Persistent Inflammatory Process Research Articles

Relapsing polychondritis (clinical observations)

Relapsing polychondritis (RPC) is an autoimmune disease manifested by both repeated attacks and a persistent inflammatory process with progressive destruction of cartilaginous structures, in particular, chondritis of the ears, nose, larynx, bronchi, and joints. RPC is a rare disease (about 1000 cases have been described worldwide). Diagnosis of RPC and the choice of treatment tactics are very difficult, which is associated with the rarity of the pathology, undulating, unpredictable course, and the lack of specific laboratory markers.The clinical observations presented in the article confirm the complexity of diagnosing RPC. Before the disease was verified, both patients repeatedly consulted different specialists: the first patient was diagnosed 3 months after the onset of characteristic symptoms of RPC, and the second patient – 1.5 years later. Late diagnosis and the lack of a unified approach to treatment were the reason for the development of prognostically unfavorable lesions in the second patient – chondritis and perichondritis of the larynx.

The novel vaccines targeting interleukin-1 receptor type I

ObjectiveThere is mounting evidence indicating that atherosclerosis represents a persistent inflammatory process, characterized by the presence of inflammation at various stages of the disease. Interleukin-1 (IL-1) precisely triggers inflammatory signaling pathways by binding to interleukin-1 receptor type I (IL-1R1). Inhibition of this signaling pathway contributes to the prevention of atherosclerosis and myocardial infarction. The objective of this research is to develop therapeutic vaccines targeting IL-1R1 as a preventive measure against atherosclerosis and myocardial infarction. MethodsILRQβ-007 and ILRQβ-008 vaccines were screened, prepared and then used to immunize high-fat-diet fed ApoE-/- mice and C57BL/6J mice following myocardial infarction. Progression of atherosclerosis in ApoE-/- mice was assessed primarily by oil-red staining of the entire aorta and aortic root, as well as by detecting the extent of macrophage infiltration. The post-infarction cardiac function in C57BL/6J mice were evaluated using cardiac ultrasound and histological staining. ResultsILRQβ-007 and ILRQβ-008 vaccines stimulated animals to produce high titers of antibodies that effectively inhibited the binding of interleukin-1β and interleukin-1α to IL-1R1. Both vaccines effectively reduced atherosclerotic plaque area, promoted plaque stabilization, decreased macrophage infiltration in plaques and influenced macrophage polarization, as well as decreasing levels of inflammatory factors in the aorta, serum, and ependymal fat in ApoE-/- mice. Furthermore, these vaccines dramatically improved cardiac function and macrophage infiltration in C57BL/6J mice following myocardial infarction. Notably, no significant immune-mediated damage was observed in immunized animals. ConclusionThe vaccines targeting the IL-1R1 would be a novel and promising treatment for the atherosclerosis and myocardial infarction.

Challenges in Psoriasis Research: A Systematic Review of Preclinical Models.

Psoriasis is a chronic inflammatory skin disease with variable clinical presentation, multifactorial etiology and an immunogenetic basis. Several studies demonstrate that it results from a dysregulated interaction between skin keratinocytes, immune cells, and the environment that leads to a persistent inflammatory process modulated by cytokines and T cells. The development of new treatment options requires increased understanding of pathogenesis. However, the successful implementation of effective drugs requires well-characterized and highly available preclinical models that allow researchers to quickly and reproducibly determine their safety and efficacy. A systematic search on PubMed and Scopus databases was performed and assessed to find appropriate articles about psoriasis models applying the key words previously defined. The PRISMA guidelines were employed. A total of 45 original articles were selected that met the selection criteria. Among these, there are articles on in vivo, in vitro, and ex vivo models, with the in vitro model being the majority due to its ease of use. Within animal models, the most widely used in recent years are chemically induced models using a compound known as imiquimod. However, the rest of the animal models used throughout the disease's research were also discussed. On the other hand, in vitro models were divided into two and three dimensions. The latter were the most used due to their similarity to human skin. Lastly, the ex vivo models were discussed, although they were the least used due to their difficulty in obtaining them. Therefore, this review summarizes the current preclinical models (in vivo, in vitro, and ex vivo), discussing how to develop them, their advantages, limitations, and applications. There are many challenges to improve the development of the different models. However, research in these in vitro model studies could reduce the use of animals. This is favored with the use of future technologies such as 3D bioprinting or organ-on-a-chip technologies.

Сhanges in the composition of gut microbiota in patients with chronic hepatitis С, non-alcoholic fatty liver disease at different stages of liver disease: a review

INTRODUCTION. The human gut microbiota is a set of microorganisms that are in symbiosis with the host organism. The predominance of bacteria of Bacteroidetes, Firmicutes, Actinobacteria types is a characteristic feature of human gut microbiota. However, the composition of the gut microbiota is subject to change under the influence of a number of factors. The influence of the gut-liver axis on the pathogenesis of many chronic liver diseases of various etiologies, both infectious and metabolic, has been proven. At the same time, in the analyzed literature, the data on the relationship between the nature of GM changes and the stage of liver damage are quite controversial.
 OBJECTIVE. Updating and systematization of ideas about the nature of changes in the composition of intestinal microbiota in chronic hepatitis C (CHC) and non-alcoholic fatty liver disease (NAFLD) at different stages of the disease.
 MATERIALS AND METHODS. We analyzed the scientific literature on GM changes in chronic liver diseases with regard to their etiology and disease stage, in particular in chronic viral hepatitis C and NAFLD. The search was conducted in PubMed, Google Scholar, and eLIBRARY databases for 2000-2023 using the following keywords: gut microbiota; microbiota in hepatitis C; microbiota in NAFLD; microbiota in liver fibrosis; liver fibrosis progression. Sixty scientific articles were analyzed and 42 sources were selected, of which more than 60% were published within the last five years.
 RESULTS. This review presents the results of original studies describing the main taxonomic differences between the microbiomes of healthy individuals and patients with CHC complicated by the formation of liver cirrhosis and hepatocellular carcinoma (HCC). Thus, patients with viral cirrhosis showed impoverishment of intestinal commensals Lachnospiraceae and Ruminococcaceae and significant enrichment of Streptococcaceae, Lactobacillaceae and Enterobacteriaceae. In patients with non-alcoholic steatohepatitis (NASH) and FII, enrichment of GM Phylum Bacteroides and Proteobacteria, Families Lachnospiraceae and Enterobacteriaceae, Genera Blautia and Escherichia, with a concomitant decrease of Prevotella was detected.
 DISCUSSION. The analysis of GM taxonomic units in the previously described studies did not reveal significant differences depending on the etiology of the underlying disease. However, a decrease in the representative of the phylum Firmicutes - Ruminococcaceae was observed in CHC in contrast to NAFLD. A more distinct relationship can be observed in the changes of intestinal microbiota in F(III-IV) irrespective of etiology. Thus, in advanced liver fibrosis and cirrhosis of both CHC and NAFLD etiologies, enrichment of GM has been described due to an increase in phylum Proteobacteria, in particular the genus Escherichia and phylum Firmicutes (Blautia, Veillonellaceae). In the studies analyzed, at F(III-IV), an enrichment of the microbiota is observed due to an increase in the phylum Bacteroidetes. Regarding the genus Prevotella, contradictory results were found. In addition, there are ambiguous data regarding the genera Lactobacillus, Ruminococcaceae and Bifidobacteria.
 CONCLUSION. Based on the results of the literature review, we obtained contradictory data on GM composition in patients with CHC and NAFLD. This may be due to the size of samples, heterogeneity of initial data during the selection of patients in the study. The relationship between the composition of microbiota and persistent inflammatory process, expressed liver fibrosis is observed. GM reflects not only functional disorders in chronic liver diseases of various etiologies, but can also serve as a diagnostic indicator of their progression.

Characteristics of nutritional status in patients with chronic kidney disease

Chronic kidney disease is kidney damage that persists for three months or more due to the action of various etiological factors, the anatomical basis of which is the process of replacement of normal anatomical structures with fibrosis, leading to its dysfunction. This nosology is quite common in the modern world; it can progress and lead to disability of patients and a decrease in their quality of life. The mortality rate for this disease also remains high. About 3/4 of patients with this pathology have a terminal stage of the process, which is characterized by the development of protein-energy deficiency (due to uremia, malnutrition, acidosis and persistent inflammatory process), which significantly worsens the prognosis. Currently, the available literature contains a small number of works devoted to this problem, therefore an important part of the management of patients with chronic kidney disease (especially those on hemodialysis) is the assessment and correction of nutritional status. In this article, the authors highlight aspects of the development of protein-energy malnutrition, its possible methods of diagnosis and correction. Electrolyte disturbances, especially hyperkalemia and hyperphosphatemia, are also common complications of chronic kidney disease. Correction of these conditions, in turn, can lead to the development of deficiency of vitamins and other microelements. According to studies presented in the literature, nutritional status is one of the main factors determining the survival and degree of rehabilitation of patients on renal replacement therapy, as well as the effectiveness of dialysis treatment. Thus, a clinician’s knowledge of the nutritional status of this group of patients can improve their prognosis and quality of life.

Hand instrumentation provides improved tissue response over ultrasonic scaler and substantiates safe dental practice: An in vivo study in rats.

The aim of this study was to evaluate the effectiveness of hand debridement (HD) versus ultrasonic dental scaler (UDS) for the treatment of experimental periodontitis (EP) in rats. Thirty 3-month-old male rats were used. EP was induced around the mandibular first molars (right and left). Seven days after induction, the treatments with either HD (n = 30) or UDS (n = 30) were randomly performed in each molar. Euthanasia were performed at 7, 15, and 30 days after treatment. Histometric (percentage of bone in the furcation [PBF]), histopathological, and immunohistochemical (for detection of tartrate-resistant acid phosphatase [TRAP] and osteocalcin [OCN]). Parametric data (PBF and TRAP) was analyzed by One-way ANOVA followed by Tukey's post-test. OCN was analyzed by Kruskal-Wallis followed by Student-Newman-Keuls post-test. The level of significance was 5%. Group HD presented higher PBF and lower TRAP-immunolabeling at 30 days as compared with UDS in the same period (p≤0.05). Group HD presented higher OCN immunolabeling at 30 days as compared with 7 and 15 days (p≤0.05). Persistent and exacerbated inflammatory process was observed in some specimens from group UDS at 30 days, as well as the bone trabeculae presented irregular contour, surrounded by many active osteoclasts. Nonsurgical periodontal therapy with HD resulted in higher PBF and lower expression of TRAP as compared with UDS. Also, HD increased the expression of OCN over time.

Acute myocardial calcification in a patient with fulminant myocarditis.

Relationship with Industry: None A 38-year-old man was admitted with a 3-week history of rapid clinical deterioration. The patient presented with multisystem inflammatory syndrome associated with multi-organ failure (white blood and polynuclear cells counts at respectively 54.40 and 51.60 *109/L; C-reactive protein, Ferritin and Fibrinogen levels at respectively, 214 mg/L, 1624 μg/L, and 8.31 g/L; and creatinine and bilirubin levels at respectively 397 μmol/L (4,49 mg/dL) and 57 μMol/L (3,33 mg/dL)). Large screening and multiple testing for bacterial and viral infections remained negative in a patient with Covid-19 infection 3-months earlier without vaccination. The patient was transferred to the Intensive Care Unit necessitating mechanical ventilation, hemodialysis, and inotropic support. Rapidly, diffuse ST elevation on electrocardiogram and increased levels of high-sensitivity cardiac I troponin (hs-cTnI = 135000 ng/L) and natriuretic peptide (NT-ProBNP = 72114 ng/L) were found. Coronary angiogram showed no significant coronary disease and transthoracic echocardiography (TTE) showed reduced left ventricular ejection fraction (LVEF = 40%). Cardiac magnetic resonance imaging confirmed diffuse and extensive gadolinium uptake. Despite negative cardiac biopsies, the diagnosis of fulminant myocarditis was made and the patient underwent corticosteroids bolus and intravenous immunoglobulin therapies. Clinical evolution was deemed favourable with a progressive decrease in systemic inflammatory process associated with a decrease in cardiac biomarkers levels. However, 2 weeks later, chest X-ray (Panel A) and TTE (Panel B) showed acute and impressive left ventricular calcified remodelling process with diffuse epicardial calcification and septal patchy fibrosis (whites triangles). The positron emission tomography (PET-CT) confirmed the diffuse FDG uptakes suggesting persistent local inflammatory process (Panel C) associated with large epicardial calcified remodelling (Panel D). The patient was discharged 1 month after the index admission with optimized heart-failure therapy and planned follow-up at the Heart Failure Clinic.

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Abstract. Recent pandemic caused by the SARS-CoV-2 virus has united researchers from all over the world. However, despite their efforts, many questions remain unsolved: how the immune system is effective against this viral infection, how long the immunity persists in convalescents, what are the consequences of the disease. The inflammatory process, which is based on multicomponent immunological disorders, is one of the leading pathogenetic links of the disease caused by the SARS-Cov-2 virus. In this regard, a precise study of the immune status peculiarities in patients � convalescents after COVID-19 and their possible role in the further development of chronic pathology are relevant. The aim of the work is to investigate peculiarities of immune disorders in convalescents after acute respiratory disease COVID-19 in relation to the severity of the disease and the timing of the examination after the acute period. Methods. We examined 91 convalescents after COVID-19, aged 21-67 years, treated as inpatients during the acute period of the disease. After the acute period these patients received a course of rehabilitation treatment in the Government Institution �The Scientific-Practical Medical Centre �Rehabilitation��. For comparison, a group of 45 patients with bacterial community-acquired pneumonia of medium severity were examined. As a control for laboratory indices, 24 practically healthy persons were examined. Cytokine status was studied by determining the levels of pro- and anti-inflammatory cytokines using immunoenzymatic method. Non-specific resistance was investigated on the base of phagocytic activity and phagocytic number of monocytes. Indicators of cellular immunity were evaluated using an indirect immunofluorescence reaction using monoclonal antibodies (CD3+, CD22+, CD4+, CD8+, CD16+) and on this basis index values were calculated that characterize the relationships of the studied subpopulations. When analyzing these data, the severity of the COVID-19 and the time of examination after the acute period of the disease were taken into account. Results. At the beginning of the course of recovery treatment, a pronounced imbalance in the ratio of pro- and anti-inflammatory cytokines with a significant predominance of the first one, was revealed. These changes can contribute to the persistence of the inflammatory process with further formation of the chronic pathology. This imbalance did not depend significantly on the severity of COVID-19, persisted for a long time and was 1.9 times more pronounced than in bacterial community-acquired pneumonia. In the period of convalescence, suppression of the monocytes� phagocytic activity and significant changes in the T-cells link of immunity were also revealed. It should be noted that disorders of cellular immunity depended on the severity of COVID-19 and were most pronounced in patients with its severe course. These changes persisted for a long time (examinations were carried out 2-3 weeks and 2-3 months after the acute period), which determines the need for recovery treatment during the convalescence period. Conclusions. 1. In convalescents after acute respiratory disease caused by the SARS-CoV-2 virus, certain disturbances of the immune status remain, which significantly affect the functional state of the organism as a whole and may be the basis for a persistent inflammatory process and the development of chronic pathology in the future. 2. Immune defense of convalescents after COVID-19 is characterized by a significant decrease in non-specific protection indices and the cellular link of immunity with manifestations of cytokine imbalance and these changes persist for a long time, which can contribute to the formation of post-COVID syndrome. 3. The obtained data serve as a pathogenetic basis for carrying out complex immunorehabilitation measures in convalescents after COVID-19 in order to recover the normal functioning of immune system, correcting protective reserves of the organism and preventing the development of chronic pathology. Key words: COVID-19, cytokine status, non-specific defense, cellular immunity

Anomalous Epithelial Variations and Ectopic Inflammatory Response in Chronic Obstructive Pulmonary Disease.

Phenotypic alterations in the lung epithelium have been widely implicated in chronic obstructive pulmonary disease (COPD) pathogenesis, but the precise mechanisms orchestrating this persistent inflammatory process remain unknown because of the complexity of lung parenchymal and mesenchymal architecture. To identify cell type-specific mechanisms and cell-cell interactions among the multiple lung resident cell types and inflammatory cells that contribute to COPD progression, we profiled 57,918 cells from lungs of patients with COPD, smokers without COPD, and never-smokers using single-cell RNA sequencing technology. We predicted pseudotime of cell differentiation and cell-to-cell interaction networks in COPD. Although epithelial components in never-smokers were relatively uniform, smoker groups represent extensive heterogeneity in epithelial cells, particularly in alveolar type 2 (AT2) clusters. Among AT2 cells, which are generally regarded as alveolar progenitors, we identified a unique subset that increased in patients with COPD and specifically expressed a series of chemokines including CXCL1 and CXCL8. A trajectory analysis revealed that the inflammatory AT2 cell subpopulation followed a unique differentiation path, and a prediction model of cell-to-cell interactions inferred significantly increased intercellular networks of inflammatory AT2 cells. Our results identify previously unidentified cell subsets and provide an insight into the biological and clinical characteristics of COPD pathogenesis.

Resolvin D5 disrupts anxious- and depressive-like behaviors in a type 1 diabetes mellitus animal model.

Type 1 diabetes mellitus (T1DM) is a chronic disease related to a persistent inflammatory process reaching the central nervous system, which leads to psychiatric comorbidities such as depression and anxiety. The search for new therapeutic agents effective in alleviating the psychiatric condition associated with T1DM becomes critical. Using an animal model of T1DM, we aimed to evaluate the effect of a specific specialized pro-resolving lipid mediator Resolvin D5 (RvD5), in preventing behaviors related to depression and anxiety, investigating its influence on inflammasome in interleukin (IL)-1β in the hippocampus and prefrontal cortex. After experimental T1DM induction with streptozotocin (60mg/kg, i.p.), these animals were treated for 23days and randomly divided into 6 subgroups according to the treatment: vehicle (VEH), the antidepressant Fluoxetine (FLX; 10mg/kg), the nonsteroidal anti-inflammatory Ibuprofen (IBU; 30mg/kg) or Resolvin D5 (RvD5; 1 3, or 10ng/animal). As a control group for the experimental-T1DM condition, a group of normoglycemic animals treated with VEH underwent the same behavioral tests: elevated plus maze, open field, and modified forced swimming tests. In the end, hippocampus and prefrontal cortex samples were processed to analyze the pro-inflammatory cytokine IL-1β levels. Our data showed that RvD5 treatment prevented the more pronounced anxious-like and reduced the depressive-like behaviors of experimental-T1DM animals and significantly improved the plasma glucose levels. Additionally, RvD5 treatment prevented the increased level of pro-inflammatory cytokine IL-1β in the hippocampus and prefrontal cortex of experimental-T1DM rats. To conclude, RvD5 presents a preventive therapeutic potential in impairing the development of the emotional complications resulting from T1DM. This potential may be related to its protective profile, as demonstrated in this study by its pro-resolutive action on neuroinflammation in the hippocampus and prefrontal cortex.

Topical Aspirin Administration Improves Cutaneous Wound Healing in Diabetic Mice Through a Phenotypic Switch of Wound Macrophages Toward an Anti-inflammatory and Proresolutive Profile Characterized by LXA4 Release.

Patients with diabetes present a persistent inflammatory process, leading to impaired wound healing. Since nonhealing diabetic wound management shows limited results, the introduction of advanced therapies targeting and correcting the inflammatory status of macrophages in chronic wounds could be an effective therapeutic strategy to stop the sustained inflammation and to return to a healing state. In an excisional skin injury in a diet-induced diabetic murine model, we demonstrate that topical administration of low-dose aspirin (36 μg/wound/day) improves cutaneous wound healing by increasing wound closure through the promotion of the inflammation resolution program of macrophages. This treatment increased efferocytosis of wound macrophages from aspirin-treated diabetic mice compared with untreated diabetic mice. We also show that aspirin treatment of high-fat-fed mice oriented the phenotype of wound macrophages toward an anti-inflammatory and proresolutive profile characterized by a decrease of LTB4 production. The use of diabetic mice deficient for 5-LOX or 12/15-LOX demonstrated that these two enzymes of acid arachidonic metabolism are essential for the beneficial effect of aspirin on wound healing. Thus, aspirin treatment modified the balance between pro- and anti-inflammatory eicosanoids by promoting the synthesis of proresolving LXA4 through 5-LOX, LTA4, 12/15-LOX signaling. In conclusion, the restoration of an anti-inflammatory and proresolutive phenotype of wound macrophages by the topical administration of low-dose aspirin represents a promising therapeutic approach in chronic wounds.

Functional Implications of Oral Papillomatosis

The papillomatous lesion has a number of implications that destabilize the normal functioning of the stomatognathic system, but also it has psychological implications. A patient with a papilloma located in an area of maximum visibility tends to be less exposed in public, to reduce socialization, to feel embarrassed. Oral papilloma affects the masticatory function, phonation, but also aesthetics. Understanding how local immunity works in patients diagnosed with oral papilloma is essential. Local immunity influences the evolution of the papillomatous oral lesion. Toll-like receptors are extremely important in the immune process of oral papilloma. Toll-like receptors can be used as indicators of lesion progression. A reduced expression of these receptors in the focus of the lesion is suggestive of pathological progress. It is also emphasized that in the oral cavity we find a well-represented local immune system which cells have an immune role and whose expression influences the evolution of the disease. The most incriminating factor in the occurrence of oral papilloma is HPV infection. The persistent inflammatory process produced by the HPV virus stimulates the development of oral, pharyngeal, laryngeal neoplasms. The HPV virus acts as a direct inducer in the process of transforming the benign lesion into a malignant lesion. Macrophages play an important role in the malignancy potential induced by the HPV virus. Macrophages are activated by increasing the metabolic rate and fighting tumor cells.

Familial Mediterranean fever may actually be a persistent inflammatory process on vascular endothelium all over the body

Background: We tried to understand whether or not there is a persistent inflammatory process in Familial Mediterranean Fever (FMF). Methods: Consecutive patients with the FMF and controls were studied. Results: The study included 39 patients with the FMF (18 females) and 39 controls. Mean age of the FMF patients was 27.5 ± 11.9 (11-58) years. Although the body weight and body mass index (BMI) were retarded in the FMF patients (64.6 versus 71.7 kg and 24.1 versus 25.7 kg/m2, respectively), the differences were nonsignificant probably due to the small sample size of the study (p>0.05). The mean body heights were similar in both groups (163.4 versus 166.8 cm, p>0.05). As negative acute phase reactants (APR), low density lipoproteins (LDL) (99.0 versus 114.3 mg/dL) and high density lipoproteins (HDL) (37.5 versus 44.5 mg/dL) were suppressed whereas triglycerides (TG) increased (110.2 versus 105.1 mg/dL) as positive APR, but the differences were nonsignificant probably due to the small sample size of the study, again (p>0.05). On the other hand, systolic blood pressures (BP) (115.0 versus 124.8 mmHg, p= 0.047) and diastolic BP (79.2 versus 88.9 mmHg, p= 0.001) were suppressed parallel to the suppressed body weight and BMI, significantly. Conclusion: Although the FMF is described as intermittent attacks of painful inflammation, probably there is a persistent vascular endothelial inflammation all over the body. The suppressed body weight, BMI, LDL, HDL, and systolic and diastolic BP and the increased TG levels probably play roles of positive and negative APR in the systemic inflammatory process. Key words: Familial Mediterranean fever, chronic endothelial damage, atherosclerosis, metabolic syndrome, acute phase reactants, triglycerides, blood pressure.

Effects of Transportation Stress on Complete Blood Count, Blood Chemistry, and Cytokine Gene Expression in Heifers.

Blood samples were obtained from 16 high-risk heifers; eight were newly arrived from a 40 h road trip (0 days post-arrival (DPA)), whereas the other eight heifers had been in the feedlot at 25 DPA. Both groups were transported from the southeast tropical region of Mexico to a feedlot in the northeast and were sampled on the same day. The complete blood count, blood chemistry, and cytokine gene expression were analyzed. Gene expression was analyzed using specific primers to amplify and quantify the cDNA reverse transcribed from the mRNA transcripts for tumor necrosis factor (TNF)-α, interferon (IFN)-γ, and interleukin (IL)-2. Higher values for hematocrit (p = 0.029), hemoglobin (p = 0.002), eosinophils (0.029), albumin (p = 0.014), alanine aminotransferase (p = 0.004), bilirubin (p = 0.003), cholesterol (p = 0.014), and cortisol (p = 0.051) were observed in the 0 DPA group than the 25 DPA group. In the electrophoresis of TNF-α amplification products, two non-specific bands were observed in the 0 DPA group. These bands were sequenced, and BLAST analysis suggested that they corresponded to bovine lymphotoxin and have not been reported previously related to stress. The TNF-α expression level was higher (p = 0.001) in the 25 DPA group than the 0 DPA group according to the semi-quantitative expression analysis. This may indicate a persistent inflammatory process that could be related to trauma and disease, which can negatively impact their subsequent health and growth performance. In conclusion, homeostatic disruption was apparent in the 0 DPA heifers, which showed higher cortisol and reductions in TNF-α levels and stress-induced bovine lymphotoxin (SIBL) co-expression.

Multi-Antigen Imaging Reveals Inflammatory DC, ADAM17 and Neprilysin as Effectors in Keloid Formation.

Keloid is an aberrant scarring process of the skin, characterized by excessive extracellular matrix synthesis and deposition. The pathogenesis of this prevalent cutaneous disorder is not fully understood; however, a persistent inflammatory process is observed. To obtain more insight into this process, we analyzed lesional, perilesional and healthy tissue using multi-antigen-analysis (MAA) in conjunction with a data mining approach. Here, we demonstrate that monocyte-derived inflammatory dendritic cells (CD1a+, CD11c+, CD14+) and activated CD4+ T lymphocytes (CD45 RO+) dominated the immune infiltration in keloids while associating with fibroblasts. In perilesional tissue, precursor immune cells were dominant in the perivascular area, suggesting that they were attracted by an immune process, potentially in the lesional area. Supporting this hypothesis, only in keloid lesions, high levels of ADAM10/17 and Neprilysin (CD10) were observed in both fibroblasts and leukocytes. The spatial proximity of these two cell types, which could be confirmed by image analysis only in lesional tissue, could be a potential factor leading to the activation of fibroblasts. Our findings provide new insight into the pathogenesis of keloid formation and reveal metalloproteinases as a target for therapeutical intervention.

Dual Role of Insulin-Like Growth Factor (IGF)-I in American Tegumentary Leishmaniasis.

Background Cytokines and growth factors involved in the tissue inflammatory process influence the outcome of Leishmania infection. Insulin-like growth factor (IGF-I) constitutively present in the skin may participate in the inflammatory process and parasite-host interaction. Previous work has shown that preincubation of Leishmania (Leishmania) amazonensis with recombinant IGF-I induces accelerated lesion development. However, in human cutaneous leishmaniasis (CL) pathogenesis, it is more relevant to the persistent inflammatory process than progressive parasite proliferation. In this context, we aimed to investigate whether IGF-I was present in the CL lesions and if this factor may influence the lesions' development acting on parasite growth and/or on the inflammatory/healing process. Methodology. Fifty-one CL patients' skin lesion samples from endemic area of L. (Viannia) braziliensis infection were submitted to histopathological analysis and searched for Leishmania and IGF-I expression by immunohistochemistry. Results In human CL lesions, IGF-I was observed preferentially in the late lesion (more than 90 days), and the percentage of positive area for IGF-I was positively correlated with duration of illness (r = 0.42, P < 0.05). IGF-I was highly expressed in the inflammatory infiltrate of CL lesions from patients evolving with good response to therapy (2.8% ± 2.1%; median = 2.1%; n = 18) than poor responders (1.3% ± 1.1%; median: 1.05%; n = 6; P < 0.05). Conclusions It is the first time that IGF-I was detected in lesions of infectious cutaneous disease, specifically in American tegumentary leishmaniasis. IGF-I was related to chronicity and good response to treatment. We may relate this finding to the efficient anti-inflammatory response and the known action of IGF-I in wound repair. The present data highlight the importance of searching nonspecific factors besides adaptive immune elements in the study of leishmaniasis' pathogenesis.

Vasculitis changes in COVID-19 survivors with persistent symptoms: an [18F]FDG-PET/CT study

PurposeSeveral patients experience unexplained persistent symptoms after SARS-CoV-2 recovering. We aimed at evaluating if 2-deoxy-2-[18F]fluoro-D-glucose ([18F]FDG) was able to demonstrate a persistent inflammatory process.MethodsRecovered adult COVID-19 patients, who complained unexplained persisting symptoms for more than 30 days during the follow-up visits, were invited to participate in the study. Patients fulfilling inclusion criteria were imaged by [18F]FDG positron emission tomography/computed tomography ([18F]FDG-PET/CT). Whole-body [18F]FDG-PET/CT, performed according to good clinical practice, was qualitatively (comparison with background/liver) and semi-quantitatively (target-to-blood pool ratio calculated as average SUVmax artery/average SUVmean inferior vena cava) analyzed. Negative follow-up [18F]FDG-PET/CT images of oncologic patients matched for age/sex served as controls. Mann-Whitney test was used to test differences between groups. SPSS version 26 was used for analyses.ResultsTen recovered SARS-CoV-2 patients (seven male and three females, median age 52 years, range 46–80) with persisting symptoms were enrolled in the study. Common findings at visual analysis were increased [18F]FDG uptake in bone marrow and blood vessels (8/10 and 6/10 cases, respectively). [18F]FDG uptake in bone marrow did not differ between cases and controls (p = 0.16). The total vascular score was similar in the two groups (p = 0.95). The target-to-blood pool ratio resulted higher in recovered SARS-CoV-2 patients than in controls.ConclusionAlthough the total vascular score was similar in the two groups, the target-to-blood pool ratio was significantly higher in three vascular regions (thoracic aorta, right iliac artery, and femoral arteries) in the recovered COVID-19 cohort than in controls, suggesting that SARS-CoV-2 induces vascular inflammation, which may be responsible for persisting symptoms.

The Effect Of Giving Okra (Abelmoschus Esculentus) Extract On The Increase Of Vascular Endhothelial Growth Factor (Vegf)

Background: People with diabetes mellitus who perform tooth extraction related to the complications that disrupt the process wound healing. Diabetics have persistent inflammatory phase and abnormal angiogenesis in proliferation phase. Treatment for people with diabetes mellitus is done through increase VEGF. Herbal medicine that use extracts from plants have benefits in wound healing processes such as okra fruit extract because it contains flavonoids. Flavonoids in accelerating wound healing in patients diabetes mellitus can through its role as anti-diabetic, anti-inflammatory and antioxidant. This plays a role in the persistent inflammatory resolution process leading to proliferation by macrophages and immunomodulatory effects of macrophage function in issuing growth factors. Objective: To prove okra fruit extract (Abelmoschus esculentus) influences the increase in VEGF expression in the process of healing wounds from tooth extraction of diabetes mellitus Wistar rats. Method: Laboratory experimental research with randomized post test only The control group used 24 Wistar mice which were divided into two groups namely the control group (STZ induction) and the treatment group (STZ induction by giving okra fruit extract). Tooth extraction is done on the incisors left lower jaw. 4 mice from each group were sacrificed on day 3, 5 and 7 after revocation. A Socket is cut for inspection immunohistochemistry. Results: VEGF expression of the control group compared to the group the treatment showed significant results (p &lt;0.05). Conclusion: Administration of extracts okra (Abelmoschus esculentus) has the effect of increasing expression VEGF in the healing process of wistar tooth extraction wounds with diabetes mellitus.

Periapical bone healing following endodontic treatment on the right lower premolar

Background: Acute exacerbation represents a painful condition whereby the tooth becomes highly sensitive to percussion and bite testing, and it can be aggravated by traumatic occlusion. In general, it results from earlier acute apical periodontitis. Bone destruction can be detected via a radiographic examination, and it can be seen as a radiolucent area at the periapex. Bone resorption is caused by osteoclast activation, which results from pulp inflammation. Nonsurgical endodontic treatment is typically performed to resolve the condition. This study aimed to provide an overview of both the treatment protocol and the role of 2% chlorhexidine gluconate as an endodontic irrigant. Case Report: A 38-year-old woman presented with a major complaint regarding tenderness in her lower second right premolar. The patient reported having experienced similar pain approximately 8 months previously. Clinically, the tooth had lost 50% of its coronal structure, which indicated a Class II cavity. Radiographically, bone resorption was detected in the periapical area of the tooth. An analgesic had been consumed for approximately 3 days. The cavity was cleaned and opened, and working length measurements were performed using an electronic apex locator and conventional radiography. Biomechanical preparation was done using ProTaper NEXTTM files, until size X3. Irrigation was performed using 5.25% sodium hypochlorite at each file change and continued with 17% ethylenediaminetetraacetic acid and 2% chlorhexidine for final irrigation. Sterile Aqua Dest was used for each irrigation change to avoid interaction between irrigants. Obturation was performed by means of warm vertical compaction with an epoxy resin-based sealer. An endocrown composite was recommended for permanent restoration. Four months of follow-up revealed bone regeneration and healing. Conclusion: Bone resorption is a common finding in a diseased tooth, and it stems from the persistent inflammatory process. Osteoclasts are responsible for both bone demineralization and activated pro-inflammatory cytokines. The correct endodontic treatment protocol plays an essential role in periapical bone healing.

The benefit of minocycline on negative symptoms of schizophrenia in patients with recent-onset psychosis (BeneMin): a randomised, double-blind, placebo-controlled trial

SummaryBackgroundThe antibiotic minocycline has neuroprotective and anti-inflammatory properties that could prevent or reverse progressive neuropathic changes implicated in recent-onset schizophrenia. In the BeneMin study, we aimed to replicate the benefit of minocycline on negative symptoms reported in previous pilot studies, and to understand the mechanisms involved.MethodsIn this randomised, double-blind, placebo-controlled trial, we recruited people with a schizophrenia-spectrum disorder that had begun within the past 5 years with continuing positive symptoms from 12 National Health Service (NHS) trusts. Participants were randomly assigned according to an automated permuted blocks algorithm, stratified by pharmacy, to receive minocycline (200 mg per day for 2 weeks, then 300 mg per day for the remainder of the 12-month study period) or matching placebo, which were added to their continuing treatment. The primary clinical outcome was the negative symptom subscale score of the Positive and Negative Syndrome Scales (PANSS) across follow-ups at months 2, 6, 9, and 12. The primary biomarker outcomes were medial prefrontal grey-matter volume, dorsolateral prefrontal cortex activation during a working memory task, and plasma concentration of interleukin 6. This study is registered as an International Standard Randomised Controlled Trial, number ISRCTN49141214, and the EU Clinical Trials register (EudraCT) number is 2010-022463-35I.FindingsBetween April 16, 2013, and April 30, 2015, we recruited 207 people and randomly assigned them to receive minocycline (n=104) or placebo (n=103). Compared with placebo, the addition of minocycline had no effect on ratings of negative symptoms (treatment effect difference −0·19, 95% CI −1·23 to 0·85; p=0·73). The primary biomarker outcomes did not change over time and were not affected by minocycline. The groups did not differ in the rate of serious adverse events (n=11 in placebo group and n=18 in the minocycline group), which were mostly due to admissions for worsening psychiatric state (n=10 in the placebo group and n=15 in the minocycline group). The most common adverse events were gastrointestinal (n=12 in the placebo group, n=19 in the minocycline group), psychiatric (n=16 in placebo group, n=8 in minocycline group), nervous system (n=8 in the placebo group, n=12 in the minocycline group), and dermatological (n=10 in the placebo group, n=8 in the minocycline group).InterpretationMinocycline does not benefit negative or other symptoms of schizophrenia over and above adherence to routine clinical care in first-episode psychosis. There was no evidence of a persistent progressive neuropathic or inflammatory process underpinning negative symptoms. Further trials of minocycline in early psychosis are not warranted until there is clear evidence of an inflammatory process, such as microgliosis, against which minocycline has known efficacy.FundingNational Institute for Health Research Efficacy and Mechanism Evaluation (EME) programme, an MRC and NIHR partnership.