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1.
Adv Exp Med Biol ; 1232: 401-408, 2020.
Artigo em Inglês | MEDLINE | ID: mdl-31893437

RESUMO

Parkinson's disease, a progressive neurodegenerative disease, is caused by the loss of dopaminergic neurons in the substantia nigra (SN). It is characterized by the formation of intracytoplasmic Lewy bodies that are primarily composed of the protein alpha-synuclein (α-syn), along with dystrophic neurites. Acupuncture stimulation results in an enhanced survival of dopaminergic neurons in the SN in Parkinsonism animal models. We investigated the role of acupuncture in inhibiting the increase in α-syn expression that is related to dopaminergic cell loss in the SN in a chronic 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP) Parkinsonism mouse model. In this model, acupuncture stimulation at GB34 and LR3 attenuated the decrease in tyrosine hydroxylase in the SN. Moreover, acupuncture stimulation attenuated the increase in α-syn in SN. Acupuncture stimulation also maintained the phosphorylated α-syn on serine 129 at levels similar to the control group. Our findings indicate that the MPTP-mediated increase in α-syn, and the acupuncture-mediated inhibition of the increase in α-syn, may be responsible for the neuroprotective effects of acupuncture in the SN following damage induced by MPTP.


Assuntos
Terapia por Acupuntura , Transtornos Parkinsonianos , Substância Negra , alfa-Sinucleína , 1-Metil-4-Fenil-1,2,3,6-Tetra-Hidropiridina , Animais , Modelos Animais de Doenças , Neurônios Dopaminérgicos/patologia , Camundongos , Camundongos Endogâmicos C57BL , Fármacos Neuroprotetores , Transtornos Parkinsonianos/induzido quimicamente , Substância Negra/metabolismo , Tirosina 3-Mono-Oxigenase/metabolismo , alfa-Sinucleína/metabolismo
2.
Adv Exp Med Biol ; 1232: 415-420, 2020.
Artigo em Inglês | MEDLINE | ID: mdl-31893439

RESUMO

Murine models have become powerful tools in leukemia research for investigating interactions between blast cells niche factors. In the tumor microenvironment, immune cells are one of the most important niche factors, capable of mounting dynamic innate or adoptive responses against leukemic cells. Acute myeloid leukemia (AML) is a systemic cancer accompanied by immune disruption. In order to exploit the enhanced activity of immune cells in AML treatment, the use of syngeneic mouse models is necessary. Studies of crosstalk between cancer blast cells and immune cells in syngeneic mouse models are beneficial, as the absence of immune functions in syngeneic models enables focus on cancer-associated immune reactions. Once AML is induced, innate and adoptive immune cells respond differently, ultimately resulting in suppression of the immune cells. Murine AML models are commonly induced by intravenous or subcutaneous injection of C1498 cells. Despite the popularity of murine models, they have not yet resulted in the elucidation of distinct differences in immune cells by the injection method. Here, we investigated the frequency of immune cells and survival rate of mice with AML induced using both injection methods.


Assuntos
Leucemia Mieloide Aguda , Animais , Modelos Animais de Doenças , Leucemia Mieloide Aguda/imunologia , Leucemia Mieloide Aguda/terapia , Camundongos , Microambiente Tumoral/imunologia
3.
Anticancer Res ; 40(1): 527-534, 2020 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-31892608

RESUMO

Simple steatosis in non-alcoholic fatty liver disease (NAFLD) progresses to non-alcoholic steatohepatitis (NASH) when excessive fat accumulation is accompanied by ballooning, inflammation, and progressive hepatocellular injury. Due to the increasing global incidence of NAFLD/NASH and the lack of effective drugs, current treatment options are currently dominated by lifestyle interventions, including dietary and physical activity modifications. In this regard, vitamin D has received widespread attention in recent years. In line with its pleiotropic physiological effects, preclinical animal models and patient cohorts have demonstrated anti-inflammatory, anti-fibrotic and anti-proliferative effects of vitamin D on NAFLD and NASH. Several animal models have confirmed the association of vitamin D deficiency and NALFD/NASH severity in humans and revealed potential benefits of dietary vitamin D supplementation. These preclinical models also provide critical guidance to define the roles and therapeutic potential of vitamin D as well as its downstream functional mechanisms in the pathogenesis of fatty liver disease. This review summarizes vitamin D research in currently available animal models of fatty liver disease.


Assuntos
Fígado Gorduroso/metabolismo , Vitamina D/metabolismo , Animais , Pesquisa Biomédica , Modelos Animais de Doenças , Humanos
4.
Ultrasonics ; 101: 106001, 2020 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-31505328

RESUMO

Ultrasound is the first-line tool for screening hepatic steatosis. Statistical distributions can be used to model the backscattered signals for liver characterization. The Nakagami distribution is the most frequently adopted model; however, the homodyned K (HK) distribution has received attention due to its link to physical meaning and improved parameter estimation through X- and U-statistics (termed "XU"). To assess hepatic steatosis, we proposed HK parametric imaging based on the α parameter (a measure of the number of scatterers per resolution cell) calculated using the XU estimator. Using a commercial system equipped with a 7-MHz linear array transducer, phantom experiments were performed to suggest an appropriate window size for α imaging using the sliding window technique, which was further applied to measuring the livers of rats (n = 66) with hepatic steatosis induced by feeding the rats a methionine- and choline-deficient diet. The relationships between the α parameter, the stage of hepatic steatosis, and histological features were verified by the correlation coefficient r, one-way analysis of variance, and regression analysis. The phantom results showed that the window side length corresponding to five times the pulse length supported a reliable α imaging. The α parameter showed a promising performance for grading hepatic steatosis (p < 0.05; r2 = 0.68). Compared with conventional Nakagami imaging, α parametric imaging provided significant information associated with fat droplet size (p < 0.05; r2 = 0.53), enabling further analysis and evaluation of severe hepatic steatosis.


Assuntos
Fígado Gorduroso/diagnóstico por imagem , Ultrassonografia/métodos , Animais , Modelos Animais de Doenças , Aumento da Imagem/métodos , Processamento de Imagem Assistida por Computador/métodos , Masculino , Imagens de Fantasmas , Ratos , Ratos Wistar
5.
Chemosphere ; 238: 124753, 2020 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-31545217

RESUMO

Boscalid is a widely used fungicide in agriculture and has been frequently detected in both environments and agricultural products. However, evidence on the neurotoxic effect of boscalid is scarce. In this study, zebrafish served as an animal model to investigate the toxic effects and mechanisms of boscalid on aquatic vertebrates or higher animals. And we unravelled that boscalid induced developmental defects associated with oxidative stress. Developmental defects, including head deformity, hypopigmentation, decreased number of newborn neurons, structural defects around the ventricle, enlarged intercellular space in the brain, and nuclear concentration, were observed in zebrafish embryos after boscalid exposure at 48 hpf. Interestingly, we found that boscalid might directly induce oxidative stress and alter the activity of ATPase, which in turn disrupted the expression of genes involved in neurodevelopment and transmitter-transmitting signalings and melanocyte differentiation and melanin synthesis signalings. Ultimately, the differentiation of nerve cells and melanocytes were both impacted and the synthesis of melanin was inhibited, leading to morphological abnormalities. Additionally, exposure to boscalid led to less and imbalance motion and altered tendency of locomotor in larval fish. Collectively, our results provide new evidences for a comprehensive assessment of its toxicity and a warning for its residues in environment and agricultural products.


Assuntos
Compostos de Bifenilo/toxicidade , Fungicidas Industriais/toxicidade , Larva/efeitos dos fármacos , Niacinamida/análogos & derivados , Estresse Oxidativo/efeitos dos fármacos , Poluentes Químicos da Água/toxicidade , Peixe-Zebra/embriologia , Animais , Diferenciação Celular/efeitos dos fármacos , Modelos Animais de Doenças , Embrião não Mamífero/efeitos dos fármacos , Humanos , Melaninas/biossíntese , Melanócitos/citologia , Neurônios/citologia , Síndromes Neurotóxicas/patologia , Niacinamida/toxicidade , Peixe-Zebra/metabolismo
6.
Chemosphere ; 238: 124607, 2020 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-31524603

RESUMO

A fluoride exposure mouse model is established to evaluate the relationship between mitochondrial respiratory chain complexes and renal dysfunction. Morphological changes in kidney tissues were observed. Renal function and cell proliferation in the kidneys were evaluated. The expression of mitochondrial fusion protein including mitofusin-1 (Mfn1) and optic atrophy 1 (OPA1), and mitochondrial respiratory chain complex subunits, including NDUFV2, SDHA, CYC1 and COX Ⅳ, were detected via real-time polymerase chain reaction, immunohistochemistry staining and Western blot, respectively. Results showed that the structures of renal tubule, renal glomerulus and renal papilla were seriously damaged. Renal function was impaired, and cell proliferation was remarkably inhibited by excessive fluoride in kidney. The mRNA and protein expression levels of Mfn1, OPA1, NDUFV2, CYC1 and COX Ⅳ were significantly increased after excessive fluoride exposure. However, the mRNA and protein expression of SDHA significantly decreased. Overall, our findings revealed that excessive fluoride can damage kidney structure, inhibit renal cell proliferation, interfere with the expression of mitochondrial respiratory chain complexes and elevate mitochondrial fusion. Consequently, renal function disorder occurred.


Assuntos
Complexo de Proteínas da Cadeia de Transporte de Elétrons/metabolismo , Fluoretos/toxicidade , Doenças Mitocondriais/induzido quimicamente , Dinâmica Mitocondrial/efeitos dos fármacos , Proteínas Mitocondriais/metabolismo , Insuficiência Renal/induzido quimicamente , Animais , Western Blotting , Proliferação de Células/efeitos dos fármacos , Modelos Animais de Doenças , Transporte de Elétrons , GTP Fosfo-Hidrolases/metabolismo , Rim/patologia , Camundongos , Mitocôndrias/patologia , Proteínas Mitocondriais/genética , RNA Mensageiro/biossíntese
7.
Zhonghua Er Bi Yan Hou Tou Jing Wai Ke Za Zhi ; 54(12): 912-918, 2019 Dec 07.
Artigo em Chinês | MEDLINE | ID: mdl-31887817

RESUMO

Objective: To establish a New Zealand rabbit animal model of laryngopharyngeal reflux disease (LPRD) using esophageal balloon together with metal internal stent dilation and to investigate the changes of mucosa. Methods: 20 New Zealand rabbits were randomly divided into experimental group and control group, with 10 in each group. Balloon dilatation and metal internal stent dilation were carried out in experimental group to reproduce the animal model of LPRD.The middle of balloon was placed at the lower esophageal sphincter (LES) while the stent was placed at the upper esophageal sphincter (UES). The guide wire was placed in the control group, but the balloon was not expanded and the stent was not placed. The general condition, pH value of hypopharynx, laryngeal histopathology and changes of pepsin content of New Zealand rabbits were observed regularly. The difference between experimental group and control group was compared. Results: The 24-hour Dx-pH monitoring results showed that the number of reflux episodes(20.0[9.5, 35.0], 13.0[6.5, 22.0]), and the percent time below pH 5.5 (1.36%[0.60%, 4.57%], 1.36%[0.43%, 2.77%]) in the experimental group at the 2nd and 4th week were significantly different from those in the control group (0[0,3.0], 1.0[0.5, 3.8]; 0[0, 0.01%], 0[0, 0], respectively, all P<0.01), suggesting that the experimental group New Zealand rabbits developed LPRD. Compared with the control group under microscope, lymphocytes infiltration and submucosal gland hyperplasia increased in the mucosa of the throat of the experimental group. The results of pepsin immunohistochemical staining between the two groups were statistically significant (P=0.014). Conclusion: The use of balloon dilatation of the LES combined with metal stent dilatation of the UES can successfully establish a laryngopharyngeal reflux model, and lesions in the throat tissue can be observed.


Assuntos
Modelos Animais de Doenças , Refluxo Laringofaríngeo , Laringe , Animais , Esfíncter Esofágico Inferior , Monitoramento do pH Esofágico , Laringe/fisiopatologia , Pepsina A , Coelhos
9.
Nan Fang Yi Ke Da Xue Xue Bao ; 39(11): 1329-1336, 2019 Nov 30.
Artigo em Chinês | MEDLINE | ID: mdl-31852640

RESUMO

OBJECTIVE: To explore the effects of exogenous hydrogen sulfide (H2S) on apoptosis of corpus cavernosum smooth muscle cells (CCSMCs) and erectile dysfunction (ED) in rats with bilateral cavernous nerve injury (BCNI). METHODS: Twentyfour male SD rats were randomly divided into 3 groups (n=8):sham operation group, bilateral cavernous nerve injury group (BCNI group) and H2S intervention group (BCNI+NaHS group). In BCNI and BCNI+NaHS groups, BCNI was induced by clamp injury of the bilateral cavernous nerves, and the rats were subjected to daily intraperitoneal injection of normal saline and 100 µmol/kg NaHS solution for 4 weeks, respectively. After the treatment, the intracavernous pressure (ICP) and mean arterial pressure (MAP), ) of the rats were measured. Western blotting was used to detect the expressions of cystathionine ß synthetase (CBS), cystathionine γ lyase (CSE), α-SMA, collagen-I, caspase-3, Bax and Bcl-2 in the penile cavernous tissue, and the expressions of CBS and CSE were also detected immunohistochemically. The ratio of cavernous smooth muscle to collagen was detected using Masson's Trichrome staining. The apoptosis level of CCSMC was detected by TUNEL + α-SMA immunofluorescence double staining. RESULTS: After 4 weeks of treatment, the rats in BCNI+NaHS group showed a significantly higher ICP/MAP ratio than those in BCNI group (P < 0.05). The results of Masson's Trichrome staining showed that the ratio of cavernous smooth muscle/collagen was significantly higher in BCNI + NaHS group than in BCNI group (P < 0.05). Western blotting showed a significantly higher expression of α-SMA protein but a lower expression of collagen-I protein in BCNI + NaHS group than in BCNI group (P < 0.05). TUNEL+α-SMA immunofluorescence double staining revealed a significantly lower number of apoptotic CCSMCs in BCNI+NaHS group than in BCNI group (P < 0.05). Compared with those in BCNI group, the rats in BCNI+NaHS group had significantly decreased expressions of caspase-3 and Bax proteins (P < 0.05) with significantly enhanced Bcl-2 protein expression and an increased Bcl-2/Bax ratio (P < 0.05). The expressions of CBS and CSE were significantly lower in BCNI group than in the other two groups (P < 0.05). CONCLUSIONS: Exogenous H2S enhance the expression of the classic apoptotic protein Bcl-2 and reduces apoptosis of CCSMC to improve the erectile function in rats with BCNI.


Assuntos
Disfunção Erétil , Animais , Apoptose , Modelos Animais de Doenças , Humanos , Sulfeto de Hidrogênio , Masculino , Miócitos de Músculo Liso , Ereção Peniana , Pênis , Ratos , Ratos Sprague-Dawley
10.
Nan Fang Yi Ke Da Xue Xue Bao ; 39(11): 1370-1375, 2019 Nov 30.
Artigo em Chinês | MEDLINE | ID: mdl-31852641

RESUMO

OBJECTIVE: To explore an economical, convenient, safe and efficient method for establishing a Tibetan miniature pig model of cardiac arrest (CA). METHODS: Cardiac puncture was performed in 12 Tibetan miniature pigs using two acupuncture needles. One needle was inserted into the fourth intercostal near the right side of the sternum about 3 cm in depth at an angle of 30° to 60° between the chest and the needle, and the depth was adjusted until the handle of the needle vibrated with the heartbeat without premature ventricular contraction on the electrocardiogram; the other was inserted into the subcutaneous tissue of the left armpit about 3 cm in depth without damaging important organs. The handles of the two needles were connected with 9V dry batteries to form a circuit and generate direct current stimulation. Ventricular fibrillation was produced in the pigs to induce CA by stimulation of transcutaneous electrical induction (TCEI) for 3 s, and the success rate of modeling was recorded. After an interval of 4 min without intervention, cardiopulmonary resuscitation (CPR) was performed using the standard Utstein style, and the survival of the pigs after recovery was observed. RESULTS: The success rate of ventricular fibrillation modeling was 91.67% (11/12) using this method, and CPR achieved a success rate of 45.45% (5/11) in these models. The subsequent survival of the pigs was 100% (5/5) at 24 h and 80% (4/5) at 72 h. After observation for 72 h, the resuscitated Tibetan miniature pigs were dissected, and no significant damage was found in the vital organs in the thoracic or abdominal cavities. CONCLUSIONS: We successfully established a model of CA using acupuncture needles and dry batteries in Tibetan miniature pigs, and this method is economical, convenient, safe and efficient.


Assuntos
Reanimação Cardiopulmonar , Parada Cardíaca , Fibrilação Ventricular , Animais , Modelos Animais de Doenças , Suínos , Porco Miniatura , Tibet
11.
Zhongguo Dang Dai Er Ke Za Zhi ; 21(12): 1223-1228, 2019 Dec.
Artigo em Chinês | MEDLINE | ID: mdl-31874664

RESUMO

OBJECTIVE: To establish and evaluate an ovalbumin (OVA)-induced bronchial asthma model in mice with intrauterine growth retardation (IUGR), and to explore the molecular mechanism of relationship between IUGR and asthma. METHODS: A total of 16 pregnant BALB/c female mice were divided into a low-protein diet group (n=8) and a normal-protein diet group (n=8), which were fed with low-protein (8%) diet and normal-protein (20%) diet respectively. The neonatal mice were weighed 6 hours after birth. Sixteen male neonatal mice with IUGR were randomly chosen from the low-protein diet group and enrolled in the IUGR group, and 16 male neonatal mice from the normal-protein diet group were enrolled in the control group. Blood samples were collected from the mice in both groups for testing of blood glucose. Enzyme-linked immunosorbent assay (ELISA) was used to determine serum insulin level. The mice in the control group were randomized into a control + PBS group and a control + OVA group (n=8 each). The mice in the IUGR group were randomized into an IUGR + PBS group and an IUGR + OVA group (n=8 each). Six-week-old mice in the control + OVA and IUGR + OVA groups were subjected to intraperitoneal injection of 2 mg/mL OVA for sensitization and aerosol inhalation of 1% OVA for challenge. Mice in the control + PBS group and the IUGR + PBS group were treated with an equivalent amount of PBS. ELISA was used to determine serum IgE level in the mice in each group. Bronchoalveolar lavage fluid (BLF) was collected from the mice in each group for cell counting. The lung tissue of the mice in each group was stained with hematoxylin and eosin to observe pathological changes. RESULTS: The body weight at 6 hours after birth was significantly lower for neonatal mice in the low-protein diet group compared with those in the normal-protein diet group (P<0.01). The IUGR group had a significantly lower serum insulin level than the control group (P<0.01). The IUGR + PBS group had a significantly lower IgE level than the control + PBS group (P<0.01). Compared with the control + PBS and IUGR + PBS groups, the control + OVA and IUGR + OVA groups had a significantly increased IgE level, and the IgE level was significantly higher in the IUGR + OVA group than in the control + OVA group (P<0.01). Compared with the control + PBS and IUGR + PBS groups, the control + OVA and IUGR + OVA groups had significantly increased counts of leukocytes, eosinophils, lymphocytes, and macrophages in the BLF (P<0.01). The pulmonary alveoli of OVA-induced IUGR mice showed massive inflammatory cell infiltration and damage of intercellular continuity. Meanwhile, airway epithelial cell proliferation, bronchial wall thickening, bronchial lumen narrowing, and massive inflammatory cell infiltration around the bronchi and the vascular wall were observed. CONCLUSIONS: An OVA-induced bronchial asthma model has been successfully established in the mice with IUGR induced by low-protein diet, which provides a basis for further study of the molecular mechanism of relationship between IUGR and airway inflammation.


Assuntos
Asma , Retardo do Crescimento Fetal , Animais , Líquido da Lavagem Broncoalveolar , Modelos Animais de Doenças , Feminino , Pulmão , Masculino , Camundongos , Camundongos Endogâmicos BALB C , Ovalbumina
12.
Adv Clin Exp Med ; 28(10): 1429-1436, 2019 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-31670915

RESUMO

BACKGROUND: Hirschsprung's disease-associated enterocolitis (HE) is a life-threatening septic complication of Hirschsprung's disease (HD), leading to bacterial translocation (BT) and sepsis. Many factors, such as intestinal stasis, HD-related inherited immune disorders and abnormal mucosal secretion have been implicated in its pathogenesis. OBJECTIVES: To investigate the effect of intestinal stasis as an independent factor in the pathogenesis of HE intestinal lesions and its systematic effects. MATERIAL AND METHODS: The rectal ganglion cells of 46 Wistar rats were chemically ablated through local benzalkonium chloride (BAC) injection, in order to create a HD model (megacolon rats) that does not carry the possible genetic burden of HD. The animals were sacrificed either on the 20th or 25th day after ablation and were examined for histopathological changes on the wall of the small intestine, presence of bacterial translocation in body organs, body biometrics, and white blood cell count (WBC) and hemoglobin concentration. The results were compared to control animals. RESULTS: In the megacolon rats, severe damage on the small intestine as well as BT proportional to the extent of the intestinal damage and to the time elapsed after ablation was observed. Significant effects on the WBCs, hemoglobin concentration and biometric parameters were also observed. CONCLUSIONS: In megacolon rats, intestinal stasis can lead by itself to a full-blown HE. The HE lesions that promote BT are present even in regions distant from the aganglionic bowel and are proportional to the time elapsed under the influence of intestinal stasis. Systematic effects such as growth retardation are also produced.


Assuntos
Enterocolite , Doença de Hirschsprung/patologia , Obstrução Intestinal , Megacolo/complicações , Animais , Translocação Bacteriana , Modelos Animais de Doenças , Enterocolite/diagnóstico , Enterocolite/etiologia , Intestinos/microbiologia , Megacolo/patologia , Ratos , Ratos Wistar , Sepse
13.
Zhonghua Jie He He Hu Xi Za Zhi ; 42(11): 845-851, 2019 Nov 12.
Artigo em Chinês | MEDLINE | ID: mdl-31694095

RESUMO

Objective: To explore the role of S100A8, the receptor for advanced glycation endproducts (RAGE) and Caveolin-1 in neutrophilic asthmatic rats, and to further study the intervention of roxithromycin and the possible mechanisms. Methods: Male Brown Norway rats were randomly assigned to a control group, an asthma group and a Roxithromycin group. The asthmatic rat model was established by intraperitoneal injection of ovalbumin (OVA) and Freund's complete adjuvant (FCA) mixture, and aerosol inhalation of OVA. Rats in the Roxithromycin group were given roxithromycin injection 30 mg/kg 30 minutes before each challenge. Rats in the control and the asthma groups were replaced with equal volumes of saline, respectively. Bronchoalveolar lavage fluid (BALF) neutrophil percentage (Neu%) and pathological changes of pulmonary tissue (hematoxylin-eosin, HE staining) were measured to confirm the establishment of asthmatic models. The concentration of inflammatory cytokines and S100A8 were quantified by enzyme-linked immunosorbent assay (ELISA), and the expression of Caveolin-1 and RAGE at protein levels were detected by immunohistochemistry and Western blot. Results: Neu% in BALF of the asthma group was significantly higher than those of the control group, and Neu% in the Roxithromycin group was lower than the asthma group (all P<0.01). Pulmonary histology revealed that there were a large number of inflammatory cells infiltrated in the bronchial and perivascular, pulmonary interstitial and alveolar spaces, and the bronchial wall and smooth muscles were thickened obviously in the asthma group. Rats in the Roxithromycin group showed milder inflammation and airway remodeling change than the asthma group. There was no obvious pathological damage in the control group. The concentration of IL-6 and IL-17 in BALF and serum of rats in the asthma group were significantly higher than those in the control group (P<0.01), and Roxithromycin inhibited the high expression of these cytokines (P<0.05). The expression of S100A8 and RAGE in the asthma group were significantly higher than those in the control group [(20.6±4.4) vs (7.1±2.0) ng/L; (885±118) vs (462±102) ng/L; (14.2±1.7) vs (7.6±1.8) ng/L; (774±166) vs (406±69) ng/L, all P<0.05], and Roxithromycin inhibited the high expression of these proteins [(14.3±3.7) vs (20.6±4.4) ng/L; (650±53) vs (885±118) ng/L; (10.4±1.2) vs (14.2±1.7) ng/L; (560±64) vs (728±72) ng/L] (all P<0.05). Meanwhile, the expression of Caveolin-1 in the asthma group was significantly lower than that in the control group (P<0.01), and Roxithromycin up-regulated its expression (P<0.01). Correlation analysis showed that there was a significantly positive correlation between the expression of S100A8 and RAGE (r=0.706, P<0.01), while there was a significantly negative correlation between the expression of S100A8 and Caveolin-1 (r=-0.775, P<0.01), and between the expression of Caveolin-1 and RAGE (r=-0.919, P<0.01). Conclusion: S100A8 and Caveolin-1 may play an important role in neutrophilic asthma via RAGE, and Roxithromycin may exerts anti-inflammatory effects and inhibition of airway remodeling partly through this signaling pathway.


Assuntos
Antibacterianos/farmacologia , Asma/tratamento farmacológico , Calgranulina A/efeitos dos fármacos , Caveolina 1/efeitos dos fármacos , Roxitromicina/farmacologia , Remodelação das Vias Aéreas , Animais , Antibacterianos/administração & dosagem , Western Blotting , Líquido da Lavagem Broncoalveolar , Calgranulina A/metabolismo , Caveolina 1/metabolismo , Modelos Animais de Doenças , Ensaio de Imunoadsorção Enzimática , Imuno-Histoquímica , Pulmão/fisiopatologia , Masculino , Neutrófilos/efeitos dos fármacos , Neutrófilos/metabolismo , Ovalbumina , Ratos , Receptor para Produtos Finais de Glicação Avançada , Roxitromicina/administração & dosagem
14.
Zhongguo Ying Yong Sheng Li Xue Za Zhi ; 35(4): 351-354, 2019 Jul 28.
Artigo em Chinês | MEDLINE | ID: mdl-31701721

RESUMO

OBJECTIVE: To study the preventive and therapeutic effects of safflower water extract on systemic scleroderma (SSc) in mice and its mechanism. METHODS: Sixty BALB/C mice were randomly divided into the control group, model group, prednisone group and safflower low, middle, high dose groups, 10 mice in each group.The control group was injected with normal saline, and the other five groups were subcutaneously injected with bleomycin hydrochloride with 100 µl at the concentration of 200 µg /ml on the back, once a day for 28 days to establish the SSc models.At the same time, the control group and model group were treated with normal saline (10 ml/kg), the prednisone group was treated with prednisone 4.5 mg/kg (10 ml/kg), and the low, middle, and high dose safflower groups were treated with safflower at the doses of 1.5, 3, 6 g/kg (10 ml/kg), and all groups were treated for 28 days.After 28 days, all mice were decapitated. The blood samples and back skin of the BLM injection part were collected.After that, all the tissue slices were taken to measure the dermal thickness, and the content of hydroxyproline (HYP) in the skin tissues was detected by hydrolysis method.The contents of tissue growth factor (CTGF) and transforming growth factor-ß (TGF-ß ) in the skin tissues and the levels of interleukin-6 (IL-6) and interleukin-17 (IL-17) in serum were determined by ELISA. RESULTS: Compared with the control group, the dermal thickness of the model group was increased(P<0.05), the contents of CTGF, TGF-ß and HYP in the skin tissues and the levels of IL-6 and IL-17 in the serum of the model group were increased(P<0.05); compared with the model group, the dermal thickness in the prednisone group and safflower groups was decreased (P<0.05), the levels of CTGF, TGF-ß and HYP in the skin tissues and the serum levels of IL-6 and IL-17 in the prednisone group and safflower groups were decreased (P<0.05). CONCLUSION: Safflower water extract can improve skin condition (or dermal thickness) in SSc mice, and its mechanism may be related to reducing immune inflammatory response.


Assuntos
Carthamus tinctorius/química , Extratos Vegetais/farmacologia , Escleroderma Sistêmico/tratamento farmacológico , Animais , Bleomicina , Fator de Crescimento do Tecido Conjuntivo/metabolismo , Modelos Animais de Doenças , Hidroxiprolina/análise , Interleucina-17/metabolismo , Interleucina-6/metabolismo , Camundongos , Camundongos Endogâmicos BALB C , Distribuição Aleatória , Pele/patologia , Fator de Crescimento Transformador beta1/metabolismo
15.
Zootaxa ; 4664(3): zootaxa.4664.3.2, 2019 Sep 04.
Artigo em Inglês | MEDLINE | ID: mdl-31716664

RESUMO

The cystoid nematodes of the subfamilies Ataloderinae and Meloidoderinae include 32 recognized species belonging to 10 genera. The geographical distribution and preferred hosts of these nematodes are reviewed in the present paper. Most genera in Ataloderinae are believed to have evolved in North America, but some genera currently show different or wider distributions. Although members of Bellodera, Ekphymatodera, Rhizonemella and Sarisodera have only been recovered from North America, those of Atalodera may be found in both North America and South America. Species of the other genera tend to occur in different geographical locations: Cryphodera species have been recorded in Asia and Oceania while Camelodera and Hylonema species have only reported from Asia and Africa, respectively. Members of Meloidoderinae (Meloidodera spp.) are distributed in North America, Asia and Europe. Plant hosts for the cystoid nematodes are distributed among both monocots and dicots. Nematologists suggest an ancient origin for genera such as Meloidodera, Cryphodera and Rhizonemella which can parasitize gymnosperms.


Assuntos
Nematoides , África , Animais , Ásia , Modelos Animais de Doenças , Europa (Continente) , América do Norte , América do Sul
16.
An Acad Bras Cienc ; 91(4): e20180975, 2019.
Artigo em Inglês | MEDLINE | ID: mdl-31721920

RESUMO

This study investigated the ability of formulation containing Zingiber officinale (ginger) to reverse health changes promoted by unhealthy diet in Wistar rats. Five compounds from the gingerol family and three from the shogaol family were identified in the chromatographic analyzes of the extract. The animals were fed a combination of unhealthy foods, the cafeteria diet, which promoted increases in body weight, hepatocyte nucleus area, total hepatocyte area and liver fat accumulation, as well as reduced hepatic glutathione S-transferase concentration, compared to the control group, which received commercial chow. The treatment with ginger improved all these results, highlighting the reduction of 10% of body weight and 66% of the total area of lipid droplets deposited, compared to the group that received the cafeteria diet. Ginger treatments also attenuated lipid peroxidation, with a mean reduction of 41% in malondialdehyde levels and a mean increase of 222% in glutathione S-transferase activity in the liver. The cafeteria diet and ginger extract did not promote significant changes in glycemic and lipid profile, liver weight and liver enzymes compared to the control group. We suggest that ginger can have beneficial effects on health complications associated with unhealthy diet, such as excessive adiposity, oxidative stress and hepatic injury.


Assuntos
Antioxidantes/farmacologia , Gengibre/química , Fígado/efeitos dos fármacos , Extratos Vegetais/farmacologia , Ganho de Peso/etnologia , Animais , Biomarcadores/sangue , Modelos Animais de Doenças , Peroxidação de Lipídeos/efeitos dos fármacos , Fígado/lesões , Masculino , Estresse Oxidativo/efeitos dos fármacos , Ratos , Ratos Wistar
17.
Biochemistry (Mosc) ; 84(10): 1166-1176, 2019 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-31694512

RESUMO

The aim of this study was to evaluate changes in the content of sphingoid bases - sphingosine (SPH), sphinganine, and sphingosine-1-phosphate (SPH-1-P) - and in expression of genes encoding enzymes involved in their metabolism in the brain structures (hippocampus, cortex, and cerebellum) and spinal cord of transgenic FUS(1-359) mice. FUS(1-359) mice are characterized by motor impairments and can be used as a model of amyotrophic lateral sclerosis (ALS). Lipids from the mouse brain structures and spinal cord after 2, 3, and 4 months of disease development were analyzed by chromatography/mass spectrometry, while changes in the expression of the SPHK1, SPHK2, SGPP2, SGPL1, ASAH1, and ASAH2 genes were assayed using RNA sequencing. The levels of SPH and sphinganine (i.e., sphingoid bases with pronounced pro-apoptotic properties) were dramatically increased in the spinal cord at the terminal stage of the disease. The ratio of the anti-apoptotic SPH-1-P to SPH and sphinganine sharply reduced, indicating massive apoptosis of spinal cord cells. Significant changes in the content of SPH and SPH-1-P and in the expression of genes related to their metabolism were found at the terminal ALS stage in the spinal cord. Expression of the SGPL gene (SPH-1-P lyase) was strongly activated, while expression of the SGPP2 (SPH-1-P phosphatase) gene was reduced. Elucidation of mechanisms for the regulation of sphingolipid metabolism in ALS will help to identify molecular targets for the new-generation drugs.


Assuntos
Esclerose Amiotrófica Lateral/metabolismo , Encéfalo/metabolismo , Modelos Animais de Doenças , Proteína FUS de Ligação a RNA/metabolismo , Esfingolipídeos/metabolismo , Medula Espinal/metabolismo , Animais , Camundongos , Camundongos Transgênicos , Esfingolipídeos/química
18.
Biochemistry (Mosc) ; 84(10): 1204-1212, 2019 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-31694516

RESUMO

Cholestasis of pregnancy is a pathology associated with disruptions in the bile flow and dysregulation of salt and water homeostasis. Prolactin is one of the most important regulators of salt and water balance. Changes in the expression of long and short isoforms of the prolactin receptor (PrlR) and mediators of prolactin signaling were studied by immunoblotting and RT-qPCR in the rat kidney cortex and outer medulla in the model of cholestasis of pregnancy. Both PrlR isoforms were shown to participate in the effects of prolactin in cholestasis of pregnancy. Direct impact of prolactin on the kidney has been demonstrated: (i) mRNA expression of both PrlR isoforms in the kidney depended on the physiological conditions and prolactin levels; (ii) expression of pSTAT5, a key mediator of the long PrlR isoform signaling, was increased in animals with cholestasis of pregnancy; (iii) in the case of long PrlR isoform predomination, expression of mRNAs for the prolactin signaling inhibitors SOCS3 and PIAS3 was upregulated (the genes of these regulators contain STAT-responsive elements in their promoters); (iv) expression of the mRNA for galactose-1-phosphate uridyltransferase (GALT), a molecular target of the PrlR short isoform, was decreased in the kidney outer medulla.


Assuntos
Colestase/metabolismo , Modelos Animais de Doenças , Rim/metabolismo , Prolactina/metabolismo , Transdução de Sinais , Animais , Feminino , Gravidez , Isoformas de Proteínas/metabolismo , Ratos , Receptores da Prolactina/metabolismo
19.
Zhongguo Xue Xi Chong Bing Fang Zhi Za Zhi ; 31(5): 504-509, 2019 Oct 14.
Artigo em Chinês | MEDLINE | ID: mdl-31713379

RESUMO

OBJECTIVE: To investigate the protective effect of excretory-secretory protein (AES) from adult Trichinella spiralis on ovalbumin (OVA)-induced allergic rhinitis in mice. METHODS: Eighteen female BALB/c mice were randomly divided into three groups, including the blank control group (Group A), OVA-induced rhinitis group (Group B) and AES treatment group (Group C). Mice in Group A were given PBS. Mice in Group B were intraperitoneally injected with antigen adjuvant suspension for systemic sensitization, once every other day for seven times; then, local excitation was intranasally induced with 5% OVA solution once a day for seven times to establish a mouse model of allergic rhinitis. In addition to induction of allergic rhinitis, mice in Group C were given 25 µg AES at baseline sensitization and local excitation. Following the final challenge, mice were observed for 30 min in each group, and the behavioral score was evaluated. The serum levels of IFN-γ, IL-4, IL-5, IL-10 and TGF-ß were determined using an enzyme-linked immunosorbent assay in mice, and the pathological changes of mouse nasal mucosa were observed under a microscope. RESULTS: There was a significant difference in the mouse behavioral scores among the three groups (F = 110.12, P < 0.01). The mouse behavioral score was significantly higher in Group B than in Group A (7.17 ± 0.75 vs. 1.33 ± 0.52, P < 0.01), and more remarkable pathological damages of mouse nasal mucosa were seen in Group B than in Group A, while the mouse behavioral score was significantly decreased in Group C than in Group B (P < 0.01), and the pathological damages of mouse nasal mucosa remarkably alleviated in Group C relative to Group B. There was a significant difference in serum IFN-γ level among the three groups (F = 7.50, P < 0.01) and the serum IFN-γ level in Group B was significantly lower than in group A and C (both P < 0.05). There were significant differences in serum IL-4 (F = 470.81, P < 0.01) and IL-5 levels (F =68.20, P < 0.01) among the three groups, and significantly greater serum IL-4 and IL-5 levels were detected in Group B than in Group A (P < 0.01), while significantly lower serum IL-4 and IL-5 levels were detected in Group C than in Group B (P < 0.01). There were significant differences in serum IL-10 (F = 174.91, P < 0.01) and TGF-ß levels (F = 9.39, P < 0.01) among the three groups, and significantly greater serum IL-10 and TGF-ß levels were seen in Group C than in Group B (both P < 0.05). CONCLUSIONS: T. spiralis AES has a remarkable protective activity against OVA-induced allergic rhinitis in mice.


Assuntos
Antígenos de Helmintos , Proteínas de Helminto , Rinite Alérgica , Trichinella spiralis , Animais , Antígenos de Helmintos/imunologia , Antígenos de Helmintos/farmacologia , Modelos Animais de Doenças , Feminino , Proteínas de Helminto/imunologia , Proteínas de Helminto/farmacologia , Camundongos , Camundongos Endogâmicos BALB C , Mucosa Nasal/efeitos dos fármacos , Ovalbumina , Rinite Alérgica/induzido quimicamente , Rinite Alérgica/imunologia , Rinite Alérgica/prevenção & controle
20.
Anticancer Res ; 39(11): 5999-6005, 2019 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-31704825

RESUMO

BACKGROUND/AIM: In the present study, we aimed to determine the efficacy of trabectedin (TRAB) combined with oxaliplatinum (OXA)+5-fluorouracil (5-FU) on a colorectal cancer (CRC) patient-derived orthotopic xenograft (PDOX) mouse model. MATERIALS AND METHODS: A patient CRC tumor previously established in nude mice was implanted subcutaneously in transgenic green fluorescence protein (GFP)-expressing nude mice. Harvested tumor fragments were transplanted orthotopically in non-transgenic nude mice. Mice were randomized into three groups: Group 1 (G1), untreated-control; Group 2 (G2), OXA+5-FU; Group 3 (G3), TRAB+OXA+5-FU. Tumor width, length, and mouse body weight were measured twice a week. RESULTS: Both treatment groups inhibited tumor growth compared to the untreated control group. The combination of TRAB, OXA and 5-FU was significantly more efficacious than OXA+5-FU and arrested tumor growth. No significant changes were observed in body-weight in any of the three groups. CONCLUSION: TRAB, OXA and 5-FU combination has clinical potential for this and other CRC patients.


Assuntos
Protocolos de Quimioterapia Combinada Antineoplásica/farmacologia , Apoptose/efeitos dos fármacos , Proliferação de Células/efeitos dos fármacos , Neoplasias Colorretais/tratamento farmacológico , Modelos Animais de Doenças , Animais , Peso Corporal/efeitos dos fármacos , Neoplasias Colorretais/patologia , Fluoruracila/administração & dosagem , Humanos , Camundongos , Camundongos Nus , Oxaliplatina/administração & dosagem , Trabectedina/administração & dosagem , Células Tumorais Cultivadas , Ensaios Antitumorais Modelo de Xenoenxerto
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