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1.
Plants (Basel) ; 13(3)2024 Jan 31.
Artigo em Inglês | MEDLINE | ID: mdl-38337952

RESUMO

The growing beekeeping industry in South Korea has led to the establishment of new honey plant complexes. However, studies on honey production from each species are limited. This study aimed to assess the honey production potential of various Brassica napus cultivars and two wildflower species. The nectar characteristics of B. napus varied significantly among the cultivars. Absolute sugar concentrations differed among the cultivars, but sugar composition ratios were similar. In contrast, the amino acid content remained relatively uniform regarding percentage values, irrespective of the absolute concentrations. Estimations of honey potential production per hectare (kg/ha) resulted in the following ranking among cultivars: 'JM7003' (107.1) > 'YS' (73.0) > 'JM7001' (63.7) > 'TL' (52.7) > 'TM' (42.4). The nectar volume of Pseudolysimachion rotundum var. subintegrum and Leonurus japonicus increased during the flowering stage. P. rotundum var. subintegrum was sucrose-rich and L. japonicus was sucrose-dominant. Both species predominantly contained phenylalanine, P. rotundum var. subintegrum had glutamine as the second most abundant amino acid, and L. japonicus had tyrosine. The honey production potential was 152.4 kg/ha for P. rotundum var. subintegrum and 151.3 kg/ha for L. japonicus. These findings provide a basis for identifying food resources for pollinators and selecting plant species to establish honey plant complexes.

2.
Am J Case Rep ; 25: e941221, 2024 Jan 18.
Artigo em Inglês | MEDLINE | ID: mdl-38234083

RESUMO

BACKGROUND Myositis is an inflammatory myopathy that can be caused by a variety of drugs, diseases, and toxins. The U.S. military uses chemoprophylaxis with intramuscular penicillin G to prevent group A streptococcal infection. We present a case of penicillin G-induced myositis, a rare cause of drug-induced myositis with limited discussion in the medical literature. CASE REPORT A 25-year-old man with no pertinent medical history presented to the Emergency Department with right hip and leg pain after receiving a single dose of intramuscular penicillin G as part of standard prophylaxis for group A streptococcal infection during basic military training. He reported pain and leg weakness that was exacerbated by physical exertion and weight bearing but had no systemic symptoms, such as fevers or chills. Initial radiographs of the hip were normal; however, subsequent magnetic resonance imaging of the hip revealed intramuscular edema and features consistent with myositis of the right proximal thigh and hip musculature. He was admitted for isolated right gluteal myositis, attributed to his preceding local penicillin injection. He recovered with symptomatic care over the following 2 weeks, with return to baseline function. CONCLUSIONS This case highlights a rare complication of intramuscular penicillin G as a cause of acute isolated myositis. It serves to inform physicians of this rare complication and to recommend the consideration of intramuscular penicillin G as a causative etiology in individuals presenting with myositis and recent penicillin G exposure.


Assuntos
Militares , Miosite , Infecções Estreptocócicas , Masculino , Humanos , Adulto , Penicilina G Benzatina/efeitos adversos , Quimioprevenção , Infecções Estreptocócicas/tratamento farmacológico , Dor , Injeções Intramusculares/efeitos adversos , Miosite/induzido quimicamente , Miosite/diagnóstico , Miosite/tratamento farmacológico
3.
Nutrition ; 119: 112304, 2024 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-38154397

RESUMO

OBJECTIVE: Optical spectroscopy-measured skin carotenoid status (SCS) has been validated for estimating fruit and vegetable (F&V) intake; however, there is limited research addressing SCS kinetics in whole-diet interventions. The aim of this controlled feeding trial was to explore SCS's response to carotenoid intake changes via whole-diet intervention, evaluating its biomarker potential. METHODS: Eighty participants ages 20 to 49 y, without underlying diseases, were randomly allocated to the high-carotenoid group (HG; n = 40) or control group (CG; n = 40). The HG consumed a high-carotenoid diet (21 mg total carotenoids/2000 kcal), whereas the CG consumed a control diet (13.6 mg total carotenoids/2000 kcal) for 6 wk. Subsequently, skin and blood carotenoid concentrations were tracked without intervention for 4 wk. SCS was measured weekly via resonance Raman spectroscopy, and serum carotenoid concentrations were analyzed biweekly using high-performance liquid chromatography. Baseline carotenoid and F&V intakes were assessed via a 3-d diet record. The kinetics of SCS and serum carotenoid concentrations were analyzed using a weighted generalized estimating equation. Pearson's correlation analyses were used to examine baseline correlations between SCS and dietary carotenoid and F&V intakes, as well as serum carotenoid concentrations. RESULTS: During the intervention, the HG showed a faster and greater SCS increase than the CG (difference in slope per week = 8.87 AU, Pinteraction <0.001). Baseline SCS had positive correlations with total carotenoid intake (r = 0.45), total F&V intake (r = 0.49), and total serum carotenoid concentration (r = 0.79; P < 0.001 for all). CONCLUSION: These results suggest that SCS is a valid biomarker for monitoring changes in carotenoid intake through whole diet, which supports using SCS for assessing carotenoid-rich F&V intake.


Assuntos
Frutas , Verduras , Humanos , Biomarcadores , Carotenoides/análise , Dieta/métodos , Ingestão de Alimentos , Frutas/química , Pele/química , Verduras/química , Adulto Jovem , Adulto , Pessoa de Meia-Idade
4.
Adv Mater ; 36(14): e2309183, 2024 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-38160321

RESUMO

Development of miniaturized thin-film lithium-ion batteries (TF-LIBs) using vacuum deposition techniques is crucial for low-scale applications, but addressing low energy density remains a challenge. In this work, structures analogous to SiOx-based thin-film electrodes are designed with close resemblance to traditional LIB slurry formulations including active material, conductive agent, and binder. The thin-film is produced using mid-frequency sputtering with a single hybrid target consisting of SiOx nanoparticles, carbon nanotubes, and polytetrafluoroethylene. The thin-film SiOx/PPFC (plasma-polymerized fluorocarbon) involves a combination of SiOx and conductive carbon within the PPFC matrix. This results in enhanced electronic conductivity and superior elasticity and hardness in comparison to a conventional pure SiOx-based thin-film. The electrochemical performance of the half-cell consisting of thin-film SiOx/PPFC demonstrates remarkable cycling stability, with a capacity retention of 74.8% up to the 1000th cycle at 0.5 C. In addition, a full cell using the LiNi0.6Co0.2Mn0.2O2 thin-film as the cathode material exhibits an exceptional initial capacity of ≈120 mAh g-1 at 0.1 C and cycle performance, marked by a capacity retention of 90.8% from the first cycle to the 500th cycle at a 1 C rate. This work will be a stepping stone for the AM/CB/B composite electrodes in TF-LIBs.

5.
ACS Appl Mater Interfaces ; 15(40): 47229-47237, 2023 Oct 11.
Artigo em Inglês | MEDLINE | ID: mdl-37782228

RESUMO

Neuromorphic computing, an innovative technology inspired by the human brain, has attracted increasing attention as a promising technology for the development of artificial intelligence systems. This study proposes synaptic transistors with a Li1-xAlxTi2-x(PO4)3 (LATP) layer to analyze the conductance modulation linearity, which is essential for weight mapping and updating during on-chip learning processes. The high ionic conductivity of the LATP electrolyte provides a large hysteresis window and enables linear weight update in synaptic devices. The results demonstrate that optimizing the LATP layer thickness improves the conductance modulation and linearity of synaptic transistors during potentiation and degradation. A 20 nm-thick LATP layer results in the most nonlinear depression (αd = -6.59), whereas a 100 nm-thick LATP layer results in the smallest nonlinearity (αd = -2.22). Additionally, a device with the optimal 100 nm-thick LATP layer exhibits the highest average recognition accuracy of 94.8% and the smallest fluctuation, indicating that the linearity characteristics of a device play a crucial role in weight update during learning and can significantly affect the recognition accuracy.

6.
J Korean Med Sci ; 38(26): e200, 2023 Jul 03.
Artigo em Inglês | MEDLINE | ID: mdl-37401495

RESUMO

BACKGROUND: The nuclear factor erythroid 2-related factor 2/Kelch-like ECH-associated protein 1 (Nrf2/Keap1) signaling pathway is involved in the regulation of cellular responses to oxidative stress. Nrf2 acts as a cell protector from inflammation, cellular damage, and tumorigenesis, whereas Keap1 is a negative regulator of Nrf2. Dysregulation of the Nrf2/Keap1 pathway results in tumorigenesis and the active metabolism of tumor cells, leading to high resistance to radiotherapy. This study aimed to evaluate the predictive role of Nrf2 and Keap1 in the radiosensitivity and prognosis of locally advanced rectal cancer (LARC). METHODS: In total, 90 patients with LARC underwent surgery after preoperative chemoradiotherapy (CRT). Endoscopic biopsies from the tumors were obtained before radiation, and the Nrf2 and Keap1 expressions were assessed by immunohistochemistry. The response to therapy was evaluated after surgery following CRT according to the pathologic tumor regression grade. The disease-free survival (DFS) and overall survival rates were also documented. The association between the Nrf2 and Keap1 immunoreactivity and the clinicopathological parameters was analyzed. RESULTS: The overexpression of the nuclear Nrf2 before CRT showed a significant correlation with better DFS. The cytoplasmic Nrf2 expression was associated with more residual tumors after radiotherapy and a more unfavorable DFS, indicating lower radiosensitivity. CONCLUSION: CRT is an important issue in LARC and is a major aspect of treatment. Thus, the Nrf2/Keap1 expression may be a potential predictor of preoperative therapeutic resistance. The Nrf2-Keap1 modulators that interact with each other may also be effectively applicable to CRT effect in LARC.


Assuntos
Fator 2 Relacionado a NF-E2 , Neoplasias Retais , Humanos , Proteína 1 Associada a ECH Semelhante a Kelch/metabolismo , Fator 2 Relacionado a NF-E2/análise , Fator 2 Relacionado a NF-E2/metabolismo , Prognóstico , Carcinogênese , Neoplasias Retais/radioterapia
7.
Case Rep Ophthalmol ; 14(1): 34-38, 2023.
Artigo em Inglês | MEDLINE | ID: mdl-36741294

RESUMO

Here, we report the case of a patient with multiple parallel-line endotheliitis with myopic shift, which has not been previously reported. A 36-year-old man visited our clinic with blurred vision in his left eye. A slit lamp examination revealed an interesting pattern of multiple parallel lines of keratic precipitates, along with subtle corneal edema. The spherical equivalents measured in the right and left eyes were -9.25 and -11.875 diopter, respectively, with the left eye showing more myopic progression. On specular microscopy, endothelial cell loss was found in the left eye. After administration of a weak topical steroid, keratic precipitates and corneal edema resolved completely within 2 days. The myopic shift in his left eye recovered to -10.0 diopters. Multiple parallel-line endotheliitis can be easily treated with a weak topical steroid in a short period. A temporary myopic shift may occur, which in this case resolved upon disease recovery. However, corneal endothelial cell loss is inevitable; therefore, careful monitoring is needed.

8.
J Pathol Transl Med ; 57(1): 60-66, 2023 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-36623814

RESUMO

Fibrosis is characterized by a proliferation of fibroblasts and excessive extracellular matrix following chronic inflammation, and this replacement of organ tissue with fibrotic tissue causes a loss of function. Inflammatory bowel disease (IBD) is a chronic inflammation of the gastrointestinal tract, and intestinal fibrosis is common in IBD patients, resulting in several complications that require surgery, such as a stricture or penetration. This review describes the pathogenesis and various factors involved in intestinal fibrosis in IBD, including cytokines, growth factors, epithelial-mesenchymal and endothelial-mesenchymal transitions, and gut microbiota. Furthermore, histopathologic findings and scoring systems used for stenosis in IBD are discussed, and differences in the fibrosis patterns of ulcerative colitis and Crohn's disease are compared. Biomarkers and therapeutic agents targeting intestinal fibrosis are briefly mentioned at the end.

10.
ACS Appl Mater Interfaces ; 15(1): 1525-1534, 2023 Jan 11.
Artigo em Inglês | MEDLINE | ID: mdl-36538477

RESUMO

The top-gate structure is currently adopted in various flat-panel displays because of its diverse advantages such as passivation from the external environment and process compatibility with industries. However, the mobility of the currently commercialized top-gate oxide thin-film transistors (TFTs) is insufficient to drive ultrahigh-resolution displays. Accordingly, this work suggests metal-capped Zn-Ba-Sn-O transistors with top-gate structures for inducing mobility-enhancing effects. The fabricated top-gate device contains para-xylylene (PPx), which is deposited by a low-temperature chemical vapor deposition (CVD) process, as a dielectric layer and exhibits excellent interfacial and dielectric properties. A technology computer-aided design (TCAD) device simulation reveals that the mobility enhancement in the Al-capped (Zn,Ba)SnO3 (ZBTO) TFT is attributed not only to the increase in the electron concentration, which is induced by band engineering due to the Al work function but also to the increased electron velocity due to the redistribution of the lateral electric field. As a result, the mobility of the Al-capped top-gate ZBTO device is 5 times higher (∼110 cm2/Vs) than that of the reference device. These results demonstrate the applicability of top-gate oxide TFTs with ultrahigh mobility in a wide range of applications, such as for high-resolution, large-area, and flexible displays.

11.
Biomed Pharmacother ; 153: 113520, 2022 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-36076515

RESUMO

Oxaliplatin, a third-generation platinum derivative, has become one of the main chemotherapeutic treatments for esophagus, gastric and colorectal cancer; however, it is still unclear the potential effectiveness for pancreatic ductal adenocarcinoma (PDAC) with gemcitabine resistance. Here, we observed that PDAC tumors have low level of organic cation transporter 2 (OCT2, also known as SLC22A2) compared with non-tumor tissues and identified that OCT2 expression is positively correlated with oxaliplatin sensitivity in PDAC cells. Treatment of OCT2 inhibitors or knockdown of OCT2 expression significantly decreased the sensitivity to oxaliplatin in PANC-1 cells. In addition, bisulfite sequencing polymerase chain reaction analysis revealed that higher methylation frequency represses OCT2 expression in gemcitabine-resistant PANC-1 (PANC-1/GR) cells. Moreover, we found that treatment of DNA methyltransferase (DNMT) inhibitors, decitabine or 5-azacytidine recover OCT2 expression and oxaliplatin sensitivity in PANC-1/GR cells, and DNMT1 level has inverse correlation with OCT2 expression in PDAC cells and tumors. Our findings jointly suggest that OCT2 expression is a potential and predictive marker for evaluating oxaliplatin sensitivity and developing alternative treatments for PDAC patients with gemcitabine resistance.


Assuntos
Carcinoma Ductal Pancreático , Neoplasias Pancreáticas , Carcinoma Ductal Pancreático/patologia , Linhagem Celular Tumoral , Humanos , Transportador 2 de Cátion Orgânico/metabolismo , Oxaliplatina/farmacologia , Oxaliplatina/uso terapêutico , Neoplasias Pancreáticas/patologia , Neoplasias Pancreáticas
12.
FEBS Lett ; 596(19): 2525-2537, 2022 10.
Artigo em Inglês | MEDLINE | ID: mdl-35918185

RESUMO

The tumour suppressor p53 has been implicated in the host defence system against hepatitis C virus (HCV) infection, although the detailed mechanism remains unknown. Here, we found that p53 inhibits HCV replication by downregulating HCV Core protein levels in human hepatoma cells. For this effect, p53 potentiated the role of E6-associated protein (E6AP) as an E3 ligase to induce ubiquitination and proteasomal degradation of HCV Core. Specifically, p53 facilitated the binding of E6AP to HCV Core through direct interactions with the two proteins. In addition, E6AP failed to induce ubiquitination of HCV Core in the absence of p53, suggesting that p53 increases the E3 ligase activity of E6AP in a triple complex consisting of p53, E6AP and HCV Core.


Assuntos
Hepatite C , Neoplasias , Proteínas Oncogênicas Virais , Hepacivirus/metabolismo , Humanos , Proteínas Oncogênicas Virais/metabolismo , Complexo de Endopeptidases do Proteassoma/metabolismo , Proteína Supressora de Tumor p53/metabolismo , Ubiquitina-Proteína Ligases/genética , Ubiquitina-Proteína Ligases/metabolismo , Proteínas do Core Viral/metabolismo , Replicação Viral
13.
Mol Metab ; 65: 101576, 2022 11.
Artigo em Inglês | MEDLINE | ID: mdl-35995401

RESUMO

OBJECTIVE: Dicer is an enzyme that processes microRNAs (miRNAs) precursors into mature miRNAs, which have been implicated in various aspects of cancer progressions, such as clinical aggressiveness, prognosis, and survival outcomes. We previously showed that high expression of Dicer is associated with gemcitabine (GEM) resistance in pancreatic ductal adenocarcinoma (PDAC); thus, in this study, we aimed to focus on how Dicer is involved in GEM resistance in PDAC, including cancer prognosis, cell proliferation, and metabolic regulation. METHODS: We generated stable shRNA knockdown of Dicer in GEM-resistant PANC-1 (PANC-1 GR) cells and explored cell viability by MTT and clonogenicity assays. Metabolomic profiling was employed to investigate metabolic changes between parental cells, PANC-1, and PANC-1 GR cells, and further implied to compare their sensitivity to the glutaminase inhibitor, CB839, and GEM treatments. To identify putative phosphorylation site involves with Dicer and its effects on GEM resistance in PDAC cells, we further generated phosphomimetic or phosphomutant Dicer at S1016 site and examined the changes in drug sensitivity, metabolic alteration, and miRNA regulation. RESULTS: We observed that high Dicer levels in pancreatic ductal adenocarcinoma cells were positively correlated with advanced pancreatic cancer and acquired resistance to GEM. Metabolomic analysis indicated that PANC-1 GR cells rapidly utilised glutamine as their major fuel and increased levels of glutaminase (GLS): glutamine synthetase (GLUL) ratio which is related to high Dicer expression. In addition, we found that phosphomimetic Dicer S1016E but not phosphomutant Dicer S1016A facilitated miRNA maturation, causing an imbalance in GLS and GLUL and resulting in an increased response to GLS inhibitors. CONCLUSION: Our results suggest that phosphorylation of Dicer on site S1016 affects miRNA biogenesis and glutamine metabolism in GEM-resistant pancreatic cancer.


Assuntos
Carcinoma Ductal Pancreático , RNA Helicases DEAD-box , MicroRNAs , Neoplasias Pancreáticas , Ribonuclease III , Antimetabólitos Antineoplásicos/farmacologia , Antimetabólitos Antineoplásicos/uso terapêutico , Carcinoma Ductal Pancreático/tratamento farmacológico , Carcinoma Ductal Pancreático/genética , Carcinoma Ductal Pancreático/metabolismo , Linhagem Celular Tumoral , RNA Helicases DEAD-box/genética , Desoxicitidina/análogos & derivados , Resistencia a Medicamentos Antineoplásicos/genética , Glutamato-Amônia Ligase/farmacologia , Glutaminase/genética , Glutaminase/farmacologia , Glutaminase/uso terapêutico , Glutamina , Humanos , MicroRNAs/genética , Neoplasias Pancreáticas/tratamento farmacológico , Neoplasias Pancreáticas/genética , Neoplasias Pancreáticas/metabolismo , RNA Interferente Pequeno , Ribonuclease III/genética , Gencitabina , Neoplasias Pancreáticas
14.
Am J Ophthalmol Case Rep ; 27: 101661, 2022 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-35859701

RESUMO

Purpose: We report a case of corneal verticillata in a patient who had been taking raloxifene for a prolonged period. To our knowledge, this is the first case report of an ocular side effect of raloxifene. Observations: A 69-year-old female patient presented to our clinic for her routine eye check-up. On slit-lamp examination, whorl-like subepithelial deposits were observed in the bilateral corneas. She was diagnosed with corneal verticillata (vortex keratopathy) caused by raloxifene. A follow-up evaluation was conducted after discontinuation of the drug; however, the corneal opacity did not improve. Conclusions and importance: Patients with corneal verticillata should be asked regarding any intake of raloxifene for osteoporosis, as it may cause corneal verticillata.

15.
ACS Appl Mater Interfaces ; 14(11): 13490-13498, 2022 Mar 23.
Artigo em Inglês | MEDLINE | ID: mdl-35258276

RESUMO

Zinc oxynitride (ZnON) has the potential to overcome the performance and stability limitations of current amorphous oxide semiconductors because ZnON-based thin-film transistors (TFTs) have a high field-effect mobility of 50 cm2/Vs and exceptional stability under bias and light illumination. However, due to the weak zinc-nitrogen interaction, ZnON is chemically unstable─N is rapidly volatilized in air. As a result, recent research on ZnON TFTs has focused on improving air stability. We demonstrate through experimental and first-principles studies that the ZnF2/ZnON bilayer structure provides a facile way to achieve air stability with carrier controllability. This increase in air stability (e.g., nitrogen non-volatilization) occurs because the ZnF2 layer effectively protects the atomic mixing between ZnON and air, and the decrease in the ZnON carrier concentration is caused by a shallow-to-deep electronic transition of nitrogen deficiency diffused from ZnON into the interface. Further, the TFT based on the ZnF2/ZnON bilayer structure enables long-term air stability while retaining an optimal switching property of high field-effect mobility (∼100 cm2/Vs) even at a relatively low post-annealing temperature. The ZnF2/ZnON-bilayer TFT device exhibits fast switching behavior between 1 kHz and 0.1 MHz while maintaining a stable and clear switching response, paving the way for next-generation high-speed electronic applications.

16.
Exp Neurobiol ; 30(5): 329-340, 2021 Oct 31.
Artigo em Inglês | MEDLINE | ID: mdl-34737238

RESUMO

Pulpitis (toothache) is a painful inflammation of the dental pulp and is a prevalent problem throughout the world. This pulpal inflammation occurs in the cells inside the dental pulp, which have host defense mechanisms to combat oral microorganisms invading the pulp space of exposed teeth. This innate immunity has been well studied, with a focus on Toll-like receptors (TLRs). The function of TLR4, activated by Gram-negative bacteria, has been demonstrated in trigeminal ganglion (TG) neurons for dental pain. Although Gram-positive bacteria predominate in the teeth of patients with caries and pulpitis, the role of TLR2, which is activated by Gram-positive bacteria, is poorly understood in dental primary afferent (DPA) neurons that densely innervate the dental pulp. Using Fura-2 based Ca2+ imaging, we observed reproducible intracellular Ca2+ responses induced by Pam3CSK4 and Pam2CSK4 (TLR2-specific agonists) in TG neurons of adult wild-type (WT) mice. The response was completely abolished in TLR2 knock-out (KO) mice. Single-cell RT-PCR detected Tlr2 mRNA in DPA neurons labeled with fluorescent retrograde tracers from the upper molars. Using the mouse pulpitis model, real-time RT-PCR revealed that Tlr2 and inflammatory-related molecules were upregulated in injured TG, compared to non-injured TG, from WT mice, but not from TLR2 KO mice. TLR2 protein expression was also upregulated in injured DPA neurons, and the change was corresponded with a significant increase in calcitonin gene-related peptide (CGRP) expression. Our results provide a better molecular understanding of pulpitis by revealing the potential contribution of TLR2 to pulpal inflammatory pain.

17.
Sci Rep ; 11(1): 21242, 2021 10 28.
Artigo em Inglês | MEDLINE | ID: mdl-34711879

RESUMO

Pancreatic cancer is one of the most lethal diseases which lack an early diagnostic marker. We investigated whether serum ferritin (SF) reflects risk for pancreatic cancer and potential genes that may contribute ferritin and pancreatic cancer risks. We performed a meta-analysis of relevant studies on SF and pancreatic cancer risk by searching articles in PUBMED and EMBASE published up to 1 March 2020. We also collected serum samples from Taipei Medical University Joint Biobank and compared SF levels in 34 healthy controls and 34 pancreatic cancer patients. An Oncomine database was applied as a platform to explore a series of genes that exhibited strong associations between ferritin and pancreatic cancer. Herein, we show that high levels of SF can indicate risk of pancreatic cancer, suggesting SF as the new tumor marker that may be used to help pancreatic cancer diagnosis. We also found that expressions of iron homeostasis genes (MYC, FXN) and ferroptosis genes (ALOX15, CBS, FDFT1, LPCAT3, RPL8, TP53, TTC35) are significantly altered with pancreatic tumor grades, which may contribute to differential expression of ferritin related to pancreatic cancer prognosis.


Assuntos
Biomarcadores , Ferritinas/sangue , Neoplasias Pancreáticas/sangue , Estudos de Casos e Controles , Biologia Computacional/métodos , Suscetibilidade a Doenças , Ferroptose/genética , Perfilação da Expressão Gênica , Regulação da Expressão Gênica , Humanos , Ferro/metabolismo , Neoplasias Pancreáticas/diagnóstico , Neoplasias Pancreáticas/etiologia , Vigilância em Saúde Pública , Fatores de Risco , Taiwan/epidemiologia , Transcriptoma
18.
Cells ; 10(9)2021 09 12.
Artigo em Inglês | MEDLINE | ID: mdl-34572043

RESUMO

Extracellular vesicles (EVs) are cell-released, nanometer-scaled, membrane-bound materials and contain diverse contents including proteins, small peptides, and nucleic acids. Once released, EVs can alter the microenvironment and regulate a myriad of cellular physiology components, including cell-cell communication, proliferation, differentiation, and immune responses against viral infection. Among the cargoes in the vesicles, small non-coding micro-RNAs (miRNAs) have received attention in that they can regulate the expression of a variety of human genes as well as external viral genes via binding to the complementary mRNAs. In this study, we tested the potential of EVs as therapeutic agents for severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection. First, we found that the mesenchymal stem-cell-derived EVs (MSC-EVs) enabled the rescue of the cytopathic effect of SARS-CoV-2 virus and the suppression of proinflammatory responses in the infected cells by inhibiting the viral replication. We found that these anti-viral responses were mediated by 17 miRNAs matching the rarely mutated, conserved 3'-untranslated regions (UTR) of the viral genome. The top five miRNAs highly expressed in the MSC-EVs, miR-92a-3p, miR-26a-5p, miR-23a-3p, miR-103a-3p, and miR-181a-5p, were tested. They were bound to the complemented sequence which led to the recovery of the cytopathic effects. These findings suggest that the MSC-EVs are a potential candidate for multiple variants of anti-SARS-CoV-2.


Assuntos
COVID-19/terapia , Vesículas Extracelulares/metabolismo , Células-Tronco Mesenquimais/metabolismo , MicroRNAs/uso terapêutico , SARS-CoV-2/fisiologia , Regiões 3' não Traduzidas/genética , Animais , Antivirais/farmacologia , Sequência de Bases , Linhagem Celular , Sequência Conservada/genética , Feminino , Genoma Viral , Humanos , Modelos Biológicos , Mutação/genética , Placenta/metabolismo , Gravidez , RNA Viral/genética , SARS-CoV-2/genética
19.
Artigo em Inglês | MEDLINE | ID: mdl-34073422

RESUMO

There are reports that pregnant women infected with SARS-CoV-2 not only have increased morbidity but also increased complications and evidence of maternal and fetal vascular malperfusion on placental pathology. This was a retrospective study of pregnant women diagnosed with SARS-CoV-2 infection after March 2020. The results of reverse transcription polymerase chain reaction testing and IgM and IgG antibody testing of the amniotic fluid, cord blood, placenta, and maternal blood were confirmed at delivery. Placentas were evaluated histopathologically. The study included seven pregnant women diagnosed with SARS-CoV-2 infection during pregnancy at a mean gestational age of 14.5 weeks. Out of the seven women, five were infected during the first trimester. The mean gestational age at delivery was 38.4 weeks. The reverse transcription polymerase chain reaction results for maternal plasma, cord blood, placenta, and amniotic fluid were negative and IgG antibodies were detected in maternal plasma and cord blood. On placental pathology, maternal vascular malperfusion was found in only one case, fetal vascular malperfusion in four cases, and inflammatory changes were found in two cases. Pregnancy outcomes for women diagnosed with SARS-CoV-2 infection during early pregnancy are positive and it is likely that maternal antibodies are passed to the fetus, which results in a period of immunity.


Assuntos
COVID-19 , Complicações Infecciosas na Gravidez , Feminino , Humanos , Lactente , Transmissão Vertical de Doenças Infecciosas , Placenta , Gravidez , Resultado da Gravidez , Estudos Retrospectivos , SARS-CoV-2
20.
Biomolecules ; 11(3)2021 03 02.
Artigo em Inglês | MEDLINE | ID: mdl-33801246

RESUMO

BACKGROUND: The oncogenic Kirsten rat sarcoma viral oncogene homolog (KRAS) mutation was reported to be the signature genetic event in most cases of pancreatic ductal adenocarcinoma (PDAC). Hepassocin (HPS/FGL1) is involved in regulating lipid metabolism and the progression of several cancer types; however, the underlying mechanism of HPS/FGL1 in the KRAS mutant PDAC cells undergoing eicosapentaenoic acid (EPA) treatment remains unclear. METHODS: We measured HPS/FGL1 protein expressions in a human pancreatic ductal epithelial (HPNE) normal pancreas cell line, a KRAS-wild-type PDAC cell line (BxPC-3), and KRAS-mutant PDAC cell lines (PANC-1, MIA PaCa-2, and SUIT-2) by Western blot methods. HEK293T cells were transiently transfected with corresponding KRAS-expressing plasmids to examine the level of HPS expression with KRAS activation. We knocked-down HPS/FGL1 using lentiviral vectors in SUIT-2 cells and measured the cell viability by 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide (MTT) and clonogenicity assays. Furthermore, a lipidomic analysis was performed to profile changes in lipid metabolism after HPS/FGL1 knockdown. RESULTS: We found that the HPS/FGL1 level was significantly upregulated in KRAS-mutated PDAC cells and was involved in KRAS/phosphorylated (p)-signal transduction and activator of transcription 3 (STAT3) signaling, and the knockdown of HPS/FGL1 in SUIT-2 cells decreased cell proliferation through increasing G2/M cell cycle arrest and cyclin B1 expression. In addition, the knockdown of HPS/FGL1 in SUIT-2 cells significantly increased omega-3 polyunsaturated fatty acids (PUFAs) and EPA production but not docosahexaenoic acid (DHA). Moreover, EPA treatment in SUIT-2 cells reduced the expression of de novo lipogenic protein, acetyl coenzyme A carboxylase (ACC)-1, and decreased p-STAT3 and HPS/FGL1 expressions, resulting in the suppression of cell viability. CONCLUSIONS: Results of this study indicate that HPS is highly expressed by KRAS-mutated PDAC cells, and HPS/FGL1 plays a crucial role in altering lipid metabolism and increasing cell growth in pancreatic cancer. EPA supplements could potentially inhibit or reduce ACC-1-involved lipogenesis and HPS/FGL1-mediated cell survival in KRAS-mutated pancreatic cancer cells.


Assuntos
Ácido Eicosapentaenoico/farmacologia , Fibrinogênio/metabolismo , Mutação/genética , Neoplasias Pancreáticas/metabolismo , Neoplasias Pancreáticas/patologia , Proteínas Proto-Oncogênicas p21(ras)/genética , Fator de Transcrição STAT3/metabolismo , Pontos de Checagem do Ciclo Celular/efeitos dos fármacos , Linhagem Celular Tumoral , Proliferação de Células/efeitos dos fármacos , Sobrevivência Celular/efeitos dos fármacos , Células HEK293 , Humanos , Concentração Inibidora 50 , Lipídeos/sangue , Fosforilação/efeitos dos fármacos
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