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1.
HERD ; 17(2): 97-114, 2024 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-38293825

RESUMO

OBJECTIVE: This study aims (1) to understand the needs and challenges of the current intensive care unit (ICU) environments in supporting patient well-being from the perspective of healthcare professionals (HCPs) and (2) to explore the new potential of ICU environments enabled by technology. BACKGROUND: Evidence-based design has yielded how the design of environments can advocate for patient well-being, and digital technology offers new possibilities for indoor environments. However, the role of technology in facilitating ICU patient well-being has been unexplored. METHOD: This study was conducted in two phases. First, a mixed-method study was conducted with ICU HCPs from four Dutch hospitals. The study investigated the current environmental support for care activities, as well as the factors that positively and negatively contribute to patient experience. Next, a co-creation session was held involving HCPs and health technology experts to explore opportunities for technology to support ICU patient well-being. RESULTS: The mixed-method study revealed nine negative and eight positive patient experience factors. HCPs perceived patient emotional care as most challenging due to the ICU workload and a lack of environmental support in fulfilling patient emotional needs. The co-creation session yielded nine technology-enabled solutions to address identified challenges. Finally, drawing from insights from both studies, four strategies were introduced that guide toward creating technology to provide holistic and personalized care for patients. CONCLUSION: Patient experience factors are intertwined, necessitating a multifactorial approach to support patient well-being. Viewing the ICU environment as a holistic unit, our findings provide guidance on creating healing environments using technology.


Assuntos
Atitude do Pessoal de Saúde , Unidades de Terapia Intensiva , Humanos , Países Baixos , Masculino , Feminino , Pessoal de Saúde/psicologia , Adulto , Decoração de Interiores e Mobiliário , Pessoa de Meia-Idade , Arquitetura Hospitalar/métodos , Emoções , Ambiente de Instituições de Saúde
2.
J Ethnopharmacol ; 321: 117501, 2024 Mar 01.
Artigo em Inglês | MEDLINE | ID: mdl-38012970

RESUMO

ETHNOPHARMACOLOGICAL RELEVANCE: Psoralea corylifolia L. (PC) is widely used in traditional medicines to treat inflammatory and infectious diseases. Isobavachin (IBC) is a bioavailable prenylated flavonoid derived from PC that has various biological properties. However, little information is available on its anti-inflammatory effects and mechanisms of action. AIM OF THE STUDY: In this study, we aimed to determine the anti-inflammatory effects of IBC in vitro and in vivo by conducting a mechanistic study using murine macrophages. MATERIALS AND METHODS: We evaluated the modulatory effects of IBC on the production of pro-inflammatory cytokines and mediators in murine macrophages. In addition, we examined whether IBC inhibits lipopolysaccharide (LPS)-induced inflammatory responses in a zebrafish model. Alterations in inflammatory response-associated genes and proteins were determined using quantitative reverse transcriptional polymerase chain reaction (RT-qPCR) and Western blotting analysis. RESULTS: IBC markedly reduced the overproduction of inflammatory mediators, pro-inflammatory cytokines, inducible nitric oxide synthase (iNOS), cyclooxygenase-2 (COX-2), phosphorylation of mitogen-activated protein kinase (MAPK) and nuclear translocation of nuclear factor-kappa B (NF-κB) in macrophages induced by lipopolysaccharides (LPS). In addition, excessive NO, ROS, and neutrophil level induced by LPS, were suppressed by IBC treatment in a zebrafish inflammation model. CONCLUSIONS: Collectively, bioavailable IBC inhibited on the inflammatory responses by LPS via MAPK and NF-κB signaling pathways in vitro and in vivo, suggesting that it may be a potential modulatory agent against inflammatory disorders.


Assuntos
Proteínas Quinases Ativadas por Mitógeno , Psoralea , Animais , Camundongos , Proteínas Quinases Ativadas por Mitógeno/metabolismo , NF-kappa B/metabolismo , Lipopolissacarídeos/farmacologia , Peixe-Zebra , Psoralea/metabolismo , Transdução de Sinais , Flavonoides/farmacologia , Citocinas/metabolismo , Macrófagos , Anti-Inflamatórios/farmacologia , Anti-Inflamatórios/uso terapêutico , Anti-Inflamatórios/metabolismo , Óxido Nítrico Sintase Tipo II/metabolismo , Ciclo-Oxigenase 2/genética , Ciclo-Oxigenase 2/metabolismo
3.
PLoS One ; 18(2): e0281421, 2023.
Artigo em Inglês | MEDLINE | ID: mdl-36812289

RESUMO

Stroke is a major cause of long-term disability world-wide. Limited pharmacological therapy has been used in stroke patients. Previous studies indicated that herb formula PM012 is neuroprotective against neurotoxin trimethyltin in rat brain, and improved learning and memory in animal models of Alzheimer's disease. Its action in stroke has not been reported. This study aims to determine PM012-mediated neural protection in cellular and animal models of stroke. Glutamate-mediated neuronal loss and apoptosis were examined in rat primary cortical neuronal cultures. Cultured cells were overexpressed with a Ca++ probe (gCaMP5) by AAV1 and were used to examine Ca++ influx (Ca++i). Adult rats received PM012 before transient middle cerebral artery occlusion (MCAo). Brain tissues were collected for infarction and qRTPCR analysis. In rat primary cortical neuronal cultures, PM012 significantly antagonized glutamate-mediated TUNEL and neuronal loss, as well as NMDA-mediated Ca++i. PM012 significantly reduced brain infarction and improved locomotor activity in stroke rats. PM012 attenuated the expression of IBA1, IL6, and CD86, while upregulated CD206 in the infarcted cortex. ATF6, Bip, CHOP, IRE1, and PERK were significantly down-regulated by PM012. Using HPLC, two potential bioactive molecules, paeoniflorin and 5-hydroxymethylfurfural, were identified in the PM012 extract. Taken together, our data suggest that PM012 is neuroprotective against stroke. The mechanisms of action involve inhibition of Ca++i, inflammation, and apoptosis.


Assuntos
Fármacos Neuroprotetores , Acidente Vascular Cerebral , Ratos , Animais , Neuroproteção , Ratos Sprague-Dawley , Modelos Animais de Doenças , Fármacos Neuroprotetores/farmacologia , Acidente Vascular Cerebral/etiologia , Encéfalo/metabolismo , Infarto da Artéria Cerebral Média/complicações , Glutamatos
4.
Pharmaceuticals (Basel) ; 15(11)2022 Nov 09.
Artigo em Inglês | MEDLINE | ID: mdl-36355547

RESUMO

Jaeumgeonbi-Tang (JGT), a traditional herbal medicine, has been used to treat dizziness and vertigo in Korea and China for hundreds of years. The purpose of this study was to evaluate the pharmacological properties of JGT in chronic subjective dizziness (CSD) patients. A randomized, double-blind, parallel-group and placebo-controlled trial was performed with a total of 50 CSD patients. The patients were randomly assigned to one of two groups: JGT or placebo (n = 25 for each). All participants received the treatment (placebo or JGT, 24 g/day) for 4 weeks. We analyzed the serum levels of oxidative stressors, antioxidants, and stress hormones. Serum levels of lipid peroxidation, but not nitric oxide, were significantly decreased in the JGT group. JGT not only prevented the decline of serum total glutathione contents and total antioxidant capacity, but it also increased superoxide dismutase and catalase activities. Serum levels of stress hormones including cortisol, adrenaline, and serotonin were notably normalized by JGT treatment, but noradrenaline levels were not affected. Regarding the safety and tolerability of JGT, we found no allergic, adverse, or side effects in any of the participants. JGT showed beneficial effects on CSD patients by improving redox status and balancing psycho-emotional stress hormones.

5.
Animals (Basel) ; 12(18)2022 Sep 12.
Artigo em Inglês | MEDLINE | ID: mdl-36139238

RESUMO

In this study, we examined the effect of diets supplemented with organic and inorganic mineral premixes on the laying performance and eggshell quality of aged laying hens. A total of 600 68-week-old Hy-Line Brown laying hens were randomly assigned to 1 of 3 dietary treatments, repeated 5 times: Mash type basal diet, basal diet supplemented with an inorganic mineral premix (1.0 g/kg), and basal diet supplemented with an organic mineral premix (1.8 g/kg). The results showed that eggshell strength was higher (p < 0.01) in the inorganic mineral diet group than in the organic mineral and basal diet groups. Further, the levels of Fe and Mn in the liver were higher (p < 0.05) in the inorganic and organic mineral diet groups than in the basal diet group. The concentrations of Fe and Mg in the spleen were different (p < 0.05) among the treatment groups, with the highest levels reported in the organic mineral premix group. The concentrations of Cu, Zn, and Mn in the eggshell were different (p < 0.05) among the groups, with the highest levels reported in the inorganic and organic mineral premix diet groups. In conclusion, a diet containing organic mineral premix improved eggshell strength and had no detrimental effect on the laying performance of aged laying hens.

6.
Int J Mol Sci ; 23(18)2022 Sep 08.
Artigo em Inglês | MEDLINE | ID: mdl-36142303

RESUMO

Thyroid carcinoma, a disease in which malignant cells form in the thyroid tissue, is the most common endocrine carcinoma, with papillary thyroid carcinoma (PTC) accounting for nearly 80% of total thyroid carcinoma cases. However, the management of metastatic or recurrent therapy-refractory PTC is challenging and requires complex carcinoma therapy. In this study, we proposed a new clinical approach for the treatment of therapy-refractory PTC. We identified sarco/endoplasmic reticulum calcium ATPase (SERCA) as an essential factor for the survival of PTC cells refractory to the treatment with paclitaxel or sorafenib. We validated its use as a potential target for developing drugs against resistant PTC, by using patient-derived paclitaxel- or sorafenib-resistant PTC cells. We further discovered novel SERCA inhibitors, candidates 7 and 13, using the evolutionary chemical binding similarity method. These novel SERCA inhibitors determined a substantial reduction of tumors in a patient-derived xenograft tumor model developed using paclitaxel- or sorafenib-resistant PTC cells. These results could provide a basis for clinically meaningful progress in the treatment of refractory PTC by identifying a novel therapeutic strategy: using a combination therapy between sorafenib or paclitaxel and specific SERCA inhibitors for effectively and selectively targeting extremely malignant cells such as antineoplastic-resistant and carcinoma stem-like cells.


Assuntos
Antineoplásicos , Neoplasias da Glândula Tireoide , Antineoplásicos/farmacologia , Humanos , Recidiva Local de Neoplasia/tratamento farmacológico , Paclitaxel/farmacologia , Paclitaxel/uso terapêutico , Compostos de Fenilureia/farmacologia , Compostos de Fenilureia/uso terapêutico , Sorafenibe/farmacologia , Sorafenibe/uso terapêutico , Câncer Papilífero da Tireoide/tratamento farmacológico , Neoplasias da Glândula Tireoide/patologia
7.
Animals (Basel) ; 12(9)2022 May 02.
Artigo em Inglês | MEDLINE | ID: mdl-35565592

RESUMO

BACKGROUND: Looking for alternative omega-3 sources in broiler nutrition, microalgae began to get attention. We suspected that schizochytrium might play a similar role as other omega-3 sources that have been used before. METHODS: 20 g/kg schizochytrium powder (SP), salmon oil (SO), and flaxseed oil (FO) in each of the three treatment groups were supplemented in the basal diet (CON), and productive performance, carcass traits, and thigh meat quality of broilers were evaluated. RESULTS: There was a significantly higher weight gain in the SP treatment compared to the other groups, but no difference was found in feed intake and feed conversion ratio. Thiobarbituric acid reactive substance values increased during storage in all the treatments but were significantly lower for SP than for SO and FO after 7 days of storage. Among the ω-3 fatty acids (FAs), α-linolenic acid increased the most in the FO treatment, eicosapentaenoic acid increased the most in the SO treatment, and docosahexaenoic acid increased the most in the SP treatment in thigh meat, reflecting the FA composition of the lipid source diets. CONCLUSIONS: We suggested that all the dietary ω-3 FA sources could improve the FA composition of chicken meat and our results indicated the possibility to supplement broiler diets with 2% level of SP, SO, and FO as ω-3 FA sources to produce meat with a good nutritional quality for consumer's health benefits.

8.
Artigo em Inglês | MEDLINE | ID: mdl-35378908

RESUMO

This study was to investigate the effects of Biyeom-go (BYG, an herbal formula) on immune biomarkers present in the nasal mucosa of patients with allergic rhinitis under exposure to particulate matter 2.5 (PM2.5), and on changes in goblet cells and immune biomarkers in mice under exposure to Korea diesel particulate matter (KDP20). Thirty patients showing characteristic allergic rhinitis symptoms were enrolled in Jeonju-si, Korea, and treated with BYG thrice a day for four weeks. Changes in the expression of immune biomarkers (interleukin 4 (IL-4), IL-5, IL-8, IL-13, IL-33, and thymic stromal lymphopoietin (TSLP) mRNA), total nasal symptom scores (TNSS), mini-rhinitis-specific quality of life questionnaire (RQLQ) results, and visual analog scale scores were evaluated after 4 weeks of treatment. Additionally, the difference in PM2.5 concentrations in the air in Jeonju-si, Korea (November, 2019 ∼ March, 2020), was analyzed to determine the change in TNSS. KDP20 (100 µg/mL) was exposed to C57BL/6 mice for 10 days; 0.05% Nasonex (a positive control, mometasone furoate), or BYG was administrated for 5 days twice a day. The expression of inflammatory factors was detected via qRT-PCR using nasopharynx tissue samples of mice. BYG treatment was found to be associated with significant improvement in total nasal symptoms, especially itching and sneezing (p < 0.0001), and mini-RQLQ after 4 weeks. IL-8 (p < 0.01), IL-33 (p < 0.01), and TSLP (p < 0.001) expression levels decreased after BYG treatment. In mice, administration of BYG reduced the number of goblet cells increased through KDP20 treatment. KDP20-induced immune biomarkers (IL-33, TSLP, tumor necrosis factor alpha, and IL-8) were also significantly downregulated in the nasopharynx tissue after BYG treatment. Therefore, BYG may show therapeutic effects against allergic rhinitis in humans, and it was confirmed that the expression of PM-induced inflammatory factors in mice was decreased via BYG treatment.

9.
Korean J Intern Med ; 37(3): 520-533, 2022 05.
Artigo em Inglês | MEDLINE | ID: mdl-35417937

RESUMO

Kidney transplantation is the preferred treatment for patients with end-stage kidney disease, because it prolongs survival and improves quality of life. Allograft biopsy is the gold standard for diagnosing allograft rejection. However, it is invasive and reactive, and continuous monitoring is unrealistic. Various biomarkers for diagnosing allograft rejection have been developed over the last two decades based on omics technologies to overcome these limitations. Omics technologies are based on a holistic view of the molecules that constitute an individual. They include genomics, transcriptomics, proteomics, and metabolomics. The omics approach has dramatically accelerated biomarker discovery and enhanced our understanding of multifactorial biological processes in the field of transplantation. However, clinical application of omics-based biomarkers is limited by several issues. First, no large-scale prospective randomized controlled trial has been conducted to compare omics-based biomarkers with traditional biomarkers for rejection. Second, given the variety and complexity of injuries that a kidney allograft may experience, it is likely that no single omics approach will suffice to predict rejection or outcome. Therefore, integrated methods using multiomics technologies are needed. Herein, we introduce omics technologies and review the latest literature on omics biomarkers predictive of allograft rejection in kidney transplant recipients.


Assuntos
Rejeição de Enxerto , Qualidade de Vida , Aloenxertos , Biomarcadores , Rejeição de Enxerto/diagnóstico , Rejeição de Enxerto/genética , Humanos , Rim , Estudos Prospectivos
10.
Antioxidants (Basel) ; 11(1)2022 Jan 17.
Artigo em Inglês | MEDLINE | ID: mdl-35052678

RESUMO

Near-infrared (NIR) light-mediated photothermal therapy (PTT) and photodynamic therapy (PDT) have widely been used for cancer treatment applications. However, a number of limitations (e.g., low NIR absorption capacity of photothermal agents, insufficient loading efficiency of photosensitive molecules) have hindered the widespread use of NIR-mediated cancer therapy. Therefore, we developed a mesoporous silica-coated reduced graphene oxide (rGO) nanocomposite that could provide a high encapsulation rate of indocyanine green (ICG) and enhance PTT/PDT efficiency in vitro and in vivo. The ICG-encapsulated nanocomposite not only enhances the photothermal effect but also generates a large number of tumor toxic reactive oxygen species (ROS). By conjugation of polyethylene glycol (PEG) with folic acid (FA) as a tumor targeting moiety, we confirmed that ICG-encapsulated mesoporous silica (MS)-coated rGO nanocomposite (ICG@MS-rGO-FA) exhibited high colloidal stability and intracellular uptake in folate receptor-expressing CT-26 colorectal cancer cells. Upon NIR laser irradiation, this ICG@MS-rGO-FA nanocomposite induced the apoptosis of only CT-26 cells via enhanced PTT and PDT effects without any damage to normal cells. Furthermore, the ICG@MS-rGO-FA nanocomposite revealed satisfactory tumor targeting and biocompatibility in CT-26 tumor-bearing mice, thereby enhancing the therapeutic effects of PTT and PDT in vivo. Therefore, this tumor-targeted ICG@MS-rGO-FA nanocomposite shows a great potential for phototherapy applications.

11.
Phytomedicine ; 94: 153794, 2022 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-34775362

RESUMO

BACKGROUND: Moutan radicis cortex (MRC) and Cinnamomi ramulus (CR) are commonly used in eastern Asian traditional medicine to treat various diseases including cerebrovascular and cardiovascular, and have wide spectrum of pharmacological activities. However, the effect against laser-induced choroidal neovascularization (CNV) of extract of MRC and CR (1:1) (MRCCR) has not yet been studied. PURPOSE: Our aim was to investigate the inhibitory effect of MRCCR on pathological CNV in laser-treated Brown-Norway (BN) rats. METHODS: MRCCR (60, 90 mg/kg) was orally administered twice per day for 15 days from the day of CNV formation in laser-treated BN rats. Effects of MRCCR or its constituents on cell migration, tube formation, hyperpermeability and phosphorylation of FAK/p38 MAPK were confirmed in humane retinal microvascular endothelial cells or human retinal pigment epithelial cells. RESULTS: MRCCR significantly reduced the CNV lesions areas and the extent of fluorescein leakage. MRCCR and its constituents such as ellagic acid, paeonol or gallic acid decreased cell migration, tube formation or hyperpermeability. MRCCR inhibited the phosphorylation of FAK and p38 MAPK. CONCLUSION: Combining the oral MRCCR and intravitreal injection of anti-VEGF medicine may result in a more potent therapeutic effect and consequently bring the reduction in eye injection numbers for patients with wet AMD.


Assuntos
Neovascularização de Coroide , Animais , Neovascularização de Coroide/tratamento farmacológico , Modelos Animais de Doenças , Células Endoteliais , Angiofluoresceinografia , Humanos , Lasers , Extratos Vegetais/farmacologia , Ratos , Ratos Endogâmicos BN , Fator A de Crescimento do Endotélio Vascular
12.
J Anim Sci Technol ; 63(6): 1355-1361, 2021 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-34957449

RESUMO

Digestibility of pet food can affect the health of dog, especially of aged animals. To maintain the health of dogs in an overall good status it is necessary to provide nutritionally balanced food. For example, the digestibility of dogs was known to be decreased along aging. In addition, losing teethes is an often event in aged dogs that could induce a problem to eat a large size dry pet food. Nonetheless, few detailed information is available on the most suited feeding for aged dogs. As part of the nutritional study of food for aged dogs, in this study, we tested whether food type impacts on digestibility on adult versus senior dogs. The methodology to measure the digestibility of nutrients was chosen the index method using chromium oxide. Dogs were fed the same commercial dry or wet diets, which were supplemented with 0.5% chromium oxide. The wet food was prepared by adding twice volume of water in the dry food prior to incubated overnight (14-16 hours) at room temperature. After five days, their feces were collected up to a total weight of > 200 g which was the amount to analyze undigested nutrients in feces as 3 repeats. In the apparent total tract digestibility analysis of the experimental breed, no difference in the digestibility of crude protein, crude fat, crude fiber, ash, and energy was observed regarding the moisture content of the food. Noteworthy, the digestibility of nitrogen free extract was significantly increased in senior dogs fed dry dog food compared with adult dogs fed the same diet, whereas no difference was observed between senior and adult dogs fed wet food. The small breed dogs showed similar results to the experimental breed dogs. However, the digestibility of crude fat was additionally affected by age and food type unlike the experimental breed dogs. This finding suggests that the food moisture content affects the digestibility of nutrients in dogs with aging. Hence, it may be helpful to determine the nutrient contents in foods for senior dogs depending on the food type.

13.
J Affect Disord ; 295: 856-864, 2021 12 01.
Artigo em Inglês | MEDLINE | ID: mdl-34706456

RESUMO

BACKGROUND: Cranial Electrotherapy Stimulation (CES) is a promising non-invasive brain stimulation technique with the potential to alleviate anxiety. We examined the effectiveness of home-based CES with novel, headphone-like, in-ear electrodes on anxiety-related symptoms and resting-state brain activity. METHODS: This study spanned 3-weeks, with randomized, double blind, and active-controlled design. Nonclinical volunteers experiencing daily anxiety were randomly assigned to either the active or the sham groups. CES provides an alternating current (10 Hz frequency, 500 µA intensity), connected to smartphone recording treatment logs. Participants treated themselves with 20 trials of CES at home. We evaluated the effectiveness using State-Trait Anxiety Inventory (STAI), Beck Depression Inventory (BDI), Wisconsin Card Sort Test (WCST), and resting-state electroencephalography (EEG). RESULTS: The active group showed a significant improvement in state-anxiety compared to sham, while there was a statistical trend in the WCST-Category Completed (p = .061) and no change in depression. In EEG analysis, the active group showed significantly increased relative power for theta in the left frontal region compared with the sham, and this significantly correlated with the changes in state-anxiety. The active group exhibited significantly increased high-beta source activity in cuneus and middle occipital gyrus after intervention compared with the baseline. LIMITATIONS: This study had a relatively short treatment period and small sample size. CONCLUSIONS: Our findings provide the first electrophysiological evidence for CES for novel in-ear electrodes to improve anxiety. The modulatory effects of CES on resting-state oscillations of EEG imply that CES could beneficially affect functional brain activity.


Assuntos
Terapia por Estimulação Elétrica , Ansiedade/terapia , Transtornos de Ansiedade , Encéfalo , Método Duplo-Cego , Eletrodos , Humanos
14.
Biomed Res Int ; 2021: 5515478, 2021.
Artigo em Inglês | MEDLINE | ID: mdl-34195263

RESUMO

BACKGROUND: ML171 is a potent nicotinamide adenine dinucleotide phosphate oxidase (NOX) inhibitor with isoform selectivity only for NOX1. This study is aimed at investigating the safety of ML171 after a single intraperitoneal (IP) injection in mice. METHODS: The toxicity of a single dose of ML171 was evaluated in 6-week-old Institute of Cancer Research (ICR) mice in a good laboratory practice (GLP) laboratory. Twenty-five mice of each sex were assigned to five groups: negative control, vehicle control, and 125, 250, and 500 mg/kg of ML171. All mice were acclimatized for one week before beginning the study. Mice received an IP injection of ML171 or vehicle. The general condition and mortality of the animals were observed. The mice were sacrificed to evaluate histopathology 14 days after the administration of ML171 or vehicle. RESULTS: Bodyweights were not significantly different in any group. Three males and one female died due to ML171 administration in the 500 mg/kg dose group. Autopsies of the surviving mice did not reveal any significant abnormalities after the injection of 125 mg/kg of ML171. However, the anterior lobe edge of the liver was thickened and adhesions between the liver and adjacent organs were observed in mice treated with 250 or 500 mg/kg of ML171. In addition, hypertrophy of centrilobular hepatocytes and inflammatory cell infiltration were observed after injection of 250 and 500 mg/kg of ML171. CONCLUSION: Our results indicate that the lethal IP injection dose of ML171 is 500 mg/kg for both males and females. Mortality were not observed for lower doses of ML171. The safe dose of single IP ML171 in ICR mice was 250 mg/kg or less. Further studies are needed to confirm the safety of ML171 in the human body.


Assuntos
NADPH Oxidase 1/antagonistas & inibidores , Fenotiazinas/farmacologia , Fenotiazinas/toxicidade , Animais , Avaliação Pré-Clínica de Medicamentos , Feminino , Masculino , Camundongos , Camundongos Endogâmicos ICR , Isoformas de Proteínas , Testes de Toxicidade
15.
Antiviral Res ; 193: 105126, 2021 09.
Artigo em Inglês | MEDLINE | ID: mdl-34217753

RESUMO

Baloxavir marboxil (BXM) treatment-emergent polymerase acid (PA) I38X amino acid substitution (AAS) in the resistant variants of influenza viruses raise concerns regarding their emergence and spread. This study investigated the impact of 1 or 5 mg/kg BXM and 25 mg/kg oseltamivir phosphate (OS) (single or combination therapy) on the occurrence of resistance-related substitutions during the sequential lung-to-lung passages of AH1N1)pdm09 virus in mice. Deep sequencing analysis revealed that 67% (n = 4/6) of the population treated with BXM single therapy (1 or 5 mg/kg) possessed the treatment-emergent PA-I38X AAS variants (I38T, I38S, and I38V). Notably, BXM-OS combination therapy impeded PA-I38X AAS emergence. Although the doses utilized in the mouse model may not be directly translated into the clinically equivalent doses of each drugs, these findings offer insights toward alternative therapies to mitigate the emergence of influenza antiviral resistance.


Assuntos
Dibenzotiepinas/farmacologia , Vírus da Influenza A Subtipo H1N1/efeitos dos fármacos , Vírus da Influenza A Subtipo H1N1/genética , Morfolinas/farmacologia , Infecções por Orthomyxoviridae/tratamento farmacológico , Oseltamivir/farmacologia , Piridonas/farmacologia , Triazinas/farmacologia , Substituição de Aminoácidos , Animais , Antivirais/farmacologia , Modelos Animais de Doenças , Farmacorresistência Viral/efeitos dos fármacos , Camundongos , Infecções por Orthomyxoviridae/virologia , Carga Viral/efeitos dos fármacos
16.
J Ethnopharmacol ; 274: 113944, 2021 Jun 28.
Artigo em Inglês | MEDLINE | ID: mdl-33711437

RESUMO

ETHNOPHARMACOLOGICAL RELEVANCE: The root of Achyranthes bidentata Blume, Achyranthis Radix (AR), is used as a traditional medicine ingredient in East Asia. It has anti-inflammatory, anti-oxidative, and anti-diabetic activities. AIM OF THE STUDY: In the present study, we aimed to evaluate the oral toxicity and genotoxicity of single-dose and 4-week repeated-doses of AR hot water extract (ARE), under the good laboratory practice principles. MATERIALS AND METHODS: For oral toxicity studies, SD rats (n = 5 per sex and group) were administered ARE at concentrations of 500, 1000, and 2000 mg/kg/day once (single dose) or once per day for 4 weeks (repeated dose). The non-clinical genotoxicity study consisted of bacterial reverse mutation using Escherichia coli (WP2 uvrA) and Salmonella typhimurium (TA98, TA100, TA1535, and TA1537), in vitro chromosomal aberration test with Chinese hamster lung cells (CHL/IU), and in vivo mouse bone marrow micronucleus test using bone marrow cells collected from male ICR mice (n = 5) that were orally administered ARE. RESULTS: In the single-dose oral toxicity study, mortality and treatment-related changes in body weight were not observed throughout the study, and the lethal dose was estimated to be > 2000 mg/kg in rats. In the 4-week repeated-dose oral toxicity study, ARE did not induce significant changes in body weight, organ weight, food intake, or hematological and serum biochemical parameters in any group. In the bacterial reverse mutation test, ARE did not induce gene mutations in any tested strain. In the chromosomal aberration test, ARE did not cause chromosomal aberrations. The micronucleus test showed no significant increase in the number of micronucleated polychromatic erythrocytes or the mean ratio of polychromatic to total erythrocytes. CONCLUSIONS: These results showed that ARE does not induce oral toxicity and genotoxicity in the in vivo and in vitro test systems.


Assuntos
Achyranthes/química , Extratos Vegetais/toxicidade , Administração Oral , Animais , Bactérias/efeitos dos fármacos , Bactérias/genética , Medula Óssea/efeitos dos fármacos , Linhagem Celular , Aberrações Cromossômicas/efeitos dos fármacos , Cricetulus , Dano ao DNA , Masculino , Medicina Tradicional do Leste Asiático , Camundongos Endogâmicos ICR , Testes para Micronúcleos , Testes de Mutagenicidade , Mutação/efeitos dos fármacos , Extratos Vegetais/administração & dosagem , Ratos Sprague-Dawley
17.
Anim Biotechnol ; 32(4): 401-412, 2021 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-31900040

RESUMO

This study elucidated the molecular markers that decrease oocyte quality during in vitro culture, restricting optimal developmental potential. Here, we evaluated the transcriptomic differences between cysteamine-treated and non-treated bovine cumulus oocyte complexes (COCs) after 22 h of co-culture in the maturation media using RNA sequencing. In total, 39,014 transcripts were sequenced between cysteamine-treated and non-treated mature COCs. We evaluated the relative expression of 21,472 genes, with 59 genes showing differential expression between the two COC groups. The cysteamine-treated group had 36 up-regulated gene transcripts and 23 down-regulated gene transcripts. Moreover, gene ontology (GO) enrichment analysis revealed that multiple biological processes were significantly enriched after cysteamine supplementation. Differentially expressed genes appeared to maintain normal oocyte physiology, regulation of apoptosis, differentiation, ossification or bone formation, cardiac and muscle physiology, hormonal secretion, and membrane construction for further embryonic development. In conclusion, cysteamine affects the mRNA level of COCs during oocyte maturation by upregulating potential molecular markers and downregulating genes that affect further embryonic development.


Assuntos
Bovinos , Cisteamina , Oócitos , Transcriptoma , Animais , Bovinos/genética , Cisteamina/farmacologia , Suplementos Nutricionais , Perfilação da Expressão Gênica , República da Coreia
18.
J Sports Med Phys Fitness ; 61(10): 1380-1386, 2021 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-33269887

RESUMO

BACKGROUND: Few epidemiological studies have investigated pain and time loss due to sports injury. We analyzed the specific patterns of injury among Korean elite judo athletes and examined the effects of pain on time loss. We also assessed the association between the type of injury and time loss. METHODS: We prospectively collected data on elite judo athletes at the Korean Training Center for the year 2019. The athletes were assessed by sports medicine doctors, and data were stratified according to sex, weight class, and injury location. We used χ2 tests to compare groups. Injury rates were expressed as Poisson rates with 95% confidence intervals. One-way analysis of variance was used to investigate the pain scores and time losses due to sports injury. RESULTS: The study included 232 athletes whose 606 injuries (annual average, 2.61 injuries/athlete) were recorded. Female athletes had higher injury rates than male athletes. Overall, most injuries occurred in the lower extremities (38.12%), followed by the upper extremities (36.80%), trunk (17.66%), and head and neck area (7.43%). Injury severity significantly differed according to the body regions in the weight classes. The pain score and time loss differed significantly according to the type of injury. When the pain score increased by 1, the time loss increased by approximately 1.47 days. CONCLUSIONS: Among all weight classes, female athletes had a higher injury rate than male athletes. The pain score and time loss varied depending on the type of injury, with pain score being associated with time loss.


Assuntos
Traumatismos em Atletas , Artes Marciais , Atletas , Traumatismos em Atletas/epidemiologia , Feminino , Humanos , Incidência , Masculino , Estudos Prospectivos , República da Coreia/epidemiologia
19.
Nutrients ; 12(12)2020 Nov 24.
Artigo em Inglês | MEDLINE | ID: mdl-33255404

RESUMO

This study investigated the effects of the n-BuOH soluble fraction of Polygoni Cuspidati 80% ethanol extract (POCU1b) on high-fat diet (HFD)-induced obesity, non-alcoholic fatty liver (NAFL), and insulin resistance (IR) to find a safe and more effective agent. HPLC profiling of POCU1b identified seven marker compounds. POCU1b increased glycerol release, cyclic adenosine monophosphate (cAMP) level, and inhibited phosphodiesterase (PDE) activity. Seven weeks of POCU1b treatment decreased body weight gain, weight and adipocyte size in fat tissues, serum lipids, and triglyceride and lipid droplets in the livers of HFD-fed rats. POCU1b improved blood glucose, insulin sensitivity, and impaired insulin secretion in the pancreas. Further, POCU1b ameliorated adiponectin, leptin, IL-6 and TNF-α levels, increased AMPK and p-ACC expression, activated CPT-1 activity, and suppressed FAS mRNA, SOCS-3 protein expression, and NF-κB DNA-binding activity. When compared with the Xenical®-treated group, a positive group, the action of POCU1b on body weight was more effective than that of Xenical. POCU1b did not show side effects, such as oily spotting and loss of appetite. These results suggest that POCU1b possesses therapeutic or preventive potential for obesity, NAFL and IR via inhibitions of pancreatic lipase and cAMP-dependent PDE activity, AMPK activation, and SOCS-3 suppression, without oily spotting and loss of appetite.


Assuntos
Proteínas Quinases Ativadas por AMP/efeitos dos fármacos , Fallopia japonica , Resistência à Insulina , Hepatopatia Gordurosa não Alcoólica/tratamento farmacológico , Obesidade/tratamento farmacológico , Extratos Vegetais/farmacologia , Proteína 3 Supressora da Sinalização de Citocinas/efeitos dos fármacos , 1-Butanol , Animais , Lipase/efeitos dos fármacos , Masculino , Pâncreas/efeitos dos fármacos , Pâncreas/enzimologia , Diester Fosfórico Hidrolases/efeitos dos fármacos , Ratos , Ratos Wistar
20.
Neurorehabil Neural Repair ; 34(12): 1111-1123, 2020 12.
Artigo em Inglês | MEDLINE | ID: mdl-33198568

RESUMO

BACKGROUND: Parkinson's disease (PD) leads to impaired mobility and limited independence. OBJECTIVE: We investigated the effects of acupuncture on gait disturbance and analyzed hemodynamic changes caused by acupuncture in the cerebral cortex of patients with PD. METHODS: Participants (n = 26) with gait disturbance due to PD were randomly assigned to the intervention (acupuncture twice a week for 4 weeks + conventional therapy) or control (conventional therapy) groups. We analyzed gait parameters using the GAITRite system and hemodynamic responses in the cerebral cortices using functional near-infrared spectroscopy, Unified Parkinson's Disease Rating Scale (UPDRS) scores, neurotransmitter levels, as well as the immediate effects of acupuncture in patients with PD. RESULTS: The participants tended to walk with hypometric gait (high cadence, short steps) overground. After acupuncture treatment, those in the intervention group showed a significant reduction in cadence and the UPDRS scores involving "walking and balance" compared with those in the control group (P = .004 and P = .020, respectively); the stride, swing, and single support times were significantly increased (P = .006, P = .001, and P = .001, respectively). Oxyhemoglobin levels in the intervention group while walking on a treadmill were significantly increased in the prefrontal and supplementary motor areas. The oxyhemoglobin levels in the prefrontal cortex and swing time revealed significant positive correlations. CONCLUSIONS: Our findings indicated that acupuncture tended to improve hypometric gait and rearranged activation of the cerebral cortex. Thus, acupuncture may be a useful complementary treatment for gait disturbance, including hypometric gait, in patients with PD. Trial Registration Number. Clinical Research Information Service (KCT0002603), https://cris.nih.go.kr/cris/index.jsp.


Assuntos
Terapia por Acupuntura , Córtex Cerebral/fisiopatologia , Transtornos Neurológicos da Marcha/terapia , Plasticidade Neuronal/fisiologia , Doença de Parkinson/terapia , Idoso , Animais , Córtex Cerebral/diagnóstico por imagem , Feminino , Neuroimagem Funcional , Transtornos Neurológicos da Marcha/diagnóstico por imagem , Transtornos Neurológicos da Marcha/etiologia , Humanos , Masculino , Pessoa de Meia-Idade , Avaliação de Resultados em Cuidados de Saúde , Doença de Parkinson/complicações , Doença de Parkinson/diagnóstico por imagem , Projetos Piloto , Método Simples-Cego , Espectroscopia de Luz Próxima ao Infravermelho
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