Granuloma Formation Research Articles

Review of the Adverse Effects Associated with Dermal Filler Treatments: Part I Nodules, Granuloma, and Migration.

The increase in the use of filler treatments within minimally invasive cosmetic surgery has correspondingly escalated the variety and frequency of associated side effects. Initially, unregulated procedures led to primary side effects such as infections, foreign body reactions, and granuloma formation. However, severe vascular complications like skin and tissue necrosis and blindness have emerged as recognized risks. Side effects from filler treatments can range from mild to life-threatening, including edema, pain, tenderness, numbness, bleeding, bruising, hematoma, redness, erythema, pigmentation, allergic reactions, itching, pruritus, the Tyndall effect, asymmetry, irregularity, migration, skin and soft tissue infections, nodules, granulomas, and vascular compromise. These side effects are categorized into early and delayed types. Many complications, particularly those related to vascular abnormalities, are frequently linked to procedural issues, emphasizing the importance of understanding filler properties, injection techniques, and facial anatomy. Preventing side effects is ideal, but early detection and treatment are crucial. Recognizing potential side effects based on their timing and understanding appropriate preemptive treatment methods is essential. This discussion addresses non-vascular side effects, highlighting their onset, symptoms, and management strategies. The comprehensive understanding and careful management of these side effects are vital for minimizing complications and ensuring patient safety in filler treatments.

Exploring the Intersection of Sarcoidosis and Cardiac Arrhythmias

Sarcoidosis is a multi-organ granulomatous disease of uncertain origin, characterized by the formation of non-necrotizing granulomas in various organs, including the heart. Cardiac involvement in sarcoidosis is rare, with approximately 5% of sarcoidosis patients developing clinically apparent cardiac disease, which is associated with significant morbidity and mortality. Genetically predisposed individuals develop granuloma in myocardium musculature, leading to aberrant conduction of cardiac impulses and the development of various arrhythmias. Common arrhythmias range from atrial fibrillation to ventricular tachycardia and can lead to sudden cardiac death because of ventricular fibrillation. The diagnostic challenge results from high specificity but rather limited sensitivity of endomyocardial biopsy, which is the gold standard diagnostic test, making advanced imaging techniques, such as cardiac magnetic resonance imaging and fluorine-18 fluorodeoxyglucose positron emission tomography, crucial for early detection. Management involves a complex approach with immunosuppression, antiarrhythmic medications, and catheter ablation, often supplemented by implantable cardioverter-defibrillators to prevent sudden cardiac death. In cardiac sarcoidosis, ventricular arrhythmias are common and cause high mortality. Timely intervention and management are crucial for a better prognosis. The disease's growing prevalence requires further research on refining early detection techniques and developing efficient treatment strategies for these high-risk patients. This review focuses on the etiopathogenesis of arrhythmias in cardiac sarcoidosis, diagnosis, and effective management strategies.

The impact of ICOSL/ICOS pathway-regulated long non-coding RNAs on liver fibrosis in mice infected with Schistosoma japonicum

BackgroundThe primary pathogenic mechanism of schistosomiasis-associated liver fibrosis involves the deposition of schistosome eggs, leading to the formation of liver egg granulomas and subsequent liver fibrosis. Hepatic stellate cells are abnormally activated, resulting in excessive collagen deposition and fibrosis development. While specific long non-coding RNAs (lncRNAs) have been associated with fibrotic processes, their roles in schistosomiasis-associated liver fibrosis remain unclear.MethodsOur previous research indicated that downregulating the ICOSL/ICOS could partially alleviate liver fibrosis. In this study, we established a schistosomiasis infection model in C57BL/6 and ICOSL knockout (KO) mice, and the liver pathology changes were observed at various weeks postinfection (wpi) using hematoxylin and eosin and Masson’s trichrome staining. Within the first 4 wpi, no significant liver abnormalities were observed. However, mice exhibited evident egg granulomas and fibrosis in their livers at 7 wpi. Notably, ICOSL-KO mice had significantly smaller pathological variations compared with simultaneously infected C57BL/6 mice. To investigate the impact of lncRNAs on schistosomiasis-associated liver fibrosis, quantitative real-time polymerase chain reaction (RT-qPCR) was used to monitor the dynamic changes of lncRNAs in hepatic stellate cells of infected mice.ResultsThe results demonstrated that lncRNA-H19, -MALAT1, -PVT1, -P21 and -GAS5 all participated in liver fibrosis formation after schistosome infection. In addition, ICOSL-KO mice exhibited significantly inhibited expression of lncRNA-H19, -MALAT1 and -PVT1 after 7 wpi. In contrast, they showed enhanced expression of lncRNA-P21 and -GAS5 compared with C57BL/6 mice, influencing liver fibrosis development. Furthermore, small interfering RNA transfection (siRNA) in JS-1 cells in vitro confirmed that lncRNA-H19, -MALAT1, and -PVT1 promoted liver fibrosis, whereas lncRNA-P21 and -GAS5 had the opposite effect on key fibrotic molecules, including α- smooth muscle actin and collagen I expression.ConclusionsThis study uncovers that ICOSL/ICOS may play a role in activating hepatic stellate cells and promoting liver fibrosis in mice infected with Schistosoma japonicum by dynamically regulating the expression of specific lncRNAs. These findings offer potential therapeutic targets for schistosomiasis-associated liver fibrosis.Graphical

Breaking the Cycle: Matrix Metalloproteinase Inhibitors as an Alternative Approach in Managing Tuberculosis Pathogenesis and Progression.

Mycobacterium tuberculosis (Mtb) has long posed a significant challenge to global public health, resulting in approximately 1.6 million deaths annually. Pulmonary tuberculosis (TB) instigated by Mtb is characterized by extensive lung tissue damage, leading to lesions and dissemination within the tissue matrix. Matrix metalloproteinases (MMPs) exhibit endopeptidase activity, contributing to inflammatory tissue damage and, consequently, morbidity and mortality in TB patients. MMP activities in TB are intricately regulated by various components, including cytokines, chemokines, cell receptors, and growth factors, through intracellular signaling pathways. Primarily, Mtb-infected macrophages induce MMP expression, disrupting the balance between MMPs and tissue inhibitors of metalloproteinases (TIMPs), thereby impairing extracellular matrix (ECM) deposition in the lungs. Recent research underscores the significance of immunomodulatory factors in MMP secretion and granuloma formation during Mtb pathogenesis. Several studies have investigated both the activation and inhibition of MMPs using endogenous MMP inhibitors (i.e., TIMPs) and synthetic inhibitors. However, despite their promising pharmacological potential, few MMP inhibitors have been explored for TB treatment as host-directed therapy. Scientists are exploring novel strategies to enhance TB therapeutic regimens by suppressing MMP activity to mitigate Mtb-associated matrix destruction and reduce TB induced lung inflammation. These strategies include the use of MMP inhibitor molecules alone or in combination with anti-TB drugs. Additionally, there is growing interest in developing novel formulations containing MMP inhibitors or MMP-responsive drug delivery systems to suppress MMPs and release drugs at specific target sites. This review summarizes MMPs' expression and regulation in TB, their role in immune response, and the potential of MMP inhibitors as effective therapeutic targets to alleviate TB immunopathology.

Kupffer cell and recruited macrophage heterogeneity orchestrate granuloma maturation and hepatic immunity in visceral leishmaniasis.

In murine models of visceral leishmaniasis (VL), parasitization of resident Kupffer cells (resKCs) is responsible for early growth of Leishmania infantum in the liver, which leads to granuloma formation and eventual parasite control. We employed the chronic VL model, and revealed an open niche established by KCs death and their migration outside of the sinusoids, resulting in their gradual replacement by monocyte-derived KCs (moKCs). While early granulomas were composed of resKCs, late granulomas were found outside of the sinusoids and contained resKC-derived macrophages, and monocyte-derived macrophages (momacs). ResKCs and moKCs within the sinusoids were identified as homeostatic/regulatory cells, while resKC-derived macrophages and momacs within late granulomas were pro-inflammatory. Despite the infection being largely confined to the resKC-derived macrophages, in the absence of monocyte recruitment, parasite control was strongly compromised. Macrophage heterogeneity, involving migration and reprogramming of resKCs, along with recruitment of monocyte-derived cells, is a hallmark of granuloma maturation and hepatic immunity in VL.

Targeting mycobacterial efflux system to enhance tuberculosis therapy

The worldwide health epidemic of tuberculosis (TB) persists. It still claims millions of lives each year despite medical breakthroughs. Long-term therapies, drug-resistant TB strains, and co-infections with conditions like HIV necessitate novel approaches. The use of Mycobacterium tuberculosis (Mtb) efflux pumps, which actively expel drugs and decrease their effectiveness, is one such approach. EPIs (Efflux Pump Inhibitors) have the potential to treat tuberculosis. This review offers insights into Mtb's immune evasion mechanisms, including its strong cell wall, granuloma formation, immunological modulation, and dormancy, as well as TB epidemiology, worldwide eradication efforts, and those processes. Dissecting Efflux Pumps highlights their significance in drug resistance, particularly against first-line TB medications. Efflux pumps are notorious for causing antibiotic resistance. EPIs may have benefits such as increased drug efficacy, resistance reversal, shortened treatment durations, less toxicity, improved adherence, and targeting of latent TB. The effectiveness of various EPI classes, including phenylalkylamines, protonophores, phenothiazines, and plant-derived derivatives, against Mtb growth and efflux pumps is evaluated. The creation of effective EPIs, a clearer understanding of efflux pump control, and essential clinical trials for validation remain obstacles.

Peritoneal bile granuloma formation at the site of caesarean surgical scar

Bile granuloma is a rare complication associated with cholecystectomy about which few case reports have been written. Herein we present the case of a patient who underwent laparoscopic bilateral salpingectomy for the purpose of sterilization and was incidentally found to have a linear collection of bile granulomas along the site of adhesions from her cesarean section. We also present a review of case reports on bile granuloma that have presented in OB/GYN and suggest that this rare pathology should be cited as a differential more often when considering intra-abdominal pathology, particularly for pelvic surgeons. We argue that this condition is likely more common than previously thought and suggest that without further research into this topic, routine biopsy or removal of encountered lesions may not always be necessary in patients at low likelihood for having a malignant pathology.

Addressing Glass Contamination in Radiology: What Can We Do to Minimize Its Impact?

Abstract Introduction There is a risk of glass contamination with the use of single-dose glass ampoules. Complications of injection include infection and granuloma formation and this is widely described in anesthetic literature. To date, there is no data on the effect of different ampoule opening methods on the degree of glass contamination. Purpose This article explores different ampoule opening methods and determines if any method is superior to the others with respect to glass contamination frequency. This article also increases awareness of glass contamination and its potential complications in the radiology community. Methods A controlled trial was undertaken with 15 glass ampoules filled with normal saline, divided into three groups. The ampoules in each of the group were opened via each method: freehand, ampoule breaker, and ampoule opener. The solution was aspirated with an 18-gauge drawing-up needle, which was centrifuged and decantered to be placed onto slides and inspected under light microscopy to assess the glass contaminants. Results Between each cohort, the freehand opening provided the least number of glass particles with 42, followed by the ampoule breaker and snapper. The greatest size of glass contamination was seen from the ampoule snapper at 300 μm, while the lowest average particle size was seen from the ampoule breaker. Conclusion The study confirmed presence of glass contamination in all three methods. Freehand opening minimized the number of particulates, while the ampoule breaker minimized the average particulate size. The ampoule snapper produced larger glass particulates in the trials and was deemed the least effective method.

Characterization of a model of liver regeneration: Role of hedgehog signaling in experimental hepatic amoebiasis

The development of amoebic liver abscess (ALA) leads to liver necrosis, accompanied by an exacerbated inflammatory response and the formation of multiple granulomas. Adequate management of the infection through the administration of treatment and the timely response of the organ to the damage allows the injury to heal with optimal regeneration without leaving scar tissue, which does not occur in other types of damage such as viral hepatitis that may conducts to fibrosis or cirrhosis. The Hedgehog signaling pathway (Hh) is crucial in the embryonic stage, while in adults it is usually reactivated in response to acute or chronic injuries, regeneration, and wound healing. In this work, we characterized Hh in experimental hepatic amoebiasis model, with the administration of treatment with metronidazole, as well as a pathway inhibitor (cyclopamine), through histological and immunohistochemical analyses including an ultrastructure analysis through transmission electron microscopy. The results showed an increase in the percentage of lesions obtained, a decrease in the presence of newly formed hepatocytes, a generalized inflammatory response, irregular distribution of type I collagen accompanied by the presence of fibroblast-type cells and a decrease in effector cells of this pathway. These results constitute the first evidence of the association of the activation of Hh with the liver regeneration process in experimental amebiasis.

Comparative Study between Endoscopic Surgical Excision of Anterior Glottic Web with or without Keel Placement

Abstract Background A focal narrowing of the airway caused by fibrotic tissue at the level of the true vocal folds is known as anterior glottic web. Congenital anterior glottic webs are less common than acquired anterior glottic webs. Endotracheal intubation, laryngeal trauma or surgery close to the anterior commissure, radiotherapy, and, in rare cases, inflammatory processes can cause them at any age. Objective To decide the need for endoscopic keel placement for management of anterior glottic web, prevention of vocal cord adhesions and to reduce the recurrence. Patients and Methods This study was systematic review and meta-analysis study included research articles with the following criteria; retrospective, prospective, case series, case report studies, published in English language, in the last 25 years, only studies on humans, studies on congenital and acquired anterior glottic web, studies with endoscopic keel placement, and studies without keel placement. Results The main findings of the current study was that; among keel used studies, the recurrence proportion was 13.5% with 95% Confidence interval (5.5%-24.2%), the proportion of granulation from pooled studies was found in 3.44% with 95% Confidence interval (1.16%-7.5%)and regarding voice improvement in this meta-analysis high significant improvement (94.2%) with 95% Confidence interval (85.8%-99%) was reported; Recurrence among the 3 studies did not use keel was 30.6% with 95% Confidence interval (7%-61. 8%). However, the voice improvement was reported among 97.4% with 95% Confidence interval (91.5 %-99.9%) Data Sources Medline databases (PubMed, Medscape, ScienceDirect. EMF-Portal) and all materials available in the Internet till 2019. Conclusion The optimal treatment of acquired anterior glottic web remains controversial; Placement of a keel has low recurrent rate and good voice improvement but had several disadvantages such as the need for two separate operations under general anaesthesia, prolonged recovery, and the risk of infection and granuloma formation. However other techniques as the mucosal flap technique had better voice improvement without granulation formation with high success rates.

Unmasking the nature of granulomatosis with polyangiitis – a diagnostic odyssey revealed through a compelling case report

Introduction and aim. Granulomatosis with polyangiitis (GPA), formerly known as Wegener’s granulomatosis, presents a formidable challenge in the realm of autoimmune diseases. Granulomatosis, characterized by vasculitis and granuloma formation, exhibits diverse clinical manifestations. The rarity of GPA is evident, with an estimated incidence between 0.4 and 11.9 cases per 1 million person-years. The aim of this report is to show the complex diagnostic challenges inherent in GPA, demonstrating the diagnostic process from initial symptoms. Description of the case. This case report unfolds the diagnostic journey of a 52-year-old Caucasian male. The presented case, initially suspected as a respiratory infection, led to a comprehensive investigation owing to persistent symptoms, abnormal blood counts, and elevated inflammatory markers. This narrative aims to depict the patient’s diagnostic journey. Key diagnostic tools include ANCA testing, imaging studies, and tissue biopsy. Pulmonary nodules, lymphangitic changes, and renal involvement culminating in a GPA diagnosis confirmed by positive ANCA and anti-PR3 antibodies. The successful management of this case involved a tailored therapeutic regimen, including cyclophosphamide and methylprednisolone, addressing both vasculitic and renal components. Conclusion. This case contributes to the understanding of atypical presentations of GPA, emphasizing the importance of a holistic and dynamic diagnostic approach.

IQGAP1 domesticates macrophages to favor mycobacteria survival via modulating NF-κB signal and augmenting VEGF secretion

Tuberculosis, caused by Mycobacterium tuberculosis (Mtb), still ranks among the leading causes of annual human death by infectious disease. Mtb has developed several strategies to survive for years at a time within the host despite the presence of a robust immune response, including manipulating the progression of the inflammatory response and forming granulomatous lesions. Here we demonstrate that IQGAP1, a highly conserved scaffolding protein, compartmentalizes and coordinates multiple signaling pathways in macrophages infected with Mycobacterium marinum (Mm or M.marinum), the closest relative of Mtb. Upregulated IQGAP1 ultimately suppresses TNF-α production by repressing the MKK3 signal and reducing NF-κBp65 translocation, deactivating the p38MAPK pathway. Accordingly, IQGAP1 silencing and overexpression significantly alter p38MAPK activity by modulating the production of phosphorylated MKK3 during mycobacterial infection. Pharmacological inhibition of IQGAP1-associated microtubule assembly not only alleviates tissue damage caused by M.marinum infection but also significantly decreases the production of VEGF—a critical player for granuloma-associated angiogenesis during pathogenic mycobacterial infection. Similarly, IQGAP1 silencing in Mm-infected macrophages diminishes VEGF production, while IQGAP1 overexpression upregulates VEGF. Our data indicate that mycobacteria induce IQGAP1 to hijack NF-κBp65 activation, preventing the expression of proinflammatory cytokines as well as promoting VEGF production during infection and granuloma formation. Thus, therapies targeting host IQGAP1 may be a promising strategy for treating tuberculosis, particularly in drug-resistant diseases.

The Renin-Angiotensin-Aldosterone System Regulates Sarcoidosis Granulomatous Inflammation.

Rationale: Sarcoidosis is a granulomatous disorder of unclear cause notable for abnormal elevation of blood and tissue ACE1 (angiotensin converting enzyme 1) levels and activity. ACE1 regulates the renin-angiotensin-aldosterone system (RAAS), the terminal product of which is aldosterone, which selectively engages mineralocorticoid receptors to promote inflammation. Objectives: We sought to determine whether the RAAS promotes sarcoidosis granuloma formation and related inflammatory responses. Methods: Using an established ex vivo model, we first determined whether aldosterone was produced by sarcoidosis granulomas and verified the presence of CYP11B2, the enzyme required for its production. We then evaluated the effects of selective inhibitors of ACE1 (captopril), angiotensin type 1 receptor (losartan), and mineralocorticoid receptors (spironolactone, eplerenone) on granuloma formation, reflected by computer image analysis-generated granuloma area, and selected cytokines incriminated in sarcoidosis pathogenesis. Measurements and Main Results: Aldosterone was spontaneously produced by sarcoidosis peripheral blood mononuclear cells, and both intra- and extracellular levels steadily increased during granuloma formation. In parallel, peripheral blood mononuclear cells were shown to express more CYP11B2 during granuloma formation. Significant inhibition of sarcoidosis granulomas and related cytokines (TNFα, IL-1β, IFNγ, IL-10) was observed in response to pretreatments with captopril, losartan, spironolactone, or eplerenone, comparable to that of prednisone. Conclusions: The RAAS is intact in sarcoidosis granulomas and contributes significantly to early granuloma formation and to related inflammatory mediator responses, with important implications for clinical management.

Air pollution and incident sarcoidosis in central Pennsylvania

ABSTRACT Sarcoidosis is a chronic granulomatous disease predominantly affecting the lungs and inducing significant morbidity and elevated mortality rate. The etiology of the disease is unknown but may involve exposure to an antigenic agent and subsequent inflammatory response resulting in granuloma formation. Various environmental and occupational risk factors have been suggested by previous observations, such as moldy environments, insecticides, and bird breeding. Our study investigated the association of air pollution with diagnosis of sarcoidosis using a case-control design. Penn State Health electronic medical records from 2005 to 2018 were examined for adult patients with (cases) and without (controls) an International Classification of Disease (ICD)-9 or −10 code for sarcoidosis. Patient addresses were geocoded and 24-hr residential-level air pollution concentrations were estimated using spatio-temporal models of particulate matter <2.5 μm (PM2.5), ozone, and PM2.5 elemental carbon (EC) and moving averages calculated. In total, 877 cases and 34,510 controls were identified. Logistic regression analysis did not identify significant associations between sarcoidosis incidence and air pollution exposure estimates. However, the odds ratio (OR) for EC for exposures occurring 7–10 years prior did approach statistical significance, and ORs exhibited an increasing trend for longer averaging periods. Data suggested a latency period of more than 6 years for PM2.5 and EC for reasons that are unclear. Overall, results for PM2.5 and EC suggest that long-term exposure to traffic-related air pollution may contribute to the development of sarcoidosis and emphasize the need for additional research and, if the present findings are substantiated, for public health interventions addressing air quality as well as increasing disease surveillance in areas with a large burden of PM2.5 and EC.

Immune Responses to Mycobacterium tuberculosis Infection in the Liver of Diabetic Mice.

Individuals with uncontrolled diabetes are highly susceptible to tuberculosis (TB) caused by Mycobacterium tuberculosis (M. tb) infection. Novel treatments for TB are needed to address the increased antibiotic resistance and hepatoxicity. Previous studies showed that the administration of liposomal glutathione (L-GSH) can mitigate oxidative stress, bolster a granulomatous response, and diminish the M. tb burden in the lungs of M. tb-infected mice. Nonetheless, the impact of combining L-GSH with conventional TB treatment (RIF) on the cytokine levels and granuloma formation in the livers of diabetic mice remains unexplored. In this study, we evaluated hepatic cytokine profiles, GSH, and tissue pathologies in untreated and L-GSH, RIF, and L-GSH+RIF treated diabetic (db/db) M. tb-infected mice. Our results indicate that treatment of M. tb-infected db/db mice with L-GSH+RIF caused modulation in the levels of pro-inflammatory cytokines and GSH in the liver and mitigation in the granuloma size in hepatic tissue. Supplementation with L-GSH+RIF led to a decrease in the M. tb burden by mitigating oxidative stress, promoting the production of pro-inflammatory cytokines, and restoring the cytokine balance. These findings highlight the potential of L-GSH+RIF combination therapy for addressing active EPTB, offering valuable insights into innovative treatments for M. tb infections.

Computational Analysis of Polymeric Biodegradable and Customizable Airway Stent Designs.

The placement of endotracheal prostheses is a procedure used to treat tracheal lesions when no other surgical options are available. Unfortunately, this technique remains controversial. Both silicon and metallic stents are used with unpredictable success rates, as they have advantages but also disadvantages. Typical side effects include restenosis due to epithelial hyperplasia, obstruction and granuloma formation. Repeat interventions are often required. Biodegradable stents are promising in the field of cardiovascular biomechanics but are not yet approved for use in the respiratory system. The aim of the present study is to summarize important information and to evaluate the role of different geometrical features for the fabrication of a new tracheo-bronchial prosthesis prototype, which should be biodegradable, adaptable to the patient's lesion and producible by 3D printing. A parametric design and subsequent computational analysis using the finite element method is carried out. Two different stent designs are parameterized and analyzed. The biodegradable material chosen for simulations is polylactic acid. Experimental tests are conducted for assessing its mechanical properties. The role of the key design parameters on the radial force of the biodegradable prosthesis is investigated. The computational results allow us to elucidate the role of the pitch angle, the wire thickness and the number of cells or units, among other parameters, on the radial force. This work may be useful for the design of ad hoc airway stents according to the patient and type of lesion.

Deciphering lung granulomas in HIV & TB co-infection: unveiling macrophages aggregation with IL6R/STAT3 activation

ABSTRACT Tuberculosis (TB) remains a leading cause of mortality among individuals coinfected with HIV, characterized by progressive pulmonary inflammation. Despite TB’s hallmark being focal granulomatous lung lesions, our understanding of the histopathological features and regulation of inflammation in HIV & TB coinfection remains incomplete. In this study, we aimed to elucidate these histopathological features through an immunohistochemistry analysis of HIV & TB co-infected and TB patients, revealing marked differences. Notably, HIV & TB granulomas exhibited aggregation of CD68 + macrophage (Mφ), while TB lesions predominantly featured aggregation of CD20+ B cells, highlighting distinct immune responses in coinfection. Spatial transcriptome profiling further elucidated CD68+ Mφ aggregation in HIV & TB, accompanied by activation of IL6 pathway, potentially exacerbating inflammation. Through multiplex immunostaining, we validated two granuloma types in HIV & TB versus three in TB, distinguished by cell architecture. Remarkably, in the two types of HIV & TB granulomas, CD68 + Mφ highly co-expressed IL6R/pSTAT3, contrasting TB granulomas’ high IFNGRA/SOCS3 expression, indicating different signaling pathways at play. Thus, activation of IL6 pathway may intensify inflammation in HIV & TB-lungs, while SOCS3-enriched immune microenvironment suppresses IL6-induced over-inflammation in TB. These findings provide crucial insights into HIV & TB granuloma formation, shedding light on potential therapeutic targets, particularly for granulomatous pulmonary under HIV & TB co-infection. Our study emphasizes the importance of a comprehensive understanding of the immunopathogenesis of HIV & TB coinfection and suggests potential avenues for targeting IL6 signaling with SOCS3 activators or anti-IL6R agents to mitigate lung inflammation in HIV & TB coinfected individuals.

Converging paths: Microneedle-based dual intervention of IL-23/IL-17 axis and granuloma formation in rheumatoid nodules

Rheumatoid nodules (RNs) are an extra-articular manifestation of rheumatoid arthritis and are frequently observed in patients with autoimmune and inflammatory conditions. The development of RNs involves several stages, including inflammation of blood vessels, cell death triggered by medications, and infiltration of inflammatory cells leading to nodule formation. Recent studies highlight the importance of the IL-23/IL-17 axis and the migration of chronic inflammatory cells in this process, forming palisading granulomas. Current treatments often fail to manage RNs effectively because they tend to reoccur and appear in multiple locations. This study proposes a new therapeutic strategy combining corticosteroid treatment with gene silencing therapy using small interfering RNA (siRNA) targeting IL-23. Targeting these inflammatory pathways simultaneously aims to reduce both the size and number of nodules, potentially shortening the treatment duration. An innovative delivery system utilizing lipid-polymer hybrid nanoparticles (LPNs) and hyaluronic acid-based dissolving microneedles (MNs) is proposed to be developed. The LPNs will be designed with DOTAP (1,2-dioleoyl-3-trimethylammonium propane) and DSPE-PEG (distearoyl-phosphoethanolamine-polyethylene glycol) as the lipid core, along with poly-lactic-co-glycolic acid (PLGA) polymer. These MN patches would improve the skin’s permeability, allowing LPN carrying the siRNA and corticosteroid to penetrate effectively. This non-invasive approach is expected to enhance the diffusion of LPNs into the skin, thereby increasing the availability of the therapeutic payload. Therefore, we hypothesize that targeting the IL-23/IL-17 axis and granuloma formation with the synergistic combination of targeted therapy and advanced delivery technology will revolutionize the treatment of RNs.

Malnutrition disrupts adaptive immunity during visceral leishmaniasis by enhancing IL-10 production.

Malnutrition contributes to the development of VL. Despite the advances regarding this association, how malnutrition affects the adaptive immune mechanisms in VL is still unclear. We found that malnutrition disrupts the ability to control parasite replication in the spleen and liver in VL due to defective IFN-γ-mediated immunity, reduced hepatic granuloma formation, and enhanced IL-10 production. Blocking IL-10R signaling restored the protective mechanisms to control parasite replication in the malnourished mice without interfering with the undernutrition state. Thus, we demonstrate that malnutrition disrupts the adaptive immunity against VL due to an aberrant IL-10 production. Understanding the association between malnutrition and VL will provide insights into therapeutic approaches.

Immune system triggers as a factor for the formation of foreign body granuloma after hyaluronic acid fillers treatment.

Immune system triggers as a factor for the formation of foreign body granuloma after hyaluronic acid fillers treatment.