Doxorubicin Induced Apoptosis Enhances Monocyte Infiltration and Adverse Cardiac Remodeling in Diabetic Animals

Diabetic cancer patients treated with Doxorubicin (DOX), a potent chemotherapeutic drug induces cardiac toxicity. However, molecular mechanisms of cardiac toxicity in this specific disease progression in patients and animal models are completely unknown. Therefore, we designed a study to understand the effects of doxorubicin induced cardiac toxicity in diabetic animals and involved pathophysiological mechanisms. C57BL/6J mice were divided into DOX and diabetic (STZ) treated four groups; control, STZ, DOX and DOX+STZ. At Day 14, animals were sacrificed, echocardiography was used to examine heart function, heart and blood samples were collected to investigate apoptotic mechanisms (Caspase 3, BAX, Bcl2), inflammation and cardiac remodeling. Our data shows a significant (p<0.05) increase in glucose levels, apoptotic markers, monocyte infiltration at the site of apoptosis and triggered inflammatory immune response (TNF-α and IL-6), in DOX+STZ animals compared to control and experimental groups. We also observed significant (p<0.05) increase in myofibrillar area, fibrosis and significantly decreased (p<0.05) cardiac function in DOX-treated diabetic animals compared with controls. In conclusion, our data suggest that DOX-induces significantly increased apoptosis, fibrosis and structural alterations in diabetic hearts compared to non-diabetic animals.

Anemia and The Level of IL-6 in Children Infected with Entamoeba histolytica and Giardia lamblia

The relation between anemia and inflammatory immune response has lately had much attention. This research was conducted from October 2018 until April 2019, including (110) children below 12 years from both gender in some Hospitals, Primary Health care centers, Public Primary Schools and Kindergarten in Baghdad, Iraq. The objective of this study is to determine the possible correlation between iron deficiency anemia and inflammatory immune response among children infected with Entamoeba histolytica or Giardia lamblia. Blood samples were taken from all groups to measure hemoglobin level, serum iron, total iron binding capacity (TIBC), mean corpuscular volume (MCV), and mean corpuscular hemoglobin concentration (MCHC), while the inflammatory related immune response was evaluated by measuring IL-6 and ferritin. Student T-Test was used to compare between means. The results showed that both hemoglobin and iron concentrations were significantly (P) ˂ 0.01 lower in infected children compared with control, as well as both IL-6 and ferritin levels were significant where (P) ˂0.05 amplified among infected children compared to control. Microcytic hypochromic anemia was observed in the majority of infected children, while normocytic normochromic RBCs was recorded in the majority of control children.

A Vicious Circle of Clonal Haematopoiesis of Indeterminate Potential and Cardiovascular Disease

Clonal haematopoiesis of indeterminate potential (CHIP) represents a recently identified overlap between cancer and cardiovascular disease (CVD). CHIP develops as a result of certain acquired somatic mutations that predispose to leukaemia, but clinically even more prevalent, associate with increased risk for CVD and CVD-related death. Experimental studies suggest a causal role for CHIP aggravating inflammatory processes in CVD, and recent epidemiologic and genetic studies indicate that classical CVD risk factors may increase the risk of acquiring CHIP driver mutations, thus fuelling a vicious circle. The potential mechanism underlying the associative link between CHIP and CVD and mortality has been the focus of a few recent excellent experimental and observational studies which are summarized and discussed in this concise non-systematic review article. These data support a pathomechanistic view of a spiralling vicious circle in which CHIP aggravates the inflammatory immune response in CVD, and CVD-driven elevated haematopoietic activity promotes CHIP development.

Influence of infectious factors on changes in hormonal indicators in women in the early period of miscarriage

The work studied the influence of infectious factors on changes in immunological and hormonal parameters in women who have a full pregnancy without infections of the genitourinary system and women with an infection of the genitourinary system and have miscarriages in the early stages of up to 12 weeks of pregnancy. It was concluded that in women in early pregnancy, the presence of infections of the genitourinary system, with insufficient corrective effect of protease inhibitors and TGF-?1. The formation of a pronounced pro-inflammatory immune response is possible, which can contribute to an imbalance of sex hormones. It manifests itself in a slight decrease in prolactin, FSH, LH, but at the same time a pronounced and reliable decrease in the value of progesterone and an increase in the level of estradiol. Thus, all this can contribute to the unfavorable course of early pregnancy and the development of miscarriages.

A Pro-Inflammatory Gut Microbiome Characterizes SARS-CoV-2 Infected Patients and a Reduction in the Connectivity of an Anti-Inflammatory Bacterial Network Associates With Severe COVID-19

The gut microbiota contributes to maintaining human health and regulating immune responses. Severe COVID-19 illness is associated with a dysregulated pro-inflammatory immune response. The effect of SARS-CoV-2 on altering the gut microbiome and the relevance of the gut microbiome on COVID-19 severity needs to be clarified. In this prospective study, we analyzed the gut microbiome of 212 patients of a tertiary care hospital (117 patients infected with SARS-CoV-2 and 95 SARS-CoV-2 negative patients) using 16S rRNA gene sequencing of the V3-V4 region. Inflammatory markers and immune cells were quantified from blood. The gut microbiome in SARS-CoV-2 infected patients was characterized by a lower bacterial richness and distinct differences in the gut microbiome composition, including an enrichment of the phyla Proteobacteria and Bacteroidetes and a decrease of Actinobacteria compared to SARS-CoV-2 negative patients. The relative abundance of several genera including Bifidobacterium, Streptococcus and Collinsella was lower in SARS-CoV-2 positive patients while the abundance of Bacteroides and Enterobacteriaceae was increased. Higher pro-inflammatory blood markers and a lower CD8+ T cell number characterized patients with severe COVID-19 illness. The gut microbiome of patients with severe/critical COVID-19 exhibited a lower abundance of butyrate-producing genera Faecalibacterium and Roseburia and a reduction in the connectivity of a distinct network of anti-inflammatory genera that was observed in patients with mild COVID-19 illness and in SARS-CoV-2 negative patients. Dysbiosis of the gut microbiome associated with a pro-inflammatory signature may contribute to the hyperinflammatory immune response characterizing severe COVID-19 illness.

Infections due to dysregulated immunity: an emerging complication of cancer immunotherapy

Immune checkpoint inhibitors (ICIs) have revolutionised cancer treatment. However, immune-related adverse events (irAEs) are a common side effect which can mimic infection. Additionally, treatment of irAEs with corticosteroids and other immunosuppressant agents can lead to opportunistic infection, which we have classed as immunotherapy infections due to immunosuppression. However, emerging reports demonstrate that some infections can be precipitated by ICIs in the absence of immunosuppressive treatment, in contrast to the majority of reported cases. These infections are characterised by a dysregulated inflammatory immune response, and so we propose they are described as immunotherapy infections due to dysregulated immunity. This review summarises the rapidly emerging evidence of these phenomena and proposes a new framework for considering infection in the context of cancer immunotherapy.

Subacute thyroiditis as evidence of SARS-CoV2 related autoimmune disorders and case descriptions

Context: Subacute thyroiditis has been classified as an auto inflammatory condition and occurs mainly due to a viral infection. According to the pathogenesis of SARS-CoV2 infection, which is mainly based on the uncontrolled inflammatory immune response, several studies have investigated the possible association between SARS-CoV2 and subacute thyroiditis. In this regard, we aimed to review and organize these studies. Evidence Acquisition: First, we observed and provided evidence on the possible roles and mechanisms of SARS-CoV2 in inflammatory and autoimmune diseases, and then we discussed the findings on the association between subacute thyroiditis and SARS-CoV2 infection. Results: Regarding other autoimmune and inflammatory disorders, together with previous experience on the role of viruses in the pathogenesis of subacute thyroiditis, as well as studies on the inflammatory mechanism of SARS-CoV2 infection, support this hypothesis that SARS-CoV2 may initiate subacute thyroiditis. Conclusions: Evidence so far suggests that subacute thyroiditis should be considered as a later symptom of covid-19.

Characterisation of the blood RNA host response underpinning severity in COVID-19 patients

Infection with SARS-CoV-2 has highly variable clinical manifestations, ranging from asymptomatic infection through to life-threatening disease. Host whole blood transcriptomics can offer unique insights into the biological processes underpinning infection and disease, as well as severity. We performed whole blood RNA Sequencing of individuals with varying degrees of COVID-19 severity. We used differential expression analysis and pathway enrichment analysis to explore how the blood transcriptome differs between individuals with mild, moderate, and severe COVID-19, performing pairwise comparisons between groups. Increasing COVID-19 severity was characterised by an abundance of inflammatory immune response genes and pathways, including many related to neutrophils and macrophages, in addition to an upregulation of immunoglobulin genes. Our insights into COVID-19 severity reveal the role of immune dysregulation in the progression to severe disease and highlight the need for further research exploring the interplay between SARS-CoV-2 and the inflammatory immune response.

Krueppel-Like Factor 4 Expression in Phagocytes Regulates Early Inflammatory Response and Disease Severity in Pneumococcal Pneumonia

The transcription factor Krueppel-like factor (KLF) 4 fosters the pro-inflammatory immune response in macrophages and polymorphonuclear neutrophils (PMNs) when stimulated with Streptococcus pneumoniae, the main causative pathogen of community-acquired pneumonia (CAP). Here, we investigated the impact of KLF4 expression in myeloid cells such as macrophages and PMNs on inflammatory response and disease severity in a pneumococcal pneumonia mouse model and in patients admitted to hospital with CAP. We found that mice with a myeloid-specific knockout of KLF4 mount an insufficient early immune response with reduced levels of pro-inflammatory cytokines and increased levels of the anti-inflammatory cytokine interleukin (IL) 10 in bronchoalveolar lavage fluid and plasma and an impaired bacterial clearance from the lungs 24 hours after infection with S. pneumoniae. This results in higher rates of bacteremia, increased lung tissue damage, more severe symptoms of infection and reduced survival. Higher KLF4 gene expression levels in the peripheral blood of patients with CAP at hospital admission correlate with a favourable clinical presentation (lower sequential organ failure assessment (SOFA) score), lower serum levels of IL-10 at admission, shorter hospital stay and lower mortality or requirement of intensive care unit treatment within 28 days after admission. Thus, KLF4 in myeloid cells such as macrophages and PMNs is an important regulator of the early pro-inflammatory immune response and, therefore, a potentially interesting target for therapeutic interventions in pneumococcal pneumonia.

Research Progress of Metabolomics in Asthma

Asthma is a highly heterogeneous disease, but the pathogenesis of asthma is still unclear. It is well known that the airway inflammatory immune response is the pathological basis of asthma. Metabolomics is a systems biology method to analyze the difference of low molecular weight metabolites (<1.5 kDa) and explore the relationship between metabolic small molecules and pathophysiological changes of the organisms. The functional interdependence between immune response and metabolic regulation is one of the cores of the body’s steady-state regulation, and its dysfunction will lead to a series of metabolic disorders. The signal transduction effect of specific metabolites may affect the occurrence of the airway inflammatory immune response, which may be closely related to the pathogenesis of asthma. Emerging metabolomic analysis may provide insights into the pathogenesis and diagnosis of asthma. The review aims to analyze the changes of metabolites in blood/serum/plasma, urine, lung tissue, and exhaled breath condensate (EBC) samples, and further reveals the potential pathogenesis of asthma according to the disordered metabolic pathways.