Immune-mediated Research Articles

Hidradenitis Suppurativa from a Multi-Omic Scope.

Hidradenitis suppurativa (HS) is recognized as a systemic immune-mediated disease (IMID), sharing genetic and environmental risk factors with other IMIDs such as inflammatory bowel disease and psoriasis. Over time, correlating clinical findings with genetic, proteomic, and metabolomic results has been challenging due to diverse sampling methods, analysis techniques, and the use of variable clinical phenotype descriptions across studies. This review aims to summarize the results from various omics fields to explore the etiopathology of HS. Genetic studies highlight defects in Notch and γ-secretase signaling and inflammasome function. Syndromic HS involves specific mutations in autoinflammatory syndromes such as pyogenic sterile arthritis, pyoderma gangrenosum, and acne (PAPA) and pyoderma gangrenosum, acne, and HS (PASH). Proteomic analyses reveal key inflammatory pathways indicating activation of both innate and adaptive immunity. Additionally, microbiome studies show an increased presence of anaerobes like Prevotella in HS lesions and a decreased presence of commensals such as Staphylococcus epidermidis. Gut microbiota dysbiosis, particularly involving Ruminococcus gnavus and Clostridium ramosum, is associated with HS. Moreover, metabolomic profiling indicates dysregulated tryptophan catabolism and lipid metabolism, with increased 5-lipoxygenase-derived metabolites and odd-chain fatty acids suggesting bacterial involvement. In summary, despite advances, robust associations between genetics, proteomics, microbiome, and metabolomics in HS are still lacking. Integrating these datasets could identify new clinical phenotypes, genetic predispositions, microbial signatures, and therapeutic targets, enhancing personalized treatment strategies and biomarker discovery for HS classification, prognosis, and treatment response.

Immune checkpoint inhibitors-related thyroid dysfunction: influencing factor analysis, prediction model development, and management strategy proposal

BackgroundWith the extensive utilization of immune checkpoint inhibitors (ICIs) across various cancers, ICIs-related thyroid dysfunction (ICI-TD) has become a growing concern in clinical practice. This study aimed to devise an individualized management strategy for ICI-TD to enhance the early identification and proactive management in cancer patients.MethodsWe designed and conducted a three-phase study. Initially, we analyzed the influencing factors through a systematic review and meta-analysis, which adhered to the Preferred Reporting Items for Systematic Reviews and Meta-analyses (PRISMA) guidelines. Moreover, the study protocol was registered with PROSPERO (CRD42019131133). Subsequently, prediction models for ICI-TD were developed utilizing 11 algorithms based on the real-world cohort data from July 20, 2018 (the approval date of the first ICIs, Pembrolizumab in China), to October 31, 2022. Considering discrimination, calibration, and clinical utility, we selected the model with the best performance for web calculator development. Finally, individualized management strategies for ICI-TD were proposed by combining evidence-based analysis with practical considerations.ResultsThe systematic review encompassed 21 observational studies involving 4,145 patients, revealing associations between ICI-TD and factors such as female gender, age, receipt of Pembrolizumab (versus other ICIs), and baseline levels of thyroid-stimulating hormone, free thyroxine, and antithyroid antibodies. In the prediction model development phase, 621 participants were enrolled, with 36 patients developing ICI-TD. The model based on the LightGBM algorithm demonstrated superior performance, leading to the development of a web calculator. Based on these findings and existing guidelines, individualized monitoring and treatment pathways for pharmacists were devised.ConclusionThis study offers comprehensive insights into managing ICI-TD, potentially enhancing tailored cancer immunotherapy management.

Review article: Prevention of inflammatory bowel disease-The path forward.

The possibility of preventing inflammatory bowel disease (IBD) is becoming more plausible due to advances in understanding preclinical disease and successful prevention trials in other immune-mediated diseases, such as type 1 diabetes and rheumatoid arthritis. However, before that possibility becomes reality, several efforts need to occur in parallel and in a coordinated way. To propose some critical steps necessary for advancing the field of IBD prediction and prevention. We reviewed the current literature to identify the necessary steps toward a preventive strategy for IBD. The first step should determine the most robust predictive biomarkers and validate them across independent cohorts, creating a multidimensional predictive tool. The second step is to gain a better understanding of the preferences of first-degree relatives and people at risk for IBD, informing the implementation of screening and preventive strategies. Third, these efforts should contribute to the development of high-risk clinics and establish the necessary networks for disease prevention trials. Advancing the field of IBD prediction and prevention will require a multifaceted approach, integrating biomarker discovery, understanding patient preferences, and establishing infrastructure for a collaborative network to support the practical implementation of IBD prevention strategies.

Treatment with Leflunomide in Conjunction with Glucocorticoids for Dogs with Immune-Mediated Polyarthritis Is Not Associated with Improved Outcomes: A Retrospective Cohort Study of 93 Dogs from Australia (2017–2024)

Immune-mediated polyarthritis (IMPA) has a relatively high relapse rate compared to other immune-mediated diseases. Leflunomide is frequently used to treat dogs with IMPA in conjunction with prednisolone. This retrospective cohort study aimed to evaluate the therapeutic efficacy of leflunomide as an adjunctive therapy to prednisolone in reducing relapse and mortality rates in dogs diagnosed with IMPA in Australia. The medical records of client-owned dogs diagnosed with IMPA at a specialist referral hospital in Southeast Queensland from 2017 to 2024 were reviewed. A total of 93 dogs were included in this study, divided into two groups based on the treatment received: Group PRED, consisting of 53 dogs treated with prednisolone as the sole immunosuppressive agent, and Group L+PRED, consisting of 40 dogs that received leflunomide as adjunctive therapy alongside prednisolone. Data collected included breed, age, weight, sex, serum C-reactive protein concentration, results of synovial fluid analysis and microbial culture, treatment protocol, relapse rates and time to relapse, and mortality rates. There was no difference in relapse or mortality rates, time to relapse, nor time to discontinue prednisolone between the PRED and L+PRED groups. The L+PRED group had higher body weights and lower prednisolone dose rate at discharge compared to those in the PRED group. This study demonstrated that the use of leflunomide as an adjunctive therapy to prednisolone for the treatment of dogs with IMPA had no improved outcomes, reduced relapse rates, or shortening in the duration of prednisolone therapy when compared to dogs receiving prednisolone monotherapy.

Association of innate versus specific immunity with heart failure incidence: a prospective study.

Immune disorders are key heart failure (HF) triggers, but little is known about whether the status of immunity affects the incidence of HF. To explore this, we used blood cell counts and derived ratios to investigate the association between immunity status markers and HF incidence. The number and proportion of peripheral blood leucocytes in a physiological state are related to the body's immune status. Neutrophils, monocytes, SII (systemic immune-inflammatory index), NLR (neutrophil-to-lymphocyte ratio), and PLR (platelet-to-lymphocyte ratio) serve as innate immunity status markers, while lymphocytes and LMR (lymphocyte-to-monocyte ratio) serve as specific immunity status markers. 330 362 UK Biobank (UKB) participants were finally examined. Cox proportional hazard models were used to explore the relationship between immunity status markers and HF incidence. Flexible parametric survival models were used to capture time-varying relationships between blood cell ratios and HRs for HF. Subgroup analyses were conducted by age, sex, and body mass index. Finally, sensitivity analyses were performed to validate the results. During a median follow-up of 14.1 years, 9611 (2.9%) participants developed HF. Neutrophils, monocytes, SII, and NLR were positively associated with HF incidence, with fully adjusted per SD increment HR (95% CI) of 1.20 (1.17 to 1.22), 1.09 (1.07 to 1.12), 1.12 (1.10 to 1.14), and 1.16 (1.14 to 1.18), respectively. Platelets, lymphocytes, and LMR were inversely correlated with HF incidence, with fully adjusted per SD increment HR (95% CI) of 0.97 (0.95 to 1.00), 0.97 (0.95 to 0.99), and 0.90 (0.88 to 0.92), respectively. The innate immunity status markers were positively associated with HF incidence, while specific immunity status markers exhibited an inverse association, offering novel insights for HF prediction and intervention.

A critical role for microglia in regulating metabolic homeostasis and neural repair after spinal cord injury

Traumatic spinal cord injury (SCI) often results in severe immune and metabolic disorders, aggravating neurological damage and inhibiting locomotor functional recovery. Microglia, as resident immune cells of the spinal cord, play crucial roles in maintaining neural homeostasis under physiological conditions. However, the precise role of microglia in regulating immune and metabolic functions in SCI is still unclear and is easily confused with that of macrophages. In this study, we pharmacologically depleted microglia to explore the role of microglia after SCI. We found that microglia are beneficial for the recovery of locomotor function. Depleting microglia disrupted glial scar formation, reducing neurogenesis and angiogenesis. Using liquid chromatography tandem mass spectrometry (LC‒MS/MS), we discovered that depleting microglia significantly inhibits lipid metabolism processes such as fatty acid degradation, unsaturated fatty acid biosynthesis, glycophospholipid metabolism, and sphingolipid metabolism, accompanied by the accumulation of multiple organic acids. Subsequent studies demonstrated that microglial depletion increased the inhibition of FASN after SCI. FASN inhibition exacerbated malonyl-CoA accumulation and significantly impeded the activity of mTORC1. Moreover, microglial depletion exacerbated the oxidative stress of neurons. In summary, our results indicate that microglia alleviate neural damage and metabolic disorders after SCI, which is beneficial for achieving optimal neuroprotection and neural repair.

A new era in the treatment of kidney diseases: NLRP3 inflammasome and cytokine-targeted therapies.

The kidneys are crucial for filtering blood, managing overall body water, electrolyte, and acid-base balance, and regulating blood pressure. They remove metabolic waste products, toxins, and drugs. In addition, they limit inflammation by clearing cytokines and reduce immune cell activation by removing bacterial components. Dendritic cells (DCs) in the kidney maintain peripheral tolerance. About 85% of filtered water is reabsorbed by the proximal tubule, exposing distal nephron cells to high concentrations of low molecular weight antigens. These antigens are captured by DCs, helping to inactivate potentially autoreactive T cells and maintain tolerance to circulating antigens. In kidney failure, immune function is severely compromised due to the retention of toxins and cytokines, which activate immune cells and increase systemic inflammation. The kidneys are also vulnerable to immune-mediated diseases. Loss of immune homeostasis, characterized by over- or under-activity of the immune response, can adversely affect kidney function. With advances in immunology and cellular biology, biologic therapies targeting various pathways involved in the pathophysiology of kidney diseases are being developed. In this review, the immunologic aspects of kidney diseases and focus on cytokine-based therapies that may hold promise for the treatment of kidney diseases in the future will be presented.

Advancements in Autologous Stem Cell Transplantation for Parkinson's Disease.

Parkinson's disease (PD) is a progressive neurodegenerative disease marked by comparatively focal dopaminergic neuron degeneration in the substantia nigra of the midbrain and dopamine loss in the striatum, which causes motor and non-motor symptoms. Currently, pharmacological therapy and deep brain stimulation (DBS) are the primary treatment modalities for PD in clinical practice. While these approaches offer temporary symptom control, they do not address the underlying neurodegenerative process, and complications often arise. Stem cell replacement therapy is anticipated to prevent further progression of the disease due to its regenerative capacity, and considering the cost of immunosuppression and the potential immune dysfunctions, autologous stem cell transplantation holds promise as a significant method against allogeneic one to treat Parkinson's disease. In this review, the safety concerns surrounding tumorigenicity and complications associated with transplantation are discussed, along with methods utilized to evaluate the efficacy of such procedures. Subsequently, we summarize the preclinical and clinical studies involving autologous stem cell transplantation for PD, and finally talk about the benefits of autologous stem cell transplantation against allogeneic transplants.

Immune-Mediated Inflammatory Diseases, Dyslipidemia, and Cardiovascular Risk: A Complex Interplay.

Individuals with autoimmune inflammatory diseases, such as systemic lupus erythematosus, rheumatoid arthritis, and psoriasis, are at increased risk for cardiovascular disease. While these diseases share common features of systemic inflammation, the impact of individual autoimmune inflammatory conditions on circulating lipids and lipoproteins varies by specific disease, disease activity, and the immune-suppressing medications used to treat these conditions. A common feature observed in many autoimmune inflammatory diseases is the development of a proatherogenic dyslipidemic state, characterized by dysfunctional HDLs (high-density lipoproteins) and increased oxidation of LDLs (low-density lipoproteins). Various disease-modifying antirheumatic drugs also have complex and variable effects on lipids, and it is critical to take this into consideration when evaluating lipid-related risk in individuals with immune-mediated inflammatory conditions. This review aims to critically evaluate the current understanding of the relationship between immune-mediated inflammatory diseases and dyslipidemia, the underlying mechanisms contributing to atherogenesis, and the impact of various pharmacotherapies on lipid profiles and cardiovascular risk. We also discuss the role of lipid-lowering therapies, particularly statins, in managing residual risk in this high-risk population and explore the potential of emerging therapies with complementary anti-inflammatory and lipid-lowering effects.

Antioxidant and Anti-Inflammatory Effects of Curcuma Longa Extracts and Fractions on Skin Inflammation

Addresses the impact of modern society’s rapid industrialization and environmental pollution, leading to increased oxidative stress and immune system disorders. Skin barrier issues have resulted in a rise in inflammatory skin conditions, sparking heightened interest in functional cosmetics to address these concerns and combat aging. The research focused on exploring natural ingredients, particularly specific fractions of <i>Curcuma Longa</i> extracts, known for their antioxidant properties. The results of this study are summarized as follows. In the first stage experiment, DPPH radical scavenging activity and ABTS radical scavenging activity were investigated, and fractions exhibiting higher scavenging activity than extracts were sought. In the 2nd-step experiment, the cell survival rate was examined to determine the concentration that would not affect cytotoxicity. To demonstrate significant anti-inflammatory effects on RAW 264.7 cells, inflammation reactions were induced by LPS and the production of Nitric Oxide (NO) was controlled. As a result, <i>Curcuma Longa</i> extracts and fractions all proved excellent control effects on NO production. In HaCaT cells, skin inflammation was induced with TNF-α/IFN-γ and the control of interleukin (IL)-6 production was measured. As a result, <i>Curcuma Longa</i> extracts and fractions proved to facilitate the immune reaction and control the reaction that would lead to inflammation. In the following 3rd-step experiment, the control of Chemokine’s major factors IL-8, RANTES, and TARC was measured. As a result, it was verified that certain fractions of <i>Curcuma Longa</i> of extract showed excellent Chemokine production control effects and thus that these specific fractions are effective on various inflammatory skin diseases. ICAM-1 expressions were observed to control the initial stage of inflammation in a way of cellular adhesion regulation, and the MAPK path which is important to regulate inflammatory reactions in the signaling system was measured. As a result, the inhibition of phosphorylation, which is important for initial inflammation inhibition and inflammatory reaction control, was verified. Based on the above-stated findings, active ingredients containing certain fractions were analyzed, and color reactions in specific fractions were induced from active ingredient spots of extract. In consideration of future material development and production, the quantitative and qualitative characteristics of active ingredients of certain fractions were examined with the HPLC, and it was verified that certain fractions contained more active ingredients than extracts. In conclusion, certain fractions of natural elements proved the great potentials as a cosmetics ingredient. Therefore, these fractions proved excellent anti-oxidative and anti-inflammatory effects in certain fractions, and the efficiency is quite high with only a small quantity of them. It is expected that these fractions are widely utilized as a cosmetic element, and the future study will examine natural cosmetic elements from these fractions with the aim to contribute to the functional cosmetics industry and anti-aging product market.

The Role of Gut Microbioma in Human Health: Exploring the Impact on Metabolism, Immunity, and Neurological Disorders

Abstract: The human microbiota has been progressively accepted for its role in sustaining overall health and well-being. The gut microflora vigorously communicates with the host metabolic system that exert influence on the progression, maturation, immune cells development and immune homeostasis maintenance. For the proper functioning of the immune system a diversified and steady gut microflora is needed, while “Dysbiosis” or an imbalance in the gut microbioma will lead to autoimmune and inflammatory diseases. The gut microbiota provides shape to our immune response and contribute to host protection against pathogen or bacterium through mechanisms such as the transformation of pro- inflammatory cytokine production, regulatory T-cell inductor and by intestinal mucosaql barrier. In addition to gut microbiota can affect our neurological function and play a key role in the pathogenesis of psychological disorders such as autism, depression, anxiety, Parkinson and Alzheimer’s disease. Gut microbiota can regulate neurological disorders by supplementing them with fecal transplantation, probiotics and antibiotics. An important parameter to consider gut microbioma disorder is Firmicutes/ Bacteroidetes.

Replacing Hydrolyzed Soybean Meal with Recombinant β-Glucosidase Enhances Resistance to Clostridium perfringens in Broilers Through Immune Modulation

Aglycone soy isoflavones have notable immune-regulatory bioactivity, while glycosidic forms in soybean meal pose challenges for absorption. β-Glucosidase (EC 3.2.1.21) catalyzes the non-reducing terminal β-d-glucosidic bonds, releasing β-d-glucan and aglycones. This study evaluated the impact of enzymatically hydrolyzed soybean meal (ESM) using recombinant β-glucosidase from Aspergillus niger on the growth performance and intestinal immune function of broilers under Clostridium perfringens infection. Prior to the feeding trial, soybean meal was enzymatically digested with recombinant β-glucosidase, ensuring almost complete conversion of glycosides to aglycones. After a week of pre-feeding, a total 180 healthy AA broilers were randomly assigned to three groups—control, semi-replacement of ESM (50% ESM), and full-replacement of ESM (100% ESM)—with 6 replicates of 10 chickens, and the trial lasted 28 days. On the 36th day, broilers were challenged with 1 mL of 1 × 1010 CFU/mL Clostridium perfringens (Cp) via gavage for 3 days. The results showed that the substitution of ESM had no effect on the body weight gain of broilers but significantly reduced the feed consumption and feed-to-gain ratio (p < 0.01). The study revealed that Cp significantly disrupted jejunal morphology, while ESM significantly mitigated this damage (p < 0.05). Real-time PCR results demonstrated that compared to the Cp group, ESM restored Cp-induced intestinal barrier impairments (e.g., Occludin, Claudin-1, Muc2), normalized aberrant cellular proliferation (PCNA) and apoptosis (Caspase-1 and Caspase-3), and upregulated the expression of anti-inflammatory factor Il-10 while suppressing pro-inflammatory cytokines (Il-1β, Il-6, and Il-8) (p < 0.05). Moreover, flow cytometry analyses demonstrated that ESM promoted Treg cell-derived Il-10, which alleviated macrophage-derived inflammation. Substituting conventional soybean meal with β-glucosidase, enzymatically treated, significantly reduced feed consumption and alleviated the intestinal damage and immune dysfunctions induced by Clostridium perfringens infection in broilers.

Nutrition, immunity, and infectious diseases in the context of climate change and health syndemic: A scoping review for North America

Abstract Climate change exacerbates global food insecurity, leading to undernutrition and immunodeficiency, which in turn increases susceptibility to infectious diseases. In this way, climate change creates a syndemic, with undernutrition, immunity, and infectious disease risk adversely interacting. This scoping review aims to map: 1) trends in research about climate change impacts on food security; and 2) the extent to which food security is connected to the immune system and infectious diseases in published climate change research in North America. Using a scoping review process, we identified studies that described food security in the context of climate change in North America. A search string was developed and used to search five electronic databases for articles without language restriction. Data on food security pillars and their relationship with infectious diseases and the immune system were extracted from relevant articles and descriptively synthesized. We identified 204 published articles that met the inclusion criteria. The number of articles linking climate change to food security in North America increased yearly, with regional differences in the number of publications, climate variables analyzed, and study methods used. At least one connection between food security and the immune system or infectious diseases was discussed in 72 articles (35.3%). Of these, eleven articles mentioned both the immune system and infectious diseases and separately described their relationship with food security. However, only eight articles linked or described the relationship between food, immune systems, and infection - for example, by describing extreme weather events that reduced food security, resulting in malnutrition causing immunosuppression, thereby increasing the likelihood of infections. This highlights a gap in research on the adverse interaction between undernutrition, the immune system, and infectious disease risk in the context of climate change. This review underscores the need to study the interconnected and cascading health outcomes of climate change.

Pathogenesis of psoriatic arthritis: new insights from a bone marrow perspective.

Psoriatic arthritis is an immune-mediated disease that primarily affects the skin and joints. It falls under the umbrella term of rheumatic diseases, which describes a group of closely related yet distinct disorders with many common underlying molecular pathways. Despite the distinct clinical manifestation of each disorder, the shared therapeutic strategies attest to the commonality of cellular and molecular underpinnings. Herein we provide a concise yet comprehensive overview of the interleukin (IL)-23/IL-17 axis and its involvement in mechanistic pathways leading to the pathogenesis of this dual skin and joint clinical manifestation which is characteristic of psoriatic arthritis and other rheumatic diseases. The interconnection between activated innate immune cells and adaptive immunity has transformed current thinking to include other organs such as the bone marrow as potential tissue of disease origin. A plethora of animal models and genetic studies converge on the critical role of IL-23/IL-17 axis, and highlight the importance of myeloid cell activation as common pathways between autoinflammatory and autoimmune diseases and chronic inflammation. These findings underscore the intricate immune mechanisms involved in inflammatory arthritis and highlight molecular mechanisms in disease pathogenesis. These insights pave the way for the development of novel diagnostic and therapeutic strategies, with a focus on translating these findings into improved clinical practice.

Molecular patterns of microbial and metabolic interactions in septic patients with persistent lymphopenia.

Persistent lymphopenia can be regarded as an important index of acquired immune dysfunction in sepsis. Whether the specific immune factor changes in septic patients with lymphopenia and the correlation to gut microbiota and metabolites remain unclear. This single-center prospective observation conducted lymphocyte subgroup analysis of blood samples and 16S rRNA gene amplicons sequencing and untargeted metabolomics analysis of fecal samples from 36 subjects with the persistent (≥3d) (n=21) and non-persistent lymphopenia (<3d) (n=15). The persistent lymphopenia showed higher the 28d mortality and 90d mortality, while significantly lower CD3+T/LY, CD3+T cells, CD3+CD4+T cells, CD3+CD8+T cells, Th1 cells, Th2 cells, CD45RA+Treg cells. The 16S rRNA results showed that Staphylococcus, Peptostreptococcus, Bulleidia, Leuconostoc were significant enriched in the persistent lymphopenia. The metabolomics analysis showed that α-Ketoisovaleric acid was increased and 7-DHCA, α-MCA, β-MCA, HCA, LCA-3S, CA, UCA and Citramalic acid were decreased in the persistent lymphopenia. In the process of interaction between host receptors and gut microbiota in patients with persistent lymphopenia sepsis, with a significant reduction in gut microbiota diversity and bile acid metabolites. That can affect various inflammatory pathways of gut immune cells, causing immune dysfunction in the body, which may be one of the main causes of death.

GPR55 antagonist CID16020046 suppresses DNCB-induced atopic dermatitis-like symptoms by suppressing Th1/Th2/Th17 populations in mice.

G protein-coupled receptor 55 (GPR55) is a lipid-sensing receptor that plays a role as an immune mediator and is primarily upregulated during immune cell activation. There is a lack of knowledge about the role of GPR55 in allergic inflammatory diseases such as atopic dermatitis. The purpose of this study was to investigate the role of GPR55 through the use of its antagonist, CID16020046, in an atopic dermatitis mouse model. It was found that BALB/c mice develop lesions similar to those associated with atopic dermatitis following sensitization and repeated exposure to 1-chloro-2,4-dinitrobenzene (DNCB). It was found that CID16020046 (1 mg/kg, i.p.) alleviated the atopic dermatitis-like symptoms as well as immune dysregulation caused by DNCB. Based on histopathological analysis, CID16020046 reduced ear thickening and mast cell counts in the dermis. CID16020046 decreased DNCB-induced increases in serum IgE levels, as measured using enzyme-linked immunosorbent assays. A significant reduction in lymph node hypertrophy was also observed with CID16020046 as well as significant reductions in CD4+ T helper 1 (Th1), Th2, and Th17 cells in the lymph nodes. As a result of the administration of CID16020046, cytokines of Th1 (IFN-γ), Th2 (IL-4 and IL-13), and Th17 (IL-17A) types were also reduced in the skin and lymph nodes. In conclusion, blocking GPR55 alleviates DNCB-induced atopic dermatitis-like symptoms, suggesting that GPR55 is a potential therapeutic target for allergic inflammatory diseases via immunoregulation.

Functional Foods in Preventing Human Blood Platelet Hyperactivity-Mediated Diseases—An Updated Review

Backgrounds/Objectives: Abnormal platelet functions are associated with human morbidity and mortality. Platelets have emerged as critical regulators of numerous physiological and pathological processes beyond their established roles in hemostasis and thrombosis. Maintaining physiological platelet function is essential to hemostasis and preventing platelet-associated diseases such as cardiovascular disease, cancer metastasis, immune disorders, hypertension, diabetes, sickle cell disease, inflammatory bowel disease, sepsis, rheumatoid arthritis, myeloproliferative disease, and Alzheimer’s disease. Platelets become hyperactive in obesity, diabetes, a sedentary lifestyle, hypertension, pollution, and smokers. Platelets, upon activation, can trawl leukocytes and progenitor cells to the vascular sites. Platelets release various proinflammatory, anti-inflammatory, and angiogenic factors and shed microparticles in the circulation, thus promoting pathological reactions. These platelet-released factors also maintain sustained activation, further impacting these disease processes. Although the mechanisms are unknown, multiple stimuli induce platelet hyperreactivity but involve the early pathways of platelet activation. The exact mechanisms of how hyperactive platelets contribute to these diseases are still unclear, and antiplatelet strategies are inevitable for preventing these diseases. Reducing platelet function during the early stages could significantly impact these diseases. However, while this is potentially a worthwhile intervention, using antiplatelet drugs to limit platelet function in apparently healthy individuals without cardiovascular disease is not recommended due to the increased risk of internal bleeding, resistance, and other side effects. The challenge for therapeutic intervention in these diseases is identifying factors that preferentially block specific targets involved in platelets’ complex contribution to these diseases while leaving their hemostatic function at least partially intact. Since antiplatelet drugs such as aspirin are not recommended as primary preventives, it is essential to use alternative safe platelet inhibitors without side effects. Methods: A systematic search of the PUBMED database from 2000 to 2023 was conducted using the selected keywords: “functional foods”, “polyphenols”, “fatty acids”, “herbs”, fruits and vegetables”, “cardioprotective agents”, “plant”, “platelet aggregation”, “platelet activation”, “clinical and non-clinical trial”, “randomized”, and “controlled”. Results: Potent natural antiplatelet factors have been described, including omega-3 fatty acids, polyphenols, and other phytochemicals. Antiplatelet bioactive compounds in food that can prevent platelet hyperactivity and thus may prevent several platelet-mediated diseases, including cardiovascular disease. Conclusions: This narrative review describes the work during 2000–2023 in developing functional foods from natural sources with antiplatelet effects.

Dual-Action Psoriasis Therapy: Antiproliferative and Immunomodulatory Effects via Self-Locking Microneedles.

Psoriasis is a chronic, immune-mediated disorder characterized by immune regulation disorders and abnormal keratinocyte proliferation. Deucravacitinib (Deu), a selective oral Tyrosine Kinase 2 (TYK2) inhibitor, shows promise in treating psoriasis but may cause systemic side effects and fail to address persistent localized thickened lesions. Herein, a self-locking microneedle (MN) patch with a polyvinyl alcohol (PVA) inner ring loaded with Deu is developed, designed to penetrate the transdermal barriers and dissolve rapidly, downregulating the IL-23/IL-17 pathway and serve as the first line of defense against the spread of skin-originated inflammation. Additionally, Calcipotriol (Cal), a vitamin D derivative, is incorporated into a methacrylated hyaluronic acid (HAMA) backing layer and outer ring that mimics occlusive administration, maintaining localized skin surface retention for prolonged anti-proliferative therapy. The Deu@Cal MN demonstrates satisfactory adhesiveness due to swelling-mediated mechanical interlocking via the outer ring, ensuring targeted drug release at lesion site. Besides its effectiveness in alleviating both skin inflammation and proliferation, it inhibits the differentiation of Th17 cells in the spleen, suggesting potential to reduce systemic inflammation. These findings offer a new therapeutic approach for treating psoriasis and other autoimmune and inflammatory conditions.

Development of interleukin-27 recombinant Lactococcus lactis and its efficacy in treating psoriasis and colitis in mice.

Psoriasis and inflammatory bowel disease (IBD) are chronic immune-mediated diseases that adversely affect patients' quality of life. Interleukin (IL)-27 plays an important role in a variety of infectious diseases, autoimmune disorders, and cancers. However, its therapeutic effects in psoriasis and colitis remain underexplored. In this study, we evaluated the therapeutic potential of recombinant Lactococcus lactis (L. lactis) expressing IL-27 (pIL-27) in imiquimod-induced psoriasis and dextran sodium sulfate-induced colitis mouse models. In the psoriasis mouse model, oral administration of pIL-27 significantly reduced skin scaling, mitigated weight loss, lowered psoriasis area and severity index scores, diminished epidermal hyperplasia and inflammatory cell infiltration, and decreased inflammatory cytokine levels. In the colitis mouse model, oral administration of pIL-27 alleviated weight loss, improved disease activity index scores, prevented colon shortening, ameliorated histopathological changes, and decreased inflammatory cytokine levels. Furthermore, recombinant L. lactis expressing IL-27 could modulate the gut microbiota, increasing the amount of beneficial bacteria and reducing harmful bacteria in the intestine, thereby alleviating the progression of psoriasis and colitis. These results suggest the potential of IL-27 as a therapeutic option for treating psoriasis and IBD.

NONTYPHOIDAL SALMONELLA OSTEOMYELITIS IN IMMUNOCOMPETENT CHILDREN: REPORT OF TWO CASES AND LITERATURE REVIEW.

Salmonella is a rare causative pathogen of osteomyelitis and is commonly detected in patients with sickle cell disease. We described 2 consecutive cases of nontyphoidal Salmonella osteomyelitis identified in immunocompetent children. It is evident that even children without apparent risk factors for immune dysfunctions can be affected, so maintaining clinical suspicion is crucial for early diagnosis and prompt treatment.