International Journal of Immunopathology and Pharmacology最新文献

Protein-losing enteropathy (PLE) is a rare but recognized manifestation of systemic lupus erythematosus (SLE). As an initial presentation of SLE, PLE is exceptionally uncommon, particularly in pediatric patients. We report the case of a 15-year-old Vietnamese girl with no significant past medical or family history, who presented with PLE as the initial manifestation of SLE. Clinical features included bilateral eyelid and lower extremity edema, ascites, and hypoalbuminemia, in the absence of nephrotic-range proteinuria, hepatic dysfunction, or malnutrition. Stool α1-antitrypsin concentration was markedly elevated at >231 mg/dL (normal <26.8 mg/dL), supporting the diagnosis of PLE in conjunction with clinical features and therapeutic response. Immunological evaluation revealed positive antinuclear antibody (ANA), anti-double-stranded DNA (anti-dsDNA) antibody, and lupus anticoagulant, hypocomplementemia, along with proteinuria equivalent to >0.5 g/24 h, fulfilling the 2019 EULAR/ACR classification criteria for SLE. The patient also developed cerebral venous sinus thrombosis. Treatment with corticosteroids, hydroxychloroquine, and warfarin resulted in significant clinical improvement. At 7 months of follow-up, she remained clinically stable, with normalized serum albumin levels and resolution of thrombosis. This case highlights the challenges of diagnosing PLE as an initial symptom of SLE in resource-limited settings. Heightened awareness of this rare presentation can facilitate early diagnosis and optimal management, improving patient outcomes.

The treatment approach to RA has changed over time, but the main goal of treatment has remained the same, that is, achieving disease remission. Given the lack of RA disease activity tools and biomarkers that can reliably predict RA drug effectiveness not just on joints but also on extra-articular manifestations. The involvement of galectins, especially Galectin-1 (Gal1) in the regulation of immune regulation makes them potential good candidate non-specific biomarkers of autoimmune diseases like RA. Examining the possibility of applying Gal1 as a potential biomarker for evaluating the effectiveness of therapy. A quasi-experimental study was conducted to assess changes in serum Gal1 concentrations in patients with RA, compared with a healthy control group. The study included a total of 88 participants, consisting of 48 patients diagnosed with RA and 40 healthy voluntary blood donors. Patients were enrolled in the study based on a selective recruitment process, provided they met the criteria outlined in the Inclusion Criteria section. The diagnosis of RA was established by physicians in accordance with the ACR/EULAR2010 classification criteria. The collected samples were subjected to concentration determination using a commercial ELISA kit for human Gal1. The serum Gal1 concentration of the examined groups differed significantly (P < 0.0001). There was a significant difference in serum concentration of Gal1 between first and second measurement (pre- and post-intervention) (P = 0.015). The obtained values of post-intervention Gal1 did not show a positive correlation with the values of DAS28-ESR, HAQ-DI, and CDAI. The conducted study showed a pronounced statistical significance in the values of Gal1 concentrations in RA patients (in both time points) compared to the group of healthy subjects, suggesting that lower levels of this marker may be associated with the degree of inflammation characteristic of RA. No significant correlation was observed between Gal1 levels and clinical disease activity indices, limiting conclusions.

Introduction: Patients with locally advanced gastric cancer often face postoperative complications and insufficient short-term outcomes. Understanding the changes in peripheral lymphocyte subsets following laparoscopic D2 gastrectomy is critical to addressing these challenges and enhancing postoperative recovery.

Objective: This study investigates the dynamics of peripheral lymphocyte subsets in gastric cancer patients post-laparoscopic D2 gastrectomy. Our goal is to identify factors contributing to postoperative reductions in these immune cells, thereby improving management strategies.

Methods: We retrospectively analyzed clinicopathological data from 169 gastric cancer patients, focusing on perioperative lymphocyte subset variations. Utilizing univariate and multivariate analyses, we identified factors significantly influencing lymphocyte reductions after surgery.

Results and conclusion: By postoperative day 7, we observed median decreases in T cells, B cells, NK cells, and memory T cells of -26.1%, -30.8%, -44.8%, and -2.3%, respectively. In contrast, naive T cells and regulatory T cells increased by 6.0% and 15.0%. Thymosin alpha 1 (Tα1) treatment proved to be a protective factor, significantly reducing the decline in T and B cell counts (p = 0.05). Multivariate analysis identified higher Interleukin-1β levels (HR = 3.66, p = 0.01), longer operation times (HR = 2.98, p = 0.02), and Tα1 therapy (HR = 0.15, p = 0.01) as independent predictors of T cell reduction. These findings highlight Tα1's potential as a therapeutic intervention to mitigate lymphocyte depletion, suggesting its incorporation into postoperative care could enhance immune recovery and patient outcomes. This study illuminates key immunological changes following gastric cancer surgery, offering pathways to improve postoperative management and patient health.

Tyrosine kinase 2 (TYK2) deficiency is a rare primary immunodeficiency disease (PID). Patients carry TYK2 gene mutations and suffer from recurrent infections by intracellular pathogens, including mycobacteria. Delayed diagnosis often hinders timely and effective treatment, resulting in poor prognosis. In this study, we report a newly discovered TYK2 deficiency patient with recurrent pulmonary infections. The patient, a 27-year-old Chinese man with a history of tuberculosis, presented with recurrent cough, phlegm, and purulent sputum. Lung CT scan showed bronchiectasis with concomitant infection. Next-generation sequencing (NGS) identified Mycobacterium gordonae and Mycobacterium chelonae in lung, along with heterozygous c.997G>A&c.10C>T (p.V333M&p.R4C) mutation in TYK2. Further pathogenicity prediction analysis via dbNSFP (v5.1a) suggested the potential pathogenicity of this genetic variant. Additionally, TYK2 mRNA expression in peripheral blood mononuclear cells (PBMCs) also decreased significantly. Following anti-infective treatment, the patient improved and was discharged with regular human immunoglobulin infusion. However, the patient unfortunately succumbed to disease exacerbation in October 2021, 15 months after diagnosis. Furthermore, a literature review was conducted on cases of TYK2 deficiency. Previous studies have identified 24 mutation sites within TYK2 gene, which impair immune function and lead to early-onset recurrent infections. These mutations contribute to clinical heterogeneity, with the most common manifestation being recurrent infections by opportunistic pathogens, particularly mycobacteria. Our discovery of a novel TYK2 mutation expands the gene's mutation spectrum. Analyzing the characteristics of reported cases enhances understanding of TYK2 deficiency's clinical manifestations and facilitates early diagnosis of this rare condition.

Introduction and objectives: Sepsis is a critical, life-threatening condition marked by organ dysfunction. Patients undergoing surgery for cancer are especially susceptible, facing a significantly increased risk compared to the general population. Prompt diagnosis is essential for optimal treatment outcomes. This study investigates the expression levels of IL-17 and CD4/CD25 in postoperative surgical oncology patients diagnosed with sepsis and examines their association with various clinicopathological parameters, including mortality.

Methods: Peripheral blood samples were collected 48 h following admission to the surgical ICU. Flow cytometry was employed to measure the expression of IL-17 and CD4/CD25 in both septic patients and non-septic controls.

Results: The study included 30 septic patients and an equal number of controls. The expression of IL-17 and CD4/CD25 was significantly higher in septic patients compared to non-septic patients, demonstrating high diagnostic performance. Additionally, elevated IL-17 expression was strongly associated with an increased risk of mortality.

Conclusion: Our study provides insight into immune dysregulation in postoperative cancer patients with sepsis, highlighting the dual arms of active inflammation and immunoparalysis. Elevated IL-17 levels, coupled with Treg activation, were linked to poorer outcomes. Therapeutic strategies that target IL-17 signaling and modulate Treg activity may help restore immune balance and improve prognosis in immunocompromised individuals. Furthermore, developing predictive models using machine learning to classify sepsis severity based on immune markers could enhance diagnosis and prognosis.

Objective: The aim of this study was to investigate the role of glutathione peroxidase 7 (GPX7) in mitigating oxidative stress-induced cellular ageing and its contribution to intervertebral disc degeneration (IVDD).

Introduction: Human nucleus pulposus (NP) cells in degenerated intervertebral discs (IVDs) show signs of ageing, such as telomere shortening, DNA damage, and mitochondrial dysfunction. GPX7, known for its ability to protect against ageing in cancer cells, may also play a role in NP cell ageing.

Methods: Two datasets (GSE34095 and GSE147383) were analysed to compare GPX7 expression in normal and degenerated IVDs and used KEGG analysis to identify related pathways. An H₂O₂-induced cell model and a natural ageing model were used to simulate ageing. GPX7 was transfected into and overexpressed in NP cells, and its protective effects were examined. Molecular docking identified GNF-5837 as a potential compound to prevent GPX7 cleavage, which was tested in an IVDD rat model.

Results: The expression of GPX7 was increased in degenerated IVDs and H₂O₂-induced models. GPX7 overexpression reduced ageing in NP cells. GNF-5837 alleviated IVDD in rats by upregulating GPX7.

Conclusion: Our study demonstrates that GNF-5837 reduced the expression of ageing markers by upregulating GPX7, suggesting it could serve as a potential treatment for IVDD.

Henoch-Schönlein purpura (HSP) is the most common systemic vasculitis in children. It often follows a viral infection. Although it is a self-limiting disease, various acute, and chronic complications can occur. We describe a case of a 6-year-old boy presenting with HSP and secondary multi-organ involvement. Because of diffuse purpura and arthralgia associated with acute abdominal pain, oral corticosteroid was administered but with no clinical improvement. Despite steroid treatment, the child developed hematemesis and massive intestinal hemorrhage, so he was treated with one dose of intravenous immunoglobulin (IVIG). This produced significant improvement in the gastrointestinal, cutaneous, and articular symptoms. Our case report demonstrates that IVIG may be useful in the treatment of complicated HSP with gastrointestinal involvement, but more structured research and guidelines are necessary for a correct therapeutic approach.

Objectives: Baicalein, a flavonoid derived from the roots of Scutellaria baicalensis Georgi, demonstrates multifarious pharmacological effects due to its high antioxidant activity. However, the latent mechanisms remain insufficiently resolved. In the present research, we evaluated the therapeutic effects of baicalein on isoprenaline (ISO)-induced heart failure and investigated the possible underlying mechanisms.

Methods: Toxicity was analyzed in zebrafish embryos and mouse atrial myocytes HL-1. The MTT assay was used to evaluate the effectiveness of baicalein. DCFH-DA was used as a fluorescence probe to detect intracellular reactive oxygen species (ROS). Superoxide dismutase (SOD), malondialdehyde (MDA), and glutathione peroxidase (GSH-Px) levels were measured using SOD, MDA and GSH-Px commercial kits. Adult BALB/c mice were randomized into six groups of ten animals each. Cardiac function was analyzed by echocardiographic images. Structural changes were analyzed by hematoxylin & eosin (HE) staining, Masson staining and TUNEL staining. The mechanism of baicalein was investigated by analyzing relative signaling pathways through western blotting.

Results: Our studies show that baicalein both significantly reduces ISO-induced oxidative stress, apoptosis and cardiac fibrosis in vitro and vivo, this phenomenon was related to mitochondrial fusion/fission balance and inhibiting GRP78/CHOP pathway.

Conclusions: Our results suggested that baicalein controls mitochondrial fusion/fission balance and inhibits GRP78/CHOP pathway, thus exerting therapeutic effects in ISO-induced heart failure in HL-1 cells and BALB/c mice. These results suggested that baicalein may be a potential therapeutic agent for heart failure.

Knowledge about total RNA molecules in Parkinson's disease is limited. This gene expression profiling study was conducted with a preclinical experimental design using a mouse model to examine the molecular-biological characteristics and the pathological implication of total RNA gene interaction in Parkinson's disease in silico. In silico analysis of total RNA molecules, the Gene Expression Omnibus database, published results, and preliminary findings of available patient samples apply. The potential signaling network and the effect of the interaction of molecules with total RNA was predicted and confirmed. The research consists of four parts. At first, we analyzed the control and MPTP groups. In the second part, we analyzed FVB-N control and MPTP. In the third part, we analyzed controls. In the fourth part, we analyzed MTPT separately. The constructed network contains total RNA, where the Kyoto Encyclopedia of Genes and Genomes database analysis showed that genes from the signaling pathway are involved in the development and complications of Parkinson's disease in male and female rats. Identified total RNA and genes are involved in altered signaling. There is direct interconnection and interdependence of interactions in the signaling network. Results identified the significant total-RNA molecules of the signaling pathway that connect other molecules. In silico analysis shows upregulated and downregulated genes in Parkinson's disease rats. Preliminary data shows that total RNA molecules interact with other genes, and they are applicable in Parkinson's disease course monitoring, shedding light on how factors impact the expression of genes and offering strategies for management.