Allergic asthma is a chronic inflammatory disease characterized by airway remodeling, hyperresponsiveness, and exacerbated inflammation. While most patients respond well to current treatments, a small subset remains resistant necessitating new therapeutic strategies. Due to their immunomodulatory properties, stem cells have been proposed as a promising treatment option for asthma. Stem cells can reduce airway inflammation and restore immune balance, demonstrating positive outcomes, particularly in cases of steroid-resistant asthma. However, the mechanisms underlying lung tissue repair are not clearly defined. On the other hand, there are limitations in using these cells and for clinical use of mesenchymal stem cells, which must be produced in accordance with Good Manufacturing Practice. This review article discusses the mechanisms by which stem cells may aid in asthma treatment and addresses and explores the challenges associated with their use. By addressing these areas, we can better understand the potential and limitations of stem cell therapy in asthma and develop more effective strategies to harness their therapeutic benefits for patients with uncontrolled asthma.

Pancreatic ductal adenocarcinoma (PDAC) is a common digestive system tumor with high mortality rates and a poor prognosis. Reports suggest that microRNA (miR)-486-3p in PDAC can be used as a diagnostic biomarker. This research aimed to elucidate the mechanisms by which miR-486-3p regulates PDAC progression.
miR-486-3p and chymotrypsin C (CTRC) expression in PDAC were measured using quantitative real-time polymerase chain reaction. Changes in the biological properties of PDAC cells were assessed by Transwell assay, scratch-wound assay, cell counting kit (CCK)-8 assay, and plate cloning assay. The protein expression of immunosuppressive factors (vascular endothelial growth factor, interleukin-6, and transforming growth factor-β) in PDAC cells was detected by western blot. Additionally, a subcutaneous graft tumor model was constructed to explore the influence of silencing miR-486-3p on PDAC in vivo.
PDAC showed a pronounced increase in miR-486-3p expression. Upregulation of miR-486-3p stimulated PDAC cell proliferation, migration, invasion, and immunosuppressive factor protein expression, whereas silencing miR-486-3p hindered PDAC malignant development. miR-486-3p targets and negatively regulates CTRC expression. Silencing CTRC partially rescued the restraining impact of silencing miR-486-3p on PDAC malignant progression. In vivo experiments also indicated that silencing miR-486-3p inhibited PDAC malignant progression and immunosuppressive factor expression in vivo.
In summary, miR-486-3p promotes immunosuppressive factor protein expression by targeting and negatively regulating CTRC expression, which in turn promotes PDAC malignant progression.

This study explored the link between clinical features, immune markers, and asthma-chronic obstructive pulmonary disease overlap (ACO), aiming to enhance diagnostic precision and tailor treatment.
The study included 60 patients per group: COPD patients, ACO patients, and healthy controls. Biological indicators such as fractional exhaled nitric oxide (FeNO), eosinophils, immunoglobulin E (IgE), T helper (Th) 17 cell counts, regulatory T-cell (Treg) counts, and cytokine levels of interleukin-17 (IL-17) and interleukin-10 (IL-10) were measured using standard enzyme-linked immunosorbent assay and flow cytometry techniques.
Elevated Th17 cells, IL-17, and Th17/Treg ratio, alongside reduced IL-10 and Treg levels, were observed in COPD and ACO patients. ACO patients showed worse lung function, with a negative correlation between FeNO, Th17 cells, Th17/Treg ratio, IL-17, and lung function indices, and a positive correlation with residual volume/total lung capacity (RV/TLC) ratio.
The study suggests that Th17/Treg imbalance, FeNO, eosinophils, and IgE could be key in ACO pathogenesis, potentially aiding early diagnosis and targeted treatment. Future research may utilize these findings to develop preventative and therapeutic strategies for ACO.

The exact cause of psoriatic arthritis is still unknown, but hypotheses suggest the role of hematological parameters in the onset and severity of the disease. This study evaluated the hematological indices and their association with skin and joint activity in psoriatic arthritis.
This cross-sectional study included 74 patients with psoriatic arthritis. Demographical and clinical data, blood indices, psoriasis area and severity index (PASI) score and disease activity in psoriatic arthritis (DAPSA) scores were calculated for all patients.
The mean age of the patients was 48.89±12.03 years and most were female (n=49). A significant correlation was observed between age and number of underlying diseases with PASI and DAPSA scores. Mean PASI and DAPSA scores were 5.19 and 15.13, respectively. The severity of psoriasis was mild in 58.1%, moderate in 36.5%, and severe in 4.5% of the cases. The activity of psoriatic arthritis was improved in 2.1%, low in 55.4%, moderate in 24.3%, and high in 1.8% of the patients. A significant association was found between erythrocyte sedimentation rate (ESR), C-reactive protein (CRP), red cell distribution width (RDW), neutrophil-to-lymphocyte ratio (NLR), platelet (PLT) count, mean platelet volume (MPV), and PASI scores, while no statistically significant association was reported for PLR. A significant correlation was observed between ESR, CRP, RDW, NLR, PLR, PLT, and DAPSA scores, while no statistically significant association was found for MPV.
The findings indicated that inflammatory and hematological markers can be helpful factors in evaluating the severity of psoriasis and psoriatic arthritis.

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.

Extended endoscopic sinus surgery (EESS) can reduce the recurrence rate of chronic rhinosinusitis (CRS). The purpose of this study was to investigate the effect of the application of modified “protective middle turbinate-EESS” (mEESS) on patients with CRS with nasal polyps (CRSwNP) and allergic rhinitis (AR).
Forty-three patients with CRSwNP and AR were classified into 2 groups, the mEESS group (n=23) and the functional endoscopic sinus surgery (FESS) group (n=20), and were followed up for 6 months and 1 year after surgery. The disease severity was assessed by the Lund-Mackay score, the Lund-Kennedy score, and the visual analog scale (VAS) score. The patency rate of the frontal sinus was evaluated by endoscopy. Patient satisfaction was also followed up.
No preoperative differences or postoperative complications were found between the 2 groups. The VAS score and Lund-Kennedy score of the 2 groups were lower at 6 months and 1 year after surgery. The olfactory function of the mEESS group was significantly better than that of the FESS group at 6 months post-operative. The patency rate of the frontal sinus orifice in the mEESS group was significantly higher than that in the FESS group at 6 months and 1 year post-operative. Patient satisfaction in the mEESS group was relatively higher than that in the FESS group.
mEESS improves frontal sinus drainage, olfactory sense, and patient satisfaction in the short term.

Despite therapeutic advancements, treatment failure in hepatocellular carcinoma (HCC) continues to pose a significant obstacle. Given the vital role of the tumor immune microenvironment (TIM) in HCC and the promising effectiveness of immune therapies, we aimed to elucidate potential predictive biomarkers by developing a prognostic model based on immune-related genes (IRGs).
After obtaining data, differentially expressed IRGs were identified, and prognostic models were developed using Cox regression analyses. Key contributors of the model were identified and the results were validated by experimental assays in HCC cell lines.
Our eight-IRG signature can serve as an independent prognostic factor in HCC. The low-risk group exhibited superior overall survival and lower tumor mutation burden (TMB). The high-risk group showed elevated proportions of immune cells, including regulatory T cells and resting CD4+ memory T cells. We found that the "NEAT1-C1/miR-542-5p/BIRC5" regulatory network may serve as a potential target in HCC. The experimental investigations showed that BIRC5 inhibition reduced the metabolic activity in four HCC cell lines.
The results of this study facilitate patient stratification and the development of more effective treatment strategies, particularly for high-risk HCC patients.

Multiple sclerosis (MS) is a chronic autoimmune disease affecting the central nervous system. Current treatments aim to manage symptoms and slow disease progression, but there is a need for effective interventions that target underlying disease mechanisms. In this study, we investigated the effects of exercise, MitoQ (a mitochondria-targeted antioxidant), and their combination on the gene expression of various biomarkers associated with MS in postmenopausal and non-menopausal women, including inflammatory cytokine (IL-6), and key molecular pathways involved in MS pathogenesis, such as SMAD2, signal transducer and activator of transcription 1 (STAT1), and transforming growth factor beta (TGF-β) using real-time PCR. According to the results, all interventions effectively lowered IL-6 levels and STAT1, especially in non-menopausal women. Also, both exercise and MitoQ led to increased SMAD2 and TGF-β expression, with a more pronounced effect in non-menopausal women. Noteworthy, the effectiveness of the combination of exercise and MitoQ was considerably higher than each one alone. These findings suggest that exercise and MitoQ, either alone or combined, can modulate various biological pathways implicated in MS pathogenesis.

Melittin is a natural toxin used in traditional medicine as an anti-inflammatory drug. It seems that the anti-inflammatory properties of melittin are caused by suppressing the expression
of inflammatory genes and inhibiting signaling pathways. However, the use of melittin is limited
due to instability, rapid degradation, and impurity. The aim of this study was to investigate the intranasal administration of a melittin-encoded plasmid as a new melittin delivery method for allergic diseases.
After the induction of a mouse model of allergic rhinitis, mice received intranasal melittin plasmid. After the final challenge with allergen and allergic symptom assessment, the required samples were collected and transforming growth factor-beta (TGF-β), interferon-gamma (IFN-γ), and interleukin-4 (IL-4) cytokine levels, serum levels of ovalbumin-specific immunoglobulin (Ig) E, and histopathological changes were assessed. In addition to investigating the immune response, the effect of melittin on the expression level of genes involved in apoptosis was also investigated.
The melittin plasmid significantly improved nasal symptoms and decreased eosinophil infiltration into the nasal mucosa. Moreover, melittin decreased the expression levels of IL-4 and TGF-β in nasal lavage fluid, while IFN-γ expression was increased. Regarding the expression level of genes involved in apoptosis, melittin led to an increase in BAX mRNA expression.
These results suggest intranasal administration of a plasmid encoding melittin can suppress nasal symptoms, eosinophil infiltration, and immunomodulation of the immune response, which can be considered a promising approach in the treatment of inflammatory diseases.

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.

Cytotoxic CD4⁺ T cells eliminate human cytomegalovirus (HCMV)-infected cells through direct cytotoxic granules exocytosis. We aimed to evaluate the functional cytotoxic gene profile of CD4⁺ T cells alongside the frequency of the cytotoxic phenotype in renal transplant recipients with cytomegalovirus reactivation.
Blood samples were collected from twenty renal recipients with and without HCMV reactivation (HCMV+ and HCMV- groups) and ten healthy adults (control group). CD4⁺ T cells were isolated to assess the frequency of cytotoxic CD4⁺ T cells via CD107a surface staining using flow cytometry and to evaluate gene expression of perforin, granzyme B, Runt-related transcription factor 3 (RUNX3), and Eomesodermin (Eomes) by quantitative PCR.
The frequency of CD4⁺ CD107a⁺ T cells was higher in the HCMV+ group compared to the HCMV- group and significantly higher than in the control group (22.69±3.47 vs. 16.41±2.24 and 11.60±1.17, respectively). Perforin gene levels were reduced in the HCMV+ group compared to the other two groups, while granzyme B gene levels were similar between HCMV+ and HCMV- groups but lower than in the control group (0.63±1.24 vs. 0.67±2.27 and 1.00±0.00, respectively).
This study demonstrated an increased frequency of cytotoxic CD4⁺ T cells with potentially reduced functionality in kidney transplant patients with HCMV infection. It also suggests that these cells might employ other mechanisms, such as death receptor-mediated killing, or the production of other granules.

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.

Cisplatin resistance presents a considerable hurdle in the treatment of ovarian cancer, significantly impacting patient outcomes and limiting the effectiveness of chemotherapy. This study employs advanced bioinformatics techniques-including RNA sequencing (RNA-seq), DNA sequencing (DNA-seq), and chromatin immunoprecipitation sequencing (ChIP-seq)-to elucidate the molecular mechanisms underlying this resistance, with a particular focus on the long non-coding RNA (lncRNA) LINC02381.
Our findings reveal that LINC02381 is significantly upregulated in ovarian cancer cells exhibiting resistance to cisplatin, suggesting its pivotal role in mediating this phenomenon. We further demonstrate that cytokines, particularly interleukin-12 (IL-12), secreted by immune cells within the tumor microenvironment, activate the Wnt signaling pathway. This activation leads to the binding of the transcription factor TCF7 to the promoter region of LINC02381, resulting in enhanced expression of this lncRNA.
Notably, this interaction establishes a positive feedback loop in which LINC02381 not only promotes its own expression but also amplifies Wnt signaling activity. This cascade ultimately drives the upregulation of ATP-binding cassette (ABC) transporters, which are crucial for the efflux of cisplatin from cancer cells. Thus, the drug's intracellular concentration is reduced, and cell survival under chemotherapy pressure is facilitated. These insights uncover a novel mechanism of cisplatin resistance driven by the IL-12/Wnt/TCF7/LINC02381 axis, highlighting the complex interplay between immune signaling and drug resistance in ovarian cancer.
Our findings suggest that targeting this regulatory pathway may offer promising therapeutic strategies to overcome chemotherapy resistance, paving the way for improved treatment outcomes in patients with ovarian cancer. Future research should focus on validating these mechanisms and exploring potential interventions that disrupt this feedback loop.

Cytokines play an essential role in regulating the interaction of immune cells in diabetes and infections such as toxoplasmosis. The purpose of this study was to examine the serum levels of interleukin (IL)-6, IL-17, and transforming growth factor-beta (TGF-β) in patients with type 1 and type 2 diabetes mellitus with toxoplasmosis, and to explore their inter-relationship.
Forty patients with diabetes mellitus, including 20 with type 1 and 20 with type 2, as well as 20 healthy subjects, voluntarily participated in the study. Each subject provided 5 mL of peripheral blood for enzyme-linked immunosorbent assay.
Subjects with type 2 diabetes mellitus who also had toxoplasmosis showed a significant increase in TGF-β levels and a decrease in IL-6 levels. In contrast, patients with type 1 diabetes mellitus displayed a slight increase in IL-6 and IL-17 levels compared to both the patients with type 2 diabetes and the healthy control group.
Our findings show an increase in TGF-β and a decrease in IL-6, which may suggest a reduction in inflammation and beta cell destruction in individuals with type 2 diabetes and toxoplasmosis. The elevated serum levels of IL-6 and IL-17 in individuals with type 1 diabetes further support the exacerbation of inflammation.

Asthma is a prevalent chronic inflammatory disorder in children, and poor therapeutic response in asthmatic children could result from various factors related to the doctor, patient, disease, and treatment. This study aimed to evaluate the most important causes of failure in asthma control.
One hundred three children referred to the Children’s Medical Center in Tehran, Iran, participated in this study in 2017. A specific questionnaire was organized and completed by telephone interviews with parents.
The mean age of participants was 10.30 years, and 68.9% were male. More action plans (45/53) were received from hospitalized patients in the asthma and allergy ward than from hospitalized patients in the emergency department (13/46). Moreover, 85% of admitted patients in the asthma and allergy ward were visited by a specialist compared with 50% in the emergency department (23/46).
Hospitalization in the asthma and allergy ward resulted in receiving more action plans, spirometry tests, and visits by an allergist after discharge compared with admission to the emergency department.