金城学院大学

Trichloroethylene (TCE) remains a versatile organic solvent used globally. In recent years, immunological occupational diseases such as hypersensitivity syndrome (HS) and systemic sclerosis (SSc) have attracted attention in terms of the number of patients and the life-threatening consequences. This review summarizes mechanisms underlying HS pathogenesis based on the available literature. TCE-HS is a disease attributable to anti-CYP2E1 autoantibodies and HLA-B13:01 as susceptibility gene and is characterized by systemic skin lesions, severe-to-moderate liver damage, fever above 38 °C, leukocytosis, lymphadenopathy, and human herpesvirus 6 (HHV6) reactivation with elevated inflammatory cytokines, which are all similar to the characteristics of drug-induced HS. TCE-HS occurs on average 1 month after the commencement of exposure to TCE, which is shorter than the corresponding period for SSc. Recent epidemiological and animal studies have clarified the mechanism of pathogenesis: the oxidative metabolites chloral hydrate, dichloroacetyl chloride, and trichloroethanol, which are produced by CYP2E1, amplify the methylation of CD4+ T cells and activate them, resulting in the upregulation of cytokines such as TNF-α. Subsequently, some unidentified but oxidized metabolite haptens are assumed to activate CD8+ T cells with HLA-B*13:01, resulting in the production of anti-CYP2E1 autoantibodies. Subsequently, HHV6 is reactivated, leading to the development of skin and hepatic injuries. Whether skin lesions develop through a pathophysiological mechanism originating from hepatic lesions or by the same mechanism as the development of hepatic lesions remains unclear. Although disease contours have been clarified, further studies are required to elucidate its pathogenesis.

Abstract Background Plantago major subsp. intermedia has been traditionally used in Türkiye for the treatment of wounds, abscesses, constipation, pain, ulcers, hemorrhoids and gynecological diseases. In the present study, the phytochemical composition of P. major subsp. intermedia (Gilib.) Lange was investigated and its anti-inflammatory and wound healing effects were examined in light of existing experimental evidence from related Plantago species. Methods MeOH, 80% EtOH and water extracts of the plant were prepared. In vivo anti-inflammatory effects of these extracts were investigated using an acetic acid-induced capillary permeability model and their wound healing effects were studied using linear incision and circular excision wound models. Isolation studies were performed on the 80% EtOH extract. Furthermore, in vitro studies were conducted on the 80% EtOH extract, the main fractions obtained from this extract and the some of the isolated pure compounds. In these in vitro studies, anti-inflammatory effects were investigated by measuring nitric oxide (NO), interleukin-6 (IL-6) and tumor necrosis factor-alpha (TNF-α) levels and wound healing effects were investigated using the scratch test. Results A total of six compounds were isolated from P. major subsp. intermedia: Isotachioside (1), aucubin (2), 10-hydroxymajoroside (3), 10-acetoxymajoroside (4), martynoside (5) and acteoside (6). All tested compounds significantly inhibited NO production at concentrations of 25, 50 and 100 µM (12.68%-61.89%). Although in vivo results were not statistically significant, the 80% EtOH extract showed the highest efficacy in linear incision and circular excision wound models. Conclusions The results of this study indicate the in vitro anti-inflammatory and wound healing activities of P. major subsp. intermedia and are consistent with previously reported biological activities of P. major.

Patients undergoing hemodialysis are at increased risk of physical, psychological, and lifestyle-related complications that negatively impact clinical outcomes. Although comprehensive medical care support (CMCS), particularly from nurse-inclusive multidisciplinary teams, may help address these challenges, its effectiveness remains uncertain. This study evaluated the effectiveness of CMCS provided by nurse-inclusive healthcare professionals in improving outcomes among adult patients undergoing hemodialysis. We conducted a systematic review and meta-analysis of randomized controlled trials (RCTs) assessing comprehensive care interventions delivered by nurse-inclusive healthcare professionals. Eligible studies included adult patients undergoing hemodialysis and reported outcomes related to physical function, dialysis-related complications, health-related quality of life (HR-QOL), or self-management ability. Literature searches were conducted in MEDLINE (via PubMed) and Ichushi-Web (January 1970–April 2024). The risk of bias was assessed using the Cochrane Risk of Bias Tool (RoB 2) tool, and the certainty of evidence (COE) was evaluated using the Grading of Recommendations, Assessment, Development, and Evaluation (GRADE) approach. The qualitative synthesis and meta-analysis comprised 25 and 11 RCTs, respectively. A total of 2093 participants were enrolled across the 25 studies. Comprehensive care interventions significantly improved normal gait speed (mean difference [MD] = 10.51 cm/s; 95

This study aimed to evaluate the effectiveness of comprehensive medical care support (CMCS) by healthcare professionals, including nurses, for patients with chronic kidney disease (CKD) in the preservation phase. All relevant studies were identified through comprehensive literature searches conducted in PubMed (MEDLINE) and Ichushi-Web. Randomized controlled trials involving patients aged ≥ 18 years with dialysis-independent CKD were included. The trials had to include nurses in the intervention details and provide CMCS by two or more healthcare professionals. A total of 20 studies were included in the systematic review, of which 14 were eligible for meta-analysis. A significant positive effect of CMCS was observed in terms of physical function, quality of life (QOL), and self-management ability. However, in the pooled analysis, no significant differences regarding renal function and blood pressure were found between the groups. The findings suggest that multidisciplinary team-based CMCS, including nursing involvement, may be associated with improvements in physical function, quality of life, and self-management in patients with CKD; however, substantial heterogeneity across studies warrants cautious interpretation and generalization. PROSPERO registration no. CRD42024529378.

Metallo-β-lactamases (MBLs)-Zn2+-dependent β-lactamases that compromise the efficacy of most β-lactam antibiotics, including carbapenems-are difficult to monitor rapidly with broadly applicable small-molecule probes due to the structural diversity among the MBLs. Fluorescent thiol-based probes that bind to the dinuclear Zn2+ active site would offer a mechanistically different approach for the selective detection and inhibition of MBLs compared to serine β-lactamases (SBLs); however, their performance across genetically divergent MBLs remains poorly defined. To clarify the structural determinants governing probe recognition across different MBLs, we examined the structure-activity relationships using a homologous series of dansyl-based thiol probes, DansylCnSH (n = 2 and 4-6) toward BlaB, a class B MBL of Elizabethkingia meningoseptica, and compared their behavior with those of the clinically relevant MBLs imipenemase-1 (IMP-1) and Verona integron-encoded metallo-β-lactamase 2 (VIM-2). Consistent with the minimal differences in fluorescence enhancement among the series, BlaB inhibition exhibited only modest spacer-length dependence (IC50 = 29-51 μM; apparent inhibition constants (Kiapp) = 3600-5910 nM). In contrast, IMP-1 and VIM-2 showed markedly stronger fluorescence emission and inhibitory potencies (IMP-1: IC50 = 0.7-5.2 μM; Kiapp = 140-1100 nM; VIM-2: IC50 = 1.5-2.1 μM; Kiapp = 286-370 nM), reflecting their distinct active-site architectures. Docking analyses further revealed distinct binding orientations that explain their photophysical behaviors. No fluorescence enhancement or inhibition was observed with the class A SBL Guiana extended-spectrum β-lactamase-3 (GES-3), confirming the high selectivity and specificity of the DansylCnSH series. These findings allow identifying key structural determinants governing selective activation and inhibition of fluorescence from each MBL.