literature search was conducted in PubMed, Scopus, and Web of Science for studies published between 2014 and 2024. The search focused on pyridoxine's relationship with inflammation, inflammasomes, and pyroptosis pathways using keywords such as "pyridoxine," "Vitamin B6," "pyroptosis," "inflammasome," "caspase-1," and "gasdermin D." Both preclinical and human studies were reviewed, with emphasis on molecular mechanisms underlying pyridoxine's anti-inflammatory effects. Studies consistently showed that pyridoxine reduced inflammasome activation, decreased pro-inflammatory cytokine production, and inhibited caspase-1 (CASP-1) activity, thereby suppressing pyroptosis. Human studies, though indirect, linked higher pyridoxine levels to reduced systemic inflammation, suggesting a possible anti-pyroptotic effect. Pyridoxine shows potential as an anti-pyroptotic agent due to its anti-inflammatory and immunomodulatory properties. However, further well-designed clinical trials are needed to confirm its role in controlling pyroptosis, especially in diseases associated with excessive inflammasome activation.

Ligilactobacillus salivarius Lac45 inhibits MRSA and suppresses inflammation in human keratinocyte.

Dysbiosis, an imbalance in skin microflora, is a key contributor to inflammatory skin conditions, including atopic dermatitis (AD), seborrheic dermatitis (SD), and psoriasis. In AD, Staphylococcus aureus colonization of skin lesions is prevalent approximately 70% of cases, with disease severity positively correlating with bacterial presence. Moreover, methicillin-resistant Staphylococcus aureus (MRSA) is found in 10-30% of AD skin lesions, highlighting the need for novel therapeutic strategies that target both microbial imbalance and inflammation. This study evaluates Ligilactobacillus salivarius Lac45 (LS-Lac45), a breast milk-derived bacterial strain, for its antimicrobial and anti-inflammatory potential in dermatology. We assessed its antimicrobial activity against MRSA using an agar disk-diffusion assay and its anti-inflammatory effects in a peptidoglycan (PGN)-induced inflammation model in HaCaT keratinocytes. To elucidate its mechanisms of action, mass spectrometry was used to analyze protein expression changes in LS-Lac45-treated keratinocytes. Our results demonstrate that live LS-Lac45 effectively inhibits MRSA growth. Additionally, heat-killed LS-Lac45 significantly reduces PGN-induced production of pro-inflammatory cytokines IL-6, IL-8, and TNF-α. Proteomic analysis further identifies LS-Lac45-mediated modulation of immune-related proteins, including heat shock protein 60, metallothionein 2A, and antioxidant-1, suggesting a role in inflammatory regulation. These findings highlight LS-Lac45 as a candidate for managing MRSA-associated inflammatory skin conditions, particularly AD. While this study provides key insights into its antimicrobial and immunomodulatory properties, further research is needed to evaluate its probiotic characteristics and clinical applicability in dermatology.

Fine-tuning licensing strategies to boost MSC-based immunomodulatory secretome

BackgroundImmune-mediated inflammatory diseases (IMIDs) are a major global health challenge, affecting millions of people and often lacking effective treatments. The mesenchymal stromal cell (MSC)-derived secretome has emerged as a promising therapeutic approach owing to its potent immunomodulatory properties. However, progress has been hindered by the lack of standardized protocols for inducing a robust immunomodulatory MSC phenotype.MethodsIn this study, we focused on optimizing the MSC-derived secretome to enhance its ability to suppress activated immune cells. Specifically, we examined (1) the effects of IFN-γ and TNF-α, individually and in combination, to uncover potential synergy; (2) the ideal cytokine ratio and (3) concentration; (4) the best production time for the secretome; and (5) the impact of cellular confluence. These factors were systematically evaluated to assess their influence on cell behavior, viability, cytosolic content release, and the secretion of key immunomodulatory and regenerative factors.ResultsOur results demonstrate that overnight licensing with a 1:1 ratio of IFN-γ and TNF-α at 60 ng/mL, followed by 48 h of incubation at 90% confluence, yields an optimized conditioned media (CM) with significantly enhanced immunomodulatory properties. Functional assays showed that this CM can inhibit human peripheral blood mononuclear cell (PBMC) activation with more than twice the effectiveness of suboptimal protocols. Additionally, we found that direct cell-cell contact was critical for inducing regulatory T cells (Tregs), highlighting the complex dynamics of immune regulation.ConclusionsThese findings establish a robust and standardized MSC licensing protocol, paving the way for the development of innovative and effective therapies to combat IMIDs.Clinical trial numberNot applicable.

Preclinical and mechanistic perspectives on adipose-derived stem cells for atherosclerotic cardiovascular disease treatment.

Adipose-derived mesenchymal stem cells (AD-MSCs) are a promising therapeutic modality for cardiovascular diseases due to their immunomodulatory, anti-inflammatory, and pro-angiogenic properties. This manuscript explores the current status, challenges, and future directions of AD-MSC therapies, focusing on their application in atherosclerosis (AS), myocardial infarction (MI), and heart failure (HF). Preclinical studies highlight AD-MSC's ability to stabilise atherosclerotic plaques, reduce inflammation, and enhance myocardial repair through mechanisms such as macrophage polarisation, endothelial protection, and angiogenesis. Genetically and pharmacologically modified AD-MSCs, including those overexpressing SIRT1, IGF-1, and PD-L1 or primed with bioactive compounds, exhibit superior efficacy compared to unmodified cells. These modifications enhance cell survival, immunopotency, and reparative capacity, showcasing the potential for tailored therapies. However, clinical translation faces significant hurdles. While recent clinical trials have confirmed the safety of AD-MSC therapy, their efficacy remains inconsistent, necessitating further optimisation of patient selection, dosing strategies, and delivery methods. Donor variability, particularly in patients with co-morbidities like type 2 diabetes (T2D) or obesity, impairs AD-MSC efficacy. Emerging research on extracellular vesicles (EVs) derived from AD-MSC offers a promising cell-free alternative, retaining the therapeutic benefits while mitigating risks. Future perspectives emphasise the need for multidisciplinary approaches to overcome these limitations. Strategies include refining genetic modifications, exploring EV-based therapies, and integrating personalised medicine and advanced diagnostic tools. By addressing these challenges, AD-MSC therapies hold the potential to revolutionise the treatment of cardiovascular diseases, providing innovative solutions to improve patient outcomes.

Polysaccharides from Ganoderma lucidum attenuate cognitive impairment in 5xFAD mice by inhibiting oxidative stress and modulating mitochondrial dynamics via the Nrf2/antioxidative axis activation.

Oxidative stress and mitochondrial dynamics imbalance are key contributors to AD pathogenesis. GLPS, an extract from Ganoderma lucidum spores, exhibits anti-inflammatory, antioxidant, and immunomodulatory properties. However, the roles of GLPS in regulating oxidative stress and mitochondrial dynamics in AD remain poorly understood. Here, the underlying mechanisms of neuroprotective effects on cognitive dysfunction in 5 × FAD mice were explored. C57BL/6 mice served as WT controls, while 5 × FAD mice were divided into an AD group and an AD + GLPS group. The mice in AD + GLPS group were administered daily GLPS (25 mg/kg) by i.p. injection for two months, while WT and AD mice received an equivalent volume of normal saline. The results indicated that GLPS markedly improved cognitive function and decreased p-tau and Aβ levels in 5 × FAD mice. Moreover, GLPS alleviated oxidative stress by increasing SOD levels and decreasing MDA concentrations. It also inhibited excessive mitochondrial fragmentation by decreasing the expression of p-Drp1 and Fis1, while increasing the levels of Mfn1, Mfn2, and OPA1 in 5 × FAD mice. Mechanistically, GLPS activated Nrf2, leading to a marked upregulation of antioxidant enzymes, including HO- 1, NQO1, and SOD2 in 5 × FAD mice. Collectively, these findings suggest that GLPS ameliorates cognitive deficits in 5 × FAD mice by reducing oxidative stress and modulating mitochondrial dynamics through Nrf2-mediated antioxidant enzyme activation.

Transplantation of Exercise-Enhanced Mesenchymal Stem Cells Improves Obesity and Glucose Tolerance via Immune Modulation in Adipose Tissue.

Exercise-conditioned mesenchymal stem cells (MSCs) may modulate immune responses and improve white adipose tissue (WAT) function. While MSCs are known to reduce inflammation, it remains unclear if exercise-stimulated MSCs can improve obesity-related dysfunctions. This study is the first to explore how exercise-conditioned MSCs may influence adipose tissue inflammation and remodeling in the context of obesity. MSCs were isolated from exercised- and sedentary donor mice, then cultured in vitro. After culture, MSCs were assessed for differentiation capacity and cytokine gene expression, including Il10, as indicators of immune modulation. Exercise-conditioned MSCs were then transplanted into obese recipient mice. Following transplantation, immune cell profiles, inflammatory markers, and adipocyte morphology in recipient WAT were analyzed. Flow cytometry was used to quantify macrophage subtypes (pro-inflammatory and anti-inflammatory), and histological analysis was performed to measure changes in adipocyte size. Exercise-activated MSCs showed a ± 35% increase in Il10 expression and a ± 20% enhancement in differentiation capacity compared to controls, indicating improved immunomodulatory potential. In recipient mice, transplantation led to a ± 25% reduction in pro-inflammatory macrophages (CD86+ CD206-) and a 15% decrease in adipocyte size within WAT. Additionally, WAT in treated mice showed balanced inflammatory profiles and reduced adipose hypertrophy, suggesting restored immune balance and metabolic health. These findings suggest that exercise-modified MSCs exhibit enhanced immunomodulatory and metabolic regulatory properties. This study provides evidence that exercise enhances MSC characteristics, potentially improving their capacity to modulate adipose tissue immune balance and metabolic function in obesity. Exercise-conditioned MSCs may serve as a foundation for future strategies that integrate exercise-induced stem cell modifications to modulate obesity-related metabolic dysfunction.

Assembly of MSCs into a spheroid configuration increases poly(I:C)-mediated TLR3 activation and the immunomodulatory potential of MSCs for alleviating murine colitis

BackgroundInflammatory bowel disease (IBD) is associated with significant clinical challenges due to the limitations of current therapeutic approaches. Mesenchymal stem cell (MSC)-based therapies have shown promise in alleviating IBD owing to their potent immunomodulatory properties. However, the therapeutic efficacy of these cells remains suboptimal, primarily due to the harsh peritoneal microenvironment, which compromises MSC viability and functional capacity after transplantation.MethodsTo address these limitations, this study aimed to improve MSC engraftment and functionality by assembling MSCs into three-dimensional (3D) spheroids and priming them with the Toll-like receptor 3 (TLR3) agonist polyinosinic-polycytidylic acid (poly(I:C)). Their potential for treating IBD was evaluated using male C57BL/6 mice with dextran sulfate sodium-induced colitis.ResultsWhile 3D spheroid formation alone upregulated TLR3 expression and increased MSC survival under oxidative stress, poly(I:C) priming had a pronounced synergistic effect, significantly increasing MSC-mediated splenocyte modulation and oxidative stress resistance. In a murine colitis model, compared with unprimed spheroids or MSC suspensions, poly(I:C)-primed MSC spheroids administered intraperitoneally exhibited increased survival and therapeutic efficacy, effectively alleviating colitis symptoms, reducing colonic inflammation, and promoting tissue recovery.ConclusionCollectively, these findings highlight the synergistic benefits of combining 3D spheroid assembly with TLR3 activation as an innovative strategy to improve the therapeutic efficacy of MSC-based treatments for IBD and other inflammatory diseases by increasing post-engraftment cell survival and immunomodulatory capacity.

The role of mesenchymal stem cell‑derived exosomes in asthma (Review).

Asthma is a chronic respiratory disorder characterized by persistent inflammation, airway hyper‑responsiveness and remodeling, leading to notable morbidity and decreased quality of life for patients. Mesenchymal stem cells (MSCs) have potential in regenerative medicine due to their potent immunomodulatory properties and anti‑inflammatory effects. The therapeutic benefits of MSCs are largely mediated by secreted exosomes that facilitate intercellular communication by transferring bioactive molecules, including proteins, lipids and microRNAs. The present review explores the therapeutic potential of MSC‑derived exosomes in asthma, highlighting their ability to modulate key pathological mechanisms underlying the disease.

Saikosaponin D inhibits the inflammatory response of secretory otitis media through FTO-mediated N6-methyladenosine modification of TLR4 mRNA

Secretory Otitis Media (SOM) is a non-suppurative inflammatory disease of the middle ear. Saikosaponin D (SSD), a compound with significant anti-inflammatory and immunomodulatory properties, was investigated for its preventive effects and underlying mechanisms against SOM. A rat model of SOM was established through intraperitoneal ovalbumin injection. Middle ear lavage fluid (MELF) and tissue samples were collected for comprehensive analysis, including bacterial load quantification, neutrophil enumeration, and inflammatory factor assessment. HEK293T cells were utilized for mechanistic validation. Our findings demonstrated that SSD preventive treatment significantly reduced colony-forming units (CFUs) in SOM-induced rats, attenuated middle ear mucosal thickening, and suppressed pro-inflammatory cytokine levels (TNF-α, IL-6, and INF-γ). Mechanistically, SSD treatment counteracted SOM-induced m6A level elevation and reversed the downregulation of FTO expression. Functional studies revealed that FTO inhibition exacerbated inflammatory responses, while SSD treatment mitigated these effects. Further investigation demonstrated that SSD decreased TLR4 mRNA stability through FTO-mediated m6A modification. In conclusion, SSD alleviates SOM progression by reducing bacterial load and neutrophil infiltration. The therapeutic effects are mediated through FTO upregulation and subsequent m6A-dependent TLR4 mRNA degradation. This study elucidates a novel molecular mechanism underlying SSD’s preventive action against SOM development.

Mesenchymal stem cell therapy for ischemic cardiomyopathy: Research progress and prospects for application

This review aims to explore the research progress and application prospects of mesenchymal stem cells (MSCs) in the treatment of ischemic cardiomyopathy (ICM). ICM is a severe heart disease characterized by the death of myocardial cells due to long-term ischemia, leading to impaired heart function. MSCs have become one of the promising therapeutic methods for treating ICM due to their unique anti-inflammatory, anti-apoptotic, immunomodulatory, and pro-angiogenic properties. Studies have shown that MSCs can improve heart function by promoting neovascularization, reducing myocardial cell apoptosis, inhibiting inflammatory responses, and regulating immune reactions. Additionally, MSCs can be sourced from various tissues, including bone marrow, adipose tissue, and umbilical cord/placenta, with different sources of MSCs possessing distinct characteristics and therapeutic effects. Clinical studies have indicated that MSC therapy can improve the physical capacity and left ventricular ejection fraction (LVEF) in patients with intractable angina, and enhance myocardial perfusion and overall heart function in patients with myocardial infarction. However, issues such as the therapeutic mechanisms of MSCs, the optimal source, infusion routes, and dose optimization still require further research. Future studies need to address these issues to transform MSC therapy from clinical trials to routine clinical practice, thereby revolutionizing the management and prognosis of ICM.

Multifunctional Nanoplatform Based on Gelatin Nanoparticles with Immunomodulatory Capabilities for Combined Immunotherapy and Chemotherapy of Melanoma.

Tumor immunotherapy has shown considerable therapeutic potential, especially when combined with chemotherapy. In this study, we developed a multifunctional nanoplatform GNPs-DOX/R848 that combined immunotherapy and chemotherapy for the treatment of melanoma, in which gelatin nanoparticles (GNPs) were loaded with the immunomodulatory agent resiquimod (R848) and the chemotherapy drug doxorubicin (DOX). GNPs possessed inherent immunomodulatory properties; when combined with R848, they induced a more pronounced polarization of M1-like macrophages by activating the NF-κB signaling pathway, thereby reversing the immunosuppressive tumor microenvironment. Meanwhile, GNPs effectively delivered R848 and DOX to tumor cells, promoting stronger therapeutic effects of the drugs, which strongly induced the immunogenic cell death triggered by DOX, leading to the infiltration of T cells into the tumor tissue. The treatment of melanoma demonstrated that GNPs-DOX/R848 significantly reduced tumor volume, enhanced the therapeutic effects of chemotherapy, providing a new approach for the combined treatment of cancer with immunotherapy and chemotherapy.

Marine-inspired near-infrared-activated multifunctional hydrogel with immunomodulatory properties for multidrug-resistant bacterial infected wound healing.

Marine-inspired near-infrared-activated multifunctional hydrogel with immunomodulatory properties for multidrug-resistant bacterial infected wound healing.

A PD-L1/CD3 BISPECIFIC ANTIBODY ENHANCES THE ANTI-TUMOR EFFECTS OF REGORAFENIB AGAINST COLON CANCER.

Colorectal cancer (CRC) is a leading cause of cancer-related deaths worldwide. The current standard of care for patients may involve surgery, chemotherapy, and immune checkpoint inhibitors (ICIs), but these approaches typically fail to secure durable responses against late-stage disease. Regorafenib (REG) is an FDA-approved tyrosine kinase inhibitor with immunomodulating properties for CRC patients who progress on standard care, but 5-year relative survival rates for individuals dosed with the drug as a monotherapy are poor. We hypothesize that REG may be more appropriately leveraged alongside immunotherapeutic agents that specifically stimulate T cell infiltration and activation within the tumor microenvironment (TME). We engineered a PD-L1/CD3 bispecific antibody (bsAb) that simultaneously binds PD-L1-expressing CRC cells and stimulates activated T cells in order to investigate combination strategies with REG in pre-clinical models of CRC. Combined REG + bsAb therapy safely initiated and sustained inhibition against MC38 and CT26 progression in vivo, and these effects correlated to improved CD8+ T cell infiltration and activity within a Type-1-prone TME. Additionally, cytotoxic CD8+ T cells from REG + bsAb-sensitized mice exhibited heightened tumor cell reactivity compared to animals treated with either agent alone. Therefore, the immunomodulatory benefits of REG can be effectively paired with a bsAb that anchors to CRC cells, diminishes immunosuppression (through PD-L1 blockade), and activates/sustains antigen-specific CD8+ T cells within the TME. Our newly described REG + bsAb regimen led to improved anti-tumor outcomes pre-clinically and may represent a promising future approach for CRC patients.

Astragalus Membranaceus—Can It Delay Cellular Aging?

Astragalus membranaceus, a plant that has been utilized in traditional Chinese medicine for centuries, is widely regarded as one of the most valuable herbs in this medicinal tradition. It is commonly referred to as the “yellow leader”, a designation that stems from the yellow hue of its most significant organ, the root, and its adaptogenic properties. The plant Astragalus is renowned for its abundance of active components, including polysaccharides, flavonoids, saponins, and an array of trace elements. It has been demonstrated that the administration of Astragalus can prevent cellular aging, owing to its diverse range of actions that provide protection to the body from both external and internal factors. The antioxidant, immunomodulatory, anti-inflammatory, and regenerative properties of this plant contribute to the maintenance of good skin condition, preventing atrophy of subcutaneous tissue and degeneration of facial bones. Systemic actions encompass the maintenance of function and protection of the cardiovascular, nervous, respiratory, digestive, excretory, immune, and endocrine systems. This article reviews the composition of Astragalus membranaceus and the beneficial effects of its root extract and its active substances on the whole body, with a particular focus on the anti-aging effects on the skin.