The integration of foreign DNA into algal and plant plastid genomes is a rare event, with only a few known examples of horizontal gene transfer (HGT). Plasmids, which are well-studied drivers of HGT ...in prokaryotes, have been reported previously in red algae (Rhodophyta). However, the distribution of these mobile DNA elements and their sites of integration into the plastid (ptDNA), mitochondrial (mtDNA), and nuclear genomes of Rhodophyta remain unknown. Here we reconstructed the complex evolutionary history of plasmid-derived DNAs in red algae. Comparative analysis of 21 rhodophyte ptDNAs, including new genome data for 5 species, turned up 22 plasmid-derived open reading frames (ORFs) that showed syntenic and copy number variation among species, but were conserved within different individuals in three lineages. Several plasmid-derived homologs were found not only in ptDNA but also in mtDNA and in the nuclear genome of green plants, stramenopiles, and rhizarians. Phylogenetic and plasmid-derived ORF analyses showed that the majority of plasmid DNAs originated within red algae, whereas others were derived from cyanobacteria, other bacteria, and viruses. Our results elucidate the evolution of plasmid DNAs in red algae and suggest that they spread as parasitic genetic elements. This hypothesis is consistent with their sporadic distribution within Rhodophyta.
The chronic use of the novel synthetic cathinone mexedrone, like other psychoactive drugs, can be considered addictive, with a high potential for abuse and the ability to cause psychological ...dependence in certain users. However, little is known about the neurobehavioral effects of mexedrone in association with its potential for abuse. We investigated the abuse potential for mexedrone abuse through multiple behavioral tests. In addition, serotonin transporter (SERT) levels were measured in the synaptosome of the dorsal striatum, and serotonin (5-HT) levels were measured in the dorsal striatum of acute mexedreone (50 mg/kg)-treated mice. To clarify the neuropharmacological mechanisms underlying the locomotor response of mexedrone, the 5-HT2A receptor antagonist M100907 (0.5 or 1.0 mg/kg) was administered prior to the acute injection of mexedrone in the locomotor activity experiment in mice. Mexedrone (10–50 mg/kg) produced a significant place preference in mice and mexedrone (0.1–0.5 mg/kg/infusion) maintained self-administration behavior in rats in a dose-dependent manner. In the drug discrimination experiment, mexedrone (5.6–32 mg/kg) was fully substituted for the discriminative stimulus effects of cocaine in rats. Mexedrone increased locomotor activity, and these effects were reversed by pretreatment with M100907. Acute mexedrone significantly increased c-Fos expression in the dorsal striatum and decreased SERT levels in the synaptosome of the dorsal striatum of mice, resulting in an elevation of 5-HT levels. Taken together, our results provide the possibility that mexedrone has abuse potential, which might be mediated, at least in part, by the activation of the serotonergic system in the dorsal striatum.
•Mexedrone produces addictive-like behaviors similar to methamphetamine in rodents.•Mexedrone increases 5-HT levels via inhibition of SERT in the dorsal striatum.•M100907 attenuates acute mexedrone-induced hyperlocomotion.
Allium hookeri is widely consumed as a vegetable and herbal medicine in Asia. A. hookeri has been reported anti-inflammatory, anti-obesity, osteoblastic, anti-oxidant, and anti-diabetic effects in ...animal studies. We investigated the anti-diabetic effects of A. hookeri aqueous extract (AHE) in the Korean subjects.
Prediabetic subjects (100 ≤ fasting plasma glucose (FPG) < 126 mg/dL) who met the inclusion criteria were recruited for this study. The enrolled subjects (n = 30) were randomly divided into either an AHE (n = 15, 486 mg/day) or placebo (n = 15) group. Outcomes were measurements of FPG, glycemic response to an oral glucose tolerance test (OGTT), insulin, C-peptide, hemoglobin A1c (HbA1c), total cholesterol, triglyceride, HDL-cholesterol, and LDL-cholesterol. The t-test was used to assess differences between the groups. A p-value < 0.05 was considered statistically significant.
Eight weeks after AHE supplementation, HbA1c level was significantly decreased in the AHE group compared with the placebo group. No clinically significant changes in any safety parameter were observed.
The findings suggest that AHE can be effective in reducing HbA1c, indicating it as an adjunctive tool for improving glycemic control.
The study protocol was retrospectively registered at www.clinicaltrials.gov ( NCT03330366 , October 30, 2017).
Capsaicinoids in red pepper powder are known to show anti-bacterial effects; however, their effects during kimchi fermentation are not known. This study aimed to investigate the effects of various ...concentrations of capsaicinoids on kimchi fermentation. Five sets of kimchi samples were prepared using 0 mg/kg (control), 98.34 ± 5.34 mg/kg (mild), 243.47 ± 3.71 mg/kg (medium), 428.63 ± 30.78 mg/kg (hot), and 1,320.49 ± 28.27 mg/kg (extreme) capsaicinoid. The characteristics of each kimchi sample, including pH, acidity, organic acid, sugars, sugar alcohol, capsaicinoid content, and microbial community were periodically investigated during fermentation. Kimchi with red pepper powder shows significantly higher acidity than control kimchi, whereas pH values were the same. Organic acid in kimchi with red pepper powder was higher than in control kimchi, probably caused by higher lactic acid bacteria (LAB) counts in kimchi samples with red pepper powder. Our results show that addition of red pepper powder decreased Leuconostoc spp. counts in the bacterial community. In particular, Lactobacillus sakei and Leuconostoc gelidum counts increased and decreased, respectively, with increasing capsaicinoid content of red pepper powder added to kimchi. Overall, the results of this study indicate that physicochemical properties and LAB such as L. sakei and L. gelidum are influenced by capsaicinoid content. However, further studies are necessary to investigate the effects of the percentage of red pepper powder in kimchi on fermentation to provide practical guidelines for producing standardized kimchi.
Melanoma incidence is on the rise in East Asia, yet studies of the molecular landscape are lacking in this population. We examined patients with melanoma who underwent next-generation sequencing ...(NGS) at a single tertiary center in South Korea, focusing on patients harboring NRAS or RAF alterations who received belvarafenib, a pan-RAF dimer inhibitor, through the Expanded Access Program (EAP).
Data were collected from 192 patients with melanoma who underwent NGS between November 2017 and May 2023. Variant call format data were obtained and annotated. Patients in the EAP received 450 mg twice daily doses of belvarafenib.
Alterations in the RAS/RTK pathway were the most prevalent, with BRAF and NRAS alteration rates of 22.4% and 17.7%, respectively. NGS enabled additional detection of fusion mutations, including 6 BRAF and 1 RAF1 fusion. Sixteen patients with NRAS or RAF alterations received belvarafenib through the EAP, and disease control was observed in 50%, with 2 patients demonstrating remarkable responses.
Our study highlights the value of NGS in detecting BRAF, NRAS mutations and RAF fusions, expanding possibilities for targeted therapies in malignant melanoma. Belvarafenib showed clinical benefit in patients harboring these alterations. Ongoing trials will provide further insights into the safety and efficacy of belvarafenib.
Renin-angiotensin system blockade (RAB) is the cornerstone in the management of patients with heart failure. However, the benefit of RAB in patients with accompanying severe renal impairment is not ...clear. We aimed to examine the effect of RAB and the differential effect of RAB depending on renal replacement (RR) in patients with severe renal insufficiency and acute heart failure.
Among 5625 patients from the Korean Acute Heart Failure registry, 673 in-hospital survivors (70.9 ± 12.8 years, 376 men) who had left ventricular ejection fraction < 40% and estimated glomerular filtration rate < 30 mL/min/1.73 m2 during hospitalization were analyzed. The inverse probability of treatment weighting (IPTW)-adjusted survival analysis was used to compare the composite of all-cause mortality and rehospitalization between patients with and without pre-discharge RAB. A total of 334 (49.6%) adverse events were observed during the 1-year follow-up. The IPTW-adjusted Kaplan-Meier survival analysis showed that the 1-year event rate was 48.7% and 53.8% for patients with RAB and those without, respectively (log rank p = 0.048). RAB was significantly related to better prognosis in patients receiving RR therapy (hazard ratio HR = 0.436 0.269–0.706, p = 0.001), but not in patients not receiving RR therapy (HR 0.956 0.731–1.250, p = 0.742) in a weighted cohort (p for interaction = 0.005).
Early RAB treatment in patients with heart failure and severe renal insufficiency was related to better prognosis. The benefit of RAB was particularly prominent in patients receiving RR therapy.
•Renin-angiotensin blockade (RAB) was associated with favorable prognosis.•RAB was more effective in patients with renal replacement therapy (RR).•Patients with RR were taking higher intensity of RAB at 1-year follow-up.
Seasonal Influenza is still considered associated with seasonal morbidity and hospitalization in the elderly population. The World Health Organization (WHO) recommended seasonal quadrivalent ...influenza vaccine (QIV) to reduce burden of two currently circulating influenza B lineages. Until 2019 Korean National Immunization Program (NIP) recommended trivalent influenza vaccine (TIV) after ongoing debates on cost effectiveness of QIV for elderly population. Although influenza vaccine only showed modest effect on reducing influenza in elderly, this study aimed to evaluate the immunogenicity and safety of inactivated QIV in healthy participants ≥ 65 years of age.
A total of 274 healthy participants aged ≥ 65 years received a QIV. Seroconversion-based vaccine efficacy of 4 strains of seasonal influenza was assessed 21 days after vaccination and adverse events were monitored until 180 days after vaccination.
The percentages of participants seroconverted after vaccination on HI antibody against each strain were 36.5% (99/271) to A/H1N1, 47.6% (129/271) to A/H3N2, 40.6% (110/271) to B Yamagata, and 49.1% (133/271) to B Victoria. The percentages of participants seroprotected after vaccination on HI antibody against each strain were 81.2% (220/271) to A/H1N1, 98.5% (267/271) to A/H3N2, 95.2% (258/271) to B Yamagata, and 93.7% (254/271) to B Victoria. There was no serious adverse event (SAE) related with the study vaccine.
The quadrivalent split influenza vaccine is expected to offer seroprotection against influenza A and both influenza B lineages even in the elderly population.
Ototoxicity is an important issue in patients receiving cisplatin chemotherapy. Numerous studies have demonstrated that cisplatin-induced ototoxicity is related to oxidative stress and DNA damage. ...However, the precise mechanism underlying cisplatin-associated ototoxicity is still unclear. The cofactor nicotinamide adenine dinucleotide (NAD+) has emerged as an important regulator of energy metabolism and cellular homeostasis. Here, we demonstrate that the levels and activities of sirtuin-1 (SIRT1) are suppressed by the reduction of intracellular NAD+ levels in cisplatin-mediated ototoxicity. We provide evidence that the decreases in SIRT1 activity and expression facilitated by increasing poly(ADP-ribose) polymerase-1 (PARP-1) activation and microRNA-34a levels through cisplatin-mediated p53 activation aggravate the associated ototoxicity. Furthermore, we show that the induction of cellular NAD+ levels using dunnione, which targets intracellular NQO1, prevents the toxic effects of cisplatin through the regulation of PARP-1 and SIRT1 activity. These results suggest that direct modulation of cellular NAD+ levels by pharmacological agents could be a promising therapeutic approach for protection from cisplatin-induced ototoxicity.
•SIRT1 activity is suppressed by the reduction of cellular NAD+ levels.•Decreases in SIRT1 expression facilitated by p53-microRNA34a pathway.•Induction of cellular NAD+ levels using dunnione prevents the cisplatin ototoxicity.
Tumor metastasis to the eyelids is very rare. The authors report the first case of a neuroendocrine tumor that originated from the ampulla of Vater in the gastrointestinal tract and metastasized to ...the eyelid. The patient with a hospice care was referred to the authors' eye clinic after presenting with a palpable mass on the left eyelid and blinking discomfort. He was previously diagnosed with a neuroendocrine tumor arising from the ampulla of Vater. The eyelid tumor was simply removed to relieve discomfort, and histological and immunophenotypic evaluation of the resected eyelid mass showed a poorly differentiated neuroendocrine tumor with large cell types, similar to specimens from the duodenum.
The onset of inflammatory bowel disease (IBD) usually occurs at young age, and therefore, women IBD patients experience pregnancy during their disease progression. Recently, the use of anti-tumor ...necrosis factor-α (anti-TNF-α) has been rapidly increasing. The aim of this study was to evaluate pregnancy related outcomes in women with IBD who were treated with anti-TNF-α during pregnancy and immunity of their children.
Korean women with IBD who had been treated with anti-TNF-α during pregnancy had been enrolled. Medical records were reviewed and a survey was performed for each patient. For the patients who agreed on additional examination for their children, children's growth, medical history and antibody to hepatitis B surface antigen (anti-HBs) titer were checked.
All 18 patients had been diagnosed with Crohn's disease. There was not any case of preterm delivery, low birth-weight infant, congenital anomaly, nor stillbirth. All 12 children had followed the regular vaccination schedule for hepatitis B and 4 of them showed negative results for anti-HBs. After the 1 booster vaccination, all children demonstrated seroconversion. Regarding live vaccines, 4 children had bacillus Calmette-Guerin and 4 had rotavirus vaccine before 6 months, without any specific side effects.
This was the first study of immunity of the children born from IBD women who had been treated with anti-TNF-α medication during their pregnancy. IBD women had comparable pregnancy outcomes with the general women population, suggesting that the disease activity rather than the administered medication would be more important in healthy pregnancy. Considering the history of vaccination and anti-HBs titers, immunity seems to be intact in the children.
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