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1.
J Med Food ; 2024 Oct 09.
Artigo em Inglês | MEDLINE | ID: mdl-39382491

RESUMO

Saxidomus purpurata extract (SPE) is a highly consumable seafood worldwide with known health-related benefits. However, there are no reports of its' anti-obesity effect. This study explores the potential of SPE for anti-obesity effects by modulating adipogenesis and lipolysis. SPE reduced intracellular lipid and triglyceride accumulation while increasing free glycerol release in adipocytes. SPE inhibited lipogenesis protein expressions and increased the phosphorylation of hormone-sensitive lipase and Adenosine monophosphate-activated protein kinase (AMPK) to promote lipolysis. In addition, SPE suppressed adipogenesis by downregulating protein expression of key adipogenic markers, peroxisome proliferator-activated receptor gamma (PPARγ), CCAAT/enhancer-binding protein α (C/EBPα), and sterol regulatory element-binding protein 1 (SREBP1) via Wnt/ß-catenin signaling. SPE augmented the heme oxygenase-1 (HO-1) expression. Thus, pharmacological intervention with Zinc protoporphyrin (ZnPP-HO-1 antagonist) was employed to validate the HO-1 role. The presence of ZnPP increased the lipid accumulation and reduced the free glycerol release. At the molecular level, adipogenic transcription factors (PPARγ, C/EBPα, and SREBP1) expressions were restored in the presence of ZnPP. GC-MS analysis revealed that SPE was comprised of several fatty acids, contributing to its anti-obesity activity. SPE is an effective nutraceutical that can be used to reduce the progression of obesity. HO-1 expression during adipogenesis might be the mechanism of action for the anti-obesity effect of SPE.

3.
Artigo em Inglês | MEDLINE | ID: mdl-39384358

RESUMO

Background: In-depth investigation is imperative to scrutinize medical costs associated with the periods before and after biopsies for diverse kidney diseases in South Korea. Long-term epidemiological data, including follow-up information, is essential for comparing risks linked to various kidney diseases and their adverse outcomes. Methods: Patients diagnosed with glomerulonephritis (GN), tubulointerstitial nephritis (TIN), and acute tubular necrosis (ATN) at Seoul National University Hospital between 2012 and 2018 were included. We linked the prospective cohort data of biopsy-confirmed kidney disease patients (KORNERSTONE) from our study hospital to the national claims database of Korea, covering both medical events and insured costs. We analyzed medical costs during the periods before and after kidney biopsies, categorized by specific diagnoses, and delved into adverse prognostic outcomes. Results: Our study involved 1,390 patients with biopsy-confirmed GN, TIN, and ATN. After diagnosis, monthly average medical costs increased for most kidney diseases, excluding membranous nephropathy, Henoch-Schönlein purpura, and amyloidosis. The most substantial yearly average medical cost increase was observed in the ATN, acute TIN (ATIN), and chronic TIN (CTIN) groups. Costs rose for most kidney disease categories, except for amyloidosis. Higher myocardial infarction, stroke, and death rates were noted in CTIN, ATIN, and ATN compared to other types, with lupus nephritis displaying the highest end-stage kidney disease progression rate. Conclusion: In South Korea, medical costs for the majority of GN, TIN, and ATN patients increased following kidney biopsy diagnosis. This current data provides valuable epidemiological insights into the medical costs and prognosis of various kidney diseases in the country.

4.
Int J Syst Evol Microbiol ; 74(10)2024 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-39412864

RESUMO

Three Gram-stain-negative, strictly aerobic, non-motile, oxidase- and catalase-positive, short-rod-shaped bacteria, designated as strains G8-12T, SS1-5T and BS5-3T, were isolated from marine algae in South Korea. Strain G8-12T exhibited optimal growth at 20-25 °C, pH 8.0 and 2.0-2.5% (w/v) NaCl, while strains SS1-5T and BS5-3T grew optimally at 25 °C, pH 7.0 and 1.5% NaCl. All strains contained ubiquinone-10 as the sole respiratory quinone, with phosphatidylglycerol and phosphatidylcholine as major polar lipids, and C18 : 1 ω7c and C16 : 0 as major fatty acids (>5 %); C18 : 1 ω7c 11-methyl and C18 : 1 2-OH were additionally identified as major fatty acids in strain SS1-5T. The genomic DNA G+C contents were 57.0, 58.3 and 56.4% for strains G8-12T, SS1-5T and BS5-3T, respectively. Strains G8-12T, SS1-5T and BS5-3T exhibited less than 74.8% average nucleotide identity (ANI) and 19.7% digital DNA-DNA hybridization (dDDH) values with each other, indicating that they represent different species. Phylogenetic analyses based on both 16S rRNA gene and genome sequences revealed that strains G8-12T, SS1-5T and BS5-3T form distinct phylogenetic lineages within the genus Yoonia. Relative to other closely related Yoonia species, these strains exhibited ANI and dDDH values below 83.5 and 26.9%, respectively, suggesting that they constitute novel species within the genus Yoonia. Based on their phenotypic, chemotaxonomic and phylogenetic characteristics, strains G8-12T, SS1-5T and BS5-3T represent three novel species of the genus Yoonia, for which the names Yoonia algicola sp. nov. (G8-12T=KACC 22753T=JCM 35790T), Yoonia rhodophyticola sp. nov. (SS1-5T=KACC 22649T=JCM 35753T) and Yoonia phaeophyticola sp. nov. (BS5-3T=KACC 22648T=JCM 35751T) are proposed, respectively.


Assuntos
Técnicas de Tipagem Bacteriana , Composição de Bases , DNA Bacteriano , Ácidos Graxos , Hibridização de Ácido Nucleico , Filogenia , RNA Ribossômico 16S , Análise de Sequência de DNA , Ubiquinona , RNA Ribossômico 16S/genética , DNA Bacteriano/genética , Ubiquinona/análogos & derivados , República da Coreia , Água do Mar/microbiologia
5.
J Nephrol ; 2024 Oct 16.
Artigo em Inglês | MEDLINE | ID: mdl-39412740

RESUMO

BACKGROUND: Hormone replacement therapy (HRT) is recommended for alleviating vasomotor symptoms or preventing bone loss in postmenopausal women. This study aimed to investigate the impact of hormone replacement therapy on major adverse cardiovascular events, kidney failure, and mortality in women with chronic kidney disease (CKD). METHODS: This population-based cohort study analyzed data from the National Cancer Screening Program and the national health examination of South Korea. Data on postmenopausal women were extracted from the 2009 National Cancer Screening Program. Among these postmenopausal women, those with CKD without kidney replacement therapy were selected through a national health examination from 2009 to 2013. The study outcomes were the risks of major adverse cardiovascular events, kidney failure, and all-cause mortality according to hormone replacement therapy. RESULTS: A total of 768,279 postmenopausal women with CKD were enrolled in this study; of these women, 13.8% (N = 106,052) had a history of hormone replacement therapy. The user and non-user groups differed with respect to baseline characteristics, with the latter being older and having risk factors for cardiovascular disease. After adjustment for confounding factors, the group exposed to hormone replacement therapy showed lower risks of major adverse cardiovascular events, kidney failure, and all-cause mortality. CONCLUSIONS: This study suggests the potential benefits of hormone replacement therapy in postmenopausal women with CKD and highlighted its potential advantages for cardiovascular and kidney outcomes.

6.
Mar Drugs ; 22(9)2024 Sep 15.
Artigo em Inglês | MEDLINE | ID: mdl-39330302

RESUMO

Excessive melanogenesis leads to hyperpigmentation-related cosmetic problems. UV exposure increases oxidative stress, which promotes melanogenesis-related signal pathways such as the PKA, microphthalmia-associated transcription factor (MITF), tyrosinase (TYR), tyrosinase-related protein-1 (TRP1), and tyrosinase-related protein-2 (TRP2) pathways. Glycine is a source of endogenous antioxidants, including glutathione. Fermented fish collagen (FC) contains glycine; thus, we evaluated the effect of FC on decreasing melanogenesis via decreasing oxidative stress. The glycine receptor (GlyR) and glycine transporter-1 (GlyT1) levels were decreased in UV-irradiated keratinocytes; however, the expression levels of these proteins increased upon treatment with FC. The FC decreased oxidative stress, as indicated by the decreasing expression of NOX1/2/4, increased expression of GSH/GSSG, increased SOD activity, and decreased 8-OHdG expression in UV-irradiated keratinocytes. Administration of conditioned media from FC-treated keratinocytes to melanocytes led to decreased p38, PKC, MITF, TRP1, and TRP2 expression. These changes induced by the FC were also observed in UV-irradiated animal skin. FC treatment increased the expression of GlyR and GlyT, which was accompanied by decreased oxidative stress in the UV-irradiated skin. Moreover, the FC negatively regulated the melanogenesis signaling pathways, leading to decreased melanin content in the UV-irradiated skin. In conclusion, FC decreased UV-induced oxidative stress and melanogenesis in melanocytes and animal skin. FC could be used in the treatment of UV-induced hyperpigmentation problems.


Assuntos
Colágeno , Queratinócitos , Melaninas , Estresse Oxidativo , Raios Ultravioleta , Estresse Oxidativo/efeitos dos fármacos , Estresse Oxidativo/efeitos da radiação , Raios Ultravioleta/efeitos adversos , Animais , Melaninas/biossíntese , Colágeno/metabolismo , Humanos , Queratinócitos/efeitos dos fármacos , Queratinócitos/efeitos da radiação , Queratinócitos/metabolismo , Peixes , Fermentação , Melanócitos/efeitos dos fármacos , Melanócitos/metabolismo , Melanócitos/efeitos da radiação , Antioxidantes/farmacologia , Transdução de Sinais/efeitos dos fármacos , Pele/efeitos dos fármacos , Pele/metabolismo , Pele/efeitos da radiação , Melanogênese
7.
Medicina (Kaunas) ; 60(9)2024 Sep 02.
Artigo em Inglês | MEDLINE | ID: mdl-39336475

RESUMO

Background and Objectives: Fine particulate matter, PM2.5, is becoming a major threat to human health, particularly in terms of respiratory diseases. Pyroptosis is a recently discovered and distinct form of cell death, characterized by pore formation in the cell membrane and secretions of proinflammatory cytokines. There has been little research on the effect of PM2.5 on pyroptosis, especially in airway epithelium. We investigated whether PM2.5-related oxidative stress induces pyroptosis in bronchial epithelial cells and defined the underlying mechanisms. Materials and Methods: After exposure of a BEAS-2B cell line to PM2.5 concentration of 20 µg/mL, reactive oxygen species (ROS) levels, parameters related to pyroptosis, and NF-κB signaling were measured by Western blotting, immunofluorescence, and ELISA (Enzyme-linked immunosorbent assay). Results: PM2.5 induced pyroptotic cell death, accompanied by LDH (Lactate dehydrogenase) release and increased uptake of propidium iodide in a dose-dependent manner. PM2.5 activated the NLRP3-casp1-gasdermin D pathway, with resulting secretions of the proinflammatory cytokines IL-1ß and IL-18. The pyroptosis activated by PM2.5 was alleviated significantly by NLRP3 inhibitor. In PM2.5-exposed BEAS-2B cells, levels of intracellular ROS and NF-κB p65 increased. ROS scavenger inhibited the expression of the NLRP3 inflammasome, and the NF-κB inhibitor attenuated pyroptotic cell death triggered by PM2.5 exposure, indicating that the ROS/NF-κB pathway is involved in PM2.5-induced pyroptosis. Conclusions: These findings show that PM2.5 exposure can cause cell injury by NLRP3-inflammasome-mediated pyroptosis by upregulating the ROS/NF-κB pathway in airway epithelium.


Assuntos
Células Epiteliais , NF-kappa B , Proteína 3 que Contém Domínio de Pirina da Família NLR , Material Particulado , Piroptose , Espécies Reativas de Oxigênio , Transdução de Sinais , Piroptose/efeitos dos fármacos , Piroptose/fisiologia , Humanos , Material Particulado/efeitos adversos , Espécies Reativas de Oxigênio/metabolismo , NF-kappa B/metabolismo , Transdução de Sinais/efeitos dos fármacos , Células Epiteliais/efeitos dos fármacos , Células Epiteliais/metabolismo , Proteína 3 que Contém Domínio de Pirina da Família NLR/metabolismo , Linhagem Celular , Brônquios/efeitos dos fármacos , Brônquios/metabolismo , Estresse Oxidativo/efeitos dos fármacos , Interleucina-1beta/metabolismo , Interleucina-18/metabolismo
8.
Pathogens ; 13(9)2024 Aug 28.
Artigo em Inglês | MEDLINE | ID: mdl-39338920

RESUMO

Caseous lymphadenitis (CLA) is a chronic and subclinical bacterial disease of ruminants caused by Corynebacterium pseudotuberculosis (C. pseudotuberculosis) infection. Until 2014, there were no reports of CLA outbreaks in South Korea; however, the prevalence of CLA cases has steadily increased. In this study, we used recently obtained field isolates to develop the first inactivated CLA vaccine in South Korea and evaluated it in various animal models. The inactivated vaccine was evaluated for virulence and effectiveness. Mice were tested for virulence and immunization challenges, and guinea pigs and Korean Native Black Goats (KNBGs) evaluated various vaccine concentrations to determine the optimal dose and effectiveness. In the case of KNBGs, clinical symptoms were not observed after vaccination. In addition, CLA-specific IgG was detected at a significantly (p < 0.05) high level and was maintained. In histopathological evaluations, inflammation was predominantly observed in the prefemoral lymph nodes in the non-vaccinated+CHAL group. The genetic diversity of C. pseudotuberculosis, which has become widespread in South Korea, is less than 0.5% our vaccine is expected to prevent infection by a wide range of strains effectively. In summary, our CLA vaccine can potentially prevent CLA and foster the growth of South Korea's domestic KNBG industry.

9.
bioRxiv ; 2024 Sep 06.
Artigo em Inglês | MEDLINE | ID: mdl-39282427

RESUMO

APOBEC3 (or A3) enzymes have emerged as potential therapeutic targets due to their role in introducing heterogeneity in viruses and cancer, often leading to drug resistance. Inhibiting these enzymes has remained elusive as initial phosphodiester (PO) linked DNA based inhibitors lack stability and potency. We have enhanced both potency and nuclease stability, of 2'-deoxy-zebularine (dZ), substrate-based oligonucleotide inhibitors for two critical A3's: A3A and A3G. While replacing the phosphate backbone with phosphorothioate (PS) linkages increased nuclease stability, fully PS-modified inhibitors lost potency (1.4-3.7 fold) due to the structural constraints of the active site. For both enzymes, mixed PO/PS backbones enhanced potency (2.3-9.2 fold), while also vastly improving nuclease resistance. We also strategically introduced 2'-fluoro sugar modifications, creating the first nanomolar inhibitor of A3G-CTD2. With hairpin-structured inhibitors containing optimized PS patterns and LNA sugar modifications, we characterize the first single-digit nanomolar inhibitor targeting A3A. These extremely potent A3A inhibitors, were highly resistant to nuclease degradation in serum stability assays. Overall, our optimally designed A3 oligonucleotide inhibitors show improved potency and stability, compared to previous attempts to inhibit these critical enzymes, opening the door to realize the therapeutic potential of A3 inhibition.

10.
Virus Res ; 350: 199471, 2024 Sep 25.
Artigo em Inglês | MEDLINE | ID: mdl-39306246

RESUMO

As COVID-19 has become endemic, SARS-CoV-2 variants are becoming increasingly diverse, underscoring the escalating importance of global genomic surveillance. This study analyzed 86,762 COVID-19 samples identified in the Republic of Korea from September 2022 to November 2023. The results revealed a consistent increase in the prevalence of the XBB variants following the dominance of BN.1, with various XBB sub-lineages co-circulating in the Republic of Korea. The overall nucleotide diversity (π) among the SARS-CoV-2 genomes was 0.00155. Evolutionary analysis revealed that the average time interval between the first detection and estimated date of the most recent common ancestor of Korean XBB sub-lineages was 47 d, suggesting that the novel variants were efficiently identified in the Korean surveillance system. The mutation rate was determined to be in the range of 5.6 × 10-4 to 9.1 × 10-4 substitutions/site/year. In conclusion, this study provides insights into the genetic diversity and evolutionary interpretation of the XBB sub-lineages during the XBB wave in the Republic of Korea, highlighting the importance of continued genomic surveillance for emerging variants.

11.
Spectrochim Acta A Mol Biomol Spectrosc ; 326: 125166, 2024 Sep 21.
Artigo em Inglês | MEDLINE | ID: mdl-39342719

RESUMO

In this study, we introduce novel colorimetric pH-sensing probes based on naphthalimide malonate derivatives. These probes were synthesized by reacting 4-bromo-1,8-naphthalimide with various malonates, including malononitrile, ethyl cyanoacetate, and diethyl malonate. Each derivative exhibited distinct pH-sensing characteristics due to their differing CH acidities. The malononitrile-based probe, NPI-N2, demonstrated pronounced chromogenic pH-signaling behavior, transitioning from colorless to red-violet, accompanied by a decrease in fluorescence intensity. Notably, NPI-N2 retained its pH-sensing capability in the presence of common metal ions, anions, and pepsin, a key component of gastric fluid. The pKa of NPI-N2 was determined to be 3.08 through pH-dependent absorbance curve fitting. To modulate the pH-sensing range, ester-nitrile (NPI-EN) and diethyl ester (NPI-E2) subunits were incorporated into the naphthalimide framework, resulting in increased pKa values of 6.73 and 10.76, respectively. The pH-signaling mechanism of NPI-N2 was elucidated by 1H and 13C NMR spectroscopy, revealing deprotonation of the malononitrile moiety and subsequent resonance extension through the naphthalimide structure. To facilitate practical pH determination, NPI-N2 was integrated into a paper-based test strip, enabling convenient and reliable pH measurement of artificial gastric fluid.

12.
Carbohydr Polym ; 345: 122546, 2024 Dec 01.
Artigo em Inglês | MEDLINE | ID: mdl-39227091

RESUMO

Herein, dexamethasone (DEX) nanocrystalline suspension (NS)-embedded hydrogel (NS-G) was constructed using a hydroxypropyl methylcellulose (HPMC) polymer to enhance cochlear delivery and attenuate hearing loss following intratympanic (IT) injection. Hydrophobic steroidal nanocrystals were prepared using a bead milling technique and incorporated into a polysaccharide hydrogel. The NS-G system with HPMC (average molecular weight, 86,000 g/mol; 15 mg/mL) was characterized as follows: rod-shaped drug crystalline; particle size <300 nm; and constant complex viscosity ≤1.17 Pa·s. Pulverization of the drug particles into submicron diameters enhanced drug dissolution, while the HPMC matrix increased the residence time in the middle ear cavity, exhibiting a controlled release profile. The IT NS-G system elicited markedly enhanced and prolonged drug delivery (> 9 h) to the cochlear tissue compared with that of DEX sodium phosphate (DEX-SP), a water-soluble prodrug. In mice with kanamycin- and furosemide-induced ototoxicity, NS-G markedly enhanced hearing preservation across all frequencies (8-32 kHz), as revealed by an auditory brainstem response test, compared with both saline and DEX-SP. Moreover, treatment with NS-G showed enhanced anti-inflammatory effects, as evidenced by decreased levels of inflammation-related cytokines. Therefore, the IT administration of DEX NS-loaded HPMC hydrogels is a promising strategy for treating hearing loss.


Assuntos
Cóclea , Dexametasona , Perda Auditiva , Hidrogéis , Derivados da Hipromelose , Injeção Intratimpânica , Nanopartículas , Dexametasona/química , Dexametasona/administração & dosagem , Animais , Derivados da Hipromelose/química , Hidrogéis/química , Nanopartículas/química , Camundongos , Cóclea/efeitos dos fármacos , Cóclea/patologia , Perda Auditiva/tratamento farmacológico , Perda Auditiva/induzido quimicamente , Liberação Controlada de Fármacos , Masculino , Sistemas de Liberação de Medicamentos/métodos
13.
J Hazard Mater ; 480: 135815, 2024 Sep 11.
Artigo em Inglês | MEDLINE | ID: mdl-39278036

RESUMO

Nano- and microplastics (NMPs), ubiquitous in the environment, pose significant health risks. We report for the first time a comprehensive study using in-vitro, in-vivo, and ex-vivo models to investigate the penetration and inflammatory effects of fragmented polystyrene (fPS) on human skin, including the analysis of both penetration depth and fPS amounts that penetrate the skin. Human keratinocyte (HaCaT) and human dermal fibroblast (HDF) cells exposed to fPS exhibited notable internalization and cytotoxicity. In a 3D human skin model, fPS particles penetrated the dermal layer within one hour, with an average maximum penetration of 4.7 µg for particles smaller than 2 µm. Similarly, mouse dorsal skin and human abdominal skin models confirmed fPS penetration. RNA sequencing revealed substantial upregulation of inflammatory genes, including IL-1α, IL-1ß, IL-18, IL-6, IL-8, ICAM-1, FOS, and JUN, following fPS exposure. These findings were validated at both the mRNA and protein levels, indicating a robust inflammatory response. Notably, the inflammatory response in both the 3D human skin and mouse models increased in a dose-dependent manner, underscoring the toxicological impact of fPS on skin health. This study provides crucial insights into the mechanisms through which NMPs affect human health and underscores the need for further research to develop effective mitigation strategies.

14.
Small Methods ; : e2400310, 2024 Sep 03.
Artigo em Inglês | MEDLINE | ID: mdl-39225357

RESUMO

Lead-based halide perovskites have gained significant prominence in recent years in optoelectronics and photovoltaics, owing to their exceptional optoelectronic properties. Nonetheless, the toxicity of lead (Pb) and the stability concern pose obstacles to their potential for future large-scale market development. Herein, stable lead-free Cs3Bi2I9 (CBI) films are presented with smooth and compact morphologies synthesized via chemical vapor deposition (CVD), demonstrating their application as an UV photodetector in a self-powered way. The self-powered photodetectors (SPDs) exhibit remarkable characteristics, including a responsivity of 1.57 A W-1 and an impressive specific detectivity of 3.38 × 1013 Jones under the illumination of 365 nm at zero bias. Furthermore, the SPDs exhibit a nominal decline (≈2.2%) in the photocurrent under constant illumination over 500 h, highlighting its impressive long-term operational stability. Finally, the real-time UV-detection capability of the device is demonstrated by measuring the photocurrent under various conditions, including room light and sunlight at different times. These findings offer a new platform for synthesizing stable and high-quality perovskite films, and SPDs for advancing the development of wearable and portable electronics.

15.
J Korean Med Sci ; 39(36): e250, 2024 Sep 23.
Artigo em Inglês | MEDLINE | ID: mdl-39315442

RESUMO

BACKGROUND: Achieving a definitive genetic diagnosis of unexplained multiple congenital anomalies (MCAs) in neonatal intensive care units (NICUs) infants is challenging because of the limited diagnostic capabilities of conventional genetic tests. Although the implementation of whole genome sequencing (WGS) has commenced for diagnosing MCAs, due to constraints in resources and faculty, many NICUs continue to utilize chromosomal microarray (CMA) and/or karyotyping as the initial diagnostic approach. We aimed to evaluate the diagnostic efficacy of WGS in infants with MCAs who have received negative results from karyotyping and/or CMA. METHODS: In this prospective study, we enrolled 80 infants with MCAs who were admitted to a NICU at a single center and had received negative results from CMA and/or karyotyping. The phenotypic characteristics were classified according to the International Classification of Diseases and the Human Phenotype Ontology. We assessed the diagnostic yield of trio-WGS in infants with normal chromosomal result and explored the process of diagnosing by analyzing both phenotype and genotype. Also, we compared the phenotype and clinical outcomes between the groups diagnosed with WGS and the undiagnosed group. RESULTS: The diagnostic yield of WGS was 26% (21/80), of which 76% were novel variants. There was a higher diagnostic yield in cases of craniofacial abnormalities, including those of the eye and ear, and a lower diagnostic yield in cases of gastrointestinal and genitourinary abnormalities. In addition, higher rates of rehabilitation therapy and gastrostomy were observed in WGS-diagnosed infants than in undiagnosed infants. CONCLUSION: This prospective cohort study assessed the usefulness of trio-WGS following chromosomal analysis for diagnosing MCAs in the NICU and revealed improvements in the diagnostic yield and clinical utility of WGS.


Assuntos
Anormalidades Múltiplas , Cariotipagem , Sequenciamento Completo do Genoma , Humanos , Recém-Nascido , Estudos Prospectivos , Masculino , Feminino , Anormalidades Múltiplas/genética , Anormalidades Múltiplas/diagnóstico , Fenótipo , Unidades de Terapia Intensiva Neonatal , Lactente , Genótipo , Testes Genéticos/métodos
16.
Nat Biotechnol ; 2024 Sep 25.
Artigo em Inglês | MEDLINE | ID: mdl-39322763

RESUMO

In primary cell types, intracellular deoxynucleotide triphosphate (dNTP) levels are tightly regulated in a cell cycle-dependent manner. We report that prime editing efficiency is increased by mutations that improve the enzymatic properties of Moloney murine leukemia virus reverse transcriptase and treatments that increase intracellular dNTP levels. In combination, these modifications produce substantial increases in precise editing rates.

17.
Ultrasound Med Biol ; 2024 Sep 20.
Artigo em Inglês | MEDLINE | ID: mdl-39306481

RESUMO

PURPOSE: This study aimed to evaluate the effectiveness of two contrast agents, SonoVue (SV) and Sonazoid (SZ), by comparing them intra-individually in contrast-enhanced ultrasound (CEUS)-CT/MRI fusion imaging (FI) to improve the visibility of inconspicuous liver malignancies on B-mode sonography for guiding percutaneous radiofrequency ablation (RFA). Additionally, the radiologists' preference between SonoVue- CT/MRI FI (SV-FI) and Sonazoid-CT/MRI FI (SZ-FI) was determined. METHODS: This prospective study enrolled 23 patients with inconspicuous hepatic malignancies (≤ 3 cm) on B-mode US who underwent both SV-FI and SZ-FI for RFA guidance. The patients underwent real-time CEUS FI with CT/MRI on the same day, utilizing both SV and SZ with at least 15-min intervals. Tumor visibility and radiologists' preferences were assessed and graded using a 4-point scale during the dynamic phases of both SV-FI and SZ-FI and the Kupffer phase of SZ-FI. RESULTS: The tumor visibility scores obtained from CEUS-CT/MRI FI were significantly better than those obtained from US-FI. Indeed, SV-FI and SZ-FI demonstrated comparable visibility scores when corresponding phases were compared (p > 0.05). However, the Kupffer phase images of SZ-FI displayed superior visibility scores (3.70 ± 0.56 vs. 2.96 ± 0.88; p = 0.002) than the late vascular phase images of SV-FI. The radiologists favored SZ-FI in many cases, exhibiting moderate inter-observer agreement (Kappa value = 0.587; 95% CI, 0.403-0.772). CONCLUSION: Although CEUS-CT/MRI FI with either SV or SZ substantially improved the visibility of inconspicuous tumors on US-CT/MRI FI, radiologists preferred SZ to SV to guide the RFA procedure.

18.
Sci Total Environ ; 954: 176438, 2024 Sep 20.
Artigo em Inglês | MEDLINE | ID: mdl-39307361

RESUMO

The objectives of this study were to produce biochars using sulfur-rich acidified lignin discharged from a biorefinery process and to evaluate their physicochemical properties and Pb adsorption capacity. As the pyrolysis temperature increased, the lignin acidified by the desulfurization process was converted to neutralized biochar (LBC), which exhibited high carbon content and stability. The carbon content of biochar manufactured at a pyrolysis temperature of 600 °C or higher was over 90 % and showed no significant difference, and their surface structures were found to be different, as revealed through XRD and FTIR analyses. The adsorption capacity of Pb by LBC increased with increasing pyrolysis temperature, and their adsorption capacity was well described by the pseudo-second-order model and the Langmuir isotherm adsorption model. In particular, the internal diffusion effect on the adsorption capacity of Pb was greater for LBC900 than for LBC600. In complex heavy metal solutions, LBC selectively exhibited high affinity for Pb, while the adsorption capacity of other metals was significantly reduced. The adsorption mechanism of Pb by LBC was verified through various analytical methods, and these results demonstrated that the adsorption of Pb by LBC was influenced by functional groups existing on the surface and inside of LBC and by some cation exchange.

19.
Artigo em Inglês | MEDLINE | ID: mdl-39264709

RESUMO

A Gram-stain-negative, yellow-pigmented, and strictly aerobic bacterium, designated as strain MSW5T, was isolated from seawater of the Yellow Sea in South Korea. The cells were non-motile rods exhibiting oxidase- and catalase-positive activities. Growth was observed at 15-25 °C (optimum, 25 °C) and pH 5.0-9.0 (optimum, pH 7.0-8.0) and in the presence of 1.0-5.0% (w/v) NaCl (optimum, 2.0%). Menaquinone-6 was the sole respiratory quinone, and iso-C15 : 0, summed feature 3 (C16 : 1 ω7c and/or C16 : 1 ω6c), iso-C15 : 0 3-OH, and C15 : 1 ω6c were the major cellular fatty acids. Major polar lipids included phosphatidylethanolamine, two unidentified aminolipids, and three unidentified lipids. Phylogenetic analyses based on 16S rRNA gene sequences and 92 concatenated core protein sequences revealed that strain MSW5T formed a distinct lineage within the genus Polaribacter. The genome of strain MSW5T was 3582 kb in size with a 29.1 mol% G+C content. Strain MSW5T exhibited the highest similarity to Polaribacter atrinae WP25T, with a 97.9% 16S rRNA gene sequence similarity. However, the average nucleotide identity and digital DNA-DNA hybridization values were 79.4 and 23.3%, respectively, indicating that strain MSW5T represents a novel species. Based on its phenotypic, chemotaxonomic, and phylogenetic characteristics, strain MSW5T is proposed to represent a novel species, with the name Polaribacter ponticola sp. nov. The type strain is MSW5T (=KACC 22340T=NBRC 116025T). In addition, whole genome sequence comparisons and phenotypic features suggested that Polaribacter sejongensis and Polaribacter undariae belong to the same species, with P. undariae proposed as a later heterotypic synonym of P. sejongensis. An emended description of Polaribacter sejongensis is also proposed.


Assuntos
Técnicas de Tipagem Bacteriana , Composição de Bases , DNA Bacteriano , Ácidos Graxos , Filogenia , RNA Ribossômico 16S , Água do Mar , Análise de Sequência de DNA , Vitamina K 2 , RNA Ribossômico 16S/genética , Ácidos Graxos/análise , Água do Mar/microbiologia , República da Coreia , DNA Bacteriano/genética , Vitamina K 2/análogos & derivados , Vitamina K 2/análise , Fosfatidiletanolaminas , Hibridização de Ácido Nucleico , Bacteroidetes/genética , Bacteroidetes/classificação , Bacteroidetes/isolamento & purificação , Fosfolipídeos/análise , Fosfolipídeos/química
20.
Front Oncol ; 14: 1442737, 2024.
Artigo em Inglês | MEDLINE | ID: mdl-39267822

RESUMO

Background: Pancreatic cancer (PC), sometimes referred to as pancreatic ductal adenocarcinoma (PDAC), is a major cause of global mortality from cancer. Pancreatic cancer is a very aggressive and devastating kind of cancer, characterized by limited options for therapy and low possibilities of survival. Sulforaphane (SFN), a naturally occurring sulfur-containing compound, is believed to possess anti-inflammatory, anti-obesity, and anti-cancer characteristics. Objective: However, efficient preventative and treatment measures are essential and SFN has been studied for its ability to suppress pancreatic cancer cell proliferation and induce apoptosis. Methods: Here, SFN induced cytotoxicity and apoptosis in PDAC cell lines such as MIA PaCa-2 and PANC-1 cells, as evaluated by cytotoxicity, colony formation, western blot analysis, fluorescence-activated cell sorting (FACS), reactive oxygen species (ROS) detection, caspase-3 activity assay, immunofluorescence assay, and mitochondrial membrane potential assay. Results: In MIA PaCa-2 and PANC-1 cells, SFN inhibited cell survival and proliferation in a dose-dependent manner. The activation of caspase zymogens results in cleaved PARP and cleaved caspase-3, which is associated with an accumulation in the sub G1 phase. Furthermore, SFN increased ROS level and γH2A.X expression while decreasing mitochondrial membrane potential (ΔΨm). Notably, the ROS scavenger N-Acetyl-L-cysteine (NAC) was shown to reverse SFN-induced cytotoxicity and ROS level. Subsequently, SFN-induced cell cycle arrest and apoptosis induction as a Trojan horse to eliminate pancreatic cancer cells via ROS-mediated pathways were used to inhibit pancreatic cancer cells. Conclusion: Collectively, our data demonstrates that SFN-induced cell death follows the apoptosis pathway, making it a viable target for therapeutic interventions against pancreatic cancer.

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