Review Article
Anil Philip Kunnath; Sorfina Ahmad Hilmi; Dinesh Kumar
Abstract
Type 1 diabetes (T1DM) is an autoimmune disorder marked by a characteristic dysfunction of insulin-secreting beta-cells in the pancreatic islets. This destructive process is not a single event but a chronic inflammatory cascade, propelled by immune cells—including T-lymphocytes and macrophages—that ...
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Type 1 diabetes (T1DM) is an autoimmune disorder marked by a characteristic dysfunction of insulin-secreting beta-cells in the pancreatic islets. This destructive process is not a single event but a chronic inflammatory cascade, propelled by immune cells—including T-lymphocytes and macrophages—that release potent pro-inflammatory cytokines.
This review delves into the growing body of evidence implicating specific inflammation-promoting mediators—including Interleukin-1β (IL-1β), Tumor Necrosis Factor-α (TNF-α) and Interferon-γ (IFN-γ) —as master regulators of beta-cell death. We also explore how modern analytical techniques enable precise mapping of cytokine patterns in the blood, revealing a dynamic and ongoing disease process long that precedes clinical symptoms onset.
By weaving together findings from clinical and preclinical studies, this article argues that profiling these inflammatory signals provides a crucial real-time, functional readout of autoimmune activity that complements traditional, static autoantibody measurements. We conclude by discussing the significant potential of integrating cytokine data into existing models to create more robust risk stratification tools and to pave the way for interventions that could intercept the disease pathway before critical beta-cell mass is lost.
Original Article
hea-ju Cho; eui-hong Byun
Abstract
Background: Immunity protects organisms from pathogens, diseases, and external noxious agents. Naturally derived polysaccharides are well-documented to exhibit potent immunomodulatory effects. However, the exact immunostimulatory properties and underlying mechanisms of polysaccharides derived from Momordica ...
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Background: Immunity protects organisms from pathogens, diseases, and external noxious agents. Naturally derived polysaccharides are well-documented to exhibit potent immunomodulatory effects. However, the exact immunostimulatory properties and underlying mechanisms of polysaccharides derived from Momordica charantia (MCPS) remain to be clearly elucidated.
Objective: To investigate the immunomodulatory effects of MCPS on murine macrophages and to elucidate the underlying molecular mechanisms.
Methods: MCPS was isolated from Momordica charantia. RAW 264.7 murine macrophages were treated with varying concentrations of MCPS, and its effects on cell viability, nitric oxide (NO) production, cytokine secretion, surface marker expression, and key intracellular signaling pathways were evaluated using standardized analytical assays. Potential endotoxin contamination was systematically excluded using a polymyxin B neutralization assay.
Results: MCPS exhibited no cytotoxicity across all tested concentrations. Notably, MCPS significantly stimulated NO production and enhanced the secretion of pro-inflammatory cytokines, indicative of robust macrophage activation. This was accompanied by a marked upregulation of macrophage surface activation markers. Furthermore, MCPS activated the MAPK and NF-κB signaling pathways. This cytokine production was significantly attenuated by pathway-specific inhibitors, confirming the functional involvement of these cascades. Importantly, polymyxin B suppressed LPS-induced responses but did not alter MCPS- stimulated activation, indicating that the immunomodulatory effects were independent of endotoxin contamination.
Conclusion: MCPS effectively promotes murine macrophage activation without cytotoxicity by stimulating NO production, cytokine secretion, and activation marker expression through the MAPK and NF-κB signaling pathways. These findings demonstrate that MCPS holds strong potential as a natural immunostimulatory agent capable of enhancing host immune responses.
Original Article
Liqiang Zhang; Nan Luo; Haiying Zan; Xia Li; Peichun Li
Abstract
Background: Patients with advanced non-small cell lung cancer (NSCLC) often experience poor clinical outcomes following chemotherapy. Heat-sensitive moxibustion (HSM), a traditional therapeutic intervention, has been reported to improve symptoms and quality of life in patients with cancer.Objective: ...
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Background: Patients with advanced non-small cell lung cancer (NSCLC) often experience poor clinical outcomes following chemotherapy. Heat-sensitive moxibustion (HSM), a traditional therapeutic intervention, has been reported to improve symptoms and quality of life in patients with cancer.Objective: To evaluate the effect of HSM in patients with advanced NSCLC following chemotherapy.Methods: Between January 2023 and February 2024, patients with advanced NSCLC were enrolled. Eligible patients were randomly assigned to either the chemotherapy (control) group or the chemotherapy plus HSM treatment (HSM) group. Following treatment, the percentages of CD4+ T cell subsets were evaluated, and the serum levels of CD4+ T cells-associated cytokines were measured using enzyme-linked immunosorbent assay (ELISA). The expression levels of CD4+ T cells-related factors were assessed by RT-qPCR and Western blot analysis. The overall response rate (OPR) and disease control rate (DCR), Karnofsky Performance Status (KPS) score, and incidence of adverse events were compared between the two groups.Results: A total of 90 patients with NSCLC were included with 45 patients in each group. The ratio of Th1/Th2 was significantly elevated, whereas the Treg/Th17 ratio was significantly decreased in the HSM group compared with the control group. The HSM group exhibited higher serum levels of IL-2, IL-17A and IFN-γ, and lower levels of IL-4 and IL-10 than the control group. HSM treatment significantly upregulated the expression of T-bet and IL-17A while downregulating GATA3 expression at both the mRNA and protein levels. The HSM group demonstrated superior clinical outcomes, as evidenced by higher KPS score, ORR, DCR, along with a lower incidence of adverse events.Conclusion: HSM may enhance immune function in patients with advanced NSCLC undergoing chemotherapy by modulating the balance of Th1/Th2 and Treg/Th17 cell subsets.
Original Article
Gulnihal Sisman; Ayfer Sendul; Abdurrahim Kocyigit
Abstract
Background: Natural Killer (NK) cells are innate lymphoid cells that eliminate malignant cells via perforin/granzyme-mediated cytotoxicity. This study investigates whether Olive Leaf Extract (OLE), rich in oleuropein and hydroxytyrosol, can enhance NK-cell cytotoxicity against colorectal cancer (CRC) ...
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Background: Natural Killer (NK) cells are innate lymphoid cells that eliminate malignant cells via perforin/granzyme-mediated cytotoxicity. This study investigates whether Olive Leaf Extract (OLE), rich in oleuropein and hydroxytyrosol, can enhance NK-cell cytotoxicity against colorectal cancer (CRC) cells. Although OLE exhibits direct anticancer effects, its therapeutic utility is constrained by poor bioavailability, requiring supraphysiological concentrations for direct cytotoxicity.
Objective: To evaluate the effect of OLE on the cytotoxic activity of NK-92 cells against HT-29 colorectal cancer cells within a co-culture model.
Methods: Olive leaves obtained from Balıkesir, Türkiye were dried and extracted with 70% methanol. The effects of OLE on the viability of HT-29 cells and NK-92 cells were evaluated using MTT and ATP assays. Additionally, the cytotoxic activity of NK-92 cells against HT-29 cells was assessed in a direct co-culture system. Granzyme B and perforin levels were measured using ELISA kits.
Results: OLE inhibited the proliferation of HT-29 cells in a dose-dependent manner, with an IC₅₀ values of 548 µg/mL. In NK-92 cells, low concentrations of OLE (100–200 µg/mL) promoted cell proliferation, whereas higher concentrations exerted cytotoxic effects. In co-culture experiments, NK-92-mediated cytotoxicity against HT-29 cells was significantly enhanced by the addition of OLE at non-toxic concentrations (100 and 200 µg/mL). This enhanced cytotoxicity was further supported by a significant increase in granzyme B and perforin levels following OLE treatment.
Conclusion: Our findings suggest that OLE can elicit a potent anticancer response via NK cells at lower, physiologically achievable doses. These results highlight a promising therapeutic strategy for CRC, leveraging OLE's immunomodulatory effects to enhance innate antitumor defenses.
Original Article
Saghi Khatami; Saba Ebrahimi; Fatemeh Elham Mahjoub; Azizollah Yousefi; Amirhossein Hosseini; Majid Khoshmirsafa; Fatemehsadat Mousavinasab; Mahboubeh Mansouri; Mahdi Shabani; Mehrnaz Mesdaghi
Abstract
Background: Eosinophilic colitis (EC) is a rare eosinophilic gastrointestinal disorder with increasing frequency in recent years. Although normal eosinophil density varies substantially by colonic segment, several proposed eosinophil thresholds have been used in the literature to support the diagnosis ...
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Background: Eosinophilic colitis (EC) is a rare eosinophilic gastrointestinal disorder with increasing frequency in recent years. Although normal eosinophil density varies substantially by colonic segment, several proposed eosinophil thresholds have been used in the literature to support the diagnosis in the appropriate clinical context. However, some patients with clinical features suggestive of eosinophilic colitis (EC) do not demonstrate increased tissue eosinophil counts on histopathologic examination..
Objective: To compare eosinophil-derived cell-free granules based on expression of their surface markers between two groups of patients with symptoms consistent with EC: those with increased tissue eosinophils and those without tissue eosinophilia.
Methods: This study included 10 pediatric patients with histologically confirmed EC and 13 patients with clinical suspicion of EC. Eosinophil-derived cell-free granules were evaluated in colonic tissue samples using immunohistochemistry (IHC), with antibodies against MBP and CCR3.
Results: Eosinophil-derived cell-free granules were detected in all specimens from patients with suspected EC and in the majority of specimens from patients with confirmed EC. Degranulating eosinophils were identified in all specimens from both groups, although the proportion of degranulating eosinophils varied among patients. Furthermore, the abundance of granules was significantly associated with the percentage of degranulating eosinophils.
Conclusion: Our findings indicate that IHC can be used to detect eosinophil-derived granules in colonic tissue. The presence of cell-free eosinophil granules with varying abundance, along with evidence of eosinophil degranulation in all specimens from patients with suspected EC, may provide supportive histopathological features that contribute to improving the diagnostic assessment of EC.
Original Article
Long Gao; Nara Davtyan; Ruiyong Zhang
Abstract
Background: Streptococcus pneumoniae remains a leading cause of community-acquired pneumonia. Severe pulmonary inflammation and subsequent tissue damage are driven significantly by the overexpression of both the Nuclear Factor kappa-light-chain-enhancer of activated B cells (NF-κB) and Mitogen-Activated ...
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Background: Streptococcus pneumoniae remains a leading cause of community-acquired pneumonia. Severe pulmonary inflammation and subsequent tissue damage are driven significantly by the overexpression of both the Nuclear Factor kappa-light-chain-enhancer of activated B cells (NF-κB) and Mitogen-Activated Protein Kinase (MAPK) signaling pathways.
Objective: To investigate the immunomodulatory effects of rhein in a mouse model of Streptococcus pneumoniae-induced pneumonia .
Methods: Forty male C57BL/6 mice were randomly assigned to four experimental groups: healthy control, S. pneumoniae infected control, and two rhein-treatment groups (10 mg/kg and 30 mg/kg). Expression levels of tumor necrosis factor-α (TNF-α), interleukin (IL)-1β, IL-6, IL-10, transforming growth factor (TGF)-β, monocyte chemoattractant protein-1 (MCP-1), cyclooxygenase-2 (COX-2), and inducible nitric oxide synthase (iNOS) in lung tissues and bronchoalveolar lavage fluid (BALF) were quantified using reverse transcription-polymerase chain reaction (RT-PCR) and enzyme-linked immunosorbent assay (ELISA). Additionally, ELISA and Western blotting were employed to assess the phosphorylation profiles of MAPK and NF-κB.
Results: Rhein significantly decreased the lung wet/dry weight ratio, reduced bacterial load, and downregulated COX-2 and iNOS expression. Cytokine analysis revealed marked reductions in pro-inflammatory mediators (IL-6, IL-1β, TNF-α, and MCP-1) alongside elevated levels of the anti-inflammatory cytokine IL-10 in both lung tissues and BALF. Furthermore, ELISA and Western blotting confirmed that rhein significantly inhibited the phosphorylation of MAPK and NF-κB.
Conclusion: Rhein attenuates S. pneumoniae-induced pulmonary inflammation and injury by modulating the MAPK/NF-κB signaling pathways. These findings highlight Rhein as a promising potential therapeutic agent for pneumococcal pneumonia and related inflammatory lung diseases.
Original Article
Zainab Abdul Ammer Hasan; Hanaa Kamil Hamad
Abstract
Background: Toxoplasma gondii is an obligate intracellular protozoan parasite with a unique global prevalence and is the causative agent of toxoplasmosis. MicroRNAs are key epigenetic elements crucial that modulate the immune response by influencing cytokine expression.
Objectives: To investigate ...
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Background: Toxoplasma gondii is an obligate intracellular protozoan parasite with a unique global prevalence and is the causative agent of toxoplasmosis. MicroRNAs are key epigenetic elements crucial that modulate the immune response by influencing cytokine expression.
Objectives: To investigate serum levels of IL-37 alongside the expression of microRNAs miR-604 and miR-1302-3p in Iraqi patients with toxoplasmosis, and to evaluate their potential correlations and regulatory relationships.
Methods: A total of 200 non-pregnant women were enrolled in the present study, consisting of 100 toxoplasmosis- positive and 100 healthy controls. Toxoplasmosis status was determined via serological screening using a rapid diagnostic test (TORCH) and ELISA for IgM, IgG antibodies. For the molecular analysis, total RNA was extracted from whole blood samples and reverse-transcribed into cDNA. Quantitative real-time PCR (RT-qPCR) was then performed on both groups to quantify the expression levels of microRNA-604 and microRNA-1302-3p.
Result: The expression levels of both microRNA-604 and microRNA 1302-3p were significantly reduced in toxoplasmosis patients compared to the control group in patients (relative expression: 2.1896 ± 1.12221 ng/L vs. 1.6384 ± 1.09466 for microRNA-604; 4.0896 ± 1.42896vs. 2.5764 ± 1.16224 for microRNA 1302-3p). ). Conversely, serum levels of IL-37 were significantly higher in the patient group (295.0604 ± 45.79983 ng/L) compared to the control group (36.7183 ± 3.83299 ng/L).
Conclusion: Our findings demonstrate that miRNA-604 and 1302-3p are downregulated in toxoplasmosis patients, a state associated with the marked induction of pro-inflammatory cytokine IL-37. These altered expression profiles suggest a coordinated role in the pathogenesis of toxoplasmosis, highlighting their potential utility as novel diagnostic biomarkers or therapeutic targets.
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