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1.
Biomol Ther (Seoul) ; 2024 Apr 09.
Artigo em Inglês | MEDLINE | ID: mdl-38589300

RESUMO

In this study, we investigated the efficacy of kaempferol (a flavonoid found in plants and plant-derived foods such as kale, beans, tea, spinach and broccoli) on vascular contractibility and aimed to clarify the detailed mechanism underlying the relaxation. Isometric contractions of divested muscles were stored and linked with western blot analysis which was carried out to estimate the phosphorylation of myosin phosphatase targeting subunit 1 (MYPT1) and phosphorylation-dependent inhibitory protein for myosin phosphatase (CPI-17) and to estimate the effect of kaempferol on the RhoA/ROCK/CPI-17 pathway. Kaempferol conspicuously impeded phorbol ester-, fluoride- and a thromboxane mimetic-derived contractions regardless of endothelial nitric oxide synthesis, indicating its direct effect on smooth muscles. It also conspicuously impeded the fluoride-derived elevation in phospho-MYPT1 rather than phospho-CPI-17 levels and phorbol 12,13-dibutyrate-derived increase in phospho-CPI-17 and phospho-ERK1/2 levels, suggesting the depression of PKC and MEK activities and subsequent phosphorylation of CPI-17 and ERK1/2. Taken together, these outcomes suggest that kaempferol-derived relaxation incorporates myosin phosphatase retrieval and calcium desensitization, which appear to be modulated by CPI-17 dephosphorylation mainly through PKC inactivation.

2.
Drug Saf ; 47(4): 365-375, 2024 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-38483767

RESUMO

INTRODUCTION: Seasonal influenza is associated with substantial public health burden. The objective of this study was to assess the safety of inactivated quadrivalent seasonal influenza vaccine (IIV4, Fluarix Tetra, GSK, Belgium) in subjects aged ≥ 6 months in Korea. METHODS: This prospective, observational, non-comparative, multi-centre post-marketing surveillance study was conducted in Korea in subjects aged ≥ 3 years for 6 years (2014-2020) and extended to subjects aged 6-35 months for 4 years (2018-2022). Subjects received IIV4 in routine clinical practice according to local prescribing information. Adverse events (AEs) were recorded over 21 days post-vaccination. RESULTS: The group aged ≥ 3 years included 701 subjects (mean 31.97 years, range 3-86 years, 46.36% male), and the group aged 6-35 months included 687 subjects (mean 16.31 months, 47.02% male). In the group aged ≥ 3 years, 98 subjects (13.98%) reported 140 AEs, of which 42 events in 34 subjects (4.85%) were adverse reactions to vaccine (ARVs). Most of the ARVs were expected, mainly administration site reactions. There were seven mild unexpected ARVs. In the group aged 6-35 months, 248 AEs were reported in 149/687 subjects (21.69%). ARVs were reported in 25/687 subjects (3.64%, 29 events); one was considered unexpected. There were five serious AEs overall, none of which were considered related. CONCLUSION: No safety concerns were found during this surveillance study of IIV4 in subjects aged ≥ 6 months in Korea. The findings of this study suggest IIV4 is safe and well tolerated for use in all age groups with a vaccine indication.


Seasonal influenza is associated with over 5000 deaths annually in Korea, mainly in older adults. Annual vaccination is the most effective way of preventing seasonal influenza. The influenza virus strains in the vaccine are updated each year as the strains circulating change constantly. Monitoring of any unwanted medical incidents (adverse events) after vaccination is required to help assess vaccine safety. In this study, we monitored adverse events reported within 21 days of administration of Fluarix Tetra seasonal influenza vaccine (IIV4) in participants aged 6 months and older in Korea over a period of 4­6 years. Of the participants aged ≥ 3 years, 98 (14%) reported 140 adverse events, most commonly infections and infestations (most commonly nasopharyngitis such as the common cold), or general disorders and administration site conditions (most commonly pain or swelling at the injection site). In the participants aged 6­35 months, 149 (22%) reported 248 adverse events, also most commonly infections and infestations (such as the common cold) or general disorders and administration site conditions (most commonly fever or swelling at the injection site). There were five serious adverse events in total (adverse events that are life threatening or require hospitalization), but none of them were related to IIV4. In this study, we did not find any safety concerns for IIV4 in participants aged ≥ 6 months in Korea. The findings of this study suggest IIV4 is safe and well tolerated in all age groups with a vaccine indication.


Assuntos
Vacinas contra Influenza , Influenza Humana , Vigilância de Produtos Comercializados , Feminino , Humanos , Masculino , Vacinas contra Influenza/efeitos adversos , Influenza Humana/prevenção & controle , Estudos Prospectivos , República da Coreia/epidemiologia , Estações do Ano , Vacinas de Produtos Inativados/efeitos adversos , Pré-Escolar , Criança , Adolescente , Adulto Jovem , Adulto , Pessoa de Meia-Idade , Idoso , Idoso de 80 Anos ou mais
3.
High Blood Press Cardiovasc Prev ; 31(2): 177-187, 2024 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-38436891

RESUMO

INTRODUCTION: Clinical guidelines recommend measurement of arterial (carotid and femoral) plaque burden by vascular ultrasound (VUS) as a risk modifier in individuals at low or moderate risk without known atherosclerotic cardiovascular disease (ASCVD). AIM: To evaluate the prevalence of carotid and femoral plaques by age and sex, the burden of subclinical atherosclerosis (SA), and its association with classic CVRF in subjects over 30 years of age without ASCVD. METHODS: We prospectively enrolled 5775 consecutive subjects referred for cardiovascular evaluation and determined the prevalence and burden of SA using 2D-VUS in carotid and femoral arteries. RESULTS: Sixty-one percent were men with a mean age of 51.3 (SD 10.6) years. Overall, plaque prevalence was 51% in carotid arteries, 39.3% in femoral arteries, 62.4% in carotid or femoral arteries, and 37.6% in neither. The prevalence of plaques and SA burden showed an increasing trend with age, being higher in men than in women and starting before the age of 40, both in the carotid and femoral sites. There was also an increasing prevalence of plaques according to the number of CVRF, and interestingly we found a high prevalence of plaques in subjects with 0 or 1 classic CVRF. CONCLUSIONS: We observed an increased prevalence and burden of carotid or femoral SA, higher in men, beginning before the fourth decade of life and increasing with age. Despite a significant association with classic CVRF, a significant number of subjects with low CVRF were diagnosed with SA.


Assuntos
Doenças das Artérias Carótidas , Artéria Femoral , Hospitais Comunitários , Doença Arterial Periférica , Placa Aterosclerótica , Humanos , Masculino , Feminino , Artéria Femoral/diagnóstico por imagem , Prevalência , Pessoa de Meia-Idade , Doenças das Artérias Carótidas/epidemiologia , Doenças das Artérias Carótidas/diagnóstico por imagem , Estudos Prospectivos , Adulto , Placa Aterosclerótica/epidemiologia , Doença Arterial Periférica/epidemiologia , Doença Arterial Periférica/diagnóstico por imagem , Doença Arterial Periférica/diagnóstico , Medição de Risco , Valor Preditivo dos Testes , Idoso , Doenças Assintomáticas , Fatores Sexuais , Fatores Etários , Fatores de Risco , Ultrassonografia , Distribuição por Idade , Estudos Transversais
4.
Alzheimers Dement ; 19(11): 5198-5208, 2023 11.
Artigo em Inglês | MEDLINE | ID: mdl-37171018

RESUMO

INTRODUCTION: This discrete choice experiment (DCE) identified Asian American and Pacific Islander (AAPI) adults' preferences for recruitment strategies/messaging to enroll in the Collaborative Approach for AAPI Research and Education (CARE) registry for dementia-related research. METHODS: DCE recruitment strategy/messaging options were developed in English, Chinese, Korean, and Vietnamese. AAPI participants 50 years and older selected (1) who, (2) what, and (3) how they would prefer hearing about CARE. Analyses utilized conditional logistic regression. RESULTS: Participants self-identified as Asian Indian, Chinese, Filipino, Japanese, Korean, Samoan, or Vietnamese (N = 356). Overall, they preferred learning about CARE from the healthcare community (vs. community champions and faith-based organizations), joining CARE to advance research (vs. personal experiences), and hearing about CARE through social media/instant messaging (vs. flyer or workshop/seminar). Preferences varied by age, ethnic identity, and survey completion language. DISCUSSION: DCE findings may inform tailoring recruitment strategies/messaging to engage diverse AAPI in an aging-focused research registry.


Assuntos
Asiático , População das Ilhas do Pacífico , Seleção de Pacientes , Sistema de Registros , Adulto , Humanos , Inquéritos e Questionários , Envelhecimento
5.
Alzheimers Dement ; 19(2): 433-443, 2023 02.
Artigo em Inglês | MEDLINE | ID: mdl-35420258

RESUMO

INTRODUCTION: Clinical research focused on aging, Alzheimer's disease and related dementias (ADRD), and caregiving often does not recruit Asian Americans and Pacific Islanders (AAPIs). METHODS: With funding from the National Institute on Aging, we designed and launched the Collaborative Approach for AAPIs Research and Education (CARE), a research recruitment registry to increase AAPIs' participation in ADRD, aging, and caregiving research. We present the design of this novel recruitment program. RESULTS: CARE uses community-based participatory research methods that are culturally and linguistically appropriate. Since CARE's launch, it has enrolled >7000 AAPIs in a 1-year period. The majority enrolled in CARE via community organizations and reported never having participated in any kind of research before. CARE also engages researchers by establishing a recruitment referral request protocol. DISCUSSION: CARE provides a promising venue to foster meaningful inclusion of AAPIs who are under-represented in aging and dementia-related research.


Assuntos
Doença de Alzheimer , Humanos , Cuidadores , Asiático , População das Ilhas do Pacífico , Sistema de Registros , Envelhecimento
6.
Biomol Ther (Seoul) ; 31(2): 193-199, 2023 Mar 01.
Artigo em Inglês | MEDLINE | ID: mdl-36065763

RESUMO

In this investigation, we made a study of the efficacy of luteolin (a flavonoid found in plants such as vegetables, herbs and fruits) on vascular contractibility and to elucidate the mechanism underlying the relaxation. Isometric contractions of denuded muscles were stored and combined with western blot analysis which was conducted to assess the phosphorylation of myosin phosphatase targeting subunit 1 (MYPT1) and phosphorylation-dependent inhibitory protein for myosin phosphatase (CPI-17) and to examine the effect of luteolin on the RhoA/ROCK/CPI-17 pathway. Luteolin significantly alleviated phorbol ester-, fluoride- and thromboxane mimetic-elicited contractions regardless of endothelial nitric oxide synthesis, implying its direct effect on smooth muscle. It also significantly alleviated the fluoride-elicited elevation in pCPI-17 and pMYPT1 levels and phorbol 12,13-dibutyrate-elicited increase in pERK1/2 level, suggesting depression of ROCK and PKC/MEK activity and ensuing phosphorylation of MYPT1, CPI-17 and ERK1/2. Taken together, these results suggest that luteolin-elicited relaxation includes myosin phosphatase reactivation and calcium desensitization, which seems to be arbitrated by CPI-17 dephosphorylation via ROCK/PKC inhibition.

7.
Sci Rep ; 12(1): 16519, 2022 10 03.
Artigo em Inglês | MEDLINE | ID: mdl-36192565

RESUMO

Aceclofenac controlled-release (CR) is a once-a-day tablet with 200 mg of aceclofenac, and is bioequivalent to conventional aceclofenac. However, its safety in humans has not been well studied in Korea. Therefore, we aimed to evaluate the overall incidence and patterns of adverse events (AEs), the effectiveness of aceclofenac CR, and the differences in incidence rates of the AEs based on each patient's baseline charateristics. This study was conducted on patients receiving aceclofenac CR in clinical practice at each investigational institution to treat musculoskeletal pain and inflammation. The subjects were administered one tablet of aceclofenac CR (200 mg once-a-day) and were observed for 4 weeks post-administration. Factors affecting the occurrence of AEs were evaluated, and the Visual Analogue Scale (VAS) was used to measure the pain intensity. Among 14,543 subjects, the incidence rate of AEs was 0.86%, and that of adverse drug reactions was 0.74%. No serious AEs and unexpected adverse drug reactions were monitored. The incidence rates of AEs were significantly higher in females, inpatient treatment, individuals with concurrent disorders, and those receiving concomitant medications, respectively (all P < 0.05). Four weeks post-using aceclofenac CR, the mean changes in VAS was significantly decreased compared to prior administration. The overall clinical efficacy rate was 91.63%. This study confirmed that no severe adverse reactions were observed for aceclofenac CR exceeding those previously reported for safety results of conventional formulation of this drug in routine clinical practice settings. The use of aceclofenac CR might not violate the previously reported information on the safety and effectiveness of aceclofenac.


Assuntos
Anti-Inflamatórios não Esteroides , Efeitos Colaterais e Reações Adversas Relacionados a Medicamentos , Anti-Inflamatórios não Esteroides/efeitos adversos , Preparações de Ação Retardada , Diclofenaco/efeitos adversos , Diclofenaco/análogos & derivados , Método Duplo-Cego , Efeitos Colaterais e Reações Adversas Relacionados a Medicamentos/epidemiologia , Feminino , Humanos , Comprimidos , Resultado do Tratamento
9.
J Med Food ; 25(10): 943-951, 2022 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-36178947

RESUMO

Humulus japonicus (HJ) is an herbal medicine, which has been reported as being antioxidative and anti-inflammatory. The present study aimed to investigate the effect of oral administration of HJ water extract (HJW) on cognitive function through the cholinergic system in Alzheimer's disease (AD) mouse models. Institute of Cancer Research mice injected with beta-amyloid (Aß) (1-42) (i.c.v.) and APP/PS1 transgenic (TG) mice were orally administered with HJW at 500 mg/kg/day for 3 weeks. Aß-injected mice and APP/PS1 TG mice showed cognitive dysfunction, which was evaluated by various behavioral tests. HJW treatment significantly attenuated memory impairments in Aß-injected mice and APP/PS1 TG mice. Aß injection decreased acetylcholine (ACh) concentrations and choline acetyltransferase (ChAT) activity, and increased acetylcholinesterase (AChE) activity. These cholinergic impairments were also found in APP/PS1 TG mice. HJW significantly attenuated cholinergic alterations in Aß-injected mice and TG mice. In addition, HJW significantly decreased Aß plaque deposition in the cerebral cortex and hippocampus of TG mice. Therefore, the present study demonstrated that HJW protected against AD-related memory impairments via enhancing the cholinergic system and inhibiting Aß plaque deposition.


Assuntos
Doença de Alzheimer , Disfunção Cognitiva , Humulus , Animais , Camundongos , Doença de Alzheimer/tratamento farmacológico , Acetilcolinesterase , Colina O-Acetiltransferase/metabolismo , Colina O-Acetiltransferase/farmacologia , Acetilcolina , Peptídeos beta-Amiloides/metabolismo , Placa Amiloide , Camundongos Transgênicos , Modelos Animais de Doenças , Hipocampo , Transtornos da Memória , Água , Colinérgicos/farmacologia
10.
Int J Mol Sci ; 23(15)2022 Aug 01.
Artigo em Inglês | MEDLINE | ID: mdl-35955672

RESUMO

A kenaf-derived activated carbon (KAC) for a high-power density supercapacitor was developed in this study through phosphoric acid activation. The N2/77K isothermal adsorption-desorption curve was used to estimate the textural properties of KAC based on BET and BJH and the pore size distribution based on NLDFT. The electrochemical properties of KAC were analyzed by using the coin-type cell applying 1 M SPBBF4/PC electrolyte, and the specific surface area and total pore volume were 1490-1942 m2/g and 1.18-3.18 cm3/g, respectively. The pore characteristics of KAC varied according to the activation temperature, and most KAC showed a mesoporous structure. As the activation temperature increased, the mesopore volume increased up to 700 °C, then decreased. The mesoporous structure of KAC resulted in a substantial decrease in the Warburg impedance as the ion diffusion resistance decreased. Hence, the specific capacitance of KAC decreased from 82.9 F/g to 59.48 F/g as the charge-discharge rate increased from 1 mA/g to 10 mA/g, with the rate of reduction at approximately 30%. The rate of reduction of KAC's specific capacitance was 50% lower compared with commercial activated carbon; hence, KAC is a more suitable electrode-active material for high power density supercapacitors.


Assuntos
Carvão Vegetal , Adsorção , Biomassa , Carvão Vegetal/química , Capacitância Elétrica , Eletrodos
11.
J Med Internet Res ; 24(8): e38443, 2022 08 09.
Artigo em Inglês | MEDLINE | ID: mdl-35658091

RESUMO

BACKGROUND: During the COVID-19 pandemic, there have been increased reports of racial biases against Asian American and Native Hawaiian and Pacific Islander individuals. However, the extent to which different Asian American and Native Hawaiian and Pacific Islander groups perceive and experience (firsthand or as a witness to such experiences) how COVID-19 has negatively affected people of their race has not received much attention. OBJECTIVE: This study used data from the COVID-19 Effects on the Mental and Physical Health of Asian Americans and Pacific Islanders Survey Study (COMPASS), a nationwide, multilingual survey, to empirically examine COVID-19-related racial bias beliefs among Asian American and Native Hawaiian and Pacific Islander individuals and the factors associated with these beliefs. METHODS: COMPASS participants were Asian American and Native Hawaiian and Pacific Islander adults who were able to speak English, Chinese (Cantonese or Mandarin), Korean, Samoan, or Vietnamese and who resided in the United States during the time of the survey (October 2020 to May 2021). Participants completed the survey on the web, via phone, or in person. The Coronavirus Racial Bias Scale (CRBS) was used to assess COVID-19-related racial bias beliefs toward Asian American and Native Hawaiian and Pacific Islander individuals. Participants were asked to rate the degree to which they agreed with 9 statements on a 5-point Likert scale (ie, 1=strongly disagree to 5=strongly agree). Multivariable linear regression was used to examine the associations between demographic, health, and COVID-19-related characteristics and perceived racial bias. RESULTS: A total of 5068 participants completed the survey (mean age 45.4, SD 16.4 years; range 18-97 years). Overall, 73.97% (3749/5068) agreed or strongly agreed with ≥1 COVID-19-related racial bias belief in the past 6 months (during the COVID-19 pandemic). Across the 9 racial bias beliefs, participants scored an average of 2.59 (SD 0.96, range 1-5). Adjusted analyses revealed that compared with Asian Indians, those who were ethnic Chinese, Filipino, Hmong, Japanese, Korean, Vietnamese, and other or multicultural had significantly higher mean CRBS scores, whereas no significant differences were found among Native Hawaiian and Pacific Islander individuals. Nonheterosexual participants had statistically significant and higher mean CRBS scores than heterosexual participants. Compared with participants aged ≥60 years, those who were younger (aged <30, 30-39, 40-49, and 50-59 years) had significantly higher mean CRBS scores. US-born participants had significantly higher mean CRBS scores than foreign-born participants, whereas those with limited English proficiency (relative to those reporting no limitation) had lower mean CRBS scores. CONCLUSIONS: Many COMPASS participants reported racial bias beliefs because of the COVID-19 pandemic. Relevant sociodemographic contexts and pre-existing and COVID-19-specific factors across individual, community, and society levels were associated with the perceived racial bias of being Asian during the pandemic. The findings underscore the importance of addressing the burden of racial bias on Asian American and Native Hawaiian and Pacific Islander communities among other COVID-19-related sequelae.


Assuntos
COVID-19 , Racismo , Adolescente , Adulto , Idoso , Idoso de 80 Anos ou mais , Asiático , Feminino , Humanos , Pessoa de Meia-Idade , Havaiano Nativo ou Outro Ilhéu do Pacífico , Pandemias , Estados Unidos , Adulto Jovem
12.
Biomol Ther (Seoul) ; 30(4): 348-359, 2022 Jul 01.
Artigo em Inglês | MEDLINE | ID: mdl-35768332

RESUMO

Gastric adenocarcinoma is among the top causes of cancer-related death and is one of the most commonly diagnosed carcinomas worldwide. Benzyl isothiocyanate (BITC) has been reported to inhibit the gastric cancer metastasis. In our previous study, BITC induced apoptosis in AGS cells. The purpose of the present study was to investigate the effect of BITC on autophagy mechanism in AGS cells. First, the AGS cells were treated with 5, 10, or 15 µM BITC for 24 h, followed by an analysis of the autophagy mechanism. The expression level of autophagy proteins involved in different steps of autophagy, such as LC3B, p62/SQSTM1, Atg5-Atg12, Beclin1, p-mTOR/mTOR ratio, and class III PI3K was measured in the BITC-treated cells. Lysosomal function was investigated using cathepsin activity and Bafilomycin A1, an autophagy degradation stage inhibitor. Methods including qPCR, western blotting, and immunocytochemistry were employed to detect the protein expression levels. Acridine orange staining and omnicathepsin assay were conducted to analyze the lysosomal function. siRNA transfection was performed to knock down the LC3B gene. BITC reduced the level of autophagy protein such as Beclin 1, class III PI3K, and Atg5-Atg12. BITC also induced lysosomal dysfunction which was shown as reducing cathepsin activity, protein level of cathepsin, and enlargement of acidic vesicle. Overall, the results showed that the BITC-induced AGS cell death mechanism also comprises the inhibition of the cytoprotective autophagy at both initiation and degradation steps.

13.
Biochem Biophys Res Commun ; 608: 142-148, 2022 06 11.
Artigo em Inglês | MEDLINE | ID: mdl-35398611

RESUMO

Abietic acid (AA), the main component of pine resin that has been traditionally used as Asian medicine, has been reported to demonstrate anti-inflammatory activities. Despite this, little is known about the effects of AA on hepatic endoplasmic reticulum (ER) stress and lipid metabolism. This study investigated the impacts of AA on ER stress and steatosis in in vitro obesity models. We found that Treatment with AA reduced lipid deposition and lipogenesis-related proteins expression in human primary hepatocytes. Augmented expression of ER stress markers (phospho-eukaryotic initiation factor-2α (eIF2α) and C/EBP homologous protein (CHOP)) in palmitate-treated hepatocytes were reversed by AA treatment. Further, AA treatment increased the expression of phospho-AMPK and oxygen-regulated protein 150 (ORP150) in hepatocytes. siRNA-associated knockdown of AMPK or ORP150 expression reduced the effects of AA on not only hepatic ER stress but also lipogenesis and apoptosis. These results denote that AA attenuates lipid accumulation in hepatocytes in the presence of palmitate through the suppression of ER stress by AMPK/ORP150 signaling. AA could be a potential candidate for treating non-alcoholic fatty liver disease.


Assuntos
Proteínas Quinases Ativadas por AMP , Abietanos , Estresse do Retículo Endoplasmático , Proteínas de Choque Térmico HSP70 , Hepatócitos , Proteínas Quinases Ativadas por AMP/metabolismo , Abietanos/farmacologia , Estresse do Retículo Endoplasmático/efeitos dos fármacos , Proteínas de Choque Térmico HSP70/metabolismo , Hepatócitos/metabolismo , Humanos , Hipercolesterolemia/metabolismo , Metabolismo dos Lipídeos , Fígado/metabolismo , Hepatopatia Gordurosa não Alcoólica/tratamento farmacológico , Hepatopatia Gordurosa não Alcoólica/metabolismo , Oxigênio/metabolismo , Palmitatos/metabolismo , Palmitatos/farmacologia
14.
Artigo em Inglês | MEDLINE | ID: mdl-35055744

RESUMO

Reports of escalated discrimination among Asian Americans and Pacific Islanders (AAPIs) due to COVID-19 are alarming, making this a public health priority. However, there are limited empirical studies on the scope and impact of COVID-19-related discrimination among AAPIs. Using the COVID-19 Effects on the Mental and Physical Health of AAPI Survey Study (COMPASS) data (N = 4971; survey period: October 2020-February 2021), which is a U.S.-wide multi-lingual survey, we examined the prevalence of, and factors associated with discrimination experiences attributable to being an AAPI during the COVID-19 pandemic. Overall, 60.7% reported experiencing discrimination; the group prevalence ranged from 80.0% (Hmong) to 40.5% (Native Hawaiians and Pacific Islanders). Multivariable logistic regression models revealed that COVID-19-related factors were associated with many discrimination experiences: having a shelter-in-place order of ≥1 month, living in areas with perceived similar/higher COVID-19 severity, and negative impact in family income/employment due to COVID-19. Additionally, being Asian American (versus Native Hawaiians and Pacific Islanders), females, non-heterosexuals, younger, more severe effect on family income, living in the non-West, and poorer health were significantly correlated with discrimination experiences. Findings may assist in formulating anti-AAPI-discrimination policies and programs at the local, state, and federal levels. Culturally appropriate programs and policies to combat this are urgently needed.


Assuntos
COVID-19 , Havaiano Nativo ou Outro Ilhéu do Pacífico , Asiático , Feminino , Humanos , Pandemias , Prevalência , SARS-CoV-2
15.
Biomol Ther (Seoul) ; 30(2): 145-150, 2022 Mar 01.
Artigo em Inglês | MEDLINE | ID: mdl-34231489

RESUMO

In this study, we investigated the influence of galangin on vascular contractibility and to determine the mechanism underlying the relaxation. Isometric contractions of denuded aortic muscles were recorded and combined with western blot analysis which was performed to measure the phosphorylation of phosphorylation-dependent inhibitory protein of myosin phosphatase (CPI-17) and myosin phosphatase targeting subunit 1 (MYPT1) and to evaluate the effect of galangin on the RhoA/ROCK/CPI-17 pathway. Galangin significantly inhibited phorbol ester-, fluoride- and thromboxane mimetic-induced vasoconstrictions regardless of endothelial nitric oxide synthesis, suggesting its direct effect on vascular smooth muscle. Galangin significantly inhibited the fluoride-dependent increase in pMYPT1 and pCPI-17 levels and phorbol 12,13-dibutyrate-dependent increase in pERK1/2 level, suggesting repression of ROCK and MEK activity and subsequent phosphorylation of MYPT1, CPI-17 and ERK1/2. Taken together, these results suggest that galangin-induced relaxation involves myosin phosphatase reactivation and calcium desensitization, which appears to be mediated by CPI-17 dephosphorylation via not PKC but ROCK inactivation.

16.
Biochem Biophys Res Commun ; 577: 17-23, 2021 11 05.
Artigo em Inglês | MEDLINE | ID: mdl-34487960

RESUMO

3-hydroxymorphinan (3-HM), a metabolite of dextromethorphan, has previously been reported to have anti-inflammatory, anti-oxidative stress, and neuroprotective effects. However, its effect on energy metabolism in adipocytes remains unclear. Herein, we investigated 3-hydroxymorphinan (3-HM) effects on mitochondrial biogenesis, oxidative stress, and lipid accumulation in 3T3-L1 adipocytes. Further, we explored 3-HM-associated molecular mechanisms. Mouse adipocyte 3T3-L1 cells were treated with 3-HM, and various protein expression levels were determined by western blotting analysis. Mitochondria accumulation and lipid accumulation were measured by staining methods. Cell toxicity was assessed by cell viability assay. We found that treatment of 3T3-L1 adipocytes with 3-HM increased expression of brown adipocyte markers, such as uncoupling protein-1 (UCP-1) and peroxisome proliferator-activated receptor-gamma coactivator 1-alpha (PGC-1α). 3-HM promotes mitochondrial biogenesis and its-mediated gene expression. Additionally, 3-HM treatment suppressed mitochondrial ROS generation and superoxide along with improved mitochondrial complex I activity. We found that treatment of 3-HM enhanced AMPK phosphorylation. siRNA-mediated suppression of AMPK reversed all these changes in 3T3-L1 adipocytes. In sum, 3-HM promotes mitochondrial biogenesis and browning and attenuates oxidative stress and lipid accumulation in 3T3-L1 adipocytes via AMPK signaling. Thus, 3-HM-mediated AMPK activation can be considered a therapeutic approach for treating obesity and related diseases.


Assuntos
Proteínas Quinases Ativadas por AMP/metabolismo , Adipócitos Marrons/efeitos dos fármacos , Adipócitos/efeitos dos fármacos , Dextrometorfano/análogos & derivados , Biogênese de Organelas , Transdução de Sinais/efeitos dos fármacos , Células 3T3-L1 , Proteínas Quinases Ativadas por AMP/genética , Adipócitos/citologia , Adipócitos/metabolismo , Adipócitos Marrons/citologia , Adipócitos Marrons/metabolismo , Animais , Western Blotting , Sobrevivência Celular/efeitos dos fármacos , Dextrometorfano/farmacologia , Metabolismo dos Lipídeos/efeitos dos fármacos , Lipogênese/efeitos dos fármacos , Camundongos , Mitocôndrias/efeitos dos fármacos , Mitocôndrias/metabolismo , Estresse Oxidativo/efeitos dos fármacos , Coativador 1-alfa do Receptor gama Ativado por Proliferador de Peroxissomo/metabolismo , Fosforilação/efeitos dos fármacos , Interferência de RNA , Proteína Desacopladora 1/metabolismo
17.
Alzheimers Dement (N Y) ; 7(1): e12195, 2021.
Artigo em Inglês | MEDLINE | ID: mdl-34295961

RESUMO

INTRODUCTION: This study elicited Asian Americans and Pacific Islanders' (AAPI) perspectives about recruitment strategies/messaging for participation in an aging, Alzheimer's disease and related dementias (ADRD), and caregiving research recruitment registry. METHODS: Using a mixed methods design, CARE (Collaborative Approach for AAPI Research and Education) conducted 14 focus groups (N = 123) with AAPI cultural groups (Asian Indian, Chinese, Filipino, Japanese, Korean, Samoan, Vietnamese) in different languages. Descriptive statistics and thematic qualitative analyses were conducted. RESULTS: Mean age of participants was 54 years (median: 61; range 18-80), 66% were female, and 81% were foreign-born. Themes of consideration for recruitment emerged: (1) culturally/linguistically appropriate outreach in culturally specific spaces, (2) motivations for research participation, and (3) approaches to outreach and recruitment methods. Within each of these themes, there were ethnic differences in specific strategies/approaches reflected as subthemes. DISCUSSION: Recruitment and messaging strategies should be tailored uniquely for each targeted AAPI group, with a thorough understanding of the cultural/linguistic factors that facilitate research participation to increase AAPI participation in ADRD, aging, and caregiver-related research. .

18.
Mol Cell Endocrinol ; 534: 111364, 2021 08 20.
Artigo em Inglês | MEDLINE | ID: mdl-34126189

RESUMO

Capmatinib (CAP) has been used to treat metastatic non-small lung cancer (NSCL) and suppress inflammation. It causes hypoglycemia in NSCL patients. Therefore, it is expected that CAP improves inflammation-mediated insulin resistance due to its anti-inflammatory effect. However, the impacts of CAP on insulin signaling in skeletal muscle cells have not yet been fully elucidated. Herein, we investigated the effect of CAP on insulin resistance in palmitate-treated C2C12 myocytes and explored the related molecular mechanisms. We found that treatment of C2C12 myocytes with CAP reversed palmitate-induced impairment of insulin signaling and glucose uptake. CAP treatment ameliorated phosphorylation of inflammatory markers, including NFκB and IκB, in palmitate-treated C2C12 myocytes. Further, it augmented PPARδ expression and suppressed palmitate-induced p38 phosphorylation in a dose-dependent manner. siRNA-mediated suppression of PPARδ abolished the effects of CAP on palmitate-induced insulin resistance and inflammation as well as p38 phosphorylation. Therefore, it has been shown that CAP treatment ameliorates insulin resistance in palmitate-treated C2C12 myocytes via PPARδ/p38 signaling-mediated suppression of inflammation. These results may represent a novel therapeutic approach that could halt insulin resistance and type 2 diabetes.


Assuntos
Benzamidas/farmacologia , Imidazóis/farmacologia , Sistema de Sinalização das MAP Quinases/efeitos dos fármacos , Fibras Musculares Esqueléticas/citologia , Palmitatos/efeitos adversos , Triazinas/farmacologia , Animais , Linhagem Celular , Relação Dose-Resposta a Droga , Regulação da Expressão Gênica/efeitos dos fármacos , Glucose/metabolismo , Proteínas I-kappa B/metabolismo , Resistência à Insulina , Camundongos , Modelos Biológicos , Fibras Musculares Esqueléticas/efeitos dos fármacos , Fibras Musculares Esqueléticas/metabolismo , NF-kappa B/metabolismo , PPAR delta/metabolismo , Fosforilação/efeitos dos fármacos
19.
Pharmaceutics ; 12(8)2020 Aug 10.
Artigo em Inglês | MEDLINE | ID: mdl-32785038

RESUMO

This study aimed to restore the skin barrier function from atopic dermatitis (AD) via treatment with leucine-rich glioma inactivated 3 (LGI3) peptide. Male NC/Nga mice (7 weeks, 20 g) were randomly allocated into three groups (control, AD, and LGI3 group). After induction of AD skin lesions with Dermatophagoides farinae ointment, mice were treated with LGI3. The clinical score of AD was the highest and the dorsal skin thickness was the thickest in the AD group. In contrast, LGI3 treatment improved the clinical score and the dorsal skin thickness compared to the AD model. LGI3 treatment suppressed histopathological thickness of the epithelial cell layer of the dorsal skin. LGI3 treatment could indirectly reduce mast cell infiltration through restoring the barrier function of the skin. Additionally, the filaggrin expression was increased in immunohistochemical evaluation. In conclusion, the ameliorating effect and maintaining skin barrier homeostasis in the AD murine model treated with LGI3 could be attributed to complete re-epithelialization of keratinocytes. Hence, LGI3 might be considered as a new potential therapeutic target for restoring skin barrier function in AD.

20.
J Photochem Photobiol B ; 209: 111946, 2020 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-32659645

RESUMO

The skin keeps the human body healthy from extrinsic stimuli such as ultraviolet (UV) irradiation. However, chronic exposure of these stimuli reduces the number of proteins that constitute the extracellular matrix (ECM) and causes wrinkle formation. The amount of collagen, the main protein that constitutes connective tissue, is reduced in the human skin due to UV radiation. When human dermal fibroblasts were damaged by UVB, UVB increased the MMPs expressions and degraded type I collagen and other ECM proteins. Oyster (Crassostrea gigas) hydrolysate (OH) is known to have anticancer, antioxidant, and anti-apoptotic effects. To scrutinize the anti-wrinkle effect of the OH in the viewpoint of the balance between collagen degradation and synthesis, we conducted the study in UVB damaged human dermal fibroblasts. We determined type I procollagen, MMPs and related proteins using ELISA kit, qRT-PCR and western blot. In our study, we discovered that OH inhibits collagen degradation by regulating MAPKs, AP-1 and MMPs expression. Also, we found that OH promotes collagen production by enhancing TGFß receptor II expression and Smad3 phosphorylation. These results showed that OH regulates collagen degradation and stimulates collagen synthesis. Through this study, we found that OH is effective in inhibiting wrinkle formation and restore photo-aged human skin. It indicates that OH can be one of the functional materials in the fields of anti-wrinkle research.


Assuntos
Sistema de Sinalização das MAP Quinases/efeitos dos fármacos , Envelhecimento da Pele/efeitos dos fármacos , Pele/efeitos dos fármacos , Proteínas Smad/metabolismo , Fator de Transcrição AP-1/metabolismo , Fator de Crescimento Transformador beta/metabolismo , Raios Ultravioleta , Animais , Colágeno/metabolismo , Humanos , Hidrólise , Sistema de Sinalização das MAP Quinases/efeitos da radiação , Ostreidae , Pele/enzimologia , Pele/metabolismo , Pele/efeitos da radiação , Envelhecimento da Pele/efeitos da radiação
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