Chronic Granulomatous Disease (CGD) is a defect or abnormality in the immune system that produces severe and persistent signs and symptoms in affected individuals. Phenotypic diversity and genetic heterogeneity exist amo...Chronic Granulomatous Disease (CGD) is a defect or abnormality in the immune system that produces severe and persistent signs and symptoms in affected individuals. Phenotypic diversity and genetic heterogeneity exist among patients with inborn errors of immunity (IEI). Symptoms may vary even when the mutations are identical; conversely, patients with different mutations may have similar clinical features. The expression of phenotype may be determined by the gene sequence, epigenetic changes, and sometimes environmental factors. Some of these outcomes are influenced by the individual's past immunological exposure. This study discusses two CGD cases, a father and son; after the diagnosis of CGD in the child and confirmation of the genetic mutation, the same mutation was also identified in the father. Therefore, physicians should have more awareness that a single genetic mutation can have different clinical manifestations.
This study aimed to identify a novel microRNA (miRNA)-related circulating biomarker that is easily accessible for clinical use and can dynamically monitor the biological characteristics of diffuse large B-cell lymphoma (...This study aimed to identify a novel microRNA (miRNA)-related circulating biomarker that is easily accessible for clinical use and can dynamically monitor the biological characteristics of diffuse large B-cell lymphoma (DLBCL). We analyzed miRNA expression profiles in DLBCL from the Gene Expression Omnibus (GEO) (GSE171272 and GSE173080) and The Cancer Genome Atlas (TCGA). The immune microenvironment and immune-related gene differences associated with hsa-miR-23a-5p were assessed through the single-sample gene set enrichment analysis and CIBERSORT. Gene set enrichment analysis identified expression trends related to hsa-miR-23a-5p. The 50% inhibitory concentration of chemotherapy agents was estimated for hsa-miR-23a-5p. Potential miRNA targets were identified using TargetScan, miRWalk, and RNA22, and validated with miRTarBase, DIANA-TarBase, and NPInter. Gene functions and associated pathways were analyzed through Gene Ontology and the Kyoto Encyclopedia of Genes and Genomes. Protein-Protein Interaction networks were built using Cytoscape. SNRPD1-related analysis was conducted using TCGA and GEO data. Hsa-miR-23a-5p was significantly overexpressed in the tumor tissues and serum exosomes of patients with DLBCL. The expression levels of hsa-miR-23a-5p were associated with distinct prognostic outcomes, immune landscapes, chemoresistance, and biological processes, serving as potential risk factors. The target gene SNRPD1 was an independent prognostic factor significantly associated with patient survival. This study identifies hsa-miR-23a-5p and its target SNRPD1 as potential prognostic factors for DLBCL. Specifically, the overexpression of hsa-miR-23a-5p in serum exosomes of patients with DLBCL suggests that it could serve as a convenient, non-invasive biomarker for clinical evaluation of DLBCL. However, further research and validation are necessary to confirm these findings.
Ulcerative colitis (UC) is a chronic immune-mediated disease with a growing global burden. In this study, bioinformatics analysis and machine learning methods were employed to screen the potential immune microenvironment...Ulcerative colitis (UC) is a chronic immune-mediated disease with a growing global burden. In this study, bioinformatics analysis and machine learning methods were employed to screen the potential immune microenvironment-related feature genes. We identified 4 immune-related genes that are consistently dysregulated in UC and correlate with immune infiltration, including APOBEC3B (Apolipoprotein B mRNA Editing Enzyme Catalytic Subunit 3B), CXCL11, PLA2G2A, and TMEM173. Their diagnostic performance was verified in an external cohort and in our clinical samples. Then, the proportion of ambiguous clustering (PAC) successfully classified UC patients into 2 molecular subtypes, including subtype 1 (metabolism-related subtype) and subtype 2 (immune-related subtype). The single sample gene set enrichment analysis (ssGSEA) algorithm revealed that subtype 2, with a higher score, of the majority of immune cells presented a worse inflammatory response. In addition, we assessed scores of partial novel drugs querying the cMAP database and found that the efficacy of clinical small-molecule compounds presented different results across UC subtypes. These findings identify biomarkers, establish a concise immune-based classification of UC, and support subtype-guided therapy.
Allergic rhinitis (AR), as a chronic disease, seriously affects the quality of life of patients while concurrently exerting a significant economic and healthcare burden on the medical system. However, the existing treatm...Allergic rhinitis (AR), as a chronic disease, seriously affects the quality of life of patients while concurrently exerting a significant economic and healthcare burden on the medical system. However, the existing treatment methods have certain limitations, and more effective treatment strategies are needed. To this end, we proposed an ovalbumin-induced guinea pig model of AR to investigate the potential impact of activated polyethylene glycol (PEG) with varying molecular weights and concentrations in local nasal treatment. The therapeutic effect was evaluated by behavioral score, serological detection, and histopathological observation. The behavioral assessment demonstrated significant alleviation of sneezing frequency, nasal pruritus, and clear nasal discharge in the activated PEG-600 treatment groups relative to the sham group. However, statistical analysis revealed no appreciable intergroup differences between the activated PEG-3400 treatment groups and the sham group. Histopathological evaluation disclosed a marked reduction in eosinophilic infiltration in the activated PEG-600 group, accompanied by preservation of nasal mucosal structural integrity and notable attenuation of inflammatory infiltration. In contrast, the activated PEG-3400 group exhibited comparatively limited therapeutic efficacy, demonstrating only a subtle reduction in inflammatory cell counts and more pronounced disorganization of mucosal epithelial architecture compared to the PEG-600-treated group. Serum immunological profiling indicated that while local inflammatory markers showed evidence of mitigation, systemic immune parameters remained unaffected by either activated PEG formulation. These findings underscore the differential efficacy profile between PEG-600 and PEG-3400 derivatives in ameliorating AR symptoms, among which PEG-600 exhibits superior anti-inflammatory effects.
This study integrated and analyzed two sets of gene expression data related to intervertebral disc degeneration (IVDD) to elucidate its key molecular mechanisms. Through screening and enrichment analysis of differentiall...This study integrated and analyzed two sets of gene expression data related to intervertebral disc degeneration (IVDD) to elucidate its key molecular mechanisms. Through screening and enrichment analysis of differentially expressed genes (DEGs), 112 DEGs were identified, primarily involved in extracellular matrix remodeling, cytoplasmic translation, and signaling pathways such as PI3K-Akt. A protein-protein interaction network combined with LASSO and SVM-RFE machine learning algorithms identified 13 hub genes. Immune infiltration analysis revealed reduced infiltration of suppressor cells and monocytes in IVDD samples. In an IL-1β-induced human nucleus pulposus cell degeneration model, qPCR and Western blot experiments confirmed significant downregulation of ADM, ITGB5, RTN4, SLPI, and CSNK1E expression. This study systematically reveals the potential molecular networks and immune characteristics of IVDD, providing new candidate biomarkers and therapeutic insights for subsequent targeted drug development.
Hepatocellular carcinoma (HCC) is the predominant type of primary liver cancer. This study aimed to elucidate the involvement of genes associated with 25 cell-death modalities in HCC development and progression. HCC tran...Hepatocellular carcinoma (HCC) is the predominant type of primary liver cancer. This study aimed to elucidate the involvement of genes associated with 25 cell-death modalities in HCC development and progression. HCC transcriptomic datasets were integrated with curated cell death-related genes. Candidate genes were screened by differential expression analysis and protein-protein interaction network construction. Prognostic genes were identified using univariate Cox regression, proportional hazards assumption testing, and stepwise multivariate Cox regression. A risk score model and a nomogram were established, followed by risk stratification and analyses of immune infiltration, immune checkpoints, somatic mutations, and in silico drug sensitivity. Single-cell RNA sequencing was used to identify key cell types, infer temporal dynamics, and characterize intercellular communication, and findings were validated by quantitative real-time PCR (qRT-PCR). MAPT, CDKN2A, NQO1, CHGA, SERPINE1, and RET were identified as prognostic genes, and the risk model and nomogram showed good prognostic performance. Immune profiling revealed significant differences in multiple immune cell subsets between risk groups, including activated CD4+ T cells. Notably, CDKN2A correlated with activated CD4+ T cells, NQO1 with natural killer cells, RET with CD4+ central memory cells, and SERPINE1 with activated dendritic cells; RET also showed the strongest positive correlation with HAVCR2. Mutation spectra differed across risk groups, and ten drugs displayed significant predicted IC50 differences; all six genes were negatively correlated with KIN001.135. Single-cell analyses highlighted hepatocytes as a key cell type with strong hepatocyte-epithelial communication. qRT-PCR confirmed higher MAPT, CDKN2A, NQO1, and SERPINE1 expression in HCC tissues than in normal tissues.
Type 2 diabetes (T2D) is defined by persistent inflammatory processes. This study evaluated the anti-inflammatory properties of empagliflozin in combination with metformin therapy in patients with T2D. In this prospectiv...Type 2 diabetes (T2D) is defined by persistent inflammatory processes. This study evaluated the anti-inflammatory properties of empagliflozin in combination with metformin therapy in patients with T2D. In this prospective cohort study, 50 individuals with type 2 diabetes were non-randomly assigned to receive metformin (MTF, n = 25) or empagliflozin (10 mg/day) and metformin (EMPA+MTF, n = 25) and followed for 6 months. Fasting blood glucose (FPG), HbA1c, body mass index (BMI), glomerular filtration rate (GFR), and urinary albumin were measured at baseline and then 6 months later. Interleukin-1beta (IL-1β) and interleukin-6 (IL-6) secretion from isolated and stimulated peripheral blood mononuclear cells were measured using ELISA and compared in the different study groups. The MTF+EMPA group showed significantly decreased levels of FPG, HbA1C, and body mass index compared to the baseline. FPG and HbA1c in the MTF+EMPA group showed a significant decrease six months after treatment versus the MTF group. A significant reduction in IL-1β levels was observed at the six months post-treatment compared to baseline and in relation to the MTF group after six months. The levels of IL-6 exhibited no significant differences, both within and between the study groups. Significant direct correlations were observed between IL-1β levels and FPG as well as HbA1c within the MTF+EMPA group following six months of treatment. Incorporating empagliflozin (10 mg/day) into metformin treatment markedly enhanced glycemic regulation and lowered IL-1β secretions, indicating a possible anti-inflammatory benefit in overweight individuals with T2D following six months of treatment.
T helper 1 (TH1) and T helper 2 (TH2) cells can secrete various proinflammatory and anti-inflammatory factors, which can serve as indicators for predicting the severity of pneumonia. However, they are rarely used in comb...T helper 1 (TH1) and T helper 2 (TH2) cells can secrete various proinflammatory and anti-inflammatory factors, which can serve as indicators for predicting the severity of pneumonia. However, they are rarely used in combination with procalcitonin (PCT) and high-sensitivity C-reactive protein (hsCRP) detection to predict the severity of pneumonia. The purpose of this study is to investigate the combination of serum TH1/TH2 cytokines, PCT, and hsCRP for predicting the severity of community-acquired pneumonia (CAP). This study observed 58 inpatients with CAP. Analyses were conducted on the serum levels of TH1/TH2 cytokines, PCT, and hsCRP; imaging examination results; underlying diseases; pathogens; and the pneumonia severity index (PSI). The severe pneumonia group showed significantly higher PSI scores, age, and complication rates. Serum IL-2 was notably elevated in severe cases, while a combination of PCT, IL-4, TNF-α, and IFN-γ effectively predicted severe pneumonia, with an AUC of 0.712. Specific alterations in cytokines and biomarkers were identified as risk factors for higher PSI, complications, and prolonged hospitalization. The combined detection of PCT, IL-4, TNF-α, and IFN-γ provides a potential tool for predicting severe CAP, and distinct biomarker profiles are associated with different clinical outcomes.
This study aimed to explore the effects of different dexmedetomidine (DEX) administration routes on anesthesia quality in pediatric patients undergoing endoscopic low-temperature plasma adenotonsillar ablation. We select...This study aimed to explore the effects of different dexmedetomidine (DEX) administration routes on anesthesia quality in pediatric patients undergoing endoscopic low-temperature plasma adenotonsillar ablation. We selected 120 children with obstructive sleep apnea hypopnea syndrome scheduled for surgery between May and December 2023. Participants were divided into four groups (n=30 each): a control group (Group S) receiving standard anesthesia without DEX; a local anesthesia group (Group L) receiving ropivacaine infiltration with 0.3 µg·kg-1 DEX; an intravenous group (Group T) receiving 0.6 µg·kg-1 DEX infusion post-induction; and a nasal drip group (Group N) receiving 0.6 µg·kg-1 DEX intranasally upon room entry. We compared operation/extubation/recovery times, and scores from the Observer Assessment of Alertness and Sedation (OAA/S), Objective Pain Scale (OPS), and Pediatric Anesthesia Emergence Delirium (PAED) scales. Rescue sedation and safety were also assessed. Group T showed lower heart rates at specific timepoints, while Group L had lower blood pressures. Recovery time (Steward score ≥4) was longer in Groups L and T compared to Group S, but not in Group N. Groups T and N showed increased OAA/S scores post-awakening, with Group N having the highest scores. OPS and PAED scores decreased in all DEX groups, with Group N demonstrating the lowest scores, followed by Group L and then Group T. No significant differences were found in operation time, extubation time, or the incidence of rescue sedation/complications among groups. Intranasal DEX emerged as the optimal route, providing effective analgesia and sedation without prolonging recovery time.
Traditional radical cystectomy has a high recurrence rate, a high probability of metastasis, and a reduced quality of life for patients. This study aimed to explore the efficacy of combining immunotherapy and surgical re...Traditional radical cystectomy has a high recurrence rate, a high probability of metastasis, and a reduced quality of life for patients. This study aimed to explore the efficacy of combining immunotherapy and surgical resection for high-risk muscle-invasive bladder cancer. In a retrospective study, 231 patients with high-risk muscle-invasive bladder cancer admitted to Yueyang People's Hospital between January 2019 and May 2024 were selected. After exclusions, 200 cases were analyzed and divided into two groups according to the treatment modality: the control group (surgical resection alone, n=100) and the intervention group (combination of immunotherapy and surgical resection, n=100). The cellular immune function indexes (CD3+, CD4+/CD8+, and natural killer cell levels), tumor markers (carcinoembryonic antigen, carbohydrate antigen 125, cytokeratin 21-1, and neuron-specific enolase), serum cytokines (basic fibroblast growth factor, vascular endothelial growth factor, and tumor necrosis factor-α), pathological complete remission (pCR), 1-year survival, and Functional Assessment of Cancer Therapy-Bladder (FACT-BL) quality-of-life scores were assessed in the two groups. After 1 year of treatment, the indicators of the two groups of patients were statistically significant in comparison with each other. Patients in the intervention group had substantial improvements in immune function indexes, pCR, 1-year survival rate, and FACT-BL scores in comparison with the control group. Tumor markers and serum cytokines were lower than those in the control group. The combination of immunotherapy and surgical resection can enhance clinical efficacy, providing a scientific basis for optimizing the clinical treatment plan.
Acute calculous cholecystitis (ACC) often triggers transient perioperative elevations in liver enzymes and systemic inflammation, yet existing complication-prediction tools seldom incorporate dynamic biomarker changes. O...Acute calculous cholecystitis (ACC) often triggers transient perioperative elevations in liver enzymes and systemic inflammation, yet existing complication-prediction tools seldom incorporate dynamic biomarker changes. Our goal was to establish and develop, using internal validation, a multivariable risk model that incorporates perioperative variations in liver function tests (LFTs) and the Systemic Immune-Inflammation Index (SII) in order to predict Clavien-Dindo grade ≥II complications following cholecystectomy for ACC. In this retrospective cohort study at a tertiary academic center (January 2022-December 2024), we analyzed 260 adult patients undergoing laparoscopic or open cholecystectomy for ACC. We calculated Δ-values (day 1 minus baseline) for alanine aminotransferase (ALT), aspartate aminotransferase (AST), total bilirubin, and SII (platelet × neutrophil/lymphocyte). Multivariable logistic regression with backward stepwise selection was used to derive the final model, which included ΔALT, ΔAST, Δbilirubin, ΔSII, age, American Society of Anesthesiologists (ASA) status, and operative duration. Internal validation employed 1 000 bootstrap replications. The model demonstrated good discrimination (optimism-corrected area under the curve, 0.82; 95% CI, 0.77-0.87) and excellent calibration (slope, 0.95; intercept, -0.02). Significant predictors included ΔALT, ΔAST, Δbilirubin, and ΔSII, along with age, ASA III status, and longer operative duration. The decision-curve analysis demonstrated net benefit across threshold probabilities of 5% to 40%, with 15 additional true positives per 1 000 at the 20% threshold. Integrating dynamic perioperative changes in LFTs and SII with key clinical factors yields a robust risk prediction model for postoperative complications after ACC surgery.
The responses of patients with chronic spontaneous urticaria (CSU) to regular therapeutic options vary. While these methods are effective for some patients, many do not respond successfully. Despite several studies condu...The responses of patients with chronic spontaneous urticaria (CSU) to regular therapeutic options vary. While these methods are effective for some patients, many do not respond successfully. Despite several studies conducted to identify immunologic and inflammatory biomarkers in patients that can predict response, our current knowledge is insufficient. This study aimed to identify biomarkers that may predict therapeutic response. The present interventional study evaluated 61 moderate-to-severe CSU patients aged 20 to 50 years who presented to our clinic from January 2024 to January 2025. Peripheral blood samples, serum, and plasma were collected to measure inflammatory and immunological variables, and were analyzed at a reference laboratory. Subsequently, patients were treated with cetirizine 10 mg every 12 hours and famotidine 40 mg every night. After 1month, urticarial severity was reassessed using the same questionnaire. Severity scores were compared between patients with elevated biomarkers and those with normal levels. Sixty-one patients with chronic spontaneous urticaria were enrolled; 77% female and 23% male. Forty-one patients experienced a good response to treatment, while 20 patients did not. The average (Urticaria Activity Score) UAS7 scores before and after treatment were 27.72 and 12.67, respectively. Among the serum biomarkers evaluated, only the neutrophil-to-lymphocyte ratio (NLR) and serum eosinophil count showed a significant relationship with treatment response. To conclude, a high eosinophil count and NLR may serve as predictors of a poor clinical response to antihistamine therapy. However, further clinical trials are needed to confirm these findings.
Allergy and lung cancer are two distinct health concerns. While allergies are typically associated with heightened immune activity, such immune responses may also influence the tumor microenvironment. This study aimed to...Allergy and lung cancer are two distinct health concerns. While allergies are typically associated with heightened immune activity, such immune responses may also influence the tumor microenvironment. This study aimed to investigate a potential link between allergic conditions and the risk of lung cancer. We conducted a case-control study analyzing 82 histologically confirmed lung cancer patients and 82 healthy controls from 2019 to 2022. Data were collected through structured questionnaires assessing asthma, allergic rhinitis (AR), food/drug allergies, and chronic urticaria. Statistical analyses included independent samples t-tests and chi-square tests, with significance set at a predetermined threshold. We observed a significant inverse association between AR and lung cancer (8.54% vs 47.56% in controls; OR=0.14, 95% CI: 0.06-0.32). No significant associations were found for asthma (7.32% vs 3.66%), chronic urticaria (3.66% vs 3.66%), drug allergy (4.88% vs 1.22%), or food allergy (2.44% vs 6.10%). The association between AR and lung cancer remained robust after adjustment for demographic factors. AR demonstrated a strong negative association with lung cancer, suggesting potential protective mechanisms distinct from other allergic conditions. These findings support the growing evidence for allergy-cancer immunomodulatory interactions and highlight the need for mechanistic studies on AR-specific pathways in oncogenesis.
Alternaria alternata is one of the most potent fungal allergens associated with allergic respiratory diseases, particularly asthma. Sensitization to A alternata has been linked to poor asthma control and increased morbid...Alternaria alternata is one of the most potent fungal allergens associated with allergic respiratory diseases, particularly asthma. Sensitization to A alternata has been linked to poor asthma control and increased morbidity, yet its prevalence varies widely across populations due to environmental and methodological differences. This study aimed to determine the prevalence and demographic predictors of A alternata sensitization among patients with moderate to severe asthma. A cross-sectional study was conducted from March to September 2024 among 80 patients with physician-diagnosed moderate or severe asthma in Shiraz, Iran. Participants underwent skin prick testing (SPT) for A. alternata. Demographic and clinical data were collected and analyzed using descriptive statistics, χ2 tests, and logistic regression. Among the 80 patients (mean age 29.03 ± 20.45 years; 53.8% male), 28.8% tested positive for Alternaria sensitization. Sensitization was significantly more prevalent in patients younger than 18 years (44.1%) compared to adults (17.4%). No significant difference was observed based on sex. Although sensitization was more frequent in patients with severe asthma (40.6%) than moderate asthma (20.8%), this trend was not statistically significant. Logistic regression identified younger age as the only independent predictor of sensitization. Alternaria alternata sensitization is common among individuals with moderate to severe asthma, particularly in younger patients. These findings underscore the importance of routine fungal allergen screening in asthmatics, especially children, to inform targeted management strategies and potentially reduce asthma-related morbidity.
Good's syndrome (GS), a rare immunodeficiency disorder characterized by thymoma and hypogammaglobulinemia, presents diagnostic and therapeutic challenges due to recurrent infections. We report a 53-year-old male farmer w...Good's syndrome (GS), a rare immunodeficiency disorder characterized by thymoma and hypogammaglobulinemia, presents diagnostic and therapeutic challenges due to recurrent infections. We report a 53-year-old male farmer with GS complicated by recurrent pulmonary infections and COVID-19. Initial management focused on antiviral/anti-infective therapy and corticosteroids, but persistent hypogammaglobulinemia, B-cell depletion, and thymoma history were overlooked. Diagnosis was confirmed upon integrating the thymoma history, immunological profiling, and bronchial alveolar lavage-next generation sequencing, revealing Pneumocystis jirovecii and Herpes Simplex Virus-1 coinfections. Treatment with intravenous immunoglobulin loading dose (2 g/kg), pathogen-targeted therapy (voriconazole, cotrimoxazole), and tapered corticosteroids achieved clinical remission, with immunoglobulin G (IgG) elevating to 6.35 g/L. This case underscores the necessity of a "four-dimensional early warning system" integrating thymoma history, immune, imaging, and pathogen for timely GS diagnosis. Multidisciplinary collaboration and personalized regimens combining immunoglobulin replacement, precision anti-infectives, and immunomodulation are pivotal for optimizing outcomes in GS patients with complex infections.
Common variable immunodeficiency disorder (CVID) is the most prevalent primary immunodeficiency in adults. Pathogenic mutations of the TNFRSF13B gene were identified in CVID patients and associated with autoimmunity and...Common variable immunodeficiency disorder (CVID) is the most prevalent primary immunodeficiency in adults. Pathogenic mutations of the TNFRSF13B gene were identified in CVID patients and associated with autoimmunity and lymphoproliferation. A study on Swedish children unaffected by CVID has shown that rare variants in the TNFRSF13B gene increase the risk of asthma. To the best of our knowledge, asthma has not been reported in CVID patients with TNFRSF13B gene mutations. We described a patient suffering from asthma and CVID with a heterozygous mutation in the TNFRSF13B gene. According to our findings and previous studies, mutations in the TNFRSF13B gene seem to be possibly associated with the occurrence of asthma in CVID patients.
Sulfur mustard (SM) is a potent chemical warfare agent that causes severe cutaneous, ocular, and pulmonary injuries, with respiratory tract damage being the most life-threatening. Despite its well-documented toxicity, th...Sulfur mustard (SM) is a potent chemical warfare agent that causes severe cutaneous, ocular, and pulmonary injuries, with respiratory tract damage being the most life-threatening. Despite its well-documented toxicity, the cellular mechanisms driving SM-induced apoptosis remain poorly understood. This study seeks to elucidate the apoptotic pathways involved in SM-induced pulmonary injury using a rat model. We induced acute lung injury through two delivery methods: intraperitoneal injection (8 mg/kg) and intratracheal instillation (2 mg/kg) of SM, with both doses representing 1 LD50. We assessed apoptosis-related proteins and gene expression through TUNEL staining, immunohistochemistry, and quantitative real-time PCR analyses. Intraperitoneal administration of SM resulted in significantly elevated expression of apoptotic markers including annexin A1, annexin A2, cytochrome C, caspase-12, and JNK3, in alveolar epithelial cells compared to intratracheal delivery. Both TUNEL assays and immunohistochemical staining confirmed these findings. These results indicate that intraperitoneal SM exposure triggers more severe apoptotic responses in alveolar epithelial cells than intratracheal exposure at equivalent doses. These findings demonstrate that intraperitoneal models can effectively identify apoptosis-related molecular targets suitable for therapeutic development.
Tumor microenvironment modulators have produced durable effects in cancer treatment. Targeting immune checkpoint receptors, such as PD-L1, has demonstrated efficacy in eliciting antitumor responses. However, resistance t...Tumor microenvironment modulators have produced durable effects in cancer treatment. Targeting immune checkpoint receptors, such as PD-L1, has demonstrated efficacy in eliciting antitumor responses. However, resistance to immune checkpoint blockers (ICBs) has constrained the efficacy of these therapies. Previous studies showed a link between the expression of AXL receptor tyrosine kinase and resistance to ICBs. Therefore, designing combination treatments with synergistic mechanisms to overcome ICB-based resistance is needed. In addition to antibody-based therapies, gene silencing with siRNAs has recently been explored to alter the cancer environment to enhance the immune response. In this study, we targeted PD-L1 using an siRNA and AXL using a blocker (R428) in OVACAR-3 and CaSki cells, ovarian and cervical cancer cell lines, respectively, in the following groups: Scramble-siRNA, PD-L1-siRNA, Scramble-siRNA in conjunction with R428, PD-L1-siRNA in conjunction with R428, R428 monotherapy and untreated controls. Cell viability was assessed by MTT assay after 48 hours of treatment, and cisplatin sensitization was evaluated in resistant OVACAR-3 cells. Gene expression was analyzed by qRT-PCR, while flow cytometry quantified CD44+PD-L1+ populations, apoptosis (Annexin V/PI), and cell cycle distribution. The results showed a significant decrease in cell proliferation, suppression of EMT-regulating genes, reduction of stemness in cancer cells, increased apoptosis and disruption of the cell cycle in the studied cell lines. These findings suggest that simultaneous blockade of PD-L1 and AXL could serve as a novel tumor-suppressive strategy, especially for cancer patients resistant to ICBs.
Asthma is a chronic inflammatory disease characterized byimmune dysregulation. This study aimed to perform unbiased analysis of transcriptomic data to identify differentially expressed m6A-related genes in asthma, with a...Asthma is a chronic inflammatory disease characterized byimmune dysregulation. This study aimed to perform unbiased analysis of transcriptomic data to identify differentially expressed m6A-related genes in asthma, with a focus on exploring their potential as biomarkers and therapeutic targets. Gene Expression Omnibus (GEO) (GSE134544) dataset was analyzed to identify differentially expressed m6A-related genes. Functional enrichment analysis was performed clusterProfiler, immune infiltration profiling was conducted with CIBERSORT, and a competing endogenous RNA (ceRNA, including microRNA [miR] and lncRNA) network was constructed. Drug enrichment analysis was carried out using DSigDB, and molecular docking was utilized to assess the interaction between dabigatran and the METTL3 protein. From 192 differentially expressed genes, four m6A-related genes (METTL3, HNRNPC, IGFBP2, and RBMX) were identified as the intersecting genes between the m6A-related gene set and differentially expressed genes (DEGs) from the GSE134544 dataset. Gene Ontology (GO) analysis revealed significant enrichment in biological processes related to RNA metabolic processes and post-transcriptional regulation, while Kyoto Encyclopedia of Genes and Genomes (KEGG) analysis identified important pathways such as spliceosome and p53 signaling pathways. METTL3 and HNRNPC were central in the ceRNA network, interacting with miRs such as hsa-miR-93-3p and lncRNAs like LINC01529. Drug enrichment analysis identified dabigatran as a potential METTL3 inhibitor, with molecular docking confirming a stable binding affinity (-5.9 kcal/mol). This study emphasizes the critical role of m6A-related genes, particularly METTL3 and HNRNPC, as macromolecules in asthma pathophysiology, and provides insights into their potential as biomarkers and therapeutic targets for asthma treatment.
Aziz-Ahari S, Aminian M, Rahimian A
… +19 more, Nafissi S, Heidari M, Rabbani A, Zarnani AH, Mohebbi A, Badv RS, Salajegheh N, Mortezagholi S, Masoumi S, Hadipour Z, Boostani R, Beiraghi Toosi M, Sayadpour Zanjani K, Khajeh A, Tonkaboni SH, Sadeghi M, Fatehi F, Vafaei E, Ashrafi MR
Anti-recombinant human acid α-glucosidase (anti-rhGAA) antibody formation is a major challenge in patients with Pompe disease receiving enzyme replacement therapy (ERT). The clinical significance of these antibodies and...Anti-recombinant human acid α-glucosidase (anti-rhGAA) antibody formation is a major challenge in patients with Pompe disease receiving enzyme replacement therapy (ERT). The clinical significance of these antibodies and their detection methods remain uncertain. This study aimed to evaluate the diagnostic and functional relevance of anti-rhGAA antibodies in late-onset Pompe disease (LOPD) and to compare the performance of ELISA and Western blot assays. Fourteen patients with LOPD undergoing ERT and 14 age- and sex-matched healthy controls were studied. Serum anti-rhGAA antibodies and their IgG, IgM, and IgA isotypes were quantified using ELISA and verified by Western blot. Motor function was assessed using the Pompe Motor Function Levels Questionnaire, an adapted version of the GMFCS validated for Pompe disease. Total and isotype-specific anti-rhGAA antibody levels were significantly higher in patients than in controls. ROC analysis showed excellent discrimination between groups. Strong agreement was observed between ELISA and Western blot results. However, antibody levels were not significantly correlated with motor function grade. Given the small sample size (n = 14), this non-significant result may reflect limited statistical power rather than a true lack of association. Anti-rhGAA antibody detection effectively distinguishes LOPD patients from healthy individuals. Western blot provides a reliable, low-cost alternative to ELISA, particularly useful in resource-limited settings. Nevertheless, the prognostic utility of antibody titers for functional outcomes remains uncertain and warrants larger, multicenter validation studies.