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1.
Int J Mol Sci ; 22(19)2021 Oct 05.
Artigo em Inglês | MEDLINE | ID: mdl-34639103

RESUMO

Various pathogens, such as Ebola virus, Marburg virus, Nipah virus, Hendra virus, Severe Acute Respiratory Syndrome Coronavirus (SARS-CoV), Middle East Respiratory Syndrome Coronavirus (MERS-CoV), and SARS-CoV-2, are threatening human health worldwide. The natural hosts of these pathogens are thought to be bats. The rousette bat, a megabat, is thought to be a natural reservoir of filoviruses, including Ebola and Marburg viruses. Additionally, the rousette bat showed a transient infection in the experimental inoculation of SARS-CoV-2. In the current study, we established and characterized intestinal organoids from Leschenault's rousette, Rousettus leschenaultii. The established organoids successfully recapitulated the characteristics of intestinal epithelial structure and morphology, and the appropriate supplements necessary for long-term stable culture were identified. The organoid showed susceptibility to Pteropine orthoreovirus (PRV) but not to SARS-CoV-2 in experimental inoculation. This is the first report of the establishment of an expandable organoid culture system of the rousette bat intestinal organoid and its sensitivity to bat-associated viruses, PRV and SARS-CoV-2. This organoid is a useful tool for the elucidation of tolerance mechanisms of the emerging rousette bat-associated viruses such as Ebola and Marburg virus.

2.
Nihon Yakurigaku Zasshi ; 156(5): 275-281, 2021.
Artigo em Japonês | MEDLINE | ID: mdl-34470931

RESUMO

Nonalcoholic steatohepatitis (NASH) is one of the most common causes of chronic liver disease, with the increased prevalence of obesity, type 2 diabetes, and metabolic disorders in recent years. As the disease progresses, it leads to hepatic fibrosis, which may progress to hepatocellular carcinoma, but there is still no cure for severe hepatic fibrosis. Currently, in order to develop drugs for the treatment of NASH, the effects of candidate drugs are evaluated by a long-term administration to mice and rats that are fed a high-fat or methionine-deficient diet to reproduce the pathology of fatty liver and liver fibrosis. Since drug development using these experimental animals is time-consuming and costly, in vitro models that reproduce the pathology of NASH have recently been developing. In this review, we will outline the current issues in the diagnosis and treatment of NASH, and introduce our research for the discovery of early diagnostic markers and the development of new therapeutic agents using liver organoid cultures derived from mouse models of NASH.


Assuntos
Diabetes Mellitus Tipo 2 , Hepatopatia Gordurosa não Alcoólica , Animais , Dieta Hiperlipídica , Modelos Animais de Doenças , Descoberta de Drogas , Fígado , Cirrose Hepática , Camundongos , Camundongos Endogâmicos C57BL , Hepatopatia Gordurosa não Alcoólica/tratamento farmacológico , Hepatopatia Gordurosa não Alcoólica/patologia , Organoides , Ratos
3.
J Vet Med Sci ; 2021 Sep 06.
Artigo em Inglês | MEDLINE | ID: mdl-34483187

RESUMO

Previous studies reported that diabetes alters the activities of hepatic cytochrome P450 (CYP) enzymes, which, in turn, affects the disposition of some drugs. We herein examined and compared the effects of the combination of dapagliflozin with a low insulin dose, a full dose of insulin alone, and dapagliflozin alone for 3 and 8 weeks on CYP activities in a diabetes type 1 rat model. We induced type 1 diabetes in rats using a single intraperitoneal injection of 60 mg/kg streptozotocin (STZ). Daily treatment with the full dose of insulin alone, dapagliflozin alone, or dapagliflozin in combination with a low dose of insulin was then initiated. STZ-induced rats developed marked hyperglycemia and altered CYP2E activities. Dapagliflozin in combination with a low dose of insulin stabilized hyperglycemia and CYP1A, 2D, 2E and 3A activities. However, dapagliflozin alone did not improve blood glucose levels or CYP activities. These results suggest that the effects of dapagliflozin in combination with a low dose of insulin are similar to those of a full dose of insulin, and stabilize CYP activities in type 1 diabetes.

4.
Zebrafish ; 18(5): 316-325, 2021 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-34491109

RESUMO

The zebrafish is a valuable model organism that is widely used in studies of vertebrate development. In the laboratory, zebrafish embryonic development is normally carried out at 28.5°C. In this study, we sought to determine whether it was possible to modify the speed of embryonic development through the use of short- and long-term variations in incubation temperature. After incubation at 20°C-32°C, most early-stage embryos survived to the epiboly stage, whereas more than half of the embryos died at <20°C or >32°C. The rate of development differed between embryos incubated at the lowest (18°C) and highest (34°C) temperatures: a difference of 60 min was observed at the 2-cell stage and 290 min at the 1k-cell stage. When blastulae that had developed at 28°C were transferred to a temperature lower than 18°C for one or more hours, they developed normally after being returned to the original 28°C. Analyses using green fluorescent protein-buckyball mRNA and in situ hybridization against vasa mRNA showed that primordial germ cells increase under low-temperature culture; this response may be of use for studies involving heterochronic germ cell transplantation. Our study shows that embryonic developmental speed can be slowed, which will be of value for performing time-consuming, complicated, and delicate microsurgical operations.

5.
Biomed Pharmacother ; 142: 112043, 2021 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-34411919

RESUMO

Despite its adverse effects, chemotherapy is generally used for the treatment of colorectal cancer (CRC). Development of supplement preparations targeting cancer stem cells (CSCs) that cause distant metastasis and drug resistance is required. Although curcumin is known to have anti-tumor, hepatoprotective, and hypoglycemic-like actions, its low water solubility, oral absorption, and bioavailability impede its therapeutic uses. Patient-derived organoid cultures can recapitulate heterogeneity, epithelial structures, and molecular imprints of their parental tissues. In the present study, anti-carcinogenic properties of amorphous curcumin (AC), a compound with improved solubility and bioavailability, were evaluated against human CRC organoids. Treatment with AC inhibited the cell viability of CRC organoids in a concentration-dependent manner. AC arrested the cell cycle of CRC organoids and induced apoptosis. AC inhibited phosphorylation of ERK. Expression of downstream signals of ERK, namely c-MYC and cyclin-D1, were inhibited. Expressions of CSC markers, CD44, LGR5, and CD133, were declined in the AC-treated CRC organoids. The combinational treatment of CRC organoids with AC and anti-cancer drugs, oxaliplatin, 5-FU, or irinotecan showed a synergistic activity. In vivo, AC decreased the tumor growth of CRC organoids in mice with the induction of necrotic lesions. In conclusion, AC diminished the cell viability of CRC organoids through the inhibition of proliferation-related signals and CSC marker expression in addition to arresting the cell cycle. Collectively, these data suggest the value of AC as a promising supplement that could be used in combination with anti-cancer drugs to prevent the recurrence and metastasis of CRC.

6.
Cancer Biol Ther ; 22(5-6): 357-371, 2021 06 03.
Artigo em Inglês | MEDLINE | ID: mdl-34034619

RESUMO

Bladder cancer (BC), a main neoplasm of urinary tract, is usually inoperable and unresponsive to chemotherapy. As a novel experimental model for muscle-invasive BC, we previously established a culture method of dog BC organoids. In the present study, the detailed in vitro and in vivo anti-tumor effects of trametinib were investigated by using this model. In each BC organoid strain, epidermal growth factor receptor (EGFR)/ERK signaling was upregulated compared with normal bladder cells. Trametinib even at a low concentration inhibited the cell viability of BC organoids and the activation of ERK through decreasing expression of c-Myc, ELK1, SIK1, and PLA2G4A. Trametinib arrested cell cycle of BC with few apoptosis. Dual treatment of BC organoids with trametinib and YAP inhibitor, verteporfin extremely inhibited the cell viability with apoptosis induction. Moreover, trametinib induced basal to luminal differentiation of BC organoids by upregulating luminal markers and downregulating basal ones. In vivo, trametinib decreased the tumor growth of BC organoids in mice and the xenograft-derived organoids from trametinib-administered mice showed enhanced sensitivity to carboplatin due to MSH2 upregulation. Our data suggested a new strategy of trametinib-YAP inhibitor or trametinib-carboplatin combination as a promising treatment of BC.

7.
Environ Sci Pollut Res Int ; 28(7): 7815-7827, 2021 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-33037959

RESUMO

Copper deficiency (CuD) is a common mineral disorder in ruminants, which causes histomorphological changes in the heart due to disturbances in copper-dependent metalloenzymes. However, alterations in the measurable cardiac parameters during CuD have not been studied in ruminants, especially in goats. Therefore, the current study aimed to investigate longitudinally the potential role of electrocardiography (ECG) and echocardiography to detect the CuD-induced cardiac damage at different time intervals and concomitantly highlighting the impact of CuD on specific hemato-biochemical parameters and histological cardiac disruption in goats. Eight Shiba goats were included and divided into two equal groups; copper adequate (CuA) as a control and copper-deficient (CuD) that supplemented with copper-chelating agents (sulfur 3 g/kg DM and molybdenum 40 mg/kg DM). The hemato-biochemical analysis, ECG assessment at the base apex lead, and right-side echocardiography were performed just before the experimental onset (T0), and later on at two-time intervals after existing of CuD, at the fifth (T5) and seventh (T7) months. Necropsy and histopathological examination of the heart were performed at the end of the experiment. In the CuD group, the heart dimensions at T5 and T7 showed significant increase in QRS duration, ST-segment duration, the left atrial area in systole, left ventricular diameter and volume in diastole, stroke volume, and cardiac output compared with CuA (P < 0.05). Also, myocardial degeneration, necrosis, and fibrosis were evidenced with a concurrent increase of plasma creatine kinase, lactate dehydrogenase, aspartate aminotransferase, and cardiac troponin I (P < 0.05). In conclusion, CuD disturbs hemato-biochemical parameters and results in myocardial damage and cardiac dilatation that increases some ECG and echocardiographic parameters without development of systolic dysfunction. The ECG and echocardiography can potentially detect cardiac changes in long-lasting CuD in goats.


Assuntos
Cobre , Cabras , Animais , Ecocardiografia/veterinária , Eletrocardiografia , Coração/diagnóstico por imagem
8.
Theriogenology ; 157: 238-244, 2020 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-32818881

RESUMO

The current study aimed to investigate whether steroids (testosterone, estradiol, and cortisol) in the saliva of goats reflects their concentrations in the plasma. Also, it aimed at ascertaining, for the first time, the effect of changes in climatic conditions (spring versus summer) on the aforementioned steroids, testicular volume, testicular echotexture (pixel intensity; PI, and integrated density; ID), and semen quality in goats. Saliva and plasma samples were collected from 7 male Shiba goats weekly in spring and summer for measurement of testosterone (T; ng/ml), estradiol (E2; pg/ml), and cortisol (ng/ml) using radioimmunoassay. The changes in testicular volumes (TV/ml) and echogenicity were monitored weekly using ultrasonographic assessments concomitantly with subjective evaluations of semen parameters. Results revealed a highly significant positive correlation (r = 0.72; P < 0.0001) between plasma and salivary cortisol. Mild significant positive correlation was found between salivary and plasma T levels (r = 0.31; P < 0.002). However, low non-significant negative correlation was reported between salivary and plasma E2 levels (r = -0.24; P > 0.05). Higher levels of salivary cortisol were found in summer than in the spring (3.8 ± 0.6 ng/ml versus 1.4 ± 0.3 ng/ml; P < 0.001). However, no differences in levels of T, E2, and plasma cortisol were recorded between spring and summer (P > 0.05). Values of testicular PI and ID were significantly (P < 0.001) higher in the summer (94.5 ± 4.9, 258,388 ± 13,190, respectively) than in the spring (74.0 ± 2.1, 200,922 ± 5704, respectively). Meanwhile, TV and semen parameters did not significantly differ between spring and summer. In conclusion, saliva can be considered as an alternative biological fluid for the measurement of cortisol and T, but not suitable for E2. Climatic conditions significantly impact the levels of cortisol in saliva and testicular echogenicity in goats.


Assuntos
Cabras , Análise do Sêmen , Esteroides , Testículo , Animais , Hidrocortisona , Masculino , Saliva , Sêmen , Análise do Sêmen/veterinária , Esteroides/análise , Testículo/diagnóstico por imagem , Testosterona
10.
Sci Rep ; 10(1): 9393, 2020 06 10.
Artigo em Inglês | MEDLINE | ID: mdl-32523078

RESUMO

Three-dimensional (3D) organoid culture holds great promises in cancer precision medicine. However, Matrigel and stem cell-stimulating supplements are necessary for culturing 3D organoid cells. It costs a lot of money and consumes more time and effort compared with 2D cultured cells. Therefore, the establishment of cheaper and Matrigel-free organoid culture that can maintain the characteristics of a part of 3D organoids is demanded. In the previous study, we established a dog bladder cancer (BC) 3D organoid culture system by using their urine samples. Here, we successfully isolated cells named "2.5D organoid" from multiple strains of dog BC 3D organoids using 2.5 organoid media. The cell proliferation speed of 2.5D organoids was faster than parental 3D organoid cells. The expression pattern of stem cell markers was close to 3D organoids. Injection of 2.5D organoid cells into immunodeficient mice formed tumors and showed the histopathological characteristics of urothelial carcinoma similar to the injection of dog BC 3D organoids. The 2.5D organoids had a similar sensitivity profile for anti-cancer drug treatment to their parental 3D organoids. These data suggest that our established 2.5D organoid culture method might become a reasonable and useful tool instead of 3D organoids in dog BC research and therapy.


Assuntos
Organoides/patologia , Neoplasias da Bexiga Urinária/patologia , Animais , Antineoplásicos/farmacologia , Biomarcadores Tumorais/metabolismo , Técnicas de Cultura de Células/métodos , Proliferação de Células/efeitos dos fármacos , Proliferação de Células/fisiologia , Cães , Ensaios de Seleção de Medicamentos Antitumorais/métodos , Masculino , Camundongos , Organoides/efeitos dos fármacos , Organoides/metabolismo , Células-Tronco/efeitos dos fármacos , Células-Tronco/metabolismo , Células-Tronco/patologia , Células Tumorais Cultivadas , Neoplasias da Bexiga Urinária/tratamento farmacológico
11.
Theriogenology ; 147: 85-91, 2020 Apr 15.
Artigo em Inglês | MEDLINE | ID: mdl-32120186

RESUMO

The present study investigated whether or not passive immunization against inhibin modulates testicular blood flow in goats. Male Shiba goats were injected with either 10 ml of inhibin antiserum (INH group; n = 5) or 10 ml of normal castrated goat serum (NGS group; n = 4). Concentrations of FSH, LH, testosterone (T), and estradiol (E2) in the plasma were measured by radioimmunoassay. Blood flow within the supratesticular (STA) and marginal testicular arteries (MTA) were measured by color pulsed-Doppler ultrasonography, and Doppler indices (resistive index; RI and pulsatility index; PI) were recorded. Results revealed significant increases in concentrations of FSH and E2 in the INH group compared to those in the NGS group (P < 0.05). Animals in the INH group had greater (P < 0.05) FSH concentrations than those in the NGS group in the period between 60 h and 144 h after treatment than at any other time. Estradiol concentrations were greater (P < 0.05) in the INH group than in the NGS group at 6 h (12.15 ± 2.09 pg/ml vs 5.49 ± 1.17 pg/mL), 12 h (8.27 ± 1.29 pg/mL vs 3.05 ± 0.38 pg/mL), and 36 h (9.35 ± 1.31 pg/mL vs 5.09 ± 0.46 pg/mL) after treatment than at any other time. Concentrations of LH and T did not significantly change between the two groups. Goats in the INH group had lesser (P < 0.05) RI of the STA than those in the NGS group and RI values were lesser at 24 h (0.37 ± 0.031 vs 0.49 ± 0.004) and 120 h (0.38 ± 0.028 vs 0.55 ± 0.048) after treatment than at any other time. Furthermore, values of RI and PI of the MTA were significantly lesser (P < 0.05) in the INH group compared to those in the control group at 48 h (RI of MTA: 0.21 ± 0.014 vs 0.37 ± 0.039; PI of MTA: 0.24 ± 0.016 vs 0.46 ± 0.058) after treatment than at any other time. In conclusion, passive immunization against inhibin has a stimulatory effect on testicular blood flow in goats by inducing decreases in the RI values of the STA and MTA.


Assuntos
Circulação Sanguínea/efeitos dos fármacos , Cabras/fisiologia , Imunização Passiva , Inibinas/imunologia , Testículo/irrigação sanguínea , Animais , Circulação Sanguínea/imunologia , Estradiol/sangue , Hormônio Foliculoestimulante/sangue , Masculino , Ultrassonografia Doppler em Cores
12.
J Vet Med Sci ; 82(5): 598-606, 2020 May 15.
Artigo em Inglês | MEDLINE | ID: mdl-32213749

RESUMO

Four commonly used organophosphates (fenitrothion, dichlorvos, chlorpyrifos, and trichlorfon) were orally administered to male Sprague-Dawley rats for five days in order to explore their effects on the activities of liver cytochrome P450 (CYP). In addition, Michaelis-Menten kinetics of the metabolic reactions catalyzed by liver CYPs were analyzed following the addition of these compounds to the assay system to examine their potential inhibitory effects on liver CYPs activities. These reactions included ethoxyresorufin O-deethylation, midazolam 4-hydroxylation, tolbutamide hydroxylation, and bufuralol 1'-hydroxylation for CYP1A, 3A, 2C, and 2D activities, respectively. Total CYP content was also examined after oral administration of each organophosphate. Results revealed that oral giving of fenitrothion inhibited significantly CYP1A and 3A activities while elevated activity of CYP2C. Fenitrothion is a potent inhibitor for CYP1A and 2C with Ki values of 0.42 and 36.1 µM, respectively but had a weak inhibitory effect on CYP2D and 3A with Ki values of 290 and 226 µM, respectively. Chlorpyrifos is a potent inhibitor of CYP1A with Ki 0.24 µM and moderately inhibited CYP2C or 3A with Ki values of 84.8 and 77.7 µM, respectively. On the other hand, dichlorvos and trichlorfon caused extremely low or negligible inhibition of different CYP activities. From these results, it is concluded that both fenitrothion and chlorpyrifos may increase the toxicity of chemicals in environmental living organisms through their potent inhibitory effects on these CYP activities, but dichlorvos and trichlorfon may not.


Assuntos
Sistema Enzimático do Citocromo P-450/efeitos dos fármacos , Fígado/enzimologia , Organofosfatos/farmacologia , Administração Oral , Animais , Sistema Enzimático do Citocromo P-450/metabolismo , Masculino , Organofosfatos/administração & dosagem , Farmacocinética , Ratos Sprague-Dawley
13.
J Vet Med Sci ; 82(4): 467-474, 2020 Apr 09.
Artigo em Inglês | MEDLINE | ID: mdl-32161237

RESUMO

Dapagliflozin is a selective sodium-glucose cotransporter 2 (SGLT2) inhibitor; it reduces glucose reabsorption via the kidney and increases the glucose excretion in urine. This inhibitor functions through a unique insulin-independent mechanism, and is therefore a potential new approach for the treatment of hyperglycemia in patients with diabetes. In this study, we evaluated the effectiveness of the SGLT2 inhibitor, dapagliflozin, by using a rat model of type 1 diabetes. Type 1 diabetes was induced by a single intraperitoneal injection of 60 mg/kg streptozotocin (STZ). The STZ-induced rats showed marked hyperglycemia and other metabolic abnormalities. We clarified the hypoglycemic effect of the combination treatment of dapagliflozin with a low dose of insulin compared with dapagliflozin alone and insulin alone in 3-week and 8-week studies. Our results showed that dapagliflozin in combination with a low dose of insulin significantly lowered hyperglycemia, hypercholesterolemia, and hypertriglyceridemia. Furthermore, the antioxidant status and body weight were improved. In contrast, treatment with dapagliflozin alone did not improve the blood glucose levels, lipid profile, antioxidant status, or body weight. These findings suggested that in type 1 diabetes, dapagliflozin was effective in combination with a low dose of insulin; however, the administration of dapagliflozin alone did not achieve a significant effect.


Assuntos
Compostos Benzidrílicos/farmacologia , Diabetes Mellitus Tipo 1/tratamento farmacológico , Glucosídeos/farmacologia , Hipoglicemiantes/farmacologia , Insulina/farmacologia , Inibidores do Transportador 2 de Sódio-Glicose/farmacologia , Animais , Antioxidantes/análise , Peso Corporal/efeitos dos fármacos , Diabetes Mellitus Experimental/tratamento farmacológico , Quimioterapia Combinada , Hipercolesterolemia/tratamento farmacológico , Hiperglicemia/tratamento farmacológico , Hipertrigliceridemia/tratamento farmacológico , Masculino , Ratos Sprague-Dawley
14.
Cancers (Basel) ; 12(4)2020 Mar 25.
Artigo em Inglês | MEDLINE | ID: mdl-32218271

RESUMO

Prostate cancer (PC) is the most prevalent cancer in men and the second main cause of cancer-related death in Western society. The lack of proper PC models that recapitulate the molecular and genomic landscape of clinical disease has hampered progress toward translational research to understand the disease initiation, progression, and therapeutic responses in each patient. Although several models have been developed, they hardly emulated the complicated PC microenvironment. Precision medicine is an emerging approach predicting appropriate therapies for individual cancer patients by means of various analyses of individual genomic profiling and targeting specific cancer pathways. In PC, precision medicine also has the potential to impose changes in clinical practices. Here, we describe the various PC models with special focus on PC organoids and their values in basic medicine, personalized therapy, and translational researches in vitro and in vivo, which could help to achieve the full transformative power of cancer precision medicine.

15.
Biomaterials ; 237: 119823, 2020 04.
Artigo em Inglês | MEDLINE | ID: mdl-32044522

RESUMO

Non-alcoholic steatohepatitis (NASH) is associated with liver fibrosis and cirrhosis, which eventually leads to hepatocellular carcinoma. Although several animal models were developed to understand the mechanisms of NASH pathogenesis and progression, it remains obscure. A 3D organoid culture system can recapitulate organ structures and maintain gene expression profiles of original tissues. We therefore tried to generate liver organoids from different degrees [defined as mild (NASH A), moderate (NASH B) and severe (NASH C)] of methionine- and choline-deficient diet-induced NASH model mice and analyzed the difference of their architecture, cell components, organoid-forming efficacy, and gene expression profiles. Organoids from each stage of NASH model mice were successfully generated. Interestingly, epithelial-mesenchymal transition was observed in NASH C organoids. Expression of Collagen I and an activated hepatic stellite cell marker, α-sma was upregulated in the liver organoids from NASH B and C mice. The analysis of RNA sequencing revealed that several novel genes were upregulated in all NASH liver organoids. These results suggest that our generated liver organoids from different stages of NASH diseased mice might become a useful tool for in vitro studies of the molecular mechanism of NASH development and also for identifying novel biomarkers for early diagnosis of NASH disease.


Assuntos
Neoplasias Hepáticas , Hepatopatia Gordurosa não Alcoólica , Animais , Modelos Animais de Doenças , Fígado/patologia , Cirrose Hepática/patologia , Neoplasias Hepáticas/patologia , Camundongos , Camundongos Endogâmicos C57BL , Organoides
16.
Theriogenology ; 146: 111-119, 2020 Apr 01.
Artigo em Inglês | MEDLINE | ID: mdl-32078960

RESUMO

Despite the role of melatonin in the regulation of the sleep-wake cycle and seasonal-reproduction, the present study investigated, for the first time, the potential role of melatonin on testicular blood flow (TBF) in goats. Twelve sexually mature male Shiba goats were exposed to a single s.c. injection of either melatonin suspended in one ml of corn oil (melatonin group; 36 mg/goat; n = 5) or one ml of corn oil (control group; n = 7). Monitoring the changes in TBF was done one week before (W-1), at the time of injection (W0), and once a week for 8 weeks after injection using color-pulsed Doppler ultrasonography. Concentrations of FSH, LH, inhibin, testosterone (T), estradiol (E2), and insulin-like growth factor-1 (IGF-1) in plasma were determined by radioimmunoassay. Melatonin and nitric oxide (NO) concentrations were measured using enzyme immunoassay kits. Moreover, semen collection and evaluation of some sperm parameters were performed once a week. Results revealed decreases (P < 0.05) in the Doppler indices (resistive index, pulsatility index) of the testicular arteries from W2 till W6 in the melatonin group. FSH, LH, and inhibin concentrations did not change between the two groups, while T, E2, IGF-1, NO, and melatonin concentrations increased (P < 0.05) in the melatonin group compared to the control. Estradiol and NO concentrations increased (P < 0.05), coinciding with decreases in the values of Doppler indices. Notable (P < 0.05) improvements in most parameters of semen quality were seen in the melatonin group. In conclusion, melatonin induced a stimulatory effect on TBF in Shiba goats and possibly, it could be a potential to improve male goats fertility.


Assuntos
Circulação Sanguínea/efeitos dos fármacos , Cabras/fisiologia , Hormônios/sangue , Melatonina/farmacologia , Análise do Sêmen/veterinária , Sêmen/fisiologia , Testículo/efeitos dos fármacos , Animais , Antioxidantes/farmacologia , Masculino , Óxido Nítrico/metabolismo , Testículo/irrigação sanguínea
17.
Cells ; 9(1)2020 01 17.
Artigo em Inglês | MEDLINE | ID: mdl-31963556

RESUMO

Bladder cancer (BC) is a complex and highly heterogeneous stem cell disease associated with high morbidity and mortality rates if it is not treated properly. Early diagnosis with personalized therapy and regular follow-up are the keys to a successful outcome. Cancer stem cells (CSCs) are the leading power behind tumor growth, with the ability of self-renewal, metastasis, and resistance to conventional chemotherapy. The fast-developing CSC field with robust genome-wide screening methods has found a platform for establishing more reliable therapies to target tumor-initiating cell populations. However, the high heterogeneity of the CSCs in BC disease remains a large issue. Therefore, in the present review, we discuss the various types of bladder CSC heterogeneity, important regulatory pathways, roles in tumor progression and tumorigenesis, and the experimental culture models. Finally, we describe the current stem cell-based therapies for BC disease.


Assuntos
Resistencia a Medicamentos Antineoplásicos , Células-Tronco Neoplásicas/metabolismo , Transdução de Sinais , Neoplasias da Bexiga Urinária/metabolismo , Linhagem Celular Tumoral , Transformação Celular Neoplásica/metabolismo , Transformação Celular Neoplásica/patologia , Progressão da Doença , Resistencia a Medicamentos Antineoplásicos/genética , Proteínas de Choque Térmico HSP90/antagonistas & inibidores , Proteínas de Choque Térmico HSP90/metabolismo , Humanos , Masculino , MicroRNAs/metabolismo , Células-Tronco Neoplásicas/efeitos dos fármacos , Células-Tronco Neoplásicas/imunologia , Receptor de Morte Celular Programada 1/imunologia , Receptor de Morte Celular Programada 1/metabolismo , Transdução de Sinais/efeitos dos fármacos , Transdução de Sinais/genética , Telomerase/antagonistas & inibidores , Neoplasias da Bexiga Urinária/tratamento farmacológico , Neoplasias da Bexiga Urinária/imunologia , Neoplasias da Bexiga Urinária/patologia
18.
J Vet Med Sci ; 81(11): 1616-1620, 2019 Nov 29.
Artigo em Inglês | MEDLINE | ID: mdl-31588073

RESUMO

It is known that oxidative stress is related to disease in humans and dogs. Many traditional Chinese medicines have been reported to have anti-oxidative effects, but there are no reports that they have anti-oxidative effects in dogs. In this study, we examined the anti-oxidative effects of Juzen-taiho-to, a traditional Chinese medicine, in dogs. Five healthy female beagle dogs (38-41 months of age weighing 8.6-10.7 kg) were orally administered Juzen-taiho-to at 450 mg/kg with food for 28 days. Blood samples were taken from all five dogs on days 0, 7, 14, 21, and 28. Using the blood samples, improvement of the antioxidant level as assessed by the biological antioxidant potential (BAP), reduced oxidative stress level as assessed by derivatives of reactive oxygen metabolites (d-ROMs), and improvement of blood fluidity were examined. Regarding the antioxidant level and blood fluidity, no significant difference was observed, but the oxidative stress level on days 14, 21, and 28 was significantly lower than that on day 0. Thus, Juzen-taiho-to may have anti-oxidative effects in dogs by reducing oxidative stress and be useful for oxidative stress-related diseases in dogs.


Assuntos
Antioxidantes/administração & dosagem , Medicamentos de Ervas Chinesas/administração & dosagem , Administração Oral , Animais , Antioxidantes/análise , Viscosidade Sanguínea/efeitos dos fármacos , Cães , Feminino , Estresse Oxidativo/efeitos dos fármacos , Espécies Reativas de Oxigênio/sangue
19.
J Vet Med Sci ; 81(11): 1680-1684, 2019 Dec 05.
Artigo em Inglês | MEDLINE | ID: mdl-31582600

RESUMO

The molecular clock network in mast cells has been shown to be a factor responsible for circadian regulation of allergic inflammation. PF670462 is a selective inhibitor of casein kinase 1δ and ε (CK1δ/ε) that control the posttranslational modification of clock proteins. The aims of this study were to evaluate the effects of PF670462 on gene and protein expression of FcεRI, the high-affinity IgE receptor, in canine mast cells and on IgE-mediated immediate-type cutaneous reactions in dogs. PF670462 decreased mRNA expression of FcεRIα and ß, but not γ, and protein expression of FcεRI in a canine mast cell line. Furthermore, PF670462 suppressed IgE-mediated immediate-type cutaneous erythema in dogs. These findings indicate that CK1δ/ε function as regulators for FcεRI expression and IgE-mediated cutaneous reactions in dogs.


Assuntos
Caseína Quinase Idelta/antagonistas & inibidores , Caseína Quinase Iépsilon/metabolismo , Doenças do Cão/metabolismo , Imunoglobulina E/metabolismo , Pirimidinas/farmacologia , Receptores de IgE/metabolismo , Anafilaxia , Animais , Caseína Quinase Iépsilon/genética , Doenças do Cão/genética , Cães , Regulação da Expressão Gênica/efeitos dos fármacos , Regulação da Expressão Gênica/imunologia , Mastócitos/metabolismo , Inibidores de Proteínas Quinases/farmacologia , RNA Mensageiro/genética , RNA Mensageiro/metabolismo , Receptores de IgE/genética
20.
J Vet Med Sci ; 81(12): 1810-1816, 2019 Dec 26.
Artigo em Inglês | MEDLINE | ID: mdl-31645506

RESUMO

Vincristine, one of the anti-cancer drugs used in veterinary practice, has adverse hematological and gastrointestinal effects in dogs. Juzen-taiho-to is a traditional Chinese medicine used for patients with anorexia in human medicine. However, the protective effects of Juzen-taiho-to against anti-cancer drug-induced toxicity in dogs have not been investigated. We therefore examined whether the administration of Juzen-taiho-to to dogs affects gastric motility, and vincristine-induced gastrointestinal and hematological toxicity. The study was composed of three trials. In the first trial, Juzen-taiho-to (450 mg/kg/day) was orally administered to five dogs. In the second and third trials, vincristine (0.75 mg/m2) was intravenously administered to each dog in the absence or presence of Juzen-taiho-to (450 mg/kg/day). During these trials, gastric motility and blood parameters were assessed. Juzen-taiho-to increased gastric motility and improved vincristine-induced gastrointestinal, but not hematological, adverse effects in dogs. This study suggested that Juzen-taiho-to may be applicable for gastrointestinal care in dogs receiving chemotherapy.


Assuntos
Antineoplásicos/toxicidade , Medicamentos de Ervas Chinesas/farmacologia , Motilidade Gastrointestinal/efeitos dos fármacos , Vincristina/toxicidade , Animais , Contagem de Células Sanguíneas/veterinária , Cães , Feminino , Hematócrito/veterinária , Hemoglobinas/efeitos dos fármacos , Antro Pilórico/diagnóstico por imagem , Ultrassonografia/veterinária
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