RESUMEN
The accumulation of arsenic (As) in rice (Oryza sativa L.) grain poses a significant health concern in Bangladesh. To address this, we investigated the efficacy of various organic amendments and phytoremediation techniques in reducing As buildup in O. sativa. We evaluated the impact of five doses of biochar (BC; BC0.1: 0.1%, BC0.28: 0.28%, BC0.55: 0.55%, BC0.82: 0.82% and BC1.0: 1.0%, w/w), vermicompost (VC; VC1.0: 1.0%, VC1.8: 1.8%, VC3.0: 3.0%, VC4.2: 4.2% and VC5.0: 5.0%, w/w), and floating duckweed (DW; DW100: 100, DW160: 160, DW250: 250, DW340: 340 and DW400: 400 g m- 2) on O. sativa cultivated in As-contaminated soil. Employing a three-factor five-level central composite design and response surface methodology (RSM), we optimized the application rates of BC-VC-DW. Our findings revealed that As contamination in the soil negatively impacted O. sativa growth. However, the addition of BC, VC, and DW significantly enhanced plant morphological parameters, SPAD value, and grain yield per pot. Notably, a combination of moderate BC-DW and high VC (BC0.55VC5DW250) increased grain yield by 44.4% compared to the control (BC0VC0DW0). As contamination increased root, straw, and grain As levels, and oxidative stress in O. sativa leaves. However, treatment BC0.82VC4.2DW340 significantly reduced grain As (G-As) by 56%, leaf hydrogen peroxide by 71%, and malondialdehyde by 50% compared to the control. Lower doses of BC-VC-DW (BC0.28VC1.8DW160) increased antioxidant enzyme activities, while moderate to high doses resulted in a decline in these activities. Bioconcentration and translocation factors below 1 indicated limited As uptake and translocation in plant tissues. Through RSM optimization, we determined that optimal doses of BC (0.76%), VC (4.62%), and DW (290.0 g m- 2) could maximize grain yield (32.96 g pot- 1, 44% higher than control) and minimize G-As content (0.189 mg kg- 1, 54% lower than control). These findings underscore effective strategies for enhancing yield and reducing As accumulation in grains from contaminated areas, thereby ensuring agricultural productivity, human health, and long-term sustainability. Overall, our study contributes to safer food production and improved public health in As-affected regions.
Asunto(s)
Arsénico , Biodegradación Ambiental , Carbón Orgánico , Oryza , Contaminantes del Suelo , Oryza/metabolismo , Oryza/crecimiento & desarrollo , Arsénico/metabolismo , Contaminantes del Suelo/metabolismo , Compostaje/métodos , Araceae/metabolismo , Araceae/efectos de los fármacos , Araceae/crecimiento & desarrollo , Suelo/químicaRESUMEN
Microplastic (MP) pollution in terrestrial ecosystems is gaining attention, but there is limited research on its effects on leafy vegetables when combined with heavy metals. This study examines the impact of three MP types-polyethylene (PE), polyethylene terephthalate (PET), and polystyrene (PS)-at concentrations of 0.02, 0.05, and 0.1% w/w, along with cadmium (Cd) and biochar (B), on germination, growth, nutrient absorption, and heavy metal uptake in red amaranth (Amaranthus tricolor L.). We found that different MP types and concentrations did not negatively affect germination parameters like germination rate, relative germination rate, germination vigor, relative germination vigor, and germination speed. However, they increased phytotoxicity and decreased stress tolerance compared to an untreated control (CK1). The presence of MPs, particularly the PS type, reduced phosphorus and potassium uptake while enhancing Cd uptake. For example, treatments PS0.02CdB, PS0.05CdB, and PS0.1CdB increased Cd content in A. tricolor seedlings by 158%, 126%, and 44%, respectively, compared to the treatment CdB (CK2). Additionally, MP contamination led to reduced plant height, leaf dry matter content, and fresh and dry weights, indicating adverse effects on plant growth. Moreover, the presence of MPs increased bioconcentration factors and translocation factors for Cd, suggesting that MPs might act as carriers for heavy metal absorption in plants. On the positive side, the addition of biochar improved several root parameters, including root length, volume, surface area, and the number of root tips in the presence of MPs, indicating potential benefits for plant growth. Our study shows that the combination of MPs and Cd reduces plant growth and increases the risk of heavy metal contamination in food crops. Further research is needed to understand how different MP types and concentrations affect various plant species, which will aid in developing targeted mitigation strategies and in exploring the mechanisms through which MPs impact plant growth and heavy metal uptake. Finally, investigating the potential of biochar application in conjunction with other amendments in mitigating these effects could be key to addressing MP and heavy metal contamination in agricultural systems.
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Amaranthus , Cadmio , Carbón Orgánico , Microplásticos , Amaranthus/efectos de los fármacos , Amaranthus/crecimiento & desarrollo , Amaranthus/metabolismo , Cadmio/metabolismo , Contaminantes del Suelo/metabolismo , Germinación/efectos de los fármacos , Nutrientes/metabolismo , Plantones/crecimiento & desarrollo , Plantones/efectos de los fármacos , Plantones/metabolismoRESUMEN
The hallmark of pathological cardiac hypertrophy is the decline in myocardial contractility caused by an energy deficit resulting from metabolic abnormalities, particularly those related to glucose metabolism. Here, we aim to explore whether D-Allose, a rare sugar that utilizes the same transporters as glucose, may restore metabolic equilibrium and reverse cardiac hypertrophy. Isolated neonatal rat cardiomyocytes were stimulated with phenylephrine and treated with D-Allose simultaneously for 48 h. D-Allose treatment resulted in a pronounced reduction in cardiomyocyte size and cardiac remodelling markers accompanied with a dramatic reduction in the level of intracellular glucose in phenylephrine-stimulated cells. The metabolic flux analysis provided further insights revealing that D-Allose exerted a remarkable inhibition of glycolysis as well as glycolytic capacity. Furthermore, in mice subjected to a 14-day continuous infusion of isoproterenol (ISO) to induce cardiac hypertrophy, D-Allose treatment via drinking water notably reduced ISO-induced cardiac hypertrophy and remodelling markers, with minimal effects on ventricular wall thickness observed in echocardiographic analyses. These findings indicate that D-Allose has the ability to attenuate the progression of cardiomyocyte hypertrophy by decreasing intracellular glucose flux and inhibiting glycolysis.
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Cardiomegalia , Glucosa , Glucólisis , Isoproterenol , Miocitos Cardíacos , Fenilefrina , Animales , Cardiomegalia/tratamiento farmacológico , Cardiomegalia/patología , Miocitos Cardíacos/efectos de los fármacos , Miocitos Cardíacos/metabolismo , Miocitos Cardíacos/patología , Glucólisis/efectos de los fármacos , Glucosa/metabolismo , Fenilefrina/farmacología , Masculino , Células Cultivadas , Ratones Endogámicos C57BL , Ratas , Ratones , Modelos Animales de Enfermedad , Ratas Sprague-DawleyRESUMEN
BACKGROUND: The nonsteroidal mineralocorticoid receptor blocker esaxerenone is effective in reducing blood pressure (BP). OBJECTIVE: In this study, we investigated esaxerenone-driven sodium homeostasis and its association with changes in BP in Dahl salt-sensitive (DSS) hypertensive rats. METHODS: In the different experimental setups, we evaluated BP by a radiotelemetry system, and sodium homeostasis was determined by an approach of sodium intake (food intake) and excretion (urinary excretion) in DSS rats with a low-salt diet (0.3% NaCl), high-salt diet (HSD, 8% NaCl), HSD plus 0.001% esaxerenone (w/w), and HSD plus 0.05% furosemide. RESULTS: HSD-fed DSS rats showed a dramatic increase in BP with a non-dipper pattern, while esaxerenone treatment, but not furosemide, significantly reduced BP with a dipper pattern. The cumulative sodium excretion in the active period was significantly elevated in esaxerenone- and furosemide-treated rats compared with their HSD-fed counterparts. Sodium content in the skin, skinned carcass, and total body tended to be lower in esaxerenone-treated rats than in their HSD-fed counterparts, while these values were unchanged in furosemide-treated rats. Consistently, sodium balance tended to be reduced in esaxerenone-treated rats during the active period. Histological evaluation showed that esaxerenone, but not furosemide, treatment attenuated glomerulosclerosis, tubulointerstitial fibrosis, and urinary protein excretion induced by high salt loading. CONCLUSIONS: Collectively, these findings suggest that an esaxerenone treatment-induced reduction in BP and renoprotection are associated with body sodium homeostasis in salt-loaded DSS rats.
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Hipertensión , Enfermedades Renales , Animales , Antihipertensivos/farmacología , Antihipertensivos/uso terapéutico , Presión Sanguínea , Furosemida/farmacología , Enfermedades Renales/patología , Pirroles , Ratas , Ratas Endogámicas Dahl , Sodio/metabolismo , Cloruro de Sodio/farmacología , Cloruro de Sodio Dietético/farmacología , SulfonasRESUMEN
We investigated the effects of esaxerenone, a novel, nonsteroidal, and selective mineralocorticoid receptor blocker, on cardiac function in Dahl salt-sensitive (DSS) rats. We provided 6-week-old DSS rats a high-salt diet (HSD, 8% NaCl). Following six weeks of HSD feeding (establishment of cardiac hypertrophy), we divided the animals into the following two groups: HSD or HSD + esaxerenone (0.001%, w/w). In survival study, all HSD-fed animals died by 24 weeks of age, whereas the esaxerenone-treated HSD-fed animals showed significantly improved survival. We used the same protocol with a separate set of animals to evaluate the cardiac function by echocardiography after four weeks of treatment. The results showed that HSD-fed animals developed cardiac dysfunction as evidenced by reduced stroke volume, ejection fraction, and cardiac output. Importantly, esaxerenone treatment decreased the worsening of cardiac dysfunction concomitant with a significantly reduced level of systolic blood pressure. In addition, treatment with esaxerenone in HSD-fed DSS rats caused a reduced level of cardiac remodeling as well as fibrosis. Furthermore, inflammation and oxidative stress were significantly reduced. These data indicate that esaxerenone has the potential to mitigate cardiac dysfunction in salt-induced myocardial injury in rats.
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Cardiotónicos/uso terapéutico , Hipertensión/tratamiento farmacológico , Antagonistas de Receptores de Mineralocorticoides/uso terapéutico , Pirroles/uso terapéutico , Receptores de Mineralocorticoides/metabolismo , Sulfonas/uso terapéutico , Animales , Cardiotónicos/farmacología , Electrocardiografía , Fibrosis , Hipertensión/diagnóstico por imagen , Hipertensión/fisiopatología , Inflamación/complicaciones , Inflamación/tratamiento farmacológico , Masculino , Pirroles/farmacología , Ratas Endogámicas Dahl , Cloruro de Sodio Dietético , Sulfonas/farmacología , Análisis de Supervivencia , Remodelación Ventricular/efectos de los fármacosRESUMEN
We examined the effect of D-Tagatose on the growth of oral bacteria including Streptococcus mutans (S. mutans). Saliva collected from 10 healthy volunteers was plated on BHI medium (to culture total oral bacteria) and MBS medium (to culture S. mutans, specifically). Agar plates of BHI or MBS containing xylitol or D-Tagatose were cultured under aerobic or anaerobic conditions. We then counted the number of colonies. In BHI plates containing D-Tagatose, a complete and significant reduction of bacteria occurred under both aerobic and anaerobic conditions. In MSB medium, significant reduction of S. mutans was also observed. We then performed a doubleblind parallel randomized trial with 19 healthy volunteers. They chewed gum containing xylitol, D-Tagatose, or both for 4 weeks, and their saliva was collected weekly and plated on BHI and MSB media. These plates were cultured under anaerobic conditions. Total bacteria and S. mutans were not effectively reduced in either the D-Tagatose or xylitol gum group. However, S. mutans was significantly reduced in volunteers chewing gum containing both D-Tagatose and xylitol. Thus, D-Tagatose inhibited the growth of S. mutans and many types of oral bacteria, indicating that D-Tagatose intake may help prevent dental caries, periodontitis, and many oral diseases.
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Caries Dental/prevención & control , Hexosas/administración & dosificación , Streptococcus mutans/efectos de los fármacos , Edulcorantes/administración & dosificación , Adulto , Goma de Mascar , Método Doble Ciego , Femenino , Humanos , Masculino , Proyectos Piloto , Saliva/microbiología , Streptococcus mutans/crecimiento & desarrollo , Xilitol/administración & dosificaciónRESUMEN
Glucose is a major energy source for mammalian cells and is transported into cells via cell-specific expression of various glucose transporters (GLUTs). Especially, cancer cells require massive amounts of glucose as an energy source for their dysregulated growth and thus over-express GLUTs. d-allose, a C-3 epimer of d-glucose, is one of rare sugars that exist in small quantities in nature. We have shown that d-allose induces the tumor suppressor gene coding for thioredoxin interacting protein (TXNIP) and inhibits cancer cell growth by G1 cell cycle arrest. It has also been reported that GLUTs including GLUT1 are over-expressed in many cancer cell lines, which may contribute to larger glucose utilization. Since d-allose suppresses the growth of cancer cells through the upregulation of TXNIP expression, our present study focused on whether d-allose down-regulates GLUT1 expression via TXNIP expression and thus suppresses cancer cell growth. Western blot and real-time PCR analyses revealed that d-allose significantly induced TXNIP expression and inhibited GLUT1 expression in a dose-dependent manner in three human cancer cell lines: hepatocellular carcinoma (HuH-7), Caucasian breast adenocarcinoma (MDA-MB-231), and neuroblastoma (SH-SY5Y). In these cell lines, d-allose treatment inhibited cell growth. Importantly, d-allose treatment decreased glucose uptake, as measured by the uptake of 2-deoxy d-glucose. Moreover, the reporter assays showed that d-allose decreased the expression of luciferase through the hypoxia response element present in the tested promoter region. These results suggest that d-allose may cause the inhibition of cancer growth by reducing both GLUT1 expression and glucose uptake.
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Transportador de Glucosa de Tipo 1/genética , Glucosa/farmacología , Neoplasias/genética , Neoplasias/patología , Proteínas Portadoras/genética , Proteínas Portadoras/metabolismo , Línea Celular Tumoral , Proliferación Celular/efectos de los fármacos , Regulación hacia Abajo/efectos de los fármacos , Regulación Neoplásica de la Expresión Génica/efectos de los fármacos , Técnicas de Silenciamiento del Gen , Glucosa/metabolismo , Transportador de Glucosa de Tipo 1/metabolismo , Humanos , ARN Mensajero/genética , ARN Mensajero/metabolismo , Elementos de Respuesta , Regulación hacia Arriba/efectos de los fármacosRESUMEN
BACKGROUND: Recently, one of the rare sugars, D-allose, has received attention from many researchers because of its availability for mass production and its various physiological functions. Among these, an antioxidative effect has been strongly suggested. In this study, we investigated whether this effect is also applicable to the field of skin surgery. METHODS: In ischemia-reperfusion injury model using the rat abdominal skin island flap (male Wistar rats, n = 110), D-allose was injected intravenously 15 min before 8-h ischemia. The survival area (%) was measured by digital photographic assessment 1 wk after surgery, and multiple comparisons (Fisher's protected least significant difference) were carried out. Histopathological examination (neutrophilic infiltration into dermis in hematoxylin and eosin stain) and immunostaining (of ectodermal dysplasia-1 (ED1)-positive cells/flap) were assessed. Myeloperoxidase (MPO) activity in the skin flap (sampling at the time of 8 h after reperfusion) was measured spectrophotometrically, and Student t-test was performed. RESULTS: D-allose extended the survival of the remaining flaps, and a dose greater than 30 mg (0.1 mg/g) was necessary to be effective. The flap survival rates in the 30, 60, and 150 mg groups were significantly higher than that in the control (saline) group: 75.87 ± 5.90, 79.27 ± 7.81, and 77.87 ± 6.20 versus 50.53 ± 9.66, respectively (P < 0.05). ED1-positive cells/flap in 60 mg of D-allose and control (saline) were 78 ± 25.7 versus 124 ± 15.8, respectively (P = 0.08). The MPO activity in the D-allose 60 mg group was 0.40 ± 0.04, and that in the control (saline) was 0.72 ± 0.12. D-allose significantly reduced the skin tissue MPO activity (P < 0.05) compared with that in the control (saline) group. CONCLUSIONS: We proved that D-allose has a reducing effect against ischemia-reperfusion injury on the skin island flap model, and the mechanism is related to inhibiting the activity of neutrophils in the skin tissues. Compared with chemo-synthetic materials, rare sugars are safer for our bodies as well as the environment; therefore, this rare sugar project is expected to lead to the development of a safer antioxidant for skin flap surgery.
Asunto(s)
Antioxidantes/uso terapéutico , Glucosa/uso terapéutico , Daño por Reperfusión/prevención & control , Piel/irrigación sanguínea , Colgajos Quirúrgicos/irrigación sanguínea , Abdomen/irrigación sanguínea , Abdomen/patología , Abdomen/cirugía , Animales , Relación Dosis-Respuesta a Droga , Masculino , Modelos Animales , Peroxidasa/metabolismo , Ratas , Ratas Wistar , Daño por Reperfusión/metabolismo , Daño por Reperfusión/patología , Piel/metabolismo , Piel/patología , Colgajos Quirúrgicos/patología , Colgajos Quirúrgicos/cirugíaRESUMEN
Rare sugar D-psicose has cropped up as a non-toxic and effective compound to protect and preserve pancreatic ß-islets in the growing type 2 diabetes mellitus (T2DM) rats through the regulation of glucose and fat metabolism. The present study was undertaken to examine the effect of rare sugar D-psicose on the protection of pancreatic ß-islets using Otsuka Long-Evans Tokushima Fatty (OLETF) rats, a T2DM model. Treated rats were fed with 5% D-psicose or 5% D-glucose supplemented drinking water, and only water in the control for 13 weeks. A non-diabetic Long-Evans Tokushima Otsuka (LETO), fed with water served as a counter control of OLETF. D-Psicose significantly attenuated progressive ß-islet fibrosis and preserved islets, evaluated by hematoxylin-eosin staining, Masson's trichrome staining and immunostainings of insulin and α-smooth muscle actin (SMA). D-Psicose significantly reduced increase in body weight and abdominal fat deposition. Oral glucose tolerance test (OGTT) showed reduced blood glucose levels suggesting the improvement of insulin resistance. All these data suggests that D-psicose protected and preserved pancreatic ß-islets through the maintenance of hyperglycemia and by the prevention of fat accumulation in OLETF rats.
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Citoprotección , Diabetes Mellitus Tipo 2/tratamiento farmacológico , Fructosa/administración & dosificación , Resistencia a la Insulina , Células Secretoras de Insulina/efectos de los fármacos , Obesidad/tratamiento farmacológico , Grasa Abdominal/efectos de los fármacos , Grasa Abdominal/patología , Actinas/metabolismo , Adipoquinas/sangre , Animales , Índice de Masa Corporal , Peso Corporal/efectos de los fármacos , Ingestión de Alimentos/efectos de los fármacos , Fibrosis , Glucosa/metabolismo , Prueba de Tolerancia a la Glucosa , Insulina/metabolismo , Células Secretoras de Insulina/metabolismo , Células Secretoras de Insulina/patología , Masculino , Obesidad/sangre , Ratas , Ratas Endogámicas OLETFRESUMEN
Brucellosis is an occupational hazard of livestock farmers, dairy workers, veterinarians, slaughterhouse workers, and laboratory personnel, all of whom are considered to belong to the high-risk occupational group (HROG). A study was undertaken to determine the seroprevalence of brucellosis, identify risk factors associated with brucellosis seropositivity, and detect Brucella at genus level using real-time polymerase chain reaction (PCR) among people in the HROG in the Dhaka division of Bangladesh. A sample of 500 individuals from the HROG was collected from three districts of Dhaka division of Bangladesh. A multiple random effects logistic regression model was used to identify potential risk factors. Two types of real-time PCR methods were applied to detect Brucella genus-specific DNA using serum from seropositive patients. The prevalence of brucellosis based on the three tests was observed to be 4.4% based on a parallel interpretation. The results of the multiple random effects logistic regression analysis with random intercept for district revealed that the odds of brucellosis seropositivity among individuals who had been in contact with livestock for more than 26 years was about 14 times higher as compared to those who had less than 5 years of contact with livestock. In addition, when the contact was with goats, the odds of brucellosis seropositivity were about 60 times higher as compared to when contact was with cattle only. Noticeable variation in brucellosis seropositivity among humans within the three districts was noted. All of the 13 individuals who tested positive for the serological tests were also positive in two types of real-time PCR using the same serum samples. Livestock farmers of brucellosis positive herds had a significantly higher probability to be seropositive for brucellosis. The study emphasized that contact with livestock, especially goats, is a significant risk factor for the transmission of brucellosis among individuals in the HROG.
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Brucella/aislamiento & purificación , Brucelosis/microbiología , Zoonosis/microbiología , Adolescente , Adulto , Anciano , Anciano de 80 o más Años , Crianza de Animales Domésticos/métodos , Animales , Bangladesh/epidemiología , Brucella/clasificación , Brucella/patogenicidad , Brucelosis/sangre , Brucelosis/epidemiología , Brucelosis/transmisión , Femenino , Cabras/microbiología , Humanos , Modelos Logísticos , Masculino , Persona de Mediana Edad , Prevalencia , Factores de Riesgo , Estudios Seroepidemiológicos , Recursos Humanos , Adulto Joven , Zoonosis/epidemiología , Zoonosis/transmisiónRESUMEN
Dallose is a rare sugar which has been shown to have growth inhibitory effects in several kinds of malignancies. However, the effect of Dallose on lung cancer progression has not been previously studied. To investigate the antitumour effect of Dallose in lung cancer cells and its mechanism, human non-small cell lung cancer (NSCLC) cell lines (squamous cell carcinomas: EBC1 and VMRCLCD; adenocarcinomas: A549, HI1017, RERFLCA1 and NCI-H1975) were treated with Dallose (50 mM) with or without cisplatin (5 µM). Dallose inhibited cell growth, particularly in EBC1 and VMRCLCD cells. In combination with cisplatin, Dallose had a synergistic growth inhibitory effect. Dallose increased the expression of thioredoxin interacting protein (TXNIP) at mRNA and protein levels. Dallose decreased the proportion of cells in G1 phase and increased those in S and G2/M phases. For in vivo experiments, EBC1 cells were inoculated into BALB/c-nu mice. After tumourigenesis, Dallose and cisplatin were injected. In this mouse xenograft model, additional treatment with Dallose showed a significantly greater tumour inhibitory effect compared with cisplatin alone, accompanied by lower Ki67 and higher TXNIP expression. In conclusion, Dallose inhibited NSCLC cell proliferation in vitro and tumour progression in vivo. In combination with cisplatin, Dallose had an additional antitumour effect. Specifically, increased TXNIP expression and subsequent G2/M arrest play a role in Dallose-mediated antitumour effects in NSCLC.
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Carcinoma de Pulmón de Células no Pequeñas/tratamiento farmacológico , Cisplatino/farmacología , Sinergismo Farmacológico , Glucosa/farmacología , Neoplasias Pulmonares/tratamiento farmacológico , Animales , Antineoplásicos/farmacología , Carcinoma de Pulmón de Células no Pequeñas/patología , Quimioterapia Combinada , Femenino , Humanos , Neoplasias Pulmonares/patología , Ratones , Ratones Endogámicos BALB C , Ratones Desnudos , Transducción de SeñalRESUMEN
Thioredoxin interacting protein (TXNIP) is a novel tumor suppressor that is down-regulated in several cancer tissues and tumor cell lines. Overexpression of TXNIP causes cell cycle arrest at the G1/S checkpoint in the hepatocellular carcinoma cell line HuH-7. TXNIP contains putative phosphorylation sites, but the effects of its phosphorylation have not been fully characterized. TXNIP also contains two α-arrestin domains (N-arrestin and C-arrestin) whose functions are not fully understood. Here, we reveal an association between TXNIP and cell cycle regulatory proteins (p27kip1, Jun activation domain-binding protein 1 (JAB1), Cdk2, and cyclin E), suggesting its participation in cell cycle regulation. We observed phosphorylation of TXNIP and used both in vivo and in vitro kinase assays to demonstrate that TXNIP can be phosphorylated by p38 mitogen-activated protein kinase. Furthermore, we also identified Ser361 in TXNIP as one of the major phosphorylation sites. Cell cycle analysis showed that Ser361 phosphorylation participates in TXNIP-mediated cell cycle arrest. In addition, the C-arrestin domain may also play an important role in cell cycle arrest. We also showed that phosphorylation at Ser361 may be important for the association of TXNIP with JAB1 and that the C-arrestin domain is necessary for the nuclear localization of this molecule. Collectively, these studies reveal that TXNIP participates in cell cycle regulation through association with regulatory proteins, especially JAB1, and that C-arrestin-dependent nuclear localization is important for this function. This work may facilitate the development of a new cancer therapy strategy that targets TXNIP as a key molecule inhibiting cancer cell growth via cell cycle blockade at the G1/S checkpoint.
RESUMEN
INTRODUCTION: This study describes the seroprevalence of human brucellosis among pyretic patients and detection of Brucella abortus DNA from seropositive pyretic patients using real-time polymerase chain reaction (rtPCR) for the first time in Bangladesh. METHODOLOGY: Blood samples were collected from 300 pyretic patients from October 2007 to May 2008 and subjected to three serological tests: Rose-Bengal plate test (RBT), standard tube agglutination test (STAT), and indirect enzyme-linked immunosorbent assay (iELISA). Risk factors were identified by multivariate Firth's logistic regression analysis. Brucella genus (BCSP31) and species-specific (IS711) rtPCR were applied to six human sera samples. RESULTS: The seroprevalence of brucellosis among pyretic patients was estimated to be 2.0% (95% confidence interval [CI]: 0.74-4.30). The odds of brucellosis seropositivity were 8.9 (95% CI: 1.26-63.0) times higher in pyretic patients who handled goats than those who handled only cattle, whereas the odds of brucellosis seropositivity were 9.7 (95% CI: 1.28-73.68) times higher in pyretic patients who had backache compared to those without backache. B. abortus DNA was amplified from all six human sera that tested positive by RBT, STAT, and iELISA. As the agreement between the tests was very strong, RBT is recommended as a screening test for the diagnosis of human brucellosis in Bangladesh because it is easier to use, cheaper, and faster. CONCLUSIONS: Brucellosis among pyretic patients is common, and B. abortus is responsible for brucellosis in such patients. Pyretic patients who handle goats and those with backaches should be screened for brucellosis.
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Brucella abortus/inmunología , Brucelosis/epidemiología , Brucelosis/patología , Fiebre/etiología , Adolescente , Adulto , Anciano , Anciano de 80 o más Años , Crianza de Animales Domésticos , Animales , Bangladesh/epidemiología , Brucella abortus/genética , Bovinos , Niño , Preescolar , ADN Bacteriano/sangre , Femenino , Humanos , Inmunoensayo , Masculino , Persona de Mediana Edad , Reacción en Cadena en Tiempo Real de la Polimerasa , Factores de Riesgo , Estudios Seroepidemiológicos , Adulto JovenRESUMEN
BACKGROUND: Pretransplant restoration of islets damaged during isolation remains to be solved. In this study, we examined the effect of D-allose on islets isolated from rat pancreata prior to islet transplantation. METHODS: Rat islets isolated from fresh pancreata were cultured overnight in Roswell Park Memorial Institute 1640 solution in the absence (group 1) or presence (group 2) of D-allose. Then we assessed stimulation index of insulin, and cure rate after islet transplantation to diabetic nude mice. We also measured malondialdehyde level and caspase 3 activity of islets after the overnight culture for assessment of the oxidative stress and the apoptosis. RESULTS: D-allose significantly improved insulin secretion of islets. The stimulation index in group 2 was significantly higher than in group 1. Cure rate after transplantation in group 2 was higher than in group 1 especially in the first week. The malondialdehyde level in group 2 was significantly lower than in group 1. But the caspase 3 activities in both groups did not differ. CONCLUSIONS: D-allose treatment of isolated islet culture prior to transplantation restored islet function and increased successful transplant rate. The results of this study suggested that D-allose improved function of damaged islets through its anti-oxidative activity.
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Glucosa/uso terapéutico , Trasplante de Islotes Pancreáticos/métodos , Animales , Apoptosis/efectos de los fármacos , Caspasa 3/análisis , Diabetes Mellitus Experimental/cirugía , Islotes Pancreáticos/efectos de los fármacos , Malondialdehído/análisis , Ratones , Ratones Desnudos , Estrés Oxidativo/efectos de los fármacos , Ratas , EstereoisomerismoRESUMEN
Although various parts of J. curcas (Jatropha curcas L., Euphorbiaceae) have long been used as traditional folk medicines for their antiviral, analgesic, and/or antidotal efficacies, we are the first to investigate the role of anti-carcinogenicity of isoamericanol A (IAA) from the seed extract. Our results showed that IAA is capable of inhibiting cell proliferation in a dose-dependent manner on the human cancer cell lines of MCF-7, MDA-MB231, HuH-7, and HeLa. Flow cytometry analysis showed IAA significantly induces cell cycle arrest at G2/M on MCF-7 cells. At both protein and mRNA levels examined by western blot and real-time PCR, the results revealed increased expression of BTG2 (B-cell translocation gene 2), p21 (p21(WAF1/CIPI) ), and GADD45A (growth arrest and DNA-damage-inducible, alpha) after IAA treatment, but inversed expression in CDK1 (cyclin-dependent kinase 1) and cyclins B1 and B2. All these effects contribute to G2/M cell cycle arrest. Furthermore, these results coincide with the changes in molecular expressions determined by DNA-microarray analysis. Our findings indicate that IAA has an inhibitory effect on cell proliferation of MCF-7 through cell cycle arrest, giving it great potential as a future therapeutic reagent for cancers.
RESUMEN
A rare sugar, D-allulose (also called D-psicose), has recently been applied as a food supplement in view of controlling diabetes and obesity in Japan. D-allulose has been proven to have unique effects against hyperglycemia and hyperlipidemia in a number of studies using several species of rats and mice. However, the antiobesity effects of D-allulose have not yet been assessed in Lep(ob)/Lep(ob) (ob/ob) mice. Therefore, this study explored the dietary supplemental effects of this sugar in leptin-deficient ob/ob mice. Consequently, the subchronic ingestion of D-allulose in ob/ob mice for 15 wk significantly decreased the body and liver weights, and the loss of body weight was involved in the reduction of the total fat mass, including abdominal visceral fat, and not fat-free body mass, including muscle. Furthermore, D-allulose improved hepatic steatosis, as evaluated using hepatic histological studies and MRI. In the normal mice, none of these parameters were influenced by the single or long-term ingestion of D-allulose. These results indicate that dietary supplementation of D-allulose especially influences postprandial hyperglycemia and obesity-related hepatic steatosis, without exercise therapy or dietary restriction. Therefore, D-allulose may be useful as a supplement for preventing and improving obesity and obesity-related disorders.
Asunto(s)
Suplementos Dietéticos , Hígado Graso/tratamiento farmacológico , Fructosa/administración & dosificación , Obesidad/tratamiento farmacológico , Células 3T3-L1 , Tejido Adiposo/efectos de los fármacos , Tejido Adiposo/metabolismo , Animales , Composición Corporal , Peso Corporal , Diferenciación Celular/efectos de los fármacos , Leptina/deficiencia , Hígado/efectos de los fármacos , Hígado/metabolismo , Imagen por Resonancia Magnética , Ratones , Ratones Endogámicos C57BL , Ratones Noqueados , Tamaño de los Órganos/efectos de los fármacosRESUMEN
Obesity and type 2 diabetes mellitus (T2DM) are the leading worldwide risk factors for mortality. The inextricably interlinked pathological progression from excessive weight gain, obesity, and hyperglycemia to T2DM, usually commencing from obesity, typically originates from overconsumption of sugar and high-fat diets. Although most patients require medications, T2DM is manageable or even preventable with consumption of low-calorie diet and maintaining body weight. Medicines like insulin, metformin, and thiazolidinediones that improve glycemic control; however, these are associated with weight gain, high blood pressure, and dyslipidemia. These situations warrant the attentive consideration of the role of balanced foods. Recently, we have discovered advantages of a rare sugar, D-allulose, a zero-calorie functional sweetener having strong anti-hyperlipidemic and anti-hyperglycemic effects. Study revealed that after oral administration in rats D-allulose readily entered the blood stream and was eliminated into urine within 24h. Cell culture study showed that D-allulose enters into and leaves the intestinal enterocytes via glucose transporters GLUT5 and GLUT2, respectively. In addition to D-allulose's short-term effects, the characterization of long-term effects has been focused on preventing commencement and progression of T2DM in diabetic rats. Human trials showed that D-allulose attenuates postprandial glucose levels in healthy subjects and in borderline diabetic subjects. The anti-hyperlipidemic effect of D-allulose, combined with its anti-inflammatory actions on adipocytes, is beneficial for the prevention of both obesity and atherosclerosis and is accompanied by improvements in insulin resistance and impaired glucose tolerance. Therefore, this review presents brief discussions focusing on physiological functions and potential benefits of D-allulose on obesity and T2DM.
Asunto(s)
Antiinflamatorios/uso terapéutico , Diabetes Mellitus Tipo 2/tratamiento farmacológico , Fructosa/uso terapéutico , Hipoglucemiantes/uso terapéutico , Hipolipemiantes/uso terapéutico , Obesidad/tratamiento farmacológico , Animales , Antiinflamatorios/farmacocinética , Diabetes Mellitus Tipo 2/metabolismo , Monitoreo de Drogas , Fructosa/farmacocinética , Glucosa/metabolismo , Humanos , Hipoglucemiantes/farmacocinética , Hipolipemiantes/farmacocinética , Hígado/metabolismo , Obesidad/metabolismoRESUMEN
BACKGROUND: The fundamental cause of overweight and obesity is consumption of calorie-dense foods. We have introduced a zero-calorie sweet sugar, d-psicose (d-allulose), a rare sugar that has been proven to have strong antihyperglycemic and antihyperlipidemic effects, and could be used as a replacement of natural sugar for the obese and diabetic subjects. AIM: Above mentioned efficacy of d-psicose (d-allulose) has been confirmed in our previous studies on type 2 diabetes mellitus (T2DM) model Otsuka Long-Evans Tokushima Fatty (OLETF) rats with short-term treatment. In this study we investigated the long-term effect of d-psicose in preventing the commencement and progression of T2DM with the mechanism of preservation of pancreatic ß-cells in OLETF rats. METHODS: Treated OLETF rats were fed 5% d-psicose dissolved in water and control rats only water. Nondiabetic control rats, Long-Evans Tokushima Otsuka (LETO), were taken as healthy control and fed water. To follow the progression of diabetes, periodic measurements of blood glucose, plasma insulin, and body weight changes were continued till sacrifice at 60 weeks. Periodic in vivo body fat mass was measured. On sacrifice, pancreas, liver, and abdominal adipose tissues were collected for various staining tests. RESULTS: d-Psicose prevented the commencement and progression of T2DM till 60 weeks through the maintenance of blood glucose levels, decrease in body weight gain, and the control of postprandial hyperglycemia, with decreased levels of HbA1c in comparison to nontreated control rats. This improvement in glycemic control was accompanied by the maintenance of plasma insulin levels and the preservation of pancreatic ß-cells with the significant reduction in inflammatory markers. Body fat accumulation was significantly lower in the treatment group, with decreased infiltration of macrophages in the abdominal adipose tissue. CONCLUSION: Our findings suggest that the rare sugar d-psicose could be beneficial for the prevention and control of obesity and hyperglycemia with the preservation of ß-cells in the progression of T2DM.
Asunto(s)
Diabetes Mellitus Tipo 2/prevención & control , Fructosa/farmacología , Hipoglucemiantes/farmacología , Grasa Abdominal/efectos de los fármacos , Grasa Abdominal/metabolismo , Grasa Abdominal/fisiopatología , Adiposidad/efectos de los fármacos , Animales , Antiinflamatorios/farmacología , Fármacos Antiobesidad/farmacología , Biomarcadores/sangre , Glucemia/efectos de los fármacos , Glucemia/metabolismo , Diabetes Mellitus Tipo 2/sangre , Diabetes Mellitus Tipo 2/diagnóstico , Diabetes Mellitus Tipo 2/fisiopatología , Modelos Animales de Enfermedad , Progresión de la Enfermedad , Hemoglobina Glucada/metabolismo , Inflamación/sangre , Inflamación/fisiopatología , Inflamación/prevención & control , Mediadores de Inflamación/metabolismo , Insulina/sangre , Resistencia a la Insulina , Células Secretoras de Insulina/efectos de los fármacos , Células Secretoras de Insulina/metabolismo , Obesidad/sangre , Obesidad/fisiopatología , Obesidad/prevención & control , Ratas Endogámicas OLETF , Factores de Tiempo , Aumento de Peso/efectos de los fármacosRESUMEN
OBJECTIVE: Bangladesh is a high tuberculosis burden country. It is always challenging to diagnose active pulmonary tuberculosis (PTB) cases in rural areas where the setting up of conventional microscopic and cultural diagnostic tools is difficult. The objective of the present study is to find a feasible, reliable and easily accessible alternative diagnostic approach for PTB in the rural areas of Bangladesh. METHODS: A total of 86 sputum samples were collected from clinically suspected PTB patients of Anantapur village, an underdeveloped remote area of Netrokona district, Bangladesh. Sputum samples were screened by Ziehl-Neelsen (Z-N) and fluorescence staining methods and were categorized as smear-positive active PTB cases (n=50) and smear-negative controls (n=36); then the performance of three popular immunological tests were evaluated, including ICT, ELISA and Mantoux tests (MT). RESULTS: The sensitivity of ICT, ELISA, and MT (10mm induration size) was 68%, 84% and 96%, respectively, and the specificity of these tests was 94.4%, 80.6% and 52.8%, respectively. When the cut-off size of induration in MT was changed from 10 to ⩾15mm, the sensitivity and specificity of MT became 92% and 83.3%, respectively. It was also found that the interpretation of MT was not significantly affected by BCG vaccination when ⩾15mm induration was taken as a cut-off value. CONCLUSION: Considering the resource-constraints of rural and remote areas, the Mantoux test could be an alternative tool for the diagnosis of active PTB.
RESUMEN
BACKGROUND: The purpose of this study was to evaluate intestinal absorption, organ distribution, and urinary elimination of the rare sugar D-psicose, a 3-carbon stereoisomer of D-fructose that is currently being investigated and which has been found to be strongly effective against hyperglycemia and hyperlipidemia. METHODS: This study was performed using radioactive D-psicose, which was synthesized enzymatically from radioactive D-allose. Concentrations in whole blood, urine, and organs were measured at different time points until 2 hours after both oral and intravenous administrations and 7 days after a single oral administration (100 mg/kg body weight) to Wistar rats. Autoradiography was also performed by injecting 100 mg/kg body weight of (14)C-labeled D-psicose or glucose intravenously to C3H mice. RESULTS: Following oral administration, D-psicose easily moved to blood. The maximum blood concentration (48.5±15.6 µg/g) was observed at 1 hour. Excretion to urine was 20% within 1 hour and 33% within 2 hours. Accumulation to organs was detected only in the liver. Following intravenous administration, blood concentration was decreased with the half-life=57 minutes, and the excretion to urine was up to almost 50% within 1 hour. Similarly to the results obtained with oral administration, accumulation to organs was detected only in the liver. Seven days after the single-dose oral administration, the remaining amounts in the whole body were less than 1%. Autoradiography of mice showed results similar to those in rats. High signals of (14)C-labeled D-psicose were observed in liver, kidney, and bladder. Interestingly, no accumulation of D-psicose was observed in the brain. CONCLUSION: D-psicose was absorbed well after oral administration and eliminated rapidly after both oral and intravenous administrations, with short duration of action. The study provides valuable pharmacokinetic data for further drug development of D-psicose. Because the findings were mainly based on animal study, it is necessary to implement human trials to study the metabolism pathway, which would give an important guide for human intake and food application of D-psicose.