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Background/aim: Coexisting Sjögren's syndrome (SS) and human leukocyte antigen-B27 (HLA-B27)-negative ankylosing spondylitis (AS) is rare and therapeutically challenging. In patients with prior Stevens-Johnson syndrome (SJS), non-steroidal anti-inflammatory drugs (NSAIDs) are contraindicated and tumor necrosis factor (TNF) inhibitors may be insufficient. Interleukin-17A (IL-17A) blockade with secukinumab offers an alternative, though its long-term effects on T cell exhaustion and regulation remain unclear. This report examines immune exhaustion and regulatory dynamics during IL-17A inhibition in a complex autoimmune case.

Case report: A 52-year-old man with SJS, SS, and HLA-B27-negative AS switched to secukinumab after inadequate TNF inhibition. Flow cytometry over five years (2020, 2023, 2025) tracked early therapy, steroid tapering, and long-term stability. Initial immune profiling revealed expanded effector T cells [Fas cell surface death receptor (Fas)⁺, programmed death protein 1 (PD-1)⁺, T-cell immunoglobulin and mucin-domain containing-3 (Tim-3)⁺] and reduced regulatory subsets. Over time, as disease activity improved, exhaustion markers declined and regulatory T cell (Treg) populations partially recovered. By 2025, the patient maintained low disease activity with minimal steroid exposure. Laboratory data confirmed remission [C-reactive protein (CRP) 0.10 mg/dl, erythrocyte sedimentation rate (ESR) 2 mm/h], while patient-reported indices [Bath ankylosing spondylitis disease activity index (BASDAI) 4.1, ankylosing spondylitis disease activity score using C-reactive protein (ASDAS-CRP) 2.0] reflected stable low-to-moderate disease activity. Naïve T cells continued to show intermittent PD-1 and killer cell lectin-like receptor G1 (KLRG1) expression, suggesting persistent low-level immune adaptation.

Conclusion: This case shows phased immune rebalancing under long-term IL-17A blockade. Serial monitoring revealed dynamic exhaustion marker changes and partial regulatory recovery linked to clinical improvement, underscoring the value of longitudinal immune profiling for personalized management of complex autoimmune syndromes.

Background/aim: Mesalazine is a cornerstone therapy in the treatment of inflammatory bowel disease (IBD). Although formulated for local action, it can cause serious adverse events (AEs), such as interstitial lung disease and myocarditis, as well as mesalazine-specific drug intolerance. However, the timing of onset and associated risk factors remain insufficiently understood. This study aimed to analyze the onset timing and risk factors for mesalazine-related AEs using the Japanese Adverse Drug Event Report (JADER) database to provide pharmacists with essential information for effective monitoring of AEs.

Patients and methods: Reporting odds ratios (RORs) for mesalazine-associated AEs in the JADER database were calculated to detect safety signals. Time-to-onset analyses were performed to classify patterns of mesalazine-induced AEs. Risk factors for mesalazine-induced drug intolerance were further evaluated using multivariate logistic regression analysis.

Results: Among the 25 prespecified AEs, signals were detected for 15. Nine AEs were classified as early onset, and one as late-onset. Male sex and the concomitant use of budesonide, golimumab, vedolizumab, and upadacitinib were significantly detected signals of drug intolerance (all p-values <0.01).

Conclusion: Most mesalazine-associated AEs occurred shortly after treatment initiation, although some manifested later. Although direct risk quantification could not be performed from individual RORs, the indicated factors associated with mesalazine intolerance-including sex and specific concomitant drugs might be useful as items for monitoring AEs. These findings provide meaningful insights that may contribute to optimizing therapeutic strategies and improving the quality of life of patients with IBD.

Background/aim: Pancreatic adenocarcinoma (PAAD) is an aggressive cancer type with high mortality rates. The Argonaute (AGO) gene/protein family is an evolutionary conserved family, which is responsible for post-transcriptional regulation of gene expression. Despite the fact that this family members (AGO1-4) have been linked to prognosis in some cancers, they have not been comprehensively investigated in PAAD. Therefore, this study investigates the role of AGO family members on PAAD.

Materials and methods: In our research, bioinformatics analyses were performed to study gene, protein and methylation levels, prognostic importance, gene-gene and protein-protein interactions, enrichment analysis, and immune infiltration analysis, using online and publicly available platforms. Additionally, real-time PCR was used to check mRNA levels in the pancreatic cell line BxPC-3.

Results: mRNA (p<0.05), protein (p<0.001) and methylation (p<0.001) levels of AGO2 were statistically different between normal and tumor samples in the in silico and laboratory analyses, and high AGO2 levels were found to be linked to poor prognosis (p=0.037). Additionally, immune infiltration analysis demonstrated a close relationship between AGO2 mRNA expression and immune cells. In contrast to the consistent results of AGO2, other AGO family members (AGO1, AGO3, or AGO4) differed at the protein or methylation levels but had non-significant prognostic values.

Conclusion: The findings of this study indicate the potential importance of AGO2 in terms of biological functions and prognostication in PAAD.

Background/aim: Delayed childbearing has increased the reliance on in vitro fertilization (IVF) with donor oocytes for women of advanced maternal age often facing more obstetric complications compared to younger women using self-oocytes. This study evaluated and contrasted key obstetric and perinatal parameters between these two groups.

Patients and methods: In this retrospective multicenter study, completed IVF embryo transfer cycles were analyzed. Clinical data including clinical pregnancy, miscarriage, ectopic pregnancy rates, and major pregnancy complications were collected. Obstetric outcomes (e.g., mode of delivery, preterm birth, and neonatal parameters such as birth weight, Apgar scores, and NICU admissions) were compared between the donor-oocyte recipients (DOR-IVF) and self-oocyte (SO-IVF) groups. Statistical analysis comprised chi-square tests, t-tests, and multivariable logistic and linear regressions to adjust for potential confounders.

Results: The DOR-IVF group demonstrated a clinical pregnancy rate of 44.8% (196 cases) with an 8.8% miscarriage rate, while the SO-IVF group reported 242 clinical pregnancies with an 8.1% miscarriage rate. Overall, nine ectopic pregnancies (2%) were noted, with statistically significant differences in ectopic and miscarriage rates between the groups (p=0.008 and p=0.025, respectively). Although the mean gestational age was similar and NICU admissions did not differ significantly (p=0.125), the DOR-IVF group exhibited a higher incidence of pregnancy complications (p=0.009). Multivariable logistic regression identified DOR-IVF as an independent predictor for pregnancy complications (adjusted odds ratio 2.38; 95% confidence interval=1.53-3.70). Additionally, subgroup analyses revealed that 1-minute Apgar scores were positively associated with DOR-IVF status (p=0.048) and birth weight was inversely related to the number of babies transferred (p=0.006).

Conclusion: DOR-IVF patients experience significantly increased risk in obstetric complications compared to younger women using SO-IVF, although neonatal outcomes remain largely similar.

Background/aim: Prurigo nodularis (PN) is a chronic inflammatory skin disorder characterized by intense pruritus and nodular lesions. Emerging evidence suggests PN may be associated with systemic conditions, including liver diseases. This study aimed to investigate the relationship between PN and non-alcoholic fatty liver disease (NAFLD) and liver fibrosis/cirrhosis.

Patients and methods: This study was conducted using the TriNetX Research Network. Adults diagnosed with PN between 2005 and 2018 were compared with a propensity score-matched control group without PN. Patients with prior liver disease or neoplasms were excluded. The outcomes of interest were incident NAFLD, liver fibrosis, and cirrhosis, assessed using ICD-10-CM codes. Hazard ratios (HRs) and 95% confidence intervals (CIs) were calculated and sensitivity and stratification analyses were conducted to evaluate the robustness of the findings.

Results: Among 28,390 PN patients and matched controls, PN was associated with an elevated risk of NAFLD (HR=1.27, 95% CI=1.17-1.38) and liver fibrosis/cirrhosis (HR=2.01, 95% CI=1.65-2.45) over a 15-year follow-up. Stratified analyses revealed higher risks in males and younger patients (18-64 years). Sensitivity analyses confirmed consistent findings across various definitions, follow-up durations, and active comparators.

Conclusion: PN is associated with an increased risk of NAFLD, liver fibrosis, and cirrhosis. These findings highlight the need for monitoring and proactive management of liver health in PN patients. Further research is warranted to elucidate the mechanisms underlying this association and explore potential therapeutic strategies.

Background/aim: Ulcerative colitis (UC) is colonic inflammation associated with increased production of pro-inflammatory cytokines, oxidative stress, and disturbances of immune responses. Mitragynine is the most abundant active alkaloid in Mitragyna speciosa (kratom) and may have anti-inflammatory, antioxidant, and antispasmodic properties. In this study, we investigated the palliative effects of mitragynine in kratom leaf extract on the symptoms of UC.

Materials and methods: Mice were divided into six groups (n=9): control; colitis; colitis plus syrup with kratom extract containing 5, 10, or 20 mg/kg mitragynine; and a positive control group treated with 4 mg/kg loperamide. The treatments were orally administered for 5 days after colitis was induced by transrectal administration of 5% acetic acid.

Results: The results showed that syrup with 10 and 20 mg/kg mitragynine significantly alleviated colonic tissue damage caused by acetic acid-induced colitis. Furthermore, the disease activity index, colonic weight, colonic lesions, and levels of malondialdehyde and inflammatory cytokines (tumor necrosis factor-α and interleukin-1β) decreased in these groups in comparison with the colitis-only group. With regard to antispasmodic activity, kratom extract significantly increased colonic smooth muscle relaxation by acting on μ-opioid receptor signaling and inhibited induced muscular contraction in mice with colitis. Moreover, kratom extract attenuated nitric oxide levels and enhanced the phagocytic activity of mouse peritoneal macrophages.

Conclusion: Kratom leaf extract, which contains mitragynine, alleviated acetic acid-induced colitis in mice by modulating immune responses and by its anti-inflammatory, antioxidative, and antispasmodic effects. Therefore, kratom leaves may be an effective therapeutic candidate for subsequent development as a multitarget drug for UC.

Background/aim: Emerging evidence suggests that sodium-glucose co-transporter 2 inhibitors (SGLT2i) and glucagon-like peptide-1 receptor agonists (GLP-1RA) may offer neuroprotective effects. This study aimed to compare the risk of new-onset fibromyalgia between diabetic patients starting SGLT2i versus those using GLP-1RA.

Patients and methods: A target trial emulation was conducted using the TriNetX Global Collaborative Network. Adult patients with type 2 diabetes mellitus starting use of SGLT2i or GLP-1RA were included, excluding those with prior fibromyalgia or psychiatric disorders. Propensity score-matching (1:1) was applied to demographics, comorbidities, laboratory data, and co-medications. The primary outcome was incidence of fibromyalgia. Hazard ratios (HRs) with 95% confidence intervals (CIs) were estimated.

Results: After matching, 297,937 patients per group were analyzed. During follow-up, fibromyalgia occurred in 6,963 (2.3%) of SGLT2i users and 7,855 (2.6%) of GLP-1RA users. SGLT2i use was associated with significantly lower fibromyalgia risk (HR=0.896, 95% CI=0.867-0.925). Findings remained robust in sensitivity analyses, including in 1-year (HR=0.884, 95% CI=0.855-0.914), 3-year (HR=0.880, 95% CI=0.850-0.912), and 5-year (HR=0.889, 95% CI=0.860-0.918) follow-up.

Conclusion: In this large real-world cohort, SGLT2i use in diabetic patients was associated with a significantly reduced risk of fibromyalgia compared to GLP-1RA.

Background/aim: The procurement of right lobe grafts while preserving the middle hepatic vein (MHV) tributaries (V5 and V8) just before graft retrieval is technically challenging. Moreover, the safe isolation of the hepatic duct from the Glissonean pedicle is essential in living donor hepatectomy. To date, few studies have reported surgical techniques for preserving the MHV tributaries during right lobe graft procurement.

Patients and methods: This report presents our modified subtraction technique for managing the MHV tributaries and Glissonean pedicle during right lobe graft procurement. First, a subtraction technique for the MHV tributaries was initiated by isolating the right Glissonean pedicle. The lower tip of the tape was placed behind the caudate lobe and passed behind the right hepatic vein. Each end of the tape was then passed behind V5 and V8, followed by dissection of the remaining liver parenchyma between them. Subsequently, a subtraction technique for the Glissonean pedicle was applied to safely isolate the right hepatic duct and hilar plate.

Results: Between September 2011 and May 2025, seven donors underwent right lobe graft procurement using the subtraction technique for the middle hepatic vein tributaries. The mean operative time was 381 min with an estimated blood loss of 217 ml. Using the subtraction technique, all middle hepatic vein tributaries were preserved just before graft retrieval.

Conclusion: This study presents subtraction techniques used during living donor hepatectomy. The technique may facilitate liver parenchyma dissection while preserving MHV tributaries just before graft retrieval and isolating the Glissonean pedicle.

Background aim: N-myristoyltransferase 1 (NMT1), which myristoylates Src, is highly expressed in oral squamous cell carcinoma (OSCC). Although targeted therapies against epidermal growth factor receptor exist, their use is limited by resistance and toxicity, and NMT1-Src interactions remain unexplored. Herein, we aimed to evaluate the role of NMT1-mediated Src myristoylation in the malignant potential of OSCC.

Materials and methods: Myristoylation and the expression of NMT1 in OSCC were assessed using click chemistry and immunocytochemistry. RNA-seq and enrichment analyses were performed to compare OSCC cells with or without NMT1-siRNA treatment. Src activity was determined by measuring Src phosphorylation via western blotting. Expression and binding of NMT1 and Src were analyzed via immunoprecipitation using specific antibodies. HSC-2, HSC-3, WK2, and WK3F derived from human OSCC in vitro were also used to confirm malignancy by siRNA of siNMT1 in OSCC cell lines.

Results: NMT1 and Src expression was detected in all OSCC cell lines. RNA-seq analysis of SAS cells transfected with NMT1-siRNA revealed decreased expression of genes related to cell adhesion and angiogenesis. WK3F cells, which exhibit high malignancy, showed markedly higher NMT1 expression than other cell lines. Immunocytochemistry showed that Src membrane localization was reduced in all of the OSCC cell lines with NMT1 knockdown. Co-immunoprecipitation analysis confirmed that NMT1 was bound to Src during myristoylation.

Conclusion: NMT1 promotes OSCC malignancy by mediating Src myristoylation.