Inflammatory Conditions Research Articles

Targeted 308-nm Excimer Laser A Safe and Effective Solution for Inflammatory Skin Disorders

Background: The 308-nanometer excimer laser is a targeted ultraviolet B (UVB) light therapy that delivers high-intensity UVB rays directly to affected skin. It has shown considerable efficacy in managing various inflammatory skin conditions, including Psoriasis, Vitiligo, Atopic dermatitis (Eczema), Leukoderma, Alopecia Areata, Chronic recalcitrant dermatitis, Lichen planus, Cutaneous T-cell Lymphoma (e.g. Mycosis fungoides/ Sezary Syndrome), Parapsoriasis, Pityriasis lichenoides chronica, Pruritus, Urticaria pigmentosa, Superficial mycoses (e.g., dermatophytosis [ringworm]. The patient demographic of some of these conditions (e.g. Vitiligo) tends to skew towards patients with darker skin tones. Results: The excimer laser is particularly effective for treating resistant areas, such as the scalp, palmoplantar psoriasis, and hand and foot dermatitis, which often do not respond well to conventional therapies. It has also demonstrated notable success in promoting repigmentation in facial vitiligo, especially in patients with Fitzpatrick skin types IV–VI. Treatment results are typically observed quickly after 5-10 sessions, with sustained improvement and psoriasis clearance evident even at 1-year follow-up. Over the years, access to the Excimer laser procedures has expanded with the availability of these procedures in many private clinics as well as academic facilities. That has increased the availability of the treatment modality and patient choice of therapy. Conclusions: The excimer laser provides a safe, non-invasive treatment option with a strong record of efficacy for multiple inflammatory skin conditions. It is a viable alternative to systemic therapies and can be used either alone or in conjunction with other treatments for optimal patient outcomes.

Lycopene alleviates chemotherapy-induced mucositis via enhancing intestinal barrier function and attenuating TLR4/MyD88/NF-κB signaling cascade

5-Fluorouracil (5-FU) is one of the most common chemotherapeutic agents used in treating solid tumors. Lycopene is a natural exogenous carotenoid with antioxidant, anti-inflammatory, immunomodulatory, and anticancer activity. Intestinal mucositis is a commonly encountered complication for chemotherapy. However, effective or preventive treatment for this common complication is still need to be elucidated. The current study aimed to appraise the effect of lycopene on 5-FU-induced intestinal mucositis (FUIIM). Twenty-eight male rats were divided randomly and equally into four groups: control, lycopene, FUIIM, and 5-FU + lycopene groups. Parameters for mucosal barrier integrity, redox and inflammatory status, and apoptosis were immunoassayed in addition to histological assessment. Decreased body weight, significantly impaired redox status, increased caspase 3 level, toll-like receptor (TLR) 4 level, myd88 and NF-κB expression. However, decreased Bcl-2, and Ki-67 expression were detected in 5-FUIIM group. Furthermore, impairment in intestinal barrier integrity, represented by decreased Occludin and claudin1 levels with impaired histological features and ultrastructural features, were also detected. Meanwhile, lycopene co-administration protected against weight loss, heightened oxidative stress, apoptosis, inflammation, disturbed intestinal barrier integrity, and impaired histological and ultrastructure features. In conclusion, lycopene significantly improved intestinal mucositis, barrier integrity and gut toxicity induced by 5-FU in rats.

Successful Treatment of Perioral Dermatitis with Upadacitinib

Perioral dermatitis (POD) is a benign, chronic inflammatory skin condition characterized by small papules, pustules, and erythematous scaly patches around the perioral region. Treatment is not reliably effective, and the condition can be prolonged. We herein report a case of the successful treatment of perioral dermatitis (POD) using upadacitinib. A 45-year-old female with a history of rosacea, presented to the clinic with a 2-3-year history of severely pruritic erythematous papules around the chin and mouth, consistent with POD. Our study demonstrates that Janus kinase inhibitors are a promising therapeutic modality for this condition.

Pharmacodynamic effects and exploratory efficacy of afimetoran, a TLR7/8 inhibitor, in patients with cutaneous lupus erythematosus

Background: Cutaneous lupus erythematosus (CLE) is a chronic inflammatory skin condition occurring alone or as a manifestation of systemic lupus erythematosus (SLE). There is an unmet need for safe and effective CLE-focused treatments. Afimetoran is an investigational, first-in-class, potent oral inhibitor of toll-like receptors (TLRs) 7/8. Given the involvement of TLRs 7/8 in SLE, afimetoran may have therapeutic potential for CLE. A phase 1b randomized, double-blind, placebo-controlled study (NCT04493541) demonstrated preliminary safety and efficacy of afimetoran in patients with active CLE. We assessed the pharmacodynamics, safety, and efficacy of afimetoran and its impact on CLE pathobiology. Methods: Patients aged 18–65 years with SLE and cutaneous manifestations by EULAR/ACR 2019 classification criteria or biopsy-proven CLE, and modified CLE Disease Area and Severity Index-Activity (CLASI-A) score ≥6, were randomized 2:1 to once-daily afimetoran (30 mg) or placebo for 16 weeks with a 4-week post-treatment follow-up period. The primary endpoints were safety and tolerability; efficacy was exploratory. Transcriptomics and cytokine analyses were performed using peripheral whole blood and serum, respectively, at baseline (pre-dose) and each study visit (weeks 1, 2, 4, 8, 12, 16, and 20 [post-dose]). Statistical analyses compared data from the 13 randomized patients with thirteen age-, ethnicity-, and gender-matched healthy volunteers. Treatment responses were evaluated longitudinally in each treatment arm. The dataset was analyzed using a linear regression model. Gene set variation analysis (GSVA) was performed for pathway enrichment. Results: 13 patients with CLE were randomized (afimetoran, n=8; placebo, n=5); 12 patients completed 16 weeks of treatment and 1 discontinued after 6 weeks due to COVID-19. Compared with placebo, afimetoran demonstrated a favorable safety profile with no serious adverse events, and showed a greater reduction in CLASI-A scores as early as week 4, which persisted to week 20. Improvement in the molecular disease profile was rapid (week 1), sustained through the 16-week treatment period, and the 4-week post-treatment follow-up period. Expression of interferon (IFN) pathway genes was significantly reduced with afimetoran compared with baseline (ΔGSVA enrichment score [ES]=1.57, P<0.0001) and placebo (ΔGSVA ES=0.56, P<0.01); this effect was maintained through week 16 and ≥4 weeks post-treatment. Expression of TLR7 and TLR8 pathway genes and key cytokines (interleukin [IL]-6, tumor necrosis factor α, IL-18, IFNγ, macrophage inflammatory protein-1 alpha [CCL3/MiP1α] or beta [CCL4/MiP1β]) were greatly reduced with afimetoran treatment. GSVA demonstrated robust pharmacodynamic activity on immune cell populations, including immature and activated dendritic cells, macrophages, and inflammatory pathway signatures. Conclusion: In patients with CLE, afimetoran was safe, well tolerated, and demonstrated durable efficacy beyond the treatment period. Afimetoran’s clinical effects and potent pharmacodynamic impact on the molecular disease profile suggest a substantial therapeutic benefit for patients with CLE.

BlephEx-treatment for blepharitis: a prospective randomized placebo-controlled trial

Abstract Background Blepharitis is a chronic inflammatory condition of the eyelids that affects a large proportion of patients in eye care settings. First-line treatments provide only partial relief for many patients. The BlephEx™ device provides automated eyelid debridement and aims to remove pathogenic biofilms from the eyelid margin to treat blepharitis long-term. However, evidence supporting the efficacy of BlephEx™ is limited. Methods In this double-masked randomized controlled trial, 42 patients with symptomatic blepharitis refractory to treatment were assigned to the BlephEx™ treatment or sham treatment group. Outcome measures including Ocular surface disease index (OSDI), tear break-up time (TBUT), Schirmer test, and Efron grading scale scores were assessed at baseline and after 4 weeks. A crossover design in which the treatment groups were swapped after 4 weeks was used as a recruitment tool. After receiving treatment, two patients (one per group) were lost to follow-up. Results The sham group exhibited a significant decrease in the Efron Grading Scale score. No significant differences were observed in the other outcomes between the two groups. The BlephEx™ group showed slightly greater decreases in the OSDI and Efron grading scale scores and an increase in the TBUT than did the sham group, but these differences were not statistically significant. Mild discomfort was the most common side effect and occurred equally in both groups. Conclusions No significant difference in outcomes was observed between patients who underwent BlephEx™ therapy and those who received sham treatment. BlephEx™ treatment cannot be recommended for treating blepharitis. Trial registration Retrospectively registered on February 16, 2024 in the DRKS (German Clinical Trials Register under https://drks.de/search/de/trial/DRKS00033492) under the trial registration number DRKS00033492.

Abstract A011: Assessing pro-tumorigenicity of the aging microenvironment in a murine ovarian cancer model

Abstract Over 70% of high-grade serous ovarian cancer (HGSOC) patients are diagnosed after age 55 and the average patient who succumbs to HGSOC is 70 years old. Despite this, the majority of ovarian cancer studies, and cancer studies generally, utilize young mice that are more representative of human children. This approach overlooks age as a variable, despite its status as a top risk factor for cancer. Our preliminary studies reveal tumor burden and disease severity is significantly higher in aged mice compared to young animals. We have developed an epithelial cell line derived from C57BL/6 oviducts and used CRISPR-Cas9 genome editing to establish tumorigenic lines for syngeneic studies. One line harbors Trp53, Pten, and Brca2 deletions, is tumorigenic, and can be serially passaged in vitro. When injected intraperitoneally (IP) into 8-week and 56-week-old mice, equating to approximately 10- and 45-year-old humans respectively, a stark increase in tumor mass was evident in aged mice. Furthermore, the aged mice succumbed to disease at a faster rate after inoculation than the young group, where all mice succumbed to disease within 1-month of IP injection compared to some young mice surviving up to 3 months after injection. These findings, combined with epidemiologic data, suggest a metastatic driver in the aged microenvironment that facilitates worsened ovarian cancer progression. We are investigating two factors that change with age, (1) a suppressed immune system and (2) age-related changes to adipose tissue, as possible mechanisms driving this difference. Histologic analysis of tumors from each cohort showed decreased cleaved caspase-3 in aged tumors, indicating a reduction in tumor cell killing in older animals. Characterization of the pre-cancerous, tumor-naive microenvironment via flow cytometry and cytokine array have revealed that aged mice microenvironment is highly inflamed and features changes in immune populations and inflammatory states. Meanwhile, total RNA-sequencing of tumors harvested from aged and young mice showed minimal changes, but DEGs point to possible roles of fat transport and metabolism in these aged tumors, indicated by upregulated CD36 and lipoprotein lipase. Follow-up ex vivo experiments had demonstrated increased adhesion and proliferation of the previously described murine cancer cells to fat pads when cultured in vitro. When assessing tumor-naive fat depots, aged adipose tissue is comprised of significantly larger adipocytes and the omentum, a common secondary site of ovarian cancer and fatty organ, was found to have increased phospholipid content in older animals. Both findings point to a change in metabolic function in aged mice. Our preliminary findings indicate an important role of the aged microenvironment in driving enhanced diseases progression in older individuals and identifying the mechanisms behind this phenotype are critical; an improved understanding of how age affects HGSOC progression could enable the development of treatment strategies to prevent cancer cells from establishing in the peritoneum. Citation Format: Katherine A. Cummins, Ronny Drapkin. Assessing pro-tumorigenicity of the aging microenvironment in a murine ovarian cancer model [abstract]. In: Proceedings of the AACR Special Conference in Cancer Research: Tumor-body Interactions: The Roles of Micro- and Macroenvironment in Cancer; 2024 Nov 17-20; Boston, MA. Philadelphia (PA): AACR; Cancer Res 2024;84(22_Suppl):Abstract nr A011.

Polytrauma impairs fracture healing accompanied by increased persistence of innate inflammatory stimuli and reduced adaptive response.

The field of bone regeneration has primarily focused on investigating fracture healing and nonunion in isolated musculoskeletal injuries. Compared to isolated fractures, which frequently heal well, fractures in patients with multiple bodily injuries (polytrauma) may exhibit impaired healing. While some papers have reported the overall cytokine response to polytrauma conditions, significant gaps in our understanding remain in how fractures heal differently in polytrauma patients. We aimed to characterize fracture healing and the temporal local and systemic immune responses to polytrauma in a murine model of polytrauma composed of a femur fracture combined with isolated chest trauma. We collected serum, bone marrow from the uninjured limb, femur fracture tissue, and lung tissue over 3 weeks to study the local and systemic immune responses and cytokine expression after injury. Immune cell distribution was assessed by flow cytometry. Fracture healing was characterized using microcomputed tomography (microCT), histological staining, immunohistochemistry, mechanical testing, and small angle X-ray scattering. We detected more innate immune cells in the polytrauma group, both locally at the fracture site and systemically, compared to other groups. The percentage of B and T cells was dramatically reduced in the polytrauma group 6 h after injury and remained low throughout the study duration. Fracture healing in the polytrauma group was impaired, evidenced by the formation of a poorly mineralized and dysregulated fracture callus. Our data confirm the early, dysregulated inflammatory state in polytrauma that correlates with disorganized and impaired fracture healing.

2D4, a humanized monoclonal antibody targeting CD132, is a promising treatment for systemic lupus erythematosus

AbstractCurrent therapies for systemic lupus erythematosus that target a particular factor or cell type exhibit limited effectiveness. To address this limitation, our focus was on CD132, a subunit common to six inflammatory factor receptors implicated in SLE. Our study revealed heightened CD132 expression in SLE patients’ lymphocytes, contributing to the production of pro-inflammatory cytokines and immunoglobulins. We developed a novel humanized anti-CD132 monoclonal antibody, named as 2D4. 2D4 efficiently blocked IL-21 and IL-15, with limited effectiveness against IL-2, thereby suppressing T and B cells without disrupting immune tolerance. In the mouse immunization model, 2D4 virtually inhibited T cell-dependent, antigen-specific B-cell response. In lupus murine models, 2D4 mitigated inflammation by suppressing multiple pro-inflammatory cytokines and anti-dsDNA antibody titers, also diminishing proteinuria and glomerulonephritis. Compared to Belimumab, 2D4 exhibited superior efficacy in ameliorating the inflammatory state and preserving renal function. Moreover, 2D4 exhibited the ability to inhibit the production of pro-inflammatory factors and autoantibodies in PBMCs from individuals with SLE, highlighting its therapeutic potential for SLE individuals. Potent, 2D4 has the potential to significantly improve clinical outcomes in SLE and other complex autoimmune disorders.

Resveratrol Enhances the Efficacy of Combined BM-MSCs Therapy for Rat Spinal Cord Injury via Modulation of the Sirt-1/NF-κB Signaling Pathway.

Spinal cord injury (SCI) represents a severe trauma to the central nervous system, resulting in significant disability and imposing heavy burdens on families and society. Pathophysiological changes following SCI often trigger secondary injuries that complicate treatment. Bone marrow mesenchymal stem cells (BM-MSCs) have become a focal point of research due to their multifunctionality and self-renewal capabilities; however, their survival and neuroprotective functions are compromised in inflammatory environments. Resveratrol, known for its anti-inflammatory, anti-aging, and anti-oxidative stress properties, has been extensively studied. This research focuses on the anti-inflammatory effects of resveratrol post-SCI and its combined application with BM-MSCs to treat rat spinal cord injuries, exploring both efficacy and mechanisms. In vivo experiments investigated changes in the Sirt-1 signaling pathway post-SCI, while in vitro studies examined the effects of resveratrol on BM-MSCs under inflammatory conditions. The assessment included recovery of motor function, neuronal survival, and apoptosis in SCI rats treated with resveratrol alone or in combination with BM-MSCs. Findings reveal a correlation between Sirt-1 and inflammation signaling pathways post-injury. Resveratrol significantly enhanced the survival and efficacy of BM-MSCs in inflammatory environments by upregulating Sirt-1 and downregulating NF-κB and other inflammatory markers, thereby reducing apoptosis. Combined treatment with resveratrol and BM-MSCs showed superior outcomes in motor function recovery and neuronal survival compared to treatment with BM-MSCs alone. This study offers a novel therapeutic strategy for SCI, enhancing stem cell survival and function through modulation of the Sirt-1/NF-κB pathway, providing a theoretical and experimental foundation for clinical applications.

Psycho-Neuro-EndocrinE-Immunology Therapy of Cancer, Autoimmunity, Geriatric Disorders, Covid-19, and Hypertension.

Despite the great number of experimental investigations in the area of psycho-neuro-endocrine-immunology showing that endocrine, nervous, and immune systems cannot be in vivo physiologically separated, the diagnosis and therapies of the pathologies of these three functional biological systems continue to be separately performed from a clinical practice point of view. The separation between experimental and clinical medicine became dramatic after the discovery of more than 10 human molecules provided by anti-inflammatory and antitumor activity, completely devoid of any toxicity, which may be subdivided into three fundamental classes, consisting of the pineal indole, beta-carboline, and methoxy-kynuramine hormones. Moreover, human systemic diseases, including cancer, autoimmunity, and cardiovascular pathologies, despite their different pathogenesis and symptomatology, are commonly characterized by a progressive decline in the endogenous production of pineal hormones, endocannabinoids, and Ang 1-7, with a consequent inflammatory status and diminished natural resistance against cancer. Then the evaluation of the functional status of the pineal gland, the endocannabinoid system, and ACE2-Ang 1-7 axis should have to be included within the laboratory analyses for the systemic diseases. Finally, the correction of cancer- and autoimmunity-related neuroimmune and neuroendocrine alterations could influence the clinical course of systemic diseases. In fact, preliminary clinical results would demonstrate that the neuroimmune regimen with pineal hormones, cannabinoids, and Ang 1-7 may allow clinical benefits also in patients affected by systemic pathologies, including cancer, autoimmunity, and cardiovascular diseases, who did not respond to the standard therapies.

The role of the Mediterranean Diet in preventing the development and complications of lifestyle diseases – a Review

IntroductionThe Mediterranean diet, inspired by traditional dietary habits of the Mediterranean region, exhibits anti-inflammatory and protective effects, reducing the risk of civilization diseases such as obesity, type 2 diabetes, and cardiovascular disorders. This diet is characterized by a high intake of plant-based foods, olive oil, and moderate consumption of fish and dairy products. These components provide unsaturated fatty acids, polyphenols, and antioxidants, which positively impact metabolic health and lower the risk of chronic diseases. In the face of the global obesity epidemic and an increasing number of individuals affected by lifestyle-related diseases, the Mediterranean diet offers a promising tool to support a healthy lifestyle. Aim of study This article aims to review current scientific studies evaluating the potential of the Mediterranean diet in preventing and managing civilization diseases. Particular attention is given to its effects on weight loss, improvements in glycemic markers, reductions in low density lipoproteins (LDL) cholesterol levels, and blood pressure control. The article also explores its benefits for athletes' health, as well as its potential to reduce oxidative stress and inflammatory states. Material and methods A literature review of the PubMed database was conducted, assessing relevant studies on the Mediterranean diet and its impact on lifestyle diseases.

Development, QbD-based optimisation, in-vivo pharmacokinetics, and ex-vivo evaluation of Eudragit® RS 100 loaded flurbiprofen nanoparticles for oral drug delivery.

This study aims to develop and evaluate flurbiprofen-loaded polymeric nanoparticles to achieve sustained drug release, enhancing therapeutic efficacy and minimising dosing frequency for improved patient outcomes. Flurbiprofen-loaded polymeric nanoparticles were prepared using a tubular microreactor and spray drying, optimised via Box-Behnken Design. Characterisation included particle size, encapsulation efficiency, in vitro and in vivo drug release, and techniques like FTIR, DSC, XRD, and SEM. Statistical analysis ensured robust formulation optimisation and evaluation of performance. The optimised batch of flurbiprofen-loaded polymeric nanoparticles was characterised for mean diameter, PDI, zeta potential, drug release, and EE% were found to be 306.1 ± 6.00 nm, 0.184 ± 0.02 Mw, -23.6 ± 1.51 mV, 85.46 ± 0.53% and 92.31 ± 0.84 (% w/w) respectively. Pharmacokinetic analysis further confirmed the sustained release, extending up to 12 hours and enhancing permeation compared to the pure flurbiprofen. Sustained release of flurbiprofen-loaded polymeric nanoparticles significantly enhances therapeutic effectiveness for inflammatory conditions.

The Association Between Periodontitis and Respiratory Diseases: A Comprehensive Review

Periodontal disease is a significant factor in periodontal destruction, primarily initiated by a multi-bacterial infection that progresses through a cascade of chronic inflammatory responses. This persistent inflammation not only affects periodontal tissues but also has systemic implications, heightening the risk of various systemic diseases. Among these, respiratory diseases—which are closely linked to inflammatory processes, are of particular concern. Conditions such as asthma, pneumonia, chronic obstructive pulmonary disease (COPD), and lung cancer have been increasingly associated with the chronic inflammatory state induced by periodontitis. The aim of this review was to elucidate the mechanisms underlying the association between periodontitis and respiratory diseases. Chronic periodontitis creates a state of systemic inflammation that can disseminate through the bloodstream, impacting distant organs, including the lungs. Emerging evidence from recent studies highlights the role of periodontitis in both the initiation and exacerbation of respiratory diseases. Microbial pathogens associated with periodontitis, such as Porphyromonas gingivalis, can be aspirated into the lower respiratory tract, leading to either direct infection or modulation of the local immune response. This can increase susceptibility to respiratory conditions such as pneumonia and exacerbate pre-existing diseases like COPD and asthma. In summary, the relationship between periodontitis and respiratory diseases is complex and multifaceted, involving direct microbial interactions, systemic inflammation, and immune modulation. Understanding these connections is crucial for developing integrated therapeutic strategies that address both oral and respiratory health.

Drug Survival, Retention, and Persistence of Dupilumab in Adults and Adolescents with Atopic Dermatitis: A Narrative Literature Review.

Atopic dermatitis (AD) is a chronic, relapsing inflammatory skin condition that can have a negative impact on a patient's quality of life. Long-term effectiveness is required to manage the symptoms of AD (skin inflammation, eczematous lesions, and itching). Because some of the systemic immunosuppressants used to treat AD have been associated with serious adverse events (AEs), other safer, more effective options, including dupilumab, have been proven effective long-term for treatment of adult and adolescent patients with moderate-to-severe AD. The long-term safety and effectiveness of a drug are usually confirmed in real-world studies by evaluating its performance over time. Measures such as drug survival, drug retention, drug persistence, or retention rates reflect whether treatment may be considered as satisfactory by both patients and physicians, meeting key clinical needs. This review aimed to describe the survival, retention, or persistence of dupilumab therapy in adults and adolescents with moderate-to-severe AD by conducting a PubMed search in March 2023 and screening for relevant publications. Globally, real-world studies with dupilumab have regularly reported high drug survival rates after 1, 2, and 3years of observation, being consistently at 80-90%, with low rates of treatment discontinuation due to lack of efficacy or AEs. These findings are notably higher than 1- and 2-year drug survival rates of systemic immunosuppressants (including cyclosporine [37% and 20%, respectively] and methotrexate [41% and 33%, respectively]). Overall, real-world data on drug survival have confirmed that dupilumab provides long-term sustained efficacy and acceptable safety in patients with moderate-to-severe AD.

Eventration of Right Hemidiaphrgm – A Post Covid -19 Infection Complication

Introduction and Significance: Diaphragmatic eventration is an uncommon disorder marked by partial or complete thinning of the diaphragm's muscle tissue. In this condition, the diaphragm, which is normally flexible and moves downward during inhalation, instead moves upward in a paradoxical manner. This abnormal movement leads to restricted lung function. The condition can be congenital or acquired, with acquired cases often resulting from trauma to the phrenic nerve, either from mechanical or surgical causes, compression by thoracic space-occupying lesions, or various infectious or inflammatory conditions impacting the phrenic nerve. Many individuals with this condition may remain asymptomatic for long periods, leading to frequent underdiagnosis. Clinical suspicion should prompt chest X-rays, and the diagnosis can be confirmed with chest computed tomography (CT).  Case Presentation: We report the case of a 65-year-old male who exhibited right-sided hemi-diaphragmatic eventration and experienced dyspnea over the past two years. The patient underwent a multilayer surgical plication of the right hemidiaphragm, which resulted in a successful outcome.  Clinical Discussion: The choice to proceed with surgical intervention for diaphragmatic eventration is influenced by the severity of associated complications. Patients who are symptomatic and exhibit compromised respiratory, cardiovascular, or gastrointestinal function generally require diaphragmatic plication.  Conclusion: Despite its rarity, diaphragmatic eventration is a condition that warrants careful evaluation by clinicians. Early detection and surgical intervention are key to managing and repairing this condition effectively.

Characterization of exosome-mediated propagation of systemic inflammatory responses into the central nervous system.

The mechanisms through which systemic inflammation exerts its effect on the central nervous system (CNS) are still not completely understood. Exosomes are small (30 to 100nm) membrane-bound extracellular vesicles released by most of the mammalian cells. Exosomes play a vital role in cell-to-cell communication. This includes regulation of inflammatory responses by shuttling mRNAs, miRNAs, and cytokines, both locally and systemically to the neighboring as well as distant cells to further modulate the transcriptional and/or translational states and affect the functional phenotype of those cells that have taken up these exosomes. The role of circulating blood exosomes leading to neuroinflammation during systemic inflammatory conditions was hereby characterized. Serum-derived exosomes from LPS-challenged mice (SDEL) were freshly isolated from the sera of the mice that were earlier treated with LPS and used to study the effects on neuroinflammation. Exosomes isolated from the sera of the mice injected with saline were used as a control. In-vitro studies showed that the SDEL upregulate pro-inflammatory cytokine gene expression in the murine cell lines of microglia (BV-2), astrocytes (C8-D1A), and cerebral microvascular endothelial cells (bEnd.3). To further study their effects in-vivo, SDEL were intravenously injected into normal adult mice. Elevated mRNA expression of pro-inflammatory cytokines was observed in the brains of SDEL recipient mice. Proteomic analysis of the SDEL confirmed the increased expression of inflammatory cytokines in them. Together, these results demonstrate and strengthen the novel role of peripheral circulating exosomes in causing neuroinflammation during systemic inflammatory conditions.

Colostrum: The Golden Elixir of Health – Unveiling Its Multifaceted Benefits in Modern Medicine

Introduction: Colostrum is uniquely rich in immunoglobulins, growth factors, antibacterial peptides, probiotics, prebiotics, and essential vitamins and minerals. Available as a supplement, BC is used to prevent gastrointestinal infections, boost immune support, and aid in managing chronic inflammation, autoimmune diseases, and even athletic recovery. Aim: The aim of this article is to assess the potential benefits of colostrum across various health areas, including gastrointestinal health, immune system support, respiratory diseases, dermatology, autoimmune conditions and the development of preterm infants. The article will also present a critical analysis of current scientific data and examine future research directions and therapeutic advancements. Review methods: This article is based on a comprehensive, non-systematic review of the scientific literature. A thorough search of the PubMed database was conducted, and 45 sources published up to 2024 were analyzed to ensure that the information presented is current and relevant. Abbreviated description of the state of knowledge: Analysis of the literature suggests that colostrum may provide passive protection, reduce inflammation and support gut integrity in preterm infants. Inflammatory bowel disease may benefit from colostrum, though results for IBS are mixed. It aids wound healing, has anti-aging effects, and shows potential in autoimmune disease management. It also boosts respiratory immunity and aids athletes' recovery and performance. Conclusions: Colostrum contains bioactive components like immunoglobulins, lactoferrin, and growth factors. While current studies highlight its benefits in enhancing immunity, supporting gut health, and managing inflammatory conditions, more comprehensive clinical trials are required to confirm its efficacy and safety across various populations and health conditions.

Importance of younger age group and high inflammatory status in the association between periodontal disease and diabetes mellitus

Importance of younger age group and high inflammatory status in the association between periodontal disease and diabetes mellitus

Scavenger Receptor CD36 in Tumor-Associated Macrophages Promotes Cancer Progression by Dampening Type I Interferon Signaling.

Tumor-associated macrophages (TAMs) are a heterogenous population of myeloid cells that dictate the inflammatory tone of the tumor microenvironment (TME). In this study, we unveiled a mechanism by which scavenger receptor CD36 suppresses TAM inflammatory states. CD36 was upregulated in TAMs and associated with immunosuppressive features, and myeloid-specific deletion of CD36 significantly reduced tumor growth. Moreover, CD36-deficient TAMs acquired inflammatory signatures including elevated type-I interferon (IFN-I) production, mirroring the inverse correlation between CD36 and IFN-I response observed in cancer patients. IFN-I, especially IFNβ, produced by CD36-deficient TAMs directly induced tumor cell quiescence and delayed tumor growth. Mechanistically, CD36 acted as a natural suppressor of IFN-I signaling in macrophages through p38 activation downstream of oxidized lipid signaling. These findings establish CD36 as a critical regulator of TAM function and the tumor inflammatory microenvironment, providing additional rationale for pharmacological inhibition of CD36 to rejuvenate anti-tumor immunity.

Fibroblast growth factor 10 alleviates LPS-induced acute lung injury by promoting recruited macrophage M2 polarization.

Acute lung injury (ALI) is characterized by damage to the alveoli and an overabundance of inflammation. Representing a serious inflammatory condition, ALI lacks a precise treatment approach. Despite the recognized benefit impacts of Fibroblast growth factor-10 (FGF10) on ALI, the underlying mechanisms remain unelucidated. To study the role of FGF10 in ALI, C57BL/6J mice were intratracheally injected with 5mg/kg Lipopolysaccharide (LPS) with FGF10 (5mg/kg) or an equal volume of PBS. Inflammatory factors were quantified in bronchoalveolar lavage fluid (BALF) and plasma using ELISA. RNA sequencing of F4/80+Ly6G- macrophages in BALF explored changes in macrophage phenotype and potential mechanisms. Macrophage polarization in BALF was assessed using qRT-PCR, flow cytometry, and Western blot analysis. In vitro, a Transwell co-culture of mouse lung epithelial cells (MLE12) and bone marrow macrophages (BMDM) validated the role of FGF10 in modulating LPS-induced macrophage phenotypic changes. FGF10 ameliorated LPS-induced ALI by diminishing pro-inflammatory factors (IL-1β, TNF-α, and IL-6) and the neutrophil accumulation in BALF. FGF10 also increased the levels of anti-inflammatory factor IL-10. The FGF10 intervention group exhibited enhanced gene expression of macrophage arginine biosynthesis marker (ARG1), and expression of M2-type marker CD206 in monocytes and macrophages. In addition, phosphorylated STAT3 expression increased in isolated monocyte-derived macrophages. Experiments in vitro confirmed that FGF10 could elevate macrophage M2 marker ARG1 expression through the JAK2/STAT3 pathway. FGF10 ameliorates acute LPS-induced lung injury by modulating the polarization of monocyte-derived macrophages recruited in the alveolar space to the M2 type.