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1.
Reprod Toxicol ; 126: 108587, 2024 Apr 24.
Artículo en Inglés | MEDLINE | ID: mdl-38663639

RESUMEN

Tdap is an acronym for tetanus(T), diphtheria(D), and acellular pertussis(aP), and is a preventive vaccine that combines vaccines against three diseases. BVN008 is a Tdap vaccine designed to protect against three diseases: diphtheria, tetanus, and pertussis. The lower-case "d" and "p" in Td and Tdap means these vaccines use smaller amounts of diphtheria and whooping cough. The lower doses are appropriate for adolescents and adults. The purpose of this study was to identify adverse effects in pregnant or lactating female Sprague-Dawley rats including maternal fertility and toxicity, and development of the embryos, fetus, and pups following intramuscular administration of BVN008. Two groups of 50 female Sprague-Dawley rats were administered four or five intramuscular injections of the vaccine (human dose of 0.5 mL at 4 and 2 weeks before pairing, on gestation day (GD) 8 and 15, and lactation day (LD) 7. A negative control group was administered 0.9% saline at the same dose four or five times. There were no adverse effects on fertility, reproductive performance, or maternal toxicity of the F0 females. There was no effect of developmental toxicity in F1 fetuses and pups including fetal body weight and morphology, postnatal growth, development, and behavior until weaning. Antibodies against tetanus, diphtheria, and pertussis were transferred to the F1 fetuses and F1 pups via placenta and milk. These results demonstrate that BVN008 had no detectable adverse effects in either the F0 female rats, the F1 fetuses or pups.

2.
Medicina (Kaunas) ; 60(3)2024 Mar 05.
Artículo en Inglés | MEDLINE | ID: mdl-38541159

RESUMEN

Background and Objectives: Muscle atrophy occurs when protein degradation exceeds protein synthesis, resulting in imbalanced protein homeostasis, compromised muscle contraction, and a reduction in muscle mass. The incidence of muscle atrophy is increasingly recognized as a significant worldwide public health problem. The aim of the current study was to evaluate the effect of whey peptide (WP) on muscle atrophy induced by dexamethasone (DEX) in mice. Materials and Methods: C57BL/6 mice were divided into six groups, each consisting of nine individuals. WPs were orally administered to C57BL/6 mice for 6 weeks. DEX was administered for 5-6 weeks to induce muscle atrophy (intraperitoneal injection, i.p.). Results: Microcomputer tomography (CT) analysis confirmed that WP significantly increased calf muscle volume and surface area in mice with DEX-induced muscle atrophy, as evidenced by tissue staining. Furthermore, it increased the area of muscle fibers and facilitated greater collagen deposition. Moreover, WP significantly decreased the levels of serum biomarkers associated with muscle damage, kidney function, and inflammatory cytokines. WP increased p-mTOR and p-p70S6K levels through the IGF-1/PI3K/Akt pathway, while concurrently decreasing protein catabolism via the FOXO pathway. Furthermore, the expression of proteins associated with myocyte differentiation increased noticeably. Conclusions: These results confirm that WP reduces muscle atrophy by regulating muscle protein homeostasis. Additionally, it is believed that it helps to relieve muscle atrophy by regulating the expression of myocyte differentiation factors. Therefore, we propose that WP plays a significant role in preventing and treating muscle wasting by functioning as a supplement to counteract muscle atrophy.


Asunto(s)
Dexametasona , Suero Lácteo , Ratones , Animales , Dexametasona/efectos adversos , Suero Lácteo/metabolismo , Fosfatidilinositol 3-Quinasas/metabolismo , Fosfatidilinositol 3-Quinasas/farmacología , Transducción de Señal/fisiología , Ratones Endogámicos C57BL , Atrofia Muscular/tratamiento farmacológico , Atrofia Muscular/etiología , Músculo Esquelético/patología , Fibras Musculares Esqueléticas/metabolismo , Fibras Musculares Esqueléticas/patología , Péptidos/efectos adversos
3.
Ann Intern Med ; 177(3): 291-302, 2024 Mar.
Artículo en Inglés | MEDLINE | ID: mdl-38437702

RESUMEN

BACKGROUND: Some data suggest a higher incidence of diagnosis of autoimmune inflammatory rheumatic diseases (AIRDs) among patients with a history of COVID-19 compared with uninfected patients. However, these studies had methodological shortcomings. OBJECTIVE: To investigate the effect of COVID-19 on long-term risk for incident AIRD over various follow-up periods. DESIGN: Binational, longitudinal, propensity-matched cohort study. SETTING: Nationwide claims-based databases in South Korea (K-COV-N cohort) and Japan (JMDC cohort). PARTICIPANTS: 10 027 506 Korean and 12 218 680 Japanese patients aged 20 years or older, including those with COVID-19 between 1 January 2020 and 31 December 2021, matched to patients with influenza infection and to uninfected control patients. MEASUREMENTS: The primary outcome was onset of AIRD (per appropriate codes from the International Classification of Diseases, 10th Revision) 1, 6, and 12 months after COVID-19 or influenza infection or the respective matched index date of uninfected control patients. RESULTS: Between 2020 and 2021, among the 10 027 506 Korean participants (mean age, 48.4 years [SD, 13.4]; 50.1% men), 394 274 (3.9%) and 98 596 (0.98%) had a history of COVID-19 or influenza, respectively. After propensity score matching, beyond the first 30 days after infection, patients with COVID-19 were at increased risk for incident AIRD compared with uninfected patients (adjusted hazard ratio, 1.25 [95% CI, 1.18 to 1.31]) and influenza-infected control patients (adjusted hazard ratio, 1.30 [CI, 1.02 to 1.59]). The risk for incident AIRD was higher with more severe acute COVID-19. Similar patterns were observed in the Japanese cohort. LIMITATIONS: Referral bias due to the pandemic; residual confounding. CONCLUSION: SARS-CoV-2 infection was associated with increased risk for incident AIRD compared with matched patients without SARS-CoV-2 infection or with influenza infection. The risk for incident AIRD was higher with greater severity of acute COVID-19. PRIMARY FUNDING SOURCE: National Research Foundation of Korea.


Asunto(s)
COVID-19 , Gripe Humana , Masculino , Humanos , Persona de Mediana Edad , Femenino , COVID-19/epidemiología , Estudios de Cohortes , SARS-CoV-2 , Estudios Longitudinales
4.
Plant Dis ; 2024 Jan 08.
Artículo en Inglés | MEDLINE | ID: mdl-38190364

RESUMEN

Amaranthus hybridus (=A. patulus), often called green amaranth, is an annual herbaceous plant of the Amaranthaceae. This plant is considered a harmful weed in the agricultural context of North America and has expanded its distribution to Asia and Europe. In Korea, it has become a problematic invasive issue, leading to economic losses due to reduced crop yields and rising weed management costs (Park et al., 2014), although its seeds and young leaves are edible and frequently consumed. In October 2020, we observed leaf spot symptoms on A. hybridus plants that were growing within perilla farms (Perilla frutescens var. japonica) located in Damyang (35°14'07"N, 126°59'40"E), Korea, with a disease incidence of 20 to 30% of the inspected plants. The initial signs appeared as grey to brown dots on the leaves, which gradually expanded into irregular, brown patches with a diameter of 2-3 cm. A single spore was isolated from the diseased leaf under a dissecting microscope, placed onto a 2% water agar plate, and incubated in darkness at 25°C for three days. Pure cultures were obtained by transferring single hyphal tips onto potato dextrose agar (PDA) plates. Five single-spore isolates were the same in the cultural and morphological examination, and a representative isolate (P309) was preserved at the Korean Agricultural Culture Collection (KACC49813), Korea. Colonies appeared light gray to white with regular margins and reached 4 to 5 cm in diameter after a week. After two weeks, black patches of spores were often visible in the aerial mycelia. Conidiophores were brown to pale brown, often branched, thick-walled, and measured 6.8 × 2.7 µm (n = 30). Conidia were single-celled, dark brown, globose to ellipsoid, and measured 6.8 × 5.0 µm (n = 50), with a ratio of length/width of 1.1 to 1.6 (n = 50). These morphological characteristics matched those of Arthrinium arundinis (Crous et al., 2013). For molecular identification, genomic DNA was extracted from conidia and mycelia on two-week-old PDA culture of the KACC49813. PCR was performed for the internal transcribed spacer (ITS) (primers ITS1/ITS4, White et al. 1990), the large subunit (LSU) rDNA (primers LROR/LR5, Vilgalys et al. 1990), the beta-tubulin gene (TUB) (primers T1/Bt-2b, O'Donnell and Cigelnik 1997), and the translation elongation factor 1-alpha (TEF) (primers EF1-728F/EF-2, Crous et al. 2013). A BLASTn search of the resulting sequences of ITS (560 bp; OL744431), LSU (881 bp; OL744432), TUB (790 bp; PP084934), and TEF (445 bp; PP084935) revealed 100 % similarity (e-value=0.0, coverage=100%) to previously reported sequences of Arthrinium arundinis (e.g. MF627422 for ITS, KF144930 for LSU, KF144973 for TUB, and KY705146 for TEF), confirming the identity of the Korean isolate. Pathogenicity assays were performed twice by spraying 1 ml of a conidial suspension (1.1 × 104 conidia per mL) onto the leaf surface of sixteen healthy A. hybridus plants. Sixteen control plants were sprayed with sterile water. All plants were kept in a growth chamber at 80% relative humidity and 23 °C with a 12-h light/dark cycle. Three weeks after the inoculation, initial symptoms mirroring the aforementioned ones appeared, while the control plants remained symptomless. Fungal isolates were successfully re-isolated from the inoculated leaves, and their identity as A. arundinis was confirmed by DNA sequencing, thus fulfilling Koch's postulates. To our knowledge, this is the first report of leaf spot caused by A. arundinis on Amaranthus hybridus, not only in Korea but globally. Arthrinium arundinis has also been reported as a plant pathogen on some agricultural crops (Ji et al. 2020; Liao et al. 2022; Farr and Rossman 2023), suggesting its polyphagous behavior. Then, this pathogen could represent a potential risk to the cultivation of edible amaranth in Korea and other crops where Amaranthus species are spread as weeds. For this reason, continuous monitoring is necessary to assess the impact of this fungus on Amaranthus and other crops.

5.
J Burn Care Res ; 45(2): 410-415, 2024 Mar 04.
Artículo en Inglés | MEDLINE | ID: mdl-37875372

RESUMEN

Lighter sedation targets over the past decade have resulted in improved outcomes for critically ill populations. Although guidelines exist for the general ICU population, these recommendations often exclude the burn population. The purpose of this study is to assess the impact of the initial continuous sedative on coma- and delirium-free days in critically ill patients with burns. This retrospective cohort study evaluated adult patients admitted to a burn intensive care unit at an academic medical center between January 2010 and September 2019. Patients were enrolled into 3 groups based on the depth of initial continuous sedation received (deep, light, or analgosedation). Intubated patients were randomly assessed for inclusion from the National V6 Burn Registry. Patients were included if they received a continuous sedative infusion for at least 48 h. A total of 107 patients were included in the study with 36, 41, and 30 patients receiving deep, light, and analgosedation, respectively. The primary outcome of coma- and delirium-free days was significantly different between sedation types with the most days free in analgosedation and the fewest in deep sedation (8 versus 3 days; P = 0.024). The composite primary outcome was divided into secondary outcomes of coma-free days and delirium-free days, with coma-free days being different (P = 0.00008). Other secondary outcomes of length of stay in the intensive care unit and hospital, time on mechanical ventilation, and survival to discharge were not statistically significant; however, a trend toward higher mortality in deep sedation was noted.


Asunto(s)
Quemaduras , Delirio , Adulto , Humanos , Hipnóticos y Sedantes/uso terapéutico , Coma/etiología , Coma/terapia , Estudios Retrospectivos , Enfermedad Crítica , Delirio/tratamiento farmacológico , Delirio/etiología , Delirio/epidemiología , Quemaduras/complicaciones , Quemaduras/terapia , Unidades de Cuidados Intensivos , Respiración Artificial , Tiempo de Internación
6.
J Korean Med Sci ; 38(49): e372, 2023 Dec 18.
Artículo en Inglés | MEDLINE | ID: mdl-38111278

RESUMEN

BACKGROUND: Infants with congenital anomalies of the digestive system and abdominal wall defects requiring surgery are at risk of growth and developmental delays. The aim of this study was to analyze long-term growth and developmental outcomes for infants with congenital anomalies of the digestive system and abdominal wall defects who underwent surgery in Korea. METHODS: We extracted data from the Korean National Health Insurance Service database for the years 2013-2019. Major congenital anomalies were defined according to the International Classification of Diseases-10 and surgery insurance claim codes. The χ² test and the Cochran-Armitage trend test were performed for data analysis. RESULTS: A total of 4,574 infants with major congenital anomalies in the digestive system and abodminal wall defects, who had undergone surgey, were reviewed. Anorectal obstruction/stenosis was the most prevalent anomaly (4.9 per 10,000 live births). The prevalence of congenital anomalies of the digestive system was 15.5 per 10,000 live births, and that of abdominal wall defects was 1.5 per 10,000 live births. Seven percent of infants with congenital anomalies in the digestive system died, of which those with diaphragmatic hernia had the highest mortality rate (18.8%). Among 12,336 examinations at 6, 12, 24, 36, 48, 60, and 72 months of age, 16.7% showed a weight below the 10th percentile, 15.8% had a height below the 10th percentile, and 13.2% had a head circumference below the 10th percentile. Abnormal developmental screening results were observed in 23.0% of infants. Infants with esophageal atresia with/without tracheoesophageal fistula most often had poor growth and development. Delayed development and cerebral palsy were observed in 490 (10.7%) and 130 (2.8%) infants respectively. Comparing the results of infants born in 2013 between their 24- and 72-month health examinations, the proportions of infants with poor height and head circumference growth increased by 6.5% and 5.3%, respectively, whereas those with poor weight growth and abnormal developmental results did not markedly change between the two examinations. CONCLUSION: Infants with congenital anomalies of the digestive system and abdominal wall defects exhibit poor growth and developmental outcomes until 72 months of age. Close monitoring and careful consideration of their growth and development after discharge are required.


Asunto(s)
Pared Abdominal , Anomalías Congénitas , Lactante , Embarazo , Femenino , Humanos , Niño , Adolescente , Pared Abdominal/cirugía , Parto , Sistema Digestivo , República de Corea/epidemiología , Anomalías Congénitas/epidemiología
7.
J Korean Med Sci ; 38(39): e304, 2023 Oct 09.
Artículo en Inglés | MEDLINE | ID: mdl-37821084

RESUMEN

BACKGROUND: In Korea, there have been no reports comparing the prevalence of major congenital anomalies with other countries and no reports on surgical treatment and long-term mortality. We investigated the prevalence of 67 major congenital anomalies in Korea and compared the prevalence with that of the European network of population-based registries for the epidemiological surveillance of congenital anomalies (EUROCAT). We also investigated the mortality and age at death, the proportion of preterm births, and the surgical rate for the 67 major congenital anomalies. METHODS: Korean National Health Insurance claim data were obtained for neonates born in 2013-2014 and admitted within one-year-old. Sixty-seven major congenital anomalies were defined by medical diagnoses classified by International Classification of Diseases-10 codes according to the EUROCAT definition version 2014. Mortality and surgery were defined if any death or surgery claim code was confirmed until 2020. Poisson distribution was used to calculate the 95% confidence interval of the congenital anomaly prevalence. RESULTS: The total prevalence of the 67 major anomalies was 433.5/10,000 livebirths. When compared with the prevalence of each major anomaly in EUROCAT, the prevalence of spina bifida, atrial septal defect (ASD), congenital megacolon, hip dislocation and/or dysplasia and skeletal dysplasia were more than five times higher in Korea. In contrast, the prevalence of aortic atresia/interrupted aortic arch and gastroschisis was less than one-fifth in Korea. The proportion of preterm births was 15.7%; however, more than 40% of infants with anencephaly, annular pancreas and gastroschisis were preterm infants. Additionally, 29.2% of the major anomalies were admitted to the neonatal intensive care units at birth, and 25.6% received surgical operation. The mortality rate was 1.7%, and 78.2% of the deaths occurred within the first year of life. However, in neonates with tricuspid valve atresia and stenosis, duodenal atresia or stenosis, and diaphragmatic hernia, more than half died within their first month of life. ASD and ventricular septal defect were the most common anomalies, and trisomy 18 and hypoplastic left heart syndrome were the most fatal anomalies. All infants with aortic atresia/interrupted aortic arch and conjoined twins received surgery. CONCLUSION: The proportion of surgeries, preterm births and mortality was high in infants with major congenital anomalies. The establishment of a national registry of congenital anomalies and systematic support by national medical policies are needed for infants with major congenital anomalies in Korea.


Asunto(s)
Enfermedades de la Aorta , Anomalías Congénitas , Gastrosquisis , Nacimiento Prematuro , Lactante , Femenino , Recién Nacido , Humanos , Niño , Nacimiento Prematuro/epidemiología , Constricción Patológica , Recien Nacido Prematuro , República de Corea/epidemiología , Anomalías Congénitas/epidemiología , Sistema de Registros , Prevalencia
8.
J Med Food ; 26(6): 379-389, 2023 Jun.
Artículo en Inglés | MEDLINE | ID: mdl-37319312

RESUMEN

The aim of this study is to investigate the efficacy and the underlying mechanism of Veronica incana in osteoarthritis (OA) induced by intraarticular injection of monosodium iodoacetate (MIA). The selected major four compounds (A-D) of V. incana were found from fractions 3 and 4. Its structure elucidation was determined by liquid chromatography-electrospray ionization-mass spectrometry (LC-ESI-MS) data analysis and nuclear magnetic resonance (NMR) data comparison with literature. MIA (50 µL with 80 mg/mL) for the animal experiment was injected into the right knee joint. The V. incana was administered orally every day to rats for 14 days from 7 days after MIA treatment. Finally, we confirmed the four compounds: (A) verproside; (B) catalposide; (C) 6-vanilloylcatapol; and (D) 6-isovanilloylcatapol. When we evaluated the effect of V. incana on the MIA injection-induced knee OA model, there were a noticeable initial decreased in hind paw weight-bearing distribution compared to the Normal group (P < .001), but V. incana supplementation resulted in a significant increase in the weight-bearing distribution to the treated knee (P < .001). Moreover, the V. incana treatment led to a decrease in the levels of liver function enzymes and tissue malondialdehyde (P < .05 and .01). The V. incana significantly suppressed the inflammatory factors through the nuclear factor-kappa B signaling pathway and downregulated the expression of matrix metalloproteinases, which are involved in the degradation of the extracellular matrix (P < .01 and .001). In addition, we confirmed the alleviation of cartilage degeneration through tissue stains. In conclusion, this study confirmed the major four compounds of V. incana and suggested that V. incana could serve as an anti-inflammatory candidate agent for patients with OA.


Asunto(s)
Osteoartritis de la Rodilla , Veronica , Ratas , Animales , Ácido Yodoacético , Modelos Animales de Enfermedad , Antiinflamatorios/farmacología , Osteoartritis de la Rodilla/inducido químicamente , Osteoartritis de la Rodilla/tratamiento farmacológico
9.
Int J Clin Pharmacol Ther ; 61(9): 410-420, 2023 Sep.
Artículo en Inglés | MEDLINE | ID: mdl-37382330

RESUMEN

PURPOSE: Tegoprazan is a differentiated gastric acid-pump blocker and belongs to a class of potassium-competitive acid secretion blockers. An orally disintegrating tablet (ODT) of tegoprazan was developed to improve patient compliance. The purpose of this study was to compare pharmacokinetics (PK) and safety profiles between the conventional tablet (as the reference drug) and the ODT (as the test drug) of 50 mg tegoprazan in healthy Korean subjects. MATERIALS AND METHODS: An open-label, randomized, single-dose, 6-sequence, 3-period crossover study was conducted in 48 healthy subjects. All subjects received a single oral dose of tegoprazan 50 mg tablet with water, tegoprazan 50 mg ODT with water, and tegoprazan 50 mg ODT without water. Serial blood samples were collected up to 48 hours after dosing. Plasma concentrations of tegoprazan and its metabolite M1 were measured by LC-MS/MS, and PK parameters were calculated with a non-compartmental method. Safety was evaluated by means of assessed adverse events, physical examinations, laboratory test results as well as measurements of vital signs and ECG throughout the study. RESULTS: A total of 47 subjects completed the study. The 90% confidence intervals of the geometric mean ratios for AUCt, Cmax, and AUCinf of tegoprazan were 0.8873 - 0.9729, 0.8865 - 1.0569, and 0.8835 - 0.9695 for the test drug with water to the reference drug and 0.9169 - 1.0127, 0.9569 - 1.1276, and 0.9166 - 1.0131 for the test drug without water to the reference drug, respectively. There were no serious adverse events, and all adverse events were mild. CONCLUSION: The PK profiles of tegoprazan were equivalent between the conventional tablet and ODT with or without water. There was no significant difference in the safety profiles. Therefore, the novel ODT of tegoprazan that can be taken without water may improve compliance among patients with acid-related diseases.


Asunto(s)
Espectrometría de Masas en Tándem , Humanos , Estudios Cruzados , Voluntarios Sanos , Cromatografía Liquida , Comprimidos , República de Corea , Administración Oral , Área Bajo la Curva
10.
Asian Pac J Cancer Prev ; 24(5): 1751-1758, 2023 May 01.
Artículo en Inglés | MEDLINE | ID: mdl-37247298

RESUMEN

BACKGROUND: Ulcerative colitis (UC) is an inflammatory bowel disease that affects people worldwide. The causes of UC are diverse, and symptoms include diarrhea, weight loss, anemia, rectal bleeding, and bloody stools. Tenebrio molitor larvae have recently gained attention as edible insects with various physiological and medical effects. Research on the anti-inflammatory effects of ingesting Tenebrio molitor larvae powder (TMLP) is being actively conducted. In this study, TMLP was administered to mice with dextran sodium sulfate (DSS)-induced colitis to investigate its effects in reducing colitis symptoms. METHODS: Mice were initially given 3% DSS in water to induce colitis and then feed containing 0%, 2%, or 4% TMLP. Pathologic changes in colon tissues were assessed by histology, and neutrophil levels were measured by myeloperoxidase (MPO) assay. Levels of IL-1ß, IL-6, and TNF-α were measured using real-time PCR and ELISA assays, and IκB and NF-kB protein levels were measured by western blotting. RESULT: Disease Activity Index (DAI) scores and MPO activity were reduced in TMLP-treated mice, and colon length increased as much as normal mice. Pathologic changes in the colon tissues of DSS-induced mice were attenuated, and the expression of inflammatory cytokine genes IL-1ß, IL-6, and TNF-α decreased. Concomitant decreases in the protein expression of IL-1ß and IL-6 were confirmed using ELISA. Western blotting revealed that levels of phosphorylated forms of IκB and NF-κB also decreased. CONCLUSION: These results show that feeding TMLP to DSS-induced mice inhibited the typical inflammatory pathway of colitis. Therefore, TMLP shows potential as a food additive that can help treat colitis.
.


Asunto(s)
Colitis Ulcerosa , Colitis , Tenebrio , Animales , Ratones , Tenebrio/metabolismo , Dextranos , Polvos/farmacología , Factor de Necrosis Tumoral alfa/metabolismo , Larva/metabolismo , Interleucina-6/metabolismo , Transducción de Señal , Colitis/inducido químicamente , Colitis/tratamiento farmacológico , Colitis Ulcerosa/inducido químicamente , Colitis Ulcerosa/tratamiento farmacológico , Colon/metabolismo , FN-kappa B/metabolismo , Sulfato de Dextran/toxicidad , Modelos Animales de Enfermedad
11.
Ageing Soc ; 43(3): 499-515, 2023 Mar.
Artículo en Inglés | MEDLINE | ID: mdl-36875285

RESUMEN

Drawing from theory and research on the role of social networks in promoting or undermining preventative public health measures, this article considers how structural, compositional and functional aspects of older adults' close social networks are associated with HIV testing in the context of rural South Africa. Analyses use data from the population-based Health and Aging in Africa: A Longitudinal Study of an INDEPTH Community in South Africa (HAALSI) - a sample of rural adults age 40+ (N = 4,660). Results from multiple logistic regression show older South African adults with larger, more heavily non-kin and more literate networks were most likely to report testing for HIV. People whose network members provided frequent information were also most likely to be tested, though interaction effects indicate that this pattern is primarily found among those with highly literate networks. Taken together, the findings reinforce a key insight from social capital perspectives: network resourcefulness - literacy in particular - is crucial for promoting preventative health practice. The synergy between network literacy and informational support reveals the complex interplay between network characteristics in shaping health-seeking behaviour. Continued research is needed on the connection between networks and HIV testing among sub-Saharan older adults, as this population is not currently well served by many public health efforts in the region.

12.
Autophagy ; 19(7): 2045-2061, 2023 07.
Artículo en Inglés | MEDLINE | ID: mdl-36849436

RESUMEN

Dysfunction of the endosomal sorting complex required for transport (ESCRT) has been linked to frontotemporal dementia (FTD) due in part to the accumulation of unsealed autophagosomes. However, the mechanisms of ESCRT-mediated membrane closure events on phagophores remain largely unknown. In this study, we found that partial knockdown of non-muscle MYH10/myosin IIB/zip rescues neurodegeneration in both Drosophila and human iPSC-derived cortical neurons expressing FTD-associated mutant CHMP2B, a subunit of ESCRT-III. We also found that MYH10 binds and recruits several autophagy receptor proteins during autophagosome formation induced by mutant CHMP2B or nutrient starvation. Moreover, MYH10 interacted with ESCRT-III to regulate phagophore closure by recruiting ESCRT-III to damaged mitochondria during PRKN/parkin-mediated mitophagy. Evidently, MYH10 is involved in the initiation of induced but not basal autophagy and also links ESCRT-III to mitophagosome sealing, revealing novel roles of MYH10 in the autophagy pathway and in ESCRT-related FTD pathogenesis.Abbreviations: ALS: amyotrophic lateral sclerosis; AP: autophagosome; Atg: autophagy-related; ESCRT: endosomal sorting complex required for transport; FTD: frontotemporal dementia.


Asunto(s)
Autofagosomas , Demencia Frontotemporal , Humanos , Autofagosomas/metabolismo , Complejos de Clasificación Endosomal Requeridos para el Transporte/metabolismo , Demencia Frontotemporal/genética , Demencia Frontotemporal/metabolismo , Miosina Tipo IIB no Muscular/metabolismo , Autofagia/fisiología , Neuronas/metabolismo , Homeostasis
13.
Autophagy ; 19(5): 1424-1443, 2023 05.
Artículo en Inglés | MEDLINE | ID: mdl-36250672

RESUMEN

ABBREVIATIONS: A:C autophagic membrane:cytosol; ALS amyotrophic lateral sclerosis; ATG4 autophagy related 4; Atg8 autophagy related 8; BafA1 bafilomycin A1; BNIP3L/Nix BCL2 interacting protein 3 like; CALCOCO2/NDP52 calcium binding and coiled-coil domain 2; EBSS Earle's balanced salt solution; GABARAP GABA type A receptor-associated protein; GST glutathione S transferase; HKO hexa knockout; Kd dissociation constant; LIR LC3-interacting region; MAP1LC3/LC3 microtubule associated protein 1 light chain 3; NLS nuclear localization signal/sequence; PE phosphatidylethanolamine; SpHfl1 Schizosaccharomyces pombeorganic solute transmembrane transporter; SQSTM1/p62 SQSTM1/p62; TARDBP/TDP-43 TAR DNA binding protein; TKO triple knockout.


Asunto(s)
Autofagia , Proteínas de la Membrana , Animales , Familia de las Proteínas 8 Relacionadas con la Autofagia/metabolismo , Proteínas de la Membrana/metabolismo , Proteína Sequestosoma-1/metabolismo , Autofagia/genética , Proteínas Reguladoras de la Apoptosis/metabolismo , Proteínas Asociadas a Microtúbulos/metabolismo , Mamíferos/metabolismo
14.
Mycobiology ; 50(5): 382-388, 2022.
Artículo en Inglés | MEDLINE | ID: mdl-36404900

RESUMEN

White mold (or Sclerotinia stem rot), caused by Sclerotinia species, is a major air, soil, or seed-transmitted disease affecting numerous crops and wild plants. Microscopic or culture-based methods currently available for their detection and identification are time-consuming, laborious, and often erroneous. Therefore, we developed a multiplex quantitative PCR (qPCR) assay for the discrimination, detection, and quantification of DNA collected from each of the three economically relevant Sclerotinia species, namely, S. sclerotiorum, S. minor, and S. nivalis. TaqMan primer/probe combinations specific for each Sclerotinia species were designed based on the gene sequences encoding aspartyl protease. High specificity and sensitivity of each probe were confirmed for sclerotium and soil samples, as well as pure cultures, using simplex and multiplex qPCRs. This multiplex assay could be helpful in detecting and quantifying specific species of Sclerotinia, and therefore, may be valuable for disease diagnosis, forecasting, and management.

15.
J Med Food ; 25(9): 882-891, 2022 Sep.
Artículo en Inglés | MEDLINE | ID: mdl-36084316

RESUMEN

Muscle atrophy (MA) is a case in which protein degeneration occurs excessively due to an imbalance between protein synthesis and breakdown, and is characterized by decreased muscle mass and weakened muscle strength. Despite mounting concern about MA, the number of patients with MA is increasing every year. The aim of the present study was to assess the impact of Gardeniae Fructus (GF) hot water extract on dexamethasone (DEX)-induced MA in mice. C57BL/6N mice were grouped (n = 8) as follows: Normal mice (Normal), MA mice were treated with distilled water (Control), MA mice were treated with GF 100 mg/kg (GF100), MA mice were treated with GF 200 mg/kg (GF200). For 10 days, DEX (25 mg/kg body weight, i.p.) injection was used to induce MA, and GF was administered. GF treatment restored the muscle weight decreased due to MA, and in particular, the weights of EDL+TA and Sol were significantly increased in the GF200 group. Also, it was confirmed that the swimming time was improved in the GF200 group. In addition, the expression of NADPH oxidase related to oxidative stress was significantly reduced, and protective (insulin-like growth factor I/phosphoinositide 3-kinase/protein kinase B pathway) and catabolic (AMP-activated kinase [AMPK]/sirtuin 1 [SIRT1]/proliferator-activated receptor-gamma coactivator-1α (PGC-1α)-forkhead box O (FOXO) pathway) pathways were significantly modulated. These results demonstrate that GF regulates muscle protein synthesis and catabolic pathways, and in particular, it is judged to improve MA by regulating the proteolytic AMPK/SIRT1/PGC-1α-FOXO pathway.


Asunto(s)
Gardenia , Proteínas Quinasas Activadas por AMP/genética , Proteínas Quinasas Activadas por AMP/metabolismo , Animales , Dexametasona/efectos adversos , Dexametasona/metabolismo , Gardenia/metabolismo , Ratones , Ratones Endogámicos C57BL , Músculo Esquelético/metabolismo , Atrofia Muscular/inducido químicamente , Atrofia Muscular/tratamiento farmacológico , Atrofia Muscular/metabolismo , Coactivador 1-alfa del Receptor Activado por Proliferadores de Peroxisomas gamma/metabolismo , Fosfatidilinositol 3-Quinasas/metabolismo , Sirtuina 1/genética , Sirtuina 1/metabolismo , Agua/metabolismo
16.
Clin Exp Pediatr ; 65(11): 540-546, 2022 Nov.
Artículo en Inglés | MEDLINE | ID: mdl-35914772

RESUMEN

BACKGROUND: Although the benefits of breastfeeding are broadly acknowledged with the efforts of the government and several medical societies, the rate of exclusive breastfeeding through 6 months is lower in Korea than in developed countries. PURPOSE: This study aimed to investigate pediatricians' perceptions of breastfeeding barriers and the current breastfeeding counseling environment and propose government policies to encourage breastfeeding in Korea. METHODS: Fourteen survey questions were developed during meetings of Korean Society of Breastfeeding Medicine experts. The Korean Pediatric Society emailed a structured questionnaire to domestic pediatricians registered as official members of the Korean Pediatric Society on May 4, 2021, and June 3, 2021. This study examined the survey responses received from 168 pediatricians. RESULTS: The 168 respondents included 62 professors, 53 paid doctors, and 53 private physicians. Breastfeeding was recommended by 146 Korean pediatricians (86.9%). However, only 99 responders (59%) currently provide breastfeeding counseling in hospitals. Most respondents stated providing less than 15 minutes of breastfeeding counseling time in the clinic. Moreover, 89.88% of the respondents responded that they would participate in breastfeeding counseling education if an appropriate breastfeeding counseling program was newly established. CONCLUSION: This study showed that, although Korean pediatricians had a positive attitude toward breastfeeding, limited counseling was provided for parents. Along with policy support to improve the medical environment through the establishment of an appropriate breastfeeding counseling program, high-quality counseling and an increased breastfeeding rate are expected.

17.
Cells ; 11(13)2022 06 29.
Artículo en Inglés | MEDLINE | ID: mdl-35805146

RESUMEN

Cells possess membraneless ribonucleoprotein (RNP) granules, including stress granules, processing bodies, Cajal bodies, or paraspeckles, that play physiological or pathological roles. RNP granules contain RNA and numerous RNA-binding proteins, transiently formed through the liquid-liquid phase separation. The assembly or disassembly of numerous RNP granules is strongly controlled to maintain their homeostasis and perform their cellular functions properly. Normal RNA granules are reversibly assembled, whereas abnormal RNP granules accumulate and associate with various neurodegenerative diseases. This review summarizes current studies on the physiological or pathological roles of post-translational modifications of various cellular RNP granules and discusses the therapeutic methods in curing diseases related to abnormal RNP granules by autophagy.


Asunto(s)
Gránulos Citoplasmáticos , Ribonucleoproteínas , Gránulos Citoplasmáticos/metabolismo , Gránulos de Ribonucleoproteínas Citoplasmáticas , Procesamiento Proteico-Postraduccional , Proteínas de Unión al ARN/metabolismo , Ribonucleoproteínas/metabolismo
18.
Biomed Res Int ; 2022: 5780964, 2022.
Artículo en Inglés | MEDLINE | ID: mdl-35572722

RESUMEN

Renal fibrosis is a type of chronic kidney disease (CKD) induced by infiltration of inflammatory cells, myofibroblast accumulation, and ECM production in the kidney. From a long time ago, Corni Fructus (CF) is known to supplement the liver and kidney with its tepid properties. In this study, we investigated the renal protective mechanism of CF, which is known to supplement the kidney, in rat model of unilateral ureteral obstruction (UUO). After inducing UUO through surgery, the group was separated (n = 8) and the drug was administered for 2 weeks; normal rats (normal), water-treated UUO rats (control), CF 100 mg/kg-treated UUO rats (CF100), and CF 200 mg/kg-treated UUO rats (CF200). As a result of histopathological examination of kidney tissue with H&E, MT, and PAS staining, it was confirmed that the infiltration of inflammatory cells and the erosion of collagen were relatively decreased in the kidneys treated with CF. Also, CF significantly reduced the levels of MDA and BUN in serum. As a result of confirming the expression of the factors through western blotting, CF treatment significantly reduced the expression of NADPH oxidase and significantly regulated the AMPK/LKB1/NF-κB pathway associated with inflammation. In addition, it downregulated the expression of major fibrotic signaling factors, such as α-SMA, collagen I, MMP-2, and TIMP-1, and significantly regulated the TGF-ß1/Smad pathway, which is known as a major regulator of renal fibrosis. Taken together, these findings indicate that CF can alleviate renal fibrosis by regulating the TGF-ß1/Smad pathway through inhibition of oxidative stress in UUO.


Asunto(s)
Cornus , Enfermedades Renales , Insuficiencia Renal Crónica , Obstrucción Ureteral , Animales , Fibrosis , Riñón/patología , Enfermedades Renales/metabolismo , Ratas , Insuficiencia Renal Crónica/metabolismo , Proteínas Smad/metabolismo , Factor de Crecimiento Transformador beta1/metabolismo , Obstrucción Ureteral/complicaciones , Obstrucción Ureteral/tratamiento farmacológico , Obstrucción Ureteral/patología
19.
Artículo en Inglés | MEDLINE | ID: mdl-35620406

RESUMEN

Aim: Citrus unshiu peel has been used to treat various diseases in traditional East Asian medicine including Korea, and many studies have been reported regarding inflammatory diseases including ulcerative colitis (UC). However, the underlying mechanism by which Citrus unshiu peel modulates inflammation in UC remains unclear. Therefore, this study aimed to evaluate the therapeutic effect and underlying mechanism of Citrus unshiu peel water extract (CUP) for UC. Methods: The experiment for UC was conducted with 8-week-old male Balb/c mice. After 1 week of adaptation, acute colitis was induced in all groups except the normal group by 5% DSS dissolved in drinking water for 1 week. Balb/c mice were divided into 5 groups (n = 8/group): control group (Control), distilled water-treated group (DSS), 100 mg/kg sulfasalazine-treated group (SASP), 100 mg/kg CUP-treated group (CUPL), and 200 mg/kg CUP-treated group (CUPH). The efficacy of CUP on UC was evaluated by biochemical analyses such as ROS and MPO in serum and MDA in tissues, and expression of proteins related to inflammation and apoptosis was evaluated through Western blot. Results: As a result of confirming the macroscopic changes and H&E staining in colon tissues to confirm the preventive and therapeutic effects of CU, decrease in colon length and inflammatory lesions were inhibited in the CUP-treated group compared to the DSS group. In addition, as a result of serum ROS and tissue MDA analysis and oxidative stress-related protein analysis, it was significantly decreased in the CUP-administered group compared to the control group. In addition, treatment with CUP not only inactivated MAPK, p-IκBα, and NF-κBp65 by blocking the PI3K/Akt pathway but also significantly reduced the expression of inflammatory cytokines. Conclusion: These results show that CUP not only suppresses oxidative stress in UC but also regulates inflammation-related proteins and apoptotic proteins by regulating the PI3K/Akt signaling pathway, suggesting that it has the potential as a material for developing new natural therapeutic agents for UC.

20.
Pediatr Neonatol ; 63(4): 373-379, 2022 07.
Artículo en Inglés | MEDLINE | ID: mdl-35437227

RESUMEN

BACKGROUND: The study aimed to identify factors associated with compliance to follow-up (FU) appointments among infants following their discharge from the neonatal intensive care unit (NICU). METHODS: This retrospective cohort study reviewed 657 infants (birth weight <1500 g or gestational age [GA] <32 weeks), born between 2011 and 2015. A total of 525 eligible infants were classified into two groups: the compliant group (n = 360), who attended clinics from 18 to 24 months, and the non-compliant group (n = 165), who were lost to FU before 18 months. RESULTS: The non-compliant group was more likely to have higher usage rate of assisted reproductive technology (p = 0.023), GA (p < 0.001), weight (p < 0.001), height (p < 0.001), and head circumference (p < 0.001) at birth. The sibling number was higher in the non-compliant group (p = 0.011). Moreover, the non-compliant group demonstrated higher Apgar scores at 1 min and 5 min (p = 0.002 and p = 0.031, respectively). The compliant group was more likely to live in metropolitan or larger cities with a borderline significance (p = 0.056). Furthermore, the non-compliant group was less likely to suffer from respiratory distress syndrome (p < 0.001), patent ductus arteriosus (p = 0.002), retinopathy of prematurity (p = 0.007), necrotizing enterocolitis (p = 0.019), and bronchopulmonary dysplasia (p < 0.001). Moreover, it demonstrated lower postmenstrual age at discharge (p = 0.005) and a shorter length of stay in the NICU (p < 0.001). The compliance with FU appointment varied with the assigned doctor (p < 0.001). The multivariate regression analysis mentioned that the birth weight (OR = 0.903), residence in metropolitan or larger cities (OR = 1.495), and an experience of magnetic resonance imaging (OR = 1.920) were associated with compliance. The compliance to FU appointments was different according to the assigned doctor at admission (OR = 0.357). CONCLUSION: The birth weight, residence in metropolitan or larger cities, an experience of MRI, and the assigned doctors were associated with compliance to FU at a corrected age of 18-24 months.


Asunto(s)
Unidades de Cuidado Intensivo Neonatal , Alta del Paciente , Peso al Nacer , Preescolar , Estudios de Seguimiento , Edad Gestacional , Humanos , Lactante , Recién Nacido , Recién Nacido de muy Bajo Peso , Estudios Retrospectivos
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