Annexin (ANX), a calcium-phospholipid-binding protein, belongs to a superfamily of calcium-dependent membrane phospholipid-binding proteins, which are widely found in prokaryotic and eukaryotic organisms. They are classified into five groups: A, B, C, D, and E according to the different species and genera. The family of Annexin A(ANXA), which consists of Annexin A1-A11 and Annexin A13, is commonly found in vertebrates. Previous studies have shown that ANXA is involved in multiple processes, such as the formation of biological membranes, the establishment of ion channels, and signal transduction, thereby playing an essential role in cellular life activities such as cell differentiation, proliferation, apoptosis, autophagy, and modulating inflammation. Annexin A1 (ANXA1), a member of the ANXA family, is involved in various disease processes, such as atherogenesis and development of atherosclerosis, tumor proliferation, apoptosis, invasion, and metastasis. This molecule has been increasingly studied, showing potential as a therapeutic target or diagnostic marker for circulatory system diseases. Therefore, this article reviews the value of ANXA1 in the diagnosis and treatment of circulatory system-related diseases.

Introduction Studies have reported differences in the gut microbiome of neuropsychiatric disorder cases associated with increased intestinal permeability and inflammatory conditions. In support of inflammatory conditions, differences in cytokine concentration between cases and controls have also been reported in Parkinson’s disease (PD), schizophrenia (SCZ), and posttraumatic stress disorder (PTSD). This study correlated the gut microbiome with the existing inflammatory cytokine concentration data within each cohort including PD, SCZ, and PTSD. Methods Utilising the 16S rRNA (V4) gut microbial data available for PD, SCZ, and PTSD, the associations between significantly different cytokine concentrations and the gut microbiome were assessed. Alpha-diversity was evaluated using Shannon and Simpson diversity measures, whereas beta-diversity was assessed with the permutational multivariate analysis variance (PERMANOVA) adonis test. The differential relative abundance of gut microbial taxa associated with altered cytokine concentrations was determined using the Multivariate Association with Linear Models 2 (MaAsLin2) test. The significance threshold was set at α = 0.05 for all tests (both p-value or q-value) and used the Benjamini-Hochberg method to correct for multiple testing. Results The differences in cytokine concentrations between cases and controls were found not to be associated with alpha- or beta-diversity. We observed an association between IL-6 and the enriched relative abundance of Lactobacillus (q = 0.023, PD) and RFN20 (q = 0.011, SCZ), and depleted relative abundance of Coprococcus (q = 0.023, PD). Conclusion Elevated levels of pro-inflammatory cytokines, particularly IL-6, are observed across neuropsychiatric disorders and may be associated with a decrease in SCFA-producing taxa such as Faecalibacterium. Further research is needed to understand how dysregulated cytokine concentrations contribute to neuropsychiatric disorders and to explore molecular pathways involving cytokines and disease-specific proteins such as alpha-synuclein for potential therapeutic strategies.

Objective: CD39 is crucial for the function of lymphocyte subsets, including CD4-positive T cells and Tregs. This study aimed to investigate the relationship between the quantities of Tregs, CD4-positive T cells, and CD39 expression on these cells with SLE disease activity. Methods: Peripheral blood from 108 SLE patients was analyzed. Patients were divided into SLE active and remission groups based on disease activity. The percentages and absolute counts of CD4-positive T cells and Tregs, along with CD39 expression, were measured by flow cytometry. Correlations between these markers and disease activity were evaluated, and the potential of CD39 as a biomarker was assessed. Results: The SLE active group had higher percentages and numbers of CD4-positive T cells compared to the remission group, while Treg levels were lower. CD39 expression was significantly higher in both Tregs and CD4-positive T cells in the active group. CD39 expression on Tregs correlated positively with their percentage and number, while CD39 expression on CD4-positive T cells showed a negative correlation with their percentage and number. ROC analysis indicated that CD39 could be a useful biomarker for SLE disease activity. Conclusion: CD39 on CD4-positive T cells exhibits immune suppressive functions similar to Tregs. CD4+CD39+ T cells represent a subset with immunosuppressive capabilities, potentially serving as a more effective marker for distinguishing SLE disease activity.

Immunotherapy for hepatocellular carcinoma (HCC) often does not achieve the desired results. Immunogenic cell death (ICD) has significant potential to trigger the body’s immune response against tumors, offering a hopeful strategy to improve immunotherapy for HCC. Arsenic trioxide (ATO), which induces ICD, may markedly increase the effectiveness of programmed cell death protein 1 (PD-1) inhibitors in the therapy of HCC. However, the complex mechanisms behind this synergistic effect are not yet fully understood. This study aims to elucidate the functions and mechanisms of ATO in HCC and to explore its potential to enhance immunotherapy for HCC. The results showed that ATO dose-dependently reduced the viability of HCC cells. Concurrently, ATO treatment led to an increase in ROS levels and induced ERS, which activated ICD-related damage associated molecular patterns (DAMPs). As a result, this process prompted dendritic cell maturation and enhanced the tumor immune microenvironment. ATO treatment increased the immunogenicity of HCC cells, allowing them to function as both prophylactic and therapeutic vaccines against HCC and to augment anti-tumor immunity. Finally, ATO was found to improve the effectiveness of PD-1 inhibitors in treating HCC in vivo. Therefore, we conclude that ATO effectively bolstered the body’s immune response by triggering ROS/ERS-mediated ICD, which significantly enhanced the therapeutic effectiveness of PD-1 inhibitors against HCC.

not-yet-known not-yet-known not-yet-known unknown Inflammatory bowel disease (IBD) is a chronic relapsing inflammatory disease of the intestines characterized by a progressive and unpredictable course, and colorectal cancer (CRC), a malignant tumor of the colon or rectum, is a malignant disease that seriously affects human health. The risk of colitis-associated cancer (CAC) is high in patients with IBD, and CRC is one of the most serious consequences for patients with IBD. Cell death is a fundamental physiological process in all living organisms, and it includes apoptosis, necroptosis, pyroptosis, autophagy, ferroptosis, and cuproptosis. Regulatory cell death (RCD), a form of cell death that can be regulated by a variety of biomolecules, plays an important role in maintaining physiological homeostasis in the body, resistance to pathogen attack, and a range of pathological states, such as inflammation and cancers. There is growing evidence that different types of RCD are involved not only in the pathogenesis of IBD, CRC, and CAC but also in the therapeutic process. The present review will provide ideas for further exploration of RCD affecting IBD, CRC, and CAC by summarizing the possible mechanisms of the involvement of different types of RCD in IBD, CRC, and CAC. Additionally, this article will discuss recent advancements in pharmacotherapy.

Introduction Co-infection with tuberculosis (TB) is the leading cause of death in individuals infected with human immunodeficiency virus (HIV)-1. Dolutegravir and lamivudine (DTG+3TC) has recently been recommended as the preferred first-line regimen for the treatment of new and treatment-experienced HIV-infected patients. The primary objective of this study was to determine the efficacy and safety of DTG 50 mg + 3TC 300 mg in HIV-positive antiretroviral therapy (ART)-naïve patients with TB who were receiving a rifampicin- or rifabutin-based treatment regimen, and to characterize viral suppression rates at week 48. Methods A single-center retrospective observational case series, spanning January 1, 2021 to March 1, 2023, was conducted in Guiyang Public Health Treatment Center. The outcomes of interest were successful TB treatment, viral load suppression, and immunological and biochemical indexes. Results All PWH had at least 48 weeks of follow-up, and all TB treatments were successful. A total of seven PWH (100%) achieved viral suppression (VL <50 copies/mL) from a baseline VL greater than 500,000 copies/mL. Among the PWH who started DTG+3TC after the initiation of the rifabutin-based anti-TB regimen, all achieved viral suppression by week 24, except for the non-suppressed PWH. CD4+ T-cell counts were greatly improved after antiretroviral treatment. The CD4+/CD8+ ratio increased by 0.38 (P < 0.001). Serum creatinine, total cholesterol, high-density lipoprotein cholesterol, and low-density lipoprotein cholesterol levels significantly increased (P = 0.054, P = 0.015, P < 0.001, and P < 0.05, respectively). There were no significant changes in body weight, alanine aminotransferase, aspartate aminotransferase, chronic kidney disease epidemiology collaboration-based serum creatinine, or triglyceride levels from baseline to week 48 (P > 0.05). No serious adverse events were observed. Conclusion This case series preliminarily validated the efficacy of DTG+3TC when combined with rifabutin-based anti-TB regimens in patients with TB and HIV.

Renal transplant recipients are at higher risk of COVID-19 infection due to chronic comorbidities and immunocompromised state. Limited information is available on the course and outcome of this infection in organ transplantation patients, especially in Nepal. This study aims to find out the impact of COVID-19 on renal transplant recipients. Methods: A retrospective cross-sectional study was conducted using census sampling technique on 601 patients who underwent renal transplant surgery at Shahid Dharmabhakta National Transplant Center (SDNTC), Bhaktapur. Both living as well as deceased donor renal transplant patients, who were COVID-19 confirmed through PCR test were included in the study. A self-developed, semi-structured telephone interview schedule was utilized for data collection. Results: Among the 601 patients that responded to our telephone calls, 37.9% were diagnosed as COVID-19 positive. The overall mortality among total respondent patient was nominal (5.7%) and 14.9% among COVID-19 positive patients. Most of the COVID-19 positive patients (79.8%) were male and residing in province 3 (Bagmati province). Among the expired patients, most of them (41.17%) were more than 45 years of age and employed (64.7%). Hypertension and diabetes mellitus were the top two comorbid condition. While, the most common presenting feature was fever followed by cough. Interestingly, 23.7 % of COVID-19 positive patient were hospitalized and among them 72.2% were admitted for more than 2 days. Notably, 65.8% of the COVID-19 patients were not vaccinated and among the vaccinated ones 73.1% had only single dose. The most common vaccine among patient was Vero Cell. Conclusion: This study highlights the heightened vulnerability of renal transplant recipients to COVID-19 as significant portion of the studied patients tested positive for COVID-19, with a notable mortality rate among these patients. The findings underscore the critical role of vaccination, as a considerable number of the COVID-19 positive patients were unvaccinated or partially vaccinated.

Infective endocarditis (IE) is a severe cardiovascular disease characterized by the formation of vegetations on heart valves. Our previous research found that streptococcal endocarditis is more common in elderly people and is prone to embolic complications leading to adverse clinical outcomes. von Willebrand Factor (VWF) is a crucial regulatory factor in the formation process and composition of vegetation in bacterial endocarditis, but its mechanism remains to be elucidated. This study investigated the role of VWF in the pathogenesis of Streptococcus mutans-induced endocarditis using two distinct mouse models: damage-induced and inflammation-induced endocarditis. We employed histological analysis, immunofluorescence, scanning electron microscopy, and molecular techniques to elucidate the mechanisms of vegetation formation and the contribution of VWF in each model.Our findings reveal significant differences in the timing and extent of VWF involvement between the two models, with a more rapid and pronounced role in the damage-induced model. VWF knockout mice showed reduced vegetation formation, particularly in the damage-induced model, while VWF supplementation restored vegetation development.These results highlight the critical role of VWF in endocarditis pathogenesis and suggest potential therapeutic strategies targeting VWF for the prevention and treatment of IE. Furthermore, our study provides novel insights into the interplay between VWF and inflammatory responses during endocarditis progression, opening new avenues for understanding the complex pathophysiology of this life-threatening condition.

Chronic spontaneous urticaria (CSU) is a debilitating inflammatory skin disease with a prevalence of approximately 1% of the population. It is characterised by recurrent itchy wheals and/or angioedema for more than 6 weeks without known triggers leading to a high quality of life impairment. The pathogenesis of CSU remains not fully understood. This study aimed to explore the pathomechanism of CSU beyond mast cells and IgE-dependent histamine release and to identify possible biomarkers for the disease and its treatment. We investigated a patient cohort in the first month of omalizumab treatment regarding the IgE levels and changes of gene and miRNA expression in peripheral blood. The cohort was divided into responders and non-responders (depending on the score of the Urticaria Control Test) and compared to a group of healthy controls. Our messenger RNA and microRNA microarray analyses revealed the greatest changes of expression levels at day 2 after the first omalizumab dose. We identified several genes and miRNAs of interest, most of which have not been described to be linked to CSU so far, underlining, for example, to T cell involvement or even suggesting platelet involvement.

Aims: The primary objective was an evaluation of the correlation between the lymphocyte-to-C-reactive protein ratio (LCR) and the prevalence of overactive bladder (OAB) within the adult United States population. Methods: Data was collected from the National Health and Nutrition Examination Survey (2005‒2010), and involved a non-pregnant cohort aged ≥20 years of age, with available LCR index and OAB information. We employed weighted univariate and multivariate logistic regression to assess the link between LCR and OAB risk. Subgroup, examinations of interaction, and restricted cubic spline analyses were also performed. Results: In all, 13723 subjects were recruited for analysis. Among them, 14.99% exhibited OAB and the mean LCR value was 2.61±0.07. The OAB risk decreased with higher quartiles of LCR. In model 2, subjects in the highest LCR quartiles showed 48% (OR: 0.52, 95%CI: 0.38–0.71, P < 0.001) reductions in the OAB risk, relative to those in the lowest LCR quartiles. These negative associations were found to be independent of various factors, shown in the subgroup analyses and interaction tests. Additionally, based on the restricted cubic spline analyses, there was a negative, non-linear relationship between LCR and OAB risk.

Background: Efficacy of allergen immunotherapy is dose-dependent; however, high doses of allergen may imply a greater risk of adverse reactions. Objective: To assess the safety and tolerability of subcutaneous immunotherapy (SCIT) with mixtures of mite allergen extracts, Dermatophagoides pteronyssinus/Blomia tropicalis (Dpt/Bt) and Dermatophagoides pteronyssinus/Lepidoglyphus destructor (Dpt/Ld) at maximum concentrations, in adult patients with allergic rhinitis or rhinoconjunctivitis, and controlled allergic asthma due to a clinically relevant sensitisation to these mites. Methods: An open-label, non-controlled, non-randomised, phase IIb clinical trial was carried out in three hospitals in Spain between September 2014 and May 2018. Patients received SCIT of either Dpt/Bt (100/1000 DPP/mL) or Dpt/Ld (100/100 DPP/mL) in two phases: a rush build-up phase on the first day (0.2 mL and 0.3 mL with a 30-minute interval) and a monthly maintenance phase administration (0.5 mL) up to 48 months. Results: Forty patients were recruited for the study, seven allocated to the Dpt/Bt group and 33 to the Dpt/Ld. None experienced immediate or delayed systemic Grade ≥2 reactions (EAACI classification) (systemic reactions were mostly Grade 1) nor died during the study. Local reactions were mostly mild (0‒10 cm). Thirty-nine patients (97.5%) experienced at least one adverse event (AE). Of the 283 reported AEs, eight (2.8%) were systemic reactions experienced by six (15%) subjects and 14 (4.9%) were local reactions sustained by ten (25%) subjects. Conclusions: SCIT treatment of patients with allergic rhinitis or rhinoconjunctivitis and controlled asthma with mixtures of Dpt/Bt and Dpt/Ld allergen extracts at maximum concentrations showed a favourable safety profile. Keywords: allergic asthma, allergic rhinitis, Blomia tropicalis, Dermatophagoides pteronyssinus, House dust mites, Lepidoglyphus destructor, maximum extract concentrations. safety,

Background: The diminished immune response observed in individuals with rheumatic diseases is a contributing factor to the occurrence of tuberculosis (TB) infection. The primary objectives of this investigation were to examine the risk factors associated with the advancement of rheumatic diseases in conjunction with latent tuberculosis infection (LTBI) leading to active tuberculosis (ATB). Methods: A retrospective study was conducted at the Xijing Hospital of the Fourth Military Medical University, utilizing the Laboratory Information System (LIS), to investigate rheumatic diseases diagnosed between January 2012 and October 2022. The collected data underwent statistical analysis using the Social Science Statistical Package (SPSS) version 26, with a significance level of p < 0.05 indicating statistical significance. Results: The research conducted involved a total of 33,020 individuals diagnosed with rheumatic conditions, of which only 18.16% underwent screening for latent tuberculosis infection (LTBI). Among the rheumatic patients, the incidence of LTBI was found to be 25.33%, with 14.57% of these cases progressing to active tuberculosis (ATB). Utilizing binary logistic regression analysis, it was determined that exposure to glucocorticoids (GCs) at a dosage of 20 mg/d or higher was an independent risk factor for the development of ATB [odds ratios (OR) = 3.59, 95% CI: 1.26-10.29, p = 0.017]. Conclusion: It is of the utmost importance to perform a screening for LTBI prior to commencing treatment in patients with rheumatic conditions, as they are at a significantly elevated risk of developing ATB due to their exposure to medium-high doses of glucocorticoids (GCs). Keywords: Latent tuberculosis infection; Active tuberculosis; Rheumatic diseases; Risk factors

Background: The pathomechanism of blast TBI and blunt TBI is different. In blast injury, evidence indicate that a single blast exposure can often manifest long-term neurological impairments. However, its pathomechanism is still elusive and treatments were symptomatic. Poly ADP Ribose Polymerase-1 (PARP1) is being implicated in the parthanatos and secondary neuroinflammation. Animal studies indicate the over-activation of as a major downstream event underlying the neurological sequalae of several traumatic and neurodegenerative disorders irrespective of the mode of cell death. PARP over-activation forms ADP polymers on several nuclear proteins known as trans-PARylation by consuming NAD+ and ATP. As NAD+ is a substrate for sirtuins, it too has been implicated in the oxidative stress underlying TBI pathology. Hypothesis: We recently established the implication of PARP1 following blast overpressure (BOP) and its differential response on astrocytes and microglial cells. We found that the inhibition of PARP is proven to be beneficial by attenuating oxidative stress. In this study, we hypothesized the involvement of the PARP1-SIRT-NRF2 axis following Blast induced PARP over-activation in glial cells for the manifestation of oxidative stress in BOP insults. Objective: Our objective is to determine the downstream modulation of the PARP-Sirt-NRF2 axis and changes in ATP levels following blast exposure in astrocytes and microglia cell lines. Results: As a result of NAD+ being a common substrate for PARP1 and Sirtuins, we found the decreased expression of SIRT1, SIRT3 and NRF2, a major transcriptional regulator for the expression of antioxidant genes. We found that ATP levels were elevated post-BOP from both glycolysis and oxidative phosphorylation (OXPHOS), an increase of ATP by glycolysis more significant than OXPHOS source indicating the pro-inflammation post-BOP. Conclusion: This result shows that blast-induced PARP over-activation impacts the deacetylation activity of sirtuins and consequently impacts the regulation of antioxidant levels in astrocytes and microglia.

Chronic lymphocytic leukemia (CLL) is characterized by the proliferation of dysfunctional B cells, resulting in significant immune dysregulation. Patients with CLL exhibit varied responses to B-cell receptor (BCR) targeted therapies, emphasizing the need for tailored immunotherapy approaches. This study investigated B cell function in untreated patients with CLL, and we further explored the effects of ex vivo protein kinase C activation on immune checkpoint expression and B cell profiles. Peripheral blood samples were collected from 21 untreated patients with CLL at King Edward Hospital in South Africa, between 2019 and 2022. B cells were stimulated with phorbol myristate acetate (PMA) and ionomycin. Using flow cytometry, the study explored the levels of B cell subsets and immune checkpoint proteins programmed cell death-ligand 2 (PD-L2) and cytotoxic T-lymphocyte associated protein 4 (CTLA-4) expression on various B cell subsets. PMA and ionomycin B cell stimulation upregulated CTLA-4 and PD-L2 expression on B cell subsets (p<0.0001). As expected, monoclonal antibodies targeting PD-1, PD-L1 and CTLA-4 significantly downregulated the CTLA-4 expression of B cell subsets (p<0.05), while PD-L2 exhibited varied responses in different B cell subsets. In addition, these monoclonal antibodies increased the levels of memory B cells (p<0.0128) and activated memory B cells (p<0.01). Protein kinase C activation on B cells stimulates immune checkpoint expression. The use of monoclonal antibodies on B cells play a critical role in the B cell function through the reduction of CD38 expressing activated B cells and upregulation of memory B cells. Moreover, the monoclonal antibody targeting PD-1, PD-L1 and CTLA-4 are effective in reducing the expression of CTLA-4 on B cell subsets.

Background: Axial spondyloarthritis (axSpA) is a chronic inflammatory disease primarily affecting the axial skeleton causing pain, inflammation, and stiffness. Individuals with axSpA are at greater risk of developing cardiovascular disease, which can be counteracted by physical activity. High-intensity interval training (HIIT) has been shown to improve cardiovascular health, but the effect on disease activity and the level of inflammation in axSpA has been less studied. With the aim of investigating how levels of inflammatory cytokines, myokines, and protein markers for bone metabolism are acutely affected by one bout of HIIT, we studied serum from individuals with axSpA and healthy controls (HC). Methods: Ten participants with axSpA and 11 age- and sex-matched HC performed a single HIIT bout on a cycle ergometer: 4x4 minutes intervals with three minutes active rest in between. Blood samples were taken before and one hour after the HIIT bout. Serum proteins (IL-6, IL-17, IL-18, TNF, CXCL-10, VEGF-A, BDNF, DKK-1, osteoprotegerin, osteocalcin, osteopontin, BMP-7, CRP) were analyzed with a Luminex system or ELISA. A two-way ANOVA was used for comparisons. Results: A main effect from baseline to one hour post HIIT showed that both groups had a significant increase in serum levels of IL-6. VEGF-A was significantly lower in the axSpA group but was not affected by the HIIT bout. BMP-7 increased in both groups after the HIIT. For the other proteins analyzed, there were no significant differences in serum concentrations between individuals with axSpA and HC, or within the two groups before and after one bout of HIIT. Conclusions: One acute bout of HIIT significantly increases the serum concentrations of IL-6 and BMP-7 after one hour in both individuals with axSpA and HC, whereas serum levels of other proteins investigated are not changed.

Background: Epidemiological data on seasonal coronaviruses (sCoVs) may provide insight on transmission patterns and demographic factors that favour coronaviruses (CoVs) with greater disease severity. This study describes the incidence of CoVs in several high-risk groups in Ottawa, Canada from October 2020 to March 2022. Methods: Serological assays quantified IgG and IgM antibodies to SARS-CoV-2, HCoV-OC43, HCoV-NL63, HCoV-HKU1, and HCoV-229E. Incident infections were compared between four population groups: individuals exposed to children, transit users, immunocompromised, and controls. Associations between antibody prevalence indicative of natural infection and demographic variables were assessed using regression analyses. Results: Transit users and those exposed to children were at no greater risk of infection compared to the control group. Fewer infections were detected in the immunocompromised group (p=0.03). SARS-CoV-2 seroprevalence was greater in individuals with low income and within ethnic minorities. Conclusions: Our findings suggest that non-pharmaceutical interventions intended to reduce SAR-CoV-2 transmission protected populations at high risk of exposure. The re-emergence of sCoVs and other common respiratory viruses alongside SARS-CoV-2 may alter infection patterns and increase the risk in vulnerable populations.

Enterovirus D68 (EV-D68) has gained attention as a respiratory and neuropathogen, particularly affecting children and causing outbreaks of severe respiratory illness and acute flaccid myelitis. This review explores the current state of knowledge regarding the immunology of EV-D68, delving into the intricate interactions between the virus and the host immune system. From the initial encounter of the virus with the innate immune response to the development of adaptive immunity, we navigate through key aspects of EV-D68 immunology. 1. Innate Immune Response: The journey begins with the recognition of EV-D68 by the innate immune system. Pattern recognition receptors (PRRs) identify viral components, triggering a cascade of antiviral responses. The role of interferons, natural killer cells, and other innate immune effectors in controlling early viral replication is highlighted. 2. Adaptive Immunity: The adaptive immune system orchestrates a more targeted and specific defense against EV-D68. B cells produce antibodies that recognize and neutralize the virus, while T cells play a crucial role in coordinating and regulating the immune response. This section explores the dynamics of antibody-mediated immunity and the cellular immune response in the context of EV-D68 infection. 3. Viral Evasion Mechanisms: EV-D68 employs various strategies to evade the host immune response, including antigenic variation and interference with host antiviral pathways. Understanding these mechanisms is vital for developing effective countermeasures. 4. Vaccine and Therapeutic Developments: A critical aspect of EV-D68 immunology is the ongoing efforts to develop vaccines and antiviral therapies. This section provides an overview of current research and potential strategies for preventing and treating EV-D68 infections. 5. Future Perspectives: The review concludes by highlighting the gaps in our understanding of EV-D68 immunology and proposing avenues for future research. The importance of a comprehensive approach to tackle this evolving respiratory pathogen is emphasized.

Recent advancements in immunotherapy spotlight the pivotal role of macrophages in disease treatment. The polarization of macrophages, wherein these immune cells differentiate into either pro-inflammatory (M1) or anti-inflammatory (M2) states, plays a vital role in the therapeutic modulation of a spectrum of diseases. Oligonucleotides have emerged as potent tools for modulating macrophage polarization with high specificity and potential cost-effectiveness compared to traditional therapies. In this review, we delve into the application of oligonucleotides for steering macrophage polarization, introducing how macrophage is polarized and how 4 different kinds of oligonucleotide (ASO, siRNA, agomir/antagomir and aptamer) works, discusses their therapeutic potentials and challenges associated with these strategies, emphasizing the importance of precise, disease-specific interventions by presenting actual examples. While the application of oligonucleotides in clinical faces challenges, we also highlights some recent, significant advances in current trials and the future potential in stimulating macrophages for therapeutic advantages in immunotherapy, signaling a frontier in disease treatment and management.