Thermography signs of lung inflammation

The purpose of the study was to find out if infrared thermography of the thorax is the method to select the patients with lung inflammationMaterial, methods: Thermograms were accumulated and processed in the «TVision» cloud storage («Dignosis», Russia). Special regions of interest (ROI) were automatically created: 1. on the front and back of the thorax roughly in the projection of the upper lobe (ULP) and the lower lobe (LLP) of the lung; 2.e lines on the front surface of the thorax. Two types of temperature gradients were calculated: between ULP and LLP (by subtraction mean temperature in LLP from mean temperature in ULP) (ΔT1); between both ULP and both LLP on the back of the thorax (ΔT2). Approximation confidence value for the polynomial trend line (R²) along the marked lines on the front surface of the thorax also calculated. Totally 489 thermograms, were analyzed, included 337 from healthy patients (group 1) and 152 from patients with confirmed diagnosis of lung inflammation (group 2)Results: R² value was higher in the group 1 compare to group 2 (0.58 ± 0.16 vs 0.3 ± 0.2, p < 0.05). ΔT1 value was negative only in patients from group 2, as well as ΔT1 value greater than 0.4 °C.Conclusion: three independent thermographic criteria suitable for detecting lung inflammation were found, so infrared thermography is the valuable method for screening this pathology.

Vernal keratoconjunctivitis activity induces decrease of ocular surface CD14, TLR-4 and TLR-9 expression

Purpose: CD14 is involved in the modulation of immune reaction via toll-like receptors (TLR) and may influence the development of allergic diseases. The role of CD14 in vernal keratoconjunctivitis (VKC) has not yet been investigated. The aim of this study is to evaluate changes of tear soluble sCD14 and conjunctival CD14, TLR-4 and 9 expression in patients with VKC in the active and quiescent phases. Methods: Eighteen patients with VKC during active inflammation (group A, N = 9), in the quiescent phase (group Q, N = 5) and after recovery (group R, N = 4) and 10 healthy subjects were included. Expression of sCD14 in tears and of CD14, TLR-4, and TLR-9 by conjunctival epithelium were evaluated by Western Blot in all groups. Results: Expression of tear sCD14 and of conjunctival CD14, TLR-4, and TLR-9 was significantly decreased in group A when compared with healthy subjects and with VKC group Q and R. Lower expression of sCD14, CD14, TLR-4, and TLR-9 were significantly correlated with the severity of papillary reaction, while the lower sCD14 was correlated with severity of conjunctival hyperemia. Conclusions: Tear sCD14, and conjunctival CD14, TLR4, and TLR-9 decreased during ocular surface inflammatory reaction in patients with VKC. CD14 and TLRs ocular surface evaluation may represent biomarkers of VKC activity and novel therapeutic target.

Description and Analysis of a Novel Subtype of the Anti-Synthetase Syndrome Characterized by Frequent Attacks of Fever and Systemic Inflammation in a Single-Center Cohort Study

ObjectivesThe aim of this study was to investigate anti-synthetase syndrome (ASyS) patients who presented with recurrent episodes of fever and systemic inflammation.MethodsA retrospective cohort of Chinese ASyS patients (n=126) in our center (between January 2013 and January 2020) was included. Patients presenting with concomitant autoimmune rheumatic diseases or malignancies were subsequently excluded. The number of non-infectious fever attacks and attack frequency were recorded and calculated. Patients with two or more attacks and within the upper three quartiles of attack frequency were defined as high-inflammation group. Univariate and multivariate analyses were carried out to characterize the high-inflammation subtype.ResultsOut of 113 eligible patients with an average of 5 years follow up, 25 patients were defined as the high-inflammation group (16 for anti-Jo1, 9 for anti-PL7), with an average of 1.12 attack/patient-year. Compared to low-inflammation group (0–1 attack only and a frequency lower than 0.5 attack/patient-year), the high-inflammation group had higher occurrence of fever and rapid progressive interstitial lung disease (RPILD) as the first presentation (84% vs. 21% and 40% vs. 9%, respectively, both p&lt;0.01). Anti-PL-7 was related to the more inflammatory phenotype (p=0.014). Cumulative disease-modifying agent exposures (&gt;=3) were much higher in the high-inflammation group (60% vs. 26%), while biological agents, i.e., rituximab and tocilizumab, showed better “drug survival” for Jo-1+ and PL-7+ ASyS patients with high inflammation, respectively, in our cohort.ConclusionsASyS with recurrent systemic inflammatory episodes reflects a subtype of more aggressive and refractory disease in the spectrum of ASyS. Increased awareness of this subtype might lead to more appropriate management.

Effect of Integrin-Linked Kinase on Osteogenesis of Bone Marrow Mesenchymal Stem Cells in Inflammatory Environment via Regulating Mitogen Activated Protein Kinase/Protein Kinase B Signaling Pathway

Osteoarthritis (OA) pathogenesis involves inflammation, age, weight and other factors. Integrin-linked kinase (ILK) regulates cell apoptosis, metastasis, and growth. However, whether ILK affects bone formation of bone marrow mesenchymal stem cells in an inflammatory environment has not been elucidated. Rat BMSCs were isolated and assigned into control group, inflammation group (lipopolysaccharide was added to cells); and si-ILK group (ILK siRNA was transfected into the inflammation group BMSCs) followed by analysis of cell proliferation by MTT assay, expression of ILK, Runx2 and OP by real time PCR, ALp activity, TNF-α and IL-6 secretion by ELISA and MAPK/AKT signaling protein expression by western blot. Compared to control, ILK in BMSCs cells in inflammatory environment was significantly upregulated, resulting in inhibition of cell proliferation, decreased ALP activity, reduced expression of osteogenic genes Runx2 and OP, increased secretion of TNF-α and IL-6, and downregulated p-AKT (P < 0.05); transfection of ILK siRNA down-regulated ILK in inflammatory environment BMSCs, which significantly increased BMSCs cell proliferation, increased ALP activity and expression of Runx2 and OP, decreased TNF-α and IL-6 secretion and increased p-AKT expression (P < 0.05). ILK expression is increased in BMSCs in an inflammatory environment. Down-regulation of ILK in BMSCs cells in an inflammatory environment can regulate MAPK/AKT signaling, inhibit inflammatory factors secretion, thereby promoting BMSCs proliferation and osteogenesis differentiation.

AST and HBeAg Level Can Help to Distinguish Non-Minimal Liver Inflammation in Persistently Normal Alanine Aminotransferase of Chronic HBV Infection

Objectives: The current study aimed to investigate the characteristics of HBV serum markers (HBsAg, HBeAg), biochemical indicators, HBV DNA, and the age to distinguish minimal from non-minimal liver histological inflammation group in HBeAg-positive chronic HBV-infected patients with ALT≤ 1ULN (40U/L). Methods: The HBeAg-positive patients with treatment-naïve hospitalized at Ditan hospital from January 2008 to January 2017 are investigated. Patients were separated into two groups of minimal and non-minimal (mild and moderate) histological inflammation group by liver biopsy specimens. Data were analyzed using the SPSS package. Results: There were both positive (age, ALT, and AST) and negative correlation factors (serum HBsAg, HBeAg, or HBV DNA quantitation) to the liver inflammation grades. Multivariate regression analysis indicated that HBeAg (P < 0.001, b = -0.554, Exp (B) = 0.575) and AST (P = 0.003, b = 0.074, Exp (B) = 1.077) were independent influential factors. The cutoff values of HBeAg and AST were separately 2.85 Log10S/CO (AUC0.724, Sensitivity64%, Specificity79%), 28U/L (AUC0.726, Sensitivity68%, Specificity 78%) to distinguish Minimal from Non-minimal liver histological inflammation in chronic HBV-infected patients with ALT ≤ 1 ULN (40U/L). Conclusions: In total, 31.34% (115/367) of patients with chronic HBV infection who had non-minimal (mild and moderate) liver histological inflammation reached the required inflammation levels for antiviral treatment in HBeAg-positive patients with persistently normal ALT. HBeAg (cutoff < 2.85 Log10S/CO) and AST (cutoff > 28 U/L) were the independent influential factors of predicting non-minimal liver inflammation with ALT ≤ 1 ULN (40U/L).

Evaluation of the Anti-Inflammatory Activities of Diclofenac Sodium, Prednisolone and Atorvastatin in Combination with Ascorbic Acid

Objectives: Inflammation is our body’s normal defense mechanism, but in some cases, it may be responsible for causing different kinds of disorders. Several antiinflammatory drugs are present for the treatment of these disorders; however, the conventional anti-inflammatory drugs cause side effects when used in the long term and therefore, it is better to use them in a low dose for a shorter duration of time. This study was designed to find out whether there is an augmentation of the therapeutic effectiveness of the antiinflammatory drugs like diclofenac sodium (NSAID), prednisolone (steroid) and atorvastatin (statin) when used in combination with ascorbic acid (antioxidant). Methods: Wistar Rats (n=144) were selected and divided into 24 groups of 6 rats in each. Carrageenan and formalin were used to induce local inflammation and neuropsychiatric effects, respectively. The inhibitions of such responses were measured after administering a drug alone and in combination with ascorbic acid. Results: In case of carrageenan mediated inflammation, the combination of 5 mg/kg diclofenac and 200 mg/kg ascorbic acid gave the highest inhibition of 74.19% compared to other groups of drugs. The combination of 5 mg/kg diclofenac and 200 mg/kg ascorbic acid gave 97.25% inhibition for formalin-mediated inflammation group. In both cases, combination therapy showed statistically significant anti-inflammatory activities compared to monotherapy (p values <0.05). Conclusion: All the data clearly indicate new combinations of drug therapy comprising diclofenac sodium, prednisolone, atorvastatin with ascorbic acid, which may be more effective against both local edema and the neuropsychiatric effect caused due to inflammation.

Comparative Analysis of C-Reactive Protein Levels in the Saliva and Serum of Dogs with Various Diseases

We performed this study to characterize the difference between the inflammatory and non-inflammatory status in diseased dogs by measuring salivary C-reactive protein (CRP) levels. In addition, we assessed whether a correlation exists between CRP levels in saliva and those in serum. CRP levels were measured in 32 client-owned dogs, which were then divided into inflammation and non-inflammation groups based on the serum CRP level. The salivary CRP level was higher in the inflammation group than in the non-inflammation group (p < 0.05). Furthermore, there was a positive correlation between the salivary and serum CRP levels (R = 0.866, p < 0.001). These data suggest that canine salivary CRP measurements can effectively and non-invasively detect an inflammatory state in dogs.

miR-184 Inhibits Inflammation Through Targeting Toll-Like Receptor 4 (TLR4)/NLR Family Pyrin Domain Containing 3 (NLRP3) Signaling Pathway in Neonatal Purulent Meningitis

Neonatal purulent meningitis (NPM) leads to higher mortality and neurological sequelae rates. miR184 involves in inflammation and tumor, but the role of miR-184 in NPM remains unclear. NPM patients and non-intracranial infected neonates were collected and miR-184 expression in cerebrospinal fluid was assessed by real-time PCR. The Neuro-2a cell line was cultured and divided into control group, inflammation group (treated with LPS), and miR-184 inhibitor group, which was transfected with miR-184 inhibitor on the basis of inflammation followed by analysis of miR-184 and TLR4 expression by Real time PCR, Caspase 3 activity, cell proliferation by MTT assay, secretion of IL-1β and IL-6 by ELISA, NLRP3 expression by real time PCR and western blot, and Caspase-1 p20 and NF- B level by western blot. miR-184 expression level was significantly increased in cerebrospinal fluid of NPM group (P < 0 05) and also elevated in inflammation group along with significantly inhibited cell proliferation was inhibited, increased Caspase 3 activity, IL-1β and IL-6 secretion, and decreased TLR4, NLRP3, Caspase-1 p20 and NFκ- B expression (P < 0 05). miR-184 inhibitor significantly down-regulated miR-184 expression in the inflammation group, promoted cell proliferation, decreased Caspase 3 activity, IL-1β and IL-6 secretion, and increased TLR4, NLRP3, Caspase1 p20 and NF- κB expression (P < 0 05). miR-184 expression is increased in neonatal purulent meningitis and it can inhibit inflammation by targeting TLR4/NLRP3 signaling pathway, leading to amelioration of the progression of neonatal purulent meningitis.

Tumor inflammatory signature as a biomarker of response to immunotherapy in lung cancer.

47 Background: Tumor Inflammation signatures (TIS) comprising multiple immune genes have been shown to enrich for response to ICI. To study this immune phenotype in a large cohort of clinically evaluated patients, we studied gene expression data for a stable pan-cancer tumor inflammation profile and clinical response to ICI. Methods: 1323 FFPE tumors from 35 histologies were tested by RNA-seq, PD-L1 IHC and DNA-seq for TMB. Unsupervised analysis of the RNA-seq data revealed a cluster of 160 genes which separated inflamed from non-inflamed tumor microenvironments (TME). A TIS, algorithmically defined as the mean mRNA expression of the 160 genes was developed with each tumor assigned into a weak, moderate or strong inflammation group. PD-L1 IHC was performed using DAKO 22C3 antibody and considered positive if TPS ≥1%. TMB > 10 mut/Mb was considered high. The TIS, PD-L1 and TMB were independently applied to 110 NSCLC cases for association with ORR to ICIs by RECIST criterion. Results: Unsupervised clustering identified 3 inflammation clusters in the 1323 samples; inflamed (n = 439; 33.2%), borderline (n = 467; 35.3%) and non-inflamed (n = 417; 31.5%). 160 genes are over-represented by T & B-cell activation, IFNg, chemokine, cytokine and interleukin pathways. The TIS algorithm results in an inflammatory score that leads to 3 distinct groups of strong (n = 384; 29.0%), moderate (n = 354; 26.8%) and weak (n = 585; 44.2%) inflammation. Strongly inflamed tumors are over-represented by PD-L1+ tumors (240/384) whereas weakly inflamed tumors are significantly under-represented by PD-L1+ tumors (369/585; p = 1.02e-14). Strongly inflamed tumors presented with improved ORR to ICI in NSCLC (36.6%; 16/44; p = 0.051). Similar results were observed for overall survival for strongly inflamed tumors (median = 16 months; p = 0.0012) vs. weakly inflamed tumors (median = 8 months). ORR for PD-L1+ 33.96% (p = 0.026) and TMB high 21.43% (p = 0.83) were observed. Conclusions: Concurrent measurement of multiple markers led to a comprehensive, stable TIS that predicts host immune response. A strongly inflamed TIS was associated with higher ORR versus single biomarker PD-L1 and TMB in NSCLC.

Effect of Silent Information Regulator on the Survival and Osteogenic Differentiation of Inflammatory Bone Marrow Mesenchymal Stem Cells by Regulating NF-κB Signaling Pathway

Osteogenic differentiation of BMSCs is beneficial for osteoarthritis (OA) treatment. Silent information regulator (SIRT1) plays a role in endocrine diseases and aging-related diseases. However, the role of SIRT1 in OA has not yet been elucidated. Rat BMSCs were isolated and divided into control group, inflammation group (BMSCs were cultured with IL-6), SIRT1 group (SIRT1 agonist Resveratrol was added under the action of IL-6) followed by analysis of cell proliferation by MTT assay, Caspase 3 activity, ALP activity, expression of osteogenic genes Runx2 and OC and adipogenic differentiation gene PPARγ2 by Real time PCR, NF-κB expression by western blot and secretion of TNF-α and IL-6 by ELISA. In inflammation group, SIRT1 expression was significantly decreased, cell proliferation was significantly inhibited, and Caspase 3 activity was increased. Meanwhile, ALP activity, Runx2 and OC expression was decreased, PPARγ2 and NF-κB expression was increased, along with elevated TNF-α and IL-6 secretion compared to control (P < 0.05). Resveratrol can significantly promote the expression of SIRT1 in BMSCs of inflammation group, promote cell proliferation, decrease Caspase 3 activity, and increase Runx2 and OC expression. In addition, it decreased PPARγ2 and NF-κB expression and reduced the secretion of TNF-α and IL-6 (P < 0.05). The expression of SIRT1 was decreased in BMSCs under inflammation. SIRT1 overexpression in BMSCs under inflammation inhibits inflammation, promotes proliferation and osteogenic differentiation of BMSCs through regulating NF-κB signaling pathway.