Low Inflammatory Activity Research Articles

H4K20me3-Mediated Repression of Inflammatory Genes is a Characteristic and Targetable Vulnerability of Persister Cancer Cells.

Anti-cancer therapies can induce cellular senescence, which is highly stable, or drug-tolerant persistence, which is efficiently reversed upon therapy termination. While approaches to target senescent cells have been extensively studied, further understanding of the processes regulating persistence is needed to develop treatment strategies to suppress persister cell survival. Here, we used mTOR/PI3K inhibition to develop and characterize a model of persistence-associated arrest in human cancer cells of various origins. Persister and senescent cancer cells shared an expanded lysosomal compartment and hypersensitivity to BCL-XL inhibition. However, persister cells lacked other features of senescence, such as loss of lamin B1, senescence-associated β-galactosidase activity, upregulation of MHC-I, and an inflammatory and secretory phenotype (SASP). Genome-wide CRISPR/Cas9 screening for genes required for the survival of persister cells revealed that they are hypersensitive to the inhibition of one-carbon (1C) metabolism, which was validated by the pharmacological inhibition of SHMT, a key enzyme that feeds methyl groups from serine into 1C metabolism. Connecting 1C metabolism with the epigenetic regulation of transcription, the repressive heterochromatic mark H4K20me3 was enriched at the promoters of SASP and interferon response genes in persister cells, while it was absent in proliferative or senescent cells. Moreover, persister cells overexpressed the H4K20 methyltransferases KMT5B/C, and their downregulation unleashed inflammatory programs and compromised the survival of persister cells. In summary, this study defined distinctive features of persister cancer cells, identified actionable vulnerabilities, and provided mechanistic insight into their low inflammatory activity.

MRI Dixon Fat-Corrected Look-Locker T1 Mapping for Quantification of Liver Fibrosis and Inflammation-A Comparison With the Non-Fat-Corrected Shortened Modified Look-Locker Inversion Recovery Technique.

This study evaluates the impact of liver steatosis on the discriminative ability for liver fibrosis and inflammation using a novel Dixon water-only fat-corrected Look-Locker T1 mapping sequence, compared with a standard shortened Modified Look-Locker Inversion Recovery (shMOLLI) sequence, with the aim of overcoming the limitation of steatosis-related confounding in liver T1 mapping. 3 T magnetic resonance imaging of the liver including the 2 T1 mapping sequences and proton density fat fraction (PDFF) was prospectively performed in 24 healthy volunteers and 38 patients with histologically proven liver fibrosis evaluated within 90 days of liver biopsy. Paired Mann-Whitney test compared sequences between participants with and without significant liver steatosis (PDFF cutoff 10%), and unpaired Kruskal-Wallis test compared healthy volunteers to patients with early (F0-2) and advanced (F3-4) liver fibrosis, as well as low (A0-1) and marked (A2-3) inflammatory activity. Univariate and multivariate logistic regression models assessed the impact of liver steatosis on both sequences. Dixon_W T1 was higher than shMOLLI T1 in participants without steatosis (median 896 ms vs 890 ms, P = 0.04), but lower in participants with liver steatosis (median 891 ms vs 973 ms, P < 0.001). Both methods accurately differentiated between volunteers and patients with early and advanced fibrosis (Dixon_W 849 ms, 910 ms, 947 ms, P = 0.011; shMOLLI 836 ms, 918 ms, 978 ms, P < 0.001), and those with mild and marked inflammation (Dixon_W 849 ms, 896 ms, 941 ms, P < 0.01; shMOLLI 836 ms, 885 ms, 978 ms, P < 0.001). Univariate logistic regression showed slightly lower performance of the Dixon_W sequence in differentiating fibrosis (0.69 vs 0.73, P < 0.01), compensated by adding liver PDFF in the multivariate model (0.77 vs 0.75, P < 0.01). Dixon water-only fat-corrected Look-Locker T1 mapping accurately identifies liver fibrosis and inflammation, with less dependency on liver steatosis than the widely adopted shMOLLI T1 mapping technique, which may improve its predictive value for these conditions.

Factors Positively Correlated with Hepatitis B Surface Antigen Seroconversion in Chronic Hepatitis B.

Chronic hepatitis B virus (HBV) infection is a global public health challenge since more than 250 million individuals are affected worldwide. Since different treatment modalities are available and not all patients are candidates for antiviral treatment, biomarkers that potentially predict the possibility of HBsAg clearance and seroconversion may be useful in clinical practice. In this retrospective study, we aimed to identify factors positively correlated with HBsAg seroconversion in a large cohort of 371 chronic hepatitis B patients treated at a German tertial center between 2005 and 2020. Seroconversion occurred in 25/371 (6.7%) and HBsAg loss in 29/371 patients (7.8%) with chronic HBV infection. Antiviral therapy was associated with a lower chance of seroconversion (seroconversion antiviral therapy 14/260 (5.4%) vs. therapy-naïve patients 11/111 (9.9%), p = 0.027). Seroconversion rates were higher in patients with (very) low titers of HBV DNA (best cut-off value 357 IU/mL) and quantitative HBsAg. The best cut-off value with regard to seroconversion was 357 IU/mL for HBV DNA (AUC 0.693 (95%-CI 0.063-0.422), sensitivity 0.714, specificity 0.729; p < 0.0005) and 33,55 IU/mL for HBsAg (AUC 0.794 (95%-CI 0.651-0.937), sensitivity 0.714, specificity 0.949; p < 0.0005). However, male gender was positively associated with seroconversion (seroconversion: males 7.6% vs. females 2.7%, p = 0.036). Treatment-naïve male chronic HBV patients with low viral load and inflammatory activity have the best chance to achieve seroconversion. In the absence of cirrhosis, antiviral therapy should therefore not be performed in this patient collective.

Circulating immune signatures in chronic pancreatitis with and without preceding acute pancreatitis: A pilot study

ObjectiveTo investigate profiles of circulating immune signatures in healthy controls and chronic pancreatitis patients (CP) with and without a preceding history of acute pancreatitis (AP). MethodsWe performed a phase 1, cross-sectional analysis of prospectively collected serum samples from the PROspective Evaluation of Chronic Pancreatitis for EpidEmiologic and Translation StuDies (PROCEED) study. All samples were collected during a clinically quiescent phase. CP subjects were categorized into two subgroups based on preceding episode(s) of AP. Healthy controls were included for comparison. Blinded samples were analyzed using an 80-plex Luminex assay of cytokines, chemokines, and adhesion molecules. Group and pairwise comparisons of analytes were performed between the subgroups. ResultsIn total, 133 patients with CP (111 with AP and 22 without AP) and 50 healthy controls were included. Among the 80 analytes studied, CP patients with a history of AP had significantly higher serum levels of pro-inflammatory cytokines (interleukin (IL)-6, IL-8, IL-1 receptor antagonist, IL-15) and chemokines (Cutaneous T-Cell Attracting Chemokine (CTACK), Monokine induced Gamma Interferon (MIG), Macrophage-derived Chemokine (MDC), Monocyte Chemoattractant Protein-1 (MCP-1)) compared to CP without preceding AP and controls. In contrast, CP patients without AP had immune profiles characterized by low systemic inflammation and downregulation of anti-inflammatory mediators, including IL-10. ConclusionCP patients with a preceding history of AP have signs of systemic inflammatory activity even during a clinically quiescent phase. In contrast, CP patients without a history of AP have low systemic inflammatory activity. These findings suggest the presence of two immunologically diverse subtypes of CP.

Influence of Spider Silk Protein Structure on Mechanical and Biological Properties for Energetic Material Detection.

Spider silk protein, renowned for its excellent mechanical properties, biodegradability, chemical stability, and low immune and inflammatory response activation, consists of a core domain with a repeat sequence and non-repeating sequences at the N-terminal and C-terminal. In this review, we focus on the relationship between the silk structure and its mechanical properties, exploring the potential applications of spider silk materials in the detection of energetic materials.

Assessment of inflammation activity in the small and large bowel using the MaRIAs index for Crohn’s disease

Aim: to evaluate diagnostic value of magnetic resonance enterocolonography (MR-enterocolonography) with the use of the segmental index MaRIAs (Simplified Magnetic Resonance Index of Activity) for inflammation activity in small and large intestine colon compared with ileocolonoscopy.Patients and Methods: the prospective cohort study included 58 patients with Crohn’s disease aged 19–45 years. All patients underwent MR-enterocolonography with intravenous contrast and ileocolonoscopy. MR-enterocolonography assessed inflammatory activity in the large and small intestine (406 segments) using the MaRIAs index (segmental). MRI data were compared with ileocolonoscopy.Results: ileocolonoscopy showed no signs of inflammatory activity in 71 (71/406, 17.5%) segments. In 168 (168/406, 41.3%) segments endoscopic signs of low or moderate inflammatory activity were detected, in 167 (167/406, 41.2%) segments inflammatory activity with the presence of ulcers were detected. MR-enterocolonography did not detect any activity in 121 (121/406, 29.8%) segments (0 points by MaRIAs index), in 285 (285/406, 70.2%) segments, the inflammation activity was revealed by MaRIAs index from 1 to 5 points. There was a moderate agreement (Cohen’s Kappa: 0.57) between the data of MR-enterocolonography and ileocolonoscopy in detection of affected segments. ROC analysis revealed that with the value of the MaRIAs index (segmental) of 1 point or more with sensitivity of 82.0% and specificity of 92.0% (AUC 0.85), it is possible to consider the presence of inflammatory activity of any severity, and with index value of 2 points or more with sensitivity of 75.0% and specificity of 91.0% (AUC 0.91) can diagnose the severe inflammation with ulcers.Conclusion: the results obtained revealed the value of MaRIAs index and the further study to evaluate the effectiveness of conservative treatment of Crohn’s disease is needed.

How Russian patients with rheumatoid arthritis assess their condition: initial data from the OPTIMA (Patient Assessment of Severity, Outcomes and Medical Care in Arthritis) pilot study

Dynamic monitoring of the patient's condition is a fundamental element of the modern strategy for the treatment of rheumatoid arthritis (RA), which aims to achieve remission or low inflammatory activity of the disease. A simple and informative indicator that can be used to assess treatment outcomes from a patient's perspective is the Patient Acceptable State Status (PASS).Objective: to determine the severity of patient-reported outcomes (PROs) and their relationship to the PASS indicator in patients with RA in reallife clinical practice.Material and methods. A one-time survey of 945 patients with RA was conducted in paper and electronic form from January to June 2023. The survey included the determination of PROs (pain, fatigue, anxiety, depression, activities of daily living, global assessment of health – GAH, – global assessment of disease activity – GADA) and PASS. The majority of patients were women – 87.8%, mean age – 46.3±13.2 years, median disease duration – 6 [3; 14] years. 80.4% of patients received synthetic disease modifying antirheumatic drugs, 23.9% – biologic disease modifying antirheumatic drugs (bDMARDs) and Janus kinase inhibitors (JAKi), 36.5% – glucocorticoids (GC), 82.8% – nonsteroidal anti-inflammatory drugs (NSAIDs).Results and discussion. According to the survey, the severity of joint pain (according to a numerical rating scale, NRS 0–10) was on average 5.3±2.6, fatigue – 6.2±2.6, GAH – 5.4±2.4, GADA – 5.4±2.7, median anxiety – 5 [3; 8], depression – 5 [2; 7], limitation of daily activity – 5 [3; 7]. Satisfaction with their health condition (PASS+) reported 54.8% of patients, dissatisfaction (PASS-) was associated with the presence of moderate/severe pain (NRS ≥4; odds ratio, OR 2.665; 95% confidence interval, CI 2.072–3.429; p&lt;0.001), fatigue (OR 2.497; 95% CI 1.818–3.430; p&gt;&lt;0.001), anxiety (OR 1.683; 95% CI 1.395–2.029; p&gt;&lt;0.001) and depression (OR 1.537; 95% CI 1.308–1.805; p&gt;&lt;0.001). PASS- was statistically significant more common in patients taking NSAIDs and GCs and significantly less common in patients receiving bDMARDs and JAKi. Conclusion. PASS is associated with the main PROs (pain, fatigue, anxiety and depression) and can be used as one of the indicators for evaluating the effectiveness of RA treatment. Keywords: rheumatoid arthritis; Patient Acceptable State Status; patient-reported outcomes; pain; fatigue; depression; anxiety&gt; ˂ 0.001), fatigue (OR 2.497; 95% CI 1.818–3.430; p&lt;0.001), anxiety (OR 1.683; 95% CI 1.395–2.029; p&gt;&lt;0.001) and depression (OR 1.537; 95% CI 1.308–1.805; p&gt;&lt;0.001). PASS- was statistically significant more common in patients taking NSAIDs and GCs and significantly less common in patients receiving bDMARDs and JAKi. Conclusion. PASS is associated with the main PROs (pain, fatigue, anxiety and depression) and can be used as one of the indicators for evaluating the effectiveness of RA treatment. Keywords: rheumatoid arthritis; Patient Acceptable State Status; patient-reported outcomes; pain; fatigue; depression; anxiety&gt; ˂ 0.001), anxiety (OR 1.683; 95% CI 1.395–2.029; p&lt;0.001) and depression (OR 1.537; 95% CI 1.308–1.805; p&gt;&lt;0.001). PASS- was statistically significant more common in patients taking NSAIDs and GCs and significantly less common in patients receiving bDMARDs and JAKi. Conclusion. PASS is associated with the main PROs (pain, fatigue, anxiety and depression) and can be used as one of the indicators for evaluating the effectiveness of RA treatment. Keywords: rheumatoid arthritis; Patient Acceptable State Status; patient-reported outcomes; pain; fatigue; depression; anxiety&gt; ˂ 0.001). PASS- was statistically significant more common in patients taking NSAIDs and GCs and significantly less common in patients receiving bDMARDs and JAKi.Conclusion. PASS is associated with the main PROs (pain, fatigue, anxiety and depression) and can be used as one of the indicators for evaluating the effectiveness of RA treatment.

Farnesoid X receptor in chronic liver diseases: an immunohistochemical study

ABSTRACT Chronic hepatitis C virus (HCV) related liver diseases are still an ongoing cause of hepatic failure despite the effective role of direct-acting anti-viral agents. Farnesoid X receptor (FXR) agonists have a potential therapeutic effect on the management of chronic liver diseases (CLD). However, data regarding FXR protein expression in human CLDs are limited and conflicting. We aimed to assess the immunohistochemical expression of FXR in HCV-related chronic hepatitis and cirrhosis in comparison with metabolic-associated fatty liver disease (MAFLD) and normal liver tissue. The expression of FXR was low both in hepatocytes and bile ducts of HCV-related chronic hepatitis and cirrhosis (p = .001, respectively). In addition, a significantly low expression of FXR was observed in HCV-related hepatitis and cirrhosis groups compared to MAFLD in hepatocytes (p < .001, for both) and bile ducts (p = .004 and p = .018). FXR expression in HCV-related cirrhosis was significantly associated with compensated liver function (p = .032) and low inflammatory activity (p = .022). FXR expression decreases in HCV-related CLDs. There was some evidence that FXR expression could protect against post-hepatitis cirrhosis.

Sulawesi propolis induces higher apoptotic activity and lower inflammatory activity in a rat endometriosis model.

Endometriosis has a major impact on women's quality of life. The two primary pathologies are chronic inflammation and altered apoptotic activity. Sulawesi propolis has been shown to have known anti-inflammatory and pro-apoptotic properties in other diseases. To investigate the effects of Sulawesi propolis in the rat endometriosis model. An autologous endometriosis model was created in 60 female Wistar rats by laparotomy. Rats were divided into four groups (n=15 in each group): control group (CG), dienogest group (DG), propolis 50mg/kg body weight (BW)/day (P50) group, and propolis 100mg/kg BW/day (P100) group. Each treatment group was divided into three different treatment durations (n=5 in each treatment group): 2, 4 and 6 weeks. After treatment, laparotomy was performed to determine endometriotic tissue growth, apoptosis [caspase-3 and Bcl-2-associated X/Bcl-2 (Bax/Bcl)] and inflammation [prostaglandin-E2 (PGE2) and interleukin-1B (IL-1B)]. A significant difference was seen in endometriotic tissue growth between the P50 group and the CG, with the greatest reduction in the P50 6-week (P50-6) group, reaching 70.66% of the initial area. Highest Bax/Bcl-2 mRNA expression was shown in the P50-4 and P100-4 groups, highest caspase-3 expression was shown in the P50-2 and P50-4 groups, and lowest IL-1B expression was shown in the P50-4 group; all differed significantly from the CG. No significant difference in PGE2S mRNA was found between the groups. Sulawesi propolis extract suppressed endometriotic tissue growth in the rat model by increasing apoptotic activity. The effects were time-dependent, with 50mg/kg BW as the optimal dose.

Further evaluation of inflammatory and non-inflammatory aspects of pain in rheumatoid arthritis patients.

A high discrepancy between the number of tender and swollen joints (e.g. ΔTSJ ≥ 7) has previously been used as an indication for the presence of changes in central mechanisms in patients with moderate-to-high disease activity. In this study, we explored whether the ΔTSJ can also be used to obtain insights into the underlying pain mechanisms in patients with on average well-controlled disease activity. A 2 year retrospective analysis of routinely obtained 28-joint DAS (DAS28) components was performed on 45 patients with low inflammatory activity at the group level. All patients underwent pressure pain threshold (PPT) and electrical pain threshold (EPT) measurements and completed four self-report questionnaires [short-form 36 (SF-36v2); central sensitization inventory (CSI); generalized pain questionnaire (GPQ); and the pain catastrophizing scale (PCS)]. Patients with a ΔTSJ ≥ 3 at least once in the past 2 years showed significantly lower EPT and PPT values and higher levels of pain and disability on the SF-36v2 compared with the ΔTSJ < 3 group. Furthermore, GPQ scores were significantly higher in those with ΔTSJ ≥ 3, while CSI and PCS scores were similar. These findings suggest that in patients in the ΔTSJ ≥ 3 group, mechanisms other than inflammation (only) underlie the pain. Moreover, our findings suggest that among the multiple potential underlying psychological mechanisms, pain catastrophizing (as measured by the PCS) and psychological hypervigilance (as measured by the CSI) do not play an important role. These findings could be useful in the clinical management of the patient. Depending on the dominant mechanism underlying the (persistent) pain, patients might respond differently to treatment.

Foreign Body Reaction (Immune Response) for Artificial Implants Can Be Avoided: An Example of Polyurethane in Mice for 1 Week.

Despite great success with artificial implants for the human body, modern implants cannot solve major health problems. The reason is an immune reaction of organisms to artificial implants, known as the foreign body reaction. We have found a way to avoid or decrease the foreign body reaction. The surface of an artificial implant is modified with condensed aromatic structures containing free radicals, which provide a covalent attachment of host proteins in a native conformation. The total protein coverage prevents the direct contact of immune cells with the implant surface, and the immune cells are not activated. As a result, the immune response of the organism is not generated, and the artificial implant is not isolated from the tissue; there is no collagen capsule, low activity of macrophages, low cell proliferation, and low inflammatory activity.

Sex-Dependent Altered Expression of Cannabinoid Signaling in Hippocampal Astrocytes of the Triple Transgenic Mouse Model of Alzheimer's Disease: Implications for Controlling Astroglial Activity.

Alzheimer's disease (AD) is a common neurodegenerative disease. In AD-associated neuroinflammation, astrocytes play a key role, finding glial activation both in patients and in animal models. The endocannabinoid system (ECS) is a neurolipid signaling system with anti-inflammatory and neuroprotective properties implicated in AD. Astrocytes respond to external cannabinoid signals and also have their own cannabinoid signaling. Our main objective is to describe the cannabinoid signaling machinery present in hippocampal astrocytes from 3×Tg-AD mice to determine if they are actively involved in the neurodegenerative process. Primary cultures of astrocytes from the hippocampus of 3×Tg-AD and non-Tg offspring were carried out. We analyzed the gene expression of astrogliosis markers, the main components of the ECS and Ca2+ signaling. 3×Tg-AD hippocampal astrocytes show low inflammatory activity (Il1b, Il6, and Gls) and Ca2+ flow (P2rx5 and Mcu), associated with low cannabinoid signaling (Cnr1 and Cnr2). These results were more evident in females. Our study corroborates glial involvement in AD pathology, in which cannabinoid signaling plays an important role. 3×Tg-AD mice born with hippocampal astrocytes with differential gene expression of the ECS associated with an innate attenuation of their activity. In addition, we show that there are sex differences from birth in this AD animal, which should be considered when investigating the pathogenesis of the disease.

Analgesics in rheumatic diseases – a necessary component of therapy aimed at improving the quality of life

Control of chronic pain is one of the main elements of the complex therapy of rheumatic diseases (RD). The use of analgesics is of fundamental importance for the management of patients with osteoarthritis (OA), since a unified system of pathogenetic therapy has not yet been developed for this disease. In immunoinflammatory rheumatic diseases (IRDs), such as rheumatoid arthritis, effective pathogenetic therapy can successfully control inflammatory activity. However, in many cases, in patients with IRDs, unpleasant symptoms (pain, fatigue, poor general well-being, etc.) persist even during remission and low inflammatory activity. This is associated with persistent structural changes, “secondary” OA, central sensitization, and concomitant fibromyalgia. Therefore, approximately 50% of patients with IRDs receiving modern pathogenetic therapy require additional use of analgesics. Therapy for musculoskeletal pain in RD should be complex, include drugs with different mechanisms of action and non-drug methods. Nonsteroidal anti-inflammatory drugs (NSAIDs) are the first line therapy, they have good analgesic and anti-inflammatory potential. The choice of a specific NSAID should be based on an individual assessment of the clinical situation and the presence of risk factors for possible complications. Among NSAIDs, aceclofenac should be singled out – an effective drug with a favorable safety profile, which is confirmed by a large number of clinical studies and real clinical practice.

Molecular Subgroups of Intrahepatic Cholangiocarcinoma Discovered by Single-Cell RNA Sequencing-Assisted Multiomics Analysis.

Intrahepatic cholangiocarcinoma (ICC) is a relatively rare but highly aggressive tumor type that responds poorly to chemotherapy and immunotherapy. Comprehensive molecular characterization of ICC is essential for the development of novel therapeutics. Here, we constructed two independent cohorts from two clinic centers. A comprehensive multiomics analysis of ICC via proteomic, whole-exome sequencing (WES), and single-cell RNA sequencing (scRNA-seq) was performed. Novel ICC tumor subtypes were derived in the training cohort (n = 110) using proteomic signatures and their associated activated pathways, which were further validated in a validation cohort (n = 41). Three molecular subtypes, chromatin remodeling, metabolism, and chronic inflammation, with distinct prognoses in ICC were identified. The chronic inflammation subtype was associated with a poor prognosis. Our random forest algorithm revealed that mutation of lysine methyltransferase 2D (KMT2D) frequently occurred in the metabolism subtype and was associated with lower inflammatory activity. scRNA-seq further identified an APOE+C1QB+ macrophage subtype, which showed the capacity to reshape the chronic inflammation subtype and contribute to a poor prognosis in ICC. Altogether, with single-cell transcriptome-assisted multiomics analysis, we identified novel molecular subtypes of ICC and validated APOE+C1QB+ tumor-associated macrophages as potential immunotherapy targets against ICC.

Analysis of factors affecting the accuracy of 18F-fluorodeoxyglucose positron emission tomography combined with computed tomography in case of suspected prosthetic valve infective endocarditis

Aim. To analyze the factors affecting the accuracy of 18F-fluorodeoxyglucose positron emission tomography combined with computed tomography (PET/CT) in case of suspected prosthetic valve endocarditis (PVE).Material and methods. The results of PET/CT performed in 66 patients after heart valve replacement were analyzed: 55 patients with suspected PVE (≥3 months after surgery) and 11 comparison groups without PVE (2 months after surgery). In the group with suspected PVE (n=55) at the time of the study, 27% (15/55) had a normal body temperature, 85% (47/55) — no leukocytosis. In 16% (9/55), the examination was performed from 3 to 6 months after surgery and in 67% (37/55) — against the background of long-term antibiotic therapy (ABT). The final diagnosis of PVE was made on the basis of clinical (including 6±3 followup), laboratory, instrumental, and intraoperative (n=40) data: confirmed — in 37 patients; ruled out — in 29 patients. In order to determine the influence of factors on obtaining false PET/CT results, the odds ratio was calculated.Results. In the group with suspected PVE (n=55), the PET/CT results made it possible to establish and rule out PVE in 92% (34/37) and 67% (12/18) of patients, respectively. In 16% (9/55) of patients, false positive (n=6) and false negative (n=3) results. Thus, the sensitivity, specificity and diagnostic accuracy of PET/CT in the diagnosis of PVE were 92%, 67% and 84%, respectively; positive and negative predictive values — 85% and 80%. The analysis of the odds ratio did not reveal the relationship of low inflammatory activity, the interval between surgery and PET/CT from 3 to 6 months, and long-term ABT before PET/CT with false PET/CT results (p&gt;0,05). In the comparison group without PVE (n=11), 91% (10/11) received false positive PET/CT results, and one patient received a true negative result.Conclusion. The data obtained indicate the high informative value of PET/CT in the diagnosis of PVE. Interval &gt;2 months between surgery and PET/CT significantly reduces the accuracy of PET/CT results. Other factors analyzed in the presented group did not affect the accuracy of PET/CT results.

Клінічно-патофізіологічне фенотипування хронічного обструктивного захворювання легень

The purpose of the study was to determine the clinical and laboratory features of inflammatory phenotypes among patients with chronic obstructive pulmonary disease, moderate respiratory failure and anemia of chronic disease. Materials and methods. The study included 150 patients with exacerbation of chronic obstructive pulmonary disease and chronic anemia, in which inflammatory phenotypes were identified, among which the largest share was neutrophilic (66/44.0±4.0%), less lymphocytic (35/23.3±3.4%) and eosinophilic (16/10.7±2.5%). In 33/22.0% of patients, the inflammatory phenotype was mixed and patients were excluded from the study. Among 117 patients included in the study, 67.5% were men and 32.5% were middle-aged (25.6%), elderly (42.7%) and senile (24.8%). The results were processed by the methods of variation statistics, the materiality threshold p &lt;0.05. Results and discussion. It was established, that peripheral blood analysis and biochemical parameters, regardless of the pathophysiological nature of inflammation in all groups showed moderate dysfunction of external respiration, normochromic normocytic nature of mild chronic anemia with activation of all components of the external coagulation mechanism and increased prothrombin time and inflammation activation (by C-reactive protein and seromucoids). The neutrophilic phenotype of inflammation, in comparison with lymphocytic and eosinophilic, was the most common and was accompanied by the most pronounced anemic syndrome, the highest activity of systemic inflammation and the most pronounced syndrome of endogenous intoxication with deterioration of liver function. The lymphocytic phenotype of inflammation was the second widespread and was characterized by the most pronounced normochromic anemic syndrome with the most pronounced predisposition to hypercoagulation (the highest prothrombin index) with high activity of the inflammatory syndrome. The eosinophilic phenotype of inflammation was significantly less common than the neutrophilic and lymphocytic with the favorable characteristics of the anemic syndrome and with low inflammatory activity and the small activity of endogenous intoxication but the highest fasting blood glucose level as normo-hyperglycemia. Conclusion. Clinical and pathophysiological phenotyping of chronic obstructive pulmonary disease makes it possible to determine not only the activity of inflammation, but also the severity of anemic syndrome, endogenous intoxication, liver status and carbohydrate metabolism, which is of practical importance for both physicians and scientists

Chronic viral HBeAg-negative hepatitis B: Epidemiological, clinical and biochemical characteristics in an outpatient descriptive cohort in Burkina Faso

IntroductionOur study aimed to describe epidemiological and diagnostic features in an outpatient's cohort with chronic HBeAg-negative hepatitis B. Patients and methodsA cross-sectional descriptive study with a retrospective data collection was implemented from January 2004 to April 2016 in the hepato-gastroenterology department of the University Teaching Hospital Yalgado Ouédraogo (CHU-YO) in Burkina Faso. ResultsOverall 325 HBeAg negative patients met the inclusion criteria. The sex ratio was 1.5 and the mean age 38.7 years. The most frequent circumstance of diagnosis was the health check-up (54.5%). The mean HBsAg concentration and viral load were 7861.6 IU/mL and 32 237.20 IU/mL, respectively. Low or moderate inflammatory activity was found in 44% and 24% of patients, respectively at the liver biopsy; 32% presented a portal fibrosis with some septa (F2). 43.9% and 41.6% had low (A1) or moderate (A2) inflammatory activity, respectively at the hepatic fibrosis blood test, while 59.1% and 20.4% had low (F1) or moderate (F2) fibrosis stage, respectively. Of the five biochemical and virological profiles among the untreated patients, the profile 1 represented 67.2% of the sample. ConclusionThe proportions of negative HBeAg in chronic hepatitis B patients are increasing in Burkina Faso. Most of the patients have a high viral load, a low to moderate inflammatory activity or fibrosis stage.

Artificial M2 macrophages for disease-modifying osteoarthritis therapeutics

Osteoarthritis (OA) is one of the most common joint diseases worldwide and the focus is shifting to disease prevention and the pharmaceutical and surgical treatment of early OA. However, at present few have proven ability to block or delay the progression of OA. Nevertheless, M2 macrophages present an anti-inflammatory function and promote cartilage repair, thereby alleviating OA in mice. However, it is a significant challenge to regulate the helpful secretion of M2 macrophages on demand toward disease-modifying osteoarthritis therapeutics. Here, artificial M2 macrophage (AM2M) with yolk-shell structure was proposed and fabricated to enhance the therapeutic efficacy of M2 macrophages in the treatment of OA. AM2M was composed of macrophage membrane as “shell” and inflammation-responsive nanogel as “yolk”. The nanogel was prepared via physical interaction of gelatin and chondroitin sulfate (ChS) through ionic bond and hydrogen bond, achieving burst release to down-regulate inflammation during acute flares and sustainable release to repair cartilage during low inflammatory activity. Furthermore, AM2M exhibited the targeting and long-term residence in the inflamed area and blocked the immune stimulation of macrophages by ChS. Therefore, our fabrication provided a new insight that artificial M2 macrophages are expected to break a vicious and self-perpetuating cycle of OA.

Cultural and life style practices associated with low inflammatory physiology in Japanese adults

Japan is an exceptionally healthy East Asian country with extended longevity. In addition, the typical levels of several proinflammatory proteins, including both C-reactive protein (CRP) and interleukin-6 (IL-6), are often reported to be low when compared to American and European populations. This analysis determined if blood levels of CRP and IL-6 were associated with 4 cultural practices reflective of Japanese behavior and customs -- drinking tea, eating seafood, consuming vegetables, and partaking in relaxing baths regularly – among 382 adults living in Tokyo. Regression models controlled for demographic factors, adiposity (BMI), physical exercise, smoking, alcohol use, and chronic illness (e.g., diabetes). Consuming a Japanese diet was associated with significantly lower CRP and IL-6 levels. More frequent bathing was associated with lower IL-6, but not specifically predictive of low CRP. This study has confirmed prior evidence for low inflammatory activity in Japanese adults and its association with several behavioral practices common in Japan.

The TGFB1 -509C/T polymorphism and elevated TGF-β1 levels are associated with chronic hepatitis C and cirrhosis

The IFN-γ and TGF-β1 cytokines perform antagonistic activities in the immune response, and polymorphisms in these genes may induce changes in their plasma levels and influence the course of chronic Hepacivirus C (HCV) infection. The present study evaluated the IFNG +874A/T and TGFB1 -509 C/T polymorphisms in 99 samples from patients with chronic hepatitis C and in 300 samples from healthy donors, and the present study also investigated the association of cytokine plasma level with disease stage. Polymorphisms were identified by real-time PCR, and cytokine levels were measured by enzyme-linked immunosorbent assay. The frequency of the IFNG +874A/T polymorphic allele was not associated with susceptibility to HCV infection, but it was associated with lower inflammatory activity (p = 0.0432). The frequency of the TGFB1 -509C/T polymorphic (TT) genotype was associated with HCV infection (p = 0.0062) and a higher risk of infection (OR = 2.0465; p = 0.0091). Plasma levels of IFN-γ were higher in TT genotype carriers among the control (p = 0.0012) and HCV groups (p = 0.0064) as well as in patients with fibrosis (p = 0.0346) and patients with a high degree of inflammatory activity (p = 0.0381). The highest TGF-β1 levels were found in HCV-infected (p = 0.0329) individuals and in TT genotype carriers. Patients with cirrhosis had higher TGF-β1 (p = 0.0400). IFN-γ and TGF-β1 levels showed a negative correlation (p = 0.0001). In conclusion, the TGFB1 -509C > T polymorphism is associated with a risk of developing chronic hepatitis C, leading to increased TGF-β1, which inhibits IFN-γ production, contributing to the progression to cirrhosis.