Role Of Proinflammatory Cytokines Research Articles

Cytosorb® haemoadsorption: a potential game changer for patients needing myocardial surgical revascularisation

Cytosorb, an extracorporeal blood purification system, utilises the principles of haemoadsorption to remove low molecular weight substances from the blood, including multiple cytokines such as interleukin (IL)-1b, IL-6, IL-8, and tumour necrosis factor-α, and anti-platelet drugs aiming to improve clinical outcomes. Given the prominent role of pro-inflammatory cytokines in various inflammatory states, Cytosorb has seen growing application as a therapeutic immunomodulator including surgery. This review focuses on the effects of the use of Cytosorb in patients undergoing coronary artery bypass grafting (CABG) and the indications of removal of cytokines and anti-platelet agents such as ticagrelor. The evidence supports the feasibility and safety profile of Cytosorb, with no device-related adverse events reported in all studies. Initial studies suggest significant potential for Cytosorb in urgent or emergency CABG surgery to remove anti-platelet medication with promising benefits on clinical outcomes including fewer blood product transfusions, decreased length of intensive care unit stay, and lower re-sternotomy rates. Furthermore, a cost saving analysis indicated that intraoperative removal of ticagrelor with Cytosorb would be cost effective in the setting of emergency cardiac surgery. However, the evidence remains inconclusive when Cytosorb is used in elective CABG surgery for cytokine removal. Definite high quality clinical trials for both indications for Cytosorb in CABG surgery are needed to clarify if there is a clinically significant benefit in clinical outcomes. There is substantial trial activity for the application of Cytosorb in higher risk cardiac surgery to establish the place of Cytosorb in future treatment pathways in cardiac surgery.

Proinflammatory cytokines and circulating tumor cells in ovarian cancer patients treated with platinum-containing chemotherapy

Summary. Circulating tumor cells (CTCs) are a potential source of tumor progression. Systemic tumor-associated inflammation can influence the cancer prognosis both independently and by changing the characteristics of CTCs. Data on the role of proinflammatory cytokines and CTCs in the ovarian cancer (OC) chemosensitivity are few and contradictory. Aim of the study. To assess the IL-17A, IL-18 levels and the number of CTCs in primary patients with OC before treatment and after 3 courses of standard platinum-containing chemotherapy, and the possibility of using these cytokines as a marker of the presence of CTCs. Materials and methods. The study included 72 patients with OC. The comparison group included 16 patients with benign ovarian tumors, the control group included 20 healthy women. The number of CTCs (CD45-/EpCam+/CK+) was determined immunofluorometrically before and after 3 courses of chemotherapy. The content of cytokines was assessed by ELISA. Statistica 13.0, jamovi 1.6.5.0 were used for data processing. Results. The level of IL-17A in blood in the benign tumors group was increased in comparison with OC (р=0.012) and control (р=0.042). The content of IL-17A increased over time in the subgroup of adjuvant chemotherapy (р=0.017). During treatment, IL-17A was higher among patients with platinum-sensitive tumors than with non-sensitive ones (р=0.054). High levels of IL-18 before treatment were associated with the development of platinum-refractory relapse (р=0.014). IL-18 levels before (р=0.027) and during treatment (p=0.052) were lower in patients with cytoreductive surgery in first line of treatment. Progression-free survival (PFS) (p = 0.012) and overall survival (OS) (p = 0.030) were lower in the cluster with high IL-18 and pretreatment leukocyte counts than in the cluster with low scores. Higher quantity of the pretreatment CTCs was associated with longer PFS in a multivariate analysis (HR 0.82 95% CI 0.69–0.98, р=0.028). The number of CTCs before treatment greater than 5 was associated with a decrease in OS (HR 1.31, 95% CI 0.98–1.73, р=0.064). Conclusions. A high level of IL-17A in the blood during treatment is associated with more favorable clinical characteristics of OC, while a high level of IL-18 in the blood before treatment is associated with less favorable characteristics and a worse prognosis. The number of CTCs in patients with OC is not related to the blood levels of IL-17A and IL-18. A greater number of CTCs before treatment in OC is associated with an increase in PFS, but a decrease in overall survival.

Onco-specific sleep disorders and fatigue: tactics of psychological test and cognitive behavioral therapy

Introduction. Sleep disorders are widespread throughout the entire period of treatment of an oncological patient from the moment of diagnosis, and in many patients persist after completion of treatment. The nature of cancer and its treatment expose patients to many potential provoking and/or supportive factors that are atypical for the general population. In addition, sleep disturbance rarely manifests as a separate symptom, but more often occurs together with such symptoms as fatigue, pain, depression and/or cognitive impairment. This complicates the assessment and often requires an individual treatment plan with a team approach.
 AIM. of the work is to acquaint mental health specialists, oncologists, chemotherapists with the specifics of the examination of cancer-specific insomnia and fatigue, the construction of team treatment tactics, the organization of psychotherapeutic care for cancer patients.
 Results. The article describes for the first time the specifics of onco-specific insomnia and fatigue. The general predisposing and supporting factors of insomnia characteristic of cancer patients are systematized. The relationship between onco-specific fatigue and sleep disorders is shown. The role of pro-inflammatory cytokines as a common neuroendocrine-immune mechanism underlying the behavioral symptoms of sleep disorders, fatigue, depression and cognitive dysfunction in people with cancer is noted. Due to the limitations of the pharmacological approach, the purpose, forms, modes and approaches of using cognitive behavioral therapy protocols to minimize insomnia and fatigue are described. Based on the data of our foreign colleagues, we have proposed an algorithm for assessing sleep disorders in a patient with an oncological profile. The effectiveness of the standard protocol of cognitive behavioral psychotherapy of insomnia (SCBT-I) in a patient of the oncological profile Lavini Fiorentino is described in detail and shown; as well as the short protocol of CBT of cancer-specific insomnia by Eric Zo et al.; remote protocol of mindfulness enhancement therapy to minimize onco-specific fatigue Z.by Fieke et al.
 Conclusions. CBT in the framework of complex treatment has a positive effect on the immune system, reducing inflammation mediated through the hypothalamic-pituitary-adrenal axis. Despite the accumulation of evidence confirming the effectiveness of this form of psychological assistance, its availability in Russia remains extremely limited and not fully appreciated.

Tendon healing is adversely affected by low-grade inflammation

BackgroundTendinopathy is common, presents with pain and activity limitation, and is associated with a high risk of recurrence of the injury. Tendinopathy usually occurs as a results of a disrupted healing response to a primary injury where cellular and molecular pathways lead to low grade chronic inflammation.Main findingsThere has been a renewed interest in investigating the role of Inflammation in the pathogenesis of tendinopathy, in particular during the initial phases of the condition where it may not be clinically evident. Understanding the early and late stages of tendon injury pathogenesis would help develop new and effective treatments addressed at targeting the inflammatory pathways.ConclusionThis review outlines the role of low-grade Inflammation in the pathogenesis of tendinopathy, stressing the role of proinflammatory cytokines, proteolytic enzymes and growth factors, and explores how Inflammation exerts a negative influence on the process of tendon healing.

Особенности механизмов патогенеза и ранние диагностические критерии гипоксически-ишемического повреждения головного мозга у новорожденных детей (часть 2)

Статья посвящена актуальной проблеме неонатологии и детской неврологии — вопросу ранней диагностики перинатального повреждения головного мозга гипоксически-ишемического генеза у новорожденных, в частности преждевременно рожденных детей. В работе проанализирована научная литература o механизмах перинатального повреждения головного мозга гипоксически-ишемического генеза. Представлены новые данные об особенностях функционирования, повреждения, а также о механизмах гибели клеток нейронального и глиального происхождения в развивающемся мозге. Показано, что в реализации механизма повреждения клеток головного мозга участвуют эксайтотоксичность, окислительный стресс и асептическое воспаление, в результате которых клетки гибнут путем некроза и патологического апоптоза. Подчеркнуто, что в незрелой нейрональной ткани гибель нейронов протекает не только вышеуказанными путями, но и по комбинированному некротически-апоптозному (некроптозный) механизму. Проанализированы особенности функционирования глутаматных рецепторов в развивающемся мозге. Приведены данные литературы о том, что вышеописанные патологические механизмы на фоне особенностей функционирования митохондрий развивающегося мозга приводят к дебюту патологического апоптоза. Определено, что наиболее перспективным в ранней диагностике гипоксически-ишемического повреждения центральной нервной системы у новорожденных детей, в частности преждевременно рожденных, является изучение уровня нейроспецифических белков и антител к ним, а также белков, связанных с плазматической мембраной клеток, в частности клеток мозга — молекул межклеточной адгезии. В статье проанализирована роль маркеров нейрональной и глиальной природы, в частности глиофибриллярно-кислого протеина (GFAP), убиквитин-С-концевой гидролазы L1 (UCHL1), основного белка миелина (MBP), с учетом роли провоспалительных цитокинов в механизмах повреждения клеток развивающегося мозга. Показана роль мембранного белка эндотелиоцитов мозговых капиляров (молекулы межклеточной адгезии 1 — sICAM-1) как одного из маркеров повреждения клеток гематоэнцефалического барьера при различных патологических процессах, в частности гипоксии и ишемии.

Identifying risk factors for chronic visceral pain: The role of pro-inflammatory cytokines

Identifying risk factors for chronic visceral pain: The role of pro-inflammatory cytokines

The development of universal alopecia during therapy with TNF-α inhibitors in patients with ankylosing spondylitis: description of three cases

Alopecia areata (АA) is an autoimmune multifactorial disease characterized by increased hair loss as a result of morphological and functional changes in hair follicles. АA is divided into four main forms, among which the most severe is the universal form (UA), in which complete hair loss is possible throughout the body. Alopecia in the practice of a rheumatologist can occur with some systemic diseases of the connective tissue, with the use of high doses of chemotherapy drugs and, more recently, with the use of inhibitors of tumor necrosis factors alpha (TNF-α). The article presents 3 clinical cases of the development of UA during therapy with TNF-α. Possible mechanisms are discussed, as well as the role of pro-inflammatory cytokines in the development of this condition.

Inflammatory Mediators of Platelet Activation: Focus on Atherosclerosis and COVID-19.

Background: Atherosclerotic cardiovascular diseases are characterized by a dysregulated inflammatory and thrombotic state, leading to devastating complications with increased morbidity and mortality rates. Summary: In this review article, we present the available evidence regarding the impact of inflammation on platelet activation in atherosclerosis. Key messages: In the context of a dysfunctional vascular endothelium, structural alterations by means of endothelial glycocalyx thinning or functional modifications through impaired NO bioavailability and increased levels of von Willebrand factor result in platelet activation. Moreover, neutrophil-derived mediators, as well as neutrophil extracellular traps formation, have been implicated in the process of platelet activation and platelet-leukocyte aggregation. The role of pro-inflammatory cytokines is also critical since their receptors are also situated in platelets while TNF-α has also been found to induce inflammatory, metabolic, and bone marrow changes. Additionally, important progress has been made towards novel concepts of the interaction between inflammation and platelet activation, such as the toll-like receptors, myeloperoxidase, and platelet factor-4. The accumulating evidence is especially important in the era of the coronavirus disease-19 pandemic, characterized by an excessive inflammatory burden leading to thrombotic complications, partially mediated by platelet activation. Lastly, recent advances in anti-inflammatory therapies point towards an anti-thrombotic effect secondary to diminished platelet activation.

PO-1159 Prognostic role of pro-inflammatory cytokines in multimodal treatment of inoperable stage III NSCLC

PO-1159 Prognostic role of pro-inflammatory cytokines in multimodal treatment of inoperable stage III NSCLC

The role of proinflammatory cytokines on liver damage after pentylenetetrazole-induced acute and chronic epilepsy models in rats

Objectives: The mechanisms of acute liver failure resulting from epilepsy are poorly defined and appear to be multifactorial, including hypoxia and steatosis. The role of inflammation on liver damage after seizures is unclear. This study aimed to investigate the relationship between proinflammatory cytokines and liver damage after pentylenetetrazole-induced acute and chronic epilepsy models in rats. Materials and methods: Male Wistar albino adult rats (n = 18), weighing 220–240 g, were used in the experiment. The animals were divided into three groups: (1) Control Group (Control; n = 6); rats were treated with a single dose of saline intraperitoneally (i.p.), (2) Acute Epileptic Model Group (n = 6); rats were treated with a single dose of i.p. PTZ (45 mg/kg), (3) Chronic Epileptic Model Group (n = 6); rats were treated with repeated doses of i.p. PTZ (35 mg/kg) every other day for 15(fifteen) times. Result: There was a significant difference between the control and acute epileptic model in terms of serum AST, TNF-α, IL-1 β and IL-6 parameters (p<0.05). On the other hand, there was a significant difference between the acute and chronic epileptic models in the serum AST, TNF-α and IL-6 parameters (p<0.05). Conclusions: As a result, while liver damage is secondary to hypoxia during epileptic seizures, multifactorial causes are blamed. Proinflammatory cytokines that increase in the liver after these factors may be responsible for liver damage in acute epileptic seizures. Compensation mechanisms such as antioxidant defence mechanism in chronic epileptic seizures may prevent liver damage.

Lanthionine, a Novel Uremic Toxin, in the Vascular Calcification of Chronic Kidney Disease: The Role of Proinflammatory Cytokines.

Vascular calcification (VC) is a risk factor for cardiovascular events and mortality in chronic kidney disease (CKD). Several components influence the occurrence of VC, among which inflammation. A novel uremic toxin, lanthionine, was shown to increase intracellular calcium in endothelial cells and may have a role in VC. A group of CKD patients was selected and divided into patients with a glomerular filtration rate (GFR) of <45 mL/min/1.73 m2 and ≥45 mL/min/1.73 m2. Total Calcium Score (TCS), based on the Agatston score, was assessed as circulating lanthionine and a panel of different cytokines. A hemodialysis patient group was also considered. Lanthionine was elevated in CKD patients, and levels increased significantly in hemodialysis patients with respect to the two CKD groups; in addition, lanthionine increased along with the increase in TCS, starting from one up to three. Interleukin IL-6, IL-8, and Eotaxin were significantly increased in patients with GFR < 45 mL/min/1.73 m2 with respect to those with GFR ≥ 45 mL/min/1.73 m2. IL-1b, IL-7, IL-8, IL-12, Eotaxin, and VEGF increased in calcified patients with respect to the non-calcified. IL-8 and Eotaxin were elevated both in the low GFR group and in the calcified group. We propose that lanthionine, but also IL-8 and Eotaxin, in particular, are a key feature of VC of CKD, with possible marker significance.

Peripheral mechanisms involved in Tityus bahiensis venom-induced pain

Scorpionism is a public health burden in Brazil. Tityus bahiensis is responsible for most accidents in the Southeastern region of Brazil. Here, the hyperalgesic mechanisms of Tityus bahiensis venom were investigated, focusing on the role of pro-inflammatory cytokines (tumor necrosis factor alpha [TNF-α] and interleukin 1 beta [IL-1β]) and activation of the transcription factor NFκB. Intraplantar (i.pl.) administration of Tityus bahiensis venom (0.2, 0.6, 1.2 and 2.4 μg/20 μL i.pl.) induced mechanical hyperalgesia and thermal hyperalgesia. The 2.4 μg dose of Tityus bahiensis venom induced overt pain-like behavior and increased myeloperoxidase (MPO) and N-acetyl-beta-D-glucosaminidase (NAG) activities, TNF-α and IL-1β levels in the paw tissue. Systemic pre-treatment with etanercept (soluble TNF-α receptor; 10 mg/kg), IL-1ra (IL-1 receptor antagonist; 30 mg/kg) and pyrrolidine dithiocarbamate (PDTC, nuclear factor kappa B [NFκB] inhibitor; 100 mg/kg) inhibited Tityus bahiensis venom-induced mechanical and thermal hyperalgesia, MPO and NAG activity and overt pain-like behavior. These data demonstrate the involvement of TNF-α and IL-1β signaling as well as NFκB activation in Tityus bahiensis venom-induced mechanical and thermal hyperalgesia, overt pain-like behavior, and MPO activity and NAG activity, indicating thus, that targeting these mechanisms might contribute to reducing the pain in this scorpionism.

Inflammatory signaling regulates hematopoietic stem and progenitor cell development and homeostasis.

Inflammation exerts multiple effects on the early hematopoietic compartment. Best studied is the role of proinflammatory cytokines in activating adult hematopoietic stem and progenitor cells to dynamically replenish myeloid lineage cells in a process known as emergency myelopoiesis. However, it is increasingly appreciated that the same proinflammatory signaling pathways are used in diverse hematopoietic scenarios. This review focuses on inflammatory signaling in the emergence of the definitive hematopoietic compartment during embryonic life, and tonic inflammatory signals derived from commensal microbiota in shaping the adult hematopoietic compartment in the absence of pathogenic insults. Insights into the unique and shared aspects of inflammatory signaling that regulate hematopoietic stem and progenitor cell function across the lifespan and health span of an individual will enable better diagnostic and therapeutic approaches to hematopoietic dysregulation and malignancies.

The role of endothelial damage and dyslipidemia in the development of cardiovascular pathology in psoriatic arthritis

An increased risk of cardiovascular events has now been identified in patients with psoriatic arthritis. The chronic immune-mediated inflammation underlying psoriatic arthritis (PA) leads to the development of dyslipidemia, atherosclerosis and its complications, in particular, a high risk of cardiovascular complications. For PA, dyslipidemias are most characteristic, manifested by an increased level of low and very low density lipoproteins, triglycerides and total cholesterol, which correlates with the activity of the disease. The literature review studied the pathogenesis of dyslipidemias and vascular wall lesions in psoriatic arthritis, analyzed the literature on cardiovascular complications and mortality among patients with PA, studied the issues of total cardiovascular risk, presented the results of numerous clinical studies that allow PA to be considered a disease associated with increased the risk of cardiovascular complications. Considering the role of proinflammatory cytokines in the pathogenesis of psoriatic arthritis, early detection of endothelial lesions represents the most promising direction in the prevention of cardiovascular diseases, which are the main cause of mortality in this group of patients.

Increased telomerase activity in major depressive disorder with melancholic features: Possible role of pro-inflammatory cytokines and the brain-derived neurotrophic factor

The biological mechanisms responsible for depression symptoms are not yet understood. For this reason, it is important to reveal the etiopathogenetic mechanisms in this disease. This study aims to compare the levels of pro-inflammatory cytokines, Brain-Derived Neurotrophic Factor (BDNF), and telomerase activity in patients with major depressive disorder (MDD) and healthy controls. Plasma BDNF, interleukin-6 (IL-6), IL-1beta, and Tumor Necrosis Factor-alpha (TNF-alpha) levels, and telomerase activity were measured in 39 patients with major depression and 39 healthy controls matched with patients in terms of age, gender, and education year. Plasma concentration of BDNF, IL-6 levels, and telomerase activity was significantly different between patients with MDD and healthy controls. Correlation analysis showed a positive trend between plasma BDNF levels and plasma IL-6 levels in patients with MDD with melancholic features. Furthermore, the path analysis results showed that the telomerase activity was indirectly affected by gender, IL-1β, IL-6, BDNF, and BMI, via the severity of depression and anxiety and MDD status as the mediators. Further studies are needed to examine the molecular mechanism of the telomerase activity and the role of BDNF and pro-inflammatory cytokines in the telomerase activation in MDD.

Anti-edema effect of Aloe vera leaf extract following traumatic brain injury: Role of pro-inflammatory cytokines.

Objective:Based on anti-inflammatory effects of Aloe vera, the effect of aqueous extract of this plant on brain edema and changes in some pro-inflammatory cytokines was investigated after traumatic brain injury (TBI).Materials and Methods:In this study, adult male Wistar rats were divided into 5 groups: Sham, TBI, vehicle (Veh), and low dose (LA) and high dose (HA) Aloe vera. The vehicle and aqueous extract of Aloe vera were injected intraperitoneally 30 min after induction of diffuse TBI by Marmarou’s method. Brain edema (brain water content), and transforming growth factor beta (TGF-β), tumor necrosis factor alpha (TNFα), interleukin 6 (IL-6) and IL-1β levels in serum and brain were measured 24 hr after TBI induction.Results:Increased brain edema by TBI was reduced by both LA and HA (p<0.01 and p<0.05, respectively). IL-6 increased in the brain of TBI group compared to sham, and which was inhibited by both Aloe vera doses compared to Veh (p<0.001). The differences in the IL-6 serum levels among Veh, LA and HA groups were not significant. Increases in serum and brain IL-1β levels were reduced only in the HA group (p<0.001). Although only in the brain, TNF-α level increased after trauma, but both LA and HA inhibited it in a dose-dependent manner (p<0.01 and p<0.05, respectively) . The amount of TGF-β in the brain was reduced by both doses of the extract (p<0.001). Conclusion:These results indicated that Aloe vera has a neuroprotective effect induced by reducing brain edema. The probable mechanism particularly for HA is decreasing levels of pro-inflammatory cytokines such as TGF-β, TNF-α, IL-6 and IL-1β.

РАННИЕ И АЛЬТЕРНАТИВНЫЕ МАРКЕРЫ РАЗВИТИЯ ХРОНИЧЕСКОЙ СЕРДЕЧНОЙ НЕДОСТАТОЧНОСТИ У ПАЦИЕНТОВ С САХАРНЫМ ДИАБЕТОМ

Aim: to assess the relationship of proinflammatory cytokines and chemokines with the levels of natriuretic peptides in patients with diabetes mellitus (DM). Materials and methods. A total of 155 patients (14 men and 61 women) with type 1 and type 2 diabetes, aged 34 to 84 years, were examined. All patients underwent standard clinical and laboratory examination, with an assessment of the levels of pro-inflammatory cytokines (interleukin 6 (IL-6), tumour necrosis factor alpha (TNF-alpha), chemokines (monokine induced by interferon-gamma (MIG), regulated upon activation, normal T cell expressed and presumably secreted (RANTES), growth factors (fibroblast growth factor-23 (FGF-23), vascular endothelial growth factor (VEGF-A), natriuretic peptides (B‐type natriuretic peptide (BNP), N‐terminal fragment of B‐type natriuretic peptide (proBNP). Renal function was assessed based on the levels of serum creatinine, glomerular filtration rate (GFR), which was calculated according to the CKD-EPI formula, and albuminuria, which was assessed as albumin/creatinine ratio (A/C). An echocardiographic examination was conducted according to the standard protocol with the calculation of dimensional, volume and speed characteristics. Statistical data analysis was performed using smSTATA 14.2 for Mac (2018). Results. 57% DM patients had BNP and proBNP levels exceeding the diagnostic values of BNP &gt;35 pg/ml and/or proBNP &gt;125 pg/ml. The levels of BNP and proBNP positively correlated with the levels of homocysteine, uric acid, IL-6, С-reactive protein (CRP), high-sensitivity C-reactive protein (hsCRP), A/С, creatinine, cystatin C, TNF-alpha, chemokines (MIG, RANTES), growth factors (FGF-23, VEGF-A) (p &lt;0.05). According to multiple regression analysis, predictors for increased proBNP were IL-6, A/K, creatinine (ß=0.70, p&lt;0.001, ß=3.51, p=0.01, ß=0.97, p=0.01, respectively). ROC analysis determined the highest diagnostic significance of creatinine for the prediction of increased proBNP. The significance of IL-6 proved higher than A/С (AUC-0.777). Thus, when the level of IL-6 (AUC-0.789) was 3.1 mg/ml, the sensitivity and specificity for increased proBNP concentration were 71.9% and 71.2%, respectively. Conclusion. IL-6 might be an independent predictor of increased levels of natriuretic peptide in patients with diabetes. Further study of the role of pro-inflammatory cytokines in the development of cardiovascular diseases will make it possible to finally decode the mechanisms of their pathogenesis, which will further allow us to understand their complex effect on the body and obtain information for the development of new effective and safe specific medicines.

Ассоциация неалкогольного стеатоза печени с гастроэзофагеальным рефлюксом у больных воспалительными заболеваниями кишечника

Background: to date, the question of possible association between non-alcoholic fatty liver disease (NAFLD) and gastroesophageal reflux disease (GERD) is being considered. This association may be due to common risk factors for these two conditions, for example, obesity. However, several study results suggest the role of pro-inflammatory cytokines in the pathogenesis of NAFLD and GERD. Of great interest is the study of these syndromes association in a group of patients with diseases accompanied by a systemic inflammatory process. Aim: study of the association of NAFLD and GERD in a group of patients with inflammatory bowel diseases (IBD) without obesity and other metabolic risk factors. Patients and Methods: the study involved 58 patients with a diagnosis of IBD. The study did not include patients with overweight, obesity and other metabolic risk factors. The presence of GERD was assessed based on survey data, the GERD-Q questionnaire and the results of an endoscopy. Results and Discussion: the presence of GERD was associated with the presence of NAFLD in the studied group of patients (odds ratio (OR)=5.17; 95% confidence interval (CI) 1.46–18.28). There were no statistically significant differences in body mass index (BMI) between the groups of patients with NAFLD and without NAFLD (21.05 kg/m2 vs. 20.04 kg/m2, respectively, p=0.419). There was no statistically significant association of NAFLD with the use of systemic glucocorticosteroids in the anamnesis (OR=1.11; 95% CI 0.3–4.05), the presence of episodes of weight loss in the anamnesis (OR=0.48; 95% CI 0.11–2.11). Conclusion: in patients with IBD, NAFLD is associated with the presence of GERD, regardless of BMI, the presence of carbohydrate metabolism disorders, as well as a history of weight loss episodes. KEYWORDS: gastroesophageal reflux disease, fatty liver disease, inflammatory bowel diseases. FOR CITATION: Krasner Ya.A., Osipenko M.F., Bikbulatova E.A., Kholin S.I. Association of non-alcoholic fatty liver disease with gastroesophageal reflux disease in patients with inflammatory bowel diseases. Russian Medical Inquiry. 2021;5(6):373–376 (in Russ.). DOI: 10.32364/2587-6821-2021-5-6-373-376.

Role of Inflammation in the Development of Colorectal Cancer.

Chronic inflammation can lead to the development of many diseases, including cancer. Inflammatory bowel disease (IBD) that includes both ulcerative colitis (UC) and Crohnmp's disease (CD) are risk factors for the development of colorectal cancer (CRC). Many cytokines produced primarily by the gut immune cells either during or in response to localized inflammation in the colon and rectum are known to stimulate the complex interactions between the different cell types in the gut environment resulting in acute inflammation. Subsequently, chronic inflammation, together with genetic and epigenetic changes, have been shown to lead to the development and progression of CRC. Various cell types present in the colon, such as enterocytes, Paneth cells, goblet cells, and macrophages, express receptors for inflammatory cytokines and respond to tumor necrosis factor-alpha (TNF-α), interleukin-1 beta (IL-1β), IL-6, and other cytokines. Among the several cytokines produced, TNF-α and IL-1β are the key pro-inflammatory molecules that play critical roles in the development of CRC. The current review is intended to consolidate the published findings to focus on the role of pro-inflammatory cytokines, namely TNF-α and IL-1β, on inflammation (and the altered immune response) in the gut, to better understand the development of CRC in IBD, using various experimental model systems, preclinical and clinical studies. Moreover, this review also highlights the current therapeutic strategies available (monotherapy and combination therapy) to alleviate the symptoms or treat inflammation-associated CRC by using monoclonal antibodies or aptamers to block pro-inflammatory molecules, inhibitors of tyrosine kinases in the inflammatory signaling cascade, competitive inhibitors of pro-inflammatory molecules, and the nucleic acid drugs like small activating RNAs (saRNAs) or microRNA (miRNA) mimics to activate tumor suppressor or repress oncogene/pro-inflammatory cytokine gene expression.

Current mechanisms in obesity and tumor progression.

Hyperadiposity, as present in obesity, is a substantial threat to cancer risk and prognosis. Studies that have investigated the link between obesity and tumor progression have proposed several mechanistic frameworks, yet, these mechanisms are not fully defined. Further, a comprehensive understanding of how these various mechanisms may interact to create a dynamic disease state is lacking in the current literature. Recent work has begun to explore not only discrete mechanisms by which obesity may promote tumor growth (for instance, metabolic and growth factor functions of insulin; inflammatory cytokines; adipokines; and others), but also how these putative tumor-promoting factors may interact. This review will highlight the present understanding of obesity, as it relates to tumor development and progression. First, we will introduce the impact of obesity in cancer within the dynamic tumor microenvironment, which will serve as a theme to frame this review. The core of this review will discuss recently proposed mechanisms that implicate obesity in tumor progression, including chronic inflammation and the role of pro-inflammatory cytokines, adipokines, hormones, and genetic approaches. Furthermore, we intend to offer current insight in targeting adipose tissue during the development of cancer prevention and treatment strategies.