Analyzing the Role of CircSnx5 in an Animal Model of Multiple Sclerosis
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).
Establishing an HLA-Typed Plateletpheresis Donor Registry at the Iranian Blood Transfusion Organization
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.
Inhibitory Effect of Propofol on Type II Inflammation in Mice with Allergic Rhinitis
Propofol, a quick‑acting systemic anesthetic agent widely used in general anesthesia, can alleviate airway T-helper 2 (TH2) 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 TH2 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 TH2 cells. When propofol was added, the percentage of TH2 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.
Ellagic Acid Ameliorates Ovarian Cancer via Modification of Pyroptosis and Inflammation
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.
Effects of c-Kit Receptor, AKT, and NF-κB Inhibitors on Immune Evasion in Multiple Myeloma Cells
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.
Evaluation of Heterologous Prime-boost Vaccine Strategy Using Full-length Cytomegalovirus Glycoprotein B to Trigger BALB/c Mice Immunity
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.
Investigating the Relationship between FGF2 Gene Expression and Airway Remodeling in Severe Asthma
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.
Rare Allergic Reaction to Local Anesthesia: A Case Report
One of the most commonly used local anesthetic (LA) agents in dentistry is lidocaine. Hypersensitivity reactions to lidocaine have been reported. In such cases, it is crucial to record a detailed clinical history and perform allergy testing to select a suitable alternative LA agent. This report presents the experience of observing a case of lidocaine allergy, supported by a review of the literature on the condition. A rare case of delayed hypersensitivity reaction to lidocaine is reported, where the patient exhibited swelling and erythema of the upper labial mucosa. Intradermal testing confirmed an allergic reaction to lidocaine. The patient was successfully treated with an alternative LA agent, allowing for the completion of dental procedures without complications. This highlights the importance of careful diagnostic measures to manage such rare but significant allergic reactions effectively. This case highlights the importance of recording a proper clinical history and performing allergy testing before the administration of LA to prevent severe allergic reactions. Additionally, patients identified as allergic to LA agents should be thoroughly counseled, informed about their condition, and provided with a clear explanation of all available treatment options.
Effectiveness of the Nasal Irrigation Effectiveness in Treating Allergic Rhinitis in Children 6 to 12 Years Old
Nasal irrigation, a nonpharmacological intervention for alleviating nasal symptoms, has yet to gain widespread acceptance among caregivers due to procedural ambiguities and the absence of a standardized protocol. This study aimed to evaluate the efficacy of normal saline nasal irrigation in managing allergic rhinitis among children aged 6 to 12 years. This prospective, randomized, single-blind trial enrolled children aged 6 to 12 with allergic rhinitis. Patients were randomly assigned to receive either standard care (oral antihistamine and intranasal corticosteroid) or standard care plus nasal irrigation with saline solution. Symptom severity, assessed using the Pediatric Rhinoconjunctivitis Quality of Life Questionnaire (PRQLQ) at baseline, 1, and 3 months, included rhinorrhea, nasal congestion, sneezing, pruritus, ocular symptoms, and functional impairment. The intervention group demonstrated statistically significant improvements in several domains post-intervention. Specifically, a marked reduction in sneezing frequency and nasal cleansing requirements was observed. Moreover, this group reported significantly lower ocular symptoms, including irritation, itching, and watering, relative to the control group. Although overall PRQLQ scores did not differ significantly between groups, the intervention group exhibited lower scores at the 1- and 3-month follow-ups, indicative of enhanced quality of life. These findings suggest a potential beneficial effect of the intervention on participant well-being. The findings of this study indicate that nasal irrigation with 0.65% saline solution 4 times daily may serve as an effective adjunct treatment for children with allergic rhinitis. This regimen was associated with significant enhancements in both nasal symptom severity and quality of life.
Neutrophil Markers as Predictors of COVID-19 Severity at Hospital Admission: A Cross-sectional Study
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 103 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.
Upregulation of MicroRNA-144 Suppresses Nrf2 Antioxidant Signaling Pathway in Patients with Severe COVID-19
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.
Effect of Remimazolam on Cellular Immune Response and Postoperative Recovery in Patients Undergoing Laparoscopic Colorectal Cancer Surgery
We aimed to evaluate the effect of remimazolam-based general anesthesia on cellular immune function and postoperative recovery quality in patients undergoing laparoscopic radical colorectal cancer surgery. A total of 90 patients scheduled for elective laparoscopic colorectal cancer radical surgery were randomly divided into 2 groups: the remimazolam group (Group R) and the propofol group (Group P), with 45 patients in each group. Anesthesia induction in Group R involved intravenous remimazolam, and in Group P, intravenous propofol until the loss of consciousness (modified observer's assessment of alertness/sedation [MOAA/S] score 1-2). Both groups then received intravenous sufentanil and cisatracurium for intubation. Cellular immune function markers (CD3+, CD4+, CD8+ T and natural killer [NK] cells) were recorded at different time points. Quality of Recovery [QoR]-15 scale scores, hemodynamic parameters, sedation scores (Riker and Ramsay scales), recovery times and adverse events were also recorded. Compared to Group P, Group R had significantly higher NK, CD3+, and CD4+ cell levels immediately after surgery and at 24 hours postoperatively. Group R showed a significantly lower incidence of intraoperative hypotension, bradycardia, and vasopressor use. Additionally, QoR-15 scores at 24 and 72 hours were higher in Group R. There were no significant differences in Riker or Ramsay scores, extubation time, post-anesthesia care unit stay, or the incidence of postoperative nausea, vomiting, and drowsiness between the 2 groups. Compared with propofol, remimazolam anesthesia results in better perioperative immune function preservation, reduced intraoperative hypotension and bradycardia, and improved postoperative recovery quality in patients undergoing laparoscopic radical colorectal cancer surgery.
Exploring the Association between Blood Indices and Skin and Joint Activity of Psoriatic Arthritis
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.
Increased Cytotoxic CD4+ T Cells with Reduced Cytotoxic Gene Profile Expression in Cytomegalovirus Reactivated Kidney Transplant Patients
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.
Effect of Exercise, MitoQ, and Their Combination on Inflammatory and Gene Expression in Women with Multiple Sclerosis
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 premenopausal women. We measured interleukin-6 (IL-6) and key molecular pathways involved in MS pathogenesis, including suppressor of mother against decapentaplegic 2 (SMAD2), signal transducer and activator of transcription 1 (STAT1), and transforming growth factor beta (TGF-β) using real-time polymerase chain reaction. All interventions significantly lowered IL-6 levels and STAT1, especially in premenopausal women. Also, both exercise and MitoQ led to a significant increase in the SMAD2 and TGF-β expression, with a more pronounced effect on premenopausal 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.
Ameliorative Effect of Melittin Encoded DNA Plasmid in an Ovalbumin-induced Murine Model of Allergy
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.
A Novel Prognostic Immune-related Gene Signature in Hepatocellular Carcinoma Through Bioinformatics and Experimental Approaches
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.
MicroRNA-486-3p Targets Chymotrypsin C to Regulate Pancreatic Cancer Progression and Immunosuppressive Factor Expression
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.
Bioinformatics-driven Identification of lncRNA LINC02381 in Mediating Cisplatin Resistance via IL-12 Induced Wnt/TCF7 Signaling in Ovarian Cancer
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.
How Hospitalizations Can Be Effective in Subsequent Care of Children with Asthma?
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.
Association of Toxoplasmosis with Serum TGF-β, IL-17, and IL-6 Levels in Individuals with Diabetes
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.