The aim of this study was to investigate the role of the ubiquitin specific peptidase 10 (USP10/methyltransferase like 3 (METTL3)/C-X-C chemokine receptor type 4 (CXCR4) axis in immunotherapy of castration-resistant prostate cancer (CRPC).
Knockdown experiments were conducted in CRPC cell lines to assess the effect of targeting CXCR4 on cell proliferation invasion and migration. Coculture experiments of CXCR4 knockdown CRPC cells with THP1-M0 were performed to evaluate their impact on macrophage polarization and migration ability. With CD8⁺ T cells was conducted to assess their effects on CD8⁺ T cell proliferation and apoptosis. CXCR4-overexpressing CRPC cells were treated with the JAK-2 specific inhibitor AG490 to assess the effect of CXCR4 through the JAK2/STAT3 pathway on CRPC. The mechanisms by which USP10 regulates CXCR4 expression through targeting METTL3 were explored through dataset analysis, bioinformatics prediction, and Western blot.
In CRPC tissues and cells, there was an observed increase in CXCR4 expression. Suppressing CXCR4 through knockdown methods resulted in the inhibition of CRPC cell growth, movement, and infiltration. Additionally, it led to a reduction in M2 polarization and the recruitment of Tohoku Hospital Pediatrics-1 (THP1) M0 macrophages, along with a mitigation of CD8⁺ T cell exhaustion. Dataset analysis, bioinformatics prediction, and Western blot validation indicated that CXCR4 activates the JAK2/STAT3 pathway to promote the expression of CCL2 and PD-L1, while USP10 promotes CXCR4 expression through METTL3.
Our study underscores the significance of the USP10/METTL3/CXCR4 axis in immunotherapy for CRPC and CXCR4 as a potential target for therapeutic intervention in CRPC treatment.

Severe asthma causes chronic airway inflammation and structural changes in the bronchial wall. Fibroblast growth factor 2 (FGF2) plays an inflammatory role in specific pathways in airway remodeling in asthma. Assessing the relationship between sputum pattern, bronchial thickness by high-resolution computed tomography (HRCT) scan, and FGF2 expression level can evaluate the role of FGF2 in asthma remodeling.
The study aimed to investigate the correlation between airway wall thickness and FGF2 gene expression in 100 participants with severe asthma. The method involved measuring airway wall thickness using HRCT and analyzing FGF2 gene expression through real-time reverse transcriptase polymerase chain reaction. The participants were divided into 2 groups based on bronchodilator responsiveness and classified into different asthma phenotypes based on sputum cell count.
The baseline data did not show a significant difference between the groups. The study found significant differences in airway variables between different asthma subgroups. FGF2 expression was associated with various characteristics of asthma, including body mass index, forced expiratory volume in 1 second (FEV1), and airway wall thickness. The receiver operating characteristic curve analysis showed that a fold change higher than 2.42 in FGF2 expression indicated asthma.
Based on our research, FGF2 may play a critical role in airway thickness regardless of inflammation. We found increased FGF2 levels with disease severity and wall thickness in atopic severe persistent asthma patients with FEV1 below 60%. Further research is needed to understand FGF2's role across broader FEV1 ranges and other phenotypes.

Ovarian cancer is 1 of the most serious female malignancies worldwide. Despite intensive efforts to overcome ovarian cancer, there remain limited treatment options for this disease. Ellagic acid (EA), a well-known phytochemical with anti-inflammatory properties, is suggested as a therapeutical strategy as it can inhibit the growth of certain cancer cells. However, its effect on human ovarian carcinoma cells has not yet been fully elucidated. The present study aimed to explore the effect of EA on ovarian carcinoma and further expound the underlying mechanisms of EA-induced ovarian cancer cell death.
Human ovarian carcinoma cell lines, A2780 and OVCAR3, were treated with EA (0, 10, 20, 50, and 100 μM) and assessed for viability, cell cycle (cyclin D1 and cyclin E), pyroptosis (gasdermin D [GSDMD] and gasdermin E [GSDME]), autophagy (microtubule-associated protein 1A/1B-light chain 3 [MAP1LC3] and autophagy protein 5 [ATG5]), and inflammation (interleukin [IL]-1b and IL-6) via 3-(4,5-dimethylthiazol-2-yl)-2,5 diphenyl tetrazolium bromide (MTT), real-time polymerase chain reaction (RT-PCR), and enzyme-linked immunosorbent assay (ELISA).
The findings showed that EA could significantly inhibit cell viability, decrease cyclin D1 and E levels, downregulate GSDMD and GSDME, and suppress the levels of inflammatory markers, including IL-1b and IL-6. However, the protein levels of autophagic markers including LC3 and ATG5 remained mostly unchanged.
The findings suggest that EA could suppress ovarian cancer cell viability and proliferation by arresting both cell lines at the G1 phase of the cell cycle through modification of cell death mediated by inflammatory-caused pyroptosis.

europathic pain can arise from injury or illness affecting the somatosensory system. It can also be triggered by cancer or chemotherapy drugs like paclitaxel. Researchers have indicated that magnesium sulfate may help in preventing neuropathy. This study aimed to investigate the effect of magnesium sulfate on paclitaxel-induced neuropathic pain by inhibiting the Tumor Necrosis Factor (TNF) Alpha - receptor-associated factor 6 - Nuclear factor kappa-light-chain-enhancer of activated B cells (TNF-α-TRAF6-NF-κB) axis.
Twenty-four male rats were divided into four groups: experiment group (E)-1, E2, E3, and the control group (Co). The experimental groups and the control group received paclitaxel at a dosage of 8 mg/kg every other day, totaling four injections over seven days. In addition, magnesium sulfate was administered daily in three doses of 300, 150, and 75 mg/kg, amounting to seven injections over the course of seven days. On the seventh day, peripheral blood samples were collected from the rats, and sera were used for the analysis of TNF-α serum levels and MicroRNA-146a-5p expression using ELISA and qRT-PCR methods, respectively.
The serum levels of TNF-α increased in the E1, E2, and E3 groups compared to the control group. However, there was a gradual decrease in the E1, E2 and E3 groups. The miR-146a-5p expression declined in the E1 group and increased in the E2 and E3 groups compared to the control group.
This study demonstrated that administering 300 and 150 mg of magnesium sulfate decreased TNF-α synthesis and reduced the function of the TNF-α-TRAF6-NF-κB axis during the initiation step.

Diabetic nephropathy is a microvascular complication that leads to renal injury. Oxymatrine (OMT) is a matrine alkaloid and has been shown to ameliorate diabetic nephropathy. However, it is still unknown whether its mechanism involves podocytes, which play a critical role in diabetic nephropathy.
High glucose-induced podocytes (MPC5) were treated with OMT, the NOD-like receptor protein 3 (NLRP3) inhibitor MCC950, and the sirtuin 1 (SIRT1) inhibitor EX527. The effects on podocyte proliferation and apoptosis were assessed using cell counting kit-8 and flow cytometry. Immunofluorescence staining was performed to detect the expression of podocyte-associated proteins, NLRP3 inflammasome, and SIRT1. The levels of interleukin (IL)-1β and IL-18 were measured by enzyme-linked immunosorbent assay. Additionally, Western blot analysis was conducted to evaluate podocyte-related proteins, NLRP3 inflammasome-dependent pyroptosis-related proteins, and SIRT1/nuclear factor kappa B (NF-κB) pathway proteins, aiming to elucidate the mechanisms by which OMT improves podocyte injury.
OMT significantly promoted the proliferation of podocytes exposed to high glucose, inhibited their apoptosis, increased the levels of nephrin, Wilms tumor 1, podocin, and zonula occludens-1, and reduced pyroptosis-related proteins, IL-1β, and IL-18 (p < 0.05). It also increased SIRT1 and decreased the acetylation of NF-κB p65 (p < 0.05). The NLRP3 inhibitor MCC950 reduced podocyte pyroptosis under high glucose conditions, while the SIRT1 inhibitor EX527 reversed the protective effects of OMT on NLRP3 inflammasome-dependent pyroptosis and podocyte injury.
OMT ameliorates high glucose-induced podocyte injury by regulating the SIRT1/NF-κB pathway and inhibiting NLRP3 inflammasome-dependent pyroptosis.

Circular RNAs (circRNAs) are endogenous non-coding RNA molecules that form covalently closed molecular loops. By regulating gene expression, circRNAs are known to play crucial roles in the development and progression of various diseases, including autoimmune, neoplastic, and neurological disorders.  
In this study, we examined the expression of circSnx5 in inflamed CNS tissue at different stages of experimental autoimmune encephalitis (EAE), an animal model for multiple sclerosis (MS), as well as in T cells that were activated and differentiated into different T helper phenotypes (Th1, Th17, Treg). EAE was induced and spinal cord tissues were isolated at different time points following disease induction. CD4⁺ T cells were isolated from mouse splenocytes and differentiated toward Th1, Th17, and Treg phenotypes, followed by the analysis of circSnx5 expression.
Compared with control mice, enhanced expression of both circular and linear forms of Snx5 was detected in EAE lumbar spinal cords at the peak and post-peak phases of the disease. However, the ratio of the circular to linear forms (CLR) was decreased in EAE mice compared with controls. Expression of circSnx5 was highly correlated with the levels of inflammatory cytokines in the spinal cord tissue. Significant decreases were observed in circSnx5 expression levels following polyclonal activation of splenocytes. The expression of circSnx5 was also downregulated in differentiated T cells directed toward Th1, Th17, and Treg.
Our findings suggest a potential role of circSnx5 in autoimmune neuroinflammation. The altered expression of circSnx5 during activation and differentiation may offer valuable insights into potential strategies for regulating inflammation in multiple sclerosis (MS).

Objective: To analyze the clinical efficacy and influencing factors of budesonide inhalation therapy in adult Cough variant asthma (CVA). Methods: This retrospective study involved 223 CVA patients who were treated in the hospital from January 2022 to February 2024. These patients received standard symptomatic treatment (such as cough suppression, expectoration, and anti-infection therapies), along with budesonide inhalation therapy. The main objective of the study was to evaluate the clinical effects before and after treatment, including lung function, serum inflammatory factor levels, and immune function, while also recording any adverse reactions that occurred during treatment. We classified the patients into effective and ineffective groups based on treatment outcomes, collected clinical factors related to efficacy, and used logistic regression analysis to investigate the factors affecting treatment effectiveness. Results: After treatment, the lung function indicators of patients showed significant improvement, with the forced expiratory volume in one second (FEV1), forced vital capacity (FVC), and peak expiratory flow (PEF) all increasing compared to before treatment. At the same time, the levels of tumor necrosis factor-alpha (TNF-α), interleukin-4 (IL-4), and immunoglobulin E (IgE) in the serum decreased. In terms of immune function, the levels of CD3+ and CD4+ cells were increased, while the level of CD8+ cells decreased. Thirteen patients (5.83%) experienced nausea and indigestion during the treatment process, nine patients (4.04%) had drowsiness and fatigue, and seven patients (3.14%) had discomfort in the throat. Based on the therapeutic efficacy evaluation after treatment, patients were divided into an effective group (n=188) and an ineffective group (n=35). Further multivariate logistic regression analysis revealed that older age (OR=1.570), lower levels of 25-hydroxyvitamin D3 [25(OH)D3] (OR=0.798), and high levels of tumor necrosis factor-alpha (TNF-α) (OR=1.850) increased the risk of reduced therapeutic efficacy. Conclusion: Budenoside inhalation therapy is effective for CVA patients, as it can improve lung function, reduce inflammation, and enhance immune function. However, factors such as age, 25(OH)D3, and TNF-α may influence the treatment outcomes.

Up-regulation of immune checkpoint ligands and secretion of soluble factors in the tumor microenvironment led to the survival of cancerous plasma cells in the bone marrow milieu. Therefore, we investigate the relationship between the inhibition of c-Kit receptor, AKT, and NF-κB signaling pathways and the regulation of immune escape mechanisms in multiple myeloma.
The U266B1 cell line was treated with Masitinib as a c-Kit receptor inhibitor, Perifosine as AKT inhibitor, and Bortezomib as NF-κB inhibitor either in single or combined form. Apoptosis and cell viability were evaluated using flow cytometry and MTT assays, respectively. The relative expression of programmed death-ligand 1 (PD-L1), poliovirus receptor (PVR), and interleukin 6 (IL-6) were determined by real-time PCR. Also, the secretion of IL-6 was measured by ELISA.
Our findings demonstrated decreased proliferation of U266B1 cells after co-treatment with Masitinib, Perifosine, and Bortezomib.  An increase in apoptosis was observed in the co-treatment of Masitinib and Perifosine. Furthermore, results elucidated that the expression of PD-L1 and IL-6 decreased after treatment with Masitinib, Perifosine, and Bortezomib in both single and co-treatments. Regarding PVR, combined treatment of U266B1 cells with Masitinib, Perifosine, and Bortezomib decreased the expression level of PVR.
We showed that c-Kit receptor, AKT, and NF-κB pathway inhibitors not only serve as cytotoxic drugs but also inhibit the immune escape mechanisms of malignant plasma cells by disrupting signaling pathways.

Administering human leukocyte antigen (HLA)-compatible platelets is a tactic for treating patients with poor responses to random platelet injections. HLA-matched platelet provision requires many donors with HLA-typed and organized information. This study, the first of its kind in Iran, aimed to develop a registry system of HLA-typed platelet donors to facilitate the provision of compatible platelets to patients, leveraging the diversity of HLA alleles across Iran's various provinces.
This study involved the HLA-typing of 1850 plateletpheresis donors, who were also registered as unrelated stem cell donors, across all blood centers in Iran from 2015 to 2022. HLA-A and HLA-B genotyping was conducted at a low-resolution using polymerase chain reaction-sequence specific primers (PCR-SSP) and real-time PCR. Statistical analysis was performed to determine allelic genotypes and donor profiles.
The majority of the donors were male (99.7%), with a mean age of 36 years. The high donor rate in Tehran indicates a larger pool of potential HLA-platelet donors due to a denser population and more donation facilities. The donors were recruited for HLA-compatible plateletpheresis. The frequency of HLA-AB alleles among donors was relatively consistent with those documented by Iranians.
Our findings can be utilized to create a foundational HLA database. A registry system for HLA-typed platelet donors is crucial due to high HLA polymorphism and ethnic diversity. This system facilitates the rapid identification of compatible donors based on HLA typing. Additional inquiries are needed to expand the plateletpheresis registry and make a request-supply mechanism between the Iranian Blood Transfusion Organization and hospitals.

Propofol, a quick‑acting systemic anesthetic agent widely used in general anesthesia, can alleviate airway T-helper 2 (T_H2) inflammation. Group 2 innate lymphoid cells (ILC2s) are a newly discovered group of lymphoid cells and play key roles in allergic rhinitis (AR). We aimed to investigate the regulation of ILC2s treated with propofol and its possible mechanisms in a mouse model.
An ovalbumin (OVA)-sensitized and challenged mouse model was established. Nasal lavage fluid (NLF) and tissue samples were collected for the detection of inflammatory cells, type II cytokines, and ILC2s using Giemsa staining, enzyme-linked immunosorbent assay, and flow cytometry. CD4⁺ T cells and ILC2s were cocultured and detected by flow cytometry to confirm the proportion of T_H2 cells.
Compared with OVA-sensitized and challenged mice, propofol-treated model mice presented decreased type II cytokine levels and total numbers of cells, eosinophils, neutrophils, and macrophages in NLF.  Mice treated with propofol presented decreased nasal ILC2 frequency. Moreover, the nasal expression of GATA binding protein 3 (GATA3) and retinoid-related orphan receptor α (RORα),  as well as the levels of IL-5 and IL-13, were significantly inhibited after propofol treatment. Compared with those cultured alone, cocultures of ILC2s and CD4⁺ T cells resulted in significantly more T_H2 cells. When propofol was added, the percentage of T_H2 cells significantly decreased. This effect was alleviated when anti-major histocompatibility complex class II (anti-MHC II) protein was added. 
Our study provides preliminary evidence that propofol can play an inhibitive role in AR by regulating innate and adaptive immunity.

COVID-19 is capable of undermining self-tolerance in a host's immune system and triggering autoimmunity by hyper-activating the innate and adaptive immune systems, which has not investigated in Iranian society until now. In the innate immune system neutrophils are the predominant immune cells that protect the human body against invaders.
Here, we sought to explore 2 important variables related to neutrophil: DNA complexes with myeloperoxidase (MPO-DNA) as a reliable indicator of neutrophil extracellular traps (NETs) by MPO-DNA complex evaluation using a sandwich ELISA and the underlying role of IL-8 in (NETs) formation during COVID-19 infection.
According to our results, in COVID-19 patients, neutrophil-to-lymphocyte ratio (NLR) was significantly higher in ICU patients (14.62±11.81) compared to non-ICU patients (3.16±3.33). Elevated IL-8 levels were observed in COVID-19 patients, particularly in ICU patients. MPO-DNA levels, indicating NETosis, were significantly higher in COVID-19 patients and strongly correlated with neutrophil counts (r=0.472).
Thus, our studies suggest that neutrophils count, IL-8, and MPO-DNA can be used as powerful biomarkers in diagnosing COVID-19 severity. patients with severe COVID-19 infection are prone to heart disease because most of them develop excessive NET formation. Additionally, In COVID-19 patients, a higher MPO-DNA level may increase the risk of developing heart disease too.

Human cytomegalovirus glycoprotein B (gB) emerges as a viable candidate for eliciting neutralizing antibodies. This research specifically focused on exploring the immune reaction prompted by the nonglycosylated variant of the gB, with a comprehensive assessment of humoral immunity in mice.
The gB coding sequence was optimized and expressed in pET-15b. Additionally, pcDNA3.1(+) vectors were also used for cloning the same gB sequence as the DNA vaccine. The gB was purified using a Ni-NTA chromatographic column. SDS-PAGE and Western blotting were used to confirm protein expression and purification. Using the prime-boost strategy, 8 different BALB/c mice were injected with DNA vaccine plus gB heterologous vaccine at 3 intervals. We evaluated the interferon (IFN-γ), interleukin (IL-4), immunoglobulin (Ig) G1, IgG2a, and IgG2b using enzyme-linked immunosorbent assay. 
It was shown that the mice administered with DNA vaccine plus gB had higher IFN- γ and IL-4 levels compared to controls. On the other hand, the mice that received 3 doses of gB showed the highest levels of IgG1 and IgG2a. However, IgG2b was at its highest in mice administrated with DNA vaccine plus gB. The total IgG was higher in mice that received gB than in other interventions.
According to the findings, the DNA vaccine enhanced total IgG in immunized mice more effectively than the gB. This could be attributed to conformational changes owing to a lack of glycan moiety. Furthermore, combining nonglycosylated gB with DNA as a heterologous vaccine strategy enhances innate immunity by increasing the IFN- γ levels.

Blood transfusion is associated with increased mortality and morbidity. This study aimed to determine the effect of blood transfusion on T-helper 1 (T_H1), T_H2, and T_H17 function in patients undergoing coronary artery bypass grafting (CABG).

Two blood samples were obtained from patients undergoing CABG, before and 14 days after surgery. Production of interleukin (IL)-2, IL-4, interferon (IFN)-γ, IL-17A, and IL-10 by CD4⁺ T cells was measured using enzyme-linked immunosorbent assay (ELISA). mRNA expression of T-box expressed in T cells (T-bet), GATA binding protein 3 (GATA3), RAR-related orphan receptor-γ (ROR-γt), signal transducer and activator of transcription 3 (STAT3), STAT4, and STAT6 were measured using quantitative reverse transcriptase polymerase chain reaction (qRT-PCR).

mRNA expression of T-bet and STAT4 showed a significant decrease after blood transfusion. However, the concentration of IFN-γ in the culture supernatant showed no significant difference after blood transfusion. mRNA expression of GATA3 and STAT6 showed a significant decrease after blood transfusion. However, the concentration of IL-4 in the culture supernatant showed no significant difference after blood transfusion. mRNA expression of ROR-γt showed no significant decrease after blood transfusion; however, the expression of STAT3 and the concentration of IL-4 in the culture supernatant did significantly decrease following blood transfusion. IL-10 production increased significantly postoperatively.

Decreased T_H1, T_H2, and T_H17 signaling pathway activity and increased IL-10 concentration indicate an immunomodulatory effect on the immune system after blood transfusion.

MicroRNAs (miRs) play a pivotal role in the pathogenesis of viral infections. It has been proven that the Nrf2 (NFE2 like bZIP transcription factor 2) antioxidant signaling pathway is inhibited in COVID-19 patients. Two microRNAs (MIR144 and MIR153-1) have been identified as important Nrf2 regulators. The aim of this study was to analyze the MIR144 and MIR153-1 expression in COVID-19 patients and investigate their association with the Nrf2 signaling pathway.
The study had 82 participants with both mild and severe COVID-19 manifestations and 25 healthy as a control group. Ficoll density-gradient centrifugation was used to separate peripheral blood mononuclear cells from ethylenediaminetetraacetic acid blood tubes. MIR144, MIR153-1, and NFE2L2 expressions were studied using real-time polymerase chain reaction. We employed the commercially available enzyme-linked immunosorbent assay to measure plasma Nrf2 protein concentration and the activity of antioxidant enzymes, superoxide dismutase, and catalase.
Compared to the control group, MIR144 expression was significantly increased in the severe group, while NFE2L2 expression decreased. There was no significant difference in the MIR153-1 expression rate between COVID-19 patients and controls. Nrf2 protein and antioxidant enzyme activity significantly decreased in the severe group. A negative correlation between MIR144 expression and Nrf2 protein concentration was observed.
Taken together, the current study's findings showed that MIR144 upregulation probably interferes with the Nrf2 antioxidant signaling pathway in COVID-19 patients.