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High-grade serous ovarian cancers (HGSOCs) likely consist of poorly differentiated stem-like cells (PDSLCs) and differentiated tumor cells. Conventional therapeutics are incapable of completely eradicating PDSLCs, contributing to disease progression and tumor relapse. Primary NK cells are known to effectively lyse PDSLCs, but they exhibit low or minimal cytotoxic potential against well-differentiated tumors. We have introduced and discussed the characteristics of super-charged NK (sNK) cells in this review. sNK cells, in comparison to primary NK cells, exhibit a significantly higher capability for the direct killing of both PDSLCs and well-differentiated tumors. In addition, sNK cells secrete significantly higher levels of cytokines, especially those known to induce the differentiation of tumors. In addition, we propose that a combination of sNK and chemotherapy could be one of the most effective strategies to eliminate the heterogeneous population of ovarian tumors; sNK cells can lyse both PDSLCs and well-differentiated tumors, induce the differentiation of PDSLCs, and could be used in combination with chemotherapy to target both well-differentiated and NK-induced differentiated tumors.

Background: Mycoplasma hyopneumoniae is the etiological agent of mycoplasmal pneumonia of swine (MPS). Commercial vaccines provide partial protection and do not prevent the colonization and transmission of M. hyopneumoniae. The bottleneck in the development of more effective vaccines for MPS is the stimulation of effective immune responses in the host. The purpose of the present study was to evaluate the immune responses of immunodominant proteins Mhp170, Mhp274 and Mhp336 in BALB/c mice. Methods: The recombinant Mhp170 (rMhp170), Mhp274 (rMhp274), and Mhp336 (rMhp336) proteins were purified from recombinant bacteria. Fifty-two six-week-old SPF female BALB/c mice were divided into five groups: a commercial inactivated vaccine-immunized group, three recombinant protein-inoculated groups, and a PBS-treated group. The physical parameters and body weights of the mice were observed during the experiment. The lung/body coefficient and macroscopic and microscopic lung lesions were evaluated. IgG and its isotypes IgG1 and IgG2a in serum and BALF and sIgA in BALF were assessed. The levels of IFN-γ, IL-4, and IL-17, in the supernatants of splenocytes and in serum were measured, and the mRNA levels of three cytokines in splenocytes were analyzed. Finally, lymphocyte proliferation after stimulation with corresponding proteins or crude extract of M. hyopneumoniae J strain was assessed. Results: We successfully constructed recombinant bacteria expressing rMhp170, rMhp274, and rMhp336. None of the mice from all groups presented adverse reactions and macroscopic and microscopic lung lesions. rMhp170 and rMhp274 were capable of inducing the production of IgG, IgG1 and IgG2 in serum and BALF, the secretion of IFN-γ, IL-4 and IL-17 in serum, the expression of IFN-γ, IL-4 and IL-17 mRNAs in splenocytes, and high levels of lymphocyte proliferation. Moreover, rMhp274 significantly increased sIgA in BALF. Nevertheless, rMhp336 induced only IgG, IgG1 and IgG2 production in sera; the secretion of IFN-γ and IL-4 in sera and BALF; the expression of IFN-γ and IL-4 mRNAs in the splenocyte population; and lymphocyte proliferation. Conclusion: Mhp170 and Mhp274 induced Th1/Th2/Th17 immune responses, and Mhp336 stimulated mixed Th1/Th2-type immune responses, in mice. Our data suggest that Mhp274 is a potential viable candidate for the development of a subunit vaccine for MPS. [ABSTRACT FROM AUTHOR]

Background: Thyroid cancer is one of the deadliest malignancies. Increasing evidence suggests that interferon-γ (IFN-γ) plays an important role in anti-tumor immunity and its treatment. However, the effectiveness of classifying, predicting prognosis, and immunotherapy for thyroid cancer based on IFN-γ-related genes has not been discovered. Methods: We used the Gene Set Enrichment Analysis (GSEA) database to obtain IFN-γ-related genes and classified thyroid cancer patients from The Cancer Genome Atlas (TCGA). We systematically explored the differences among various thyroid cancer subtypes from multiple perspectives, such as Kaplan-Meier survival analysis, tumor mutation analysis, immune analysis, enrichment analysis, and drug sensitivity analysis. Finally, we screened some potential drugs suitable for each population. Results: Through clustering analysis, we obtained three thyroid cancer subtypes with different IFN-γ-related gene expression levels. The survival analysis results showed significant survival differences among these three subtypes. In addition, gene mutation analysis in different subtypes found that BRAF, TTN, and TG were the top three genes with the highest mutation frequency in the three subtypes, which may be related to their prognosis. Cluster 1 and cluster 2 were the two subtypes with the greatest difference in immune cell infiltration levels, and the differentially expressed genes were mainly enriched in immune-related biological processes or signaling pathways such as leukocyte-mediated immunity, regulation of T cell activation, and chemokine signaling pathway. Eighteen compounds such as Cyclopamine, Erlotinib, FH535, Imatinib, and A-770,041 were selected as potential therapeutic drugs in this study, and their sensitivity to different subtypes varied. Conclusion: Based on bioinformatics analysis, we discovered a new classification method based on IFN-γ genes, which could divide thyroid cancer patients into three populations with significant characteristics. Different populations had different mutation patterns, immune infiltration levels, and candidate therapeutic drugs. [ABSTRACT FROM AUTHOR]

African swine fever virus (ASFV) is a severe threat to the global pig industry, and domestic pigs mostly develop severe clinical manifestations upon viral invasion. Currently, there is no available vaccine against ASFV. Its capsid structural protein p72 is one of the immuno-dominant proteins. In this study, we unexpectedly obtained a p72 mutant protein (p72∆377–428) which deleted the aa 377–428 within p72 and had stable and high expression in E. coli. Using SWISS-MODEL 1.0 software, the prediction showed that p72∆377–428 was quite distinct from the wild-type p72 protein in structure. p72∆377–428 induced stronger antibody production in mice on day 42 and 56 post immunization and could recognize ASFV-infected swine sera. p72∆377–428 reduced IFN-γ production in the splenocytes from p72∆377–428-immunized mice and p72∆377–428-treated swine macrophages compared to p72. p72∆377–428 also decreased the production of pro-inflammatory cytokine genes, including IL-1β, IL-6, and IL-12, compared to p72 in mice. Further, we found that p72∆377–428 reduced the induction of pro-inflammatory cytokine genes by inhibiting AKT phosphorylation and HIF1α expression. Taken together, these findings have implications for immunological function and the corresponding mechanism of ASFV p72, and our study indicates that p72∆377–428 could serve as a novel candidate for ASFV vaccines and diagnostic reagents. [ABSTRACT FROM AUTHOR]

Objective(s): Adjuvants are some of the most important components used for vaccine formulation. In addition, the efficacy of vaccines is highly dependent on the nature of the adjuvants used. Therefore, new adjuvant formulations may help develop more potent vaccines. In the present study, the potency of an in-house and water-in-oil adjuvant (Yavar-70A) was compared with Montanide ISA 206 and Montanide ISA 266 in an HPV-16E7d vaccine model. Materials and Methods: Three HPV-16 E7d vaccines were formulated using three different adjuvants, Montanide ISA 206, Montanide ISA 266, and Yavar-70A, with standard protocols. Afterward, each formulation containing 10 µg of the E7d protein was administered thrice at two-week intervals to C57BL/6 mice. Serum levels of IFN-γ and IL-4 cytokines secreted from spleen cells, total IgG, and specific IgG1 and IgG2a isotypes were assessed using ELISA two weeks after the last immunization. Lymphocyte proliferative responses were also evaluated using the BrdU method. Results: The results indicated that the vaccine formulated using the Yavar-70A adjuvant showed the highest lymphocyte proliferation responses compared with other groups and higher IFN-γ cytokine release compared with that formulated using Montanide ISA 206. However, the vaccine formulated using Montanide ISA 206 induced the highest total IgG responses compared with other groups. Importantly, the vaccine formulated using Yavar-70A decreased IL-4 secretion compared with other vaccinated groups. Conclusion: The present study demonstrated that Yavar-70A induces cellular and humoral immunologic parameters against the HPV-16 E7d vaccine model comparable to commercialized oil-based adjuvants. [ABSTRACT FROM AUTHOR]

TNF and IFN-γ are key proinflammatory cytokines implicated in the pathophysiology of COVID-19. Toll-like receptor (TLR)7 and TLR8 are known to recognize SARS-CoV-2 and induce TNF and IFN-γ production. However, it is unclear whether TNF and IFN-γ levels are altered through TLR-dependent pathways and whether these pathways mediate disease severity during COVID-19. This study aimed to investigate the association between TNF/IFN-γ levels and immune cell activation to understand their role in disease severity better. We enrolled 150 COVID-19 patients, who were classified by their systemic TNF and IFN-γ levels (high (H) or normal–low (N-L)) as TNFHIFNγH, TNFHIFNγN-L, TNFN-LIFNγH, and TNFN-LIFNγN-L. Compared to patients with TNFN-LIFNγN-L, patients with TNFHIFNγH had high systemic levels of pro- and anti-inflammatory cytokines and cytotoxic molecules, and their T cells and monocytes expressed TNF receptor 1 (TNFR1). Patients with TNFHIFNγH presented the SNP rs3853839 to TLR7 and increased levels of MYD88, NFκB, and IRF7 (TLR signaling), FADD, and TRADD (TNFR1 signaling). Moreover, critical patients were observed in the four COVID-19 groups, but patients with TNFHIFNγH or TNFHIFNγN-L most required invasive mechanical ventilation. We concluded that increased TNF/IFN-γ levels are associated with hyperactive immune cells, whereas normal/low levels are associated with hypoactivity, suggesting a model to explain that the pathophysiology of critical COVID-19 may be mediated through different pathways depending on TNF and IFN-γ levels. These findings highlight the potential for exploring the modulation of TNF and IFN-γ as a therapeutic strategy in severe COVID-19. [ABSTRACT FROM AUTHOR]

Purpose: This study aimed to investigate the relationship between the interferon-gamma (IFN-γ) pathway in different tumor microenvironments (TME) and patients' prognosis, as well as the regulatory mechanisms of this pathway in tumor cells. Methods: Using RNA-seq data from the TCGA database, we analyzed the predictive value of the IFN-γ pathway across various tumors. We employed a univariate Cox regression model to assess the prognostic significance of IFN-γ signaling in different tumor types. Additionally, we analyzed single-cell RNA sequencing (scRNA-seq) data from the Gene Expression Omnibus (GEO) database to examine the distribution characteristics of the IFN-γ pathway and explore its regulatory mechanisms, highlighting how IFN-γ influenced cellular interactions within the TME. Results: Our analysis revealed a significant association between the IFN-γ pathway and adverse prognosis in pan-cancer tissues (P < 0.001). Interestingly, this correlation varied regarding positive and negative regulation across different tumor types. Through a detailed examination of scRNA-seq data, we found that the IFN-γ pathway exerted substantial regulatory effects on stromal and immune cells. In contrast, its expression and regulatory patterns in tumor cells exhibited diversity and heterogeneity. Further analysis indicated that the IFN-γ pathway not only enhanced the immunogenicity of tumor cells but also inhibited their proliferation. Cell–cell interaction analysis confirmed the pivotal role of the IFN-γ pathway within the overall regulatory network. Moreover, we identified HMGB2 (high mobility group box 2) in T cells as a potential key regulator of tumor cell proliferation. Conclusions: The IFN-γ pathway exhibited a dual function by both suppressing tumor cell proliferation and enhancing their immunogenicity, positioning it as a pivotal target for refined cancer diagnosis and cancer strategies. [ABSTRACT FROM AUTHOR]

Glioblastoma (GBM) is a highly aggressive brain cancer with a low survival rate, prompting the exploration of novel therapeutic strategies. Immune checkpoint inhibitors have shown promise in cancer treatment but are associated with immune-related toxicities and brain penetration. Here, we present a targeted approach using an adeno-associated virus serotype 9 (AAV9) to systemically deliver a single-chain fragment variable antibody against PD-1 (scFv-PD-1) into the tumor microenvironment (TME). Single-cell RNA sequencing analysis revealed robust PD-1 expression in GBM TME, predominantly on T cells. AAV9-scFv-PD-1 expressed and secreted scFv-PD-1, which effectively binds to PD-1. Systemic administration of AAV9-scFv-PD-1 in an immunocompetent GBM mouse model resulted in a robust cytolytic T-cell activation at the tumor site, marked by accumulation of IFN-γ and Granzyme B, leading to a significant reduction in tumor growth. Importantly, AAV9-scFv-PD-1 treatment conferred a survival benefit, highlighting its therapeutic potential. This study demonstrates the feasibility of systemically delivered AAV9-mediated local expression of scFv-PD-1 for targeted immunotherapy in GBM and warrants further investigation for clinical translation. [ABSTRACT FROM AUTHOR]

We demonstrate that natural killer (NK) cells induce a higher cytotoxicity against lung cancer stem-like cells (hA549) compared to differentiated lung cancer cell lines (H292). The supernatants from split-anergized NK cells (IL-2 and anti-CD16 mAb-treated NK cells) induced differentiation in hA549. Differentiated lung cancer cell line (H292) and NK cells differentiated hA549 expressed reduced NK cell-mediated cytotoxicity but expressed higher sensitivity to chemotherapeutic drugs. This finding validated our previous reports demonstrating that the levels of tumor killing by NK cells and by chemotherapeutic drugs correlate directly and indirectly, respectively, with the stage and levels of tumor differentiation. We also demonstrate the role of IFN-γ and TNF-α in inducing tumor differentiation. NK cells' supernatants or IFN-γ and TNF-α-induced tumor differentiation was blocked when we used antibodies against IFN-γ and TNF-α. Therefore, IFN-γ and TNF-α released from NK cells play a significant role in differentiating tumors, resulting in increased susceptibility of tumors to chemotherapeutic drugs. We also observed the different effects of MHC-class I antibodies in CSCs vs. differentiated tumors. Treatment with anti-MHC-class I decreased NK cell-mediated cytotoxicity in hA549 tumors, whereas it increased NK cell-mediated cytotoxicity when differentiated tumors were treated with antibodies against MHC-class I. [ABSTRACT FROM AUTHOR]

Objective: This study explores the clinical correlation between the air pollutant PM2.5 and the induction of psoriasis flare-ups through the disruption of the immune barrier. Methods: Air quality data, the average mass concentration of the primary atmospheric pollutant PM2.5, and meteorological data spanning from November 2023 to March 2024 were gathered from 9 air quality monitoring stations situated within our city, courtesy of the local Meteorological Information Center. Psoriasis cases were sourced from our hospital's dermatology department, encompassing patients diagnosed and treated from November 2023 to March 2024 and residing within the city. Results: From January 2023 to May 2024, aberrant expression of Th1 cells and Th2 cells was observed in psoriasis flare-up patients. Spearman correlation coefficient analysis revealed a positive correlation between PM2.5, PM10, and Th1 cells, and a negative correlation with Th2 cells, exhibiting significant differences (P <.05). Supplemental Figure 1 illustrates an increase in psoriasis flare-ups on the fifth day following a unit increase in PM2.5 concentration, with an excess risk (ER) value of 0.046 [95% confidence interval (CI): 0.137-0.893]. Conversely, after an increase of 1 unit of PM10, there was a decrease on the third and fourth days, followed by increases on the fifth, sixth, and seventh days, with ER values of 0.038 (95% CI: 0.013-0.067), 0.045 (95% CI: 0.019-0.073), 0.051 (95% CI: 0.034-0.078), 0.057 (95% CI: 0.045-0.083), and 0.061 (95% CI: 0.051-0.087), respectively. Conclusion: Air pollutant PM2.5 could potentially exacerbate psoriasis flare-ups by compromising the immune barrier, suggesting a plausible mechanism linked to the onset of this condition. [ABSTRACT FROM AUTHOR]

Background: Non-Small Cell Lung Cancer (NSCLC) is the leading cause of cancer death worldwide. Although immune checkpoint inhibitors (ICIs) have shown remarkable clinical efficacy, they can also induce a paradoxical cancer acceleration, known as hyperprogressive disease (HPD), whose causative mechanisms are still unclear. Methods: This study investigated the mechanisms of ICI resistance in an HPD-NSCLC model. Two primary cell cultures were established from samples of a NSCLC patient, before ICI initiation ("baseline", NSCLC-B) and during HPD ("hyperprogression", NSCLC-H). The cell lines were phenotypically and molecularly characterized through immunofluorescence, Western Blotting and RNA-Seq analysis. To assess cell plasticity and aggressiveness, cellular growth patterns were evaluated both in vitro and in vivo through 2D and 3D cell growth assays and patient-derived xenografts establishment. In vitro investigations, including the evaluation of cell sensitivity to interferon-gamma (IFN-γ) and cell response to PD-L1 modulation, were conducted to explore the influence of these factors on cell plasticity regulation. Results: NSCLC-H exhibited increased expression of specific CD44 isoforms and a more aggressive phenotype, including organoid formation ability, compared to NSCLC-B. Plastic changes in NSCLC-H were well described by a deep transcriptome shift, that also affected IFN-γ–related genes, including PD-L1. IFN-γ–mediated cell growth inhibition was compromised in both 2D-cultured NSCLC-B and NSCLC-H cells. Further, the cytokine induced a partial activation of both type I and type II IFN-pathway mediators, together with a striking increase in NSCLC-B growth in 3D cell culture systems. Finally, low IFN-γ doses and PD-L1 modulation both promoted plastic changes in NSCLC-B, increasing CD44 expression and its ability to produce spheres. Conclusions: Our findings identified plasticity as a relevant hallmark of ICI-mediated HPD by demonstrating that ICIs can modulate the IFN-γ and PD-L1 pathways, driving tumor cell plasticity and fueling HPD development. [ABSTRACT FROM AUTHOR]

Abstract Malaria-associated acute kidney injury (MAKI) is a common complication of Plasmodium infection, affecting ~ 50% of severe malaria cases and associated with increased mortality. However, its immunopathogenesis remains unclear. Interferon-gamma (IFN-gamma) is a crucial cytokine that influences parasite clearance and mediates pathogenesis in experimental models of malaria. This study explored the role of IFN-gamma in kidney pathology in C57BL/6 mice infected with Plasmodium berghei NK65 (PbNK65) and P. chabaudi AS (PcAS). PbNK65-infected mice, normally susceptible to severe malaria, were protected from both MAKI and malaria-associated acute respiratory distress syndrome (MA-ARDS) when lacking IFN-gamma. Infected IFN-gamma knockout (KO) mice developed low parasitemia levels, minimal kidney histopathological changes and reduced expression of the kidney injury marker Neutrophil Gelatinase-Associated Lipocalin (NGAL). In contrast, upon PcAS-infection, IFN-gamma deficiency led to increased parasitemia and aggravated kidney pathology, evidenced by proteinuria, hyaline casts in kidneys and increased renal mRNA expression of Heme Oxygenase 1 (HO-1) and NGAL. In both models, IFN-gamma induced renal C-X-C Motif Chemokine Ligand 10 (CXCL10) but did not affect Tumor Necrosis Factor-alpha (TNF-alpha) expression. Our data indicate that IFN-gamma exerts a dual effect on kidney pathology, which is conditioned by the mouse model and its impact on parasitemia.

Shu-Feng Dong,1,2,&ast; Xin-Yu Shi,1,&ast; Xiu-Zhi Wu,1 Feng-Shuang Yi1,3 1Department of Respiratory and Critical Care Medicine, Beijing Institute of Respiratory Medicine and Beijing Chao-Yang Hospital, Capital Medical University, Beijing, 100020, People’s Republic of China; 2Department of Respiratory and Critical Care Medicine, Shandong Provincial Hospital Affiliated to Shandong First Medical University, Jinan, Shandong, 250021, People’s Republic of China; 3Medical Research Center, Beijing Institute of Respiratory Medicine and Beijing Chao-Yang Hospital, Capital Medical University, Beijing, 100020, People’s Republic of China&ast;These authors contributed equally to this workCorrespondence: Feng-Shuang Yi, Email yifengshuang@ccmu.edu.cn; Xiu-Zhi Wu, Email xiuzhi.wu@outlook.comBackground: Pleural mesothelial cells (PMCs) form the entire surface of the pleural cavity and interact with microorganisms in the thorax. Although PMCs are known to exert multiple immune functions, their role in pleurisy remains unclear.Methods: Pleurisy model was induced by intrapleural injection of Mycobacterium bovis bacillus Calmette-Guerin (BCG) into wild-type (WT) C57BL/6 mice. The pleural cavity was washed with Phosphate Buffered Saline (PBS) to get the immune cells. Flow cytometry was performed to identify the characteristics of the target cells.Results: We found that IFN-γ prompts PMCs to act a summon role for the recruitment of inflammatory cells in pleurisy model. Our data showed that CD4+ T cells were the main producer of IFN-γ in the pleurisy model, and IFN-γ stimulated PMCs to recruit immune cells into the pleural cavity through the CXCL10-CXCR3 axis. In addition, IFN-γ can reshape PMCs to display macrophage-like polarization. These results revealed some new immune roles of PMCs in pleurisy.Conclusion: In a mouse model of pleurisy, IFN-γ, which is mainly derived from CD4+ T cells, promoted PMCs to recruit of immune cells into the pleural cavity and exhibited macrophage-like polarization.Keywords: IFN-γ, pleurisy, pleural mesothelial cells, macrophages

Introduction: In vitro and animal model studies have shown that Nigella sativa reduces cancer cell proliferation and improves chemotherapy effectiveness. Cellular activation triggers the production of IFN-γ by natural killer (NK) cells. This study examined the effect of Nigella sativa supplementation on IFN-γ levels and quality of life in lung cancer patients before and after interferon therapy. Methods: This study used a non-equivalent control experimental design involving 21 lung cancer patients undergoing initial chemotherapy at Dr. Saiful Anwar General Hospital, Malang, in 2023. The patients were divided into two groups: one group received standard chemotherapy, and another group received a combination of chemotherapy and Nigella sativa supplementation at a dose of 2x500 mg for nine weeks. The effects of this intervention were assessed by measuring IFN-γ levels using an enzyme-linked immunosorbent assay (ELISA) kit and evaluating quality of life using the European Organization for Research and Treatment of Cancer (EORTC) Core Quality of Life (QLQ-C30) questionnaire before and after the fourth cycle of chemotherapy. Results: The results showed a significant increase in IFN-γ levels in the combination group undergoing chemotherapy and receiving Nigella sativa supplementation (6140.44±2233.89) compared to the standard chemotherapy group (3827.08±1722.79), with a p-value of 0.015. Quality of life improved in both groups, with scores of 53.70±6.05 before and 65.74±14.70 after chemotherapy (p=0.000). Conclusion: This study found that Nigella sativa supplementation can enhance IFN-γ levels and quality of life in lung cancer patients after four chemotherapy treatment cycles. These findings indicated that Nigella sativa could be a beneficial supplement for lung cancer patients.

Our previous studies have introduced osteoclasts (OCs) as major activators of NK cells. It was found that OCs exhibit the capabilities of inducing cell expansion as well as increasing the cytotoxic activity of NK cells by granule release and increasing the secretion of TNF-α and TRAIL, leading to increased lysis of tumors in short-term as well as long-term periods, respectively. OC- induced expanded NK cells were named supercharged NK cells (sNK) due to their significantly high functional activity as well as their significantly higher cell expansion rate. It is, however, unclear whether the OC-mediated effect in NK cells is specific or whether other cytotoxic immune cells can also be expanded and activated by OCs. We chose to focus on γδ T cells and pan T cells, which also include CD8+ T cells. In this paper, we report that OCs are capable of expanding and functionally activating both γδ T cells and pan T cells. Expanded γδ T and pan T cells were capable of secreting high levels of INF-γ, albeit with different dynamics to those of NK cells, and, moreover, they are unable to kill NK-specific targets. Since we used humanized-BLT (hu-BLT) mice as a model of human disease, we next determined whether NK and T cell activation through OCs is also evident in cells obtained from hu-BLT mice. Similar to humans, OCs were capable of increasing the cell expansion and secretion of IFN-γ in the culture of either NK or T cells from hu-BLT mice, providing yet further evidence that these mice are appropriate models to study human disease. Therefore, these studies indicated that CD3+ T or γδ T cells can proliferate and be supercharged by OCs similar to the NK cells; thus, they can be used individually or in combination in the cell therapy of cancers.

Background: Inflammasome complex such as nucleotide oligomerization domain-like receptor family protein 3 (NLRP3) acts as a trigger initiating inflammatory responses and could lead to endothelial dysfunction in diabetic patients and glycemic control could affect the mitochondrial stress through NLRP3 inflammasome level. Objectives: This study was conducted to ensure that type 2 diabetes mellitus (T2DM) glycemic control could affect mitochondrial stress through NLRP3 inflammasome level leading to an aberrant immune response. Materials and Methods: A case–control study was conducted on 90 Iraqi subjects, 60 of them were T2DM who were subgrouped into 30 patients with good glycemic control (HbA1c ≤ 7%) and the second group with 30 patients with poor (bad) glycemic control (HbA1c > 7%). Also, 30 healthy control subjects were enrolled in this study. HbA1c, fasting blood glucose (FBG), and serum levels of NLRP3 and interferon (IFN)-γ were quantitatively determined by means of a sandwich enzyme-linked immunosorbent assay (ELISA) test. Results: Results of this study showed a significant increase in serum levels of NLRP3 and IFN-γ in the poor glycemic control group of patients as compared to control subjects (P ≤ 0.05), while this difference was not significant when comparing the good glycemic control group of patients with control subjects. There is a significant positive correlation of serum NLRP3 with only IFN-γ (P ≤ 0.05) in both good and poor glycemic control and healthy controls. Conclusion: An increased level of NLRP3 was observed in poor glycemic control T2DM and correlated with IFN-γ, suggesting hyperglycemia’s effect on this inflammasome pathway that could be associated with aberrant cytokine induction, a key inducer of diabetic complications.

Atopic dermatitis (AD) is a chronic recurrent inflammatory skin disease. Fucoidans are reportedly effective in treating AD; however, their clinical efficacy requires further exploration. This study aimed to investigate the clinical efficacy of low-molecular-weight fucoidan (LMF) supplementation in patients with AD and reveal the underlying mechanism of its effects; this is a randomized, double-blind, placebo-controlled trial. Participants were randomly assigned to a study or control group to receive conventional AD therapy with oral supplementation of either LMF or placebo for 12 weeks. Symptom severity was measured by the SCORing Atopic Dermatitis (SCORAD) index. Each participant used a diary to record daily medication use. Blood samples were collected at three time points for assessing AD-related cytokines, immunoglobulin E (IgE), C-reactive protein (CRP), erythrocyte sedimentation rate (ESR), white blood cell (WBC) count, the percentage of eosinophils, and biochemical profiles of hepatic and renal functions. The study group showed significant symptom relief, whereas the control group showed no significant improvements. The frequency of steroid ointment application significantly decreased, and the frequency of oral antihistamine use decreased in the study group, whereas no significant changes were observed in the control group. The AD-related immune parameters serum IgE, eosinophils, CD8+ T cells, interferon-γ (IFN-γ), ESR, and CRP significantly decreased in the study group but not the control group. There were no severe adverse events in either group. This study is the first to demonstrate the effectiveness and safety of LMF as a supplemental therapy for patients with AD via its anti-inflammatory activity.

Abstract Trichinellosis is a zoonotic, foodborne parasitic infection causing muscle damage. This study investigated the potential therapeutic effects of the commercially available probiotic treatment Linex, both alone and in combination with Albendazole (ALB), on the intestinal and muscular stages of Trichinella spiralis infection in mice, assessing outcomes through parasitological, immunological, and histopathological measures. This study is the first to demonstrate the synergistic effect of combining the commercially available probiotic Linex with Albendazole for trichinellosis treatment. By enhancing both parasitological and immunological outcomes, this combined therapy not only significantly reduces parasite burden but also modulates the immune response, shifting it toward a protective Th1 profile. In parasitological terms, the highest adult and larval count reduction was observed in combined Linex and Albendazole treatment (100%, 97.7%) respectively. Lesser percentage of reduction were recorded in Linex alone therapy (43.2%, 88.4%) respectively. Histopathologically there was amelioration of the inflammatory cellular infiltration in all treated groups with best results in combined Linex and Albendazole treatment. Immunologically, serum IFN-γ levels increased significantly in all treated groups with highest levels in combined Linex and Albendazole treatment, while IL-4 and IL-13 level decreased significantly in all treated groups with best results observed in Linex alone treatment. To conclude; combined Linex and Albendazole treatment of mice infected with T. spirals could ameliorate the infection and improve the immune response.

Abstract Background Rapid diagnosis of pulmonary tuberculosis (PTB) is urgently needed. We aimed to improve diagnosis rates by combining tuberculosis-interferon (IFN)-γ release assays (TB-IGRA) with metagenomic next-generation sequencing (mNGS) for PTB diagnosis. Methods A retrospective study of 29 PTB and 32 non-TB patients from our hospital was conducted between October 2022 and June 2023. Samples were processed for TB-IGRA and mNGS tests according to the manufacturer’s protocol. Results The levels of IFN-γ release in PTB patients were significantly higher than those in non-TB patients (604.15 ± 112.18 pg/mL, and 1.04 ± 0.38 pg/mL, respectively; p

Abstract To explore the association between 25-hydroxy vitamin D [25-(OH)-D], interleukin-4 (IL-4), and interferon-γ (IFN-γ) in children with Mycoplasma pneumoniae (MP) infection-related asthma. Logistic analysis was conducted to compare general data in MP asthma and MP non-asthma groups. The level of 25-(OH)-D, IL-4, and IFN-γ were detected and compared between groups. Moreover, the receiver operating characteristic curve (ROC) was applied to test the predictive value of each variable. The results of logistic regression analysis demonstrated that recurrent upper respiratory tract infections and collective living are related to the incidence of MP infection whether with asthma or without asthma. IL-4 and IFN-γ in MP asthma group were significantly higher than those in MP non-asthma group and control group (p

Abstract Background There is substantial evidence indicating that cytokines play a role in the immune defense against tuberculosis. This study aims to evaluate the levels of various cytokines in pleural effusion to ditinguish between tuberculosis pleurisy and malignant pleurisy. Methods A total of 82 participants with pleural effusion were included in the training cohort, and 76 participants were included in the validation cohort. The individuals were divided into tuberculosis and malignant pleurisy groups. The concentrations of interleukin-1β (IL-1β), IL-4, IL-6, IL-10, IL-17 A, IL-17 F, IL-21, IL-22, IL-25, IL-31, IL-33, interferon-γ (IFN-γ), soluble CD40 ligand (sCD40L) and tumor necrosis factor-α (TNF-α) in pleural effusion were measured using a multiplex cytokine assay. The threshold values were calculated according to the receiver operating characteristic (ROC) curve analysis to aid in diagnosing tuberculosis pleurisy. Furthermore, the combined measure was validated in the validation cohort. Results The levels of all 14 cytokines in pleural effusion were significantly higher in participants with tuberculosis compared to those with malignant pleurisy (all P