Metformin is a primary treatment for type 2 diabetes (T2D), well-known for its ability to lower blood glucose levels through both AMP-activated protein kinase (AMPK)-dependent and -independent pathways. Recent evidence suggests that metformin also possesses immunomodulatory properties, indicating its potential as a therapeutic agent that extends beyond metabolic regulation. This review summarizes the current understanding of metformin's dual roles in managing diabetes and modulating the immune system. It also explores the underlying mechanisms, clinical implications, and potential directions for future research.

Natural killer (NK) cells contribute to the development of Rheumatoid Arthritis (RA). Increased expression of programmed cell death protein 1 (PD-1), encoded by the PDCD1 gene, indicates NK cell exhaustion, a process that may be influenced by microRNAs (miRNAs). In this study, we examined PD-1 expression on NK cells from RA patients and evaluated whether miRNAs modulate this pathway.
Although antibiotics are critical for treating infections, they can provoke harmful immune responses by releasing bacterial components that overstimulate the immune system. Such responses may lead to excessive inflammation or cytokine storms. To address this risk, we assessed the immune safety of a newly designed chimeric endolysin, ZAM-MSC, and compared its effects with traditional antibiotics using transcriptomic, proteomic, and computational analyses.
We analyzed public gene and protein expression datasets from antibiotic-treated human cells and performed in silico studies on ZAM-MSC. Differential expression analysis and pathway enrichment were conducted, alongside structural modeling of the endolysin and its predicted interactions with immune receptors.
Antibiotic treatment strongly activated inflammatory genes and pathways, including nuclear factor kappa B (NF-κB) and mitogen-activated protein kinase (MAPK). In contrast, ZAM-MSC minimally affected immune-related gene expression, with downregulation of interleukin-6 receptor (IL6R) and tumor necrosis factor receptor 1A (TNFRSF1A). Structural modeling showed weak interactions with Toll-like receptors, and epitope analysis predicted low immunogenicity. These results suggest ZAM-MSC may offer a safer antimicrobial alternative, though all protein-level findings are based on computational predictions and require experimental validation. 

Lipopolysaccharide (LPS)–induced inflammation in macrophages involves complex signaling pathways. This investigation explored the regulatory roles of triggering receptor expressed on myeloid cells-1 (TREM1) and interleukin (IL)-26 in the Janus kinase/signal transducer and activator of transcription (JAK/STAT) and nuclear factor-kappa B (NF-κB) p65 pathways in LPS-stimulated RAW 264.7 macrophages.

RAW 264.7 cells were treated with LPS to assess TREM1 expression. TREM1 or IL-26 was silenced using short hairpin RNA (shRNA), while IL-26 was overexpressed via plasmid transfection. The JAK2 inhibitor AG490 was used to block JAK/STAT signaling. Western blot, reverse transcription–quantitative polymerase chain reaction (RT-qPCR), and enzyme-linked immunosorbent assay (ELISA) were employed to analyze the protein and mRNA levels of inflammatory markers and signaling molecules.
Results showed that LPS upregulated TREM1 expression. In addition, TREM1 knockdown suppressed p65 activation and reduced inflammatory cytokine levels. Moreover, silencing TREM1 inhibited IL-26 and JAK/STAT phosphorylation (p-JAK1, p-JAK2, p-STAT1, and p-STAT3). Similarly, IL-26 knockdown or AG490 treatment attenuated p65 activation and inflammation. Furthermore, IL-26 overexpression reversed the anti-inflammatory effects of TREM1 silencing.
Overall, TREM1 promoted LPS-induced macrophage inflammation via IL-26–mediated JAK/STAT and NF-κB pathway activation, suggesting that TREM1 and IL-26 are potential therapeutic targets.

Predominantly a widespread beta herpesvirus, human cytomegalovirus (HCMV) triggers lifelong latent infection in most of the people, and HCMV vaccine development has been designated a high public health priority.
In the current study, the in vitro safety profile and potential immunotoxic effects of a novel messenger RNA (mRNA)-lipid nanoparticle (LNP) vaccine designed against human cytomegalovirus (HCMV) were assessed. The aim was to measure inflammation, allergic reactions, complement activation, cytotoxicity, and hemolytic effects of the mRNA-LNP vaccine. Proinflammatory cytokine secretion, evident in human peripheral blood mononuclear cells (hPBMCs) treated with unmodified mRNA-LNP, was markedly attenuated by incorporating modified nucleotides.
The vaccine appeared incapable of sparking allergic cytokine production or complement activation. Cell viability assays indicated no pronounced cytotoxicity, and hemolysis assays showed no notable hemolytic activity.
The findings suggest that the modified mRNA-LNP vaccine exhibits a promising in vitro safety profile, supporting further development of this vaccine candidate.

Liver fibrosis is a significant global health issue characterized by an abnormal accumulation of extracellular matrix proteins, that disrupts normal liver architecture and function. Mesenchymal stem cells (MSCs) show therapeutic potential by releasing extracellular vesicles (EVs) containing regulatory microRNAs like miR-10a.
This study evaluates miR-10a-enriched human umbilical cord MSC (hUCMSC)-EVs in a CCl₄-induced model of liver fibrosis, focusing on inflammatory marker modulation. Liver fibrosis was induced in experimental animals using CCl₄ administration. MSCs were isolated from the human umbilical cord and loaded with either a miR-10a mimic or a control sequence through Lipofectamine 3000. EVs were then isolated from the culture media of both miR-control and miR-10a-modified MSCs. The therapeutic potential of these miR-10a-loaded EVs was assessed by treating the CCl₄-induced fibrosis model with these vesicles. The efficacy of the treatment was evaluated by measuring two anti-inflammatory markers interleukin (IL)-10 and IL-4) and three pro-inflammatory markers (tumor necrosis factor-α (TNF-α), IL-6, and interferon-γ (IFN-γ)) using enzyme-linked immunosorbent assay (ELISA) and real-time polymerase chain reaction (PCR) techniques.
The administration of miR-10a-loaded MSC-EVs resulted in a significant modulation of inflammatory markers. Our results revealed an increase in the levels of anti-inflammatory cytokines (IL-10 and IL-4) and a concurrent decrease in pro-inflammatory cytokines (TNF-α, IL-6, and IFN-γ) in the treated group compared to the control group.
The study demonstrates the therapeutic potential of MSC-EVs encapsulating miR-10a in ameliorating CCl₄-induced liver fibrosis. By modulating the balance between pro-inflammatory and anti-inflammatory cytokines, miR-10a-loaded EVs show promise as a targeted treatment approach for liver fibrosis.

Idiopathic pulmonary fibrosis (IPF) is a progressive lung disease marked by excessive extracellular matrix (ECM) deposition, largely mediated by activated fibroblasts. Epithelial-mesenchymal transition (EMT), regulated by transcription factors such as TGF-β, Twist1, and Snail, is a critical mechanism in fibrosis progression. AMP-activated protein kinase (AMPK) has been implicated in modulating fibrotic pathways, but its role in EMT remains unclear. This study aimed to explore the interaction between EMT and AMPK signaling in pulmonary fibrosis.
A bleomycin-induced pulmonary fibrosis mouse model was used. Histological analysis assessed fibrosis and inflammation, while gene expression (TGF-β, Twist1, Snail) was measured by qPCR. Protein levels of E-cadherin, α-SMA, and phosphorylated AMPK were analyzed using Western blotting to evaluate EMT and AMPK activity.
Bleomycin-treated mice showed significant lung inflammation and fibrosis, particularly in the lower region of the left lung. Gene expression analysis revealed elevated TGF-β, Twist1, and Snail in fibrotic areas. Protein analysis demonstrated increased α-SMA and decreased E-cadherin, confirming EMT induction. Notably, AMPK phosphorylation was significantly reduced in fibrotic regions, occurring concurrently with EMT activation.
These findings indicate an inverse relationship between AMPK signaling and EMT in pulmonary fibrosis. EMT may serve as a direct therapeutic target, either by inhibiting transcription factors such as Snail and Twist1 or by modulating upstream metabolic regulators including AMPK.

We aimed to investigate the causal relationship between cardiovascular-related proteins and osteoporosis and to assess the influence of immune cell traits and lifestyle factors such as smoking and alcohol consumption on osteoporosis risk.
A two-sample Mendelian randomization (MR) approach was employed using publicly available genome-wide association study (GWAS) data. Univariable and multivariable MR analyses were conducted using the inverse variance weighted (IVW) method to evaluate causal effects. Additional sensitivity analyses were performed to validate findings.
Three cardiovascular proteins showed significant associations with osteoporosis and pathological fractures: TNF-related apoptosis-inducing ligand receptor 2 (OR=0.10), TNF-related activation-induced cytokine (OR=2.90), and C-C motif chemokine 4 (OR=1.12). Lifestyle factors, including household tobacco smoke exposure, daily smoking quantity, and alcohol consumption, were also significantly associated with increased osteoporosis risk. Immune cell traits were identified as potential mediators in the relationship between cardiovascular proteins and osteoporosis.
This study highlights a novel link between cardiovascular health and osteoporosis, suggesting that specific proteins increase risk, while immune traits mediate this effect, and lifestyle factors are independent risk factors. These findings underscore the importance of integrated strategies addressing inflammation and lifestyle in osteoporosis prevention and management.

Component- Resolved Diagnosis (CRD) is an effective tool in allergy diagnosis, that detects specific IgE to allergenic molecules. The ALEX (Allergy Explorer) test, commercially available since 2019, measures specific IgE to allergenic extracts and components associated with inhalant, food, animal, latex, and insect allergens. CRD results should be interpreted based on the patient's clinical history.
Since Children's Medical Center Hospital is one of the largest referral centers for allergic patients, we evaluated the results of the ALEX2 test in patients referred to this center and compared them with the patients’ clinical symptoms.
Clinical symptoms were concordant with positive CRD (ALEX2) test in 76.7% of cases. The overall agreement between positive allergen components and clinical symptoms was 58%.
These findings indicate that the ALEX2 test can improve diagnostic accuracy in allergic patients; however, positive test results should be interpreted in the context of the patient’s clinical history.

This study examines the interaction between the microbiota and the immune system in diseases of the gastrointestinal tract, with a special emphasis on the synergistic use of pharmacological agents.
This was a retrospective, observational study of 100 patients with moderate to severe gastrointestinal disorders, including irritable bowel syndrome and inflammatory bowel disease, receiving control, monotherapy, or combination therapy.
Over 12 weeks, combination therapy demonstrated superior efficacy in enhancing gut microbial diversity. Improvements were achieved in alpha diversity, and a decrease in inflammatory indices and a shift in the immune phenotype were observed. Patients experienced significant improvements in symptom severity, pain, and general health. In addition, the general health of patients also improved. Importantly, the combination therapy group had better responses compared with the other groups. With respect to the identified factors, regression analysis revealed that microbial diversity, immune system regulation, and inflammation had positive effects on disease symptom alleviation.
These findings therefore help support the perspective of combination therapy as a more comprehensive mode of approaching and treating gastroenteric diseases.

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.

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.

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.

Idiopathic membranous nephropathy (IMN) presents a heterogeneous clinical course, with approximately 30% to 40% of patients experiencing spontaneous remission, while others respond poorly to treatment. This study aims to identify reliable biomarkers for risk stratification in IMN patients.
We conducted a prospective observational study involving 187 patients with IMN from February 2022 to February 2024. Patients were categorized into remission and non-remission groups based on clinical outcomes one year post-treatment. Comparative analyses revealed that the non-remission group exhibited significantly higher incidences of hypertension, elevated 24-hour urinary protein, higher serum creatinine levels, and increased inflammatory markers, including the systemic immune inflammation index (SII), systemic inflammation response index (SIRI), and pan-immune inflammation value (PIV). Conversely, the estimated glomerular filtration rate (eGFR) and lymphocyte-to-monocyte ratio (LMR) were lower in non-remission patients.
Spearman correlation identified hypertension, 24-hour urinary protein, and inflammatory indexes as positive correlates with non-remission, while eGFR showed a negative correlation.
Multivariate logistic regression confirmed hypertension, high 24-hour urinary protein, SII, SIRI, and PIV as independent risk factors for non-remission; eGFR was a protective factor. Receiver operating characteristic analysis revealed that SII and PIV effectively predicted non-remission (AUC=0.743 and 0.759, respectively). These findings underscore the potential of these indicators in assessing disease severity and guiding personalized treatment strategies.

Rigid nasopharyngoscopy is a valuable diagnostic method for immune-mediated allergy conditions, particularly for children aged≤6 years. In addition to evaluating the structural characteristics of the nasal cavity, the procedure also reveals inflammatory activity in the nasopharyngeal framework.

This study assessed 110 pediatric patients between 2 and 6 years old who presented with suspected allergic conditions. Rigid nasopharyngoscopy was performed, and its diagnostic performance was high with 85.45% sensitivity, 78.18% specificity, and an overall diagnostic accuracy of 83.00%, which supports its role in diagnosing and ruling out allergic disorders.

The findings revealed strong associations between mucosal erythema, cobblestoning, and mucosal secretions with symptoms like nasal obstruction and postnasal drip. These signs have proven to be reliable indicators of inflammation and chronic irritation in this age group. The procedure was well tolerated, and over 85% of children experienced no adverse effects.

Minor discomfort and nasal bleeding were reported in a small number of cases. Taken together, the results show that rigid nasopharyngoscopy is an essential diagnostic modality for early detection of allergy conditions in the pediatric population.

The aim of this research was to evaluate the diagnostic efficacy of integrating cervical length (CL), interleukin-6 (IL-6), placental alpha microglobulin-1 (PAMG-1), and fetal fibronectin (fFN) in predicting preterm birth among pregnant women with threatened preterm labor (TPL).
This study retrospectively analyzed clinical data from 150 pregnant women admitted for TPL between January 2021 and December 2024. Participants were divided into two groups based on pregnancy outcome: full-term delivery (n=85) and preterm birth (n=65). Additionally, 100 healthy pregnant women with no history of adverse pregnancy outcomes who underwent routine prenatal examinations during the same period were selected as the healthy control group. All participants underwent transvaginal ultrasound to measure CL, and venous blood samples were collected to assess serum IL-6 levels. PAMG-1 and fFN levels were measured in vaginal secretions.
There were no significant differences in baseline characteristics among the three groups. However, significant differences in CL, serum IL-6 levels, and positive rates of PAMG-1 and fFN were detected. Pearson correlation analysis showed significant associations between CL, IL-6, PAMG-1, fFN, and preterm birth. ROC curve analysis indicated that the AUC values for CL, IL-6, PAMG-1, and fFN alone were 0.798, 0.803, 0.753, and 0.754, respectively.
The combined application of these markers yielded an AUC of 0.920, significantly higher than any single marker. The combined use of CL, IL-6, PAMG-1, and fFN significantly enhances the diagnostic accuracy of preterm birth in patients with TPL.

Since late 2019, the severe acute respiratory syndrome coronavirus 2 (SARS‑CoV‑2) pandemic has dramatically affected public health worldwide. Although systemic antibodies like Immunoglobulin G (IgG) and Immunoglobulin M (IgM)have been widely studied in Coronavirus disease 2019 (COVID-19), the role of Immunoglobulin A (IgA) in mucosal immunity remains less understood. This study evaluated whether salivary IgA levels could serve as prognostic markers for disease severity, progression, and outcomes in hospitalized patients with COVID-19.
In this cross-sectional study, 61 hospitalized patients with COVID-19 were enrolled. After obtaining informed consent, saliva samples were collected at admission to measure IgA levels using an ELISA-based assay (Dlametra kit). Comprehensive clinical and laboratory data, including chest CT results, oxygen saturation, inflammatory markers, and clinical outcomes, were also recorded. Statistical tests were used to examine the association between salivary IgA levels and disease severity, progression, and outcomes.
We enrolled 61 hospitalized patients with COVID-19 (30 females, 31 males; mean age: 56.20 ± 17.45 years; mean admission oxygen saturation: 89.98 ± 5.77%). At admission, 39.3% of patients reported dyspnea, and 40% demonstrated severe lung involvement on chest CT scans. The mean salivary IgA level was 1729.69 ± 391.35 mg/dL. No significant associations were found between salivary IgA levels and COVID-19 severity, disease progression, or clinical outcomes, including mortality.
Our findings show that salivary IgA levels did not significantly correlate with COVID-19 severity, disease progression, or clinical outcomes in hospitalized patients. Therefore, salivary IgA alone cannot be recommended as a prognostic biomarker for COVID-19. Further research is needed to identify more reliable immunological indicators for predicting COVID-19 severity and outcomes.

This study explored the diagnostic value of peripheral blood indices for acute pyelonephritis (APN) and the factors influencing poor prognosis.
A total of 118 patients with APN admitted to our hospital from January 2022 to June 2024 were retrospectively included as the observation group. Another 62 healthy volunteers were selected as the control group. Clinical data from the two groups were collected, and the diagnostic value of peripheral blood indices for APN was analyzed. The patients were divided according to their prognoses into good-prognosis group and poor-prognosis group, and the influencing factors of poor prognosis were identified by multivariate logistic regression analysis.
Compared to the control group, the white blood cell count (WBC) and C-reactive protein (CRP) were higher in the observation group, while IgG and C3 were lower. The areas under the curves (AUCs) of WBC, CRP, IgG, and C3 in the diagnosis of APN were 0.857, 0.846, 0.902, and 0.893, respectively, and their combined AUC was 0.981. After 3 months of follow-up, there were 43 cases of recurrence (36.44%). The multivariate logistic analysis showed that serum albumin< 35 g/L and a decrease of the IgG level were the influencing factors of poor prognosis in patients with APN.
In conclusion, WBC, CRP, IgG, and C3 had high value for the diagnosis of APN, and serum albumin< 35 g/L and the decrease of IgG level were the i factors influencing prognosis.

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. 

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.

Chronic Granulomatous Disease (CGD) is a defect or abnormality in the immune system that produces severe and persistent signs and symptoms in affected individuals. 

There are phenotypic diversity and genetic heterogeneity 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.