Systemic Inflammatory Process Research Articles

Cardiac wasting in patients with cancer

AbstractPatients with cancer face a significant risk of cardiovascular death, regardless of time since cancer diagnosis. Elderly patients are particularly more susceptible as cancer-associated cardiac complications present in advanced stage cancer. These patients may often present with symptoms observed in chronic heart failure (HF). Cardiac wasting, commonly observed in these patients, is a multifaceted syndrome characterized by systemic metabolic alterations and inflammatory processes that specifically affect cardiac function and structure. Experimental and clinical studies have demonstrated that cancer-associated cardiac wasting is linked with cardiac atrophy and altered cardiac morphology, which impairs cardiac function, particularly pertaining to the left ventricle. Therefore, this review aims to present a summary of epidemiologic data and pathophysiological mechanisms of cardiac wasting due to cancer, and future directions in this field.

The relationship between severity of periapical periodontitis and next-generation systemic inflammatory biomarkers in children with early childhood caries

IntroductionEarly childhood caries (ECC) is closely associated with poor oral hygiene and cariogenic diet. Untreated ECC results in recurrent odontogenic infections and local and systemic consequences. In this study, our goal is to assess the relationship between the intensity of odontogenic infection-associated periapical periodontitis and new generation of systemic inflammatory markers (SII, NLR, PLR) in ECC-affected children.Material and method95 healthy patients in early childhood and demonstrating periapical periodontitis who underwent dental treatment under general anesthesia (GA) in the last two years were included in the present study. Their periapical statuses were dichotomized as mild and severe. Periapical Index (PAI) scores of 2 and 3 were regarded as “mild” whereas 4 and 5 as “severe”. Of the complete blood test (CBC) parameters, systemic inflammatory index (SII), neutrophil-to-lymphocyte ratio (NLR), platelet–lymphocyte ratio (PLR), neutrophilic granulocyte (NEUT), lymphocyte (LYMPH) and platelet (PLT) were recorded. The relationship between the degree of periapical pathology and the evaluated markers was assessed using Receiver Operating Characteristic (ROC) analysis.ResultsResults of the present study revealed that mean NLR, SII and NEUT index scores of the patients having severe periapical periodontitis were statistically higher than those of the ones with mild pathology (p < 0.05). A positive, statistically significant interrelationship was found between the number of teeth demonstrating a PAI score of severe periapical periodontitis with the signs of exacerbation (PAI 5) and NLR and SII values (p < 0.05). Area under the ROC curve (AUC) values for NLR and SII were determined as 66.8% and 66.6% respectively, indicating that classification performance was sufficient and statistically significant (p < 0.05).ConclusionPostponing the management of odontogenic infections will induce some complications such as, infective endocarditis and cause the systemic inflammatory process to continue by aggravating the systemic effects of local lesions. Thus, underlying mechanism should be eliminated and oral hygiene should be maintained, also novel biomarkers may be recommended to be used for the decision-making process for the teeth with persistent periapical lesions unresponsive to treatment.

Rethinking Mitral Annular Calcification and Its Clinical Significance: From Passive Process to Active Pathology.

Mitral annulus calcification is a chronic degenerative condition affecting the fibrous base of the mitral valve. Historically viewed as an age-related phenomenon, recent studies suggest it is driven by active mechanisms involving systemic inflammation, hemodynamic stress, abnormal calcium-phosphorus metabolism, and lipid accumulation. Despite often being asymptomatic and incidentally detected, its clinical relevance stems from its strong association with increased cardiovascular disease risk, higher cardiovascular mortality, and elevated overall mortality. This article investigates the complexities and controversies surrounding mitral annular calcification as a potential embolic source, focusing on its diagnosis, its relationship with systemic inflammation, and its links to metabolic and chronic disorders. The findings highlight that mitral annular calcification is not merely a passive marker of aging but an active indicator of atherosclerotic burden with significant implications for cardiovascular health. Mitral annulus calcification should be recognized as an important factor in cardiovascular risk assessment, offering insight into systemic inflammatory processes and metabolic dysregulation.

“The effects of non-surgical periodontal treatment plus zinc and magnesium supplementation on oxidative stress and antioxidants enzymes in type 2 diabetes patients: a quasi-experimental study”

BackgroundPeriodontal Disease (PD) associated with Type 2 Diabetes Mellitus (T2DM) is a chronic condition that affects the oral cavity of people living with T2DM. The mechanisms of the interaction between type 2 Diabetes Mellitus and Periodontal diseases are complex and involve multiple pathophysiological pathways related to the systemic inflammatory process and oxidative stress. Non-surgical periodontal treatment (NSTP) is considered the standard for the management of this disease; however, patients with systemic conditions such as type 2 Diabetes Mellitus do not seem to respond adequately. For this reason, the use of complementary treatments has been suggested to support non-surgical periodontal treatment to reduce the clinical consequences of the disease and improve the systemic conditions of the patient. The use of zinc gluconate and magnesium oxide as an adjunct to non-surgical periodontal treatment and its effects on periodontal clinical features and oxidative stress in patients with Periodontal diseases -type 2 Diabetes Mellitus is poorly understood.MethodsA quasi-experimental study was performed in patients with periodontal diseases associated with T2DM. Initially, 45 subjects who met the selection criteria were included. 19 were assigned to a control group [non-surgical periodontal treatment] and 20 to the experimental group (non-surgical periodontal treatment + 500 mg of magnesium oxide and 50 mg of zinc gluconate for oral supplementation for 30 days) and the data of 6 patients were eliminated. Sociodemographic characteristics, physiological factors, biochemical parameters, and clinical features of periodontal diseases were assessed.ResultsIn this research a change in periodontal clinical characteristics was observed, which has been associated with disease remission. Additionally, a shift in MDA levels was presented for both groups. Furthermore, the supplementation group showed an increase in antioxidant enzymes when compared to the group that only received NSPT.ConclusionThe use of Zinc gluconate and magnesium oxide can serve as a complementary treatment to non-surgical periodontal treatment, that supports the remission of PD as a result of regulation-reduction of oxidative biomarkers and increase in antioxidant enzymes activity.Trial Registrationhttps://www.isrctn.com ISRCTN 14,092,381. September 13º 2023. Retrospective Registration.Graphical

Exploring Headaches in Pediatric Behçet Disease: Prevalence, Clinical Impact, and Management.

Behçet's Disease (BD), also recognized as Behçet Syndrome, manifests uniquely in pediatric populations as Pediatric Behçet's Disease (PBD), characterized by multisystemic inflammatory symptoms including recurrent oral and genital aphthae, and diverse ocular, vascular, and neurological involvements. This review elucidates the prevalence, burden, and management strategies of headaches in children with PBD, focusing on both primary headaches, such as migraine and tension-type headaches, and secondary headaches linked to systemic disease manifestations. It explores the pathophysiological underpinnings specific to PBD-related headaches and discusses the intricate relationship between systemic inflammatory processes and neurological symptoms. By examining the literature from 2004 to 2024, this study highlights the high frequency of headache in PBD patients, underscoring its diagnostic and clinical significance. We aim to provide a detailed understanding of headache management in PBD, emphasizing tailored therapeutic strategies that address the unique challenges faced by this patient population. This review also underscores the importance of comprehensive clinical evaluations to optimize outcomes and mitigate long-term sequelae, proposing that awareness and understanding of headache in PBD can significantly enhance both diagnosis and management.

РАЗВИТИЕ ХРОНИЧЕСКОГО МУЛЬТИОЧАГОВОГО НЕБАКТЕРИАЛЬНОГО ОСТЕОМИЕЛИТА У ПАЦИЕНТА С ИСХОДНО ДИАГНОСТИРОВАННЫМ СИСТЕМНЫМ ЮВЕНИЛЬНЫМ АРТРИТОМ: КЛИНИЧЕСКОЕ НАБЛЮДЕНИЕ

Systemic juvenile arthritis (sJA) is a special variant of chronic arthritis in children belonging to the spectrum of polygenic autoinflammatory diseases whose main features are persistent febrile fever, skin rashes, other systemic manifestations (serositis, lymphadenopathy, hepatosplenomegaly) as well as the presence of joint damage with the frequent development of destructive polyarthritis and osteonecrosis, high laboratory indicators of systemic inflammation either at the disease onset or delayed. The list of differentiated conditions includes many diseases such as infections, cancer, primary immunodeficiencies, monogenic autoinflammatory diseases etc. Authors represent a clinical case of a patient with sJA manifestations who was diagnosed with chronic multifocal nonbacterial osteomyelitis (CMNO), that demonstrates the great difficulties in diagnosis and the variability of the course of rheumatic diseases in childhood, which in its turn causes a delay in the timely prescription of effective therapy. Thus, patients with manifestations of a systemic inflammatory process, joint changes, especially those with an atypical course of the disease, pain in the bones and joints of a nocturnal nature, as well as an insufficient response to the therapy even long-term, are in need of conducting of a differential diagnostic search with the inclusion of CMNO, the ‘whole body’ mode magnetic-resonance tomography prescribed by a rheumatologist practitioner.

Sarcopenia and Dinapenia in Patients with Ulcerative Colitis (Cross-Sectional Observational Study)

Background. Sarcopenia is a generalised, progressive decline in skeletal muscle mass, strength and performance leading to reduced quality of life, increased risk of falls, hospitalisation and mortality. Primary sarcopenia results from age-related changes in muscle tissue. In certain cases, sarcopenia develops secondary as a consequence of diseases including ulcerative colitis (UC), which is associated with a systemic inflammatory process, malabsorption syndrome, restriction of patients’ physical activity and nutrient deficiencies. The term “dynapenia” or “probable sarcopenia” has been proposed to describe the decrease in muscle strength. Studies have demonstrated that muscle strength is a more relevant marker for predicting adverse outcomes because its measurement is more practical, whereas muscle mass is technically difficult to measure. Aims — to increase the effectiveness of the diagnosis of dinapenia, to assess the prevalence and risk factors of its formation in patients with UC. Methods. A single-centre, observational cross-sectional study included 80 UC patients. To identify factors associated with the development of dinapenia, patients with dinapenia were compared with patients without dinapenia. The investigated parameters in patients: sex, age, body mass index, peculiarities of the course of the disease, ongoing treatment, concomitant pathology, peculiarities of nutrition, nutritional deficiency, malabsorption syndrome, bad habits, psychological stress and sleep duration, physical activity, laboratory indicators of inflammation, myokine-adipokine profile. Statistical parameters were calculated using Statistica 10.0.1011.0 programme. Results. Dinapenia is present in 32.5% of UC patients. Risk factors for the formation of dinapenia in UC patients include female sex (p = 0.0003); nutritional insufficiency (p = 0.021); low physical activity (p = 0.010); artificial feeding in infancy (p = 0.024); inflammation, namely C-reactive protein, autoantibodies of class G against double-stranded DNA (p = 0.006; p = 0.002 respectively). Patients with UC with dinapenia significantly more often gave a positive answer to the questionnaire question “Does daily activity cause you a lot of stress?” (p = 0.048). In the group of UC patients with dinapenia, the level of cortisol in evening saliva was significantly higher than in the comparison group (p = 0.005). Conclusions. Sarcopenia and UC are multifactorial conditions with common developmental mechanisms that can burden each other. Dynamometry is not technically difficult and is justified from an economic point of view. The timely detection of dinapenia and its correction will additionally affect the mechanisms of UC pathogenesis in order to improve the quality of life and prognosis of patients.

New insights into sodium phenylbutyrate as a pharmacotherapeutic option for neurological disorders.

Neurological disorders (NDs) are diseases of the central and peripheral nervous systems that affect more than one billion people worldwide. The risk of developing an ND increases with age due to the vulnerability of the different organs and systems to genetic, environmental, and social changes that consequently cause motor and cognitive deficits that disable the person from their daily activities and individual and social productivity. Intrinsic factors (genetic factors, age, gender) and extrinsic factors (addictions, infections, or lifestyle) favor the persistence of systemic inflammatory processes that contribute to the evolution of NDs. Neuroinflammation is recognized as a common etiopathogenic factor of ND. The study of new pharmacological options for the treatment of ND should focus on improving the characteristic symptoms and attacking specific molecular targets that allow the delay of damage processes such as neuroinflammation, oxidative stress, cellular metabolic dysfunction, and deregulation of transcriptional processes. In this review, we describe the possible role of sodium phenylbutyrate (NaPB) in the pathogenesis of Alzheimer's disease, hepatic encephalopathy, aging, Parkinson's disease, Huntington's disease, and amyotrophic lateral sclerosis; in addition, we describe the mechanism of action of NaPB and its beneficial effects that have been shown in various in vivo and in vitro studies to delay the evolution of any ND.

Markers associated with the development of osteoporosis in children with juvenile idiopathic arthritis

Background. The purpose of the study was to investigate the association between bone mineralization le­vel in children with juvenile idiopathic arthritis (JIA) and various exogenous and endogenous factors. Materials and ­me­thods. The study group consisted of 162 children diagnosed with JIA. Medical history, clinical features, and treatment of JIA were studied. Disease activity was evaluated using the Juvenile Arthritis Disease Activity Score (JADAS-27), health status — with the Childhood Health Assessment Questionnaire (CHAQ). Complete blood count with erythrocyte sedimentation rate, biochemical analysis (C-reactive protein, total and ionized calcium) were performed, and instrumental methods (ultrasound densitometry, X-ray and ultrasound examination of joints) were used. Serum levels of osteocalcin, 25-hydroxyvitamin D (25(OH)D), and parathyroid hormone were evaluated using an enzyme-linked immunosorbent assay on an ER500 analyzer (Sinnowa, China). Results. According to our study, osteoporosis was observed in 19 patients (11 girls and 8 boys) out of 162 children with JIA, accounting for 11.7 %. It was significantly more frequent in patients with polyarthritis (73.7 %) compared to those with oligoarthritis (26.3 %) (p &lt; 0.05). Conclusions. Osteoporosis can develop in children with JIA who do not receive systemic glucocorticoid therapy. The main markers associated with osteoporosis in children with JIA include non-infectious disease onset trigger, cervical joint involvement at disease onset, involvement of more than 3 joint groups at onset, gait disturbances, high JADAS-27 and CHAQ scores, signs of systemic inflammatory process, including elevated erythrocyte sedimentation rate.

Inflammation as a Neurobiological Mechanism of Cognitive Impairment in Psychological Stress.

The feeling of emotional tension, restlessness, pressure, and inability to relax is referred to as psychological stress. Although it is unclear how psychological stress affects neurobiological processes, several factors are thought to be involved, including central and peripheral neuroinflammation, structural degeneration in the prefrontal cortex and hippocampus, alterations in fear neurocircuitry, and neuroplasticity. Aside from data relating cognitive impairment to chronic low-grade inflammatory stress, there is growing evidence linking mental stress, oxidative stress, and systemic inflammation to the development of psychological disorders. After chronic and acute illnesses, insomnia, depression, anxiety, posttraumatic stress disorder, and cognitive impairment were reported. Cognitive impairment is exacerbated by systemic and central inflammatory processes. There is uncertainty about the potential mechanisms causing these symptoms, although they are likely complex, with systemic inflammation playing a significant role. Therefore, this review aims to investigate the role of inflammation in stress-induced cognitive impairment. Depicting the inflammatory mechanisms of cognitive impairment is critical for understanding and treating illnesses, such as chronic stress exposure and anxiety disorders.

Autoimmune Disease Pathogenesis Exacerbates Inflammation Following Myocardial Infarction in a Rodent Model of Systemic Lupus Erythematosus

Patients with systemic autoimmune diseases such as systemic lupus erythematosus (SLE) have an increased risk of suffering a myocardial infarction (MI), and are also more likely to die, develop heart failure, or suffer a second cardiac event than patients without an autoimmune disease. SLE primarily affects women and is characterized by autoreactive T and B lymphocytes that lead to widespread production of autoantibodies to a variety of nuclear and cytoplasmic antigens. Autoantibody-antigen immune complexes deposit in tissues and activate downstream inflammatory pathways leading to end-organ damage to tissues such as the heart, lungs, kidneys, and vasculature. However, the mechanisms whereby SLE disease may exacerbate MI and lead to poor outcomes in autoimmune patients is not well understood. The purpose of the present study was to test the hypothesis that SLE disease pathogenesis contributes to worsened outcomes after MI because of systemic inflammatory processes taking place. To test this hypothesis, saline (control, n=7) and pristane-treated (SLE, n=8) C57BL/6 mice were subjected to permanent coronary artery ligation (MI) and studied at 7 days post MI. Left ventricular (LV) function was examined at baseline (D0) and D7 using echocardiography (VEVO 3100). Control and SLE mice had similar LV parameters at baseline, but SLE mice had significantly more wall thinning in the infarct area (Control: 0.54±0.05 vs. SLE: 0.36±0.03 mm, p=0.005) as well as in the remote area (Control: 0.59±0.07 vs. SLE: 0.38±0.03 mm, p=0.01). SLE mice also displayed increased LV dilation (Control: 61.7±5.3 vs. SLE: 78.9±3.8 μL, p=0.02) at 7 days post MI. Ejection fraction was significantly lower in SLE mice as well (Control: 26.3±2.0% vs. 19.0±2.5%, p=0.045). We examined expression of inflammatory cytokines and collagen subunit genes in infarcted heart tissue using qPCR. SLE mice had increased expression of several inflammatory cytokines, including IL-6 and IL-18, while other cytokines such as IL-1β and TNF-α were not significantly different between the groups. In addition, SLE mice had decreased expression of the Col1a1, which encodes the alpha subunit of Type I Collagen, and Cd31, an endothelial cell marker, suggesting impairment of scar formation and angiogenesis post MI in SLE mice. Flow cytometric analyses of infiltrating LV immune cells showed increased total CD45+ cells in the infarcted area of SLE mice (Control: 10.6±1.2% vs. SLE: 13.8±0.6%, p=0.03), and a trend for an increase in CD45R+ B cells (Control: 7.5±1.1% vs. SLE: 12.5±2.1%, p=0.05). Taken together, these data indicate that SLE disease impacted recovery post MI, possibly due to increased B cell infiltration in the heart. Future studies will assess outcomes at later time points and also examine the progression of renal injury post MI. NIH/NHLBI R00 HL146888 and U54 HL169191 to Taylor NHLBI R01 HL166737 and AHA CDA856365 to Mouton NIGMS P20 GM104357 and P30 GM149404 to Department of Physiology and Biophysics. This is the full abstract presented at the American Physiology Summit 2024 meeting and is only available in HTML format. There are no additional versions or additional content available for this abstract. Physiology was not involved in the peer review process.

Immune Dysregulation in Endometriomas: Implications for Inflammation.

The most common manifestation of endometriosis, a condition characterized by the presence of endometrial-like tissue outside of the uterus, is the endometrioma, a cystic ovarian lesion. It is a commonly occurring condition associated with chronic pelvic pain exacerbated prior to and during menstruation, as well as infertility. The exact pathomechanisms of the endometrioma are still not fully understood. Emerging evidence suggests a pivotal role of immune dysregulation in the pathogenesis of endometriomas, primarily influencing both local and systemic inflammatory processes. Among the factors implicated in the creation of the inflammatory milieu associated with endometriomas, alterations in both serum and local levels of several cytokines stand out, including IL-6, IL-8, and IL-1β, along with abnormalities in the innate immune system. While numerous signaling pathways have been suggested to play a role in the inflammatory process linked to endometriomas, only NF-κB has been conclusively demonstrated to be involved. Additionally, increased oxidative stress, both resulting from and contributing to endometriomas, has been identified as a primary driver of both systemic and local inflammation associated with the condition. This article reviews the current understanding of immune dysfunctions in the endometrioma and their implications for inflammation.

Persistent neuroinflammation and functional deficits in a murine model of decompression sickness.

We hypothesized that early intra-central nervous system (CNS) responses in a murine model of decompression sickness (DCS) would be reflected by changes in the microparticles (MPs) that exit the brain via the glymphatic system, and due to systemic responses the MPs would cause inflammatory changes lasting for many days leading to functional neurological deficits. Elevations on the order of threefold of blood-borne inflammatory MPs, neutrophil activation, glymphatic flow, and neuroinflammation in cerebral cortex and hippocampus were found in mice at 12 days after exposure to 760 kPa of air for 2 h. Mice also exhibited a significant decline in memory and locomotor activity, as assessed by novel object recognition and rotarod testing. Similar inflammatory changes in blood, neuroinflammation, and functional impairments were initiated in naïve mice by injection of filamentous (F-) actin-positive MPs, but not F-actin-negative MPs, obtained from decompressed mice. We conclude that high pressure/decompression stress establishes a systemic inflammatory process that results in prolonged neuroinflammation and functional impairments in the mouse decompression model.NEW & NOTEWORTHY Elevated glymphatic flow due to astrocyte and microglial activation from high-pressure exposure triggers release of microparticles (MPs) to the circulation where neutrophil activation and production of filamentous (F)-actin expressing MPs result in a persistent feed-forward neuroinflammatory cycle and functional deficits lasting for at least 12 days.

The influence of chronic inflammation on the illnesscourse of bipolar disorder: A longitudinal study

IntroductionC-reactive protein (CRP) is a systemic inflammatory marker, which indicates systemic inflammatory processes It is involved in different inflammatory processes of the body and is a reliable marker for the general inflammatory state of the body. High sensitive CRP seems to play a key role as a state and trait marker of bipolar disorder (BD). In the current study, we tried to determine the long-term effect of CRP levels on clinical symptoms and illness course of bipolar disorder. MethodsFor the current study, we examined 106 patients with BD for a period of four years. Participants underwent a clinical screening for depressive and manic episodes with the Hamilton Depression Scale (HAMD) and the Young Mania Rating Score (YMRS) and a serological diagnostic for inflammatory parameters every six months, thus leading to 8 measurement times in total. Patients with the presence of severe medical or neurological comorbidities such as active cancer, chronic obstructive lung disease, rheumatoid arthritis, systemic lupus erythematosus, Alzheimer's disease, Parkinson's disease, Huntington's disease or multiple sclerosis and acute infections were not included in the study. ResultsIn our sample, 26% showed a mean hsCRP above 5 mg/dl. Those patients showed a significantly higher mean YMRS score than those with a mean hsCRP under 5 mg/dl during our observation period. Regarding HAMD there was no significant difference in hsCRP values. The existence of lithium treatment showed no significant influence on mean hsCRP levels between the start and endpoint. ConclusionIndividuals who were exposed to a higher level of inflammation over time suffered from more manic symptoms in this period. These findings underline the hypothesis that inflammatory processes have an accumulative influence on the illness course of BD, especially concerning manic symptoms and episodes.

Inflammation in Posttraumatic Stress Disorder: Dysregulation or Recalibration?

Despite ample experimental data indicating a role of inflammatory mediators in the behavioral and neurobiological manifestations elicited by exposure to physical and psychologic stressors, causative associations between systemic low-grade inflammation and central nervous system inflammatory processes in posttraumatic stress disorder (PTSD) patients remain largely conceptual. As in other stress-related disorders, pro-inflammatory activity may play an equivocal role in PTSD pathophysiology, one that renders indiscriminate employment of anti-inflammatory agents of questionable relevance. In fact, as several pieces of preclinical and clinical research convergingly suggest, timely and targeted potentiation rather than inhibition of inflammatory responses may actually be beneficial in patients who are characterized by suppressed microglia function in the face of systemic low-grade inflammation. The deleterious impact of chronic stress-associated inflammation on the systemic level may, thus, need to be held in context with the - often not readily apparent - adaptive payoffs of low-grade inflammation at the tissue level.

Cellular and Mitochondrial Pathways Contribute to SGLT2 Inhibitors-mediated Tissue Protection: Experimental and Clinical Data.

In metabolic syndrome and diabetes, compromised mitochondrial function emerges as a critical driver of cardiovascular disease, fueling its development and persistence, culminating in cardiac remodeling and adverse events. In this context, angiotensin II - the main interlocutor of the renin-angiotensin-aldosterone system - promotes local and systemic oxidative inflammatory processes. To highlight, the low activity/expression of proteins called sirtuins negatively participates in these processes, allowing more significant oxidative imbalance, which impacts cellular and tissue responses, causing tissue damage, inflammation, and cardiac and vascular remodeling. The reduction in energy production of mitochondria has been widely described as a significant element in all types of metabolic disorders. Additionally, high sirtuin levels and AMPK signaling stimulate hypoxia- inducible factor 1 beta and promote ketonemia. Consequently, enhanced autophagy and mitophagy advance through cardiac cells, sweeping away debris and silencing the orchestra of oxidative stress and inflammation, ultimately protecting vulnerable tissue from damage. To highlight and of particular interest, SGLT2 inhibitors (SGLT2i) profoundly influence all these mechanisms. Randomized clinical trials have evidenced a compelling picture of SGLT2i emerging as game-changers, wielding their power to demonstrably improve cardiac function and slash the rates of cardiovascular and renal events. Furthermore, driven by recent evidence, SGLT2i emerge as cellular supermolecules, exerting their beneficial actions to increase mitochondrial efficiency, alleviate oxidative stress, and curb severe inflammation. Its actions strengthen tissues and create a resilient defense against disease. In conclusion, like a treasure chest brimming with untold riches, the influence of SGLT2i on mitochondrial function holds untold potential for cardiovascular health. Unlocking these secrets, like a map guiding adventurers to hidden riches, promises to pave the way for even more potent therapeutic strategies.

Effects of Helicobacter pylori infection on the components of metabolic syndrome. Review

The article emphasizes the ability of Helicobacter pylori (H. pylori) to influence metabolic processes and considers possible mechanisms of such influence. The data presented that H. pylori infection increases the frequency of metabolic syndrome and its components. It is emphasized that systemic chronic inflammatory processes (one of the main links in the pathogenesis of metabolic‑associated diseases) can be initiated by H. pylori due to the activation of «classical» mechanisms inherent in metabolic diseases: activation of pro‑inflammatory cytokines (tumor necrosis factor‑α, interleukins‑1, ‑6,) and adipocyte hormones. This is primarily due to the ability of H. pylori to produce cytotoxins (Cag/Vac A) and the presence of lipopolysaccharide in its own cell wall (endotoxin), which can both directly and indirectly induce a pro‑inflammatory response, including a systemic one. In support of this, the data showing that H. pylori eradication prevents repeated stenosis of the coronary arteries after stent placement, leads to an improvement in the course of arterial hypertension, and a significant decrease in the levels of C‑reactive protein. In addition, the effect of H. pylori on pro‑inflammatory cytokines and adipocyte hormones can contribute to the formation of an abnormal proatherogenic lipid profile. This is confirmed by data on the decrease in the levels of total cholesterol, triglycerides, low‑density lipoprotein cholesterol against the background of an increase in the concentration of high‑density lipoprotein cholesterol after successful eradication of H pylori. Also noted that H. pylori infection is a potential contributing factor to insulin resistance and chronic hyperglycemia, and this is also largely related to the ability of Helicobacter pylori to produce cytotoxins. Some investigators haven’t established the relationship between H. pylori and glycosylated hemoglobin levels, that can be explained by the use of serological methods for H. pylori diagnosis. The differences in research results may be associated with methodological errors, therefore, further research is needed in this direction, which will contribute to the development of preventive and therapeutic strategies.&#x0D;

Elevated tumor necrosis factor alpha and vascular endothelial growth factor in intermediate age-related macular degeneration and geographic atrophy.

Tumor necrosis factor alpha (TNF-α) is an inflammatory cytokine implicated in pathological changes to the retinal pigment epithelium that are similar to changes in geographic atrophy (GA), an advanced form of age related macular degeneration (AMD). TNF-α also modulates expression of other cytokines including vascular endothelial growth factor (VEGF), leading to choroidal atrophy in models of AMD. The purpose of this study was to investigate systemic TNF-α and VEGF in patients with GA and intermediate AMD (iAMD) compared to controls without AMD. We examined plasma levels of TNF-α and VEGF in patients with GA, iAMD, and controls without AMD from the University of Colorado AMD registry (2014 to 2021). Cases and controls were characterized by multimodal imaging. TNF-α and VEGF were measured via multiplex immunoassay and data were analyzed using a non-parametric rank based linear regression model fit to plasma biomarkers. There were 97 GA, 199 iAMD patients and 139 controls. TNF-α was significantly increased in GA (Median:9.9pg/ml, IQR:7.3-11.8) compared to iAMD (Median:7.4, IQR:5.3-9.1) and in both GA and iAMD compared to controls (Median:6.4, IQR:5.3-7.8), p<0.01 for all comparisons. VEGF was significantly increased in iAMD (Median:8.9, IQR:4.8-14.3) compared to controls (Median:7.7, IQR:4.6-11.1), p<0.01. There was a significant positive correlation between TNF-α and VEGF in GA (0.46, p<0.01), and iAMD (0.20, p=0.01) with no significant interaction between TNF-α and VEGF in any group. These findings suggest TNF-α and VEGF may contribute to systemic inflammatory processes associated with iAMD and GA. TNF-α and VEGF may function as systemic biomarkers for disease development.

Pasteurella multocida activates Rassf1-Hippo-Yap pathway to induce pulmonary epithelial apoptosis

Pasteurella multocida is an opportunistic zoonotic pathogen that primarily causes fatal respiratory diseases, such as pneumonia and respiratory syndromes. However, the precise mechanistic understanding of how P. multocida disrupts the epithelial barrier in mammalian lung remains largely unknown. In this study, using unbiased RNA-seq analysis, we found that the evolutionarily conserved Hippo-Yap pathway was dysregulated after P. multocida infection. Given the complexity of P. multocida infection associated with lung injury and systemic inflammatory processes, we employed a combination of cell culture models, mouse models, and rabbit models to investigate the dynamics of the Hippo-Yap pathway during P. multocida infection. Our findings reveal that P. multocida infection activates the Hippo-Yap pathway both in vitro and in vivo, by upregulating the upstream factors p-Mst1/2, p-Lats1, and p-Yap, and downregulating the downstream effectors Birc5, Cyr61, and Slug. Conversely, pharmacological inhibition of the Hippo pathway by XMU-MP-1 significantly rescued pulmonary epithelial cell apoptosis in vitro and reduced lung injury, systemic inflammation, and mouse mortality in vivo. Mechanistic studies revealed that P. multocida induced up-regulation of Rassf1 expression, and Rassf1 enhanced Hippo-Yap pathway through phosphorylation. Accordingly, in vitro knockdown of Rassf1 significantly enhanced Yap activity and expression of Yap downstream factors and reduced apoptosis during P. multocida infection. P. multocida-infected rabbit samples also showed overexpression of Rassf1, p-Lats1, and p-Yap, suggesting that P. multocida activates the Rassf1-Hippo-Yap pathway. These results elucidate the pathogenic role of the Rassf1-Hippo-Yap pathway in P. multocida infection and suggest that this pathway has the potential to be a drug target for the treatment of pasteurellosis.

Cardiovascular risk in patients with inflammatory arthritis

Rheumatoid and other inflammatory arthritis (ankylosing spondylitis and psoriatic arthritis) have a high risk of cardiovascular disease (CVD). It is caused by the accelerated development of atherosclerosis associated with a chronic systemic inflammatory process. Nevertheless, traditional CVD risk factors (hypertension, smoking, dyslipidemia) are also important for patients with inflammatory arthritis. The greatest amount of data has been accumulated regarding the relationship between CVD and rheumatoid arthritis. Due to the difficulties in diagnosing coronary heart disease and other CVD, it is of great importance to identify patients at high and very high risk. The use of scales for assessing the total cardiovascular risk SCORE/SCORE 2 with a coefficient of 1.5 allows to identify patients who need measures to reduce their high risk of CVD. Control of the of the disease activity, lifestyle modification, therapy with statins and antihypertensive drugs in accordance with current guidelines, caution when prescribing non-steroidal anti-inflammatory drugs and minimizing the dose of glucocorticoids are the main components of the strategy for reducing the risk of CVD in patients with inflammatory arthritis.