Elevated Serum Midkine Levels in Severe Acute Respiratory Syndrome Coronavirus 2 (SARS-CoV-2) Infected Patients

The coronavirus disease-2019 (COVID-19) pandemic has caused important health, economic, social, and cultural problems worldwide. Recent findings demonstrate an excessive cytokine release during the disease development, especially in the seriously life-threatening form of COVID-19. Among other chemokines and cytokines that are released in high amounts at the infection site of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), midkine (MK), which is an important pro-inflammatory growth factor/ cytokine, can be also overexpressed and contribute to the pathophysiological process in patients infected with SARS-CoV-2. Serum was collected from 87 intensive care unit (ICU) patients that are COVID-19 positive and 50 healthy volunteers in the control group with a negative PCR test and without disease symptoms. Circulating MK concentration was measured by enzyme-linked immunosorbent assay (ELISA) using a commercial human MK kit. COVID-19 patients had a significantly higher serum MK concentration compared to non-COVID-19 control subjects (1892.8 ± 1615.8 pg/ml versus 680.7 ± 907.6 pg/ml, respectively; P < 0.001). The cut-off MK concentration was 716.7 pg/ml, with the sensitivity and specificity of 75.9 % and 76.0 %, respectively. The area under the receiver operating characteristic (ROC) curve (AUCROC) of MK was = .827. Our findings showed that circulating MK levels are significantly increased in SARS-CoV-2 infected patients. We suggest that MK is involved in the pathogenesis of COVID-19 and may be a part of hypercytokinaemia. Therefore, MK may serve as a supporting inflammatory marker in the diagnosis of COVID-19 and by blocking MK actions or its targets may attenuate the inflammatory process and the severity of the disease.

Chemical Components and Biological Effects of Genus Origanum

The plants from genus Origanum are common folk Chinese herbs used to treat a variety of diseases. They are also used as a spice, a seasoning, and an ornament. Origanum plants are rich in essential oils and also have other compounds including terpenoids, flavonoids, organic acids, and sterols. They have a variety of biological activities such as antispasmodic, anti-inflammatory, growth-promoting, antibacterial, antioxidant, and anticancer properties. The chemical components and biological effects of genus Origanum were summarized by different scientific databases such as Web of Science, SciFinder, Baidu Scholar, PubMed, ScienceDirect, and SpringerLink. In conclusion, recent studies were mainly focused on the activities of their essential oils. The research studies for nonvolatile constituents and their pharmacological activities are few. Therefore, research on compounds in genus Origanum plants can be strengthened and their application prospect can be explored so as to make better use of the resources of these plants.

Ulcerative colitis immune cell landscapes and differentially expressed gene signatures determine novel regulators and predict clinical response to biologic therapy

The heterogeneous pathobiology underlying Ulcerative Colitis (UC) is not fully understood. Using publicly available transcriptomes from adult UC patients, we identified the immune cell landscape, molecular pathways, and differentially expressed genes (DEGs) across patient cohorts and their association with treatment outcomes. The global immune cell landscape of UC tissue included increased neutrophils, T CD4 memory activated cells, active dendritic cells (DC), and M0 macrophages, as well as reduced trends in T CD8, Tregs, B memory, resting DC, and M2 macrophages. Pathway analysis of DEGs across UC cohorts demonstrated activated bacterial, inflammatory, growth, and cellular signaling. We identified a specific transcriptional signature of one hundred DEGs (UC100) that distinctly separated UC inflamed from uninflamed transcriptomes. Several UC100 DEGs, with unidentified roles in UC, were validated in primary tissue. Additionally, non-responders to anti-TNFα and anti-α4β7 therapy displayed distinct profiles of immune cells and pathways pertaining to inflammation, growth, and metabolism. We identified twenty resistant DEGs in UC non-responders to both therapies of which four had significant predictive power to treatment outcome. We demonstrated the global immune landscape and pathways in UC tissue, highlighting a unique UC signature across cohorts and a UC resistant signature with predictive performance to biologic therapy outcome.

The Role of Bone Morphogenetic Protein 7 (BMP-7) in Inflammation in Heart Diseases

Bone morphogenetic protein-7 is (BMP-7) is a potent anti-inflammatory growth factor belonging to the Transforming Growth Factor Beta (TGF-β) superfamily. It plays an important role in various biological processes, including embryogenesis, hematopoiesis, neurogenesis and skeletal morphogenesis. BMP-7 stimulates the target cells by binding to specific membrane-bound receptor BMPR 2 and transduces signals through mothers against decapentaplegic (Smads) and mitogen activated protein kinase (MAPK) pathways. To date, rhBMP-7 has been used clinically to induce the differentiation of mesenchymal stem cells bordering the bone fracture site into chondrocytes, osteoclasts, the formation of new bone via calcium deposition and to stimulate the repair of bone fracture. However, its use in cardiovascular diseases, such as atherosclerosis, myocardial infarction, and diabetic cardiomyopathy is currently being explored. More importantly, these cardiovascular diseases are associated with inflammation and infiltrated monocytes where BMP-7 has been demonstrated to be a key player in the differentiation of pro-inflammatory monocytes, or M1 macrophages, into anti-inflammatory M2 macrophages, which reduces developed cardiac dysfunction. Therefore, this review focuses on the molecular mechanisms of BMP-7 treatment in cardiovascular disease and its role as an anti-fibrotic, anti-apoptotic and anti-inflammatory growth factor, which emphasizes its potential therapeutic significance in heart diseases.

Antiinflammatory effect of androgen receptor activation in human benign prostatic hyperplasia cells

Progression of benign prostatic hyperplasia (BPH) involves chronic inflammation and immune dysregulation. Preclinical studies have demonstrated that prostate inflammation and tissue remodeling are exacerbated by hypogonadism and prevented by testosterone supplementation. We now investigated whether, in humans, hypogonadism was associated with more severe BPH inflammation and the in vitro effect of the selective androgen receptor agonist dihydrotestosterone (DHT) on cultures of stromal cells derived from BPH patients (hBPH). Histological analysis of inflammatory infiltrates in prostatectomy specimens from a cohort of BPH patients and correlation with serum testosterone level was performed. Even after adjusting for confounding factors, hypogonadism was associated with a fivefold increased risk of intraprostatic inflammation, which was also more severe than that observed in eugonadal BPH patients. Triggering hBPH cells by inflammatory stimuli (tumor necrosis factor α, lipopolysaccharide, or CD4+T cells) induced abundant secretion of inflammatory/growth factors (interleukin 6 (IL6), IL8, and basic fibroblast growth factor (bFGF)). Co-culture of CD4+T cells with hBPH cells induced secretion of Th1 inducer (IL12), Th1-recruiting chemokine (interferon γ inducible protein 10, IP10), and Th2 (IL9)- and Th17 (IL17)-specific cytokines. Pretreatment with DHT inhibited NF-κB activation and suppressed secretion of several inflammatory/growth factors, with the most pronounced effects on IL8, IL6, and bFGF. Reduced inflammatory cytokine production by testosterone cells, an increase in IL10, and a significant reduction of testosterone cells proliferation suggested that DHT exerted a broad antiinflammatory effect on testosterone cells. In conclusion, our data demonstrate that DHT exerts an immune regulatory role on human prostatic stromal cells, inhibiting their potential to actively induce and/or sustain autoimmune and inflammatory responses.

The ABCs of Rhinophyma Management

Background Rhinophyma is a benign inflammatory growth of the nose. It usually involves the caudal one-third of the nose in men. It not only affects the patient's appearance, but also can have profound functional implications. Many difficult treatment methods have been advocated, often with acceptable success. Because there appears to be no distinct advantages in the different therapeutic modalities, no one modality is universally endorsed. Methods We performed a retrospective review of patients from 1990–2001 who underwent treatment of their rhinophyma at Louisiana State University, Health Science Center and Overton Brooks Veteran's Hospital in Shreveport, LA. The tumescent anesthesia, Weck blade excision and argon beam coagulator technique (TWA) was used on 51 patients. Results Patients undergoing this technique have operating times no greater than ten minutes. The average blood loss was less than 5cc. No surgical complications were noted. Conclusion The TWA technique yields good cosmetic results and is cost-effective.