Search Results (87)

Donepezil (DPZ) is an Alzheimer’s disease (AD) drug that promotes cholinergic neurotransmission and exhibits excellent acetylcholinesterase (AChE) selectivity. The current oral formulations of DPZ demonstrate decreased bioavailability, attributed to limited drug permeability across the blood–brain barrier (BBB). In order to overcome these limitations, various dosage forms aimed at delivering DPZ have been explored. This discussion will focus on the nose-to-brain (N2B) delivery system, which represents the most promising approach for brain drug delivery. Intranasal (IN) drug delivery is a suitable system for directly delivering drugs to the brain, as it bypasses the BBB and avoids the first-pass effect, thereby targeting the central nervous system (CNS). Currently developed formulations include lipid-based, solid particle-based, solution-based, gel-based, and film-based types, and a systematic review of the N2B research related to these formulations has been conducted. According to the in vivo results, the brain drug concentration 15 min after IN administration was more than twice as high those from other routes of administration, and the direct delivery ratio of the N2B system improved to 80.32%. The research findings collectively suggest low toxicity and high therapeutic efficacy for AD. This review examines drug formulations and delivery methods optimized for the N2B delivery of DPZ, focusing on technologies that enhance mucosal residence time and bioavailability while discussing recent advancements in the field. Full article

Sarcoptic mange is a highly contagious and often lethal parasitic skin disease caused by the mite Sarcoptes scabiei, which is frequently reported in red foxes (Vulpes vulpes). However, there is a lack of documented cases and treatment strategies for sarcoptic mange in reintroduced red fox populations, particularly in South Korea. This study describes 27 cases of sarcoptic mange outbreaks in 26 red foxes reintroduced into South Korea between 2019 and 2024. Of these, 15 foxes were rescued alive, while 12 were found dead. Blood tests of the surviving animals (n = 15) showed significant leukocytosis, anemia, decreased albumin levels, increased globulin levels, elevated blood urea nitrogen levels, and decreased creatinine levels, indicative of a chronic wasting infection. Treatment with ivermectin or fluralaner resulted in complete recovery in 12 of 15 animals, while three animals died during treatment. Necropsy of the deceased animals (n = 12) revealed characteristic skin lesions, such as alopecia, hyperkeratosis, epidermal hyperplasia, and dermatitis. The study findings highlight the importance of long-term monitoring and active, continuous treatment of sarcoptic mange, a major threat, for the stable re-establishment of reintroduced foxes in South Korea. Full article

Extensive antibiotic use in swine production contaminates manure and wastewater with antibiotics. Discharging this waste into the environment, even after treatment, potentially fuels the spread of antibiotic resistance. This study investigated a full-scale swine wastewater treatment plant that combines coagulation–sedimentation, sand filtration, ozonation, activated carbon filtration, and a deaeration process. At each stage of this process, samples were collected and analyzed to determine their water quality parameters, antibiotic concentrations, and antibiotic resistance genes (ARGs). The experimental results showed coagulation–sedimentation effectively removed suspended solids (92.2%) and total phosphorus (96.9%). Ozonation significantly reduced antibiotic levels, including sulfamethazine by over 99.9%, although ARGs such as tetM, sul1, and sul2 were only removed at levels up to 95.9%. Interestingly, partial rebounds of sulfamethazine (438.9 μg/L) and marbofloxacin (0.40 μg/L) appeared in the final effluent, suggesting that desorption or operational factors (e.g., hydraulic fluctuation, filter media saturation, and pH) may affect the treatment process. In addition, strong correlations emerged between the levels of suspended solids and those of certain antibiotics (lincomycin, tiamulin), indicating particle-mediated sorption as a key mechanism. Even though ozonation and coagulation–sedimentation were found to contribute to the substantial removal of pollutants, the observed rebounds and residual ARGs highlight the need for optimized operational strategies and multi-barrier approaches to fully mitigate antibiotic contamination and inhibit the proliferation of resistant bacteria in swine wastewater. Full article

The purpose of this study was to evaluate the gene expression pattern of the caries-inhibiting effect of Cudrania tricuspidata (C. tricuspidata) extract on cariogenic bacteria Streptococcus mutans (S. mutans). We examined bacterial growth, tooth surface attachment, biofilm formation, acid production, free calcium release, and toxicity gene expression. The major components of the extract were investigated by UPLC-Q-TOF-MS analysis. Exposure to C. tricuspidata inhibited bacterial growth and attachment at concentrations of ≥15 μg/mL. Inhibition effects on biofilm formation, acid production, and free calcium release due to acid production were observed at concentrations ≥ 30 μg/mL. S. mutans virulence gene expression analysis showed that it inhibited the expression of gbpB and spaP, which mediate bacterial attachment to the tooth surface, and that of genes contributing to biofilm formation (gtfB, gtfC, and gtfD) and acid resistance (brpA and relA), and regulation (vicR). Analysis using UPLC–Q–TOF–MS/MS showed that the main component was phenylpropanoids. These results suggest that C. tricuspidata may inhibit the cariogenic properties associated with the expression of caries-related genes in S. mutans. Full article

Severe fever with thrombocytopenia syndrome (SFTS) is an acute febrile illness caused by the SFTS virus (SFTSV). We conducted this study to propose a scientific evidence-based treatment that can improve prognosis through changes in viral load and inflammatory cytokines according to the specific treatment of SFTS patients. This prospective and observational study was conducted at 14 tertiary referral hospitals, which are located in SFTS endemic areas in Korea, from 1 May 2018 to 31 October 2020. Patients of any age were eligible for inclusion if they were polymerase chain reaction positive against SFTSV, or showed a four-fold or higher increase in IgG antibody titers between two serum samples collected during the acute and convalescent phases. On the other hand, patients with other tick-borne infections were excluded. In total, 79 patients were included in the study. The viral load of the group treated with steroids was 3.39, 3.21, and 1.36 log₁₀ RNA copies/reaction at each week since the onset of symptoms, and the viral load in patients treated with plasma exchange was 4.47, 2.60, and 2.00 log₁₀ RNA copies/reaction at each week after symptom onset. The inflammatory cytokines were not reduced effectively by any specific treatment except IVIG for the entire treatment period. Secondary infections according to pathogens revealed four bacterial (26.7%) and one fungal (6.7%) infection in the steroid group. The viral load of SFTSV and inflammatory cytokines cannot be decreased by steroid and plasma exchange treatments. Secondary bacterial infections can occur when steroids are administered for the treatment of SFTS. Therefore, caution should be exercised when choosing treatment strategies for SFTS. Full article

The risk factors and outcomes associated with persistent Stenotrophomonas maltophilia bacteremia are not well-defined. This retrospective cohort study analyzed 214 cases of S. maltophilia bacteremia diagnosed between 2005 and 2022 at two university hospitals, focusing on the clinical and microbiologic characteristics and outcomes of persistent bacteremia. Persistent S. maltophilia bacteremia, defined as the detection of S. maltophilia for ≥5 days after the initial blood culture, occurred in 25.7% of cases and was significantly associated with mechanical ventilation, polymicrobial infections, and increased 30-day mortality. The early administration of appropriate antibiotics reduced the likelihood of persistence. Isolates from persistent cases demonstrated increased biofilm formation. Molecular typing revealed no specific genotype linked to bacteremia persistence. Resistance to trimethoprim-sulfamethoxazole significantly increased over the study period. Our study offers new insights into the under-explored issue of persistent S. maltophilia bacteremia, a condition that constitutes a notable proportion of bloodstream infections and carries high mortality. Full article

Objectives: We investigated potential antihyperglycemic effects of HM-chromanone (HMC), a homoisoflavonoid isolated from Portulaca oleracea, in mice fed a high-fat diet (HFD). Methods: Five-week-old male C57BL/6J mice (n = 24) were divided into three groups: controls, mice fed an HFD (11 weeks), and HFD-fed mice receiving HMC supplementation (8 weeks). Various analyses assessed liver and skeletal muscle proteins, pancreatic β-cell histology, blood glucose and HbA1c levels, and homeostatic index of insulin resistance (HOMA-IR). Results: HMC supplementation significantly reduced fasting blood glucose and postprandial blood glucose levels in HFD-fed mice. HbA1c and serum insulin levels reduced significantly, and HOMA-IR improved. Compensatory β-cell hyperplasia was reduced, and pancreatic β-cell function improved. AMP-activated protein kinase (AMPK) was significantly activated in skeletal muscle and liver tissues. IRS-1tyr612 expression increased significantly. PI3K activation and Akt phosphorylation in skeletal muscles improved insulin signaling. Forkhead box protein O1 phosphorylation increased through hepatic AMPK activation. Phosphoenolpyruvate carboxykinase and glucose-6-phosphatase expression was inhibited. Glycogen synthase kinase 3β phosphorylation increased. Conclusions: HMC supplementation alleviated hyperglycemia by activating the AMPK and PI3K/Akt pathways in skeletal muscles and the AMPK pathway in the liver of HFD-fed mice. Full article

This study explored the anti-pruritic and immunomodulatory effects of Coix sprouts extract, focusing on histamine release and IL-31 cytokine production in HMC-1 cells. The extract significantly inhibited both factors, indicating its potential for pruritus relief. In a pruritus induction mouse model, Coix sprouts extract outperformed prednisolone in anti-pruritus effectiveness, also improving skin lesions and inhibiting mast cell infiltration. The extract suppressed tryptase expression, reduced release, inhibited mast cell proliferation, and lowered nitric oxide production, suggesting anti-inflammatory properties. Coix sprouts extract shows promise in suppressing inflammation and pruritus, making it a valuable candidate for clinical use. Additionally, the analysis of coixol content in Coix sprouts revealed variations in growth time, indicating their potential as functional materials with anti-pruritus and immune-enhancing applications. Full article

Background: Rheumatoid arthritis (RA) is a chronic inflammatory disorder primarily targeting joints, significantly impacting patients’ quality of life. The introduction of tumor necrosis factor-alpha (TNF-α) inhibitors has markedly improved RA management by reducing inflammation. However, these medications are associated with adverse skin reactions, which can vary greatly among patients due to genetic differences. Objectives: This study aimed to identify risk factors associated with skin adverse events by TNF-α in RA patients. Methods: A cohort study was conducted, encompassing patients with RA who were prescribed TNF-α inhibitors. This study utilized machine learning algorithms to analyze genetic data and identify markers associated with skin-related adverse events. Various machine learning algorithms were employed to predict skin and subcutaneous tissue-related outcomes, leading to the development of a risk-scoring system. Multivariable logistic regression analysis identified independent risk factors for skin and subcutaneous tissue-related complications. Results: After adjusting for covariates, individuals with the TT genotype of rs12551103, A allele carriers of rs13265933, and C allele carriers of rs73210737 exhibited approximately 20-, 14-, and 10-fold higher incidences of skin adverse events, respectively, compared to those with the C allele, GG genotype, and TT genotype. The machine learning algorithms used for risk prediction showed excellent performance. The risk of skin adverse events among patients receiving TNF-α inhibitors varied based on the risk score: 0 points, 0.6%; 2 points, 3.6%; 3 points, 8.5%; 4 points, 18.9%; 5 points, 36.7%; 6 points, 59.2%; 8 points, 90.0%; 9 points, 95.7%; and 10 points, 98.2%. Conclusions: These findings, emerging from this preliminary study, lay the groundwork for personalized intervention strategies to prevent TNF-α inhibitor-associated skin adverse events. This approach has the potential to improve patient outcomes by minimizing the risk of adverse effects while optimizing therapeutic efficacy. Full article

Astaxanthin (AST)-encapsulated nanoparticles were fabricated using glycol chitosan (Chito) through electrostatic interaction (abbreviated as ChitoAST) to solve the aqueous solubility of astaxanthin and improve its biological activity. AST was dissolved in organic solvents and then mixed with chitosan solution, followed by a dialysis procedure. All formulations of ChitoAST nanoparticles showed small diameters (less than 400 nm) with monomodal distributions. Analysis with Fourier transform infrared (FT-IR) spectroscopy confirmed the specific peaks of AST and Chito. Furthermore, ChitoAST nanoparticles were formed through electrostatic interactions between Chito and AST. In addition, ChitoAST nanoparticles showed superior antioxidant activity, as good as AST itself; the half maximal radical scavenging concentrations (RC₅₀) of AST and ChitoAST nanoparticles were 11.8 and 29.3 µg/mL, respectively. In vitro, AST and ChitoAST nanoparticles at 10 and 20 µg/mL properly inhibited the production of intracellular reactive oxygen species (ROSs), nitric oxide (NO), and inducible nitric oxide synthase (iNOS). ChitoAST nanoparticles had no significant cytotoxicity against RAW264.7 cells or B16F10 melanoma cells, whereas AST and ChitoAST nanoparticles inhibited the growth of cancer cells. Furthermore, AST itself and ChitoAST nanoparticles (20 µg/mL) efficiently inhibited the migration of cancer cells in a wound healing assay. An in vivo study using mice and a pulmonary metastasis model showed that ChitoAST nanoparticles were efficiently delivered to a lung with B16F10 cell metastasis; i.e., fluorescence intensity in the lung was significantly higher than in other organs. We suggest that ChitoAST nanoparticles are promising candidates for antioxidative and anticancer therapies of B16F10 cells. Full article

There is a debate regarding the prediction of lymph node metastasis (LNM) in pedunculated T1 colorectal cancer (CRC). In this study with four cases of pedunculated T1 CRCs, we aimed to investigate gene expression variations based on the distance from the Haggitt line (HL) and identify potential molecular risk factors for LNM. By leveraging the Cancer Transcriptome Atlas and digital spatial profiling technology, we meticulously analyzed discrete regions, including the head, HL, proximal stalk region (300–1000 μm from HL), and distal stalk region (1500–2000 μm from HL) to identify spatially sequential molecular changes. Our findings showed significant overall gene expression variations among the head, proximal stalk, and distal stalk regions of pedunculated T1 CRCs compared to the control adenoma. Compared to LNM-negative T1 CRCs, LNM-positive T1 CRC showed that the expression of genes involved in immune-related pathways such as B2M, HLA-B, and HLA-E were significantly downregulated in the distal stalk region compared to the proximal stalk region. In summary, our results may tentatively suggest considering endoscopic resection of the stalk with a minimum 2000 μm margin from the HL, taking into account the gene expression alterations related to immune-related pathways. However, we acknowledge the limitations of this pilot study, notably the small case series, which may restrict the depth of interpretation. Further validation is imperative to substantiate these findings. Full article

A liver injury was recently reported for saxagliptin, which is a dipeptidyl peptidase-4 (DPP-4) inhibitor. However, the underlying mechanisms of saxagliptin-induced liver injury remain unknown. This study aimed to evaluate whether saxagliptin, a potent and selective DPP-4 inhibitor that is globally used for treating type 2 diabetes mellitus, binds to the nucleophiles in vitro. Four DPP-4 inhibitors, including vildagliptin, were evaluated for comparison. Only saxagliptin and vildagliptin, which both contain a cyanopyrrolidine group, quickly reacted with L-cysteine to enzyme-independently produce thiazolinic acid metabolites. This saxagliptin–cysteine adduct was also found in saxagliptin-administered male Sprague–Dawley rats. In addition, this study newly identified cysteinyl glycine conjugates of saxagliptin and 5-hydroxysaxagliptin. The observed metabolic pathways were hydroxylation and conjugation with cysteine, glutathione, sulfate, and glucuronide. In summary, we determined four new thiazoline-containing thiol metabolites (cysteine and cysteinylglycine conjugates of saxagliptin and 5-hydroxysaxagliptin) in saxagliptin-administered male rats. Our results reveal that saxagliptin can covalently bind to the thiol groups of cysteine residues of endogenous proteins in vivo, indicating the potential for saxagliptin to cause drug-induced liver injury. Full article

Brown leaf spot disease caused by Alternaria spp. is among the most common diseases of potato crops. Typical brown spot symptoms were observed in commercial potato-cultivation areas of northern Korea from June to August 2020–2021. In total, 68 isolates were collected, and based on sequence analysis of the internal transcribed spacer (ITS) region, the collected isolates were identified as Alternaria spp. (80.9%). Phylogenetic analysis revealed that a majority of these isolates clustered within a clade that included A. alternata. Additionally, the ITS region and rpb2 yielded the most informative sequences for the identification of A. alternata. Pathogenicity tests confirmed that the collected pathogens elicited symptoms identical to those observed in the field. In pathogenicity tests performed on seven commercial cultivars, the pathogens exhibited strong virulence in both wound and non-wound inoculations. Among the cultivars tested, Arirang-1ho, Arirang-2ho, and Golden Ball were resistant to the pathogens. Furthermore, among the fungicides tested in vitro, mancozeb and difenoconazole were found to be effective for inhibiting mycelial growth. In summary, our findings suggest that A. alternata plays a critical role in leaf disease in potato-growing regions and emphasise the necessity of continuous monitoring and management to protect against this disease in Korea. Full article

Accurate prediction of postnatal growth failure (PGF) can be beneficial for early intervention and prevention. We aimed to develop a machine learning model to predict PGF at discharge among very low birth weight (VLBW) infants using extreme gradient boosting. A total of 729 VLBW infants, born between 2013 and 2017 in four hospitals, were included. PGF was defined as a decrease in z-score between birth and discharge that was greater than 1.28. Feature selection and addition were performed to improve the accuracy of prediction at four different time points, including 0, 7, 14, and 28 days after birth. A total of 12 features with high contribution at all time points by feature importance were decided upon, and good performance was shown as an area under the receiver operating characteristic curve (AUROC) of 0.78 at 7 days. After adding weight change to the 12 features—which included sex, gestational age, birth weight, small for gestational age, maternal hypertension, respiratory distress syndrome, duration of invasive ventilation, duration of non-invasive ventilation, patent ductus arteriosus, sepsis, use of parenteral nutrition, and reach at full enteral nutrition—the AUROC at 7 days after birth was shown as 0.84. Our prediction model for PGF performed well at early detection. Its potential clinical application as a supplemental tool could be helpful for reducing PGF and improving child health. Full article

Color development in various rice organs results from the complementary expression of genes involved in anthocyanin biosynthesis. The Purple pericarp (Prp) trait and the Purple leaf (Pl) trait both display epistasis, relying on the complement of the Pb and Pp genes for pericarp coloration and the Pl and Pp genes for leaf coloration, respectively. However, there is still genetic uncertainty in identifying the genes responsible for the various color expressions and intensities of rice grain pericarp and leaves. In this study, we characterized the inheritance patterns of color development and the mode of anthocyanin pigments in rice by crossing two parental mutant lines. YUM051, exhibiting dark purple leaves (Pl^w) and purple pericarp (Prp), was crossed with YUM144, which displayed light purple leaves (Plⁱ) and a white pericarp (prp). The F1 plants exhibited dark purple leaves with purple pericarps, indicating the dominant nature of the purple leaf (Pl) and purple pericarp (Prp) traits. The rice Prp traits display a complementary interaction, reflected in a 9:7 ratio of purple to white pericarp. However, the Prp trait followed Mendelian segregation with a 3:1 ratio of purple to white pericarp in this cross, indicating homozygous dominant Pp alleles in both parental plants. Meanwhile, the segregation of the purple leaf color in the F₂ generation of this cross followed complementary inheritance, exhibiting a 9:7 segregation ratio between purple leaves and greenish leaves with purple leaf margins. Moreover, the co-segregation of Prp and Pl traits in the cross between YUM051 (Pl^w) and YUM144 (Plⁱ) plants did not adhere to the Mendelian 9:3:3:1 independent assortment ratio, confirming that the Pl gene and Pb gene are linked on the same chromosome. Cyanidin-3-O-glucoside (C3G) was detected in the leaves of all progeny resulting from the Pl^w and Plⁱ cross. However, C3G was exclusively identified in the seeds of offspring carrying the dominant Pb gene. Therefore, the Pl^w and Plⁱ alleles are Pl genes responsible for purple leaf color, while the Pb gene is responsible for purple pericarp color in rice; these genes function independently of each other. Full article