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1.
Biochem Biophys Res Commun ; 534: 639-645, 2021 01 01.
Artigo em Inglês | MEDLINE | ID: mdl-33220923

RESUMO

The intestinal epithelium is one of the fastest renewing tissues in mammals and is a barrier against toxic substances such as alcohol. Excessive alcohol can induce intestinal damage leading to intestinal bowel diseases. Thus, the control of small intestinal epithelial cell (IEC) regeneration is thought to be important for homeostasis in response to epithelium damage. However, reports on how epithelial cells respond to small intestinal damage are scarce. We investigated the effects of alcohol consumption on small intestinal epithelial cells of mice. To verify that alcohol altered the small intestinal epithelium, we used 8-10 weeks old male C57BL/6J mice for models of chronic and binge alcohol consumption (the NIAAA model) in addition to an organoid model. Alcohol promoted the proliferative activity of IECs and intestinal stem cells (ISCs) in intestinal crypts. Alcohol consumption increased expression of the proliferation marker cyclin D1 and activated the p44/42 MAPK (Erk1/2) signaling pathway in small intestinal epithelial cells. The Wnt target genes were markedly increased in IECs from alcohol-treated mice. In the small intestinal organoid model exposed to alcohol, the organoid area and numbers of buds increased with alcohol concentrations up to 0.5% similar to in vivo observations. These results suggest that alcohol consumption stimulates the proliferation of small intestinal epithelial cells via Wnt signaling.


Assuntos
Etanol/toxicidade , Mucosa Intestinal/efeitos dos fármacos , Alcoolismo/metabolismo , Alcoolismo/patologia , Animais , Consumo Excessivo de Bebidas Alcoólicas/metabolismo , Consumo Excessivo de Bebidas Alcoólicas/patologia , Movimento Celular/efeitos dos fármacos , Proliferação de Células/efeitos dos fármacos , Modelos Animais de Doenças , Células Epiteliais/efeitos dos fármacos , Células Epiteliais/metabolismo , Células Epiteliais/patologia , Mucosa Intestinal/metabolismo , Mucosa Intestinal/patologia , Intestino Delgado/efeitos dos fármacos , Intestino Delgado/metabolismo , Intestino Delgado/patologia , Masculino , Camundongos , Camundongos Endogâmicos C57BL , Organoides/efeitos dos fármacos , Organoides/metabolismo , Organoides/patologia , Células-Tronco/efeitos dos fármacos , Células-Tronco/metabolismo , Células-Tronco/patologia , Via de Sinalização Wnt/efeitos dos fármacos , Via de Sinalização Wnt/genética
2.
Biochem Biophys Res Commun ; 571: 125-130, 2021 09 24.
Artigo em Inglês | MEDLINE | ID: mdl-34325127

RESUMO

This study investigated the properties of Latilactobacillus curvatus MS2 isolated from Korean traditional fermented seafood as probiotics and the effect of reducing cholesterol as a synbiotic with isomalto-oligosaccharide (IMO) in BALB/c mice. The isolated strain showed high resistance to acids and bile acids and exhibited a high DPPH scavenging capacity of 72.27 ± 0.38 %. In the intestinal adhesion test using HT-29 cells, the adhesion rate of MS2 was 17.10 ± 1.78 %, which was higher than the adhesion rate of the other investigated probiotics. MS2 showed good antimicrobial activity against food-borne pathogens, especially Staphylococcus aureus, S. epidermidis, Escherichia coli, and Vibrio vulnificus. This strain had high availability for IMO among the prebiotics of fructo-oligosaccharide, inulin and IMO. Oral administration of MS2 and IMO to BALB/c mice for 5 weeks resulted in a significant reduction in blood cholesterol levels by regulating liver lipid metabolism. These results suggest that the combination of MS2 and IMO has potential for application in functional foods.


Assuntos
Colesterol/metabolismo , Fermentação , Lactobacillaceae/isolamento & purificação , Oligossacarídeos/metabolismo , Prebióticos/microbiologia , Alimentos Marinhos/microbiologia , Animais , Masculino , Camundongos , Camundongos Endogâmicos BALB C , República da Coreia , Simbióticos
3.
Int J Obes (Lond) ; 45(4): 776-786, 2021 04.
Artigo em Inglês | MEDLINE | ID: mdl-33473176

RESUMO

OBJECTIVE: We investigated the efficacy and safety of liraglutide 3 mg daily in combination with diet and exercise 2, 4, and 6 months after initiation in real-world settings in Korea. METHODS: People first using liraglutide starting in 2018 were recruited from ten sites in Korea. Body weight and body mass index (BMI) were measured after 2, 4, and 6 months and compared with baseline values. RESULTS: The full cohort comprised 769 participants: 672 in the 2-month group, 427 in the 4-month group, and 219 in the 6-month group. The baseline mean ± standard deviation of BMI and body weight were 32.2 ± 5.1 kg/m2, and 87.5 ± 18.8 kg, respectively. Body weight and BMI decreased after initiation of liraglutide treatment: -2.94 kg and -1.08 kg/m2 at 2 months; -4.23 kg and -1.55 kg/m2 at 4 months, and -5.14 kg and -1.89 kg/m2 at 6 months (all P < 0.001). In the 6-month cohort, 52.5% and 18.3% of subjects lost ≥5% and ≥10% of body weight, respectively. After 6 months, systolic and diastolic blood pressure decreased significantly by 3.90 and 1.93 mmHg, respectively. In those with diabetes mellitus, HbA1c and fasting glucose levels decreased significantly by 1.14% and 27.8 mg/dl, respectively. Among all participants, 27.6% experienced adverse effects, including nausea (20.8%), vomiting (5.2%), diarrhoea (2.5%), and skin rash (3.6%). Documented reasons for discontinuation of treatment were lack of effect (4.4%), adverse events (4.3%), and high cost (3.1%). CONCLUSIONS: In real-world settings in Korea, daily treatment with liraglutide 3 mg was associated with clinically meaningful weight loss without serious adverse events.


Assuntos
Estilo de Vida , Liraglutida/uso terapêutico , Obesidade/terapia , Redução de Peso , Adulto , Pressão Sanguínea , Índice de Massa Corporal , Peso Corporal , Exercício Físico , Feminino , Fatores de Risco de Doenças Cardíacas , Humanos , Masculino , Pessoa de Meia-Idade , República da Coreia
4.
Fish Shellfish Immunol ; 119: 182-192, 2021 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-34607010

RESUMO

The purpose of this study was to characterize the bacteria isolated from rockfish intestines and to investigate the effects of feed supplementation in rockfish aquaculture. Bacillus sp. KRF-7 isolated from the intestine of rockfish (Sebastes schlegelii) was demonstrated to be safe based on in vitro tests confirming the absence of hemolysis, cytotoxicity, and genes with toxigenic potential. In a feeding trial, providing a supplemental diet of 1 × 108 CFU g-1Bacillus sp. KRF-7 was observed to positively alter the weight gain, specific growth rate, feed conversion ratio, and protein efficiency ratio of juvenile rockfish. KRF-7 supplementation showed positive regulation of nonspecific immune parameters, such as superoxide dismutase, lysozyme activity, and myeloperoxidase activity. This analysis also revealed a change in the composition of the intestinal microbiota at the phylum level from Proteobacteria to Firmicutes. In both the kidney and spleen, the expression levels of IL-10, NF-κB, and B cell activating factors in the KRF-7-supplemented group were significantly increased compared to those in the control group. Therefore, this study verified the safety of KRF-7 isolated from the intestine of rockfish and suggests that dietary supplementation with KRF-7 enhances the growth performance of rockfish and has beneficial effects on the regulation of the intestinal microbiota and immune response.


Assuntos
Bacillus , Bass , Probióticos , Ração Animal/análise , Animais , Aquicultura , Dieta/veterinária , Suplementos Nutricionais , Intestinos , Mananas , Oligossacarídeos
5.
BMC Womens Health ; 21(1): 96, 2021 03 04.
Artigo em Inglês | MEDLINE | ID: mdl-33663465

RESUMO

BACKGROUND: Lower urinary tract symptoms (LUTS) including frequency, nocturia, urgency, and incontinence, are common in women and cause significant discomfort in daily life. However, diagnosis and treatment of LUTS are often delayed because many patients with such symptoms do not complain to the physician of discomfort and do not seek medical attention. LUTS are known to be associated with muscle weakness. We investigated the association between grip strength and LUTS in women of different ages. METHODS: This study included 4225 women (mean age 48.6 years) who underwent self-referred health screening between April 2015 and December 2019. LUTS were evaluated using a self-reported questionnaire, and the overactive bladder symptom score was used to screen for an overactive bladder. Low muscle strength was defined as a hand grip strength of < 18 kg (decreased grip strength). RESULTS: We observed decreased grip strength in 13.7% (n = 580) of the participants. Nocturia, urgency, incontinence, and overactive bladder were more common in women with decreased grip strength than in women with normal grip strength. After adjusting for age, comorbidities (hypertension, diabetes, hyperlipidemia), smoking status, alcohol consumption, regular exercise, and stress, nocturia (odds ratio [OR] 1.19, 95% confidence interval [CI] 1.01-1.52), urinary incontinence (OR 1.32, 95% CI 1.01-1.72), and an overactive bladder (OR 1.75, 95% CI 1.35-2.27) were significantly associated with decreased grip strength. CONCLUSIONS: The findings suggest that LUTS, especially nocturia, incontinence, and an overactive bladder are associated with decreased grip strength in women. Therefore, physicians should be aware that patients may not seek help, even if they are uncomfortable, and it is important to obtain a detailed medical history and perform additional tests, even in the absence of complaints, in patients with low grip strength, who are at high risk of LUTS.


Assuntos
Sintomas do Trato Urinário Inferior , Bexiga Urinária Hiperativa , Estudos Transversais , Feminino , Força da Mão , Humanos , Sintomas do Trato Urinário Inferior/epidemiologia , Pessoa de Meia-Idade , Prevalência , República da Coreia/epidemiologia , Inquéritos e Questionários , Bexiga Urinária Hiperativa/complicações , Bexiga Urinária Hiperativa/epidemiologia
6.
Nutr J ; 19(1): 116, 2020 10 16.
Artigo em Inglês | MEDLINE | ID: mdl-33066775

RESUMO

BACKGROUND: Obesity defined solely by the Body Mass Index (BMI) may not reflect the true heterogeneity of the obese population. This study aimed to classify the dietary behaviours of overweight and obese individuals and to explore the relationship between patterns of dietary behaviour and cardiometabolic risk factors. METHODS: A total of 259 patients who visited an outpatient weight management clinic at a tertiary hospital and underwent a dietary behaviour assessment between January 2014 and February 2019 were enrolled in the study. Dietary behaviours were assessed in three domains with nine categories, including choice of food (frequently eating out and consumption of instant/fast/takeaway food), eating behaviour (irregular meals; frequent snacking, including eating at night; emotional eating; and overeating/binge eating), and nutrient intake (high-fat/high-calorie foods, salty food, and poorly balanced diet). Latent class analysis (LCA) was used to classify the subjects according to these categories. Associations between latent class and metabolic syndrome were assessed by logistic regression. RESULTS: The subjects were classified into three LCA-driven classes, including a referent class of healthy but unbalanced eaters (n = 118), a class of emotional eaters (n = 53), and a class of irregular unhealthy eaters (n = 88). Compared with the referent class, emotional eaters had a significantly higher BMI (beta = 3.40, P < 0.001) accompanied by metabolic syndrome (odds ratio 2.88, 95% confidence interval 1.16-7.13). CONCLUSIONS: Our three LCA-driven obesity phenotypes could be useful for assessment and management of obesity and metabolic syndrome. The association between emotional eaters and higher BMI and metabolic syndrome was stronger than that with other eaters. Thus, emotional regulation strategies might have benefit for emotional eater's diet.


Assuntos
Síndrome Metabólica , Índice de Massa Corporal , Estudos Transversais , Dieta , Comportamento Alimentar , Humanos , Análise de Classes Latentes , Síndrome Metabólica/epidemiologia , Estudos Retrospectivos
7.
Genes Cells ; 20(7): 578-89, 2015 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-25908210

RESUMO

Carcinoembryonic antigen-related cell adhesion molecule (CEACAM) 1 and CEACAM20, immunoglobulin superfamily members, are predominantly expressed in intestinal epithelial cells (IECs) and co-localized at the apical surface of these cells. We here showed that the expression of mouse CEACAM1 and CEACAM20 at both mRNA and protein levels was markedly reduced in IECs of the small intestine by the treatment of mice with antibiotics against Gram-positive bacteria. The expression of both proteins was also decreased in IECs of the small intestine from germ-free mice, compared with that from control specific-pathogen-free mice. Exposure of intestinal organoids to IFN-γ markedly increased the expression of either CEACAM1 or CEACAM20, whereas the exposure to TNF-α increased the expression of the former protein, but not that of the latter. In contrast, the expression of CEACAM20, but not of CEACAM1, in intestinal organoids was markedly increased by exposure to butyrate, a short-chain fatty acid produced by bacterial fermentation in the intestine. Collectively, our results suggest that Gram-positive bacteria promote the mRNA expression of CEACAM1 or CEACAM20 in the small intestine. Inflammatory cytokines or butyrate likely participates in such effects of commensal bacteria.


Assuntos
Antígeno Carcinoembrionário/metabolismo , Moléculas de Adesão Celular/metabolismo , Regulação da Expressão Gênica , Bactérias Gram-Positivas/metabolismo , Intestino Delgado/metabolismo , RNA Mensageiro/metabolismo , Animais , Antibacterianos/farmacologia , Butiratos/metabolismo , Antígeno Carcinoembrionário/genética , Moléculas de Adesão Celular/genética , Células Epiteliais/metabolismo , Ácidos Graxos Voláteis/metabolismo , Bactérias Gram-Positivas/efeitos dos fármacos , Interferon gama/metabolismo , Mucosa Intestinal/metabolismo , Intestino Delgado/citologia , Intestino Delgado/microbiologia , Intestinos/citologia , Intestinos/microbiologia , Camundongos Endogâmicos C57BL , Fator de Necrose Tumoral alfa/metabolismo
8.
Korean J Parasitol ; 53(4): 497-9, 2015 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-26323851

RESUMO

To determine whether pinworm infections and head lice infestations spread among children in orphanages, 117 children from 4 orphanages in Busan-si and Ulsan-si, Korea, were examined for enterobiasis and head lice infestation between January and February 2014. The overall rate of Enterobius vermicularis egg positivity was 0.85%, whereas none of the children had head lice infestations. The rate of pinworm infection was much lower among the orphanage children compared to the rates observed in previous studies among kindergarten and primary school students. Moreover, the risk factors for enterobiasis were less frequent among these subjects than previously reported. The personal hygiene and health of the orphanage children were supervised by a regular, employed nurse through a health education program. In conclusion, pinworm infection was efficiently controlled among the children in orphanages, and this might be related to good personal hygiene practices in Korea.


Assuntos
Enterobíase/epidemiologia , Enterobius/isolamento & purificação , Infestações por Piolhos/epidemiologia , Pediculus/fisiologia , Adolescente , Animais , Criança , Pré-Escolar , Enterobíase/parasitologia , Enterobius/genética , Enterobius/fisiologia , Feminino , Humanos , Higiene , Infestações por Piolhos/parasitologia , Masculino , Orfanatos/estatística & dados numéricos , Pediculus/genética , Prevalência , República da Coreia/epidemiologia
9.
Korean J Fam Med ; 2024 Mar 25.
Artigo em Inglês | MEDLINE | ID: mdl-38523423

RESUMO

Background: Chronic stress is associated with an increased risk of cognitive impairment and Alzheimer's disease. This study aimed to assess whether better coping with stress, as assessed using the Brief Resilience Scale (BRS), is associated with slower cognitive decline in community-dwelling older adults. Methods: This study used 2018/2019 data and 2-year follow-up data from the Korean Frailty and Aging Cohort Study. Of the 3,014 total participants, we included 1,826 participants (mean age, 77.6±3.7 years, 51.9% female) who completed BRS and Korean version of the Consortium to Establish a Registry for Alzheimer's Disease Assessment Battery and the Korean version of the Frontal Assessment Battery (FAB). Results: Higher BRS score at baseline was associated with a lesser decline in the Mini-Mental State Examination score over 2 years after adjusting for age, sex, years of education, smoking status, hypertension, diabetes, and depression (B, 0.175; 95% confidence interval, 0.025-0.325) for 2 years, which represents global cognitive function. Other cognitive function measurements (Word List Memory, Word List Recall, Word List Recognition, Digit Span, Trail Making Test-A, and FAB) did not change significantly with the BRS score at baseline. Conclusion: These findings suggest that better stress-coping ability, meaning faster termination of the stress response, may limit the decline in cognitive function.

10.
J Biol Chem ; 287(9): 6275-83, 2012 Feb 24.
Artigo em Inglês | MEDLINE | ID: mdl-22223646

RESUMO

In mammalian cells Cdk2 activity during the G(1)-S transition is mainly controlled by p27(KIP1). Although the amount and subcellular localization of p27 influence Cdk2 activity, how Cdk2 activity is regulated during this phase transition still remains virtually unknown. Here we report an entirely new mechanism for this regulation. Cdc6 the AAA+ ATPase, known to assemble prereplicative complexes on chromosomal replication origins and activate p21(CIP1)-bound Cdk2, also activated p27-bound Cdk2 in its ATPase and cyclin binding motif-dependent manner but only after the p27 bound to the Cdk2 was phosphorylated at the C terminus. ROCK, which mediates a signal for cell anchorage to the extracellular matrix and activates the mTORC1 cascade as well as controls cytoskeleton assembly, was partly responsible for C-terminal phosphorylation of the p27. In vitro reconstitution demonstrated ROCK (Rho-associated kinase)-mediated phosphorylation of Cdk2-bound p27 at the C terminus and subsequent activation of the Cdk2 by Cdc6.


Assuntos
Proteínas de Ciclo Celular/metabolismo , Quinase 2 Dependente de Ciclina/metabolismo , Inibidor de Quinase Dependente de Ciclina p27/metabolismo , Fibroblastos/enzimologia , Proteínas Nucleares/metabolismo , Substituição de Aminoácidos/fisiologia , Animais , Proteínas de Ciclo Celular/química , Proteínas de Ciclo Celular/genética , Divisão Celular/fisiologia , Células Cultivadas , Ciclina D3/genética , Ciclina D3/metabolismo , Inibidor de Quinase Dependente de Ciclina p27/química , Citoesqueleto/fisiologia , Ativação Enzimática/fisiologia , Fibroblastos/citologia , Humanos , Camundongos , Proteínas Monoméricas de Ligação ao GTP/metabolismo , Neuropeptídeos/metabolismo , Proteínas Nucleares/química , Proteínas Nucleares/genética , Fosforilação/fisiologia , Ligação Proteica/fisiologia , Estrutura Terciária de Proteína/fisiologia , RNA Interferente Pequeno/farmacologia , Proteína Enriquecida em Homólogo de Ras do Encéfalo , Ratos , Treonina/metabolismo , Quinases Associadas a rho/metabolismo
11.
Iran J Public Health ; 52(9): 1942-1951, 2023 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-38033839

RESUMO

Background: We aimed to investigate the effects of a nonviolent and nonverbal communication and self-acceptance training program among Korean nursing students. Methods: We enrolled students in nursing departments at three universities in Busan Metropolitan City, South Korea. The students were randomly allocated to the experimental (n = 38) and control groups (n = 36); subsequently, they completed questionnaires before and after training. Data were collected on March 2023. The experimental group was enrolled in a program comprising 390 minutes of lecture, practice, role play, discussion, and reflection in 8-h daily sessions, with a total of eight sessions. The training sought to allow students to understand and practice nonviolent and nonverbal communication. Data were analyzed using descriptive statistics, chi-square tests, and a paired t-test. Results: Compared with the control group, the experimental group showed a significant post-intervention improvement in the nonviolent communication scores (t = -2.442, P= 0.020); however, there were no significant between-group differences in the post-intervention nonverbal communication or self-acceptance scores. Conclusion: Customized communication training programs are required to address communication competencies among medical personnel, including nursing students. Moreover, it is crucial to set standards for communication competency. Specifically, from a long-term perspective, a continuous educational strategy is required to effectively improve the communication capabilities of nursing students in Korea. It is possible to develop training programs that can systematically improve communication competency among nursing students.

13.
Sleep Biol Rhythms ; 21(1): 51-58, 2023 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-38468911

RESUMO

Determining whether weekend catch-up sleep (CUS) is related to high risk of depression in the general middle-aged population in Korea. This study is a cross-sectional study analyzing data from 2016 to 2017 collected in the Korea National Health and Nutrition Examination Survey VII-1, 2; less than 35 years, and more than 65 years were excluded. Interviews on sociodemographic characteristics, mood and sleep-related profiles, and comorbid medical conditions were conducted. Participants were divided into three groups according to weekday sleeping time (< 6 h, 6 to ≤ 8 h, and ≥ 8 h). Weekend CUS was identified when nocturnal sleep extension occurred over the weekend. The risk of depression was evaluated using the PHQ-9. The PHQ-9 score differed among the three groups. The prevalence of moderate to severe depressive symptom and PHQ-9 score ≥ 10 was the highest in the group sleep over 8 h and the next highest in the group sleep less than 6 h. In the group sleep less than 6 h, PHQ-9 score ≥ 10 was significantly higher in the without CUS group than the with CUS group. The risk of depression in middle-aged individuals was associated with both short and long sleep duration, and the severity and prevalence of depression were lower in the group with CUS when a shortened sleep pattern was observed. Supplementary Information: The online version contains supplementary material available at 10.1007/s41105-022-00415-3.

14.
J Obes Metab Syndr ; 32(1): 1-24, 2023 Mar 30.
Artigo em Inglês | MEDLINE | ID: mdl-36945077

RESUMO

The goal of the 8th edition of the Clinical Practice Guidelines for Obesity is to help primary care physician provide safe, effective care to patients with obesity by offering evidence-based recommendations to improve the quality of treatment. The Committee for Clinical Practice Guidelines comprised individuals with multidisciplinary expertise in obesity management. A steering board of seven experts oversaw the entire project. Recommendations were developed as the answers to key questions formulated in patient/problem, intervention, comparison, outcomes (PICO) format. Guidelines underwent multi-level review and cross-checking and received endorsement from relevant scientific societies. This edition of the guidelines includes criteria for diagnosing obesity, abdominal obesity, and metabolic syndrome; evaluation of obesity and its complications; weight loss goals; and treatment options such as diet, exercise, behavioral therapy, pharmacotherapy, and bariatric and metabolic surgery for Korean people with obesity. Compared to the previous edition of the guidelines, the current edition includes five new topics to keep up with the constantly evolving field of obesity: diagnosis of obesity, obesity in women, obesity in patients with mental illness, weight maintenance after weight loss, and the use of information and communication technology-based interventions for obesity treatment. This edition of the guidelines features has improved organization, more clearly linking key questions in PICO format to recommendations and key references. We are confident that these new Clinical Practice Guidelines for Obesity will be a valuable resource for all healthcare professionals as they describe the most current and evidence-based treatment options for obesity in a well-organized format.

15.
J Biol Chem ; 286(26): 23132-41, 2011 Jul 01.
Artigo em Inglês | MEDLINE | ID: mdl-21561859

RESUMO

When deprived of anchorage to the extracellular matrix, fibroblasts arrest in G(1) phase at least in part due to inactivation of G(1) cyclin-dependent kinases. Despite great effort, how anchorage signals control the G(1)-S transition of fibroblasts remains highly elusive. We recently found that the mammalian target of rapamycin (mTOR) cascade might convey an anchorage signal that regulates S phase entry. Here, we show that Rho-associated kinase connects this signal to the TSC1/TSC2-RHEB-mTOR pathway. Expression of a constitutively active form of ROCK1 suppressed all of the anchorage deprivation effects suppressible by tsc2 mutation in rat embryonic fibroblasts. TSC2 contains one evolutionarily conserved ROCK target-like sequence, and an alanine substitution for Thr(1203) in this sequence severely impaired the ability of ROCK1 to counteract the anchorage loss-imposed down-regulation of both G(1) cell cycle factors and mTORC1 activity. Moreover, TSC2 Thr(1203) underwent ROCK-dependent phosphorylation in vivo and could be phosphorylated by bacterially expressed active ROCK1 in vitro, providing biochemical evidence for a direct physical interaction between ROCK and TSC2.


Assuntos
Fase G1/fisiologia , Fase S/fisiologia , Transdução de Sinais/fisiologia , Serina-Treonina Quinases TOR/metabolismo , Proteínas Supressoras de Tumor/metabolismo , Quinases Associadas a rho/metabolismo , Animais , Linhagem Celular , Fosforilação/fisiologia , Ratos , Serina-Treonina Quinases TOR/genética , Proteína 1 do Complexo Esclerose Tuberosa , Proteína 2 do Complexo Esclerose Tuberosa , Proteínas Supressoras de Tumor/genética , Quinases Associadas a rho/genética
16.
Mol Cell Biochem ; 363(1-2): 281-9, 2012 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-22160829

RESUMO

Widdrol is an odorant compound isolated from Juniperus chinensis. We previously reported that widdrol induces Gap 1 (G1) phase cell cycle arrest and leads to apoptosis in human colon adenocarcinoma HT29 cells. It was also reported that this cell cycle arrest is associated with the induction of checkpoint kinase 2 (Chk2), p53 phosphorylation and cyclin dependent kinase (Cdk) inhibitor p21 expression. In this paper, we investigated the molecular mechanisms of widdrol on the activation of G1 DNA damage checkpoint at early phase when DNA damages occurred in HT29 cells. First of all, we examined that widdrol breaks DNA directly or not. As the results of DNA electrophoresis and formation of phosphorylated histone H2AX (γH2AX) foci in HT29 cells, widdrol generates DNA double-strand breaks directly within 0.5 h both in vitro and in vivo. Based on this result, the change of proteins related in checkpoint pathway was examined over a time course of 0.5-24 h. Treatment of HT29 cells with widdrol elicits the following: (1) phosphorylation of Chk2 and p53, (2) reduction of cell division cycle 25A (Cdc25A) expression, (3) increase of Cdk inhibitor p21 expression, and (4) decrease of the levels of Cdk2 and cyclin E expression in a time-dependent manner. Moreover, only the expression level of mini-chromosome maintenance 4 (MCM4) protein, a subunit of the eukaryotic DNA replicative helicase, is rapidly down-regulated in HT29 cells treated with widdrol over the same time course, but those of the other MCM proteins are unchanged. Overall, our results indicated that widdrol breaks DNA directly in HT29 cells, and this DNA damage results in checkpoint activation via Chk2-p53-Cdc25A-p21-MCM4 pathway and finally cells go to G1-phase cell cycle arrest and apoptosis.


Assuntos
Adenocarcinoma/enzimologia , Antineoplásicos Fitogênicos/farmacologia , Benzocicloeptenos/farmacologia , Proteínas de Ciclo Celular/metabolismo , Neoplasias do Colo/enzimologia , Inibidor de Quinase Dependente de Ciclina p21/metabolismo , Quebras de DNA de Cadeia Dupla , Proteínas de Ligação a DNA/metabolismo , Pontos de Checagem da Fase G1 do Ciclo Celular/efeitos dos fármacos , Proteínas Nucleares/metabolismo , Proteínas Serina-Treonina Quinases/metabolismo , Transdução de Sinais/efeitos dos fármacos , Proteína Supressora de Tumor p53/metabolismo , Fosfatases cdc25/metabolismo , Adenocarcinoma/patologia , Animais , Apoptose/efeitos dos fármacos , Quinase do Ponto de Checagem 2 , Neoplasias do Colo/patologia , Fibroblastos/efeitos dos fármacos , Células HT29 , Histonas/metabolismo , Humanos , Camundongos , Componente 4 do Complexo de Manutenção de Minicromossomo , Fosforilação , Fatores de Tempo
17.
J Microbiol Biotechnol ; 32(2): 238-247, 2022 Feb 28.
Artigo em Inglês | MEDLINE | ID: mdl-34949744

RESUMO

Since the skin covers most surfaces of the body, it is susceptible to damage, which can be fatal depending on the degree of injury to the skin because it defends against external attack and protects internal structures. Various types of artificial skin are being studied for transplantation to repair damaged skin, and recently, the production of replaceable skin using three-dimensional (3D) bioprinting technology has also been investigated. In this study, skin tissue was produced using a 3D bioprinter with human skin cell lines and cells extracted from mouse skin, and the printing conditions were optimized. Gelatin was used as a bioink, and fibrinogen and alginate were used for tissue hardening after printing. Printed skin tissue maintained a survival rate of 90% or more when cultured for 14 days. Culture conditions were established using 8 mM calcium chloride treatment and the skin tissue was exposed to air to optimize epidermal cell differentiation. The skin tissue was cultured for 14 days after differentiation induction by this optimized culture method, and immunofluorescent staining was performed using epidermal cell differentiation markers to investigate whether the epidermal cells had differentiated. After differentiation, loricrin, which is normally found in terminally differentiated epidermal cells, was observed in the cells at the tip of the epidermal layer, and cytokeratin 14 was expressed in the lower cells of the epidermis layer. Collectively, this study may provide optimized conditions for bioprinting and keratinization for three-dimensional skin production.


Assuntos
Bioimpressão , Animais , Bioimpressão/métodos , Linhagem Celular , Epiderme , Humanos , Camundongos , Impressão Tridimensional , Pele
18.
J Cancer Prev ; 27(4): 221-228, 2022 Dec 31.
Artigo em Inglês | MEDLINE | ID: mdl-36713942

RESUMO

Cedrol, a sesquiterpene alcohol, isolated from Juniperus chinensis has been reported to inhibit minichromosome maintenance (MCM) proteins as cancer biomarkers in human lung cancer in vitro. In the present study, we investigated the anti-cancer activity of cedrol in vitro and in vivo using human colorectal cancer HT29 cells and a human colorectal tumor xenograft model. Cedrol inhibited MCM protein expression and cell growth in HT29 cells, which are associated with G1 arrest and the induction of apoptosis. We demonstrated that cedrol effectively reduced HT29 tumor growth without apparent weight loss in a human tumor xenograft model. Compared with vehicle- and adriamycin-treated tumor tissues, cedrol induced changes in the tumor tissue structure, resulting in a reduced cell density within the tumor parenchyma and reduced vascularization. Moreover, the expression of MCM7, an important subunit of MCM helicase, was significantly suppressed by cedrol in tumor tissue. Collectively, these results suggest that cedrol may act as a potential anti-cancer agent for colorectal cancer by inhibiting MCM protein expression and tumor growth.

19.
Biosci Trends ; 16(4): 291-300, 2022 Sep 17.
Artigo em Inglês | MEDLINE | ID: mdl-35691912

RESUMO

Loganin is a type of iridoid glycosides isolated from Corni fructus and is known to have various pharmacological properties, but studies on its antioxidant activity are still lacking. Therefore, in this study, the preventive effect of loganin on oxidative stress-mediated cellular damage in human keratinocyte HaCaT cells was investigated. Our results show that loganin pretreatment in a non-toxic concentration range significantly improved cell survival in hydrogen peroxide (H2O2)-treated HaCaT cells, which was associated with inhibition of cell cycle arrest at the G2/M phase and induction of apoptosis. H2O2-induced DNA damage and reactive oxygen species (ROS) generation were also greatly reduced in the presence of loganin. Moreover, H2O2 treatment enhanced the cytoplasmic release of cytochrome c, upregulation of the Bax/Bcl-2 ratio and degradation of cleavage of poly (ADP-ribose) polymerase, whereas loganin remarkably suppressed these changes. In addition, loganin obviously attenuated H2O2-induced autophagy while inhibiting the increased accumulation of autophagosome proteins, including as microtubule-associated protein 1 light chain 3-II and Beclin-1, and p62, an autophagy substrate protein, in H2O2-treated cells. In conclusion, our current results suggests that loganin could protect HaCaT keratinocytes from H2O2-induced cellular injury by inhibiting mitochondrial dysfunction, autophagy and apoptosis. This finding indicates the applicability of loganin in the prevention and treatment of skin diseases caused by oxidative damage.


Assuntos
Antioxidantes , Peróxido de Hidrogênio , Difosfato de Adenosina/metabolismo , Difosfato de Adenosina/farmacologia , Antioxidantes/farmacologia , Apoptose , Proteína Beclina-1/metabolismo , Citocromos c/metabolismo , Células HaCaT , Humanos , Peróxido de Hidrogênio/metabolismo , Peróxido de Hidrogênio/toxicidade , Glicosídeos Iridoides/metabolismo , Glicosídeos Iridoides/farmacologia , Iridoides , Queratinócitos/metabolismo , Proteínas Associadas aos Microtúbulos/metabolismo , Proteínas Associadas aos Microtúbulos/farmacologia , Estresse Oxidativo , Proteínas Proto-Oncogênicas c-bcl-2/metabolismo , Espécies Reativas de Oxigênio/metabolismo , Ribose/metabolismo , Ribose/farmacologia , Proteína X Associada a bcl-2/metabolismo
20.
J Microbiol Biotechnol ; 32(7): 918-926, 2022 Jul 28.
Artigo em Inglês | MEDLINE | ID: mdl-35880481

RESUMO

Proteins related to DNA replication have been proposed as cancer biomarkers and targets for anticancer agents. Among them, minichromosome maintenance (MCM) proteins, often overexpressed in various cancer cells, are recognized both as notable biomarkers for cancer diagnosis and as targets for cancer treatment. Here, we investigated the activity of cedrol, a single compound isolated from Juniperus chinensis, in reducing the expression of MCM proteins in human lung carcinoma A549 cells. Remarkably, cedrol also strongly inhibited the expression of all other MCM protein family members in A549 cells. Moreover, cedrol treatment reduced cell viability in A549 cells, accompanied by cell cycle arrest at the G1 phase, and enhanced apoptosis. Taken together, this study broadens our understanding of how cedrol executes its anticancer activity while demonstrating that cedrol has potential application in the treatment of human lung cancer as an inhibitor of MCM proteins.


Assuntos
Carcinoma , Juniperus , Neoplasias Pulmonares , Células A549 , Apoptose , Pontos de Checagem do Ciclo Celular , Proteínas de Ciclo Celular/metabolismo , Linhagem Celular Tumoral , Humanos , Juniperus/metabolismo , Pulmão/patologia , Neoplasias Pulmonares/patologia , Sesquiterpenos Policíclicos
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