Background Venoarterial extracorporeal membrane oxygenation (VA-ECMO) is an essential life-saving technology used to treat refractory cardiopulmonary failure, commonly utilized in cases of cardiogenic shock, postoperative circulatory assistance, and resuscitation after cardiac arrest. While improving circulation and oxygenation, VA-ECMO often triggers a significant systemic inflammatory response, which can result in secondary lung damage and negatively impact patient outcomes. Corylin, a flavonoid found in the traditional Chinese herb Psoralea corylifolia, has shown properties that reduce inflammation and protect tissues. However, it’s possible protective effect against lung injury during VA-ECMO has not yet been investigated. Methods Thirty rats were randomly assigned to the sham group, the ECMO group, and the ECMO + Corylin group. A VA-ECMO model was established and maintained for three hours. Lung tissue and blood samples were collected and further evaluated using hematoxylin-eosin staining, immunohistochemistry, enzyme-linked immunosorbent assay, and transcriptomic analysis. Results During VA-ECMO, we observed lung injury characterized by neutrophil and macrophage infiltration, along with elevated lung injury biomarkers, including soluble advanced glycation end-product receptors and pulmonary surfactant protein D. We also found increased serum expression levels of inflammatory cytokines, including tumor necrosis factor-α, interleukin-1β, and interleukin-6. Following corylin administration, reduced neutrophil and macrophage infiltration in lung tissue was observed, along with decreased levels of the aforementioned biomarkers. Transcriptomic analysis revealed a downregulation trend in inflammatory response-related genes. Conclusions Corylin mitigates lung injury and inflammatory responses, potentially reducing pulmonary complications during VA-ECMO support.
Cardiovascular Diseases (CVDs) still reign as the leading cause of mortality worldwide, with Myocardial Infarction (MI) being one of the most life-threatening manifestations. Mounting evidence highlights the critical role of inflammation, specifically neutrophil activity, in MI pathogenesis, progression, resolution, and complications. Neutrophil Extracellular Traps (NETs), originally thought of only as antimicrobial defense mechanisms, have become widely accepted as key mediators of thrombo-inflammation, plaque rupture, microvascular obstruction, and maladaptive cardiac remodeling following an MI. This narrative review explores the multifaceted involvement of NETosis in MI, from its role in atherosclerotic plaque instability and thrombus formation to its influence on reperfusion injury and development of heart failure. Additionally, the use of circulating NET markers as potential diagnostic markers of MIs is discussed, along with novel therapeutic strategies aimed at modulating NET formation or promoting their clearance in an effort to treat MIs and prevent NET-mediated complications. Collectively, current evidence highlights NETs as both drivers of myocardial injury and as promising targets for therapeutic interventions in MI-patients.
Background Early prediction of wound healing after flap reconstruction for stage IV pressure injuries remains challenging. This study evaluated the neutrophil-to-lymphocyte ratio (NLR) and systemic immune-inflammation index (SII) as predictors of healing outcomes. Methods This retrospective cohort study included 127 patients with stage IV pressure injuries who underwent negative-pressure wound therapy and flap reconstruction between January 2020 and December 2024. Blood samples were collected at baseline, 72 hours, day 7, and day 14 post-surgery. The primary outcome was complete wound healing. Receiver operating characteristic curve analysis was used to assess the predictive performance of inflammatory indices. Results Complete healing was achieved in 72 patients (56.7%) over a median follow-up of 18 weeks. The delayed/non-healing group had higher baseline NLR (9.2 vs 6.0, P<0.001) and SII (2068.3 vs 1351.2, P<0.001). Day 7 NLR reduction was greater in the healing group (-22.9% vs -10.6%, P<0.001). Baseline SII had the highest predictive value among individual markers (area under the curve [AUC] 0.774). Day 7 NLR change achieved AUC 0.784. The combined model incorporating baseline NLR and day 7 NLR change yielded an AUC of 0.838, with 81.9% sensitivity and 70.9% specificity. Time-dependent analysis showed consistent performance across 30-day, 60-day, and 90-day time points (AUC 0.798-0.838). Conclusions Baseline SII and NLR, combined with early dynamic changes, may serve as potential predictors of healing after flap reconstruction for stage IV pressure injuries. Early assessment of NLR trajectory may provide adjunctive prognostic information, though prospective validation is required.
Objectives Accumulating evidence suggests that ursodeoxycholic acid (UDCA) has therapeutic potential for osteoarthritis (OA); however, the underlying molecular mechanisms remain poorly understood. Methods The chemical components of UDCA were retrieved from PubChem. Potential UDCA targets were collected from three databases. OA-related targets were obtained from GeneCards, OMIM (Online Mendelian Inheritance in Man), and TTD (Therapeutic Target Database) databases. Venny 2.1.0 was used to identify common targets between OA and UDCA. A protein-protein interaction network was constructed using the STRING database and subsequently analyzed using Cytoscape software to identify core genes. Gene Ontology and Kyoto Encyclopedia of Genes and Genomes pathway enrichment analyses were performed using DAVID. Molecular docking validation was conducted using AutoDock software, followed by molecular dynamics simulations using Amber to assess stability of interactions between UDCA and key targets. Results 194 common targets associated with UDCA and OA were identified. Among these, Albumin ( ALB ), Epidermal growth factor receptor ( EGFR ), Matrix metalloproteinase-9 ( MMP9 ), Proto-oncogene tyrosine-protein kinase Src ( SRC ), Caspase-3 ( CASP3 ), and Estrogen receptor ( ESR1 ) were identified as core targets. UDCA exerts its therapeutic effects on OA primarily through the modulation of protein hydrolysis, negative regulation of apoptosis, and promotion of cell proliferation and differentiation, as well as by influencing the PI3K-Akt, MAPK, and cancer-related signaling pathways. Molecular docking and molecular dynamics simulations demonstrated that UDCA exhibits good binding affinity and forms stable interactions with multiple core targets. Conclusion By targeting molecules such as ALB, EGFR, MMP9, SRC, CASP3 , and ESR1 , UDCA may interfere with the PI3K-Akt, MAPK, and other signaling pathways, thereby regulating the expression of inflammatory mediators, chondrocyte apoptosis, and cartilage matrix degradation and synthesis, thus contributing to OA treatment.
Background Inflammatory joint destruction releases intracellular components like ATP and triggers an acidic microenvironment. Detection of ATP and ischemia by sensory neurons leads to pain sensation, but little is known about the presence of purinoceptors and regulating factors in synovial tissue. The current study investigates the presence of ATP-receptor P2X5, acid-sensing ion channel ASIC3, and ATP degrading ectonucleotidases NTPDase1 (CD39) and NTPDase2 in human rheumatoid arthritis (RA) and osteoarthritis (OA) synovial tissue. Methods H&E and immunofluorescent staining on 8 rheumatoid arthritis (2 male, 6 female) and 8 osteoarthritis specimens (1 male, 7 female) were analyzed. Results Synovitis score was significantly higher in RA compared to OA (p=0.0002*, 7.38 ± 1.30 versus 2.75 ± 1.28 points, mean±SD). ASIC3 and P2X5 as well as NTPDase1 and NTPDase2 show a very high, significant correlation in synovial tissue of RA lining and sublining layer (r>93%, double staining in 11.2-24.6% of all cells, single staining in 0.5-10%). A high correlation for NTPDase1 and NTPDase2 was observed also in OA sublining layer (r>94%, double staining in 15.2-37.6% of cells, 0.8-8.1% single staining). Conclusions ASIC3 and P2X5 together with NTPDase1 and NTPDase2 indicate a tightly regulated purinergic microenvironment in RA and OA synovial tissue. Data suggests that nucleotide turnover, including ATP breakdown and subsequent adenosine generation, modulates inflammatory and nociceptive processes and purinergic signaling pathways in synovitis.
Cardiovascular diseases (CVDs) remain the foremost global cause of mortality, largely driven by endothelial dysfunction and vascular remodelling. The RhoA/Rho-associated coiled-coil containing protein kinase (ROCK) signalling pathway is central to vascular homeostasis, regulating vascular smooth muscle cell (VSMC) phenotypic plasticity, contraction, nitric oxide (NO) bioavailability, and cytoskeletal organization. Aberrant RhoA/ROCK activation contributes to hypertension, atherosclerosis, heart failure, and vascular stiffness through impaired endothelial function, oxidative stress, and maladaptive remodelling. This narrative review summarises current evidence on molecular mechanisms linking RhoA/ROCK activity with endothelial dysfunction and vascular pathology, highlighting its crosstalk with phosphoinositide-3-kinase–protein kinase B/Akt (PI3K-PKB/Akt), reactive oxygen species (ROS), and inflammatory mediators. Therapeutic insights focus on ROCK inhibitors, particularly fasudil, their limitations in isoform selectivity, and recent advances in structure-based drug design and targeted delivery systems. Isoform-specific and next-generation inhibitors represent a new frontier in therapy, with the potential to precisely suppress pathogenic RhoA/ROCK-driven inflammation, restore endothelial function, and markedly diminish cardiovascular disease burden.
Systemic lupus erythematosus (SLE) is a systemic autoimmune disease with manifestations ranging from mild skin symptoms to severe organ and neurological involvement. Thrombosis is a major complication and leading cause of mortality, though its mechanisms remain unclear. Emerging evidence highlights platelets, beyond their hemostatic role, as central players in SLE pathogenesis. This narrative review summarizes platelet-driven pathways in SLE, emphasizing their roles in thrombosis and immune regulation. Platelets interact with immune complexes, complement, and infectious agents, triggering activation and the release of mediators and microparticles. These processes increase circulating autoantigens and promote both thrombosis and autoimmune responses. Understanding these non-hemostatic platelet functions offers new insight into SLE mechanisms and may guide future platelet-targeted therapies.
The COVID-19 pandemic, caused by the novel coronavirus SARS-CoV-2, has posed unprecedented challenges to global health. Understanding the complex molecular and cellular mechanisms underlying SARS-CoV-2 infection is critical for developing effective therapeutic strategies. This narrative review comprehensively examines the key pathogenesis pathways involved in SARS-CoV-2 infection, with a focus on viral entry mechanisms, innate and adaptive immune responses, and the dysregulated inflammatory cascades that drive disease severity. We highlight the pivotal roles of immune cells, such as neutrophils, macrophages, natural killer cells, and T lymphocyte subsets, in orchestrating both protective and pathological responses. Central to severe COVID-19 is the excessive release of pro-inflammatory cytokines, known as the cytokine storm, which leads to acute respiratory distress syndrome and multi-organ failure. Furthermore, we critically evaluate conflicting evidence regarding key immunopathological processes. We further explore the impact of viral variants on immune evasion and therapeutic efficacy, as well as the emerging biomarkers that may guide personalized treatment. Finally, we discuss current and prospective therapeutic interventions, analyzing the clinical evidence and limitations of strategies targeting viral replication, immune modulation, and inflammation resolution. This synthesis provides valuable insights into the pathophysiology of COVID-19 and underscores the importance of integrated, adaptive approaches to combat this evolving disease.
Background: Persistent menstrual disorders are relatively common in patients with systemic lupus erythematosus (SLE). The purpose was to shed light on the causes and associations of menstrual disorders, particularly focusing on the potential influence of immunosuppressive medications. Patients and methods: This cross-sectional pilot study was performed on all the patients with SLE referred to our medical department who were eligible for participation. Venous blood samples were taken for FSH, LH, and anti-mullerian hormone measurement. Results: This study examined menstrual disorders and their association with disease activity on 50 patients with SLE. Patients were divided into 16-35 years (n = 23) and 36-51 years (n = 27) groups. Medications included hydroxychloroquine (82%), prednisolone (80%), azathioprine (20%) and methotrexate (6%). Dysmenorrhea was more common in the older group but not significantly. A remarkably higher proportion of prednisolone users reported dysmenorrhea compared with non-users (94.7% vs 5.3%, p < 0.05) in this pilot sample. No significant association was seen between polymenorrhea/menorrhagia and hydroxychloroquine, azathioprine or no medications. FSH, LH and anti-mullerian hormone levels were comparable across SLEDAI-2K groups. Although prednisolone usage was associated with dysmenorrhea, it is important to emphasize that this study is cross-sectional and therefore cannot establish a causal relationship. The observed association should not be interpreted as a definitive cause-and-effect link, and further prospective studies are needed to test such mechanisms. Conclusion: The significant association between prednisolone usage and dysmenorrhea in our study suggests that medications may contribute to menstrual disorders in SLE, possibly alongside disease activity. This important finding underscores the need for healthcare providers to be aware of the potential side effects of medications commonly used in treatment of SLE.
ObjectiveTo investigate the effects of vitamin D (VitD) on GATA-3 and T-bet expression in the nasal mucosa of allergic rhinitis (AR) rats and on regulation of the Th1/Th2 immune balance.Methods24 rats were randomly categorized into Control, Model, and VitD groups (n = 8 per group). The Model and VitD groups were sensitized with ovalbumin and aluminum hydroxide to establish an AR rat model. The VitD group received intranasal VitD treatment; the Model group received the equivalent volume of saline. Behavioral scores were recorded before and after modeling and following the final intervention. Nasal mucosal tissues were stained with hematoxylin-eosin to assess histology and eosinophil infiltration. Serum levels of interferon-gamma (IFN-gamma) and interleukin-4 (IL-4) were measured using enzyme-linked immunosorbent assays. Western blot was used to detect GATA-3 and T-bet expression levels.ResultsCompared with the control, the Model group exhibited typical nasal symptoms with increased behavioral scores; marked inflammatory cell infiltration, tissue edema, and vascular dilation in the nasal mucosa; elevated serum IL-4 levels; reduced IFN-gamma levels; downregulated T-bet expression; and upregulated GATA-3 expression. Compared to the Model group, the VitD group showed controlled nasal symptoms, reduced behavioral scores, alleviated inflammatory cell infiltration, decreased serum IL-4 levels, increased IFN-gamma levels, upregulated T-bet expression, and downregulated GATA-3 expression.ConclusionIntranasal VitD significantly downregulated GATA-3, upregulated T-bet, reduced serum IL-4, and elevated IFN-gamma levels. This may be linked to modulation of upstream transcription factors T-bet and GATA-3, potentially altering the differentiation tendency of Th0 cells toward Th1/Th2 subsets.
Background: Veno-venous ECMO (VV ECMO) is a life-sustaining technique indicated in the most severe forms of acute respiratory distress syndrome (ARDS). VV ECMO remains associated with significant morbidity and mortality. In this context, the identification of prognostic factors during the first week following ECMO implantation seems of high interest. However, little is known about the prognostic values of the kinetics of clinical and biological parameters in this timeframe. Methods: Observational, retrospective, multicenter study conducted in three centers in France and Belgium. We enrolled patients aged 18 years or older who underwent VV ECMO for severe ARDS between March 2020 and January 2023, with at least one endocan assay within 7 days of VV ECMO implantation. Kinetics of endocan and of a panel of clinical and biological markers were compared between surviving and deceased patients. Results: Forty-nine patients were included in our study among whom 30 patients (61%) were deceased on discharge from intensive care. Compared with patients who died, surviving patients had lower membrane fraction of oxygen at D3, lower fresh gas flow at D7, higher tidal volumes at D1 and D7, higher lung compliance and mechanical power at D7, and lower SOFA score at D7. Compared with deceased patients, survivors had a higher pH and lower endocan concentration on D3, and lower fibrinogen on D3 and D7. Conclusion: One week after initiation of VV ECMO support for severe ARDS, there was a significant decrease in the level of support simultaneously with respiratory and overall improvement in surviving patients. Compared to patients discharged alive from ICU, non-survivors were characterized by lower concentrations of endocan concentration at D3.
Objective: Systemic inflammation triggered by cardiopulmonary bypass (CPB) plays a critical role in postoperative complications and mortality. The Delta Neutrophil Index (DNI), which quantifies circulating immature neutrophils, is increasingly recognized as a marker of systemic inflammation. While its utility has been demonstrated in sepsis and non-cardiac surgeries, its role in cardiac procedures remains underexplored. This study aimed to evaluate the relationship between intraoperative DNI levels and postoperative mortality in patients undergoing open-heart surgery with CPB. Methods: This retrospective observational study included 245 patients who underwent CPB between January 2022 and July 2023. DNI was measured at five predefined time points: induction, 5, 45, and 90 min after CPB initiation, and immediately postoperatively. Patients were categorized into two groups based on in-hospital mortality: those who experienced mortality ("Ex" group, n = 67) and those who survived ("Non-Ex" group, n = 178). Logistic regression was used to assess the association between DNI values and mortality. Results: DNI levels were significantly higher in the Ex group at induction (1.22 +/- 0.96 vs 0.47 +/- 0.39; p = 0.002), 5 min (2.04 +/- 1.07 vs 1.08 +/- 0.58; p < 0.001), 90 min (1.76 +/- 0.84 vs 1.07 +/- 0.81; p = 0.004), and postoperatively (2.14 +/- 1.38 vs 0.58 +/- 0.32; p < 0.001). Each unit increase in postoperative DNI was associated with a 21.78-fold increase in mortality risk (95% CI: 6.12-67.92; p < 0.001). CPB and cross-clamp durations were also significantly longer in Ex patients. Conclusions: Elevated intraoperative and postoperative DNI levels are strongly associated with increased in-hospital mortality following CPB. DNI may serve as a dynamic and practical biomarker to aid perioperative risk stratification, pending further validation. Incorporating DNI into routine intraoperative monitoring may enhance early identification of high-risk patients and improve postoperative outcomes.
The aim of this study is to investigate the role of hydroxycarboxylic acid receptor 1 (HCAR1) in glutamate-induced excitotoxic neuronal injury. The effective and safe concentrations of an endogenous HCAR1 agonist (L-lactic acid) and an exogenous HCAR1 agonist (3,5-dihydroxybenzoic acid, 3,5-DHBA) were determined using a CCK-8 assay. An excitotoxic injury model was established by stimulating mouse hippocampal neuronal cells (HT22 cells) with 20 mM glutamate, followed by intervention with safe concentrations of L-lactic acid and 3,5-DHBA. Neuronal survival and apoptosis were assessed by NeuN immunofluorescence staining and a TUNEL assay. The effects of HCAR1 agonists on glutamate transport were evaluated using vesicular glutamate transporter 1 (VGLUT1) immunofluorescence staining and qRT‒PCR. Additionally, qRT‒PCR was performed to quantify the expression of a neuronal excitability marker gene ( c-fos ), inflammatory factors and hcar1 . The results showed that HCAR1 agonists (L-lactic acid and 3,5-DHBA) significantly improved neuronal survival, reduced glutamate-induced apoptosis and decreased neuronal excitability ( p < 0.05). The activation of HCAR1 inhibited the transport of the excitatory neurotransmitter glutamate ( p < 0.05). The upregulation of HCAR1 expression led to the significant downregulation of the expression of inflammatory factors ( il-1β , il-6 and tnf-α ) ( p < 0.05). In conclusion, HCAR1 activation effectively suppresses glutamate-induced neuronal apoptosis, reduces the uptake of excitatory neurotransmitters, and downregulates proinflammatory factor expression, thereby exerting neuroprotective effects.
BackgroundThe relationship between gout pathogenesis and inflammatory cytokine alterations remains uncertain, with inconsistent findings across studies. This study evaluated the causal links between gout and 41 inflammatory cytokines using Mendelian randomization (MR).MethodsGout-related genetic variants were examined in two large public databases: the Finnish database with 8489 gout patients and 240,862 European ancestry controls and the Genome-Wide Association Studies (GWAS) catalog dataset with 375 gout cases and 455,973 European ancestry controls. Cytokine levels in 8293 healthy participants from the GWAS were analyzed. Moreover, univariate MR analysis, primarily the inverse variance weighting method, was applied to examine the causal association between these factors. The findings were further validated using four additional MR methods based on different modeling assumptions, and their robustness was examined through sensitivity analysis using the MR leave-one-out analysis, Cochran's Q test, MR-Egger intercept test, and linkage disequilibrium score regression analysis.ResultsFollowing Bonferroni correction, this study unveiled a potential connection between macrophage inflammatory protein-1 beta (MIP 1B) and the risk of gout (OR: 1.08, 95%CI: 1.03-1.13, p = 9.61 x 10-4). Additionally, growth-regulated oncogene alpha (GROA) and macrophage migration inhibitory factor (MIF) were implicated in downstream gout development (OR: 1.04, 95%CI: 1.01-1.08, p = 0.02; OR = 1.04, 95%CI: 1.01-1.07, p = 0.0079). Sensitivity analyses confirmed the findings' reliability and consistency.ConclusionOur study suggests that MIP 1B may be a risk factor for gout, and inflammatory cytokines such as GROA and MIF are involved in the progression of gout. This supports a causal relationship between inflammatory cytokines and gout.
Purpose: Acute-on-chronic liver failure (ACLF) is a major cause of mortality and morbidity owing to the lack of targeted therapeutic interventions. The molecular mechanisms underlying the complex pathogenesis of ACLF are still unclear. Therefore, in this study, we established an ACLF mouse model using a combination of carbon tetrachloride (CCl 4 ) with lipopolysaccharide (LPS) and D-galactosamine (D-Gal) (CCl 4 + LPS/D-Gal) via intraperitoneal administration. Moreover, the underlying molecular pathogenesis of ACLF was explored. Methods: Four-dimensional label-free mass spectrometry-based quantitative proteomics was used to identify liver proteins that were differentially expressed in liver samples from CCl 4 + LPS/D-Gal-induced ACLF mouse liver samples. Results: Approximately 258, 380, and 471 proteins with a minimum mean expression fold change of 2 were differentially expressed in the liver fibrosis (LF), liver cirrhosis (LC), and ACLF groups, respectively, compared with those in the control (CTRL) group. Furthermore, the mice ACLF showed increased myeloperoxidase (MPO) and coronin-1A (CORO1A) levels, consistent with the phagosome pathway. These two proteins were potential targets for regulating the clinical features and progression of liver injury in ACLF mice. Conclusion: To the best of our knowledge, we are the first to provide a global differential protein expression profile of CCl 4 + LPS/D-Gal-induced ACLF mouse liver samples using label-free mass spectrometry-based quantitative proteomics. Overall, molecular differences in ACLF regulated the phagosome pathway at different disease stages, clarifying ACLF pathogenesis. MPO and CORO1A are the underlying predictors of ACLF severity or prognosis, and their regulation may facilitate timely and intensive clinical intervention.
Introduction: Oral lichen planus (OLP) is a chronic inflammatory disease with immune system dysregulation playing a key role in its pathogenesis. Cytokines such as IFN-γ and IL-4 are critical in modulating the Th1/Th2 balance, which is implicated in the disease’s progression. This study aimed to evaluate the expression of IFN-γ and IL-4 in the peripheral blood of OLP patients and explore differences between erosive and non-erosive subtypes. Materials and Methods: A retrospective analysis included 58 OLP patients (30 non-erosive and 28 erosive) and 58 healthy controls enrolled from June 2020 to June 2022. mRNA levels of IFN-γ and IL-4 were quantified using RT-PCR, while protein expression was determined via ELISA. Results: OLP patients demonstrated significantly elevated IFN-γ and IL-4 mRNA and protein levels compared to healthy controls ( p < .05). Both erosive and non-erosive subtypes showed increased cytokine expression ( p < .05). IL-4 levels were higher in the erosive subtype ( p < .05), while IFN-γ levels showed no significant difference between subtypes ( p > .05). The IFN-γ/IL-4 ratio was significantly higher in OLP patients than in controls ( p < .05), but lower in the erosive subtype compared to the non-erosive group ( p < .05). Conclusion: Elevated IFN-γ and IL-4 expression, particularly the skewed IFN-γ/IL-4 ratio in erosive OLP, highlights the importance of Th1/Th2 imbalance in OLP pathogenesis. This warrants further investigation into cytokine-targeted therapies for this chronic condition.
Backgrounds: Tuberculosis (TB) is a contagious disease caused by Mycobacterium tuberculosis that primarily affects the lungs but can also affect other organs of the body. In 2022, World Health Organization (WHO) reported that 202 countries account for more than 99% of TB cases around the world. Pakistan ranks 5 th among the countries with the highest burden of tuberculosis. The current study was planned to evaluate the biochemical profile of TB patients coinfected with other infectious and metabolic disorders. Methods: A total of 366 Ziehl Neelsen (ZN) stain positive TB patients were included in the study, along with positive controls who had comorbidities such as diabetes (62), hepatitis C virus (HCV) (46), human immunodeficiency virus (HIV) infection (11), and myocardial infarction (MI) (9). Biochemical parameters were determined photometrically by kit methods. Results: Among the 366 cases, 52% were females and 48% were males, with a mean age of 44 ± 5.803 years. Out of the ZN positive TB patients, 258 were found TB positive through PCR. Among the PCR positive TB patients, these patients were coinfected with diabetes (24%), HCV (17.8%), HIV (4.2%), and myocardial infarction (3.4%). Significant (P < 0.0001) variation in biochemical indices were observed in TB patients alone and those coinfected with diabetes, hepatitis C virus (HCV), and human immunodeficiency virus (HIV). Patients with co-morbidities of TB + Diabetes + HCV showed an increase in the levels of blood glucose, serum urea, creatinine, bilirubin, ALT, AST, ALP, IgG, IgM, potassium, and phosphorous. The group with co-morbidities of tuberculosis, hepatitis C, and HIV showed increases in the levels of ALP, IgG, and IgM. Conclusion: The study concluded that variations in biochemical indices observed in studied population provide useful information for the diagnosis of comorbidities of TB patients with metabolic and infectious diseases.
Background: Behçet syndrome (BS) is a multisystemic inflammatory disorder with an obscure pathogenesis. Inconsistent, sometimes contrasting immunological findings observed in BS studies and considerable geographic variation in BS’s disease expression need explanation. This study compared the gene expression profiles of Portuguese and Turkish BS patients. Methods: Publicly available transcriptome datasets from Portuguese (GSE17114) and Turkish (GSE209567) BS cohorts were retrieved and analyzed. Behçet syndrome patients were grouped as mucocutaneous, ocular, and vascular. Differentially expressed genes (DEGs) were identified using p ≤ 0.05 and fold-changes (FC) ≥1.5 and ≥2. BRB-ArrayTools for class comparisons, Venny 2.1.0 for Venn diagram analyses, Cluster 3.0 and Java Treeview for clustering, and WebGestalt for functional enrichment analyses were used. Results: During the class comparison PB versus TB (PB: Portuguese and TB: Turkish BS patients), 8024 DEGs were documented with an FC ≥2. Venn diagram analysis showed no shared genes at the intersection PB versus PC ∩ TB versus TC (PC: Portuguese and TC: Turkish controls). Both populations demonstrated decreased anti-inflammatory gene expressions, albeit with distinct gene identities. A set of 20 genes including IFI27 successfully clustered PB & TB. No enriched gene ontology terms were shared during functional enrichment analyses. Conclusion: Significant molecular differences exist between Portuguese and Turkish BS patients. Decreased expression of anti-inflammatory genes (e.g., CD69 , CLEC12A , CLC ) is common in BS. The identities of these genes are different across populations. Pro-inflammatory genes (e.g., IFI27 ) may further enhance disease severity in BS. A forthcoming era of personalized therapeutics based on molecular profiles may be approaching for BS. Specifically, CD69 for Portuguese and CLEC12A , CLC , and IFI27 genes for Turkish BS patients, may prove to be promising drug targets for BS.
Background: The role of Ppih in immune infiltration and its response to immunotherapy in hepatocellular carcinoma (HCC) patients has not yet been investigated. Methods: Bioinformatics analysis and clinical sample evaluation were used to assess Ppih mRNA expression in HCC and its association with pathological features, immune infiltration, immunotherapy response, and patient prognosis. Additionally, we collected 40 serum samples from HCC patients and healthy controls to verify the secretion levels of PPIH, IFN-γ, granzyme B, and IgG. Results: This study demonstrated that Ppih mRNA levels were significantly elevated in HCC and were associated with poor prognosis. Ppih is strongly linked to the immune cell infiltration environment in HCC, where it can induce immune barriers and contribute to poor prognosis. Moreover, elevated serum PPIH levels were confirmed in patients with liver cancer. Conclusions: Our findings suggest that Ppih is a promising prognostic and immunotherapeutic marker for HCC. Its secreted protein may also serve as a potential serum biomarker, offering new insights into the role of Ppih and its interaction with the tumor immune microenvironment in HCC.
