Rubiadin exerts an acute and chronic anti-inflammatory effect in rodents

Rubiadin is identified as a bioactive anthraquinone that exists in some quinone rich plants. The current research was carried out to evaluate the potential anti-inflammatory impact of Rubiadin in acute and chronic inflammation test models in rodents. The anti-inflammatory activity of Rubiadin was examined in cotton pellet-induced granuloma and carrageenan-induced edema as chronic and acute inflammation models in rats. TNF-α level and histopathological changes were assessed using sampled foot tissue of rat in the acute model. Also, the IL-1β level was assessed in the chronic model. One-way ANOVA (post hoc Tukey’s) analysis was used for comparing the groups. Rubiadin (0.5 mg/kg, i.p.) induced a significant reduction in TNF α level and the paw edema compared to the control group in carrageenan test. Also, it was observed that the anti-inflammatory activity of Rubiadin (0.5 mg/kg, i.p.) is comparable to mefenamic acid (30 mg/kg, i.p.) as the standard drug. Rubiadin was effective in granuloma induced by cotton pellet concerning the granuloma and transudate formation amount. Rubiadin’s anti-inflammatory effects were associated with a significant IL-1β decrease in this model. The results suggest that Rubiadin as a natural compound can possess significant peripheral anti-inflammatory impacts.

CD127 imprints functional heterogeneity to diversify monocyte responses in inflammatory diseases

Inflammatory monocytes are key mediators of acute and chronic inflammation; yet, their functional diversity remains obscure. Single-cell transcriptome analyses of human inflammatory monocytes from COVID-19 and rheumatoid arthritis patients revealed a subset of cells positive for CD127, an IL-7 receptor subunit, and such positivity rendered otherwise inert monocytes responsive to IL-7. Active IL-7 signaling engaged epigenetically coupled, STAT5-coordinated transcriptional programs to restrain inflammatory gene expression, resulting in inverse correlation between CD127 expression and inflammatory phenotypes in a seemingly homogeneous monocyte population. In COVID-19 and rheumatoid arthritis, CD127 marked a subset of monocytes/macrophages that retained hypoinflammatory phenotypes within the highly inflammatory tissue environments. Furthermore, generation of an integrated expression atlas revealed unified features of human inflammatory monocytes across different diseases and different tissues, exemplified by those of the CD127high subset. Overall, we phenotypically and molecularly characterized CD127-imprinted functional heterogeneity of human inflammatory monocytes with direct relevance for inflammatory diseases.

Netrin-1: A Modulator of Acute and Chronic Inflammation

Netrins belong to the family of laminin-like secreted proteins, which guide axonal migration and neuronal growth in the developing central nervous system. Over the last 20 years, it has been established that netrin-1 acts as a chemoattractive or chemorepulsive cue in diverse biological processes far beyond neuronal development. Netrin-1 has been shown to play a central role in cell adhesion, cell migration, proliferation, and cell survival in neuronal and non-neuronal tissue. In this context, netrin-1 was found to orchestrate organogenesis, angiogenesis, tumorigenesis, and inflammation. In inflammation, as in neuronal development, netrin-1 plays a dichotomous role directing the migration of leukocytes, especially monocytes in the inflamed tissue. Monocyte-derived macrophages have long been known for a similar dual role in inflammation. In response to pathogen-induced acute injury, monocytes are rapidly recruited to damaged tissue as the first line of immune defense to phagocyte pathogens, present antigens to initiate the adaptive immune response, and promote wound healing in the resolution phase. On the other hand, dysregulated macrophages with impaired phagocytosis and egress capacity accumulate in chronic inflammation sites and foster the maintenance—and even the progression—of chronic inflammation. In this review article, we will highlight the dichotomous roles of netrin-1 and its impact on acute and chronic inflammation.

Pathophysiology of H. pylori

Helicobacter species were known for long as a causative agent of gastritis. H. pylori associated gastritis is characterized by the presence of acute and chronic inflammation. Previously, it was believed that in H. pylori gastritis, fundic inflammation was less important than that of the antral mucosa. However, H. pylori and gastroesophageal reflux disease create, or arise concurrently, may also be caused by the anatomical role of the inflammatory cell infiltrate. The source of H. pylori is mostly unknown. H. pylori has a small host range and is present in people and some non-human primates nearly exclusively. In rare cases, the presence of pets may be a concern for H. pylori infection; hence, pets should be isolated. There is also no definitive proof for zoonotic H. pylori transmission. The direct transmission from person to person, either oral or fecal-oral route or both, is expected to lead to new infections. H. pylori colonization is not an infection itself, but it impacts the relative likelihood that multiple pathological conditions of the upper gastrointestinal tract and even the hepatobiliary tract will grow. Therefore, H. pylori examination alone is not relevant but can be done in order to ascertain the cause of a basic disorder, such as peptic ulcer disease or to avoid disease, for example in subjects with family gastric carcinoma. A positive test result will validate the procedure, and a negative test result can suggest that other etiological causes or prevention steps needs to be examined. Gastritis is divided into acute and chronic. Several virulence factors play a role in the disease such as cag PAI (Pathogenicity Island) and VacA vacuolating cytotoxin. Different adhesins and their receptors aid in H. pylori colonization and invasion. Based on analogy with other mucosal infections, it was initially assumed that a protective immune response against H. pylori would predominantly be mediated by antibodies. Subsequent experiments have indicated that the relevance of the humoral system for protective immunity is only marginal. Antibodies can effectively prevent infection and reduce colonization in animal models.

Antinociceptive and anti-inflammatory effects of hydrazone derivatives and their possible mechanism of action in mice

Pain and inflammation are unpleasant experiences that usually occur as a result of tissue damage. Despite the number of existing analgesic drugs, side effects limit their use, stimulating the search for new therapeutic agents. In this sense, five hydrazone derivatives (H1, H2, H3, H4, and H5), with general structure R1R2C = NNR3R4, were synthesized with molecular modification strategies. In this paper, we describe the ability of hydrazone derivatives to attenuate nociceptive behavior and the inflammatory response in mice. Antinociceptive activity was evaluated through acetic acid-induced writhing and formalin-induced nociception tests. In both experimental models, the hydrazone with the greatest potency (H5) significantly (p < 0.05) reduced nociceptive behavior. Additionally, methods of acute and chronic inflammation induced by different chemicals (carrageenan and histamine) were performed to evaluate the anti-inflammatory effect of H5. Moreover, molecular docking analysis revealed that H5 can block the COX-2 enzyme, reducing arachidonic acid metabolism and consequently decreasing the production of prostaglandins, which are important inflammatory mediators. H5 also changes locomotor activity. In summary, H5 exhibited relevant antinociceptive and anti-inflammatory potential and acted on several targets, making it a candidate for a new multi-target oral anti-inflammatory drug.

Extensive extraintestinal manifestations of ulcerative colitis in a patient initially suspected to have disseminated malignancy

A 44-year-old patient with known ulcerative colitis presented with abdominal pain and an abdominal mass. CT revealed cecal stranding, a mass at the left colonic flexure involving the pancreas and multiple lesions in the lungs, retroperitoneum and liver. The patient had also developed a scalp rash as well as impaired hearing. Biopsies from the abdominal mass and lungs revealed necrotic inflammation, and the clinical suspicion of malignancy could not be ruled out. After further examination, the patient was treated with high-dose steroids, which rapidly reduced the extraintestinal manifestations. Due to a persistent abscess formation at the left colonic flexure and pancreas, the patient was referred to our hospital for a total colectomy. Histology showed acute and chronic inflammation with cryptitis, indicating ulcerative colitis. Our case is a rare presentation of extensive extraintestinal disease in organs such as the lungs and liver, as well as necrotic mass formation at the colon site which mimicked malignancy.

A case of osseous metaplasia in a gastric hyperplastic polyp: An unexpected finding in a common polyp

Introduction/Objective Foveolar hyperplastic polyp is a common gastric polyp characterized by foveolar hyperplasia with erosion, acute and chronic inflammation, granulation tissue formation, and smooth muscle strands extending from the muscularis mucosae. Although foveolar hyperplastic polyps may rarely contain foci of dysplasia or invasive carcinoma, osseous metaplasia/heterotopic bone formation in foveolar hyperplastic polyps of the stomach is extremely rare with a few case reports. Methods/Case Report A 63-year-old female with a history of hypertension, sick sinus syndrome, and Hashimoto’s thyroiditis was referred to our facility for evaluation of a mass in segment eight of the liver. The liver biopsy showed a moderately differentiated adenocarcinoma, most consistent with intrahepatic cholangiocarcinoma. A screening gastrointestinal endoscopy revealed a 7-mm sessile polyp in the antrum. The polyp was removed with a cold snare. No other abnormalities were identified in the stomach. Sections of the polyp showed fragments of antral-type gastric mucosa with foveolar hyperplasia, erosion, acute and chronic inflammation, and focal granulation tissue formation. In addition, multiple foci of woven bone formation without bone marrow surrounding dilated gastric foveolae were identified. No Helicobacter infection, intestinal metaplasia, dysplasia or malignancy was identified histologically. Osseous metaplasia/heterotopic bone formation is a well-known finding reported in various neoplastic and non- neoplastic conditions. However, osseous metaplasia in foveolar hyperplastic polyps of the stomach is extremely rare. There have been only four previous case reports published in English language. Our current case shows clinicopathologic features similar to those of the previous case reports including the findings of small-sized polyp found incidentally in middle-aged patients with no clinical history of hypercalcemia or any other abnormalities causing heterotopic bone formation. Results (if a Case Study enter NA) N/A Conclusion Although the pathogenesis of osseous metaplasia in a gastric hyperplastic polyp remains unknown, the finding of osseous metaplasia in a gastric hyperplastic polyp is very intriguing.

Prevalence of Anti HBC Antibodies in Blood Donors from Different Centers in Lebanon

Background: Hepatitis B virus (HBV) is a major cause of the liver disease that could lead to acute and chronic inflammation of the liver. In this study we collected anti HBC antibodies (anti hepatitis B core) results done as screening of blood donors from three hospital centers in Lebanon between Jan.2016to Jan.2019. The aim of this study is to collect epidemiological data on the prevalence of positive anti HBC antibodies in blood donors of different nationalities. Method: Blood donation records from the three hospitals were collected from Jan. 2016 till Jan. 2019 and they included 16000 volunteers for blood donation and all these donors were tested for anti HBC antibodies. Results: The total number of donors was 16000, 1224 volunteers (7.65%) had positive anti HBC test. The prevalence of anti HBC antibodies was higher in Syrian population with a prevalence of 12.9% as compared to the Lebanese donors with prevalence of 6.6%. Age was found to have a statistically significant relationship with the prevalence of hepatitis B. blood group was found not to have a statistically significant relationship with hepatitis B.

Serum Amyloid A Is Present in Human Saccular Intracranial Aneurysm Walls and Associates With Aneurysm Rupture

Saccular intracranial aneurysm (sIA) rupture leads to a disabling subarachnoid hemorrhage. Chronic inflammation and lipid accumulation in the sIA wall contribute to wall degenerative remodeling that precedes its rupture. A better understanding of the pathobiological process is essential for improved future treatment of patients carrying sIAs. Serum amyloid A (SAA) is an acute-phase protein produced in response to acute and chronic inflammation and tissue damage. Here, we studied the presence and the potential role of SAA in 36 intraoperatively resected sIAs (16 unruptured and 20 ruptured), that had previously been studied by histology and immunohistochemistry. SAA was present in all sIAs, but the extent of immunopositivity varied greatly. SAA immunopositivity correlated with wall degeneration (p = 0.028) and rupture (p = 0.004), with numbers of CD163-positive and CD68-positive macrophages and CD3-positive T lymphocytes (all p &lt; 0.001), and with the expression of myeloperoxidase, matrix metalloproteinase-9, prostaglandin E-2 receptor, and cyclo-oxygenase 2 in the sIA wall. Moreover, SAA positivity correlated with the accumulation of apolipoproteins A-1 and B-100. In conclusion, SAA occurs in the sIA wall and, as an inflammation-related factor, may contribute to the development of a rupture-prone sIA.