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1.
Neurologia (Engl Ed) ; 38(7): 475-485, 2023 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-37659838

RESUMO

INTRODUCTION: Repetitive transcranial magnetic stimulation (rTMS) has been used as a potential treatment for tinnitus; however, its effectiveness is variable and unpredictable. We hypothesized that resting-state functional connectivity before rTMS may be correlated with rTMS treatment effectiveness. METHODS: We applied 1-Hz rTMS to the left primary auditory (A1) and dorsolateral prefrontal cortices (DLPFC) of 10 individuals with tinnitus and 10 age-matched controls. Resting-state functional magnetic resonance imaging (fMRI) studies were performed approximately one week before rTMS. Seed-based connectivity analyses were conducted for each individual, with seed regions as rTMS target areas. RESULTS: Compared to controls, the left superior temporal areas showed significantly increased positive connectivity with the left A1 and negative connectivity with the left DLPFC in the tinnitus group. The left frontoparietal and right cerebellar areas showed significantly increased negative connectivity with the left A1 and positive connectivity with the left DLPFC. Seed-based hyperconnectivity was correlated with tinnitus improvement (pre-rTMS vs. 2-week post-rTMS Tinnitus Handicap Inventory scores). Tinnitus improvement was significantly correlated with left A1 hyperconnectivity; however, no correlation was observed with left DLPFC connectivity. Positive rTMS outcomes were associated with significantly increased positive connectivity in bilateral superior temporal areas and significantly increased negative connectivity in bilateral frontal areas. CONCLUSIONS: Our results suggest that oversynchronisation of left A1 connectivity before rTMS of the left A1 and DLPFC is associated with treatment effectiveness.


Assuntos
Córtex Auditivo , Zumbido , Humanos , Córtex Auditivo/diagnóstico por imagem , Estimulação Magnética Transcraniana , Zumbido/diagnóstico por imagem , Zumbido/terapia , Lobo Temporal/diagnóstico por imagem , Cerebelo
3.
Neurologia (Engl Ed) ; 2021 Mar 12.
Artigo em Inglês, Espanhol | MEDLINE | ID: mdl-33722455

RESUMO

INTRODUCTION: Repetitive transcranial magnetic stimulation (rTMS) has been used as a potential treatment for tinnitus; however, its effectiveness is variable and unpredictable. We hypothesized that resting-state functional connectivity before rTMS may be correlated with rTMS treatment effectiveness. METHODS: We applied 1-Hz rTMS to the left primary auditory (A1) and dorsolateral prefrontal cortices (DLPFC) of 10 individuals with tinnitus and 10 age-matched controls. Resting-state functional magnetic resonance imaging (fMRI) studies were performed approximately one week before rTMS. Seed-based connectivity analyses were conducted for each individual, with seed regions as rTMS target areas. RESULTS: Compared to controls, the left superior temporal areas showed significantly increased positive connectivity with the left A1 and negative connectivity with the left DLPFC in the tinnitus group. The left frontoparietal and right cerebellar areas showed significantly increased negative connectivity with the left A1 and positive connectivity with the left DLPFC. Seed-based hyperconnectivity was correlated with tinnitus improvement (pre-rTMS vs. 2-week post-rTMS Tinnitus Handicap Inventory scores). Tinnitus improvement was significantly correlated with left A1 hyperconnectivity; however, no correlation was observed with left DLPFC connectivity. Positive rTMS outcomes were associated with significantly increased positive connectivity in bilateral superior temporal areas and significantly increased negative connectivity in bilateral frontal areas. CONCLUSIONS: Our results suggest that oversynchronisation of left A1 connectivity before rTMS of the left A1 and DLPFC is associated with treatment effectiveness.

4.
Int Endod J ; 52(10): 1479-1488, 2019 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-31062874

RESUMO

AIM: To explore the involvement of TLR5 in pulp inflammation and to examine the effects of TLR5 activation with its ligand, FlaB protein, on pro-inflammatory gene expression. METHODOLOGY: TLR5 expression in dental pulp tissues and human dental pulp cells (hDPCs) were determined by immunohistochemistry, immunocytochemistry, Western blots and RT-PCR analyses. To examine the role of TLR5, hDPCs were treated with recombinant FlaB protein (500 ng mL-1 ) to activate the receptor or with a small interfering RNA against TLR5 (si-TLR5) to downregulate the receptor. After exposure to FlaB, the expression of inflammation-related proteins was screened using a protein array kit. Western blots or qRT-PCR analyses were performed to identify changes in the expression of uPA (urokinase plasminogen activator), TIMPs (tissue inhibitor of metalloproteinases), and IL-6 and to determine their signalling pathways. Statistical analysis was performed using one-way analysis of variance (anova) with Tukey post hoc test; P < 0.05 was considered statistically significant. RESULT: TLR5 expression was identified in pulp tissues and hDPCs. In the protein array analysis, treatment with FlaB significantly increased uPA expression (P < 0.01) and significantly decreased TIMP1/4 (P < 0.05). FlaB treatment also significantly increased expression of the inflammatory marker IL-6 (P < 0.01). FlaB treatment increased phosphorylation of the NF-κB p65 subunit, JNK, p38 and ERK. Chemical inhibitors of NF-κB (Bay11-7082), p38 (SB202190) or ERK (U0126) decreased the FlaB induction of uPA expression. Downregulation of TLR5 expression by siRNA decreased the FlaB induction of uPA protein and p65 phosphorylation. CONCLUSION: TLR5 activation with FlaB treatment induced the expression of uPA via the NF-κB and MAPK signalling pathways. Flagellin-bearing oral bacteria may cause pulp inflammation through TLR5. The findings provide new clues to control pulpal diseases by targeting TLR5 signalling pathways.


Assuntos
NF-kappa B , Ativador de Plasminogênio Tipo Uroquinase , Polpa Dentária , Humanos , Mediadores da Inflamação , Plasminogênio , Receptor 5 Toll-Like
5.
Transplant Proc ; 49(5): 1142-1149, 2017 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-28583545

RESUMO

BACKGROUND: In an experimental animal model of islet transplantation, stable induction of insulin-dependent diabetes mellitus (IDDM) and islet isolation from donor pancreas are essential. Total pancreatectomy for IDDM induction and islet procurement in nonhuman primates leads to unwanted loss of exocrine function and may lead to morbidities associated with IDDM. METHODS: IDDM induction with streptozotocin (STZ) is associated with drug toxicity of STZ and necessitates the killing of another animal for islet procurement. In this study, we performed a subtotal pancreatectomy combined with reduced STZ injection to induce IDDM and procure islets in a nonhuman primate model. RESULTS: Twelve cynomolgus monkeys received low-dose STZ injections (60 mg/kg) simultaneously with subtotal pancreatectomy. All monkeys recovered from the procedure without complications. IDDM was induced in the animals. 57,691 ± 16,050 islets were isolated from the resected pancreas and transplanted into other monkeys. CONCLUSIONS: Simultaneous subtotal pancreatectomy and low-dose STZ injection represent an effective and safe method to create an animal model of insulin dependence diabetes, while at the same time providing sufficient amounts of fresh islet cells for allotransplantation without requiring killing of additional animals.


Assuntos
Diabetes Mellitus Experimental , Diabetes Mellitus Tipo 1 , Modelos Animais de Doenças , Transplante das Ilhotas Pancreáticas/métodos , Pancreatectomia/métodos , Animais , Diabetes Mellitus Experimental/cirurgia , Diabetes Mellitus Tipo 1/cirurgia , Macaca fascicularis , Estreptozocina
6.
Am J Transplant ; 17(2): 365-376, 2017 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-27376767

RESUMO

We investigated whether serum deprivation induces islet amyloid polypeptide (IAPP) oligomer accumulation and/or a proinflammatory response and, if so, whether the addition of interleukin (IL)-1 receptor antagonist to the culture medium can relieve the proinflammatory response during serum-deprived culture of nonhuman primate (NHP) islets. After culture in medium with and without Ana under serum-deprived culture conditions, IAPP oligomer/amyloid accumulation, in vitro viability, islet function, cytokine secretion, and posttransplantation outcome in streptozotocin-induced diabetic nude mice were determined in islets isolated from heterozygote human IAPP transgenic (hIAPP+/- ) mice and/or NHP islets. Serum deprivation induced accumulation of IAPP oligomer, but not amyloid, in NHP islets. Anakinra (Ana) protected islets from the serum deprivation-induced impairment of in vitro viability and glucose-stimulated insulin secretion and attenuated serum deprivation-induced caspase-1 activation, transcription, and secretion of IL-1ß, IL-6, and tumor necrosis factor-α in hIAPP+/- mice and NHP islets. Supplementation of medium with Ana during serum-deprived culture also improved posttransplantation in vivo outcomes of NHP islets. In conclusion, serum deprivation induced accumulation of IAPP oligomers and proinflammatory responses in cultured isolated islets. Supplementation of the culture medium with Ana attenuated the functional impairment and proinflammatory responses induced by serum deprivation in ex vivo culture of NHP islets.


Assuntos
Antirreumáticos/farmacologia , Meios de Cultura Livres de Soro/toxicidade , Inflamação/prevenção & controle , Proteína Antagonista do Receptor de Interleucina 1/farmacologia , Ilhotas Pancreáticas/efeitos dos fármacos , Animais , Sobrevivência Celular/efeitos dos fármacos , Células Cultivadas , Humanos , Inflamação/induzido quimicamente , Ilhotas Pancreáticas/patologia , Macaca fascicularis , Camundongos , Camundongos Endogâmicos BALB C , Camundongos Nus
7.
Folia Morphol (Warsz) ; 75(4): 560-564, 2016.
Artigo em Inglês | MEDLINE | ID: mdl-27830894

RESUMO

We herein report a case showing three anatomical variations including the aberrant right subclavian artery (ARSA), the non-recurrent laryngeal nerve (NRLN) and the right thoracic duct in a 59-year-old male cadaver. The right subclavian artery (RSA) arose from the descending aorta next to the left subclavian artery and coursed in between the oesophagus and the thoracic vertebrae. The recurrent laryngeal nerve did not coil around the RSA but directly entered the larynx. Lastly the thoracic duct terminated into the right brachiocephalic vein. This study makes an embryological assumption that the abnormal development of the RSA had happened first and subsequently caused NRLN and the thoracic duct drainage variation. As to our knowledge, only two reports have been made previously concerning such concurrent variations. Therefore, this case report alerts anatomists and clinicians to the possibility of simultaneous occurrence of ARSA, NRLN and the right thoracic duct.


Assuntos
Aneurisma , Anormalidades Cardiovasculares , Artéria Subclávia/anormalidades , Aorta Torácica , Humanos , Masculino , Pessoa de Meia-Idade , Nervo Laríngeo Recorrente , Ducto Torácico
8.
Osteoporos Int ; 27(5): 1691-9, 2016 May.
Artigo em Inglês | MEDLINE | ID: mdl-26782682

RESUMO

UNLABELLED: This systematic review was performed to compare the diagnostic accuracy of vertebral fracture assessment (VFA) with that of spinal radiography for identification of vertebral fractures (VFs). VFA appeared to have moderate sensitivity and high specificity for detecting VFs when compared with spinal radiography. INTRODUCTION: VFs are recognized as the hallmark of osteoporosis, and a previous VF increases the risk of a future fracture. Therefore, the timely detection of VFs is important for prevention of further fractures. This systematic review examined the diagnostic accuracy of VFA using dual X-ray absorptiometry (DXA) to identify VFs. METHODS: We searched for potentially relevant studies using electronic databases, including Ovid-Medline, Ovid-EMBASE, Cochrane library, and four Korean databases, from their inception to May 2013. We compared the diagnostic accuracy of VFA with that of spinal radiography for detection of VFs by analyzing the sensitivity and specificity using a 2 × 2 contingency table. Subgroup analyses were also performed on studies with a low risk of bias and applicability. RESULTS: Twelve studies were analyzed for the diagnostic accuracy of VFA. The sensitivity and specificity were 0.70-0.93 and 0.95-1.00, respectively, analyzed on a per-vertebra basis, and 0.65-1.00 and 0.74-1.00 on a per-patient basis. The sensitivity and specificity of five studies in subgroups with a low risk of bias in the intervention test were 0.70-0.84 and 0.96-0.99, respectively. In studies with a low risk of bias in the patient selection, those based on a per-vertebra basis in three studies were 0.70-0.93 and 0.96-1.00, respectively. CONCLUSIONS: VFA had moderate sensitivity and high specificity for detecting VF when compared with spinal radiography. However, the present findings are insufficient to assess whether spinal radiography should be replaced by VFA.


Assuntos
Fraturas por Osteoporose/diagnóstico por imagem , Fraturas da Coluna Vertebral/diagnóstico por imagem , Absorciometria de Fóton/métodos , Feminino , Humanos , Masculino , Osteoporose Pós-Menopausa/complicações , Fraturas por Osteoporose/etiologia , Radiografia , Sensibilidade e Especificidade , Fraturas da Coluna Vertebral/etiologia
9.
J Dent Res ; 94(8): 1135-42, 2015 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-25940145

RESUMO

Chicken ovalbumin upstream promoter transcription factor 2 (COUP-TFII), an orphan nuclear receptor belonging to the steroid-thyroid hormone receptor superfamily, plays an important role in cell fate determination of various tissues. However, the specific role of COUP-TFII in tooth development has not yet been elucidated. In the present study, we aimed to explore the role of COUP-TFII in dentin sialophosphoprotein (DSPP) expression and matrix mineralization in odontoblast-lineage cells. In primary human dental pulp cells (HDPCs) and murine dental papilla-derived cells (MDPC-23) cultured in a mineralizing medium, the expression of COUP-TFII was induced along with the increased odontoblast-specific dentin matrix protein-1 (DMP-1) and DSPP expression. Endogenous expression of COUP-TFII in maxillary second molar germs of rats showed an increasing tendency as development of the tooth progressed. Also, COUP-TFII protein was detected in greater quantity in the odontoblastic layer of second molar germs than in that of third molar germs of rats. Overexpression of COUP-TFII using an adenoviral system upregulated the expression of odontoblast-specific genes with increased alkaline phosphatase activity and matrix mineralization in odontoblast-lineage cells. In contrast, knockdown of COUP-TFII using small interfering RNA decreased the expression of odontoblast-specific genes, which reduced matrix mineralization. Mechanistic studies revealed that COUP-TFII increased DSPP transcription by direct binding on the DSPP promoter. In addition, COUP-TFII physically interacted with the homeodomain transcription factor Msx2 and antagonistically regulated the Msx2 effect on DSPP promoter activity. Taken together, these results suggest that COUP-TFII has a stimulatory role in DSPP expression and matrix mineralization in odontoblast-lineage cells.


Assuntos
Fator II de Transcrição COUP/metabolismo , Dentinogênese , Proteínas da Matriz Extracelular/metabolismo , Odontoblastos/metabolismo , Fosfoproteínas/metabolismo , Sialoglicoproteínas/metabolismo , Animais , Western Blotting , Diferenciação Celular , Células Cultivadas , Proteínas de Homeodomínio/metabolismo , Humanos , Imunoprecipitação , Camundongos , Ratos , Ratos Sprague-Dawley , Reação em Cadeia da Polimerase em Tempo Real , Coloração e Rotulagem , Transfecção
10.
Am J Transplant ; 15(6): 1543-54, 2015 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-25865268

RESUMO

The spheroid culture method is an effective strategy for ex vivo expansion of an autologous therapeutic cell population. We investigated if cotransplantation of bone marrow-derived spheroids (BM-spheroid) formed using 3D culture of BM-derived mononuclear cells (BM-MNCs) could improve the posttransplant outcome of islet grafts using a mouse syngeneic marginal mass renal subcapsular islet transplantation model. Using green fluorescent protein transgenic (GFP-Tg) mice, the role of the BM-spheroids and the contribution of vessels derived from donors and recipients in grafted areas were assessed by immunohistochemistry. Compared to fresh BM-MNCs and nonspheroid remnant cells (BM-nonspheroid), the BM-spheroids, mainly composed of CXCR4(+) CD14(+) myeloid cells, showed higher angiogenic capacity, such as in vitro self-formed vessel structures; increased expression of angiogenic and chemoattractive factors; and incorporation into new vessel formation in basement membrane matrix plugs. BM-spheroid cotransplantation with islets improved the posttransplant outcomes in terms of glucose tolerance, serum insulin level, and diabetes reversal rate when compared with cotransplantation of BM-nonspheroids. Immunohistochemistry revealed that cotransplantation of the BM-spheroids increased vessel density, area of grafted endocrine and non-endocrine tissue, and ß cell proliferation. In conclusion, cotransplantation of islets and BM-spheroids improved islet function through facilitation of revascularization and an increase in cell proliferation and islet cell mass.


Assuntos
Células da Medula Óssea/citologia , Células da Medula Óssea/fisiologia , Terapia Baseada em Transplante de Células e Tecidos/métodos , Transplante das Ilhotas Pancreáticas/métodos , Ilhotas Pancreáticas/irrigação sanguínea , Células Mieloides/citologia , Células Mieloides/fisiologia , Animais , Glicemia/metabolismo , Comunicação Celular/fisiologia , Proliferação de Células/fisiologia , Transplante de Células/métodos , Células Cultivadas , Diabetes Mellitus Experimental/induzido quimicamente , Diabetes Mellitus Experimental/metabolismo , Diabetes Mellitus Experimental/cirurgia , Modelos Animais de Doenças , Sobrevivência de Enxerto/fisiologia , Técnicas In Vitro , Ilhotas Pancreáticas/fisiologia , Masculino , Camundongos , Camundongos Endogâmicos C57BL , Camundongos Transgênicos , Neovascularização Fisiológica/fisiologia , Estreptozocina/efeitos adversos
11.
Asian-Australas J Anim Sci ; 27(9): 1250-3, 2014 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-25178367

RESUMO

The objective of this study was to estimate the parameters of Gompertz growth curves with the measurements of body conformation, real-time ultrasound longissimus dorsi muscle area (LMA) and backfat thickness (BFT) in Hanwoo cows. The Hanwoo cows (n = 3,373) were born in 97 Hanwoo commercial farms in the 17 cities or counties of Gyeongbuk province, Korea, between 2000 and 2007. A total of 5,504 ultrasound measurements were collected for the cows at the age of 13 to 165 months in 2007 and 2008. Wither height (HW), rump height (HR), the horizontal distance between the top of the hips (WH), and girth of chest (GC) were also measured. Analysis of variance was conducted to investigate variables affecting LMA and BFT. The effect of farm nested in location was included in the statistical model, as well as the effects of HW, HR, WH, and GC as covariates. All of the effects were significant in the analysis of variance for LMA and BFT (p<0.01), except for the HR effect for LMA. The two ultrasound measures and the four body conformation traits were fitted to a Gompertz growth curve function to estimate parameters. Upper asymptotic weights were estimated as 54.0 cm(2), 7.67 mm, 125.6 cm, 126.4 cm, 29.3 cm, and 184.1 cm, for LMA, BFT, HW, HR, WH, and GC, respectively. Results of ultrasound measurements showed that Hanwoo cows had smaller LMA and greater BFT than other western cattle breeds, suggesting that care must be taken to select for thick BFT rather than an increase of only beef yield. More ultrasound records per cow are needed to get accurate estimates of growth curve, which, thus, helps producers select animals with high accuracy.

12.
Asian-Australas J Anim Sci ; 27(2): 155-60, 2014 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-25049938

RESUMO

The purpose of this study was to estimate genetic parameters of ultrasound measurements for longissimus dorsi muscle area (LMA), backfat thickness (BFT), and marbling score (MS) in Hanwoo cows (N = 3,062) at the ages between 18 and 42 months. Data were collected from 100 Hanwoo breeding farms in Gyeongbuk province, Korea, in 2007 and 2008. The cows were classified into four different age groups, i.e. 18 to 22 months (the first pregnancy period), 23 to 27 (the first parturition), 28 to 32 (the second pregnancy), and 33 to 42 (the second parturition), respectively. For each age group, a multi-trait animal model was used to estimate variance components and heritabilities of the three traits. The averages of LMA, BFT, and MS measurements across the cows of all age groups were 50.1 cm(2), 4.62 mm, and 3.04, respectively and heritability estimates were 0.09, 0.10, and 0.08 for the respective traits. However, when the data were analyzed in different age groups, heritability estimates of LMA and BFT were 0.24 and 0.47, respectively, for the cows of 18 to 22 months of age, and 0.21 for MS in the 28 to 32 months old cows. When the cows of all age groups were used, the estimates of genetic (phenotypic) correlations were 0.43 (0.35), -0.06 (0.34) and 0.21 (0.32) between LMA and BFT, LMA and MS, and BFT and MS, respectively. However, in the cow age group between 28 and 32 (18 and 22) months, the estimates of genetic (phenotypic) correlations were 0.05 (0.29), -0.15 (0.24) and 0.38 (0.24), for the respective pairs of traits. These results suggest that genetic, environmental, and phenotypic variations differ depending on cow age, such that care must be taken when ultrasound measurements are applied to selection of cows for meat quality.

13.
Transplant Proc ; 46(5): 1628-32, 2014 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-24935338

RESUMO

BACKGROUND: Given the fragility of adult porcine islets, reduction of shearing stress in islet purification using histidine-tryptophan-ketoglutarate (HTK) solution and iodixanol could be an effective strategy. We examined the effect of ductal preservation with HTK solution and an islet purification protocol that utilizes HTK solution and iodixanol in adult porcine islet isolation. METHODS: Islets were isolated with a modified Ricordi method using adult Prestige World Genetics (PWG) and Yucatan pigs. The discontinuous density gradient was composed of either HTK solution/iodixanol (n = 23, iodixanol group) or Hank's balanced salt solution (HBSS)/Ficoll (n = 17, Ficoll group). In the iodixanol group, ductal injection of HTK solution was performed before purification. RESULTS: In PWG pigs, significantly higher islet yield after purification (3480 ± 214.2 islet equivalent [IEQ]/g, P = .003) and higher recovery rate (85.45% ± 3.49%, P = .0043) were obtained from the HTK/iodixanol group as compared to the HBSS/Ficoll group (1905 ± 323.2 IEQ/g, and 67.22% ± 4.77%, respectively). Similar results were obtained in Yucatan pigs with greater body weight. CONCLUSION: Ductal preservation and iodixanol-based islet purification using HTK solution improved the yield of adult porcine islet isolation compared to the conventional method using HBSS and Ficoll. The results of this study support the feasibility of an adult porcine islet isolation protocol using HTK solution and iodixanol, which have the favorable physical properties.


Assuntos
Ilhotas Pancreáticas , Soluções para Preservação de Órgãos , Animais , Glucose , Manitol , Cloreto de Potássio , Procaína , Suínos , Porco Miniatura
14.
Cell Death Differ ; 21(7): 1150-9, 2014 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-24658401

RESUMO

MicroRNAs have crucial roles in lung cancer cell development. They regulate cell growth, proliferation and migration by mediating the expression of tumor suppressor genes and oncogenes. We identified and characterized the novel miR-9500 in human lung cancer cells. The miR-9500 forms a stem-loop structure and is conserved in other mammals. The expression levels of miR-9500 were reduced in lung cancer cells and lung cancer tissues compared with normal tissues, as verified by TaqMan miRNA assays. It was confirmed that the putative target gene, Akt1, was directly suppressed by miR-9500, as demonstrated by a luciferase reporter assay. The miR-9500 significantly repressed the protein expression levels of Akt1, as demonstrated via western blot, but did not affect the corresponding mRNA levels. Akt1 has an important role in lung carcinogenesis, and depletion of Akt1 has been shown to have antiproliferative and anti-migratory effects in previous studies. In the current study, the overexpression of miR-9500 inhibited cell proliferation and the expression of cell cycle-related proteins. Likewise, the overexpression of miR-9500 impeded cell migration in human lung cancer cells. In an in vivo assay, miR-9500 significantly suppressed Fluc expression compared with NC and ASO-miR-9500, suggesting that cell proliferation was inhibited in nude mice. Likewise, miR-9500 repressed tumorigenesis and metastasis by targeting Akt1. These data indicate that miR-9500 might be applicable for lung cancer therapy.


Assuntos
Movimento Celular , Proliferação de Células , Neoplasias Pulmonares/genética , MicroRNAs/fisiologia , Proteínas Proto-Oncogênicas c-akt/genética , Interferência de RNA , Regiões 3' não Traduzidas , Animais , Sequência de Bases , Sítios de Ligação , Linhagem Celular Tumoral , Regulação Neoplásica da Expressão Gênica , Humanos , Neoplasias Pulmonares/enzimologia , Neoplasias Pulmonares/patologia , Masculino , Camundongos Endogâmicos BALB C , Camundongos Nus , Metástase Neoplásica , Transplante de Neoplasias , Proteínas Proto-Oncogênicas c-akt/metabolismo
15.
Oncogene ; 33(38): 4675-84, 2014 Sep 18.
Artigo em Inglês | MEDLINE | ID: mdl-24662814

RESUMO

We provide detailed mechanisms of Ahnak-mediated potentiation of transforming growth factor ß (TGFß) signaling, which leads to a negative regulation of cell growth. We show that Smad3 interacts with Ahnak through MH2 domain and that Ahnak stimulates Smad3 localization into nucleus leading to potentiating TGFß-induced transcriptional activity of R-Smad. Moreover, overexpression of Ahnak resulted in growth retardation and cell cycle arrest through downregulation of c-Myc and cyclin D1/D2. We describe results from analyses of Ahnak(-/-) mouse model expressing middle T antigen in a mammary gland-specific manner (MMTV(Tg/+)Ahnak(-/-)), which showed significantly progressed hyperplasia of mammary glands compared with MMTV(Tg/+)Ahnak(+/+). Finally, we screened multiple human breast cancer tissues and showed that the expression of Ahnak in cancer tissues is lower than that in control tissues by 50%. Taken together, these data indicate that Ahnak mediates a negative regulation of cell growth and acts as novel tumor suppressor through potentiation of TGFß signaling.


Assuntos
Proteínas de Membrana/fisiologia , Proteínas de Neoplasias/fisiologia , Proteínas Smad/metabolismo , Animais , Células COS , Pontos de Checagem do Ciclo Celular , Proliferação de Células , Chlorocebus aethiops , Feminino , Humanos , Masculino , Camundongos , Camundongos Endogâmicos BALB C , Camundongos Endogâmicos C57BL , Camundongos Knockout , Camundongos Nus , Células NIH 3T3 , Transplante de Neoplasias , Proteínas Serina-Treonina Quinases/metabolismo , Receptor do Fator de Crescimento Transformador beta Tipo I , Receptores de Fatores de Crescimento Transformadores beta/metabolismo , Transdução de Sinais , Fator de Crescimento Transformador beta/fisiologia , Proteínas Supressoras de Tumor/fisiologia
16.
Vet Parasitol ; 200(3-4): 271-5, 2014 Mar 01.
Artigo em Inglês | MEDLINE | ID: mdl-24439849

RESUMO

The objective of this study was to determine the impact of integrated parasite management (IPM) training, including FAMACHA(©) eyelid color scoring, on the ability of U.S. sheep and goat producers to control gastrointestinal nematodes (GIN) on their farms. A survey was developed and provided to over 2000 producers trained from 2004 to 2008 in IPM with questions involving farm size (number of sheep/goats), location (U.S. state), impact of training on parasite control efforts and parasite problems on farm, and IPM practices used. Responses were divided into U.S. Census regions of the U.S. Descriptive statistics and logistic regression were used to describe results. Most of the 729 respondents were from the southern region of the U.S. (54.3%) and were small-scale producers (50 or less animals; 64.8%). Nearly all of the respondents (95.1%) agreed that IPM workshop attendance made a difference in their ability to control and monitor parasitism in their herd or flock and employed IPM practices to control GIN (96.3%). The most popular practices respondents used were rotational grazing (71.2%), genetic selection (choosing a parasite resistant breed and/or culling susceptible animals; 52.7%), grain supplementation on pasture to improve nutrition (44.0%), and increased height of plants being grazed (41.8%). Although reporting using a practice decreased (P<0.05) the likelihood of reporting fewer problems, for each 1-point increase in the number of practices which producers employed to control internal parasitism in their herd or flock, they were 16% more likely to report fewer GIN problems (P<0.05). Approximately 75% of respondents indicated an economic benefit of IPM on their farm (P<0.05), and those reporting savings of over $80 were more likely to report fewer problems (P<0.05) with parasites after the training while those reporting no economic benefit were less likely to report fewer problems with GIN (P<0.001). Overall, IPM training resulted in positive impacts for producers responding to the survey and should continue.


Assuntos
Criação de Animais Domésticos/educação , Criação de Animais Domésticos/estatística & dados numéricos , Educação/normas , Gastroenteropatias/veterinária , Doenças das Cabras/prevenção & controle , Infecções por Nematoides/veterinária , Doenças dos Ovinos/prevenção & controle , Animais , Gastroenteropatias/parasitologia , Gastroenteropatias/prevenção & controle , Doenças das Cabras/parasitologia , Cabras , Nematoides/fisiologia , Infecções por Nematoides/prevenção & controle , Avaliação de Programas e Projetos de Saúde , Ovinos , Doenças dos Ovinos/parasitologia , Estados Unidos
17.
J Appl Microbiol ; 116(1): 145-56, 2014 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-24131682

RESUMO

AIMS: This study investigated the antiobesity effect of lactic acid bacteria (Lactobacillus plantarum LG42) isolated from gajami sik-hae. METHODS AND RESULTS: Male C57BL/6J mice were divided into four groups (n = 10); NDC (normal diet & DW), HDC (high-fat diet & DW), LGLAB (high-fat diet & Lactobacillus plantarum LG42, 1 × 10(7) CFU per mouse), HGLAB (high-fat diet & L. plantarum LG42, 1 × 10(9) CFU per mouse). After 12 weeks, GLAB supplemented groups showed lower body weight, with a significant reduction in epididymal and back fat. Serum and hepatic triglyceride, serum insulin and leptin levels were significantly lowered in GLAB supplemented groups. The hepatic mRNA expression of PPARα and CPT-I were significantly increased in GLAB groups, whereas the level of ACC, SREBP-1 and LXRα were significantly decreased in GLAB groups compared with HDC group. Additionally, GLAB reduces the expression of PPARγ in the epididymal adipose tissue resulting in inhibition of genes regulated by PPARγ. CONCLUSION: These results suggest that the Lactobacillus plantarum LG42 has antiobesity effects in high-fat-diet-induced obese mice. SIGNIFICANCE AND IMPACT OF THE STUDY: These results may contribute to nutraceutical and food industries in developing functional food and probiotics based therapies for the treatment and prevention of obesity.

18.
Transplant Proc ; 45(8): 3097-101, 2013 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-24157043

RESUMO

INTRODUCTION: We investigated the optimal method for transportation of isolated porcine islets from an isolation facility to a transplant hospital or research center in terms of temperature, oxygen supply, and shaking effect. METHODS: Commercially available insulator boxes with thermoregulators exposed for 5 hours under two external temperatures (4°C and 37°C) were monitored using HOBO temperature loggers. To find the optimal transport device, we compared islet counts, viability, quality, and function in conical tubes, gas-permeable bags (GPB) and gas-permeable flasks (GPF) after 1, 3 and 5 hours. To evaluate the effects of shaking on islets, we also analyzed the difference between a control and a shaking group in each device with time. RESULTS: Commercially available Styrofoam insulators with thermoregulators maintained the internal temperature near the target. Islet recovery rate for GPF, which was higher than other devices, was maintained, while those decreased with time for conical tube and GPB containers adenosine diphosphate/adenosine triphosphate (ADP/ATP) ratio for GPF was lower than other devices, albeit not significantly fluoroscein acrimide/propidium iodide (AO/PI) ratio for GPF was higher than other devices after 5 hours. Glucose stimulated index was not different among the devices. In comparison with the control group, shaking yielded comparable islet survival, viability and function. CONCLUSION: Our study demonstrated that the use of commercially available insulator boxes with thermoregulators maintained internal temperature close to the target value and that GPF was more favorable for islet oxygenation during transportation. This study also suggested negligible impact of shaking on isolated porcine islets during transportation.


Assuntos
Ilhotas Pancreáticas/citologia , Animais , Feminino , Ilhotas Pancreáticas/fisiologia , Suínos
19.
Asian-Australas J Anim Sci ; 26(2): 151-6, 2013 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-25049770

RESUMO

Hanwoo (Also known as Korean native cattle; Bos taurus coreanae) have been used for transportation and farming for a long time in South Korea. It has been about 30 yrs since Hanwoo improvement began in earnest as beef cattle for meat yield. The purpose of this study was to determine the trend of improvement as well as to estimate genetic parameters of the traits being used for seedstock selection based on the data collected from the past. Hanwoo proven bulls in South Korea are currently selected through performance and progeny tests. National Hanwoo genetic evaluations are implemented with yearling weight (YW), carcass weight (CW), eye muscle area (EMA), backfat thickness (BF) and marbling score (MS). Yearling weights and MS are used for selecting young bulls, and EMA, BF, and MS are used for selecting proven bulls. One individual per testing room was used for performance tests, and five individuals per room for progeny tests. Individuals tested were not allowed to graze pasture, but there was enough space for them to move around in the testing room. Feeds including roughages and minerals were fed ad libitum, and concentrates were provided at the rate of about 1.8% of individual weight. Overall means of the traits were 352.8±38.56 kg, 335.09±44.61 kg, 77.85±8.838 cm(2), 8.6±3.7 mm and 3.293±1.648 for YW, CW, EMA, BF and MS. Heritabilities estimated in this study were 0.30, 0.30, 0.42, 0.50 and 0.63 in YW, CW, EMA, BF and MS, respectively, which are similar to results from previous research. Yearling weight was 315.54 kg in 1998, and had increased to 355.06 kg in 2011, resulting in about 40 kg of improvement over 13 yrs. YW and CW have improved remarkably over the past 15 yrs. Breeding values between 1996 and 2000 decreased or did not change much, but have moved in a desirable direction since 2001. These improvements correspond with the substantial increase in use of animal models since the late 1990s in Korea. Hanwoo testing programs have practically contributed to the improvement in aspects of quality and quantity. In sum, the current selection system is good enough to accommodate circumstances where fewer sires are used on many more cows. Although progeny tests take longer and cost more, they seem to be appropriate under the circumstances of the domestic market with its higher requirement for better meat quality. Consequently, accumulative data collection, genetic evaluation model development, revision of selection indices, as well as cooperation among farms, associations, National Agricultural Cooperative Federation, universities, research institutes, and government agencies must be applied to the Hanwoo selection program. All these efforts will assist the domestic market to secure a competitive position against imported beef under Free Trade Agreement trade system and will provide farmers with higher profits as well as the public with a higher quality of beef.

20.
J Appl Microbiol ; 113(6): 1507-16, 2012 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-22978326

RESUMO

AIMS: In this study, we investigated the anti-obesity effects of kimchi (Korean traditional fermented vegetable) fermented either without starter culture or with a specific starter culture, Weissella koreensis OK1-6. METHODS AND RESULTS: C57BL/6J mice were divided into four groups (n = 7); normal diet, HF (high-fat diet), HF-KC (high-fat diet containing 3% kimchi manufactured without starter) and HF-KCO (high-fat diet containing 3% kimchi manufactured with the starter culture W. koreensis OK1-6). After 12 weeks of dietary intervention, the mice were killed, and serum and tissue samples were examined. Serum and hepatic lipid profile, insulin, leptin concentration and expression level of lipid anabolic genes like peroxisome proliferator-activated receptor γ, stearoyl-CoA desaturase-1, liver X receptor α and SREBP2 were significantly decreased (<0.05) along with body and epididymal fat pad weight in the HF-KCO group compared with the HF-KC and HF group. CONCLUSIONS: These results suggested that kimchi fermented with the starter W. koreensis OK1-6 has anti-obesity effects in HF-induced obese mice. SIGNIFICANCE AND IMPACT OF THE STUDY: These results may contribute to nutraceutical and food industries in developing functional food and probiotics based therapies for the treatment and prevention of obesity.


Assuntos
Brassica/microbiologia , Microbiologia de Alimentos , Obesidade/prevenção & controle , Weissella/fisiologia , Tecido Adiposo/efeitos dos fármacos , Animais , Peso Corporal/efeitos dos fármacos , Dieta Hiperlipídica , Gorduras na Dieta/metabolismo , Modelos Animais de Doenças , Fermentação , Insulina/sangue , Insulina/metabolismo , Leptina/sangue , Leptina/metabolismo , Lipídeos/sangue , Fígado/metabolismo , Masculino , Camundongos , Camundongos Endogâmicos C57BL , Camundongos Obesos , Obesidade/metabolismo , PPAR gama/metabolismo
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