Intense Inflammation Research Articles

Ways to improve the effectiveness of uvulopalatoplasty

Ronchopathy is a complex polyethological disease that has a multifactorial negative effect on the cardiovascular, respiratory and other systems of the body. Mortality in this terrible disease, most often from vascular causes and, especially, in the presence of obstructive sleep apnea syndrome, ranges from 6 to 11%, and the consequences of various complications associated with this disease increase it to 37%. The effectiveness of surgical methods of treating patients with ronchopathy is still clearly unsatisfactory, and does not allow most of them to achieve a guaranteed recovery. At the same time, the growing number of such patients, who are in dire need of effective treatment and reliable prevention of complications of this disease, encourages specialists to further search for surgical treatment methods. Surgical interventions on the soft palate in patients with ronchopathy and obstructive sleep apnea syndrome are based on the principle of injury to the palatine curtain of varying intensity (surgical, thermal, radiofrequency, laser, chemical), independent of the methods of exposure. At the same time, depending on the intensity of exposure, inflammation, necrosis or partial tissue rejection are noted and, as a result, scarring, compaction and a decrease in the volume of the palate. At the same time, the mobility of the palatine curtain should decrease, and the intensity of snoring should decrease. However, injury caused primarily to the velopharyngeal muscles often leads to hypo- and atrophy, hypotension and significant sagging of the palate, and, subsequently, to a recurrence of the disease and increased snoring. This significantly reduces the effectiveness of surgical treatment of these patients. Increasing the effectiveness of uvulopalatoplasty is one of the tasks of modern otorhinolaryngology. Ways to increase the effectiveness of uvulopalatoplasty lie in the following directions: qualitative and adequate selection for the upcoming operation; accurate determination of the level(s) of obstruction, shape and degree of collapse of the soft tissues of the upper respiratory tract; careful consideration of the structural features of the soft palate and pharynx of each individual patient; maximum reduction of surgical trauma to the tissues of the palatine curtain during surgery.

Comparing the Accuracy and Reliability of Detecting the Intensity of Spinal Inflammation on STIR Sequence with Apparent Diffusion Coefficient Values in Axial Spondyloarthritis

Objective: To compare the accuracy and reliability of detecting the intensity of spinal inflammation on short tau inversion recovery (STIR) with the apparent diffusion coefficient (ADC) values of the active magnetic resonance imaging (MRI) lesions in axial spondyloarthritis (axSpA). Materials and methods: Fifty active lesions in the STIR sequence of spinal MRI were identified. With reference to sites of active lesions in STIR, the corresponding region of interest (ROI) on the ADC map was drawn to determine the maximum ADC (ADC[Formula: see text]), mean ADC (ADC[Formula: see text]), normalized maximum (nADC[Formula: see text]), and mean (nADC[Formula: see text]). Four independent readers scored the identified active lesions as “intense” or “non-intense” according to the Spondyloarthritis Research Consortium of Canada (SPARCC) MRI index. They were compared to various ADC parameters for assessment of accuracy and reliability. Regression analyses were used to adjust potential factors that could affect ADC. Results: Significant differences were found in ADC[Formula: see text] between “intense” and “non-intense” lesions scored by three of the four readers (1,405.7 ± 271.4 vs. 1,165.8 ± 223.8, [Formula: see text] = 0.01; 1,420.7 ± 272.1 vs. 1,209.0 ± 248.5, [Formula: see text] = 0.01; 1,438.0 ± 307.2 vs. 1,213.6 ± 231.0, [Formula: see text] = 0.01). Only one reader could differentiate a difference in “intense” and “non-intense” lesions with respect to ADC[Formula: see text] (899.2 ± 248.3 vs. 711.0 ± 222.6, [Formula: see text] = 0.01) and nADC[Formula: see text] (4.4 ± 2.1 vs. 3.4 ± 1.4, [Formula: see text] = 0.05). Inter-reader agreements were slight to moderate (kappa = 0.07–0.45). Reliability substantially improved when only the lowest and highest 25th percentiles of ADC values were included (kappa = 0.17–0.75). Regression analyses showed that the “intense” lesions were associated with higher ADC values after adjustment for confounders. Conclusion: Reading of STIR MRI is limited by the lack of ability in differentiating subtle differences of spinal inflammation. ADC could be an alternative method.

O USO DE ACUPUNTURA NO TRATAMENTO DE EQUINOS COM LAMINITE: REVISÃO DE LITERATURA

Acupuncture is explored as an alternative treatment for laminitis in horses, a condition that compromises the health and well-being of these animals due to intense pain and inflammation in the hooves. Originating from Traditional Chinese Medicine, acupuncture stands out for its ability to modulate pain and reduce inflammation by stimulating specific points on the body that promote analgesia, muscle relaxation, and improved circulation in affected tissues. This practice complements conventional treatment, reducing the need for analgesics and anti-inflammatory drugs, aiding in the animal’s clinical stabilization. The review presented in this paper highlights the importance of acupuncture in treating laminitis in horses, addressing relevant issues for veterinarians. In addition to promoting pain relief and improving blood circulation, this technique has anti-inflammatory and immunomodulatory effects that can be especially useful in managing laminitis. The study reveals acupuncture as a promising therapeutic resource that when complementing conventional treatment reduces the need for medication and minimizes side effects, benefiting the animals’ quality of life. The review aims to provide professionals comprehension about the efficacy and limitations of this practice, supporting clinical decision-making and proposing an integrative approach that enhances outcomes in the treatment of laminitis.

ScRNA-Seq Analysis of Tongue Tissues in Chronic Hyperplastic Candidiasis.

Chronic hyperplastic candidiasis (CHC) is a rare but severe subtype of oral candidiasis distinguished by its potential malignant transformation and suboptimal response to antifungal therapies. However, the cells and mechanisms that play key roles in this process remain unclear. Therefore, we performed the first single-cell RNA sequencing (scRNA-seq) analysis of CHC-affected tongue tissues to reveal the microenvironmental changes and immunological etiology of CHC. First, the features of CHC lesions manifesting as thickening and hardening nodular lesions, including their pathological and microbiological characteristics, were elucidated. Then, a comprehensive cellular atlas and distinct immune landscape in CHC compared with healthy tissues were characterized using scRNA-seq, highlighting significant modifications in the cell number and functionality of fibroblasts and T/NK cells. Importantly, the central role of fibroblasts in cell-cell interactions in CHC was hinted, and possible ligand-receptor pairs mainly associated with inflammation and carcinogenesis were identified. Moreover, it was revealed that significant functional activation of fibroblasts, related to the activation of the epithelial-mesenchymal transition pathways and increased expression of collagen I, matrix metalloproteinase 1 (MMP1), and MMP2, could be a hallmark of CHC, correlating with CHC's clinical characteristics of tongue hardening and intense inflammation. Notably, there is sequencing evidence of the recruitment of CD8+Tex cells and activation of PD-1 and TIGIT immune checkpoint pathways. Moreover, cDC_LAMP3 cells exhibited high CD274 expression, suggesting immune exhaustion and an increased susceptibility to carcinogenesis. This pioneering study provides valuable insights into CHC pathogenesis and immune responses, enhancing our understanding of potential therapeutic strategies.

The use of a heated helium-oxygen mixture in patients with severe COVID-19 and ARDS against the background of standard therapy and noninvasive ventilation

Introduction. One of the insufficiently studied methods of Acute Respiratory Distress Syndrome (ARDS) therapy is therapy with a heated helium-oxygen mixture. Due to physico-chemical properties, helium demonstrates high efficiency in the treatment of various diseases of the pulmonological profile.Aim. To study the effect of a heated helium-oxygen mixture on the course of a severe form of COVID-19 occurring with the development of ARDS.Materials and methods. The study involved 58 patients with severe and extremely severe coronavirus infection and ARDS, divided into the NVL + t-He/O2 group (n = 30) and the NVL+O2 control group (n = 28). In addition to standard treatment, patients of the NVL + t-He/O2 group received noninvasive ventilation (NVL) and therapy with a heated helium-oxygen mixture, according to clinical recommendations. In the main group, inhalations took place daily for 60 minutes per day for 5 days.Results. Against the background of therapy with a heated helium-oxygen mixture, a more intense increase in the level of lymphocytes was observed: 1.39 (1.09–1.66) × 109/l in the NVL + t-He/O2 group versus 1.02 (0.78–1.40) × 109/l (p = 0.02). Also, as a result of treatment, there was a significant decrease in RR, D-dimer and CRP in the study group: the level of RR (21 (20–22)/minute versus 22.5 (21–24)/minute, p = 0.003), D-dimer (0.44 (0.29–0.60) FEU ng/ml versus 0.79 (0.42–1.34) FEU ng/ml, p = 0.02) and CRP (1.1 (0.7–3.1)mg/l versus 16.6 (8.5–29.5) mg/l, p = 0.03), respectively. Similarly to the NVL + t-He/O2 group, an increase in the level of PaO2 and the oxygenation index was noted. In addition, there were significantly fewer patients with grade III and IV lung damage in the NVL + t-He/O2 group compared with the control (p = 0.05).Conclusion. The use of a heated helium-oxygen mixture in patients with severe COVID-19, occurring with the development of ARDS, against the background of standard therapy and NIV has shown its safety and effectiveness: there was a decrease in the intensity of inflammation, improved oxygenation and a reduction in the need for respiratory support.

Conjunctival squamous metaplasia on amniotic membrane in Stevens-Johnson syndrome: a case report

BackgroundTo present a case of conjunctival growth on the amniotic membrane and subsequent pathology revealing conjunctival squamous metaplasia in a patient with Stevens-Johnson syndrome.Case presentationA 21-year-old female presented with painful, blurred vision in both eyes for two weeks. She was diagnosed with Stevens-Johnson syndrome 5 weeks before. Due to bilateral corneal epithelial defects, ProKera®, an amniotic membrane corneal bandage with a polycarbonate ring, was placed in both eyes. However, three weeks later, a slit-lamp examination revealed vascularized tissue growth from the palpebral conjunctiva to the amniotic membrane, along with symblepharon formation in the left eye. The patient underwent conjunctival biopsy, amniotic membrane removal, and symblepharon release. Pathology report showed the growth of squamous epithelium on the acellular amniotic membrane. Immunohistochemistry further supported the diagnosis, revealing squamous markers through p40 staining and highlighting the presence of the amniotic membrane using trichrome stain. Three months later, the patient’s visual acuity had improved to 20/25 and no symblepharon was noted.ConclusionsThis is the first case of conjunctival squamous metaplasia on amniotic membrane associated with Stevens-Johnson syndrome. Our case indicates that, despite the anti-inflammatory properties of amniotic membrane, conjunctival squamous metaplasia may arise after amniotic membrane grafting due to intense inflammation in Stevens-Johnson syndrome. Clinicians should conduct regular monitoring before amniotic membrane dissolution to preclude the development of conjunctival squamous metaplasia on the membrane and potential invasion into the cornea.

An initial investigation of transcutaneous delivery of plasmid DNA encoding interleukin-10 for the treatment of psoriatic skin conditions

Psoriasis is a chronic immune-mediated skin disorder characterized by intense local inflammation, epidermal hyperplasia, and leukocyte infiltration. Current treatment approaches for psoriasis aim to alleviate symptoms and prevent disease progression, including systemically administered drugs with whole body side effects. Despite some advances in psoriasis treatment, success has been quite limited. To begin to address this challenge, we undertook an initial investigation of whether transcutaneous delivery of an endogenous anti-inflammatory cytokine could provide an effective, local treatment of psoriatic-like skin conditions. To do this, we utilized a previously documented rodent model of psoriasis, induced via a single topical application of Imiquimod (IMQ) to the shaved back of rats. The therapeutic approach used for this initial investigation was delivery of plasmid DNA encoding rat interleukin-10 (pDNA-rIL10), a non-viral gene therapy approach previously shown to be effective in suppressing neuroinflammatory disorders after localized delivery either intracerebrally or intrathecally. Translation of this CNS therapeutic for use in psoriatic-like skin disorders required reformulation to enable transcutaneous delivery. Toward that end, pDNA-rIL10 was topically applied in Lipoderm HMW, a base explicitly designed to deliver higher molecular weight compounds into skin. Here we show that a single topical application of pDNA-rIL10 in Lipoderm HMW was effective in decreasing mRNA levels of pro-inflammatory cytokines as well as reducing the recruitment of T-cells to IMQ-treated skin. Furthermore, this transcutaneous IL-10 gene therapy decreased signs of skin inflammation, reflected by reduced erythema. Moreover, the results provide an initial indication that IL10 may stimulate hair regrowth in psoriatic-like skin.

ALVEOLITE COMO COMPLICAÇÃO PÓS OPERATÓRIA DE EXODONTIAS

Alveolitis is a common postoperative complication resulting from complex extractions, particularly of lower third molars, characterized by intense pain and inflammation of the dental socket. This study aims to analyze the incidence, risk factors, treatments, and preventive measures for this condition, which significantly impacts patients’ quality of life. The methodology employed was a narrative literature review, using databases such as PubMed, SciELO, and Google Scholar, with descriptors such as “alveolitis,” “surgery oral,” and “osteitis.” The results indicate that the etiology of alveolitis is multifactorial, with factors such as smoking, the use of oral contraceptives, and surgical trauma contributing to its development. Treatment varies depending on the severity of the condition, with the application of dressings, irrigation with antiseptic solutions, and, in more severe cases, the use of antibiotics. Preventive measures, such as maintaining good oral hygiene and adopting atraumatic surgical techniques, proved effective in reducing the occurrence of alveolitis.

Evaluating the therapeutic potential of different sources of mesenchymal stem cells in acute respiratory distress syndrome

BackgroundMesenchymal stem/stromal cells (MSCs) have attracted interest as a potential therapy given their anti-inflammatory and immunomodulatory properties. However, clinical trials using MSCs for acute respiratory distress syndrome (ARDS) have produced mixed and inconclusive data. In previous work, we performed a “head-to-head” comparison between different sources of MSCs and showed that each source had a unique genomic and proteomic “signature”.MethodThis study investigated which sources of MSC: bone marrow derived-MSCs (BM-MSCs), adipose tissue derived-MSCs (AD-MSCs) and umbilical cord derived-MSCs (UC-MSCs) would be the optimal candidate to be used as a therapy in an LPS-induced mouse model of ARDS. Immune cells assessment, tissue transcriptomics, animal survival, and endothelial-epithelial barrier assessment were used to evaluate their effects.ResultsWhen comparing the three most commonly used MSC sources, we found that UC-MSCs exhibited greater efficacy compared to other MSCs in improving animal survival, mitigating epithelial/endothelial damage, decreasing lung inflammation via reducing neutrophil infiltration, T cell proliferation, and M1 polarization. Bulk RNA sequencing of lung tissue also showed that UC-MSCs have the capability to downregulate extracellular trap formation, by the downregulation of key genes like Elane and Padi4. Notably, treatment with UC-MSCs demonstrated a significant reduction in Fc-γ R mediated phagocytosis, which has been associated with monocyte pyroptosis and intense inflammation in the context of COVID-19.ConclusionOur findings suggest that UC-MSCs are an optimal source of MSC to treat acute inflammatory conditions in the lungs, such as ARDS.

Association of novel dietary and lifestyle inflammation scores with incidence and progression of coronary artery calcification in middle-late adulthood: a longitudinal cohort study

BackgroundDietary patterns and lifestyle factors can influence the intensity of systemic inflammation and, consequently, the development and progression of coronary artery calcification (CAC). This study aimed to explore the relationship between the inflammatory potentials of diet and lifestyle, as captured by novel dietary and lifestyle inflammation scores (DIS and LIS), with CAC incidence and progression.MethodsWe analyzed data on 5949 Black and White men and women ≥ 45 years old participating in the Multi-Ethnic Study of Atherosclerosis (MESA) cohort. Baseline data on diet and lifestyle factors were collected from 2000 to 2002 and used to construct the DIS and LIS, which reflect the overall inflammatory potential of diet and lifestyle. Cox proportional hazard regression was used to calculate the hazard ratios (HR) and 95% confidence intervals (95% CI) for CAC incidence and progression across quartiles of DIS and LIS, adjusting for potential confounders.ResultsOver a median follow-up of 8.0 years, among 2638 participants with zero CAC score at baseline, 977 individuals developed positive scores, and 1681 out of 2561 participants showed CAC progression. For individuals in the highest (more pro-inflammatory) compared to the lowest (more anti-inflammatory) quartiles of the LIS, the multivariable-adjusted HR for CAC incidence was 1.35 (95% CI, 1.10–1.65; P trend < 0.002). This association was stronger among younger adults aged < 60 years compared to those aged ≥ 60 years, with respective values of 1.76 (1.34–2.30) and 1.02 (0.78–1.35) (P interaction < 0.001). However, the LIS was not significantly associated with the progression of existing CAC. Among the components of the LIS, a body mas index (BMI) ≥ 25 kg/m2 and current smoking were significant predictors for the incidence and progression of CAC, respectively. No significant association was found between DIS and CAC incidence and progression.ConclusionsLifestyle factors, through their impact on systemic inflammation, may be associated with a higher risk of CAC incidence in middle and late adulthood.

Impact of Curcumin on the IL-17A-Mediated p53-Fibrinolytic System: Mouse Proteomics and Integrated Human Fibrosis scRNAseq Insights.

Acute lung injury (ALI) is primarily driven by an intense inflammation in the alveolar epithelium. Key to this is the pro-inflammatory cytokine, Interleukin 17 (IL-17), which influences pulmonary immunity and modifies p53 function. The direct role of IL-17A in p53-fibrinolytic system is still unclear, it is important to evaluate this mechanism to regulate the ALI progression to idiopathic pulmonary fibrosis (IPF). C57BL/6 mice, exposed to recombinant IL-17A protein and treated with curcumin, provided insight into IL-17A mechanisms and curcumin's potential for modulating early pulmonary fibrosis stages. A diverse methodology, including proteomics, single-cell RNA sequencing (scRNA-seq) integration, molecular, and Schroedinger approach were utilized. In silico approaches facilitated the potential interactions between curcumin, IL-17A, and apoptosis-related proteins. A notable surge in the expression levels of IL-17A, p53, and fibrinolytic components such as Plasminogen Activator Inhibitor-1 (PAI-I) was discerned upon the IL17A exposure in mouse lungs. Furthermore, the enrichment of pathways and differential expression of proteins underscored the significance of IL-17A in governing downstream regulatory pathways such as inflammation, NF-kappaB signaling, Mitogen-Activated Protein Kinases (MAPK), p53, oxidative phosphorylation, JAK-STAT, and apoptosis. The integration of scRNA-seq data from 20 IPF and 10 control lung specimens emphasized the importance of IL-17A mediated downstream regulation in PF patients. A potent immuno-pharmacotherapeutic agent, curcumin, demonstrated a substantial capacity to modulate the lung pathology and molecular changes induced by IL-17A in mouse lungs. Human IPF single cell data integration confirmed the effects of IL-17A mediated fibrinolytic components in ALI to IPF progression.

Hospital Mortality in Acute Decompensation of Alcoholic Liver Cirrhosis: Can Novel Survival Markers Outperform Traditional Ones?

Background: There is a strong correlation between systemic inflammation intensity and clinical presentation, disease progression, and survival during liver cirrhosis decompensation. This study aimed to evaluate the prognostic performance of blood-based biomarkers as meta-inflammation markers, including NLR, PLR, LMR, INPR, MPR, ALBI, FIB4, and APRI, in predicting hospital mortality in patients with acute decompensation of alcohol-related liver cirrhosis. Methods: Data from 411 patients with their first onset of acute decompensation were analyzed, forming two groups: deceased and survived during hospitalization. Generalized partial least squares regression analysis was applied to explore the effects of surrogate indicators on mortality rates, using mortality rate as the dependent variable. Root Mean Square Error, Akaike's, and Bayesian information criteria determined that four components accounted for most of the variance. Results: Variables with significant negative contributions to the outcome prediction (ranked by standardized regression coefficients) were encephalopathy grade, total bilirubin, Child-Turcotte-Pugh score, MELD, NLR, MPV, FIB4, INR, PLR, and ALT. Coefficient sizes ranged from -0.63 to -0.09, with p-values from 0 to 0.018. Conclusions: NLR, PLR, and FIB4 significantly contribute to hospital mortality prediction in patients with acute decompensation of alcohol-related liver cirrhosis. Conversely, some variables used to predict liver disease severity, including INPR, APRI, LMR, and ALBI score, did not significantly contribute to hospital mortality prediction in this patient population.

Inflammation Decreases Ciclosporin Metabolism in Allogeneic Hematopoietic Stem Cell Transplantation Recipients.

Graft-versus-host disease (GVHd) remains a significant challenge following allogeneic hematopoietic stem cell transplantation (HSCT). Prevention of GVHd relies mainly on the use of calcineurin inhibitors, notably ciclosporin that exhibits complex pharmacokinetics influenced by many factors including drug-drug interactions (DDIs). Due to the downregulation of drug metabolizing enzymes and transporters, it has been postulated that inflammation may be a contributing factor to the variability observed in ciclosporin pharmacokinetics. This study aimed to assess the impact of inflammation, as indicated by C-reactive protein (CRP) levels, on the metabolism of ciclosporin in adult allogeneic HSCT recipients. A retrospective observational study was conducted at Rennes University Hospital involving 71 adult HSCT patients. The relationship between the intensity of inflammation (no-to-mild, moderate, and severe), and the metabolism of ciclosporin (estimated by the concentration/dose ratio) was assessed. Severe inflammation significantly decreased the metabolism of ciclosporin, as evidenced by higher concentration/dose ratios. Thanks to the daily dose adjustment, inflammation did not influence the blood levels of ciclosporin. Interestingly, DDIs did not emerge as a significant covariate in influencing ciclosporin metabolism. This is likely because the CYP3A4 inhibitory potential of interacting drugs may be masked in HSCT patients where metabolism is already upstream downregulated by inflammation. The study highlights the intricate relationship between inflammation and ciclosporin pharmacokinetics in HSCT patients. This underscores the necessity for therapeutic monitoring and the potential adjustment of dosage strategies based on the inflammatory status. These insights could contribute to the development of more personalized, optimized, and effective management strategies for HSCT recipients.

Anomalous power-law behavior in the electrical impedance of endothelial cellular networks

In this paper, we report on the electrical impedance measurement of human endothelial cellular networks and show the existence of emergent power law behavior in its admittance. In particular, we find that the admittance scales with the frequency ω as ωα, with the exponent that varies with the degree of the disruption caused by the inflammation in the endothelial cellular network. We demonstrate that the power law of the measured electrical admittance can be understood by a simple percolation model of a large R–C (resistor–capacitor) network, which allows us to relate quantitatively and the intensity of inflammation. Our results suggest that the electrical properties of heterogeneous biomaterials, like living tissues, behave as a complex microstructural network.

Effects of Photobiomodulation Using Low-Power Diode Laser Therapy and Nano-bone on Mandibular Bone Regeneration in Rats.

Introduction: Recently, the positive effects of photobiomodulation (PBM) and nano-bone on bone regeneration have garnered significant attention. The purpose of the research was to assess the impact of PBM and nano-bone on the process of mandibular bone repair in mice. Methods: A 4-mm diameter bone defect was created in the left mandibular angle of 24 mice separated into 4 equal groups: group I: control; group II: PBM by irradiation at 100 mW of a 980 nm diode laser for one minute (three sessions per week; day on and day off); group III: nano-bone; group IV: PBM with nano-bone. Every group was sectioned into 3 equal subgroups corresponding to the evaluation method period: (A) one week, (B) two weeks, and (C) four weeks. Histological examination was done with hematoxylin, eosin, and Masson's Trichrome after one, two and four weeks for inflammation, bone defect coverage, vascularization within the newly formed bone, and new bone formation. Statistical analysis of the data was done and presented as percentage values using chi-square. The significance level was set at P value≤0.05 within all tests. Results: In general, by histological examination of the mandibular bone defect of the rats, the intensity of inflammation was the least in group IV when compared with groups II and III and the control group at all evaluation periods (P<0.001). Also, group IV showed a high significant rise in the percentage of new bone formation following four weeks when compared with the control (P≤ 0.001) and groups II and III (P<0.001). Conclusion: The present research results confirmed that the combination of PBM and nano-bone can aid in the repair of mandibular bone abnormalities. This animal study suggests that the use of PBM and nano-bone should be investigated further in clinical studies.

Trained immunity of synovial macrophages is associated with exacerbated joint inflammation and damage after Staphylococcus aureus infection.

Investigate whether and which synoviocytes would acquire trained immunity characteristics that could exacerbate joint inflammation following a secondary Staphylococcus aureus infection. Lipopolysaccharide (LPS) and S. aureus were separately or double injected (21 days of interval) into the tibiofemoral joint cavity of male C57BL/6 mice. At different time points after these stimulations, mechanical nociception was analyzed followed by the analysis of signs of inflammation and damage in the affected joints. The trained immunity markers, including the glycolytic and mTOR pathway, were analyzed in whole tissue or isolated synoviocytes. A group of mice was treated with Rapamycin, an mTOR inhibitor before LPS or S. aureus stimulation. The double LPS - S. aureus hit promoted intense joint inflammation and damage compared to single joint stimulation, including markers in synoviocyte activation, production of proinflammatory cytokines, persistent nociception, and bone damage, despite not reducing the bacterial clearance. The double LPS - S. aureus hit joints increased the synovial macrophage population expressing CX3CR1 alongside triggering established epigenetic modifications associated with trained immunity events in these cells, such as the upregulation of the mTOR signaling pathway (p-mTOR and HIF1α) and the trimethylation of histone H3. Mice treated with Rapamycin presented reduced CX3CR1+ macrophage activation, joint inflammation, and bone damage. There is a trained immunity phenotype in CX3CR1+ synovial macrophages that contributes to the exacerbation of joint inflammation and damage during septic arthritis caused by S. aureus.

IPNA clinical practice recommendations for the diagnosis and management of children with IgA nephropathy and IgA vasculitis nephritis.

IgA nephropathy and IgA vasculitis with nephritis, albeit rare, represent two relatively frequent glomerular conditions in childhood. Compared to adults, pediatric IgA nephropathy has a more acute presentation, most frequently with synpharyngitic macrohematuria and histologically with more intense inflammation and less intense chronic damage. Management of these conditions is controversial and supported by little high-quality evidence. The paucity of evidence is due to the disease heterogeneity, its inter-ethnic variability, and the difficulty of extrapolating data from adult studies due to the peculiarities of the condition in children. IgA vasculitis with nephritis is a kidney manifestation of a systemic disorder, typical of the pediatric age, in which both the diagnosis of kidney involvement and its management are poorly defined, and an interdisciplinary approach is crucial. Both conditions can have a profound and long-lasting impact on kidney function and the global health of affected children. The International Pediatric Nephrology Association has therefore convened a diverse international group of experts from different disciplines to provide guidance on the recommended management of these conditions in children and to establish common definitions and define priorities for future high-quality, evidence-based collaborative studies for the benefit of children.

Development of Quantitative Norms for Normal Lung Uptake Based on Three-Dimensional Gallium-67 Single Photon Emission Computed Tomography/Computed Tomography

Abstract Purpose Gallium-67 (Ga-67) lung scans assess alveolitis and interstitial lung disease, with Ga-67 accumulation correlating with inflammation intensity as seen in lung biopsy sections. Both semi-quantitative and quantitative methods have been used, with the latter providing an inflammatory activity index linked to lung lavage and histopathological scores. However, differing reference points result in varying outcomes. This study aimed to establish standard Ga-67 index parameters using semi-quantitative analysis and a linear regression model based on planar and SPECT/CT images. Methods Twenty subjects without lung disease received a 5–6 mCi Ga-67 injection via the ankle. Both planar and SPECT/CT images were analyzed, with semi-quantitative values assessed using GraphPad Prism 9.5.1. Results Compared to planar images, SPECT/CT acquisitions for the lung-to-arm uptake ratio proved the most reliable indicator for assessing lung inflammation. Increased lung Ga-67 uptake was defined as greater than 2 standard deviations from the average Ga-67 uptake for healthy subjects. The normal range was 0.065 ± 0.049 for the right side and 0.076 ± 0.070 for the left side. Conclusion Lung-to-arm ratios in SPECT/CT images are more accurate than those in planar images. This method should be adopted as a standard clinical practice, providing more reliable diagnostic information and improving patient management. Future studies should compare patients without lung disease to those with lung disease to determine the diagnostic benefit of these norms.

The involvement of HDAC3 in the pathogenesis of lung injury and pulmonary fibrosis.

Acute lung injury (ALI) and its severe counterpart, acute respiratory distress syndrome (ARDS), are critical respiratory conditions with high mortality rates due primarily to acute and intense pulmonary inflammation. Despite significant research advances, effective pharmacological treatments for ALI and ARDS remain unavailable, highlighting an urgent need for therapeutic innovation. Notably, idiopathic pulmonary fibrosis (IPF) is a chronic, progressive disease characterized by the irreversible progression of fibrosis, which is initiated by repeated damage to the alveolar epithelium and leads to excessive extracellular matrix deposition. This condition is further complicated by dysregulated tissue repair and fibroblast dysfunction, exacerbating tissue remodeling processes and promoting progression to terminal pulmonary fibrosis. Similar to that noted for ALI and ARDS, treatment options for IPF are currently limited, with no specific drug therapy providing a cure. Histone deacetylase 3 (HDAC3), a notable member of the HDAC family with four splice variants (HD3α, -β, -γ, and -δ), plays multiple roles. HDAC3 regulates gene transcription through histone acetylation and adjusts nonhistone proteins posttranslationally, affecting certain mitochondrial and cytoplasmic proteins. Given its unique structure, HDAC3 impacts various physiological processes, such as inflammation, apoptosis, mitochondrial homeostasis, and macrophage polarization. This article explores the intricate role of HDAC3 in ALI/ARDS and IPF and evaluates its therapeutic potential the treatment of these severe pulmonary conditions.

Investigating the mechanisms of inflammation and immune alterations in Parkinson's disease using spatial transcriptomics techniques

In recent years, overwhelming evidence has emphasized the crucial role of inflammation in the pathogenesis of PD. However, the exact mechanisms by which inflammation damages dopaminergic neurons in PD are still unclear. Therefore, we generated a MPTP-induced PD mouse model and performed spatial transcriptomic sequencing to provide more insight into the process of PD development at specific brain regions. Our results indicate that the pathological changes of PD are mainly manifested in the midbrain, especially in the substantia nigra region, with significant reductions in oligodendrocytes and Agt-labeled astrocytes and an increase in Gfap-labeled astrocytes. Macrophages displayed an increasing trend in the PD environment, indicating a pattern of immune modulation induced by PD. Moreover, pathway analysis revealed significant impairments in ion migration ability, abnormal Ca2+ channels, cAMP signaling, and synaptic damage in PD. Significant downregulation of Mt1 and Mt2 and upregulation of Atp1b2, Gpi1, and Cox6a1 in PD further underscored the occurrence of intense inflammation and immune alterations. On the basis of these findings, we have validated the significant accumulation of Ca2+ in the midbrain tissue in the PD environment by measuring its content. Additionally, we have demonstrated a close association between the reduction of dopaminergic neurons, represented by the midbrain region, and ferroptosis by evaluating the iron content, malondialdehyde (MDA) levels, and the protein expression of GPX4 and TH in the tissue. We propose the hypothesis that PD-related inflammation and immune changes can induce neuronal and oligodendrocyte damage through the induction of ferroptosis, thereby further accelerating the progression of PD.