Explore the vast range of titles available.

To prevent confusing Dioscorea nipponica (DN), an Oriental medicine, with Dioscorea quinquelobata (DQ) and Dioscorea septemloba (DS), a simple and accurate quantitative analysis method using HPLC combined with ultraviolet (UV) detection was developed and verified with UPLC-QTOF/MS through identification of five saponin glycosides: protodioscin (1), protogracillin (2), pseudoprotodioscin (3), dioscin (4), and gracillin (5). The newly developed analysis method showed sufficient reproducibility (<1.91%) and accuracy (92.1%–102.6%) and was able to identify DN based on the presence of compound 3 (13.821 ± 0.037 mg/mL) and the absence of 5. Compound 1, which is present in DN at a relatively high level (159.983 ± 0.064 mg/mL), was also an important marker for identification. Among the three species, DN showed the strongest activation of apoptotic signaling in osteosarcoma cells, while the four compounds detected in DN showed IC50 values of 6.43 (1), 10.61 (2), 10.48 (3), and 6.90 (4). In conclusion, the strong inhibitory effect of DN against osteosarcoma was confirmed to be associated with 1 and 4, which is also related to the quantitative results. Therefore, the results of this study might provide important information for quality control related to Oriental medicine.

Primary dysmenorrhea (PD) is characterized by excessive uterine contraction and ischemic vasoconstriction, primarily driven by elevated levels of prostaglandins (PGs; PGF2α) and inflammatory mediators. Nonsteroidal antiinflammatory drugs (NSAIDs) remain the standard treatment for PD; however, their associated adverse effects necessitate the use of alternative therapeutic strategies. Aster spathulifolius Maxim. is a perennial herb native to the coastal regions of Korea, that exhibits antiviral, anticancer, and antidiabetic effects. In this study, we investigated the potential of Aster spathulifolius Maxim. extract (PDR97) to alleviate PD in both animal models and human uterine smooth muscle cells (HUtSMCs). Our findings demonstrated that PDR97 significantly reduced pain‐related responses and restored uterine morphology in PD‐induced mice. Mechanistically, PDR97 suppressed the expression of uterine contraction‐related proteins, decreased NF‐κB phosphorylation, and downregulated the expression of proinflammatory cytokines. Furthermore, PDR97 effectively inhibited PGF2α‐ and interleukin‐1β (IL‐1β)‐induced reactive oxygen species (ROS) production in both the PD mouse model and HUtSMCs, exhibiting potent antioxidant properties. Notably, PDR97 modulated NF‐κB signaling—a key regulatory pathway associated with uterine contraction and pain relief—and its antioxidant effects contributed to the suppression of inflammatory and oxidative stress‐mediated signaling. Collectively, these findings highlight the potential of PDR97 as a promising natural therapeutic agent for PD, with potential applications in other gynecological disorders associated with inflammation and oxidative stress.

Muscle atrophy in postmenopausal women is caused by estrogen deficiency and a variety of inflammatory factors, including tumor necrosis factor alpha (TNFα). Paeoniflorin (PNF), a natural compound with anti-inflammatory properties, improves estradiol synthesis. Here, we demonstrate that PNF inhibits the progression of TNFα-induced skeletal muscle atrophy after menopause by restoring mitochondrial biosynthesis. Differentiated myoblasts damaged by TNFα were restored by PNF, as evident by the increase in the expression of myogenin (MyoG) and myosin heavy chain 3 (Myh3)—the markers of muscle differentiation. Moreover, diameter of atrophied myotubes was restored by PNF treatment. TNFα-repressed nuclear respiratory factor 1 (NRF1) and mitochondrial transcription factor A (TFAM) (a major regulator of mitochondrial biosynthesis) were restored by PNF, via regulation by estrogen receptor alpha (ERα), an upregulator of NRF1. This mechanism was confirmed in ovariectomized (OVX) mice with a ~40% reduction in the cross-sectional area of the anterior tibialis muscle. OVX mice administered PNF (100, 300 mg/kg/day) for 12 weeks recovered more than ~20%. Behavioral, rotarod, and inverted screen tests showed that PNF enhances reduced muscle function in OVX mice. ERα restored expression of mitofusin 1 (MFN1) and mitofusin 2 (MFN2) (mitochondrial fusion markers) and dynamin-related protein (DRP1) and fission 1 (FIS1) (mitochondrial fission markers). Therefore, PNF can prevent muscle atrophy in postmenopausal women by inhibiting dysfunctional mitochondrial biogenesis.

Exposure to diesel exhaust particles (DEPs), which are major constituents of urban air pollution, is associated with adverse health outcomes. Previous studies have shown that DEPs enhance the expression of pro-inflammatory cytokines and immune responses. However, few studies have focused on genomic variants that regulate DEP-induced signaling. Here, we identify a frequently found genomic variant, ACP5 , in allergic diseases, and establish an ACP5 knock-out (KO) human bronchial epithelial cell line (BEAS-2B) using CRISPR/Cas9 editing to mimic the ACP5 mutation. DEP-induced apoptosis and intracellular reactive oxygen species (ROS) were significantly increased in the ACP5 KO cells compared with controls, suggesting that ACP5 KO cells were at increased risk from DEP exposure. A gene expression profile revealed an activated aryl hydrocarbon receptor (AHR)-CYP1A1 axis followed by upregulated pro-inflammatory signaling. Treatment of a DEP-exposed ACP5 KO BEAS-2B conditioned medium (CM) supernatant induced an inflammatory response and tissue damage in mice, and AHR inhibition effectively prevented inflammation-induced damage, suggesting that AHR-CYP1A1-inflammatory signaling is a prominent mechanism responsible for detrimental effects. Collectively, our findings reveal a novel link between ACP5 KO and the AHR-CYP1A1 inflammatory signaling pathway in DEP-exposed cells, and identify the AHR-CYP1A1 axis as a potential therapeutic target in individuals suffering from DEP-induced toxicity, particularly those with ACP5 mutations.

This study aimed to assess the prognostic value of MRI-measured tumor thickness (MRI-TT) in patients with tongue squamous cell carcinoma (SCC). This single-center retrospective cohort study included 133 pathologically confirmed tongue SCC patients between January 2009 and October 2019. MRI measurements of tongue SCC were based on axial and coronal T2-weighted (T2WI) and contrast-enhanced T1-weighted (CE-T1WI) images. Two radiologists independently measured MRI-TT. Intraclass correlation coefficients (ICC) were calculated for inter-rater agreements. Spearman’s rank correlation between MRI-TT and pathologic depth of invasion (pDOI) was assessed. Cox proportional hazards analyses on recurrence-free (RFS) and overall survival (OS) were performed for MRI-TT and pDOI. Kaplan–Meier survival curves were plotted with log-rank tests. The intra- and inter-rater agreements of MRI-TT were excellent (ICC: 0.829–0.897, all P  < 0.001). The correlation between MRI-TT and pDOI was good (Spearman’s correlation coefficients: 0.72–0.76, P  < 0.001). MRI-TT were significantly greater than pDOI in all axial and coronal T2WI and CE-T1WI ( P  < 0.001). In multivariate Cox proportional hazards analysis, MRI-TT measured on axial CE-T1WI yielded a significant prognostic value for OS (hazards ratio 2.77; P  = 0.034). MRI-TT demonstrated excellent intra- and inter-rater agreements as well as high correlation with pDOI. MRI-TT may serve as a prognostic predictor in patients with tongue SCC.

Although nearly a fifth of symptomatic COVID-19 patients suffers from severe pulmonary inflammation, the mechanism of developing severe illness is not yet fully understood. To identify significantly altered genes in severe COVID-19, we generated messenger RNA and micro-RNA profiling data of peripheral blood mononuclear cells (PBMCs) from five COVID-19 patients (2 severe and 3 mild patients) and three healthy controls (HC). For further evaluation, two publicly available RNA-Seq datasets (GSE157103 and GSE152418) and one single-cell RNA-Seq dataset (GSE174072) were employed. Based on RNA-Seq datasets, thrombospondin 1 (THBS1) and interleukin-17 receptor A (IL17RA) were significantly upregulated in severe COVID-19 patients’ blood. From single-cell RNA-sequencing data, IL17RA level is increased in monocytes and neutrophils, whereas THBS1 level is mainly increased in the platelets. Moreover, we identified three differentially expressed microRNAs in severe COVID-19 using micro-RNA sequencings. Intriguingly, hsa-miR-29a-3p significantly downregulated in severe COVID-19 was predicted to bind the 3′-untranslated regions of both IL17RA and THBS1 mRNAs. Further validation analysis of our cohort (8 HC, 7 severe and 8 mild patients) showed that THBS1 , but not IL17RA , was significantly upregulated, whereas hsa-miR-29a-3p was downregulated, in PBMCs from severe patients. These findings strongly suggest that dysregulated expression of THBS1 , IL17RA , and hsa-miR-29a-3p involves severe COVID-19.

The effect of corrugated wings on the aerodynamic characteristics of a dragonfly-like hovering flapping wing is investigated using two-dimensional numerical simulations. Two types of pitch motion profiles, namely ‘sinusoidal’ and ‘trapezoidal’, are employed. The results obtained from the corrugated wings at Reynolds number Re = 2150 are then compared with the flat plate geometries to analyze the aerodynamic benefits of wing corrugation. The aerodynamic characteristics of corrugated wings are investigated quantitatively using cycle-averaged vertical force coefficient. For the qualitative investigation, time histories of vertical force coefficient, vorticity, and surface pressure distribution are used. The results reveal that the corrugated wings perform better than the flat plates in all three flapping configurations for both sinusoidal and trapezoidal pitch profiles. For a tandem wing with a sinusoidal pitch profile, the corrugated wings yield a vertical force generation nearly 14%, 22%, and 12%, higher than the flat plate geometries for ψ = 0°, 90°, and 180°, respectively. The corrugated wing sheds a relatively stronger detached counter clockwise vortex (CCWV) on the lower surface as compared to the flat plate, and hence, the vertical force is much higher for the corrugated wing. For a tandem wing with a trapezoidal pitch profile, the corrugated wings yield a vertical force generation nearly 27%, 22%, and 57%, higher than the flat plate geometries for ψ = 0°, 90°, and 180°, respectively. In corrugated wing geometry, the delayed stall mechanism is slightly postponed due to the corrugation shape’s ability to trap the vortex structures, leading to a positive effect on vertical force production.

Necroptosis is a form of programmed cell death with features of necrosis and apoptosis that occurs in the intestinal epithelium of patients with inflammatory bowel disease (IBD), including ulcerative colitis and Crohn’s disease. In addition, necroptosis has also been observed in enterocytes in animal models of dextran sulfate sodium (DSS)-induced colitis. Thus, the discovery of natural products for regulating necroptosis may represent an important therapeutic strategy for improving IBD. We found that Magnolia officinalis bark extract (MBE) prevented weight loss and suppressed the activation of the proinflammatory cytokine IL6 in DSS-induced colitis. Furthermore, MBE restored the length of the damaged colon and decreased the expression of necroptosis markers in mice with DSS-induced colitis. In vitro, necroptosis-induced reactive oxygen species (ROS) production was reduced by MBE, and the expression of COX2, a target protein of ROS, was simultaneously suppressed. Both magnolol and honokiol, the two major bioactive compounds in MBE, inhibited necroptosis in human primary intestinal epithelial cells and colorectal adenocarcinoma cells. Our findings highlight the effectiveness of MBE in modulating enterocyte necroptosis and suggest that MBE may be developed as a natural, disease-targeting drug for the treatment of colitis.

Allergic rhinitis (AR) is a chronic inflammatory condition affecting the nasal mucosa of the upper airways. Herein, we investigated the effects of extracts from Gardenia jasminoides (GJ), a traditional herbal medicine with anti-inflammatory properties, on AR-associated inflammatory responses that cause epithelial damage. We investigated the inhibitory effects of water- and ethanol-extracted GJ (GJW and GJE, respectively) in an ovalbumin-induced AR mouse model and in splenocytes, differentiated Th2 cells, and primary human nasal epithelial cells (HNEpCs). Administering GJW and GJE to ovalbumin-induced AR mice improved clinical symptoms including behavior (sneezing and rubbing), serum cytokine levels, immune cell counts, and histopathological marker levels. Treatment with GJW and GJE reduced the secretion of Th2 cytokines in Th2 cells isolated and differentiated from the splenocytes of these mice. To investigate the underlying molecular mechanisms of AR, we treated IL-4/IL-13-stimulated HNEpCs with GJW and GJE; we found that these extracts significantly reduced the production of mitochondrial reactive oxygen species via the uncoupling protein-2 and periostin, a biomarker of the Th2 inflammatory response. Our results suggest that GJ extracts may potentially serve as therapeutic agents to improve the symptoms of AR by regulating the Th2 inflammatory response of the nasal epithelium.

Maternal loss of imprinting (LOI) at the H19/IGF2 locus results in biallelic IGF2 and reduced H19 expression and is associated with Beckwith–-Wiedemann syndrome (BWS). We use mouse models for LOI to understand the relative importance of Igf2 and H19 mis-expression in BWS phenotypes. Here we focus on cardiovascular phenotypes and show that neonatal cardiomegaly is exclusively dependent on increased Igf2 . Circulating IGF2 binds cardiomyocyte receptors to hyperactivate mTOR signaling, resulting in cellular hyperplasia and hypertrophy. These Igf2 -dependent phenotypes are transient: cardiac size returns to normal once Igf2 expression is suppressed postnatally. However, reduced H19 expression is sufficient to cause progressive heart pathologies including fibrosis and reduced ventricular function. In the heart, H19 expression is primarily in endothelial cells (ECs) and regulates EC differentiation both in vivo and in vitro. Finally, we establish novel mouse models to show that cardiac phenotypes depend on H19 lncRNA interactions with Mirlet7 microRNAs.