In vivo最新文献

Background/aim: Drug-induced aseptic meningitis (DIAM) is a rare but clinically important adverse event. We identified drugs potentially associated with aseptic meningitis using the Japanese Adverse Drug Event Report (JADER) database.

Patients and methods: We conducted a disproportionality analysis of aseptic meningitis adverse events using JADER data from April 2004 to October 2024. Disproportionality signals for aseptic meningitis were detected using reporting odds ratios (RORs) with 95% confidence intervals. The Weibull distribution was analyzed to evaluate the time to onset of adverse events for drugs producing symptoms of aseptic meningitis.

Results: Nineteen drugs were identified as associated with aseptic meningitis: nine vaccines, three immunoglobulin products, two nonsteroidal anti-inflammatory drugs, and two immune checkpoint inhibitors (nivolumab and ipilimumab), among others. The onset of DIAM temporally associated with the SARS-CoV-2 RNA vaccine was typically observed within a few days following vaccination, resembling the temporal pattern reported for conventional DIAM. In contrast, the DIAM onset after nivolumab and ipilimumab treatment was delayed, leading to the classification of these drugs as random failure types, which is consistent with the timing of the immune-related adverse events.

Conclusion: DIAM onset patterns differ among therapeutic classes, including immune checkpoint inhibitors and SARS-CoV-2 RNA vaccines. These differences in onset timing suggest that DIAM onset occurs through distinct pathophysiological mechanisms. This information may support differential diagnosis and guide management of aseptic meningitis in clinical settings.

Background/aim: Hypertension is a vascular disorder that affects both the vascular system and neural tissue. Insomnia may further impair health and contribute to dementia development. This study examined the association between insomnia and dementia in individuals with hypertension using a retrospective cohort design.

Patients and methods: Participants diagnosed with hypertension were classified into insomnia (n=97,751) and non-insomnia groups. Primary outcomes included Alzheimer's disease, vascular dementia, and Parkinson's disease. Cox proportional hazards models were used to estimate adjusted hazard ratios (aHRs) and 95% confidence intervals (CIs).

Results: During follow-up, the insomnia group included 759, 611, and 825 cases of Alzheimer disease, vascular dementia, and Parkinson disease, respectively, compared with 677, 499, and 546 cases in the non-insomnia group. Insomnia was significantly associated with higher risks of Alzheimer's disease (aHR=1.178, 95% confidence interval=1.062-1.307), vascular dementia (aHR=1.282, 95% confidence interval=1.139-1.443), and Parkinson's disease (aHR=1.582, 95% confidence interval=1.420-1.763). Cumulative incidences for all outcomes were also higher in the insomnia group. Sensitivity analyses showed elevated risks of Alzheimer's disease in middle-aged and older individuals with high hemoglobin A1c (HbA1c); increased vascular dementia risk in those of younger and older age, high low-density lipoprotein cholesterol, and elevated HbA1c; and higher Parkinson's disease risk among individuals with low high-density lipoprotein cholesterol, high low-density lipoprotein cholesterol, or elevated HbA1c.

Conclusion: Insomnia substantially increases dementia risk among individuals with hypertension, underscoring the clinical importance of sleep management in this population.

Background/aim: Poly-Lactic acid (PLA) fillers are widely used for facial and body volume restoration because of their collagen-stimulating properties. However, early inflammation, oxidative stress, and variable long-term remodeling remain as concerns. Vitamin C and glutathione support collagen synthesis and redox homeostasis but degrade rapidly in conventional systems. This study evaluated a PLA filler incorporating Ethyl ascorbic acid (Vitamin C) and glutathione stabilized within an InCube^® microlattice (PLA-IC) focusing on antioxidant stability, collagen induction, and tissue response.

Materials and methods: PLA-IC were prepared by combining PLA microspheres with microlattice-encapsulated vitamin C and glutathione. Scanning and transmission electron microscopy and selected-area electron diffraction were used to characterize particle morphology and structure. Antioxidant stability was examined using high-performance liquid chromatography and DPPH radical-scavenging assays during long-term storage. In vivo, SKH mice received subcutaneous injections of PBS, commercial PLA filler, or PLA-IC. Surface volume changes were measured by Primos imaging, and histology was used to assess inflammation, neovascularisation, and collagen deposition over 12 weeks.

Results: Microlattice encapsulation preserved vitamin C and glutathione for 277 days and maintained strong DPPH-scavenging activity for up to 200 days. In vivo, PLA-IC showed significantly greater volumizing effect than standard PLA filler between weeks 4 and 12. Masson's trichrome staining demonstrated higher collagen density in the PLA-IC group, reaching nearly twice that of conventional PLA at 12 weeks. H&E sections revealed reduced inflammatory infiltration and minimal neovascularisation in PLA-IC-treated tissues.

Conclusion: Microlattice-based incorporation of vitamin C and glutathione enhances the antioxidants stability and overall biostimulatory performance of PLA filler. Compared with conventional PLA, PLA-IC demonstrated improved volume retention, increased collagen formation, and a more controlled tissue response, indicating potential advantages for aesthetic applications and warranting clinical evaluation of safety and efficacy.

Background/aim: The global prevalence of type 2 diabetes (T2D) continues to rise, with non-obese phenotypes particularly common in East Asian populations. Our previous study in male mice demonstrated that the intake of excessive high-fructose corn syrup (HFCS) under energy restriction impairs glucose tolerance without inducing obesity. This study aimed to elucidate female-specific mechanisms underlying glucose regulation under similar dietary conditions.

Materials and methods: Early middle-aged female ICR mice were randomly assigned to either the HFCS group or the control group. In the HFCS group, mice were given free access to HFCS water, and the energy intake was adjusted to be the same as that in the control group using a standard rodent diet. After 16 weeks, glucose tolerance and insulin sensitivity were assessed via the oral glucose tolerance and insulin tolerance tests, respectively. Pancreatic morphology, gene expression, and serum biochemical and hormonal parameters were analyzed.

Results: Glucose tolerance and islet size distribution were comparable between the HFCS and control groups. The HFCS group, however, exhibited lower insulin secretion and reduced pancreatic weight relative to controls. mRNA levels of insulin II, pancreatic and duodenal homeobox 1, glucose transporter 2, and glucokinase were similar between groups, whereas ketohexokinase mRNA tended to be elevated in the HFCS group. In addition, the mRNA levels of glutaminase and glutamate dehydrogenase 1 were higher than those in controls. Serum leptin and insulin-like growth factor I showed upward trends in the HFCS group, and glucagon-like peptide-1 levels were significantly increased compared with controls.

Conclusion: Excessive HFCS intake under energy restriction diminished insulin secretion but preserved glucose tolerance in female mice, which might be attributable to extrapancreatic hormonal compensation and adaptive metabolic responses.

Background/aim: Allogeneic (allo-) hematopoietic cell transplantation (HCT) may confer a survival advantage in a selected population of patients with relapsed and refractory multiple myeloma (R/R MM), however, additional data are needed to identify the patients who will benefit the most.

Patients and methods: Between January 2000 and December 2024, 32 patients with R/R MM underwent allo-HCT at the Asan Medical Center, Seoul, Korea, and were included in this retrospective study.

Results: Before allo-HCT, complete remission (CR) achievement tended to be associated with better overall survival (OS) compared to partial response and refractory status (67.7% vs. 31.7% and 16.7% at 5 years, respectively, p=0.079). The OS rate was significantly higher in patients who underwent prior autologous (auto-) HCT compared to upfront allo-HCT (47.3% vs. 0% at 5 years, p=0.016). In multivariate analysis, upfront allo-HCT without previous auto-HCT was a significant adverse factor for OS [hazard ratio (HR)=6.248, 95% confidence interval (CI)=1.541-25.330, p=0.010]. In addition, the number of chemotherapy (≥3) before allo-HCT was a significantly independent adverse factor for OS (HR=2.854; 95%CI=1.071-7.602; p=0.035).

Conclusion: In R/R MM after auto-HCT, allo-HCT for patients who attained CR following less than three lines of chemotherapy can still be a promising treatment option with long-term survival.

Background/aim: This study aimed to investigate the effect of sex-related differences on surgical outcomes, postoperative complications, and prognosis in patients undergoing minimally invasive distal gastrectomy (MIDG) for gastric cancer (GC).

Patients and methods: We retrospectively analyzed 988 patients who underwent MIDG for GC at five institutions between January 2018 and December 2024. The patients were categorized according to sex (male or female). To minimize selection bias, propensity score matching (PSM) was performed using the following covariates: age, body mass index, the American Society of Anesthesiologists physical status classification, surgical approach (laparoscopic or robotic), reconstruction method, adjuvant chemotherapy, clinical stage, postoperative complications (Clavien-Dindo classification: CD), and prognoses, including overall survival (OS), relapse-free survival (RFS), and Cancer-Specific Survival (CSS).

Results: Even after the PSM, male patients demonstrated significantly worse outcomes in surgical and long-term settings. Compared with the females, males had a longer median operation time (293 min vs. 274 min, p<0.001) and greater blood loss (median 5 ml vs. 0 ml, p<0.001). Incidence of postoperative complications (CD II) was significantly higher in the male group (15.4% vs. 9.5%, p=0.037) than that in the female group. Multivariate logistic regression analysis identified male sex as an independent risk factor for postoperative complications (odds ratio: 1.727; 95% confidence interval=1.032-2.939; p=0.037). In a multivariate Cox regression analysis, male sex was as an independent risk factor for poorer RFS.

Conclusion: Male patients undergoing MIDG face significantly higher risks of postoperative complications and cancer recurrence than female patients, independent of baseline clinical and pathological factors.

Background/aim: Rheumatoid arthritis (RA) is an autoimmune disease, with synovial inflammation as an important symptom. However, the pathogenesis of RA has not been fully elucidated. Long noncoding RNAs play a role in various biological and pathological situations, and negative regulators of interferon response (NRIR) are long noncoding RNAs that regulate immune reactions. However, the role of NRIR in rheumatoid synovial inflammation remains unclear.

Materials and methods: Cultured human rheumatoid fibroblast-like synoviocytes (RFLS) were treated with a synthetic Toll-like receptor 3 (TLR3) ligand, polyinosinic:polycytidylic acid (poly I:C). Expression of NRIR was examined using reverse transcription-quantitative polymerase chain reaction. RNA interference against interferon-b (IFNB), nuclear factor-kappa B (NFKB) p65, and NRIR was performed by transfecting the cells with specific small interfering RNAs. Interleukin-6 (IL-6) protein levels in the culture medium were measured using an enzyme-linked immunosorbent assay kit. Phosphorylation of NF-kB p65 protein was determined using western blotting.

Results: Treatment of cultured RFLS with poly I:C induced the expression of NRIR. Poly I:C-induced expression of NRIR was decreased by the knockdown of IFNB or NFKB p65. IL-6 induction by poly I:C was reduced by knockdown of NFKB p65 or NRIR, but not of IFNB. Knockdown of NRIR did not affect NF-kB p65 phosphorylation.

Conclusion: NRIR is induced by TLR3 signaling in RFLS. IFN-b and NF-kB are involved in NRIR induction via TLR3 signaling. NRIR is at least partially implicated in TLR3-mediated IL-6 expression in RFLS. NRIR may play a role in TLR3/IL-6-mediated inflammatory reactions in RFLS and may be a potential target for new therapeutic strategies against RA.

Background/aim: Healthcare-associated infections (HAIs) remain a major cause of morbidity in hospitalized patients and residents of long-term care facilities. Conventional chemical disinfectants have limitations such as corrosion, toxicity, and economic burden. This study investigated the antibacterial properties of nanobubble water (NBW) as a novel physicochemical disinfection method that does not require chemical additives.

Materials and methods: NBW was generated using four gases-air, nitrogen (N₂), oxygen (O₂), and carbon dioxide (CO₂)- and tested against Escherichia coli (E. coli), Extended-spectrum beta-lactamase (ESBL)-producing E. coli, Staphylococcus aureus, and Methicillin-resistant S. aureus (MRSA). Nanobubble size and stability were analyzed, and time-dependent antibacterial activity was evaluated by colony-forming unit (CFU) assays. Transmission electron microscopy (TEM) was used to assess bacterial ultrastructural changes following NBW exposure.

Results: Generated nanobubbles measured 50-100 nm in diameter and were stable over time. NBW exhibited intrinsic, time-dependent antibacterial effects that were independent of the solvent or dissolved gas itself. Antibacterial activity was more pronounced at lower bacterial loads and differed by gas type and bacterial species: N₂-NBW was particularly effective against MRSA, whereas CO₂-NBW and Air-NBW showed activity against ESBL-producing E. coli. Several NBW types demonstrated antibacterial effects against drug-resistant strains, although the magnitude and duration varied. Importantly, short-term exposure (≤60 min) did not reduce bacterial counts, indicating that measurable effects require prolonged immersion.

Conclusion: NBW generated using relatively safe and inexpensive gases (excluding ozone, which is known to be cytotoxic) exerts reproducible antibacterial activity against diverse bacterial species, including resistant strains. However, its lack of rapid disinfectant action suggests that NBW is better suited for long-term immersion rather than short-contact disinfection. These findings support NBW as a potential safer and cost-effective strategy for immersion-based infection control and mitigation of antimicrobial resistance.

Background/aim: Lower urinary tract symptoms (LUTS) are common symptoms after kidney transplantation (KT). This study investigated the factors affecting the quality of life (QOL) of patients with LUTS after KT.

Patients and methods: We enrolled 46 patients with LUTS who visited our institution after KT between 2020 and 2021. In addition to clinical information obtained from medical charts [patient age, sex, body mass index, duration of dialysis, and Charlson Comorbidity Index (CCI) before KT, information related to LUTS was collected, including International Prostate Symptom Score (IPSS), IPSS-QOL score, nocturia-QOL (N-QOL) score, uroflowmetry, and bladder diary. The patients were divided into groups according to IPSS score (≥8 and <8, respectively).

Results: The median age in both groups was 55 years. Charlson comorbidity index (CCI) ≥2 or duration of dialysis did not differ significantly between groups (p=0.27 and 0.91, respectively). The total N-QOL score and daytime and nighttime urinary frequency were significantly higher in the IPSS ≥8 group compared with the IPSS <8 group (p=0.034, 0.048, and 0.021, respectively). In multivariate analysis, CCI ³2 was an independent prognostic factor for severe IPSS-QOL score and total IPSS (p=0.040 and p=0.030, respectively), N-QOL score <80 was an independent prognostic factor for severe IPSS-QOL score (p=0.039), while nocturia was an independent prognostic factor for moderate or severe total IPSS (p=0.046).

Conclusion: Preoperative interventions for complications may lead to improved QOL in patients undergoing KT. The risk factors for LUTS after KT are nocturia and low N-QOL scores. Finally, treatment of nocturia can improve LUTS.

Background/aim: In this study, we aimed to evaluate the cardiovascular adverse event (CVAE) signals associated with three proteasome inhibitors (PIs), carfilzomib, bortezomib, and ixazomib, using the Japanese Adverse Drug Event Report (JADER) database, with anticancer agents as a reference.

Patients and methods: Spontaneous adverse event reports restricted to anticancer agents were extracted from the JADER database between April 2004 and March 2025. A disproportionality analysis was conducted for six predefined CVAE categories based on narrow Standardized MedDRA Queries. Additional analyses were stratified by age (≥70 vs. <70 years) and sex.

Results: In total, 12,181 CVAE reports were identified: 2,303 for carfilzomib, 6,851 for bortezomib, and 3,027 for ixazomib. The overall analysis detected multiple CVAE signals for carfilzomib and bortezomib, including cardiac failure and arrhythmia, whereas no signals were detected for ixazomib. The age-stratified analysis performed revealed new signals that were not observed overall, including venous thromboembolism in older adult patients receiving carfilzomib, cardiomyopathy in those receiving bortezomib, and cardiac failure in those receiving ixazomib. Sex-stratified analysis identified male-specific signals, including thromboembolic and arrhythmic events for carfilzomib, cardiomyopathy for bortezomib, and both cardiac failure and cardiomyopathy for ixazomib. The JADER database analysis identified multiple CVAE signals for carfilzomib and bortezomib, along with new age- and sex-specific signals not observed in the overall population.

Conclusion: These findings highlight the potential influence of patient demographics on CVAE risk and support tailored monitoring strategies for patients receiving PIs, particularly older adult and male patients.