Characterization Of Inflammatory Response Research Articles

Acute invasive fungal rhinosinusitis (AIFRS) - A histopathological analysis of expanding spectrum of fungal infections in backdrop of COVID-19 pandemic.

Acute invasive fungal rhinosinusitis (AIFRS) is an aggressive infection affecting immunocompromised patients and carries a high morbidity and mortality. It is commonly seen in immunocompromised patients, mainly in uncontrolled diabetes, malignancy, acquired immunodeficiency syndrome, and so on. However, there has been an exponential increase in the incidence of AIFRS in relation to recent coronavirus disease 2019 (COVID-19) infection. We present this study to assess histomorphological features of fungal infections in the background of COVID-19 era. The study includes interpretation of 34 biopsies of suspected AIFRS in post COVID-19 patients. The demographic details like patients age, sex, diabetic status, COVID-19 status, and history of steroid intake were collected. All specimens were stained with hematoxylin and eosin and PAS stain. Detailed microscopic examination including the presence of fungal hyphae in the tissue, characterization of inflammatory response, presence of tissue invasion, angioinvasion, and necrosis was noted for each case. Thirty-four biopsy specimens from various sites - nasal cavity, maxillary sinus, ethmoid sinus, and so on - were studied. The mean age of the patients with AIFRS was 52.68 years. The dominant fungi were Mucorales in 31 (91.3%), Aspergillus and Mucorales in 1 (2.9%), a combination of Mucorales and Candida identified in 1 (2.9%) case, and Candida alone in 1 case (2.9%). Bony invasion and perineural invasion were observed in 5 cases (14.7%) and 1 (2.9%) case, respectively. Histopathological examination plays an essential role in the diagnosis and appropriate management of the patients. Histopathological features including characterization of fungi, angioinvasion, and bone invasion may provide information on rare dreaded infections in post-COVID-19 patients for possible prognostic characteristics on histology.

Potential of [11C](R)-PK11195 PET Imaging for Evaluating Tumor Inflammation: A Murine Mammary Tumor Model.

Breast tumor inflammation is an immunological process that occurs mainly by mediation of Tumor-Associated Macrophages (TAM). Aiming for a specific measurement of tumor inflammation, the current study evaluated the potential of Positron Emission Tomography (PET) imaging with [11C](R)-PK11195 to evaluate tumor inflammation in a mammary tumor animal model. Female Balb/C mice were inoculated with 4T1 cells. The PET imaging with [11C](R)-PK11195 and [18F]FDG was acquired 3 days, 1 week, and 2 weeks after cell inoculation. The [11C](R)-PK11195 tumor uptake increased from 3 days to 1 week, and decreased at 2 weeks after cell inoculation, as opposed to the [18F]FDG uptake, which showed a slight decrease in uptake at 1 week and increased uptake at 2 weeks. In the control group, no significant differences occurred in tracer uptake over time. Tumor uptake of both radiopharmaceuticals is more expressed in tumor edge regions, with greater intensity at 2 weeks, as demonstrated by [11C](R)-PK11195 autoradiography and immunofluorescence with TSPO antibodies and CD86 pro-inflammatory phenotype. The [11C](R)-PK11195 was able to identify heterogeneous tumor inflammation in a murine model of breast cancer and the uptake varied according to tumor size. Together with the glycolytic marker [18F]FDG, molecular imaging with [11C](R)-PK11195 may provide a better characterization of inflammatory responses in cancer.

Monitoring of inflammation using novel biosensor mouse model reveals tissue- and sex-specific responses to Western diet.

ABSTRACTObesity is an epidemic, and it is characterized by a state of low-grade systemic inflammation. A key component of inflammation is the activation of inflammasomes, multiprotein complexes that form in response to danger signals and that lead to activation of caspase-1. Previous studies have found that a Westernized diet induces activation of inflammasomes and production of inflammatory cytokines. Gut microbiota metabolites, including the short-chain fatty acid butyrate, have received increased attention as underlying some obesogenic features, but the mechanisms of action by which butyrate influences inflammation in obesity remain unclear. We engineered a caspase-1 reporter mouse model to measure spatiotemporal dynamics of inflammation in obese mice. Concurrent with increased capsase-1 activation in vivo, we detected stronger biosensor signal in white adipose and heart tissues of obese mice ex vivo and observed that a short-term butyrate treatment affected some, but not all, of the inflammatory responses induced by Western diet. Through characterization of inflammatory responses and computational analyses, we identified tissue- and sex-specific caspase-1 activation patterns and inflammatory phenotypes in obese mice, offering new mechanistic insights underlying the dynamics of inflammation.

Characterization of inflammatory response in hepatorenal syndrome: Relationship with kidney outcome and survival.

BackgroundSeveral lines of evidence indicate that decompensated cirrhosis is characterized by the presence of systemic inflammation. Hepatorenal syndrome (HRS‐AKI) is a unique type of renal failure that occurs at late stages of cirrhosis. However, confirmation of the presence and significance of such inflammatory response in HRS‐AKI is lacking.Aim and MethodsTo characterize the systemic inflammatory response, as estimated by measuring a large number of cytokines, in 161 patients hospitalized for an acute decompensation of cirrhosis: 44 patients without acute kidney injury (AKI), 63 patients with hypovolaemia‐induced AKI and 58 patients with HRS‐AKI.ResultsHRS‐AKI was characterized by an altered cytokine profile compared to the other two groups, particularly IL‐6, IL‐8, TNF‐α, VCAM‐1, fractalkine and MIP‐1α. The inflammatory response was not related to presence of bacterial infection, concomitant acute‐on‐chronic liver failure or severity of renal dysfunction. Patients who responded to terlipressin and albumin had only a decrease in TNF‐α and RANTES after treatment without changes in other cytokines. Interestingly, patients with persistent HRS‐AKI had higher levels of IP‐10 and VCAM‐1 compared to those with resolution of HRS‐AKI. VCAM‐1 was also an independent predictor of 3‐month mortality. A systems biology analysis approach showed that the inflammatory status of HRS‐AKI was similar to that of chronic nonhepatic inflammatory conditions, such as lupus erythematosus or inflammatory bowel disease.ConclusionHepatorenal syndrome is characterized by a marked systemic inflammatory state, reminiscent of that of nonhepatic inflammatory diseases, that correlates with patient outcomes.

Characterization of inflammatory responses by cervical cytology, cytokine expression and ultrastructure changes in a goat subclinical endometritis model.

Endometritis is a common puerperal disease in livestock. Thus, a practical clinical test for the establishment of diagnosis is needed. We developed a goat model for subclinical endometritis diagnosis by examining cytological, ultrastructural features and molecular expression in cervical discharge collected by cervical cytobrush method. A suspension of E. coli was infused into the uterine horn of goats, and cervical discharge, peripheral blood and endomertrial biopsy samples were collected before inoculation and at 3, 6, 12, 24, 72, 120 and 168 hr post-inoculation (pi). In experimental goats, total leukocytes increased at 6–12 hr pi in hematological examinations, abundant neutrophils were observed in cervical discharge smears, and some micro-villi shortened or were lost from the epithelium at 3 hr pi, with some inflammatory cells infiltrated into the uterine glands and lamina propria. The mRNA expression levels of the Toll-like receptor 4 (TLR4), cytokines and β-defensin-2 increased significantly within 12 hr pi and returned to pre-inoculation levels at 7 day pi. The results showed that subclinical endometritis was simulated in this bacterial infusion goat model, and the evaluation of cervical cytology was in good agreement with molecular changes of cytokines in cervical discharge, hematology and histology. We thus conclude that the simple cervical cytobrush technique can effectively obtain cervical discharge samples for cytology examination in the early diagnosis of subclinical endometritis in goats.

Characterization of Inflammatory Response in Acute-on-Chronic Liver Failure and Relationship with Prognosis.

ACLF is characterized by a systemic inflammatory response, but the cytokines involved in this process have not been well studied. The aim of this study was to characterize the systemic inflammatory response in patients with cirrhosis and ACLF and its relationship with prognosis. Fifty-five patients with cirrhosis, 26 with ACLF, were studied prospectively. Systemic inflammatory response was analyzed by measuring a large array of plasma cytokines by using a multiplex kit. A principal component analysis show noticeable differences between ACLF and decompensated cirrhosis without ACLF. Patients with ACLF had significant abnormal levels of 12 cytokines compared to those without ACLF, including: VCAM-1, VEGF-A, Fractalkine, MIP-1α, Eotaxin, IP-10, RANTES, GM-CSF, IL-1β, IL-2, ICAM-1, and MCP-1. Cytokines showing the most marked relationship with ACLF were VCAM-1 and VEGF-A (AUCROC 0.77; p = 0.001). There was a significant relationship between some of inflammatory mediators and 3-month mortality, particularly VCAM-1, ICAM-1, and GM-CSF (AUCROC>0.7; p < 0.05). Functional Enrichment Analysis showed that inflammatory markers differentially expressed in ACLF patients were enriched in leukocyte migration, particularly monocytes and macrophages, and chemotaxis pathways. In conclusion, ACLF is characterized by a marked inflammatory reaction with activation of mediators of adhesion and migration of leukocytes. The intensity of the inflammatory reaction correlates with prognosis.

Non-invasive induction of focal cerebral ischemia in mice by photothrombosis of cortical microvessels: characterization of inflammatory responses

In this study, we adapted the original rat photothrombosis model of Watson et al. (Ann Neurol 17 (1985) 497) for use in mice by refining the application route of the dye, illumination and stereotactic parameters. After intraperitoneal injection of the photosensitive dye Rose bengal, subsequent focal illumination of the brain with a cold light source through the intact skull led to focal cortical infarcts of reproducible size, location and geometry. Cresyl violet histology displayed well-demarcated infarcts that matured with time in a predictable manner. Microglial responses, as assessed by immunocytochemistry, against F4/80 and CD11b antigens were rapid and complete at the infarct site, but delayed and incomplete in degenerating fiber tracts and ipsilateral thalamic nuclei. In contrast to the rat, where the expression of CD4 and CD8 antigens discriminate distinct subpopulations of lesion-associated phagocytes, the expression of both markers was low to absent in the mouse model. In both rats and mice, cerebral photothrombosis shares essential inflammatory responses with focal ischemia induced by middle cerebral artery occlusion. It may provide a useful model to study functional aspects of lesion-associated and remote molecular responses in transgenic mice.