Intense Inflammation Research Articles

Physicochemical properties and biological interaction of calcium silicate-based sealers - in vivo model.

To investigate volumetric changes, in vivo biocompatibility, and systemic migration from eight commercial endodontic sealer materials in paste/paste, powder/liquid, and pre-mixed forms. The sealers AH Plus Bioceramic, AH Plus Jet, BioRoot RCS, MTApex, Bio-C Sealer, Bio-C Sealer Ion+, EndoSequence BC Sealer and NeoSEALER Flo were studied. After characterisation by scanning electron microscopy (SEM), energy dispersive X-ray spectroscopy (EDS), Raman spectroscopy and X-ray diffractometry (XRD), tubes were implanted in Wistar rats' alveolar bone and subcutaneous tissues. Micro-CT evaluated volumetric changes pre/post 30 days of implantation. Histological and immunohistochemistry analyses assessed biocompatibility. Kidney samples underwent spectrometry (ICP-MS) for tantalum, tungsten and zirconium. Statistical analysis determined normality and significance (udp < 0.05). Characterisation revealed calcium, silicon, and radiopacifiers in the materials. Volumetric changes showed greater alteration in subcutaneous tissues than alveolar bone; BioRoot RCS and MTApex (powder/liquid) were most stable. Histological analysis indicated intense inflammation for AH Plus Jet, moderate for others; IL-10 was marked positively for all materials. AH Plus Jet had an 18-fold higher tungsten and a 37-fold higher zirconium mass fraction in kidneys versus controls, while tantalum showed lower accumulation patterns. Root canal filling materials' responses varied by implantation site and form, demonstrating acceptable biocompatibility. Tantalum and zirconium oxide radiopacifiers appear systemically safe; tungsten-based radiopacifiers are unsuitable due to metal accumulation risks. This study highlights the need for further in vivo studies on endodontic sealers' chemical, biological, and physical behaviors and their systemic migration.

The association of infectious and parasitic pathogens in the etiology of chronic stomatitis and feline gingivostomatitis: a multifactorial approach

Feline chronic gingivostomatitis (FCGS) is a common pathology located in the oral cavity of felines. It has a chronic nature and generally presents as intense inflammation and ulcerative and ulcerative-proliferative lesions on the oral mucosa. It is a disease considered severe and rapidly progressing. It is considered a challenge for veterinarians, as its etiology is not defined, limiting its treatment and making the prognosis guarded. Chronic gingivostomatitis is considered a multifactorial disease and may be related to different etiological agents, nutritional management, environmental stress, bacteria, viruses and a relationship with the immune system of the affected animal. The association of these factors can lead to bacterial tartar plaques, mucosal hyperemia, halitosis, sialorrhea, among others. Felines aged 7 to 10 years are the most affected, but it can occur in younger or older cats. The Persian, Siamese, Abyssinian, Himalayan and Burmese breeds have a higher incidence, and are considered by some authors to be predisposing breeds. The patient's sex is not relevant, as both are affected. The complaint of recurrences is recurrent, because, due to the challenges encountered in finding a totally efficient protocol, the result of these has presented variable reactions to the treatments used by each veterinarian, however, the surgical intervention, carried out by extracting the molar and premolar teeth, has if considered more appropriate, with the aim of preventing the proliferation of bacteria, stopping the most intense inflammation and providing the patient with quality of life. It is important to highlight, in order to clarify, that, if partial or complete removal of the teeth is necessary, the animal will continue with its normal routine, as felines are not dependent on the extracted teeth for food. It is concluded, after exposing the challenges and clinical difficulties of FCGS that the present work aims to review the literature, discuss its clinical aspects, aiming to explain the clinical part, possible treatments, recommended surgical procedures and their prognosis.

SALIVARY SPECIFIC IgE TO D1 AND G6 IN PATIENTS WITH RHINITIS WITH OR WITHOUT S. AUREUS COLONIZATION

Globally, allergic rhinitis impacts roughly 25% of children and 40% of adults. Immunoglobulin E (IgE) plays a crucial part in allergic inflammation, with two sources: spontaneously produced IgE, and IgE stemming from reactions to environmental allergens. The damaging effects of S. aureus, as well as Staphylococcal enterotoxins (Ses), have been proven in numerous airway illnesses. As superantigens, Ses generate intense Th2 inflammation, with 70-80% of IgE being locally synthesized. Our study aimed to determine if any correlation existed between local and systemic specific IgE responses in rhinitis patients – both treated and untreated. Furthermore, we sought to pinpoint significant disparities in serum allergy-specific IgE levels between S. aureus positive and negative patients. Results: From 70 patients with a relevant rhinitis history spanning at least two years, we found that in our rhinitis cohort, 36 were sIgE-negative for d1 in blood samples but positive in saliva samples (χ2 = 19.76, α = 0.181), while 25 tested negative for g6 in blood samples but positive for g6 in saliva samples (χ2 = 6.89, α = 0.86). No significant difference emerged between serum allergy-specific IgE levels in S. aureus positive and negative rhinitis patients (χ2 = 0.38). Similar results were noted within the saliva samples. However, mucosal-specific IgE levels were lower among patients receiving active therapy (p &lt; 0.001 for both d1 and g6). Conclusion: There is no correlation between mucosal-specific IgE levels and systemic-specific IgE levels or S. aureus carriers. We observed that salivary-specific IgE levels were lower in patients undergoing active treatment compared to untreated patients.

Chemical and in vivo analyses of calcium silicate-based materials in bone and connective tissues.

Calcium silicate-based cements have been widely used in dentistry mainly due to their physicochemical and biological properties. Commercially available materials use radiopacifiers containing metals (bismuth, tantalum, tungsten and/or zirconium). To investigate volumetric changes, in vivo biocompatibility and systemic migration from eight commercially available materials, including powder/liquid and 'ready-to-use' presentations. After characterization, tubes were implanted in healthy Wistar rats' alveolar bone and subcutaneous tissues. Micro-CT was used to evaluate volumetric change before/after 30 days of implantation. Histological and immunohistochemistry analysis were used to evaluate materials' biocompatibility. After euthanasia, kidney samples were retrieved, acidic digested and evaluated by inductively coupled plasma mass spectrometry (ICP-MS) for bismuth, tantalum, tungsten and zirconium mass fractions. Statistical analysis compared the results for normality and comparisons adopted a level of significance of 0.05. Characterization photomicrographs and spectroscopy analysis revealed calcium, silicon and radiopacifiers for tested cements. Volumetric changes after implantation showed higher alteration in subcutaneous tissues than alveolar bone indicating that Biodentine, EndoSequence BC RRM Putty and ProRoot MTA were the most stable materials. Histological analysis found intense inflammation for NeoPUTTY and moderate for the other materials; osteocalcin and osteopontin were positively marked for all materials. Despite its volumetric stability, ProRoot MTA showed a 1000-fold higher mass fraction of bismuth accumulation and MTA Repair HP a 37-fold higher tungsten accumulation in kidney samples when compared with the nonexposed controls. All tantalum-analysed samples indicated a similar mass fraction with the nonexposed controls. Biodentine exhibited a significant lower kidney mass fraction of zirconium accumulation when compared with this control. Volumetric analysis revealed that Bio-C Repair, NeoPUTTY and MTA Repair HP presented greater volumetric loss when implanted in the subcutaneous tissue. NeoPUTTY presented more intense inflammatory infiltrate. Systemic migration analysis highlighted the predominance of bismuth in the ProRoot MTA group. These results suggest that endodontic repair cements are affected by their chemical composition, the type of implant tissue and different clinical settings.

DESCRIPTION OF THE CLINICAL AND RADIOLOGICAL CHARACTERISTICS OF PULMONARY EMBOLISM IN COVID-19 VERSUS NON COVID-19 PATIENTS: A MULTICENTRIC CROSS-SECTIONAL STUDY OVER A 24-MONTH PERSPECTIVE.

COVID-19 is associated with intense systemic inflammation and abnormal coagulation profile leading to an increased incidence of pulmonary embolism (PE). This study investigates whether PE in COVID-19 patients has different clinical, laboratory and radiological characteristics when compared to traditional PE in COVID negative patients. We conducted an observational, multicentric, cross-sectional study on consecutive patients diagnosed with PE at admission or during hospital stay from February 21th 2019 to February 20th 2021. We compared clinical and laboratory data and Computer Tomography (CT) images between COVID-19 positive and COVID-19 negative patients. The extent of PE was evaluated using the Qanadli Index. Among 771 enrolled patients with acute PE, 89 were COVID-19 positive. COVID-19 patients were predominantly male (59.6% vs. 41.5%; p=0.001) and exhibited fewer classic VTE risk factors, such as previous VTE (3.5% vs. 11.5%; p=0.02) and active cancer (4.7% vs. 24.2%; p<0.0001). Additionally, these patients showed lower median Troponin-T and NT-proBNP levels (10 vs. 32 ng/L, p=0.0002; and 383 vs. 1448 pg/ml, p=0.004, respectively), a lower median Qanadli Index (4 vs. 7, p=0.0013), more distal PE obstructions (53.5% vs. 32.9%; p<0.001), and less frequent right ventricular dilatation (4.1% vs. 10.9%; p=0.09). In COVID-19 patients, traditional VTE risk factors were less frequent, a possible role for in situ thrombo-inflammatory processes. The reduced radiological extent and severity of PE observed in COVID-19 patients may riflect an in situ thrombo-inflammatory process rather than classical embolization; however, this hypotesis need to be confirmed by other studies.

The effect of transcutaneous auricular vagus nerve stimulation on cardiovascular function in subarachnoid hemorrhage patients: A randomized trial.

Subarachnoid hemorrhage (SAH) is characterized by intense central inflammation, leading to substantial post-hemorrhagic complications such as vasospasm and delayed cerebral ischemia. Given the anti-inflammatory effect of transcutaneous auricular vagus nerve stimulation (taVNS) and its ability to promote brain plasticity, taVNS has emerged as a promising therapeutic option for SAH patients. However, the effects of taVNS on cardiovascular dynamics in critically ill patients, like those with SAH, have not yet been investigated. Given the association between cardiac complications and elevated risk of poor clinical outcomes after SAH, it is essential to characterize the cardiovascular effects of taVNS to ensure this approach is safe in this fragile population. Therefore, this study assessed the impact of both acute and repetitive taVNS on cardiovascular function. In this randomized clinical trial, 24 SAH patients were assigned to either a taVNS treatment or a sham treatment group. During their stay in the intensive care unit, we monitored patient electrocardiogram readings and vital signs. We compared long-term changes in heart rate, heart rate variability (HRV), QT interval, and blood pressure between the two groups. Additionally, we assessed the effects of acute taVNS by comparing cardiovascular metrics before, during, and after the intervention. We also explored acute cardiovascular biomarkers in patients exhibiting clinical improvement. We found that repetitive taVNS did not significantly alter heart rate, QT interval, blood pressure, or intracranial pressure (ICP). However, repetitive taVNS increased overall HRV and parasympathetic activity compared to the sham treatment. The increase in parasympathetic activity was most pronounced from 2 to 4 days after initial treatment (Cohen's d = 0.50). Acutely, taVNS increased heart rate, blood pressure, and peripheral perfusion index without affecting the corrected QT interval, ICP, or HRV. The acute post-treatment elevation in heart rate was more pronounced in patients who experienced a decrease of more than one point in their modified Rankin Score at the time of discharge. Our study found that taVNS treatment did not induce adverse cardiovascular effects, such as bradycardia or QT prolongation, supporting its development as a safe immunomodulatory treatment approach for SAH patients. The observed acute increase in heart rate after taVNS treatment may serve as a biomarker for SAH patients who could derive greater benefit from this treatment. The American Association of Neurological Surgeons (ALH), The Aneurysm and AVM Foundation (ALH), The National Institutes of Health R01-EB026439, P41-EB018783, U24-NS109103, R21-NS128307 (ECL, PB), McDonnell Center for Systems Neuroscience (ECL, PB), and Fondazione Neurone (PB). NCT04557618.

Recombinant Thrombomodulin Domain 1 Modulates Macrophage Polarization and Enhances Healing in Corneal Alkali Burns.

Corneal alkali burns are severe ocular injuries characterized by intense inflammation, tissue damage, and vision impairment, with current treatments often insufficient in restoring corneal function and clarity. This study aimed to evaluate the therapeutic effects of recombinant thrombomodulin domain 1 (rTMD1) in the treatment of corneal alkali burns, focusing on its impact on inflammation, tissue repair, fibrosis, and neovascularization. A murine model of corneal alkali burn was utilized to investigate the therapeutic potential of rTMD1. The effects of rTMD1 on macrophage polarization, inflammatory response, tissue repair, fibrosis, and neovascularization were assessed through histological analysis, immunohistochemistry, and molecular studies targeting key signaling pathways such as ERK/HIF-1α and vascular endothelial growth factor (VEGF) expression. Administration of rTMD1 significantly modulated macrophage polarization, promoting a transition from the pro-inflammatory M1 phenotype to the reparative M2 phenotype via inhibition of the ERK/HIF-1α pathway. This shift resulted in reduced inflammation, enhanced tissue repair, and controlled fibrosis. Furthermore, rTMD1 inhibited neovascularization by downregulating VEGF expression, aiding in the preservation of corneal clarity. rTMD1 demonstrates substantial therapeutic potential in treating corneal alkali burns by reducing inflammation, promoting tissue repair, controlling fibrosis, and inhibiting neovascularization. These findings support the further development of rTMD1 as a promising treatment for corneal burns and possibly other inflammatory ocular conditions.

Evaluation of the Effects of Ozone and Laser Therapy on the Healing Process in Extraction Sites of Rats Treated with Zoledronic Acid

Bisphosphonates are a class of drugs extensively used in the management of numerous conditions. In patients with bisphosphonate-related osteonecrosis of the jaws, surgical interventions on bone tissue often exacerbate the condition. Alternative treatment methods, including laser and ozone therapies, are being explored to mitigate the adverse effects of bisphosphonates. Our study was a prospective, randomized, and controlled trial. Total of 80 female Wistar rats were utilized in the study. The animals were divided into five groups. Rats were measured for intravenous zoledronic acid administration. Histopathological evaluations were conducted to assess new bone formation and inflammation intensity within the extraction sockets. While there is a statistically significant difference between the groups regarding ossification rates on the 7th day, there is no statistically significant difference between the groups on the 14th day. At the end of the seventh day, no statistically significant difference in inflammation scores. At the end of the 14th day, there was a statistically significant difference between the groups regarding inflammation scores. These findings suggest that laser and ozone therapies enhance new bone formation over the long term and mitigate the adverse effects of bisphosphonates in rats.

The Monoacylglycerol Lipase Inhibitor JZL184 and ARDS: Differential Effects in Direct and Indirect Rat Models

Purpose: Acute respiratory distress syndrome (ARDS) leads to high morbidity and mortality, with limited pharmacological treatments and a reliance on supportive therapies. Recent evidence suggests cannabinoids may offer protective and therapeutic benefits against tissue damage, including lung pathologies. While cannabinoids' positive impacts on lung pathologies are known, their specific effects on ARDS mechanisms have not been thoroughly examined. The study purposes to explore the protective effects of cannabinoids on lung injury in direct and indirect ARDS models, focusing on differences in pathophysiological mechanisms. Methods: Rats received lipopolysaccharide (LPS, 5 mg/kg, intratracheally) for direct models or alpha-naphthylthiourea (ANTU, 10 mg/kg, intraperitoneally) for indirect models. Endocannabinoid degrading enzyme, MAGL inhibitor JZL184 (10 mg/kg, i.p.) was administered 30 min before LPS or ANTU. After 24 hours of LPS and 4 hours of ANTU applications lung tissue samples were collected. Results:In the LPS group, significant epithelial damage and intense NF-κB and caspase-3 staining around the bronchiolar epithelium were observed, with JZL184 effectively reducing inflammation and these markers in the area. In the ANTU group, the damage was more focused on the endothelium with similar increases in NF-κB and caspase-3 staining in the alveolar walls, where JZL184 also decreased inflammation and markers intensity. Overall, JZL184 showed a protective effect against inflammation, apoptosis, and tissue damage in lung injuries, highlighting the therapeutic potential of MAGL inhibition in ARDS treatment, with variations in effects depending on the injury model. Conclusion: MAGL inhibition showed model-specific benefits against ARDS-related inflammation, apoptosis, and tissue damage, highlighting its therapeutic potential.

Exploring the interplay between inflammation and male fertility.

Male fertility results from a complex interplay of physiological, environmental, and genetic factors. It is conditioned by the properly developed anatomy of the reproductive system, hormonal regulation balance, and the interplay between different cell populations that sustain an appropriate and functional environment in the testes. Unfortunately, the mechanisms sustaining male fertility are not flawless and their perturbation can lead to infertility. Inflammation is one of the factors that contribute to male infertility. In the testes, it can be brought on by varicocele, obesity, gonadal infections, leukocytospermia, physical obstructions or traumas, and consumption of toxic substances. As a result of prolonged or untreated inflammation, the testicular resident cells that sustain spermatogenesis can suffer DNA damage, lipid and protein oxidation, and mitochondrial dysfunction consequently leading to loss of function in affected Sertoli cells (SCs) and Leydig cells (LCs), and the formation of morphologically abnormal dysfunctional sperm cells that lay in the basis of male infertility and subfertility. This is due mainly to the production and secretion of pro-inflammatory mediators, including cytokines, chemokines, and reactive oxygen species (ROS) by local immune cells (macrophages, lymphocytes T, mast cells) and tissue-specific cells [SCs, LCs, peritubular myoid cells (PMCs) and germ cells (GCs)]. Depending on the location, duration, and intensity of inflammation, these mediators can exert their toxic effect on different elements of the testes. In this review, we discuss the most prevalent inflammatory factors that negatively affect male fertility and describe the different ways inflammation can impair male reproductive function.

Systemic Immuno-Inflammation Index May Predict the Burden of Coronary Artery Disease

Background: Atherosclerosis has a significant place in the pathophysiology of coronary artery disease. In clinical practice, complete blood count is considered as a routine laboratory technique that can be easily applied. Systemic immune inflammatory index (SII), which can be easily calculated with this laboratory method, can be used to evaluate the balance of inflammation, considering the multifaceted effects of atherosclerosis. Aim: In our investigation, we purposed to determine the relationship between the intensity of inflammation, which we calculated with whole blood using this biomarker in 166 patients, and the intensity of coronary artery disease, which was evaluated with coronary angiography. Method: 166 patients who underwent coronary angiography because of acute coronary syndrome were included in our investigation. SYNTAX scores of the patients were calculated using the application on the website (http://www.SYNTAXcore.com.) SYNTAX scores are divided into 3 groups: 0-22, low; 23-32, medium; 33 and above, high. In our study, we divided the SYNTAX score into two groups: 0-22 was defined as low, 23 and above as medium-high. We examined the relationship between the SII and the low and medium-high groups. Findings: In patients consulting with acute coronary syndrome, a statistically significant positive result was found between the coronary artery disease assessed with Systemic immune inflammatory index (SII) and SYNTAX (Synergy Between PCI With TAXUS and Cardiac Surgery) score. (p=0.022) Conclusion: SII calculation is a practical method and can provide the clinicians with important clues about the prevalence of acute coronary syndrome in terms of treatment management; however, more in-depth, well-designed studies are required for SII.

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.