Wall Inflammation Research Articles

Surgical Procedure for Pyometra and Mammae Tumor Treatment in a Pitbull Dog

Pyometra is an infection or inflammation of the uterine wall characterized by the accumulation of pus in the uterine lumen. Predisposing factors include age, breed, bacterial infection, and hormones. Another disease that is often correlated with an imbalance in reproductive hormones is mammary tumors. A 7-year-old unspayed female Pitbull dog weighed 27.9 kg has clinical symptoms of frequent discharge of mucopurulent reddish-brown discharge with a foul odor from the vagina. The left mammary glands of the second, third, and fourth nipples have lumps about 20 cm in diameter, are solid in consistency, well-defined, the same color as the skin surface, and can be moved. Diagnosis performed on physical examination, hematology, blood chemistry, and cytology was pyometra and mammary tumors. Treatment was done by ovariohysterectomy and unilateral mastectomy. Post-surgery therapy was enrofloxacin 5 mg/kg, ketoprofen 2 mg/kg, phytomenadione 1 mg/kg, and Biodin® 0.1 ml/kg, followed by intensive surgical wound care. The patient recovered after two months of treatment.

Anorectal Lesions in Children with Crohn’s Disease: A Review Article

Crohn’s disease (CD) is an inflammatory bowel disease with chronic transmural inflammation of the intestinal wall and can be observed from oral cavity to anus. There is an increasing rate of CD in children. Surgery has a role in the management of this entity when medical treatment is unsuccessful. In this review article it is aimed to review the general characteristics of anorectal disease in children with CD and principles of management are discussed under the light of relevant literature.

Inflammatory bowel disease: pathogenesis, diagnosis and current therapeutic approach

Inflammatory bowel disease is a group of conditions of unknown etiology, represented by Crohn’s disease and ulcerative colitis and characterized by the presence of intestinal wall inflammation. From the first cases described to date, several studies have been performed to elucidate the cause of inflammatory bowel disease. Generally, the genetic factors predispose to their occurrence while epigenetic and environmental factors trigger them. Genetic factors are mutations of the genes involved in the response and recognition of immune cells to different pathogens. The most studied epigenetic and environmental factors are smoking (which predisposes to Crohn’s disease and can be protective for ulcerative colitis), lack of vitamin D, a diet rich in sugars and low in flavonoids and fibers. The diagnosis is usually established by endoscopy and biopsy. Recent technologies can perform live biopsies such as endocytoscopy or confocal laser endomicroscopy, with an accuracy of 100% compared to classical methods. Therapy involves several classes of drugs, preferably in association with diet and lifestyle changes. In case of complications or in non-responsive diseases, surgery must be considered, as documented for ulcerative colitis that can be cured by removing the entire colon. The purpose of this review is to present recent findings on pathology, as well as modern diagnosis and treatment methods for IBD.

Evaluation of Serum Levels of Interlukine-17A (IL-17A), Fibrinogen, and Red Distribution Width (RDW) in Patients with Coronary Artery Ectasia, Candidate for Coronary Angiography: A Cross-Sectional Study

Background: Coronary stenosis and ectasia are cardiovascular diseases characterized by dysfunction of endothelial cells. Studies have shown that impaired blood flow due to inflammation and deposition in the endothelial cell wall can be effective in disease occurrence and progression. Although the etiologies of these diseases have not been identified accurately, it has been shown that inflammation and coagulation can be the main causes in these patients. Objectives: The aim of this study was to evaluate the levels of fibrinogen, Interlukine-17A (IL-17A), and red distribution width (RDW) in patients with coronary artery disease (CAD) and ectasia. Methods: In this study, 140 patients with CAD admitted to Shariati Hospital of Tehran University of Medical Sciences, Iran, were included from from Jun 2020 to October 2021. Based on the severity of CAD, the participants were divided into two equal groups (n = 70 in each) of mild CAD (patients with CAD less than 50%) and multi-vessels CAD (patients with more than 50% stenosis in coronary arteries) according to the number of involved vessels (one, two, or three). Then, 5 cc of peripheral blood was collected from each patient in ethylenediaminetetraacetic acid (EDTA) containing tubes. IL-17A and fibrinogen were measured using enzyme-linked immunosorbent assay (ELISA) kit, and RDW was calculated by cell counter. Results: The mean age of participants was 63.0 ± 11.0 years in the mild group (35% males vs. 65% females) and 60.1 ± 12.1 years in the multi-vessels group (28% males vs. 72% females). The results showed that IL-17A, fibrinogen, and RDW levels in patients with ectasia and multi-vessels group were significantly higher than those in patients without coronary ectasia and mild CAD, respectively (P-value = 0.01 for fibrinogen; P-value = 0.05 for IL-17A; and P-value = 0.03 for RDW). Conclusions: According to our results, identification and evaluation of fibrinogen and IL-17A, along with laboratory indices including RDW can be helpful in diagnosing high-risk individuals. Ectasia can be prevented, and it is possible to increase the patients’ survival through using some preventive and therapeutic strategies.

Circumferential wall enhancement with contrast ratio measurement in unruptured intracranial aneurysm for aneurysm instability.

BackgroundAneurysm wall enhancement on high‐resolution vessel wall imaging (HR‐VWI) may represent vessel wall inflammation for unruptured intracranial aneurysms (UIAs). Further evidence for the role of circumferential aneurysm wall enhancement (CAWE) in evaluating the instability of UIAs is required, especially in small aneurysms (<7 mm).MethodsWe analyzed patients with saccular UIAs who prospectively underwent HR‐VWI on a 3.0 T MRI scanner in our center from September 2017 to August 2021. The presence of AWE was identified and quantitatively measured using the aneurysm‐to‐pituitary stalk contrast ratio (CRstalk) with maximal signal intensity value. The PHASES and ELAPSS scores were used to assess the risk of aneurysm rupture and growth. We evaluated the association of CAWE and CRstalk value with intracranial aneurysm instability.ResultsOne hundred patients with 109 saccular UIAs were included in this study. Eighty‐three UIAs (76.1%) had a size smaller than 7 mm. PHASES and ELAPSS scores were significantly higher in UIAs with CAWE than in UIAs without CAWE (p < .01). The association of CAWE with PHASES and ELAPSS scores remained in small UIAs (<7 mm). The optimal cutoff value of CRstalk for CAWE was 0.5. PHASES and ELAPSS scores were significantly higher in UIAs with CRstalk ≥0.5 than in UIAs with CRstalk <0.5 (p < .01).ConclusionsCAWE on HR‐VWI is a valuable imaging marker for aneurysm instability in UIAs. CRstalk value ≥0.5 may be associated with a higher risk of intracranial aneurysm rupture and growth.

Atorvastatin for unruptured intracranial vertebrobasilar dissecting aneurysm (ATREAT-VBD): protocol for a randomised, double-blind, blank-controlled trial

IntroductionVertebrobasilar dissecting aneurysms (VBDAs) are associated with serious complications and a poor prognosis. It is believed that inflammation of the aneurysm wall may be the main cause of rupture or...

Regulating mitochondrial homeostasis and inhibiting inflammatory responses through Celastrol.

BackgroundThe high morbidity and mortality rate of coronary heart disease poses a serious threat to human health. Atherosclerosis, a chronic inflammation of the blood vessel wall, is a significant pathological process leading to coronary heart disease. Macrophage inflammation plays a crucial role in the occurrence and development of atherosclerosis.MethodsMacrophage inflammation model was constructed by lipopolysaccharide (LPS), and macrophages were treated with Celastrol at different concentrations (0, 0.1, 1, 10, 100 ng/mL) and different time points (0, 1, 3, 6, 12 h). Real-time quantitative PCR (qPCR) and Western Blot were used to detect the expression of Nur77 mRNA and protein. Macrophages were then pretreated with 100 nmol/L tripterine for 40min and co-cultured with 100 ng/mL LPS. The expression levels of inflammatory factors and chemokines, phosphorylation of phospho-dynamin-related protein 1 (p-Drp1) at Ser637 and expression of mitochondrial fusion protein mitochondrial fusion protein mitofusin-2 (Mfn2) were detected by qPCR, Western blot and ELISA, respectively. The changes of mitochondrial membrane potential were detected by JC-1 probe.Results100 nmol/L Celastrol can significantly inhibit LPS-induced inflammatory responses and down-regulate the expression levels of cytokines such as inducible nitric oxide synthase (iNOS), cyclooxygenase-2 (COX2), tumor necrosis factor-α (TNF-α), chemokines (CCL-2, and CXCL-10), as well as chemokines. And Celastrol could regulate mitochondrial fission and fusion by promoting the phosphorylation of the Drp1 at the Ser637 site, thereby inhibiting mitochondrial fission. At the same time, by up-regulating the level of the Mfn2, Celastrol also promoted mitochondrial fusion. In addition, we found that the nuclear factor-k-gene binding (NF-κB), extracellular signal-regulated kinase 1/2 (ERK1/2), and p38 signaling pathways aided the drug’s anti-inflammatory effects. We also explored the relationship between Celastrol and the nuclear receptor Nur77 and found that it could up-regulate the expression of Nur77.ConclusionsOur study found that Celastrol could reduce inflammation by regulating Drp1 dependent mitochondrial fission and fusion, as well as the ERK1/2, p38, NF-κB signaling pathways. This finding provides a strong direction for the development of new anti-inflammatory drugs for atherosclerosis.

Triglyceride-Rich Lipoproteins: Their Role in Atherosclerosis.

The term "triglyceride-rich lipoproteins" (TRLs) includes chylomicrons and their remnants, very low-density lipoproteins (VLDL), and intermediate-density lipoproteins (IDL). In this manuscript, the mechanisms by which atherogenic TRLs contribute to the formation of atheroma plaques are reviewed. Cholesterol from TRLs that can be retained in the subendothelial space (i.e., remnants, DLs, and small VLDLs) contributes to the genesis of atherosclerosis. Triglycerides of atherogenic TRLs induce inflammation of the arterial wall. Mechanisms that explain the involvement of TRLs in atherosclerosis are the generation of pro-atherogenic changes in high-density lipoproteins and low-density lipoproteins, accumulation of TRLs in plasma, and their passage to the subendothelial space where they cause endothelial dysfunction and inflammation of the vascular wall. Furthermore, plasma accumulation of TRLs causes hyperviscosity and a procoagulant state. Finally, this manuscript summarizes the controversial aspects of the clinical approach and the treatment of cases with dyslipidemia explained by atherogenic TRLs.

Angiopoietin-2/-1 ratios and MMP-3 levels as an early warning sign for the presence of giant cell arteritis in patients with polymyalgia rheumatica

BackgroundDiagnosing patients with giant cell arteritis (GCA) remains difficult. Due to its non-specific symptoms, it is challenging to identify GCA in patients presenting with symptoms of polymyalgia rheumatica (PMR), which is a more common disease. Also, commonly used acute-phase markers CRP and ESR fail to discriminate GCA patients from PMR and (infectious) mimicry patients. Therefore, we investigated biomarkers reflecting vessel wall inflammation for their utility in the accurate diagnosis of GCA in two international cohorts.MethodsTreatment-naïve GCA patients participated in the Aarhus AGP cohort (N = 52) and the Groningen GPS cohort (N = 48). The AGP and GPS biomarker levels and symptoms were compared to patients presenting phenotypically as isolated PMR, infectious mimicry controls and healthy controls (HCs). Serum/plasma levels of 12 biomarkers were measured by ELISA or Luminex.ResultsIn both the AGP and the GPS cohort, we found that weight loss, elevated erythrocyte sedimentation rate (ESR) and higher angiopoietin-2/-1 ratios but lower matrix metalloproteinase (MMP)-3 levels identify concomitant GCA in PMR patients. In addition, we confirmed that elevated platelet counts are characteristic of GCA but not of GCA mimicry controls and that low MMP-3 and proteinase 3 (PR3) levels may help to discriminate GCA from infections.ConclusionThis study, performed in two independent international cohorts, consistently shows the potential of angiopoietin-2/-1 ratios and MMP-3 levels to identify GCA in patients presenting with PMR. These biomarkers may be used to select which PMR patients require further diagnostic workup. Platelet counts may be used to discriminate GCA from GCA look-alike patients.

Dependence of thymic stromal lymphopoietin serum concentration from bronchial asthma control level and lung function results in patients of different age groups

Introduction. Bronchial asthma (BA) pathogenesis is settled by bronchial wall inflammation, which is the main treatment target.Aim. To study the dependence of thymic stromal lymphopoietin (TSLP) concentration in serum and nasal brush-biopsies from age, spirometry data deterioration and blood eosinophils in patients with uncontrolled BA.Materials and methods. Patients with uncontrolled BA of three age groups: children (6–11 y.o., n = 38), adolescents (14–17 y.o., n = 35) and adults (25–50 y.o., n = 31) were included in 1-year long open prospective study. Clinical history, АСТ/сАСТ questionnaires, lung function test (LFT), common blood count, serum and nasal material to evaluate TSLP were obtained during first visit, if there were no any signs of acute respiratory infection for not less than 14 days. Maintenance therapy was revised based on firstvisit findings. Patient were consequently examined twice with 6 months intervals, examination data, LFT readings, ACT results and eosinophil counts were collected. Statistical analyses included ANOVA (Kruskal-Wallis test) and Pearson’s correlation (r). Differences accepted significant with р &lt; 0,05.Results. Serum TSLP levels did not differ between age groups. TSLP concentration correlate directly and significantly with duration of uncontrolled BA in previous 12 months (r = 0.74). In patients with atopic BA, maximum TSLP level was in dust mites sensitized group (792.6 ± 114.1 pg/ml). We have found greater serum TSLP concentration in patients who demonstrated FEV1 below normal even on optimal controller therapy at Visit 3. Eosinophil count randomly changed inside normal values and did not correlate with asthma control or TSLP level.Conclusion. Prognosis of future asthma exacerbations and LFT decrease is less favourable in patients with high serum TSLP level.

Modified Lipoproteins Induce Arterial Wall Inflammation During Atherogenesis.

Circulating apolipoprotein B-containing lipoproteins, notably the low-density lipoproteins, enter the inner layer of the arterial wall, the intima, where a fraction of them is retained and modified by proteases, lipases, and oxidizing agents and enzymes. The modified lipoproteins and various modification products, such as fatty acids, ceramides, lysophospholipids, and oxidized lipids induce inflammatory reactions in the macrophages and the covering endothelial cells, initiating an increased leukocyte diapedesis. Lipolysis of the lipoproteins also induces the formation of cholesterol crystals with strong proinflammatory properties. Modified and aggregated lipoproteins, cholesterol crystals, and lipoproteins isolated from human atherosclerotic lesions, all can activate macrophages and thereby induce the secretion of proinflammatory cytokines, chemokines, and enzymes. The extent of lipoprotein retention, modification, and aggregation have been shown to depend largely on differences in the composition of the circulating lipoprotein particles. These properties can be modified by pharmacological means, and thereby provide opportunities for clinical interventions regarding the prevention and treatment of atherosclerotic vascular diseases.

Genetics and Emerging Therapies for Brain Arteriovenous Malformations

Brain arteriovenous malformations (AVMs) are characterized by a high-pressure, low-resistance vascular nidus created by direct shunting of blood from feeding arteries into arterialized veins, bypassing intervening capillaries. AVMs pose a risk of spontaneous rupture because the vessel walls are continuously exposed to increased shear stress and abnormal flow phenomena, which lead to vessel wall inflammation and distinct morphologic changes. The annual rupture rate is estimated at 2%, and once an AVM ruptures, the risk of rerupture increases 5-fold. The ability of AVMs to grow, regress, recur, and undergo remodeling shows their dynamic nature. Identifying the underlying cellular and molecular pathways of AVMs not only helps us understand their natural physiology but also allows us to directly block vital pathways, thus preventing AVM development and progression. Management of AVMs is challenging and often necessitates a multidisciplinary approach, including neurosurgical, endovascular, and radiosurgical expertise. Because many of these procedures are invasive, carry a risk of inciting hemorrhage, or are controversial, the demand for pharmacologic treatment options is increasing. In this review, we introduce novel findings of cellular and molecular AVM physiology and highlight key signaling mediators that are potential targets for AVM treatment. Furthermore, we give an overview of syndromes associated with hereditary and nonhereditary AVM formation and discuss causative genetic alterations.

Surgıcal Management of Crohn Dısease ın Chıldren: A Revıew Artıcle

Crohn’s disease (CD) is an inflammatory bowel disease with chronic transmural inflammation of the intestinal wall. It can be observed from oral cavity to anus and it typically involves the ileum, ileocecumor portions of the entire colon. With an increasing rate of CD in children, surgery still has a role in the management of this entity in children when medical treatment is unsuccessful. In this review article it is aimed to review the surgical treatment of CD under the light of relevant literature. During the management of children with CD, risks and benefits of surgical options should be carefully assessed and an appropriate surgical intervention should be performed promptly in order to avoid future complications and to gain future growth of the child with an acceptable quality of life.

Inflammatory diseases of the pharynx in children

Introduction. Inflammatory diseases of the lymphoid ring of the pharynx in children are widespread and account for more than 30% in the structure of ENT pathology. Lymphoid tissue, especially the palatine tonsils, largely determines the formation of local and general protective reactions of the child’s body.The aim of this work is to assess the efficacy and safety of using topical bacterial lysate in chronic tonsillitis of streptococcal and herpes viral etiology in frequently ill children.Materials and methods. The study was conducted on a sample of 31 children aged 7–17 who were treated in the pediatric department of the Saint Petersburg Research Institute of Ear, Throat, Nose and Speech inpatiently or outpatiently, which were divided into 2 groups. Group 1 consisted of 15 children with decompensated chronic tonsillitis of streptococcal etiology, who were prescribed tonsillectomy according to indications. Group 2 consisted of 16 children with chronic compensated tonsillitis, who, after an acute respiratory infection, showed signs of acute pharyngitis in the form of pain and discomfort in the throat, perspiration, low-grade body temperature. In both groups children were prescribed to take topical baclerial lysates.Results. A subjective pain relief of sore throat in patients (groups 1 and 2) was observed from day 2–3 of administration of the topical bacterial lysate. The clinical therapeutic effect resulted in decreased intensity of inflammation of the posterior pharyngeal wall, reduction in size and tenderness of regional lymph nodes from day 4–5 of administration of the drug. The clinical recovery from acute pharyngitis in children of both groups was observed in 98% of cases at visit 3.Conclusion. The persistence of pathogenic viruses and bacteria contributes to the development of secondary immunodeficiency states and participates in the formation of a kind of “vicious circle” In these causes prescription of topical baclerial lysates may be an effective conservation therapy as well as antibiotics and antiviral drugs. The drug showed its efficacy in the treatment of acute and chronic diseases of the pharynx in children of both viral and bacterial etiology.

Comparison of Sonographic and Pathological Findings of Patients with Appendicitis in Shahid Sadoughi Hospital in the Center of Iran

Introduction: Acute appendicitis is one of the most prevalent differential diagnosis for acute abdomen. Ultrasound is a noninvasive diagnostic procedure that does not expose the patient to ionizing radiation.We intended to compare ultrasound findings as a diagnostic tool with pathology findings in patients with appendicitis who had undergone appendectomy in this study. Methods and Materials: A total of 150 patients with abdominal pain were studied in this research. Following confirmation of the diagnosis, these patients underwent surgery. SPSS Version 26 software was used to record and evaluate all demographic information, kind of underlying disease (if any), and duration of symptoms, clinical findings, pre-operation sonography findings and type of treatment and surgery. Results: The study included 150 patients, with 53.3 percent of them being female and the rest being male. Pathologically positive patients made up 78 percent of the cases analyzed. The highest sonographic finding was 6mm Appendix in terms of sonographic data (37.3 percent). The retrocecal type of the appendix was the most frequent anatomical form, accounting for 63.3 percent of all appendixes. Pathology results and sonography observations of peri-appendiceal fluid collection and peri-appendiceal fat inflammation differ significantly. The pathology findings and the ultrasonography observation of 6mm &gt; Appendix were not significantly different. Conclusion: Inflammation of the appendix wall without necrosis and an increase in the size of the appendix (&gt;6 mm) are the key ultrasound findings in support of a diagnosis of uncomplicated appendicitis. Keywords: Ultrasonography, Appendicitis, diagnostic imaging, Surgery, pathology

Carbon monoxide releasing molecule-2 attenuates angiotensin II-induced IL-6/Jak2/Stat3-associated inflammation by inhibiting NADPH oxidase- and mitochondria-derived ROS in human aortic smooth muscle cells

Abdominal aortic aneurysm (AAA) is a common inflammatory vascular disease. Angiotensin II (Ang II) involves in AAA progression by promoting the proliferation and migration of vascular smooth muscle cells, the degradation of extracellular matrices, and the generation of ROS to lead to vascular inflammation. Carbon monoxide releasing molecule-2 (CORM-2) is known to exert anti-inflammatory and antioxidant activities. However, it remains unclear whether CORM-2 can suppress Ang II-induced vascular inflammation to prevent AAA progression. Therefore, this study aimed to investigate the vasoprotective effects of CORM-2 against Ang II-induced inflammatory responses of human aortic smooth muscle cells (HASMCs) and the underlying mechanisms of those effects. The results showed that Ang II induced inflammatory responses of HASMCs via NADPH oxidase- and mitochondria-derived ROS/NF-κB/IL-6/Jak2/Stat3 pathway which was attenuated by the pretreatment with CORM-2. Additionally, CORM-2 further exhibited anti-inflammatory activities in Ang II-stimulated HASMCs, as indicated by the reduction of monocyte adhesion to HASMCs and migration of HASMCs via the suppression of ICAM-1 and VCAM-1 as well as MMP-2 and MMP-9 levels, respectively. Moreover, Ang II-induced COX-2-mediated PGE2 secretion was also inhibited by the pretreatment with CORM-2. Importantly, our data demonstrated that CORM-2 reversed Ang II-induced IL-6 overexpression dependent on Nrf2 activation and HO-1 expression. Taken together, the present study indicates that CORM-2-induced Nrf2/HO-1 alleviates IL-6/Jak2/Stat3-mediated inflammatory responses to Ang II by inhibiting NADPH oxidase- and mitochondria-derived ROS, suggesting that CORM-2 is a promising pharmacologic candidate to reverse the pathological changes involved in the inflammation of vessel wall for the prevention and treatment of AAA.

Subcutaneous calcifications in legs with chronic venous diseases

BackgroundCalcifications in the subcutaneous layer (SCL) have been described by radiographic studies of legs with advanced chronic venous disease (CVD). However, SCL calcifications have rarely been included among the CVD-related changes. The aim of the present study was to evaluate the prevalence and morphology of SCL calcifications in legs with CVD of all grades of severity determined by ultrasound. MethodsA total of 500 legs in 250 patients (148 women and 102 men; mean age, 51 years; range, 18-87 years) referred to our vascular clinic for symptoms and signs of CVD were included. After duplex ultrasound evaluation of the deep, superficial, and perforating veins, the skin and SCL were investigated using duplex ultrasound. Those patients with other possible causes of SCL calcification were excluded. ResultsUsing the C component of the CEAP (clinical, etiologic, anatomic, pathophysiologic) classification, 43 legs were classified as C1, 189 as C2, 34 as C3, 16 as C4A, 45 as C4B or C, 18 as C5, and 16 as C6. Varicose veins were reported in 273 legs, and lipodermatosclerosis in 79 legs. Subcutaneous calcifications were demonstrated in 35 of 361 legs with CVD in two different locations: the wall of superficial varicose veins and in subcutaneous tissue unrelated to the path of the superficial veins. Superficial veins calcifications were found in 12 of 273 legs with varicose veins (4.4%) and were found in older patients with severe varicose vein disease (grade 3 using the venous clinical severity score and disease duration >30 years). Subcutaneous tissue calcifications (STCs) were found in 24 of 95 legs with a more advanced CVD stage (C4A-C6). No STCs were found in legs with a C1, C2, or C3 class. ConclusionsSuperficial veins calcifications were found only in the legs with severe and long-lasting varicose veins and seemed to be related to chronic severe inflammation of the venous wall. STCs were independent of the vein wall and were found only in the damaged areas of legs with severe CVD (C4-C6). STCs are possibly related to chronic inflammation of the subcutaneous tissue. Their avulsion from the ulcer bed has been recommended to facilitate ulcer healing and prevent recurrence.

Role of vitamin D and its receptor in regulation of mechanisms of immune inflammation in patients with ischemic heart disease

Coronary heart disease still underlies high morbidity and mortality in people of working age. Thus, today one of the most important tasks facing clinical cardiology is the search for new molecular genetic predictors of coronary artery disease associated with the unfavorable course of this disease and the development of complications. In the present review, we analyzed the available data on the mechanisms of vitamin D interrelation with the development of immune inflammation in patients with coronary heart disease. The role of vitamin D and its receptor in cardiovascular diseases and in the development of coronary heart disease, in particular, is considered.Recent studies showed that vitamin D deficiency is a new risk factor for the development of atherosclerosis and immune inflammation. Immune damage of the vascular wall increases the risk of acute coronary syndrome, especially in patients with a predisposition to atherothrombosis. Vitamin D has a multilevel effect on immune inflammation mechanisms by restoring the balance in the system of pro- and anti-inflammatory cytokines. The protective effects of vitamin D on immune inflammation in the vascular wall are realized through vitamin D receptors. The present work re-viewed the studies describing possible mechanisms of immune inflammation regulation by vitamin D and its receptor and activation of immune inflammation in patients with vitamin D deficiency. Further studies of mechanisms of influence of vitamin D receptor on the suppression of immune inflammation are needed.

Adoptive transfer of metabolically reprogrammed macrophages for atherosclerosis treatment in diabetic ApoE−/- mice

Atherosclerosis is characterized by inflammation in the arterial wall, which is known to be exacerbated by diabetes. Therapeutic repression of inflammation is a promising strategy for treating atherosclerosis. In this study, we showed that diabetes aggravated atherosclerosis in apolipoproteinE knockout (ApoE−/-) mice, in which increased expression of long-chain acyl-CoA synthetase 1 (Acsl1) in macrophages played an important role. Knockdown of Acsl1 in macrophages (MφshAcsl1) reprogrammed macrophages to an anti-inflammatory phenotype, especially under hyperglycemic conditions. Injection of MφshAcsl1 reprogrammed macrophages into streptozotocin (STZ)-induced diabetic ApoE−/- mice (ApoE−/-+ STZ) alleviated inflammation locally in the plaque, liver and spleen. Consistent with the reduction in inflammation, plaques became smaller and more stable after the adoptive transfer of reprogrammed macrophages. Taken together, our findings indicate that increased Acsl1 expression in macrophages play a key role in aggravated atherosclerosis of diabetic mice, possibly by promoting inflammation. Adoptive transfer of Acsl1 silenced macrophages may serve as a potential therapeutic strategy for atherosclerosis.

The Clinical Significance of Small Vessel Vasculitis on Temporal Artery Biopsies.

Giant cell arteritis (GCA) is the most common type of systemic vasculitis in the elderly. Untreated, it can lead to irreversible blindness. Its diagnosis relies on a temporal artery biopsy (TAB). However, a proportion of patients have small vessel vasculitis (SVV) on biopsy; the prognosis of which remains unclear. The aim of this study is to compare the clinical presentation and long-term outcomes of those with SVV with negative and positive biopsies to determine whether long-term corticosteroid therapy can be avoided in these patients. Post hoc analysis of patients with suspected GCA who underwent TAB and fluorodeoxyglucose positron emission tomography/computed tomography (PET/CT) scan as part of a prospective GCA and PET cohort. Patients were divided in to 3 groups based on TAB result: positive (inflammation in the main artery wall), negative (no inflammation), and SVV (isolated vasa vasorum or periadventitial SVV). Clinical, serological, and PET/CT data of patients with SVV were compared with those with positive and those with negative biopsies. For the 58 eligible patients recruited between May 2016 and December 2017, 11 had SVV, 12 had positive, and 35 had negative biopsies. Patients with SVV had similar clinical, serological, and PET/CT findings to those with negative biopsies. Compared with those with positive biopsies, patients with SVV had lower erythrocyte sedimentation rate (25 vs 78 mm/hour; P = 0.02), platelet count (296 vs 385 ×109/L; P = 0.03), and a lower median total vascular score on PET/CT scan (1.0 vs 13.5; P = 0.01). Median prednisone dose was lower (4.8 vs 11.7 mg; P = 0.015) and fewer were on steroid-sparing agents (20% vs 67%; P = 0.043) at 6 months. The percentage of patients with a clinical diagnosis of GCA was similar between those with SVV (3/11, 27.3%) and those with negative biopsies (5/35, 14.3%; P = 0.374). Patients with SVV on TAB had similar clinical features, PET/CT findings, and 6-month outcomes to those with negative biopsies. Small vessel vasculitis can be treated as equivalent to a negative biopsy when being considered for diagnosis and treatment of GCA.