Immune System Function Research Articles

Mechanistic insights into behavioral clusters associated with cancer-related systemic inflammatory response.

This focused, narrative review mostly describes our team's investigations into the potential inflammatory mechanisms that contribute to the development of cancer-related gastrointestinal (GI) mucositis and its associated symptoms. This review summarizes details of our clinical and preclinical findings to test the role of inflammation in the development and occurrence of these cancer-related conditions. GI mucositis (GIM) is a common, distressing condition reported by cancer patients. GIM is often clustered with other behaviors including fatigue, pain, anorexia, depression, and diarrhea. It is hypothesized that there is a common biologic mechanism underpinning this symptom cluster. Our multi-platform investigations revealed that GIM and its associated cluster of behaviors may be triggered by local inflammation spreading systemically causing pro-inflammatory-mediated toxicities, leading to alterations in immune, metabolic, and nervous system functions and activities. For example, behavioral toxicities related to local irradiation for non-metastatic cancer may be triggered by mGluR5 activation influencing prolonged T cell as well as NF-κB transcription factor activities. Thus, interventions targeting inflammation and associated pathways may be a reasonable strategy to alleviate GIM and its symptom cluster. GIM may be a sign of a broader systemic inflammatory response triggered by cancer or its treatment. Addressing GIM and its associated symptoms primarily involves supportive care strategies focused on relieving symptoms, promoting healing, and preventing complications.

Ultra-processed foods, allergy outcomes and underlying mechanisms in children: An EAACI task force report.

Consumption of ultra-processed foods [UPFs] may be associated with negative health outcomes. Limited data exist regarding the potential role of UPFs in the occurrence of allergic diseases. The underlying mechanisms underpinning any such associations are also poorly elucidated. We performed a systematic review and narrative evidence synthesis of the available literature to assess associations between UPF consumption and pediatric allergy outcomes (n = 26 papers), including data on the association seen with the gut microbiome (n = 16 papers) or immune system (n = 3 papers) structure and function following PRISMA guidelines. Dietary exposure to fructose, carbonated soft drinks, and sugar intake was associated with an increased risk of asthma, allergic rhinitis, and food allergies in children. Commercial baby food intake was associated with childhood food allergy. Childhood intake of fructose, fruit juices, sugar-sweetened beverages, high carbohydrate UPFs, monosodium glutamate, UPFs, and advanced glycated end-products (AGEs) was associated with the occurrence of allergic diseases. Exposure to UPFs and common ingredients in UPFs seem to be associated with increased occurrence of allergic diseases such as asthma, wheezing, food allergies, atopic dermatitis, and allergic rhinitis, in many, but not all studies. More preclinical and clinical studies are required to better define the link between UPF consumption and the risk of allergies and asthma. These observational studies ideally require supporting data with clearly defined UPF consumption, validated dietary measures, and mechanistic assessments to definitively link UPFs with the risk of allergies and asthma.

Childhood B cell leukemia: Intercepting the paths to progression.

B-cell Acute Lymphoblastic Leukemia (B-ALL) is the most common pediatric cancer, arising most often in children aged 2-5 years. This distinctive age distribution hints at an association between B-ALL development and disrupted immune system function during a susceptible period during childhood, possibly triggered by early exposure to infection. While cure rates for childhood B-ALL surpass 90% in high-income nations, survivors suffer from diminished quality of life due to the side effects of treatment. Consequently, understanding the origins and evolution of B-ALL, and how to prevent this prevalent childhood cancer, is paramount to alleviate this substantial health burden. This article provides an overview of our current understanding of the etiology of childhood B-ALL and explores how this knowledge can inform preventive strategies.

Immune-dysregulation harnessing in myeloid neoplasms.

Myeloid malignancies arise in bone marrow microenvironments and shape these microenvironments in favor of malignant development. Immune suppression is one of the most important stages in myeloid leukemia progression. Leukemic clone expansion and immune dysregulation occur simultaneously in bone marrow microenvironments. Complex interactions emerge between normal immune system elements and leukemic clones in the bone marrow. In recent years, researchers have identified several of these pathological interactions. For instance, recent works shows that the secretion of inflammatory cytokines such as tumor necrosis factor-α (TNF-α), from bone marrow stromal cells contributes to immune dysregulation and the selective proliferation of JAK2V617F+ clones in myeloproliferative neoplasms. Moreover, inflammasome activation and sterile inflammation result in inflamed microenvironments and the development of myelodysplastic syndromes. Additional immune dysregulations, such as exhaustion of T and NK cells, an increase in regulatory T cells, and impairments in antigen presentation are common findings in myeloid malignancies. In this review, we discuss the role of altered bone marrow microenvironments in the induction of immune dysregulations that accompany myeloid malignancies. We also consider both current and novel therapeutic strategies to restore normal immune system function in the context of myeloid malignancies.

Study on interaction with high-abundant blood proteins and identification of low-abundant proteins to 5-phenyl-1-(p-tolyl)-1 H-1,2,3-triazole by serum proteomics

In this study, a comprehensive investigation was undertaken to elucidate a simple triazole compound, 5-phenyl-1-(p-tolyl)-1 H-1,2,3-triazole (PPTT), its interactions with high-abundant proteins and identification of low-abundant proteins by serum proteomics. Employing a combination of spectroscopic techniques and computational chemistry, the interactions between PPTT and three high-abundance blood globular proteins, namely human serum albumin (HSA), human immunoglobulin G (HIgG), and hemoglobin (BHb), were explored, thereby ascertaining their binding constants and thermodynamic parameters at the molecular level. Subsequently, based on the differential proteomics, utilizing two-dimensional gel electrophoresis (2-DE) in conjunction with matrix-assisted laser desorption time-of-flight mass spectrometry (MALDI-TOF-MS), the research team isolated and identified differentially expressed low-abundance proteins in human blood serum samples following exposure to PPTT. The results showed that there were twenty highly expressed proteins identified from blood serum samples intervened by PPTT. Combining bioinformatics techniques, these proteins were classified, providing preliminary insights like preproprotein or precursors inhibiting the activity of elastase, defending and regulating the immune system, carrying lipid, and other functions into their biological functionalities. One of the differential proteins, apolipoprotein A-1 (ApoA-1) protein, was selected as a possible target to explore the mechanism of action of PPTT intervention on the related signaling pathways involved in human hepatocellular carcinomas(Hep G2) cells. These research findings offer scientifically sound guidance for further in-depth exploration, development, and application of the 1,2,3-triazole compound.

Viral Factors in Modulation of Host Immune Response: A Route to Novel Antiviral Agents and New Therapeutic Approaches.

Viruses utilize host cells at all stages of their life cycle, from the transcription of genes and translation of viral proteins to the release of viral copies. The human immune system counteracts viruses through a variety of complex mechanisms, including both innate and adaptive components. Viruses have an ability to evade different components of the immune system and affect them, leading to disruption. This review covers contemporary knowledge about the virus-induced complex interplay of molecular interactions, including regulation of transcription and translation in host cells resulting in the modulation of immune system functions. Thorough investigation of molecular mechanisms and signaling pathways that are involved in modulating of host immune response to viral infections can help to develop novel approaches for antiviral therapy. In this review, we consider new therapeutic approaches for antiviral treatment. Modern therapeutic strategies for the treatment and cure of human immunodeficiency virus (HIV) are considered in detail because HIV is a unique example of a virus that leads to host T lymphocyte deregulation and significant modulation of the host immune response. Furthermore, peculiarities of some promising novel agents for the treatment of various viral infections are described.

The kynurenine pathway in patients with rheumatoid arthritis during tumor necrosis factor α inhibitors treatment.

The importance of the kynurenine pathway in normal immune system function has led to an appreciation of its possible contribution to autoimmune disorders such as rheumatoid arthritis (RA). The aim of the study was to evaluate the effect of treatment with tumor necrosis factor α (TNF-α) inhibitors on the activity of the kynurenine pathway in patients with RA. This was an investigator-initiated, prospective, observational study. The study was performed on 30 RA patients (Caucasian, 11 male, 19 female; mean age 45 ±16 years) treated with TNF-α inhibitors. All patients were assessed before and after 6 months of therapy. As a control group, age- and sex-matched, 20 healthy volunteers were recruited. Disease activity was evaluated by the Modified Disease Activity Score with 28-joint count (DAS28). Inflammatory markers were assessed routinely by the hospital central laboratory. Serum concentrations of kynurenine, serotonin and tryptophan were measured with specific immunoassays. To estimate indoleamine 2,3-dioxygenase (IDO) activity, kynurenine-to-tryptophan ratio was calculated. The results of our study showed changes in tryptophan metabolism in RA patients, compared with healthy controls. Surprisingly, RA patients had statistically significant decreased kynurenine-to-tryptophan ratio (p = 0.003), which could indicate diminished IDO activation in RA. Moreover, we found no significant changes in kynurenine-to-tryptophan ratio after treated with TNF-α inhibitors (p = 0.490), despite disease remission. Additionally, tryptophan metabolism activity did not correlate with objective markers of inflammation. The RA patients had altered tryptophan metabolism, compared with healthy controls. The mechanisms affecting tryptophan metabolism in RA may be complex. We believe that continuing elucidation of pathophysiological pathways relevant in RA offer substantial hope for the development of specific pharmacotherapy for treatment of RA - especially for comorbidity of RA and depression.

Structure, function, and immunomodulation of the CD8 co-receptor.

Expressed on the surface of CD8+ T cells, the CD8 co-receptor is a key component of the T cells that contributes to antigen recognition, immune cell maturation, and immune cell signaling. While CD8 is widely recognized as a co-stimulatory molecule for conventional CD8+ αβ T cells, recent reports highlight its multifaceted role in both adaptive and innate immune responses. In this review, we discuss the utility of CD8 in relation to its immunomodulatory properties. We outline the unique structure and function of different CD8 domains (ectodomain, hinge, transmembrane, cytoplasmic tail) in the context of the distinct properties of CD8αα homodimers and CD8αβ heterodimers. We discuss CD8 features commonly used to construct chimeric antigen receptors for immunotherapy. We describe the molecular interactions of CD8 with classical MHC-I, non-classical MHCs, and Lck partners involved in T cell signaling. Engineered and naturally occurring CD8 mutations that alter immune responses are discussed. The applications of anti-CD8 monoclonal antibodies (mABs) that target CD8 are summarized. Finally, we examine the unique structure and function of several CD8/mAB complexes. Collectively, these findings reveal the promising immunomodulatory properties of CD8 and CD8 binding partners, not only to uncover basic immune system function, but to advance efforts towards translational research for targeted immunotherapy.

Assessment of the hormesis effect and toxic damage of short-term low-dose aflatoxin B1 in grass carp (Ctenopharyngodon idellus)

The present study was conducted to evaluate the hormesis and toxicity of short-term low-dose aflatoxin B1 in grass carp (Ctenopharyngodon idellus). Triplicate isonitrogenous and isocaloric aflatoxin B1 diets—CD (control, 0 ug/kg), D1 (20 ug/kg), and D2 (500 ug/kg)—were prepared and fed to grass carp with an initial mean body weight of (15.2 ± 0.1) g for 56 days. The results showed that the weight gain rate and specific growth rate of grass carp fed diet D2 were significantly higher, and the feed coefficient and crude fat content of the whole body were significantly lower (P < 0.05) compared with those fed diet CD. Serum superoxide dismutase content of grass carp fed D1 diet increased significantly (P < 0.05) with an increasing dose of aflatoxin B1, but when the dose reached 500 ug/kg (D2), serum superoxide dismutase, complement C3, and immunoglobulin M of grass carp decreased significantly (P < 0.05), while malondialdehyde increased significantly (P < 0.05). After short-term feeding of aflatoxin B1-containing diets (D1 and D2), liver body index, visceral body index, serum total cholesterol, triglyceride, and urea nitrogen content of grass carp increased significantly (P < 0.05), total bile acid secretion decreased significantly (P < 0.05), and structural damages such as increase in vacuoles, organizational structure loosening, and nucleus translocation were observed in the liver. Meanwhile, liver function indexes such as serum alanine aminotransferase, aspartate aminotransferase, and alkaline phosphatase increased significantly with the increase of aflatoxin B1 dose (P < 0.05). In addition, the height of intestinal villi, crypt depth, villus–crypt ratio, and tubular cell number, as well as the content of trypsin and lipase activities in the intestine of grass carp in the D2 group, were significantly higher than those in the CD group (P < 0.05). In conclusion, after a short-term intake of low doses of aflatoxin B1 (≤500 ug/kg), the toxicological damage of aflatoxin B1 was pronounced, although it produced a certain degree of hormesis on the growth performance and intestinal structure and function of grass carp. At a dose of 20 ug/kg, the non-specific immune system and liver structure and function of grass carp showed obvious toxic damage.

Obesity and the gut microbiota: implications of neuroendocrine and immune signaling.

Obesity is a major health challenge due to its high prevalence and associated comorbidities. The excessive intake of a diet rich in fat and sugars leads to a persistent imbalance between energy intake and energy expenditure, which increases adiposity. Here, we provide an update on relevant diet-microbe-host interactions contributing to or protecting from obesity. In particular, we focus on how unhealthy diets shape the gut microbiota and thus impact crucial intestinal neuroendocrine and immune system functions. We describe how these interactions promote dysfunction in gut-to-brain neuroendocrine pathways involved in food intake control and postprandial metabolism and elevate the intestinal proinflammatory tone, promoting obesity and metabolic complications. In addition, we provide examples of how this knowledge may inspire microbiome-based interventions, such as fecal microbiota transplants, probiotics, and biotherapeutics, to effectively combat obesity-related disorders. We also discuss the current limitations and gaps in knowledge of gut microbiota research in obesity.

Circular RNA Profile in Atherosclerotic Disease: Regulation during ST-Elevated Myocardial Infarction.

Circular (circ) RNAs are non-coding RNAs with important functions in the nervous system, cardiovascular system, and cancer. Their role in atherosclerosis and myocardial infarction (MI) remains poorly described. We aim to investigate the potential circRNAs in immune cells during atherogenesis and examine the most regulated during MI and the modulation by interleukin (IL)-6 receptor inhibition by tocilizumab. Wild-type (WT) and ApoE-/- mice were fed an atherogenic diet for 10 weeks, and the circRNA profile was analyzed by circRNA microarray. Whole blood from patients with ST-elevated MI (STEMI) and randomized to tocilizumab (n = 21) or placebo (n = 19) was collected at admission, 3-7 days, and at 6 months, in addition to samples from healthy controls (n = 13). Primers for human circRNA were designed, and circRNA levels were measured using RT-qPCR. mRNA regulation of predicted circRNA targets was investigated by RNA sequencing. The expression of 867 circRNAs differed between atherogenic and WT mice. In STEMI patients, circUBAC2 was significantly lower than in healthy controls. CircANKRD42 and circUBAC2 levels were inversely correlated with troponin T, and for circUBAC2, an inverse correlation was also seen with final infarct size at 6 months. The predicted mRNA targets for circUBAC2 and circANKRD42 were investigated and altered levels of transcripts involved in the regulation of inflammatory/immune cells, apoptosis, and mitochondrial function were found. Finally, tocilizumab induced an up-regulation of circANKRD42 and circUBAC2 3-7 days after percutaneous coronary intervention. CircRNA levels were dysregulated in STEMI, potentially influencing the immune system, apoptosis, and mitochondrial function.

Bacteria, Fungi, and Scalp Psoriasis: Understanding the Role of the Microbiome in Disease Severity.

Background: Psoriasis is a chronic skin condition affected by genetic and environmental factors. Changes in the skin microbiome may affect the immune system and skin barrier functions, thereby contributing to the development and progression of psoriasis. The scalp, which is a common site for psoriasis, is often resistant to therapy. Although several studies have investigated the scalp microbiome, analyses focusing on both bacteria and fungi remain scarce. Methods: We examined the scalp microbiomes of 11 patients with psoriasis complicated with scalp lesions and categorized them according to their Psoriasis Area Severity Index (PASI) scores. The bacterial and fungal data were analyzed using QIIME2 pipeline version 2021.04 and the UNITE database version 8.3, respectively. Results: The Shannon indices for mild (2 patients), moderate (4 patients), and severe (5 patients) groups were 0.97, 1.38, and 1.88, respectively. A significant correlation was observed between increased mycobiome diversity and disease severity (p = 4.07 × 10-5, Spearman's correlation: 0.9269). Compared with the mild and moderate groups, the severe group exhibited a higher abundance of Malassezia globosa. Pseudomonas and Staphylococcus were, respectively, more prevalent in the moderate and severe groups than in the mild group. Conclusions: This study highlights the potential role of increased fungal diversity and specific microbial compositions in the severity of scalp psoriasis, suggesting a possible avenue for targeted therapeutic interventions.

Advances in gene therapy for inborn errors of immunity

Inborn errors of immunity (IEI) are a diverse group of disorders caused by defects in immune system structure or function, involving both innate and adaptive immunity. The 2022 update of the IEI classification includes 485 distinct disorders, categorized into ten major disease groups. With the rapid development of molecular biology, the specific pathogenesis of many IEI has been revealed, making gene therapy possible in preclinical and clinical research of this type of disease. This article reviews the advancements in gene therapy for IEI, aiming to increase awareness and understanding of these disorders.

Pleiotropicity of immunomodulating effects of synthetic thymic hexapeptide in chronic infectious and inflammatory diseases of the genital tract in immunocompromized women

A reason for a protracted course and frequent recurrence of pelvic inflammatory diseases (PID) is dysfunction of the immune system, which dictates the need of effective immunotherapeutic approaches. Objective: to clarify the features of immune system functioning, the interferon system, the profile of cytokines during the period of exacerbation of PID in women; to develop targeted immunotherapy using hexapeptide with assessment of its effectiveness. The studied immunocompromised women 20-40 years old with exacerbation of PID were divided into study groups (SG): SG1 (n = 22), SG2 (n = 70) before treatment; SG1a, SG1 receiving standard therapy; SG2a, SG2, receiving standard therapy and hexapeptide (HP, Imunofan®). The parameters of cellular and humoral immunity, levels of serum interferons, cytokines were determined. During exacerbation of PID, a decrease in IFNα was in both groups and IFNγ, more pronounced in SG1. In SG1, the levels of IL-6, TNFα were increased, the level of IL-8 was decreased. In SG2, the level of IL-6 was increased. An increase in IL-4, IL-10 was noted in both groups. Against the background of IFNα, IFNγ deficiency and cytokine imbalance, a significant decrease in T lymphocytes, T helper cells, B lymphocytes was observed in both study groups. After standard treatment, there was no recovery of IFNα, IFNγ. Only TNFα decreased, the levels of IL-1β, IL-6 were increased at the end of treatment, there was no increase in IL-4, IL-10 and restoration of cellular and humoral immunity. It leads to maintaining chronic inflammation and exacerbation of PID within 3 months after treatment. After immunotherapy including fHP, IFNα was restored in 50% cases. There was a decrease in IL-1β, TNFα without significant changes in the levels of IL-8, IL-18. Resolution of inflammation was accompanied by an increase in IL-10. The modulating effect of fHP on interferons and cytokines contributed to the restoration of T cell and humoral immunity, which is related to the onset of clinical remission of PID at an earlier time and an increase in the duration of the inter-relapse period. The positive effectiveness of immunotherapy with Imunofan® is due to its pleiotropic effects, which provides significant advantages compared to the use of standard therapy only.

Emerging Landscape of In Vitro Models for Assessing Rheumatoid Arthritis Management.

Rheumatoid arthritis (RA) is a complex condition that is influenced by various causes, including immunological, genetic, and environmental factors. Several studies using animal models have documented immune system dysfunction and described the clinical characteristics of the disease. These studies have provided valuable insights into the pathogenesis of inflammatory arthritis and the identification of new targets for treatment. Nevertheless, none of these animal models successfully replicated all the characteristics of RA. Additionally, numerous experimental medications, which were developed based on our enhanced comprehension of the immune system's function in RA, have shown potential in animal research but ultimately proved ineffective during different stages of clinical trials. There have been several novel therapy alternatives, which do not achieve a consistently outstanding therapeutic outcome in all patients. This underscores the importance of employing the progress in in vitro models, particularly 3D models like tissue explants, and diverse multicomponent approaches such as coculture strategies, synovial membrane, articular cartilage, and subchondral bone models that accurately replicate the structural characteristics of RA pathophysiology. These methods are crucial for the advancement of potential therapeutic strategies. This review discusses the latest advancements in in vitro models and their potential to greatly impact research on managing RA.

The Protective Effect of Octanoic Acid on Sepsis: A Review.

Sepsis, a systemic inflammation that occurs in response to a bacterial infection, is a significant medical challenge. Research conducted over the past decade has indicated strong associations among a patient's nutritional status, the composition of their gut microbiome, and the risk, severity, and prognosis of sepsis. Octanoic acid (OA) plays a vital role in combating sepsis and has a protective effect on both animal models and human patients. In this discussion, the potential protective mechanisms of OA in sepsis, focusing on its regulation of the inflammatory response, immune system, oxidative stress, gastrointestinal microbiome and barrier function, metabolic disorders and malnutrition, as well as organ dysfunction are explored. A comprehensive understanding of the mechanisms by which OA act may pave the way for new preventive and therapeutic approaches to sepsis.

Colony-stimulating factor 2 (CSF2) as a gut microbiome dependent immune factor that alters molecular and behavioral responses to cocaine in male mice

Cocaine use disorder is a condition that leads to tremendous morbidity and mortality for which there are currently no FDA-approved pharmacotherapies. Previous research has demonstrated an important role for the resident population of bacteria of the large intestine, collectively dubbed the gut microbiome, in modulating brain and behavior in models of cocaine and other substance use disorders. Importantly, previous work has repeatedly shown that depletion of the gut microbiome leads to increased cocaine taking and seeking behaviors in multiple models. While the precise mechanism of these gut-brain signaling pathways in models of cocaine use is not fully clear, and intriguing possibility is through gut microbiome influences on innate immune system function. In this manuscript we identify the cytokine colony stimulating factor 2 (CSF2) as an immune factor that is increased by cocaine in a gut microbiome dependent manner. Peripherally injected CSF2 crosses the blood–brain barrier into the nucleus accumbens, a brain region central to behavioral responses to cocaine. Treatment with peripheral CSF2 reduces acute and sensitized locomotor responses to cocaine as well as reducing cocaine place preference at high doses. On a molecular level, we find that peripheral injections of CSF2 alter the transcriptional response to both acute and repeated cocaine in the nucleus accumbens. Finally, treatment of microbiome depleted mice with CSF2 reverses the behavioral effects of microbiome depletion on the conditioned place preference assay. Taken together, this work identifies an innate immune factor that represents a novel gut-brain signaling cascade in models of cocaine use and lays the foundations for further translational work targeting this pathway.

IL-33 prevents age-related bone loss and memory impairment by suppression of Th17 response: evidence in a d-galactose-induced aging mouse model.

Cytokines are the primary mediators of age-related disorders. The IL-17/IL-10 axis plays a crucial role in bone destruction and neuro-inflammation. Additionally, a new Th2 cytokine-IL-33-has gained attention for its potential implications in aging-associated conditions. However, the involvement of IL-33 in aging-mediated bone loss and memory impairment remains unclear and needs further investigation. This study reveals the impact of IL-33 on various aspects of the immune system, bone health, and neural functions. To induce senescence, we used d-galactose for its convenience and fewer side effects. The experimental design involved treating 20-week-old C57BL/6J mice with d-galactose subcutaneously for 10weeks to induce aging-like effects. Thereafter, IL-33 recombinant protein was administered intraperitoneally for 15days to evaluate its impact on various immune, skeletal, and neural parameters. The results demonstrated that d-galactose-induced aging led to bone loss and compromised osteogenic parameters, accompanied by increased oxidative stress and neurodegeneration in specific brain regions. Behavioral activities were also affected. However, supplementation with IL-33 mitigated these effects, elevating osteogenic parameters and reducing senescence markers in osteoblast cells in an aging mouse model and exerted neuroprotective potential. Notably d-galactose-induced aging was characterized by high bone turnover, reflected by altered serum levels of CTX, PTH, beta-galactosidase, and P1NP. IL-33 treatment attenuated these effects, suggesting its role in regulating bone metabolism. Furthermore, d-galactose-induced aging was associated with increased differentiation of Th17 cells and upregulation of associated markers, such as STAT-3 and ROR-γt, while downregulating Foxp3, which antagonizes Th17 cell differentiation. IL-33 treatment countered these effects by suppressing Th17 cell differentiation and promoting IL-10-producing T-regulatory cells. Overall, these findings provide insights into the potential therapeutic implications of IL-33 in addressing aging-induced bone loss and memory impairment.

Chinese guidelines for integrated diagnosis and treatment of intestinal microecology technologies in tumor application (2024 Edition).

Intestinal microecology (IM) is the largest and most important microecological system of the human body. Furthermore, it is the key factor for activating and maintaining the physiological functions of the intestine. Numerous studies have investigated the effects of the gut microbiota on the different tissues and organs of the human body as well as their association with various diseases, and the findings are gradually being translated into clinical practice. The gut microbiota affects the occurrence, progression, treatment response, and toxic side effects of tumors. The deepening of research related to IM and tumors has opened a new chapter in IM research driven by methods and technologies such as second-generation sequencing and bioinformatics. The IM maintains the function of the host immune system and plays a pivotal role in tumor-control drug therapy. Increasing evidence has proven that the efficacy of tumor-control drugs largely depends on the IM balance, and strategies based on the IM technology show promising application prospects in the diagnosis and treatment of tumor. The Tumor and Microecology Professional Committee of the Chinese Anti-cancer Association gathered relevant experts to discuss and propose the "Chinese guidelines for integrated diagnosis and treatment of IM technologies in tumor application (2024 Edition)," which was established based on the research progress of the application of the IM technology in tumor to provide a basis for the standardization of the diagnosis and treatment of the IM technology in the tumor.

Pro- and anti-inflammatory cytokines are the game-changers in childhood obesity-associated metabolic disorders (diabetes and non-alcoholic fatty liver diseases).

Childhood obesity is a chronic inflammatory epidemic that affects children worldwide. Obesity affects approximately 1 in 5 children worldwide. Obesity in children can worsen weight gain and raise the risk of obesity-related comorbidities like diabetes and non-alcoholic fatty liver disease (NAFLD). It can also negatively impact the quality of life for these children. Obesity disrupts immune system function, influencing cytokine (interleukins) balance and expression levels, adipokines, and innate and adaptive immune cells. The altered expression of immune system mediators, including interleukin-1 (IL-1), interleukin-6 (IL-6), interleukin-8 (IL-8), interleukin-17 (IL-17), interleukin-18 (IL-18), transforming growth factor (TGF), tumor necrosis factor (TNF), and others, caused inflammation, progression, and the development of pediatric obesity and linked illnesses such as diabetes and NAFLD. Furthermore, anti-inflammatory cytokines, including interleukin-2 (IL-2), have been shown to have anti-diabetes and IL-1 receptor antagonist (IL-1Ra) anti-diabetic and pro-NAFLFD properties, and interleukin-10 (IL-10) has been shown to have a dual role in managing diabetes and anti-NAFLD. In light of the substantial increase in childhood obesity-associated disorders such as diabetes and NAFLD and the absence of an effective pharmaceutical intervention to inhibit immune modulation factors, it is critical to consider the alteration of immune system components as a preventive and therapeutic approach. Thus, the current review focuses on the most recent information regarding the influence of pro- and anti-inflammatory cytokines (interleukins) and their molecular mechanisms on pediatric obesity-associated disorders (diabetes and NAFLD). Furthermore, we discussed the current therapeutic clinical trials in childhood obesity-associated diseases, diabetes, and NAFLD.