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Simple Summary: This research studied how three types of proteins, called interleukins (namely 8, 17A and 33), are present in the blood of healthy people and people with colon cancer. Colon cancer is a disease that affects the large intestine. The paper looked at 82 people, 42 of whom had colon cancer and 40 of whom did not. The researchers divided the cancer patients into four groups based on how severe their cancer was. The study measured the amount of interleukins in the blood of each person using a special test. The paper analyzed the results of the test, considering the age, gender, and cancer stage of each person. The results showed that younger people, and those with less severe cancer had more interleukins in their blood. The paper also found that two of the interleukins (8 and 17A) were higher in the cancer group, while one of them (33) was higher in the healthy group. The study also found that the interleukins were related to each other in both groups. This research concluded that the interleukins might help detect colon cancer and predict how it will progress. This paper could help improve the diagnosis and treatment of colon cancer. This research investigated the serum levels of three interleukins (IL8, IL17A, and IL33) and the possible relationships between them in healthy people and colon cancer patients at different stages. This study involved 82 participants, 42 of whom had colon cancer and 40 were healthy individuals. The cancer patients were classified into four groups according to the TNM staging classification of colon and rectal cancer. Serum levels of the interleukins were measured by the ELISA test. The data were analyzed statistically to compare the demographic characteristics, the interleukin levels across cancer stages, and the correlation between interleukins in both groups. The results showed that women had more early-stage colon cancer diagnoses, while men had more advanced-stage cancer diagnoses. Stage two colon cancer was more common in older people. Younger people, men, and those with early-stage colon cancer had higher levels of interleukins. The levels of IL8 and IL17A were higher in the cancer group, while the level of IL33 was higher in the healthy group. There was a strong correlation between IL8 and IL17A levels in both groups (p = 0.001). IL17A influenced the level of IL33 in the cancer group (p = 0.007). This study suggested that cytokine variation profiles could be useful for detecting colon cancer and predicting its outcome. [ABSTRACT FROM AUTHOR]

Introduction: The management of Crohn's disease (CD) in the Middle East, like in other parts of the world, is rapidly evolving with the introduction of novel advanced medical and biological therapies. In the United Arab Emirates (UAE), several biological therapies are used to achieve remission in severe and resistant cases of CD. We carried out a literature search to analyze the effectiveness and safety of biologic treatments currently licensed in the UAE. Methods: We searched the PubMed, Embase and Cochrane library databases from inception to January 2020 to identify relevant studies. Search terms were generated using established treatment guidelines for CD. We also manually searched the bibliographies of relevant literature to obtain additional papers. Results: Biologic and small molecule agents for CD include four core drug classes: anti-tumor necrosis factor-α agents (TNF-α), integrin receptor antagonists, Janus kinase (JAK) inhibitors and IL-12/IL-23 antagonists. All drug classes showed good efficacy and safety in managing patients with CD. Some drug classes had distinguishable side effect profiles. This included an increased lymphoma and tuberculous risk for TNF-α and integrin receptor antagonists. Many trials supported the effectiveness of these licensed drugs. Biologic agent intolerance was common; one-third of patients receiving TNF-α treatment will develop intolerance to that specific drug. Conclusions: Advanced medical therapies licensed in the UAE have proven to be safe and efficacious. Additional research is required to evaluate the safety and efficacy of newer biologics and biosimilars. [ABSTRACT FROM AUTHOR]

Simple Summary: Immunotherapeutic synergy represents the cornerstone of the treatment intended for patients with clear-cell renal-cell carcinoma. In most cases, this type of cancer manifests its first symptoms at an advanced stage, thus compromising the use of local therapies such as surgery. This paper aims to describe immune checkpoint proteins, known to suppress an anti-cancer immune response, as well as their inhibitors. Interleukin-2, a cytokine used as a therapeutic option and implicated in the activation of the immune cells, is also discussed. This review further emphasizes the role of the immunotherapeutic combination, not only as an alternative to current treatments devised to counteract the progression and metastasis of ccRCC but also as a valid solution aimed at alleviating the limitations resulting from immune-based monotherapies. Clear-cell Renal-Cell Carcinoma (ccRCC) is the most common type of renal-cell carcinoma (RCC). In many cases, RCC patients manifest the first symptoms during the advanced stage of the disease. For this reason, immunotherapy appears to be one of the dominant treatments to achieve a resolution. In this review, we focus on the presentation of the main immune checkpoint proteins that act as negative regulators of immune responses, such as PD-1, CTLA-4, LAG-3, TIGIT, and TIM-3, and their respective inhibitors. Interleukin-2, another potential component of the treatment of ccRCC patients, has also been covered. The synergy between several immunotherapies is one of the main aspects that unites the conclusions of research in recent years. To date, the combination of several immunotherapies enhances the efficacy of a monotherapy, which often manifests important limitations. Immunotherapy aimed at restoring the anti-cancer immune response in ccRCC, involved in the recognition and elimination of cancer cells, may also be a valid solution for many other types of immunogenic tumors that are diagnosed in the final stages. [ABSTRACT FROM AUTHOR]

Atopic dermatitis (AD) is an inflammatory skin condition that frequently develops before the onset of allergic rhinitis or asthma. More than 10% of children are affected by this serious skin condition, which is painful for the sufferers. Recent research has connected the environment, genetics, the skin barrier, drugs, psychological factors, and the immune system to the onset and severity of AD. The causes and consequences of AD and its cellular and molecular origins are reviewed in this paper. The exploration of interleukins and their influence on the immunological pathway in AD has been facilitated by using relevant biomarkers in clinical trials. This approach enables the identification of novel therapeutic modalities, fostering the potential for targeted translational research within the realm of personalized medicine. This review focuses on AD's pathophysiology and the ever-changing therapeutic landscape. Beyond the plethora of biologic medications in various stages of approval or development, a range of non-biologic targeted therapies, specifically small molecules, have emerged. These include Janus kinase (JAK) inhibitors like Baricitinib, Upadacitinib, and Abrocitinib, thus expanding the spectrum of therapeutic options. This review also addresses the latest clinical efficacy data and elucidates the scientific rationale behind each targeted treatment for atopic dermatitis. [ABSTRACT FROM AUTHOR]

Background: Ulcerative colitis (UC) is a relapsing–remitting inflammatory condition that has an increasing incidence across the world, including in the Middle East. Biological monoclonal antibody drugs (biologics) have been shown to be advantageous in treating UC. We undertook a review of the currently available biological and small-molecule therapies, with a particular emphasis on those currently licensed in the United Arab Emirates (UAE). Methods: We conducted a literature search for studies on biological therapies using the PubMed, MEDLINE, and Embase databases using a list of keywords that were generated following referral to existing treatment guidelines for UC. Papers looking at biological and small-molecule treatments for UC in adult populations were included. Pediatric, pregnancy, and cost-effectiveness studies were excluded. Results and Discussion: There are currently three classes of biologics (anti-tumor necrosis factors (anti-TNFs), anti-integrins, and anti-interleukins) and one class of small-molecule therapy (Janus kinase (JAK) inhibitor) licensed for UC treatment in the UAE. Within the anti-TNF class, three medications have been approved: infliximab, adalimumab, and golimumab. For JAK inhibitors, there are two: tofacitinib and upadacitinib. There is only one licensed medication in the remaining classes: vedolizumab (anti-integrin) and ustekinumab (anti-interleukin). The length of studies varied from 6–8 weeks for induction studies and 52 weeks for maintenance studies. The studies demonstrated increased efficacy in these medications compared to placebos when clinical response, clinical remission, and other secondary measures such as mucosal healing were assessed following the induction and maintenance phases. Biosimilars of infliximab and adalimumab are also available for treating UC, and their safety and efficacy were compared to their biologic originators. Conclusions: The introduction of biologics has been proven to be beneficial for the treatment of UC. This review summarizes the efficacy and safety of each biological class in the treatment of the disease; however, biological drug registries and further studies are required to offer more insight into the comparative efficacy and safety of these agents. [ABSTRACT FROM AUTHOR]

The paper reviews some of the mechanisms implicated in hepatotoxicity, which is induced by an excess of lipids. The paper spans a wide variety of topics: from the molecular mechanisms of excess lipids, to the therapy of hyperlipidemia, to the hepatotoxicity of lipid-lowering drugs. NAFLD is currently the leading cause of chronic liver disease in Western countries; the molecular mechanisms leading to NAFLD are only partially understood and there are no effective therapeutic interventions. The prevalence of liver disease is constantly increasing in industrialized countries due to a number of lifestyle variables, including excessive caloric intake, unbalanced diet, lack of physical activity, and abuse of hepatotoxic medicines. Considering the important functions of cell death and inflammation in the etiology of the majority, if not all, liver diseases, one efficient therapeutic treatment may include the administration of hepatoprotective and anti-inflammatory drugs, either alone or in combination. Clinical trials are currently being conducted in cohorts of patients with different liver diseases in order to explore this theory. [ABSTRACT FROM AUTHOR]

Simple Summary: Large intestinal cancer is one of the most common lifestyle-related types of cancer. However, the exact mechanism in the relation between adipose tissue, systemic inflammation and intestinal cancer remains unknown. Furthermore, there are many hypotheses regarding the pathways in which alcohol consumption, smoking, malnutrition and physical inactivity cause low-grade systemic inflammation. In this paper, we discuss the relation of lifestyle with inflammation, in terms of inflammatory markers at the time of diagnosis in intestinal cancer patients. Our findings suggest that an overall unhealthier lifestyle and a higher risk of malnutrition at the time of diagnosis were associated with elevated levels of inflammatory markers. These findings could contribute to formulating lifestyle advice in the future. Colorectal cancer is one of the most common lifestyle-related types of cancer. The exact pathophysiologic mechanism in the relation between (visceral) adipose tissue, systemic inflammation and colorectal cancer remains unknown. This study aimed to assess the association of lifestyle with markers of systemic inflammation at the time of diagnosis in stage I-III colorectal cancer patients. Patients (n = 298) with stage I-III colorectal cancer from three Dutch hospitals were included at diagnosis. Several lifestyle-related variables (MUST nutritional status score, WCRF/AICR healthy lifestyle score, active smoking, alcohol consumption and BMI) and inflammatory markers (plasma levels of IL-6, IL-8, IL-10, TNFα and 'high sensitive' hsCRP) were measured at the time of diagnosis. Confounder-adjusted multivariable linear regression models were used to analyse how the lifestyle variables were associated with the inflammatory markers. Statistically significant associations were found between a better WCRF/AICR lifestyle score and lower levels of IL-6 and hsCRP. A medium and high risk of malnutrition according to the MUST score was associated with elevated levels of both IL-8 and hsCRP. An overall unhealthier lifestyle indicated by a lower WCRF/AICR lifestyle score and a higher risk of malnutrition according to the MUST score at the time of diagnosis was associated with elevated levels of inflammatory markers. These findings can contribute to formulating lifestyle advice to improve treatment outcomes and prognosis in patients having CRC in the future. [ABSTRACT FROM AUTHOR]

Civilization diseases are defined as non-communicable diseases that affect a large part of the population. Examples of such diseases are depression and cardiovascular disease. Importantly, the World Health Organization warns against an increase in both of these. This narrative review aims to summarize the available information on measurable risk factors for CVD and depression based on the existing literature. The paper reviews the epidemiology and main risk factors for the coexistence of depression and cardiovascular disease. The authors emphasize that there is evidence of a link between depression and cardiovascular disease. Here, we highlight common risk factors for depression and cardiovascular disease, including obesity, diabetes, and physical inactivity, as well as the importance of the prevention and treatment of CVD in preventing depression and other mental disorders. Conversely, effective treatment of CVD can also help prevent depression and improve mental health outcomes. It seems advisable to introduce screening tests for depression in patients treated for cardiac reasons. Importantly, in patients treated for mood disorders, it is worth controlling CVD risk factors, for example, by checking blood pressure and pulse during routine visits. It is also worth paying attention to the mental condition of patients with CVD. This study underlines the importance of interdisciplinary co-operation. [ABSTRACT FROM AUTHOR]

Simple Summary: In this review paper, we explore the role of chronic inflammation in the pathogenesis of prostatic diseases, such as chronic prostatitis, benign prostatic hyperplasia (BPH), and prostate cancer. Chronic inflammation is a significant risk factor for these diseases, but the molecular mechanisms behind it are not yet fully understood. Previous attempts to investigate, link, and target inflammatory signaling molecules in men with these conditions have been clinically ambiguous and inconclusive. As a result, we proposed a paradigm shift in which less-explored molecules in the inflammatory signaling cascade are investigated as possible therapeutic targets for prostate diseases. In addition, we comprehensively discuss how aberrant signaling of these molecules may cause prostate cancer stemness, neuroendocrine differentiation, castration resistance, metabolic reprogramming, and immunosuppression. In conclusion, we forecast that targeting the interleukin-1 receptor-associated kinases (IRAKs) signaling pathway may provide a far more effective therapeutic or prophylactic strategy for the management of chronic inflammation-driven prostatic diseases. Chronic inflammation is now recognized as one of the major risk factors and molecular hallmarks of chronic prostatitis, benign prostatic hyperplasia (BPH), and prostate tumorigenesis. However, the molecular mechanisms by which chronic inflammation signaling contributes to the pathogenesis of these prostate diseases are poorly understood. Previous efforts to therapeutically target the upstream (e.g., TLRs and IL1-Rs) and downstream (e.g., NF-κB subunits and cytokines) inflammatory signaling molecules in people with these conditions have been clinically ambiguous and unsatisfactory, hence fostering the recent paradigm shift towards unraveling and understanding the functional roles and clinical significance of the novel and relatively underexplored inflammatory molecules and pathways that could become potential therapeutic targets in managing prostatic diseases. In this review article, we exclusively discuss the causal and molecular drivers of prostatitis, BPH, and prostate tumorigenesis, as well as the potential impacts of microbiome dysbiosis and chronic inflammation in promoting prostate pathologies. We specifically focus on the importance of some of the underexplored druggable inflammatory molecules, by discussing how their aberrant signaling could promote prostate cancer (PCa) stemness, neuroendocrine differentiation, castration resistance, metabolic reprogramming, and immunosuppression. The potential contribution of the IL1R-TLR-IRAK-NF-κBs signaling molecules and NLR/inflammasomes in prostate pathologies, as well as the prospective benefits of selectively targeting the midstream molecules in the various inflammatory cascades, are also discussed. Though this review concentrates more on PCa, we envision that the information could be applied to other prostate diseases. In conclusion, we have underlined the molecular mechanisms and signaling pathways that may need to be targeted and/or further investigated to better understand the association between chronic inflammation and prostate diseases. [ABSTRACT FROM AUTHOR]

Since its emergence, coronavirus disease 2019 (COVID-19) has affected the entire world and all commerce and industries, including healthcare systems. COVID-19 adversely affects cancer patients because they are immunocompromised. Increased COVID-19 infection and shortage of medical supplies, beds and healthcare workers in hospitals affect cancer care. This paper includes a description of the existing research that shows the impact of COVID-19 on the management of cancer patients. Aged people with various chronic conditions such as cancer and comorbidities face more challenges as they have a greater risk of disease severity. COVID-19 has affected care delivery, including patient management, and has been responsible for increased mortality among cancer patients. Cancer patients with severe symptoms require regular therapies and treatment; therefore, they have a higher risk of exposure. Due to the risk of transmission, various steps were taken to combat this disease; however, they have affected the existing operational efficiency. Herein, we present the changing priorities during COVID-19, which also affected cancer care, including delayed diagnosis, treatment, and surgeries. [ABSTRACT FROM AUTHOR]

Simple Summary: Colorectal cancer (CRC) cells contain elevated levels of Stat3 and Smad7, two proteins involved in the growth and survival of neoplastic cells. This study was aimed at examining whether Smad7 positively controls the expression of Stat3 in CRC cells. By employing antisense technology, which specifically inhibits Smad7 expression in selected cells, we hereby show that the reduction of Smad7 in CRC cells is paralleled by the marked suppression of the levels of Stat3 and of Stat3-related genes. Finally, we provide evidence that in human CRC tissue samples, there is a positive correlation between Smad7 expression and Stat3 content. Overall, these findings delineate a novel positive feedback loop that sustains CRC cell behavior and suggest that Smad7 is a target for therapeutic intervention in patients with such a disease. Colorectal cancer (CRC) cells contain elevated levels of active signal transducer and the activator of transcription (Stat)-3, which exerts proliferative and anti-apoptotic effects. Various molecules produced in the CRC tissue can activate Stat3, but the mechanisms that amplify such an activation are yet to be determined. In this paper, we assessed whether Smad7, an inhibitor of Transforiming Growth Factor (TGF)-β1 activity, sustains Stat3 expression/activation in CRC cells. Both Smad7 and phosphorylated (p)/activated-Stat3 were more expressed in the tumoral areas of CRC patients, compared to the normal adjacent colonic mucosa of the same patients, and were co-localized in primary CRC cells and CRC cell lines. The knockdown of Smad7 with a Smad7 antisense oligonucleotide (AS) reduced p-Stat3 in both unstimulated and interleukin (IL)-6- and IL-22-stimulated DLD-1 and HCT116 cells. Consistently, reduced levels of BCL-xL and survivin, two downstream signaling targets of Stat3 activation, were seen in Smad7 AS-treated cells. An analysis of the mechanisms underlying Smad7 AS-induced Stat3 inactivation revealed that Smad7 AS reduced Stat3 RNA and protein expression. A chromatin immunoprecipitation assay showed the direct regulatory effect of Smad7 on the Stat3 promoter. RNA-sequencing data from the Tumor, Normal and Metastatic (TNM) plot database showed a positive correlation between Smad7 and Stat3 in 1450 CRC samples. To our knowledge, this is the first evidence supporting the theory that Smad7 positively regulates Stat3 function in CRC. [ABSTRACT FROM AUTHOR]

Simple Summary: Bone metastasis in gastric cancer (GC-BM) has received little attention because of its rarity, but the increased pain and shortened survival of patients due to the bone destruction and skeletal-related events (SREs) caused by tumors cannot be ignored. Immune cells and molecules such as RANK-L and GFs in complicated bone microenvironments create suitable conditions for tumor cells to proliferate and break the balance of bone circulation, which leads to osteolysis and osteogenesis. Bone radionuclide scans now are the most sensitive examination for diagnosing bone tumors, and bone-related alkaline phosphatase (ALP) also shows a certain significance in the diagnosis of bone tumors. Combined application of chemotherapeutic drugs, targeted drugs, and immune drugs are the main treatments of GC-BM. This review paper intends to discuss the clinical status of GC-BM, as well as its possible molecular pathogenesis pathways and therapeutic options. Gastric cancer (GC) is one of the most malignant neoplasms worldwide, accounting for about 770,000 deaths in 2020. The incidence of gastric cancer bone metastasis (GC-BM) is low, about 0.9–13.4%, and GC patients develop GC-BM because of a suitable bone microenvironment. Osteoblasts, osteoclasts, and tumor cells interact with each other, secreting cytokines such as PTHrP, RANK-L, IL-6, and other growth factors that disrupt the normal bone balance and promote tumor growth. The functions and numbers of immune cells in the bone microenvironment are continuously inhibited, resulting in bone balance disorder due to the cytokines released from destroyed bone and growing tumor cells. Patients with GC-BM are generally younger than 65 years old and they often present with a later stage of the disease, as well as more aggressive tumors. They usually have shorter overall survival (OS) because of the occurrence of skeletal-related events (SREs) and undetected bone destruction due to the untimely bone inspection. Current treatments of GC-BM focus mainly on gastric cancer and SRE-related treatment. This article reviews the clinical features, possible molecular pathogeneses, and the most commonly used diagnostic methods and treatments of bone metastasis in gastric cancer. [ABSTRACT FROM AUTHOR]

Psoriasis is an inflammatory and auto-immune skin-disease characterized by uncontrolled keratinocyte proliferation. Its pathogenesis is not still fully understood; however, an aberrant and excessive inflammatory and immune response can contribute to its progression. Recently, more attention has been given to the anti-inflammatory and immunomodulators effects of melatonin in inflammatory diseases. The aim of this paper was to investigate the effect of melatonin on psoriatic phenotype and also in S. aureus infection-associated psoriasis, with an in vitro model using Skinethic Reconstructed Human Epidermis (RHE). An in vitro model was constructed using the RHE, a three-dimensional-model obtained from human primary-keratinocytes. RHE-cells were exposed to a mix of pro-inflammatory cytokines, to induce a psoriatic phenotype; cells were also infected with S. aureus to aggravate psoriasis disease, and then were treated with melatonin at the concentrations of 1 nM, 10 nM, and 50 nM. Our results demonstrated that melatonin at higher concentrations significantly reduced histological damage, compared to the cytokine and S. aureus groups. Additionally, the treatment with melatonin restored tight-junction expression and reduced pro-inflammatory cytokine levels, such as interleukin-1β and interleukin-12. Our results suggest that melatonin could be considered a promising strategy for psoriasis-like skin inflammation, as well as complications of psoriasis, such as S. aureus infection. [ABSTRACT FROM AUTHOR]

Several allergic and immunologic diseases including asthma, food allergy (FA), chronic spontaneous urticaria (CSU), atopic dermatitis (AD), systemic lupus erythematosus (SLE), systemic sclerosis (SSc), rheumatoid arthritis (RA), and Behçet's disease (BD) are characterized by the involvement of Th2 immunity. Several mediators lead to immunoglobulin (Ig)E production, thus including key cytokines such as interleukin (IL)-4, IL-5, and IL-13. Among them, IL-31 and IL-33 have been recently studied as novel biomarkers and future therapeutic targets for allergic and immunological disorders. IL-31 is a proinflammatory cytokine-it regulates cell proliferation and is involved in tissue remodeling. IL-33, acting through its receptor suppression of tumorigenity (ST2L), is an alarmin cytokine from the IL-1 family, whose expression is mediated by tissue damage. The latter has a pleiotropic effect, as it may modulate specific and innate immune cells functions. To date, several researchers have investigated the involvement of IL-31 and IL-33 in several allergic and immune-mediated diseases. Further studies are needed to understand the future applications of these molecules as novel therapeutic agents. This paper aims to give the readers a complete and updated review of IL-31 and IL-33 involvement among the most common autoimmune and allergic disorders.

Background/Objectives: The present study examined the effect of 12-week combined exercise training in normobaric hypoxia on arterial stiffness, inflammatory biomarkers, and red blood cell (RBC) hemorheological function in 24 obese older women (mean age: 67.96 ± 0.96 years). Methods: Subjects were randomly divided into two groups (normoxia (NMX; n = 12) and hypoxia (HPX; n = 12)). Both groups performed aerobic and resistance exercise training programs three times per week for 12 weeks, and the HPX group performed exercise programs in hypoxic environment chambers during the intervention period. Body composition was estimated using bioelectrical impedance analysis equipment. Arterial stiffness was measured using an automatic waveform analyzer. Biomarkers of inflammation and oxygen transport (tumor necrosis factor alpha, interleukin 6 (IL-6), erythropoietin (EPO), and vascular endothelial growth factor (VEGF)), and RBC hemorheological parameters (RBC deformability and aggregation) were analyzed. Results: All variables showed significantly more beneficial changes in the HPX group than in the NMX group during the intervention. The combined exercise training in normobaric hypoxia significantly reduced blood pressure (systolic blood pressure: p < 0.001, diastolic blood pressure: p < 0.001, mean arterial pressure: p < 0.001, pulse pressure: p < 0.05) and brachial–ankle pulse wave velocity (p < 0.001). IL-6 was significantly lower in the HPX group than in the NMX group post-test (p < 0.001). Also, EPO (p < 0.01) and VEGF (p < 0.01) were significantly higher in the HPX group than in the NMX group post-test. Both groups showed significantly improved RBC deformability (RBC EI_3Pa) (p < 0.001) and aggregation (RBC AI_3Pa) (p < 0.001). Conclusions: The present study suggests that combined exercise training in normobaric hypoxia can improve inflammatory biomarkers and RBC hemorheological parameters in obese older women and may help prevent cardiovascular diseases. [ABSTRACT FROM AUTHOR]

Pediatric acute-onset neuropsychiatric syndrome (PANS) and Pediatric Autoimmune Neuropsychiatric Disorders Associated with Streptococcal Infections (PANDAS), represent an overlapping group of disorders which is characterized by acute-onset obsessive compulsive disorders, eating restriction, tics, cognitive and behavioral deterioration which typically follows a relapsing-remitting course but some patients have a primary or secondary persistent progress. This condition is likely caused by heterogeneous inflammatory mechanisms (autoantibodies, complement activation, pro-inflammatory cytokine production) involving the basal ganglia as evidenced by imaging studies (patients vs. controls), sleep studies that found movements and/or atonia during REM sleep, and neurological soft signs that go along with basal ganglia dysfunction. The condition causes significant psychiatric and behavioral symptoms, caregiver burden and sleep abnormalities. Autoantibodies resulting from molecular mimicry of infectious agents (namely group A Streptococcus) and neuronal autoantigens that map to the basal ganglia play also a subtle role. This narrative review aims to describe the key immunological features documented thus far and that likely play a role in the pathogenesis and clinical manifestations of this disorder. [ABSTRACT FROM AUTHOR]

Humans are exposed to significant amounts of blue light from computers and smartphones. However, the effects of blue light on ulcerative colitis remain unclear. In this study, we assessed blue-light-irradiation-induced alterations in colonic symptoms using a dextran sodium sulfate (DSS)-induced ulcerative colitis model mice. Both male and female institute of cancer research (ICR) mice were administered DSS (5%) ad libitum for 5 days while irradiated with 40 kJ/m2 blue light daily. Additionally, tranexamic acid (TA) was administered daily throughout the study. Male mice treated with DSS/blue light exhibited exacerbated colitis compared to those treated with DSS alone. In contrast, female mice treated with DSS/blue light exhibited enhanced symptoms compared to those treated with DSS alone. Additionally, in male mice exposed to blue light, the clock/brain and muscle Arndt-like 1 (Bma1)/noradrenaline/macrophage or beta2-adrenergic receptor (β2-AR) pathways were activated. In female mice, the Bmal1/acetylcholine/macrophage/nicotinic acetylcholine receptor alpha 7 (α7nAChR) pathway was activated. These findings highlight sex differences in the effects of blue light on DSS-induced ulcerative colitis. Moreover, the worsening of symptoms in males was ameliorated through TA administration. [ABSTRACT FROM AUTHOR]

Rheumatoid arthritis (RA) is an autoimmune disease primarily affecting the joints and requires various treatments, including medication, injection, and physiotherapy. Wu tou decoction (WTD) is a traditional Chinese medicine prescribed for RA, with several articles documenting its effectiveness in RA treatment. This systematic review and meta-analysis aimed to evaluate the efficacy and safety of WTD for RA. We searched for randomized controlled trials (RCTs) comparing WTD with conventional treatments (including medication, injection, and physiotherapy) from its inception to May 2024. Primary outcomes were disease activity scores, including effective rate, tender joint count, and morning stiffness. Secondary outcomes comprised blood test results (erythrocyte sedimentation rate, C-reactive protein, and rheumatoid factor) and adverse events. Nineteen RCTs involving 1794 patients were included. Statistically, WTD demonstrated better improvement than conventional treatments (18 medications and 1 injection) across the effective rate, joint scale, and blood tests, regardless of the treatment type (monotherapy or combination therapy). Adverse events were reported in 11 studies, with no statistical differences observed between them. The numerical results showed that WTD may offer potential benefits for managing RA. However, the significant discrepancy between clinical practice and the low quality of the RCTs remains a limitation. Therefore, further well-designed studies with larger patient cohorts are needed to draw definitive conclusions. [ABSTRACT FROM AUTHOR]

Breast cancer is the most diagnosed cancer in the world, and it is the primary cause of cancer death for women. The risk of breast cancer is increased by endogenous factors like hormones and exogenous factors like radiation exposure that causes damage to the mammary epithelial cells leading to an inflammatory response. Chronic inflammation creates a microenvironment composed of, among other factors, chemokines, and interleukins, which promote cancer. The gene expression of the interleukin 1 receptor type 1, the interleukin 1 receptor antagonist, the Interleukin 1 Receptor Accessory Protein, the interleukin 6 cytokine family signal transducer, the C-X-C motif chemokine ligand 3, the C-X-C motif chemokine ligand 5, and the C-X-C motif chemokine ligand 6 were analyzed in an estrogen and radiation experimental breast cancer model. Furthermore, the expression of these genes was correlated with immune cell infiltration, estrogen receptor expression, and their clinical relevance in breast cancer patients based on data provided by The Cancer Genome Atlas database online. Results given by the experimental breast cancer model showed that all genes related to inflammation respond to ionizing radiation alone or in combination with estrogen. On the other hand, the immune response depended on the breast cancer type and on the expression of the gene that encoded the estrogen receptor. Finally, the importance of the expression of these genes in breast cancer is such that high IL1R1 or IL1RAP is strongly related to patient survival. These findings may help to improve the understanding of the role of immune molecules in carcinogenesis and enhance therapeutic approaches. [ABSTRACT FROM AUTHOR]

Atopic dermatitis and psoriasis are prevalent inflammatory skin conditions that significantly impact the quality of life of patients, with diverse treatment options available. Despite advances in understanding their underlying mechanisms, recent research highlights the significance of interleukins IL-18 and IL-37, in Th1, Th2, and Th17 inflammatory responses, closely associated with the pathogenesis of psoriasis and atopic dermatitis. Hence, IL-18 and IL-37 could potentially become therapeutic targets. This narrative review synthesizes knowledge on these interleukins, their roles in atopic dermatitis and psoriasis, and emerging treatment strategies. Findings of a literature search up to 30 May 2024, underscore a research gap in IL-37-targeted therapies. Conversely, IL-18-focused treatments have demonstrated promise in adult-onset Still's Disease, warranting further exploration for their potential efficacy in psoriasis and atopic dermatitis. [ABSTRACT FROM AUTHOR]

Simple Summary: Recessive dystrophic epidermolysis bullosa (RDEB) is a rare and severe hereditary skin disease characterized by skin and mucosa fragility. RDEB patients are predisposed to the development of life-threatening cutaneous squamous cell carcinoma (SCC). In this study, we investigated the immune profiles of SCCs occurring in a cohort of RDEB patients and compared them with clinical, histopathological and prognostic features. We describe two distinct clinical outcomes in RDEB patients with cutaneous SCCs. A majority of RDEB patients had local and not rapidly life-threatening SCC, while others developed early aggressive and metastatic SCCs. The high-risk primary RDEB-SCC was associated with a tumor microenvironment displaying a higher neutrophil-to-lymphocyte infiltration ratio. Increased levels of citrullinated histone H3, a marker of neutrophil extracellular traps (NET), were detected in tumoral skin and in the serum of RDEB patients with high-risk primary SCC. Recessive dystrophic epidermolysis bullosa (RDEB) is a rare severe hereditary skin disease characterized by skin and mucosa fragility, resulting in blister formation. The most severe complication in RDEB patients is the development of cutaneous squamous cell carcinoma (SCC), leading to premature death. There is a great deal of evidence suggesting a permissive tumor microenvironment (TME) as a driver of SCC development in RDEB patients. In a cohort of RDEB patients, we characterized the immune profiles of RDEB-SCCs and compared them with clinical, histopathological, and prognostic features. RDEB-SCCs were subdivided into four groups based on their occurrence (first onset or recurrences) and grading according to clinical, histopathological parameters of aggressiveness. Thirty-eight SCCs from 20 RDEB patients were analyzed. Five RDEB patients experienced an unfavorable course after the diagnosis of the first SCC, with early recurrence or metastasis, whereas 15 patients developed multiple SCCs without metastasis. High-risk primary RDEB-SCCs showed a higher neutrophil-to-lymphocyte ratio in the tumor microenvironment and an increased proportion of neutrophil extracellular traps (NETs). Additionally, citrullinated histone H3, a marker of NETs, was increased in the serum of RDEB patients with high-risk primary SCC, suggesting that this modified form of histone H3 may serve as a potential blood marker of unfavorable prognosis in RDEB-SCCs. [ABSTRACT FROM AUTHOR]

Background and Objectives: The moment of birth represents a complex physiological process that is followed by adaptive changes in the vital systems of the newborn. Such reactions have their positive but also negative effects. The aim of this research was to determine the difference in laboratory values of stress indicators in newborn children delivered by cesarean section (CS) with general and spinal anesthesia. We attempted to make a recommendation about the optimal type of anesthesia based on our results. Materials and Methods: The study was performed on 150 healthy term newborns delivered by urgent or planned CS. Samples for adrenocorticotropic hormone (ACTH), cortisol, triglycerides, and interleukin-6 (IL-6) were analyzed. Results: Leukocyte numbers, triglycerides, and blood sugar values were normal for the newborns' age, with statistically significantly lower values of blood sugar and triglycerides in newborns delivered by CS in spinal anesthesia (p < 0.005) compared to general anesthesia. There were no significant differences in ACTH, cortisol, and IL-6 levels between those newborns delivered via CS after spinal or general anesthesia. Conclusions: In cases where vaginal delivery is not possible, when CS is indicated, the use of well-controlled spinal anesthesia is followed by lower degrees of metabolic, inflammatory, and stress responses and better vitality of the baby upon birth. [ABSTRACT FROM AUTHOR]

The aim of this study was to explore the impact of anesthetic drugs currently used to perform lower digestive endoscopy on serum concentrations of inflammation markers and catecholamines. We selected 120 patients and divided them into three lots of 40 patients each: L1, in which no anesthetics were used; L2, in which propofol was used; and L3, in which propofol combined with fentanyl was used. All patients had serum concentrations of adrenaline/epinephrine (EPI), noradrenaline/norepinephrine (NE), tumor necrosis factor alpha (TNF-α), interleukin-4 (IL-4), IL-6, IL-8, and IL-10, taken at three time points: at the beginning of the endoscopic procedure (T0), 15 min after (T1), and 2 h after the end of the endoscopic procedure (T2). The results of the research showed changes in the levels of catecholamines and interleukins (ILs) at T0, with an increased response in L1 above the mean recorded in L2 and L3 (p < 0.001). At T1, increased values were recorded in all lots; values were significantly higher in L1. At T2, the values recorded in L3 were significantly lower than the values in L2 (student T, p < 0.001) and L1, in which the level of these markers continued to increase, reaching double values compared to T0 (student T, p < 0.001). In L2 at T1, the dose of propofol correlated much better with NE, EPI, and well-known cytokines. Our results show that propofol combined with fentanyl can significantly inhibit the activation of systemic immune and neuroendocrine response during painless lower digestive endoscopy. [ABSTRACT FROM AUTHOR]

Introduction: The suppression of tumorigenicity 2 (ST2) is a receptor member belonging to the interleukin-1 (IL-1) family. The ligand and soluble versions are its two isoforms. The IL-33-ST2L ligand complex's development provides protection against heart fibrosis and hypertrophy. Investigations on heart failure in adults have demonstrated that it does not change by age, body mass index (BMI), creatinine, hemoglobin, and albumin levels, in contrast to NT pro BNP. In adult heart failure patients, it has been demonstrated to be an independent predictor of mortality and cardiovascular events. The most recent guideline recommends using it as class 2b in the diagnosis of adult heart failure. Studies on ST2 in children are rare. The purpose of this study is to assess the prognostic value of ST2 for cardiovascular events in young individuals suffering from heart failure. Method: This study included pediatric patients (0–18 years old) with congenital heart disease or cardiomyopathy who needed medical care, as well as surgical or interventional treatment. Height, weight, gender, saturation, heart failure classification (Ross or NYHA), medications, the electrocardiogram, echocardiography, pro BNP, and sST2 values of the patients, as well as any hospitalization, lower respiratory tract infection, organ dysfunction, or need for angiography or surgery during follow-up data on arrhythmia and death were gathered during a 1-year follow-up. The SPSS software version 25 application was used to carry out the statistical analysis. Results: This study included 59 patients, of whom 27 (46.6%) were male. The average age of the patients was 55.5 months (1–228 months) and the average body weight was 16 kg (2.6–90 kg). Major cardiovascular events occurred in 45 of 59 patients (76.3%). Twenty-four patients experienced one MACE, while twenty-one patients experienced multiple MACEs. Pro BNP and sST2 levels were similar in the groups that developed MACE compared to those that did not. Pro BNP was discovered to be significantly higher in patients with hospitalization, growth retardation, lower respiratory tract infection, and organ failure, however, when assessing each situation (p = 0.001, p = 0.011, p = 0.001, p = 0.007, respectively). Soluble ST2 was found to be higher in patients with growth retardation than in those without (p = 0.037). Although the soluble ST2 level failed to demonstrate a correlation with pro BNP, it did show a positive correlation (r = 0.437) with the Ross score. When compared to other groups, it was discovered to be higher in patients with valvular insufficiency type heart disease. Conclusions: In this study, higher sST2 levels were discovered, particularly in the group with valve insufficiency and children with growth retardation. It was associated with the Ross score, but not with the pro BNP level. Although it increases in correlation with clinical heart failure, its predictive value for MACE is low. Similarly, pro BNP is not proven to be predictive; nonetheless, its high levels in patients with hospitalization, growth retardation, lower respiratory tract infection, and organ failure demonstrate that pro BNP may increase for a variety of causes. Long-term studies with more patients are needed for ST2 to be suitable for clinical use in pediatric patients. [ABSTRACT FROM AUTHOR]

Simple Summary: Despite the advancement of molecular biology and Next-Generation Sequencing (NGS), the study of the tumor microenvironment continues to have paradigmatic importance in research applied to malignant melanoma, and neoangiogenesis continues to exert a significant influence. In this review, we discuss the most updated knowledge about neoangiogenesis in melanoma, address the role of the TME in progression, and outline future therapeutic perspectives. Angiogenesis plays a pivotal role in tumor progression, particularly in melanoma, the deadliest form of skin cancer. This review synthesizes current knowledge on the intricate interplay between angiogenesis and tumor microenvironment (TME) in melanoma progression. Pro-angiogenic factors, including VEGF, PlGF, FGF-2, IL-8, Ang, TGF-β, PDGF, integrins, MMPs, and PAF, modulate angiogenesis and contribute to melanoma metastasis. Additionally, cells within the TME, such as cancer-associated fibroblasts, mast cells, and melanoma-associated macrophages, influence tumor angiogenesis and progression. Anti-angiogenic therapies, while showing promise, face challenges such as drug resistance and tumor-induced activation of alternative angiogenic pathways. Rational combinations of anti-angiogenic agents and immunotherapies are being explored to overcome resistance. Biomarker identification for treatment response remains crucial for personalized therapies. This review highlights the complexity of angiogenesis in melanoma and underscores the need for innovative therapeutic approaches tailored to the dynamic TME. [ABSTRACT FROM AUTHOR]

Despite great advances in the treatment of oncological diseases, the development of medical technologies to prevent or reduce complications of therapy, in particular, those associated with surgery and the introduction of antibiotics, remains relevant. The aim of this study is to evaluate the effectiveness of the use of autoprobiotics based on indigenous non-pathogenic strains of Enterococcus faecium and Enterococcus hirae as a personalized functional food product (PFFP) in the complex therapy of colorectal cancer (CRC) in the early postoperative period. A total of 36 patients diagnosed with CRC were enrolled in the study. Study group A comprised 24 CRC patients who received autoprobiotic therapy in the early postoperative period, while the control group C included 12 CRC patients without autoprobiotic therapy. Prior to surgery and between days 14 and 16 post-surgery, comprehensive evaluations were conducted on all patients, encompassing the following: stool and gastroenterological complaints analysis, examination of the gut microbiota (bacteriological study, quantitative polymerase chain reaction, metagenome analysis), and analysis of interleukins in the serum. Results: The use of autoprobiotics led to a decrease in dyspeptic complaints after surgery. It was also associated with the absence of postoperative complications, did not cause any side effects, and led to a decrease in the level of pro-inflammatory cytokines (IL-6 and IL-18) in the blood serum. The use of autoprobiotics led to positive changes in the structure of escherichia and enterococci populations, the elimination of Parvomonas micra and Fusobacterium nucleatum, and a decrease in the quantitative content of Clostridium perfringens and Akkermansia muciniphila. Metagenomic analysis (16S rRNA) revealed an increase in alpha diversity. Conclusion: The introduction of autoprobiotics in the postoperative period is a highly effective and safe approach in the complex treatment of CRC. Future studies will allow the discovery of additional fine mechanisms of autoprobiotic therapy and its impact on the digestive, immune, endocrine, and neural systems. [ABSTRACT FROM AUTHOR]

Simple Summary: FAM46C is a tumour suppressor protein originally characterized in multiple myeloma. Recent findings, however, suggest a much broader involvement of FAM46C in cancer, underlining the clinical importance of fully dissecting the intracellular pathways it modulates. To date, FAM46C mechanistic role is still disputed and studies regarding its mode of action are sometimes contradictory, urging the need to summarize and clarify the results obtained so far. Here, by focusing primarily on the intracellular pathways modulated by FAM46C, the currently accepted models regarding its mode of action, the regulators of its expression and how it associates with increased/decreased cell sensitivity to anticancer agents, we provide the first comprehensive review on FAM46C. FAM46C is a well-established tumour suppressor with a role that is not completely defined or universally accepted. Although FAM46C expression is down-modulated in several tumours, significant mutations in the FAM46C gene are only found in multiple myeloma (MM). Consequently, its tumour suppressor activity has primarily been studied in the MM context. However, emerging evidence suggests that FAM46C is involved also in other cancer types, namely colorectal, prostate and gastric cancer and squamous cell and hepatocellular carcinoma, where FAM46C expression was found to be significantly reduced in tumoural versus non-tumoural tissues and where FAM46C was shown to possess anti-proliferative properties. Accordingly, FAM46C was recently proposed to function as a pan-cancer prognostic marker, bringing FAM46C under the spotlight and attracting growing interest from the scientific community in the pathways modulated by FAM46C and in its mechanistic activity. Here, we will provide the first comprehensive review regarding FAM46C by covering (1) the intracellular pathways regulated by FAM46C, namely the MAPK/ERK, PI3K/AKT, β-catenin and TGF-β/SMAD pathways; (2) the models regarding its mode of action, specifically the poly(A) polymerase, intracellular trafficking modulator and inhibitor of centriole duplication models, focusing on connections and interdependencies; (3) the regulation of FAM46C expression in different environments by interferons, IL-4, TLR engagement or transcriptional modulators; and, lastly, (4) how FAM46C expression levels associate with increased/decreased tumour cell sensitivity to anticancer agents, such as bortezomib, dexamethasone, lenalidomide, pomalidomide, doxorubicin, melphalan, SK1-I, docetaxel and norcantharidin. [ABSTRACT FROM AUTHOR]

Simple Summary: Cancer-associated cachexia (CAC) is a serious condition wherein people with cancer lose muscle and fat, even with proper nutrition. It leads to weakness and can make treatment less effective. This review looks at how the body's immune system and certain proteins affect CAC. Studies show that specific proteins, like IL-6 and TNF-α, play a crucial role in causing muscle and fat loss. Other cells in the immune system, called MDSCs, make CAC worse by causing inflammation. Clinical studies also found high levels of certain proteins in people with CAC. Understanding these processes might improve treatments, especially for those undergoing immunotherapy. A new drug called R-ketorolac has shown promise in reversing weight loss in animals. Combining drugs like this with immunotherapy could help patients with cancer suffering from CAC. However, more research is needed to fully understand how immune problems and CAC interact during treatment. Cancer-associated cachexia (CAC) is a debilitating condition marked by muscle and fat loss, that is unresponsive to nutritional support and contributes significantly to morbidity and mortality in patients with cancer. Immune dysfunction, driven by cytokine imbalance, contributes to CAC progression. This review explores the potential relationship between CAC and anti-cancer immune response in pre-clinical and clinical studies. Pre-clinical studies showcase the involvement of cytokines like IL-1β, IL-6, IL-8, IFN-γ, TNF-α, and TGF-β, in CAC. IL-6 and TNF-α, interacting with muscle and adipose tissues, induce wasting through JAK/STAT and NF-κB pathways. Myeloid-derived suppressor cells (MDSCs) exacerbate CAC by promoting inflammation. Clinical studies confirm elevated pro-inflammatory cytokines (IL-6, IL-8, TNFα) and immune markers like the neutrophil-to-lymphocyte ratio (NLR) in patients with CAC. Thus, immunomodulatory mechanisms involved in CAC may impact the anti-neoplastic immune response. Inhibiting CAC mechanisms could enhance anti-cancer therapies, notably immunotherapy. R-ketorolac, a new immunomodulator, reversed the weight loss and increased survival in mice. Combining these agents with immunotherapy may benefit patients with cancer experiencing CAC. Further research is vital to understand the complex interplay between tumor-induced immune dysregulation and CAC during immunotherapy. [ABSTRACT FROM AUTHOR]

Sport injuries, including the anterior crucial ligament rupture (ACLR) seem to be related to complex genetic backgrounds, including the genes responsible for inflammatory response. This review and meta-analysis investigated the contribution of the polymorphisms of genes encoding inflammatory cytokines and their receptors to the risk of ACLR. The scientific databases Science Direct, EBSCO host, Scopus, PubMed, and Google Scholar were screened (completed on 14 June 2023) according to the established inclusion/exclusion criteria (only fully accessible, original, human case–control studies written in English concerning the effect of interleukin genes' polymorphisms on the occurrence of ACL injury were included) and statistical meta-analysis using R version 4.0.3 was performed. The PRISMA methodology was used to review articles. The review protocol was registered under the number CRD42024514316 in the Prospero database. Eighty-nine studies were identified and narrowed down to three original case–control studies used for the meta-analysis. The studies analyzed Polish, South African, and Swedish cohorts, altogether 1282 participants. The candidate polymorphisms indicated in the studies involved IL6 rs1800795, IL6R rs2228145 and IL1B rs16944. The systematic review showed the relationships between IL6 rs1800795 polymorphism and ACLR in the Polish subpopulation, and IL6R rs2228145 and IL1B rs16944 in the South African subpopulations. The meta-analysis revealed that the IL6 rs1800795 CG genotype was over-represented (OR = 1.30, 95% CI 1.02–1.66), while the CC genotype was under-represented (OR = 0.75, 95% CI 0.54–1.03) in ACLR subjects, but no significant impact of IL6R rs2228145 was shown. Additionally, a tendency of the IL1B rs16944 CT genotype to be protective (OR 0.89, 95% CI 0.70–1.14), while the TT to be a risk genotype (OR 1.19, 95% CI 0.84–1.68) was observed. Thus, the relationship between the interleukin receptor IL6R rs2228145 and ACLR risk was not confirmed. However, the impact of genes coding pleiotropic IL6 rs1800795 on the incidences of ACLR was clear and the effect of pro-inflammatory IL1B rs16944 was possible. [ABSTRACT FROM AUTHOR]

Functional somatic disorders (FSDs) are common in children and adolescents. Recent findings suggest that low-grade inflammation has a role in the development and maintenance of pediatric FSDs. This systematic review included studies with original data on systemic inflammatory markers in children and adolescents with an FSD compared to individuals without an FSD. The literature search identified 1374 articles. After assessment, a total of 15 studies met the inclusion criteria. In total, 41 serum or plasma cytokines were assayed in a population of 696 children and adolescents. Altered cytokine levels in patients with FSDs were reported in 12 studies, whereas three studies found no significant differences when comparing patients with FSDs and controls. The cytokine levels were significantly elevated in nine studies (i.e., IL-2, IL-6, IL-8, IL-12 (p70), CRP, hsCRP, IP-10, MCP-1, sTIM-3, sCD25 and TNF- α ). The findings indicate that inflammatory response may have a role in the pathophysiology of pediatric FSDs. However, the included studies showed limited quality with potential risk of bias, small study populations and a narrow spectrum of included FSDs, which limits the generalizability of the results. To further explore the potential link between inflammatory markers and pediatric FSDs, future research using a longitudinal study design is recommended. [ABSTRACT FROM AUTHOR]

Simple Summary: Oxygen-guided radiotherapy is a new modality for cancer irradiation. Spatially Fractionated Radiation Therapy allows the treatment of hypoxic tumor areas with high radiation doses. Radiotherapy enhances immunotherapy effectiveness. Abscopal and bystander effects are important radiobiological issues. The aim of this paper was to analyze the recent development of a particular kind of radiation therapy that is based on high-dose delivery in small areas within large tumor masses. We performed a narrative review of the radiobiological rationale behind a potential benefit by using these techniques combined with immunotherapy and employing personalized target definition according to hypoxic areas. Palliative radiotherapy has a great role in the treatment of large tumor masses. However, treating a bulky disease could be difficult, especially in critical anatomical areas. In daily clinical practice, short course hypofractionated radiotherapy is delivered in order to control the symptomatic disease. Radiation fields generally encompass the entire tumor mass, which is homogeneously irradiated. Recent technological advances enable delivering a higher radiation dose in small areas within a large mass. This goal, previously achieved thanks to the GRID approach, is now achievable using the newest concept of LATTICE radiotherapy (LT-RT). This kind of treatment allows exploiting various radiation effects, such as bystander and abscopal effects. These events may be enhanced by the concomitant use of immunotherapy, with the latter being ever more successfully delivered in cancer patients. Moreover, a critical issue in the treatment of large masses is the inhomogeneous intratumoral distribution of well-oxygenated and hypo-oxygenated areas. It is well known that hypoxic areas are more resistant to the killing effect of radiation, hence the need to target them with higher aggressive doses. This concept introduces the "oxygen-guided radiation therapy" (OGRT), which means looking for suitable hypoxic markers to implement in PET/CT and Magnetic Resonance Imaging. Future treatment strategies are likely to involve combinations of LT-RT, OGRT, and immunotherapy. In this paper, we review the radiobiological rationale behind a potential benefit of LT-RT and OGRT, and we summarize the results reported in the few clinical trials published so far regarding these issues. Lastly, we suggest what future perspectives may emerge by combining immunotherapy with LT-RT/OGRT. [ABSTRACT FROM AUTHOR]

(1) Background: Worldwide, public health policies focus on studying dietary patterns and the related anthropometric changes in children. Their aim is to improve the measures meant to reduce global malnutrition rates. Our goal was to study the main changes in the inflammatory status related to anthropometric changes and total daily energy intake. (2) Methods: We tested the study hypothesis by analyzing serum IL-6 and IL-8 levels, cholesterol and triglycerides values, as well as total proteins and creatinine levels, RMR, and food journals in a sample of 160 healthy subjects aged between 6 and 12 years old. (3) Results: IL-6 was correlated with the skinfold values. Changes in the skinfolds were significantly correlated with total proteins and triglycerides. Both weight for age and height for age were related to the skinfold values. Through the BMR measurements, peak carbohydrate metabolism changed significantly based upon IL-6 values, which were significantly correlated with the respiratory coefficient values. Based on the basal metabolic rate, an increased IL-8 ratio was related to the RQ value. (4) Conclusions: Skinfolds have been significantly correlated with IL-6 and IL-8 levels. With changes in body weight, we encountered differences in both serum cholesterol and serum triglycerides values, unlike total proteins and creatinine, which failed to change. [ABSTRACT FROM AUTHOR]

Simple Summary: In cancer, including head and neck cancer (HNC), certain key players in the body's inflammatory process, such as the interleukin (IL)-6 and IL-1 systems, are associated with outcomes. We studied some of these key players in a subgroup of HNC patients. From one blood sample measured at diagnosis, we determined high levels of molecules from members of the IL-6 and IL-1 families with their associated soluble cytokine receptors. High values indicated a lower survival rate. This prediction was to some extent better than the standard clinical predictors used. The results highlight potential new targets for immune treatment development. Additionally, these findings could contribute to the refinement of cancer treatment strategies, particularly in the context of emerging immune therapies. Activation of the acute-phase cascade (APC) has been correlated with outcomes in various cancers, including head and neck squamous cell carcinoma (HNSCC). Primary drivers of the APC are the cytokines within the interleukin-6 (IL-6) and IL-1 families. Plasma levels of IL-6 family cytokines/soluble receptors (IL-6, IL-27, IL-31, OSM, CNTF, soluble (s-)gp130, s-IL-6Rα) and IL-1 family members (IL-1RA, s-IL-33Rα) were determined at diagnosis for 87 human papillomavirus (HPV)-negative (−) HNSCC patients. We then studied the 5-year Disease-Specific Survival (DSS) and Overall Survival (OS). Increased plasma levels of IL-6 (p < 0.001/p < 0.001) (DSS/OS), IL-31 (p = 0.044/p = 0.07), IL-1RA (p = 0.004/p = 0.035), soluble (s)-IL-6Rα p = 0.022/p = 0.035), and s-gp130 (p = 0.007/p = 0.003) at diagnosis were predictors of both OS and DSS from HPV(−) HNSCC patients. The cytokine DSS/OS predictions were associated with TNM stage and smoking history, whereas the soluble receptors IL-6Rα, gp130, and IL33Rα more uniquely predicted DSS/OS. Clinically, IL-6 levels above 2.5 pg/mL yielded 75% specificity and 70% sensitivity for DSS. In conclusion, high plasma levels of IL-6, IL-31, and IL-1RA, as well as the soluble receptors IL-6Rα, gp130, and IL33Rα, predicted clinical outcome. This shows their potential as candidates for both general therapy and immune therapy stratification, as well as being future platforms for the development of new immunotherapy. [ABSTRACT FROM AUTHOR]

Vagus nerve stimulation (VNS) represents a long-term adjunctive treatment option in patients with difficult-to-treat depression (DTD). Anti-inflammatory effects have been discussed as a key mechanism of action of VNS. However, long-term investigations in real-world patients are sparse. In this naturalistic observational study, we collected data on cytokines in peripheral blood in n = 6 patients (mean age 47.8) with DTD and VNS treatment at baseline and at 6 months follow-up. We have identified clusters of peripheral cytokines with a similar dynamic over the course of these 6 months using hierarchical clustering. We have investigated cytokine changes from baseline to 6 months as well as the relationship between the cytokine profile at 6 months and long-term response at 12 months. After 6 months of VNS, we observed significant correlations between cytokines (p < 0.05) within the identified three cytokine-pairs which were not present at baseline: IL(interleukin)-6 and IL-8; IL-1β and TNF-α; IFN-α2 and IL-33. At 6 months, the levels of all the cytokines of interest had decreased (increased in non-responders) and were lower (5–534 fold) in responders to VNS than in non-responders: however, these results were not statistically significant. VNS-associated immunomodulation might play a role in long-term clinical response to VNS. [ABSTRACT FROM AUTHOR]

Background: The association of gene variants for interleukin 6 (IL-6) (rs1800796), interleukin 10 (IL-10) (rs1800896) and tumor necrosis factorα (TNFα (rs1800629) with the occurrence of spontaneous preterm birth (PTB) was investigated to determine whether these genetic variants are a risk factor. Methods: A total of 199 blood samples from pregnant women who had given birth prematurely and 200 control blood samples were analyzed to determine single nucleotide polymorphisms (SNPs) of genes for IL-6 (rs1800796), IL-10 (rs1800896) and TNFα (rs1800629). The control samples were samples from pregnant women with term delivery. The isolation of DNA was performed on mini-spin columns according to the manufacturer's protocol. The quality and purity of the isolated DNA were tested using a Qubit 3 fluorometer. Genotyping was performed with an ABI PRISM 7500 SDS using TaqMan SNP genotyping assays. The genotypes obtained were analyzed using the 7500 Software v2.3 package. Results: Carriers of the A/A genotype for the rs1800629 SNP of the TNFα gene have a 4.81 times greater chance of late-onset PTB compared to carriers of the G/G and A/G genotypes in the recessive inheritance model. The presence of the G/G genotype in the recessive inheritance model compared with the G/A and A/A genotypes for the rs1800896 SNP of the IL-10 gene represents a potentially protective factor, with mothers in the term-birth group having an almost 2-fold lower odds of PTB in general and an almost 10-fold lower odds of early PTB. On the other hand, carriers of the A/G genotype of rs1800896 have a 1.54-fold higher chance of preterm birth in general and a 1.6-fold higher chance of late preterm birth in the superdominant inheritance model compared to the A/A and G/G genotypes in the group of mothers with PTB. In this study, no association was found between PTB and the rs1800796 SNP of the IL-6 gene. Conclusions: rs1800629 in mothers was associated with PTB. rs1800896 shows a potentially protective effect for the occurrence of PTB in this study. No association was found between PTB and rs1800796. [ABSTRACT FROM AUTHOR]

Diagnosis of neonatal sepsis is difficult due to nonspecific signs and symptoms. Interleukin-6 (IL-6) is a promising marker for neonatal sepsis. We aimed to test the accuracy of IL-6 in neonates after 72 h of life in case of late onset sepsis (LOS). We searched for studies regarding IL-6 accuracy for the diagnosis of LOS between 1990 and 2020 using the PubMed database. Following study selection, the reported IL-6 sensitivities and specificities ranged between 68% and 100% and 28% and 100%, with median values of 85.7% and 82% and pooled values of 88% and 78% (respectively) in the 15 studies including 1306 infants. Subgroup analysis revealed a better sensitivity (87% vs. 82%), but not specificity (both 86%), in preterm infants compared to term infants or mixed populations. Early sample collection revealed the highest sensitivity (84%), but had the lowest specificity (86%). To assess quality, we used a STARD checklist adapted for septic neonates and the QUADAS criteria. Limitations of this review include the heterogeneous group of studies on the one side and the small number of studies on the other side that analyzed different combinations of biomarkers. We concluded that IL-6 demonstrated good performance especially in the preterm infant population and the best results were achieved by measurements at the time of LOS suspicion. [ABSTRACT FROM AUTHOR]

Invasive infections caused by Streptococcus pyogfenes (iGAS), commonly known as Group A Streptococcus, represent a significant public health concern due to their potential for rapid progression and life-threatening complications. Epidemiologically, invasive GAS infections exhibit a diverse global distribution, affecting individuals of all ages with varying predisposing factors. The pathogenesis of invasive GAS involves an array of virulence factors that contribute to tissue invasion, immune evasion, and systemic dissemination. In pediatrics, in the last few years, an increase in iGAS infections has been reported worldwide becoming a challenging disease to diagnose and treat promptly. This review highlights the current knowledge on pathogenesis, clinical presentations, and therapeutic approaches for iGAS in children. [ABSTRACT FROM AUTHOR]

Choroid plexus (CP) can be seen as a watchtower of the central nervous system (CNS) that actively regulates CNS homeostasis. A growing body of literature suggests that CP alterations are involved in the pathogenesis of multiple sclerosis (MS) but the underlying mechanisms remain elusive. CPs are enlarged and inflamed in relapsing-remitting (RRMS) but also in clinically isolated syndrome (CIS) and radiologically isolated syndrome (RIS) stages, far beyond MS diagnosis. Increases in the choroid plexus/total intracranial volume (CP/TIV) ratio have been robustly associated with increased lesion load, higher translocator protein (TSPO) uptake in normal-appearing white matter (NAWM) and thalami, as well as with higher annual relapse rate and disability progression in highly active RRMS individuals, but not in progressive MS. The CP/TIV ratio has only slightly been correlated with magnetic resonance imaging (MRI) findings (cortical or whole brain atrophy) and clinical outcomes (EDSS score) in progressive MS. Therefore, we suggest that plexus volumetric assessments should be mainly applied to the early disease stages of MS, whereas it should be taken into consideration with caution in progressive MS. In this review, we attempt to clarify the pathological significance of the temporal CP volume (CPV) changes in MS and highlight the pitfalls and limitations of CP volumetric analysis. [ABSTRACT FROM AUTHOR]

Simple Summary: Multiple myeloma is an incurable blood cancer that arises due to the uncontrolled growth of plasma cells in the bone marrow. The progression of multiple myeloma is dependent on communication between the plasma cells and other cells within the bone marrow, and extracellular vesicles (EVs) are implicated in the cell communication. The aim of this study was to investigate the role of EVs secreted by multiple myeloma cells on monocyte cells. We revealed that multiple myeloma cell-derived EVs are taken up by monocyte cells. EV uptake by monocytes led to increased secretion of pro-inflammatory factors, which in turn created an environment that enhanced myeloma cell migration and growth that is associated with cancer progression. Investigation into the EV contents revealed potential mechanisms by which multiple myeloma EVs promote cancer progression. Multiple Myeloma (MM) is an incurable haematological malignancy caused by uncontrolled growth of plasma cells. MM pathogenesis is attributed to crosstalk between plasma cells and the bone marrow microenvironment, where extracellular vesicles (EVs) play a role. In this study, EVs secreted from a panel of MM cell lines were isolated from conditioned media by ultracentrifugation and fluorescently stained EVs were co-cultured with THP-1 monocyte cells. MM EVs from three cell lines displayed a differential yet dose-dependent uptake by THP-1 cells, with H929 EVs displaying the greatest EV uptake compared to MM.1s and U266 EVs suggesting that uptake efficiency is dependent on the cell line of origin. Furthermore, MM EVs increased the secretion of MMP-9 and IL-6 from monocytes, with H929 EVs inducing the greatest effect, consistent with the greatest uptake efficiency. Moreover, monocyte-conditioned media collected following H929 EV uptake significantly increased the migration and proliferation of MM cells. Finally, EV proteome analysis revealed differential cargo enrichment that correlates with disease progression including a significant enrichment of spliceosome-related proteins in H929 EVs compared to the U266 and MM.1s EVs. Overall, this study demonstrates that MM-derived EVs modulate monocyte function to promote tumour growth and metastasis and reveals possible molecular mechanisms involved. [ABSTRACT FROM AUTHOR]

Human immunodeficiency virus (HIV) is a major cause of death worldwide. Without appropriate antiretroviral therapy, the infection can develop into acquired immunodeficiency syndrome (AIDS). AIDS leads to the dysregulation of cell-mediated immunity resulting in increased susceptibility to opportunistic infections and excessive amounts of inflammatory cytokines. HIV-positive individuals also demonstrate diminished glutathione (GSH) levels which allows for increased viral replication and increased pro-inflammatory cytokine release, further contributing to the high rates of mortality seen in patients with HIV. Adequate GSH supplementation has reduced inflammation and slowed the decline of CD4+ T cell counts in HIV-positive individuals. We aim to review the current literature regarding the role of GSH in cell-mediated immune responses in individuals with HIV- and AIDS-defining illnesses. [ABSTRACT FROM AUTHOR]

Multiple sclerosis is a disabling inflammatory disorder of the central nervous system characterized by demyelination and neurodegeneration. Given that multiple sclerosis remains an incurable disease, the management of MS predominantly focuses on reducing relapses and decelerating the progression of both physical and cognitive decline. The continuous autoimmune process modulated by cytokines seems to be a vital contributing factor to the development and relapse of multiple sclerosis. This review sought to summarize the role of selected interleukins in the pathogenesis and advancement of MS. Patients with MS in the active disease phase seem to exhibit an increased serum level of IL-2, IL-4, IL-6, IL-13, IL-17, IL-21, IL-22 and IL-33 compared to healthy controls and patients in remission, while IL-10 appears to have a beneficial impact in preventing the progression of the disease. Despite being usually associated with proinflammatory activity, several studies have additionally recognized a neuroprotective role of IL-13, IL-22 and IL-33. Moreover, selected gene polymorphisms of IL-2R, IL-4, IL-6, IL-13 and IL-22 were identified as a possible risk factor related to MS development. Treatment strategies of multiple sclerosis that either target or utilize these cytokines seem rather promising, but more comprehensive research is necessary to gain a clearer understanding of how these cytokines precisely affect MS development and progression. [ABSTRACT FROM AUTHOR]

Simple Summary: Glioblastoma is a lethal primary brain tumor, and so far, immunotherapeutic strategies have not significantly improved patients' prognosis, both in newly diagnosed and recurrent settings. Understanding the features of the immune environment of the central nervous system is crucial to designing new treatment strategies able to counteract site-specific immunosuppressive and pro-tumorigenic factors. Here, we review next-generation immunomodulating therapeutic strategies such as immune check-point blockade, vaccinations, and adoptive cell therapies, aiming to re-shape the tumor microenvironment and restore active anti-tumor immunity. The door for immunotherapeutic strategies in glioblastoma treatment is not completely closed; researchers should test combinatorial treatments and design trials with solid translational analyses to gain more close and deep insight into on-treatment modifications of the tumor microenvironment. Glioblastoma (GBM) is the most aggressive and lethal primary brain tumor, bearing a survival estimate below 10% at five years, despite standard chemoradiation treatment. At recurrence, systemic treatment options are limited and the standard of care is not well defined, with inclusion in clinical trials being highly encouraged. So far, the use of immunotherapeutic strategies in GBM has not proved to significantly improve patients' prognosis in the treatment of newly diagnosed GBM, nor in the recurrent setting. Probably this has to do with the unique immune environment of the central nervous system, which harbors several immunosuppressive/pro-tumorigenic factors, both soluble (e.g., TGF-β, IL-10, STAT3, prostaglandin E2, and VEGF) and cellular (e.g., Tregs, M2 phenotype TAMs, and MDSC). Here we review the immune composition of the GBMs microenvironment, specifically focusing on the phenotype and function of the T cell compartment. Moreover, we give hints on the therapeutic strategies, such as immune checkpoint blockade, vaccinations, and adoptive cell therapy, that, interacting with tumor-infiltrating lymphocytes, might both target in different ways the tumor microenvironment and potentiate the activity of standard therapies. The path to be followed in advancing clinical research on immunotherapy for GBM treatment relies on a twofold strategy: testing combinatorial treatments, aiming to restore active immune anti-tumor responses, tackling immunosuppression, and additionally, designing more phase 0 and window opportunity trials with solid translational analyses to gain deeper insight into the on-treatment shaping of the GBM microenvironment. [ABSTRACT FROM AUTHOR]

Simple Summary: Gastric cancer is one of the most prevalent and deadliest neoplasms worldwide. Although significant advances have been made in recent decades to improve its treatment, an incomplete understanding of its etiology and pathogenesis still limits our ability to effectively prevent and treat gastric cancer. It is well established that the most common subtype of gastric cancer (intestinal gastric cancer) develops through a multi-step process, wherein pathologic changes in gastric cells progressively occur, ultimately leading to the development of tumors. Recent evidence suggests that, aside from environmental factors, the immune system plays a key role in the sequela from gastritis to metaplasia, dysplasia and finally, gastric cancer, primarily through type 2 immune responses. In this review, we summarize the current literature and provide an overall interpretation regarding the impact of T helper 2 (Th2) immunity on the development and progression of gastric cancer. Gastric cancer is one of the leading causes of cancer deaths worldwide, with chronic gastritis representing the main predisposing factor initiating the cascade of events leading to metaplasia and eventually progressing to cancer. A widely accepted classification distinguishes between autoimmune and environmental atrophic gastritis, mediated, respectively, by T cells promoting the destruction of the oxyntic mucosa, and chronic H. pylori infection, which has also been identified as the major risk factor for gastric cancer. The original dogma posits Th1 immunity as a main causal factor for developing gastritis and metaplasia. Recently, however, it has become evident that Th2 immune responses play a major role in the events causing chronic inflammation leading to tumorigenesis, and in this context, many different cell types and cytokines are involved. In particular, the activity of cytokines, such as IL-33 and IL-13, and cell types, such as mast cells, M2 macrophages and eosinophils, are intertwined in the process, promoting chronic gastritis-dependent and more diffuse metaplasia. Herein, we provide an overview of the critical events driving the pathology of this disease, focusing on the most recent findings regarding the importance of Th2 immunity in gastritis and gastric metaplasia. [ABSTRACT FROM AUTHOR]

Diabetes can trigger an increase in cytokine levels leading to the production of C-reactive protein and fibrinogen. These molecules promote subclinical inflammation, causing the expression of adhesive molecules and endothelial dysfunction. Despite the lack of a comprehensive panel for single-nucleotide polymorphisms (SNPs) for interleukins associated with type 1 diabetes mellitus (T1DM), understanding the inflammatory role of SNPs is crucial because periodontitis, the sixth complication of diabetes, is influenced via these genetic variations. This review focuses on the interleukin levels in T1DM patients with and without periodontitis, with a particular focus on childhood and on SNPs when reported. A search of PubMed and Scopus identified 21 relevant studies from the past five years. Several ILs were analyzed, emphasizing that T1DM still needs to be thoroughly explored regarding an IL polymorphisms panel; however, the last five years have led to the increased independence of this condition, causing autonomous inflammatory effects, which require further investigation. The periodontitis and T1DM association in children and adolescents represents a severe gap in the literature that should be filled; this scarce presence of studies serves as motivation for further clinical research. [ABSTRACT FROM AUTHOR]

Introduction and aim: A direct causal relationship between vitamin D (vit D) deficiency and recurrent wheezing has not been proven. The present study investigated the role of vit D in enhancing the risk of asthma or recurrent wheezing by modifying the intensity of the inflammatory process. Material and method: Forty children with wheezing presenting at the emergency service and sixteen healthy control subjects were included in the study. Children with wheezing were either in the first episode (20) or with recurrent wheezing (20). Children with chronic diseases, and other conditions that present with acute wheezing or that might influence the vit D level, were excluded. Blood samples were taken at presentation and 3–6 months later, to evaluate the serum levels of total IgE, vit D, IL-10 and IL-31. Statistical analysis was performed using the SPSS 25 program, with a significance level of p < 0.05. Results and conclusion. The vit D level was lower in patients with recurrent wheezing compared with those with a single episode and with the control group, and this increased with time. IL-10 was significantly higher in children with wheezing than in the control group, with the highest values in those with an acute episode of wheezing. IL-31 was higher in children with recurrent wheezing than in those with a first episode only at the initial point, while at the final time point it was lower. Low levels of vit D appear to be detected more frequently in recurrent wheezing than in simple wheezing. Immune modulation, as measured by Th2 status reflected by IL-10 and IL-31 levels, appears to depend on the wheezing phenotype and on the general health status. [ABSTRACT FROM AUTHOR]

The interleukins IL-4 and IL-13 are increasingly recognized contributors to the pathogenesis of cutaneous T cell lymphomas (CTCLs), and their role in disease-associated pruritus is accepted. The prevailing Th2 profile in advanced CTCL underscores the significance of understanding IL-4/IL-13 expression dynamics from the early stages of disease, as a shift from Th1 to Th2 may explain CTCL progression. Targeted agents blocking key cytokines of type 2 immunity are established therapeutics in atopic disorders and have a promising therapeutic potential in CTCL, given their involvement in cutaneous symptoms and their contribution to the pathogenesis of disease. IL-4, IL-13, and IL-31 are implicated in pruritus, offering therapeutic targets with dupilumab, tralokinumab, lebrikizumab, and nemolizumab. This review analyzes current knowledge on the IL-4/IL-13 axis in mycosis fungoides and Sezary syndrome, the most common types of CTCL, examining existing literature on the pathogenetic implications with a focus on investigational treatments. Clinical trials and case reports are required to shed light on novel uses of medications in various diseases, and ongoing research into the role of IL-4/IL-13 axis blockers in CTCL therapy might not only improve the management of disease-related pruritus but also provide in-depth insights on the pathophysiologic mechanisms of CTCL. [ABSTRACT FROM AUTHOR]

The bulk of research on microfiltered seawater (SW) is based on its short-term effects. However, the long-term physiological adaptations to combining SW and resistance training (RT) are unknown. This study aimed to analyse the impact of an RT program using elastic bands combined with SW intake on hepatic biomarkers, inflammation, oxidative stress, and blood pressure in post-menopausal women. Ninety-three women voluntarily participated (age: 70 ± 6.26 years; body mass index: 22.05 ± 3.20 kg/m2; Up-and-Go Test: 6.66 ± 1.01 s). RT consisted of six exercises (32 weeks, 2 days/week). Nonsignificant differences were reported for hepatic biomarkers except for a reduction in glutamic-pyruvic transaminase (GPT) in both RT groups (RT + SW: p = 0.003, ES = 0.51; RT + Placebo: p = 0.012, ES = 0.36). Concerning oxidative stress, vitamin D increased significantly in RT + SW (p = 0.008, ES = 0.25). Regarding inflammation, interleukin 6 significantly decreased (p = 0.003, ES = 0.69) in RT + SW. Finally, systolic blood pressure significantly decreased in both RT groups (RT + placebo: p < 0.001, ES = 0.79; RT + SW: p < 0.001, ES = 0.71) as did diastolic blood pressure in both SW groups (RT + SW: p = 0.002, ES = 0.51; CON + SW: p = 0.028, ES = 0.50). Therefore, RT + SW or SW alone are safe strategies in the long term with no influences on hepatic and oxidative stress biomarkers. Additionally, SW in combination with RT positively influences vitamin D levels, inflammation, and blood pressure in older women. [ABSTRACT FROM AUTHOR]

Simple Summary: The use of aspirin has shown a definite role in the prevention of cancer; however, its effect on survival is still debated. The evidence from randomized trials failed to show any benefit, while cohort studies have demonstrated its usefulness. This is attributed to the use of different doses of aspirin in differing studies. This article explores the plausible mechanisms through which aspirin may exert its effect on improving survival. It is possible that the use of aspirin as adjunct to standard care may lead to better survival in cancer, though the actual effect would have to be demonstrated in clinical trials. The benefit of aspirin on cancer survival is debated. Data from randomized clinical trials and cohort studies are discordant, although a meta-analysis shows a clear survival advantage when aspirin is added to the standard of care. However, the mechanism by which aspirin improves cancer survival is not clear. A PubMed search was carried out to identify articles reporting genes and pathways that are associated with aspirin and cancer survival. Gene ontology and pathway enrichment analysis was carried out using web-based tools. Gene–gene and protein–protein interactions were evaluated. Crosstalk between pathways was identified and plotted. Forty-one genes were identified and classified into primary genes (PTGS2 and PTGES2), genes regulating cellular proliferation, interleukin and cytokine genes, and DNA repair genes. The network analysis showed a rich gene–gene and protein–protein interaction between these genes and proteins. Pathway enrichment showed the interleukin and cellular transduction pathways as the main pathways involved in aspirin-related survival, in addition to DNA repair, autophagy, extracellular matrix, and apoptosis pathways. Crosstalk of PTGS2 with EGFR, JAK/AKT, TP53, interleukin/TNFα/NFκB, GSK3B/BRCA/PARP, CXCR/MUC1, and WNT/CTNNB pathways was identified. The results of the present study demonstrate that aspirin improves cancer survival by the interplay of 41 genes through a complex mechanism. PTGS2 is the primary target of aspirin and impacts cancer survival through six primary pathways: the interleukin pathway, extracellular matrix pathway, signal transduction pathway, apoptosis pathway, autophagy pathway, and DNA repair pathway. [ABSTRACT FROM AUTHOR]

There is paucity of studies that focus on the composition of pericardial fluid under resting conditions. The purpose of this study is to determine the levels of inflammatory mediators in pericardial fluid and their correlation with plasma levels in patients undergoing elective cardiac surgery. We conducted a prospective cohort study on candidates for elective aortic valve replacement surgery. Pericardial fluid and peripheral venous blood samples were collected after opening the pericardium. Levels of interleukin 1α (IL-1α); interleukin 1β (IL-1β); interleukin 2 (IL-2) interleukin 4 (IL-4); interleukin 6 (IL-6); interleukin 8 (IL8); interleukin 10 (IL10); tumor necrosis factor-α (TNF-α), interferon-γ (IFN-γ), vascular endothelial growth factor (VEGF), monocyte chemotactic protein-1 (MCP-1) epidermal growth factor (EGF), soluble E-selectin, L-selectin, P-selectin, intercellular adhesion molecule-1 (ICAM-1), and vascular cell adhesion molecule-1 (VCAM-1) were determined in both pericardial fluid and serum samples. A total of 45 patients with a mean age of 74 years were included of which 66% were males. Serum levels of all study mediators were within normal limits. Serum and pericardial levels of IL-1 α, IL-1 β, IL-2, IL-4, and IL-10 were similar. Levels of VEGF, EGF, VCAM-2, ICAM 1, E-selectin, P-selectin, and L-selectin were significantly lower in pericardial fluid than in serum. However, levels of IL-6, IL-8, TNF-α, IFN-γ, MCP-1, and MCP-1 were significantly higher in the pericardial fluid than in serum. Under normal conditions, the pattern of distribution of different inflammatory mediators in the pericardial fluid does not reflect serum levels. This may either reflect the condition of the underlying myocardium and epicardial fat or the activity of the mesothelial and mononuclear cells present in pericardial fluid. [ABSTRACT FROM AUTHOR]

Gastrointestinal (GI) cancers are an increasingly common type of malignancy, caused by the unhealthy lifestyles of people worldwide. Limited methods of treatment have prompted the search for new compounds with antitumor activity, in which betulin (BE) is leading the way. BE as a compound is classified as a pentacyclic triterpene of the lupane type, having three highly reactive moieties in its structure. Its mechanism of action is based on the inhibition of key components of signaling pathways associated with proliferation, migration, interleukins, and others. BE also has a number of biological properties, i.e., anti-inflammatory, hepatoprotective, neuroprotective, as well as antitumor. Due to its poor bioavailability, betulin is subjected to chemical modifications, obtaining derivatives with proven enhanced pharmacological and pharmacokinetic properties as a result. The method of synthesis and substituents significantly influence the effect on cells and GI cancers. Moreover, the cytotoxic effect is highly dependent on the derivative as well as the individual cell line. The aim of this study is to review the methods of synthesis of BE and its derivatives, as well as its pharmacological properties and molecular mechanisms of action in colorectal cancer, hepatocellular carcinoma, gastric cancer, and esophageal cancer neoplasms. [ABSTRACT FROM AUTHOR]