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1.
Zhongguo Ying Yong Sheng Li Xue Za Zhi ; 37(6): 632-637, 2021 Nov.
Artigo em Chinês | MEDLINE | ID: mdl-34821097

RESUMO

Objective: To investigate the expression of Bcl-2/E1B-19K-interacting protein 3 (BNIP3) and inflammation in astrocytes under lipopolysaccharide ( LPS ) combined with hypoxia. Methods: Primary cultured astrocytes and neurons in vitro were divided into four groups: normoxia group; hypoxia group; LPS group; LPS plus hypoxia group (each group is provided with 3 duplicate holes). After treated with LPS(100 ng/ml), hypoxia group and LPS plus hypoxia group were placed in hypoxia cell incubator with 0.3% O2, and normoxia group and LPS group were placed in normal cell incubator for 24 h. Primary astrocytes were divided four groups as above for 6 h,12 h and 24 h. The expression of BNIP3 in astrocytes was detected by Western blot. The expressions of tumor necrosis factor-α(TNF-ɑ), interleukin-1ß (IL-1ß) and interleukin-6 (IL-6) mRNA in astrocytes were detected by RT-PCR. The levels of TNF-ɑ, IL-1ß and IL-6 in cultured medium were detected by ELISA. Results: Compared with the normoxia group, the expressions of inflammatory cytokines TNF-ɑ, IL-1ß and IL-6 mRNA had no change in hypoxia group and were increased in LPS group and LPS plus hypoxia group (P<0.01). Compared with the LPS group, the expressions of inflammatory cytokines IL-1ß and IL-6 mRNA were increased in LPS plus hypoxia group (P<0.05, P<0.01). Compared with the normoxia group, the levels of inflammatory cytokines had no change in hypoxia group and the levels of TNF-ɑ and IL-6 were increased in LPS group and LPS plus hypoxia group (P<0.01), the level of IL-1ß had no change in LPS group and LPS plus hypoxia group. Compared with the LPS group, the levels of TNF-ɑ and IL-6 had no more change in LPS plus hypoxia group. BNIP3 was expressed in primary neurons and astrocytes in vitro. Compared with astrocytes in the normoxia group, the expression of BNIP3 in LPS group had no change and was increased markedly in hypoxia group and LPS plus hypoxia group (P<0.01). Compared with neurons in the normoxia group, the expression of BNIP3 in LPS group had no change and was increased in hypoxia group and LPS plus hypoxia group (P<0.05, P<0.01). Compared with neurons in the hypoxia group, the expression of BNIP3 in astrocytes of hypoxia group was increased (P<0.01). Compared with the normoxia group at the same time point, the expression of BNIP3 in LPS group had no change and was increased in hypoxia group and LPS plus hypoxia group (P<0.05, P<0.01). Compared with the hypoxia group at the same time point, the expression of BNIP3 was increased markedly in LPS plus hypoxia group at 6 h and 12 h (P<0.01). Conclusion: The combination of hypoxia with LPS augmented inflammation in astrocyte and LPS enhanced the expression of BNIP3 in astrocyte under hypoxia, suggesting BNIP3 might be involved in regulating astrocyte inflammation.


Assuntos
Citocinas , Lipopolissacarídeos , Astrócitos , Humanos , Hipóxia , Proteínas de Membrana/genética , Proteínas Proto-Oncogênicas , Fator de Necrose Tumoral alfa
2.
Zhongguo Dang Dai Er Ke Za Zhi ; 23(6): 593-598, 2021 Jun.
Artigo em Chinês | MEDLINE | ID: mdl-34130781

RESUMO

OBJECTIVE: To evaluate the clinical features of preterm infants with a birth weight less than 1 500 g undergoing different intensities of resuscitation. METHODS: A retrospective analysis was performed for the preterm infants with a birth weight less than 1 500 g and a gestational age less than 32 weeks who were treated in the neonatal intensive care unit of 20 hospitals in Jiangsu, China from January 2018 to December 2019. According to the intensity of resuscitation in the delivery room, the infants were divided into three groups:non-tracheal intubation (n=1 184), tracheal intubation (n=166), and extensive cardiopulmonary resuscitation (ECPR; n=116). The three groups were compared in terms of general information and clinical outcomes. RESULTS: Compared with the non-tracheal intubation group, the tracheal intubation and ECPR groups had significantly lower rates of cesarean section and use of antenatal corticosteroid (P < 0.05). As the intensity of resuscitation increased, the Apgar scores at 1 minute and 5 minutes gradually decreased (P < 0.05), and the proportion of infants with Apgar scores of 0 to 3 at 1 minute and 5 minutes gradually increased (P < 0.05). Compared with the non-tracheal intubation group, the tracheal intubation and ECPR groups had significantly higher mortality rate and incidence rates of moderate-severe bronchopulmonary dysplasia and serious complications (P < 0.05). The incidence rates of grade Ⅲ-Ⅳ intracranial hemorrhage and retinopathy of prematurity (stage Ⅲ or above) in the tracheal intubation group were significantly higher than those in the non-tracheal intubation group (P < 0.05). CONCLUSIONS: For preterm infants with a birth weight less than 1 500 g, the higher intensity of resuscitation in the delivery room is related to lower rate of antenatal corticosteroid therapy, lower gestational age, and lower birth weight. The infants undergoing tracheal intubation or ECRP in the delivery room have an increased incidence rate of adverse clinical outcomes. This suggests that it is important to improve the quality of perinatal management and delivery room resuscitation to improve the prognosis of the infants.


Assuntos
Cesárea , Recém-Nascido Prematuro , Peso ao Nascer , China , Feminino , Idade Gestacional , Humanos , Lactente , Recém-Nascido , Gravidez , Estudos Retrospectivos
3.
Injury ; 52(6): 1549-1555, 2021 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-33097203

RESUMO

OBJECTIVES: To explore the gender differences in the concomitant articular injuries after acute lateral patellar dislocation (LPD). METHODS: Magnetic resonance images were prospectively analyzed in 166 patients after an acute LPD. Concomitant articular injuries included bone contusion, medial patellofemoral ligament (MPFL) injury, articular cartilage lesion, and vastus medialis obliquus (VMO) lesion. Statistical analyses were performed between the patient's gender and the incidence of concomitant articular injuries in adolescent and adult subgroups. RESULTS: The incidence of partial and complete MPFL tear in adolescent males and females were (45%, 50%) and (63.2%, 29.8%), respectively. Compared with adolescent females, adolescent males showed higher incidence of complete MPFL tear (P = 0.049). The incidence of articular cartilage lesion of patella in adolescent males and females were 40% and 21.1%, respectively. Compared with adolescent females, adolescent males showed higher incidence of articular cartilage lesion of the patella (P = 0.043). No correlations were identified in other injuries in the adolescent group. The incidence of partial and complete MPFL tear in adult males and females were (34.4%, 65.6%) and (56.8%, 37.8%), respectively. Compared with adult females, adult males showed higher incidence of complete MPFL tear (P = 0.036). The incidence of articular cartilage lesion of patella in adult males and females were 56.3% and 32.4%, respectively. Compared with adult females, adult males showed higher incidence of articular cartilage lesion of patella (P = 0.047). The incidence of VMO injury in adult males and females were 59.4% and 35.1%, respectively. Compared with adult females, adult males showed higher incidence of VMO injury (P = 0.044). No correlations were identified in other injuries in the adult group. CONCLUSIONS: Compared with females, males predispose to complete MPFL tear and articular cartilage lesion of patella after acute LPD. Compared with female adults, male adults predispose to VMO injury.


Assuntos
Cartilagem Articular , Luxação Patelar , Articulação Patelofemoral , Adolescente , Adulto , Cartilagem Articular/diagnóstico por imagem , Feminino , Humanos , Articulação do Joelho , Ligamentos Articulares/diagnóstico por imagem , Masculino , Patela/diagnóstico por imagem , Luxação Patelar/diagnóstico por imagem , Luxação Patelar/epidemiologia
4.
Aging (Albany NY) ; 12(24): 25172-25188, 2020 11 20.
Artigo em Inglês | MEDLINE | ID: mdl-33223512

RESUMO

Anti-vascular endothelial growth factor (anti-VEGF) drugs have long been the only first-line treatment for advanced or unresectable hepatocellular carcinoma (HCC). Recently, the combination of bevacizumab (an anti-VEGF drug) and atezolizumab (an immune checkpoint blockade, ICB) has been proven to have superior efficacy over sorafenib. However, the complex association between VEGF signaling pathway and tumor immune microenvironment is still largely unknown. Here, we analyzed the RNA sequencing and clinical data of 365 HCC patients obtained from The Cancer Genome Atlas to investigate the potential correlation between VEGF signaling pathway and tumor immune microenvironment, including immune cell infiltration, 66 immune markers, genomic instability, and immune-related pathways. Our study revealed that VEGF signaling pathway score was positively correlated with immune cell infiltration and the expression profile of 66 immune markers. Enrichment analysis indicated that genes differentially expressed between two VEGF score subtypes were enriched in many immune-related Gene Ontology terms. Most importantly, both VEGF signaling pathway and activated CD8+ T cells were positively correlated with prognosis. Our findings suggest the co-activation of VEGF signaling pathway and tumor immune microenvironment in HCC patients, indicating the underlining mechanism of combination therapy including anti-VEGF drugs and ICBs.


Assuntos
Carcinoma Hepatocelular/imunologia , Regulação Neoplásica da Expressão Gênica/imunologia , Neoplasias Hepáticas/imunologia , Microambiente Tumoral/imunologia , Receptor 2 de Fatores de Crescimento do Endotélio Vascular/metabolismo , Carcinoma Hepatocelular/genética , Carcinoma Hepatocelular/metabolismo , Perfilação da Expressão Gênica , Regulação Neoplásica da Expressão Gênica/genética , Humanos , Neoplasias Hepáticas/genética , Neoplasias Hepáticas/metabolismo , Transcriptoma , Microambiente Tumoral/genética , Fator A de Crescimento do Endotélio Vascular/metabolismo
5.
Proc Natl Acad Sci U S A ; 117(25): 14386-14394, 2020 06 23.
Artigo em Inglês | MEDLINE | ID: mdl-32513693

RESUMO

We report that two widely-used drugs for erectile dysfunction, tadalafil and vardenafil, trigger bone gain in mice through a combination of anabolic and antiresorptive actions on the skeleton. Both drugs were found to enhance osteoblastic bone formation in vivo using a unique gene footprint and to inhibit osteoclast formation. The target enzyme, phosphodiesterase 5A (PDE5A), was found to be expressed in mouse and human bone as well as in specific brain regions, namely the locus coeruleus, raphe pallidus, and paraventricular nucleus of the hypothalamus. Localization of PDE5A in sympathetic neurons was confirmed by coimmunolabeling with dopamine ß-hydroxylase, as well as by retrograde bone-brain tracing using a sympathetic nerve-specific pseudorabies virus, PRV152. Both drugs elicited an antianabolic sympathetic imprint in osteoblasts, but with net bone gain. Unlike in humans, in whom vardenafil is more potent than tadalafil, the relative potencies were reversed with respect to their osteoprotective actions in mice. Structural modeling revealed a higher binding energy of tadalafil to mouse PDE5A compared with vardenafil, due to steric clashes of vardenafil with a single methionine residue at position 806 in mouse PDE5A. Collectively, our findings suggest that a balance between peripheral and central actions of PDE5A inhibitors on bone formation together with their antiresorptive actions specify the osteoprotective action of PDE5A blockade.


Assuntos
Disfunção Erétil/tratamento farmacológico , Osteogênese/efeitos dos fármacos , Osteoporose/tratamento farmacológico , Inibidores da Fosfodiesterase 5/farmacologia , Envelhecimento/fisiologia , Animais , Densidade Óssea/efeitos dos fármacos , Densidade Óssea/fisiologia , Osso e Ossos/citologia , Osso e Ossos/efeitos dos fármacos , Osso e Ossos/metabolismo , Encéfalo/citologia , Encéfalo/efeitos dos fármacos , Encéfalo/metabolismo , Diferenciação Celular/efeitos dos fármacos , Nucleotídeo Cíclico Fosfodiesterase do Tipo 5/química , Nucleotídeo Cíclico Fosfodiesterase do Tipo 5/metabolismo , Reposicionamento de Medicamentos , Disfunção Erétil/complicações , Humanos , Masculino , Camundongos , Pessoa de Meia-Idade , Modelos Animais , Modelos Moleculares , Neurônios/efeitos dos fármacos , Neurônios/metabolismo , Osteoblastos/efeitos dos fármacos , Osteoblastos/fisiologia , Osteoclastos/efeitos dos fármacos , Osteoclastos/fisiologia , Osteoporose/complicações , Fraturas por Osteoporose/etiologia , Fraturas por Osteoporose/prevenção & controle , Inibidores da Fosfodiesterase 5/química , Inibidores da Fosfodiesterase 5/uso terapêutico , Cultura Primária de Células , Tadalafila/química , Tadalafila/farmacologia , Tadalafila/uso terapêutico , Dicloridrato de Vardenafila/química , Dicloridrato de Vardenafila/farmacologia , Dicloridrato de Vardenafila/uso terapêutico
6.
Artigo em Inglês | MEDLINE | ID: mdl-32595744

RESUMO

Radiation enteritis is a common side effect of radiotherapy for abdominal and pelvic malignancies, which can lead to a decrease in patients' tolerance to radiotherapy and the quality of life. It has been demonstrated that glycyrrhizin (GL) possesses significant anti-inflammatory activity. However, little is known about its anti-inflammatory effect in radiation enteritis. In the present study, we aimed to investigate the potential anti-inflammatory effects of GL on radiation enteritis and elucidate the possible underlying molecular mechanisms involved. The C57BL/6 mice were subjected to 6.5 Gy abdominal X-ray irradiation to establish a model of radiation enteritis. Hematoxylin and eosin staining was performed to analyze the pathological changes in the jejunum. The expression of TNF-α in the jejunum was analyzed by immunochemistry. The levels of inflammatory cytokines, such as TNF-α, IL-6, IL-1ß, and HMGB1 in the serum were determined by enzyme-linked immunosorbent assay. The intestinal absorption capacity was tested using the D-xylose absorption assay. The levels of HMGB1 and TLR4 were analyzed by western blotting and immunofluorescence staining. We found that GL significantly alleviated the intestinal damage and reduced the levels of inflammatory cytokines, such as TNF-α, IL-6, IL-1ß, and HMGB1 levels. Furthermore, the HMGB1/TLR4 signaling pathway was significantly downregulated by GL treatment. In conclusion, these findings indicate that GL has a protective effect against radiation enteritis through the inhibition of the intestinal damage and the inflammatory responses, as well as the HMGB1/TLR4 signaling pathway. Thereby, GL might be a potential therapeutic agent for the treatment of radiation enteritis.

7.
Artigo em Inglês | MEDLINE | ID: mdl-32265835

RESUMO

Macrophage migration inhibitory factor (MIF) has multiple intrinsic enzymatic activities of the dopachrome/phenylpyruvate tautomerase and thiol protein oxidoreductase, and plays an important role in the development of obesity as a pro-inflammatory cytokine. However, which enzymatic activity of MIF is responsible for regulating in obesity are still unknown. In the present study, we investigated the roles of the tautomerase of MIF in high fat diet (HFD)-induced obesity using MIF tautomerase activity-lacking (MIFP1G/P1G) mice. Our results showed that the serum MIF and the expression of MIF in adipose tissue were increased in HFD-treated mice compared with normal diet fed mice. The bodyweights were significantly reduced in MIFP1G/P1G mice compared with WT mice fed with HFD. The sizes of adipocytes were smaller in MIFP1G/P1G mice compared with WT mice fed with HFD using haematoxylin and eosin (H&E) staining. In addition, the MIFP1G/P1G mice reduced the macrophage infiltration, seen as the decreases of the expression of inflammatory factors such as F4/80, IL-1ß, TNFα, MCP1, and IL-6. The glucose tolerance tests (GTT) and insulin tolerance tests (ITT) assays showed that the glucose tolerance and insulin resistance were markedly improved, and the expressions of IRS and PPARγ were upregulated in adipose tissue from MIFP1G/P1G mice fed with HFD. Furthermore, we observed that the expressions of Bax, a pro-apoptotic protein, and the cleaved caspase 3-positive cells in white tissues were decreased and the ratio of Bcl2/Bax was increased in MIFP1G/P1G mice compared with WT mice. Taken together, our results demonstrated that the tautomerase activity-lacking of MIF significantly alleviated the HFD-induced obesity and adipose tissue inflammation, and improved insulin resistance in MIFP1G/P1G mice.


Assuntos
Dieta Hiperlipídica , Inflamação/genética , Resistência à Insulina/genética , Oxirredutases Intramoleculares/genética , Oxirredutases Intramoleculares/metabolismo , Fatores Inibidores da Migração de Macrófagos/genética , Fatores Inibidores da Migração de Macrófagos/metabolismo , Adipócitos/fisiologia , Animais , Apoptose/genética , Apoptose/fisiologia , Inflamação/sangue , Oxirredutases Intramoleculares/sangue , Fatores Inibidores da Migração de Macrófagos/sangue , Masculino , Camundongos , Camundongos Obesos , Camundongos Transgênicos , Obesidade/complicações , Obesidade/genética , Obesidade/metabolismo
8.
Zhongguo Ying Yong Sheng Li Xue Za Zhi ; 36(6): 556-561, 2020 Nov.
Artigo em Chinês | MEDLINE | ID: mdl-33719257

RESUMO

Objective: To investigate the effects of acute high altitude hypoxia on EEG power in different emotional states. Methods: This study was two-factor within-subject design (2 levels of oxygen environment ×4 levels of emotion type). Twelve male subjects aged between 20 and 25 years old were induced to produce four different types of emotions by emotional picture evoked paradigm: low valence and low arousal(LVLA), high valence and low arousal(HVLA), low valence and high arousal(LVHA), high valence and high arousal(HVHA). Brain Products 32 was used to collect EEG signals under different emotional states. The next day, a constant depressed oxygen chamber was used to simulate a 4 300 m plateau hypoxia environment, and the same group of subjects used the same experimental paradigm to collect EEG signals 10h after hypoxia. The collected EEG signals were analyzed by power spectrum (FFT), and the five frequency bands (Delta, Theta, Alpha, beta, gamma) of the frontal lobe (F3\Fz\F4) were analyzed by variance analysis of two-factor repeated measurements. Results: FFT analysis found that before and after acute hypoxia, the whole brain distribution of alpha wave in four emotional states was mainly concentrated in frontal and parietal leaves; the distribution of alpha wave in the whole brain was the least in relaxed emotional state. The results of the two-factor repeated measurement ANOVA showed that: ①the power of delta\ beta band was significantly affected by the oxygen environment(P<0.05), and the power was enhanced under hypoxia. ②The power index of theta\ alpha band showed a significant interaction between the oxygen environment and emotional types(P<0.05). Except for the HVLA emotional state, the power of theta alpha band was significantly enhanced under hypoxia. ③ The two factors had no significant influence on the gamma band(P>0.05). Conclusion: Under the four kinds of emotional states, the difference of the influence of oxygen environment on brain activity was mainly in the frontal lobe, parietal lobe and part of temporal lobe. Of the four types of emotions, the oxygen environment had the least significant effect on brain activity in HVLA emotional states, while the rest showed significant differences.


Assuntos
Doença da Altitude , Adulto , Nível de Alerta , Eletroencefalografia , Emoções , Humanos , Hipóxia , Masculino , Adulto Jovem
9.
Sheng Li Xue Bao ; 71(4): 537-546, 2019 Aug 25.
Artigo em Chinês | MEDLINE | ID: mdl-31440750

RESUMO

Intermittent hypoxia (IH) has preventive and therapeutic effects on hypertension, myocardial infarction, cerebral ischemia and depression, but its effect on post-traumatic stress disorder (PTSD) has not been known. In this study, we used inescapable electric foot shock combined with context recapture to build PTSD mouse model. The levels of fear and anxiety were valued by the open field, the elevated plus maze (EPM) and the fear conditioning tests; the level of spatial memory was valued by Y maze test; the number of Fos positive neurons in hippocampus, amygdala and medial prefrontal cortex was valued by immunohistochemical staining; and the protein expressions of hypoxia inducible factor-1α (HIF-1α), vascular endothelial growth factor (VEGF) and brain derived neurotrophic factor (BDNF) in these brain area were valued by Western blot. The results showed that IH and model (foot shock) had an interaction on percentage of entering open arms (OE%) in EPM and freezing time and the number of fecal pellets in fear conditioning test. IH increased OE% in EPM and reduced the freezing time and the number of fecal pellets in fear conditioning test in PTSD model mice. At the same time, IH reduced the number of Fos positive neurons in the hippocampus, amygdala and medial prefrontal cortex of PTSD model mice, and increased the protein expression levels of HIF-1α, VEGF and BDNF in these brain tissues. In conclusion, IH pretreatment can relieve fear and anxiety behavior in post-traumatic stress model mice, suggesting that IH may be an effective means of preventing PTSD.


Assuntos
Ansiedade/terapia , Medo , Hipóxia , Transtornos de Estresse Pós-Traumáticos/terapia , Animais , Fator Neurotrófico Derivado do Encéfalo/metabolismo , Subunidade alfa do Fator 1 Induzível por Hipóxia/metabolismo , Camundongos , Fator A de Crescimento do Endotélio Vascular/metabolismo
10.
Zhongguo Ying Yong Sheng Li Xue Za Zhi ; 35(3): 245-249, 2019 May 28.
Artigo em Chinês | MEDLINE | ID: mdl-31257807

RESUMO

OBJECTIVE: To detect the effects of metformin on the depressive-like behaviors in rats. METHODS: Forty male SD rats were randomly divided into four groups: control group (CON group), metformin group (MET group), model group (CUMS group), model + metformin group (CUMS + MET group), 10 rats in each group. Chronic unpredictable mild stress (CUMS) method was used to establish rat depression model in three weeks. After the model was established successfully, two metformin groups were intraperitoneally injected with metformin (100 mg/kg), while the control group and the model group were injected with the same amount of saline once a day for two weeks. After that, the changes of weight gain, sucrose water preference experiment, forced swimming test, tail suspension immobility test and open field test were detected. The morphological changes of hippocampus were observed by Nissl staining. RESULTS: Compared with the control group, the weight gain of rats in CUMS group was significantly slowed down (P<0.05), the sucrose preference rate and the spontaneous activity were significantly reduced (P<0.05), and the immobility time in forced swimming and tail suspension immobility test was significantly prolonged (P<0.05), and the morphological structure of hippocampus was changed, which confirmed the success of CUMS depression model. Compared with CUMS group, metformin treatment had no significant effect on body weight of rats, but it could significantly improve sucrose water intake, immobility time and spontaneous activity of CUMS depression model rats (P<0.05), and improve the abnormal morphological changes of hippocampus in CUMS rats. CONCLUSION: Metformin has a therapeutic benefit against CUMS-induced depression, which provides a new treatment for patients with diabetes mellitus complicated with depression.


Assuntos
Depressão/tratamento farmacológico , Metformina/farmacologia , Estresse Psicológico , Animais , Hipocampo/anatomia & histologia , Hipocampo/efeitos dos fármacos , Masculino , Distribuição Aleatória , Ratos , Ratos Sprague-Dawley
11.
Zhongguo Ying Yong Sheng Li Xue Za Zhi ; 35(2): 173-177, 2019 Feb.
Artigo em Chinês | MEDLINE | ID: mdl-31250612

RESUMO

OBJECTIVE: To investigate the effects of simulated hypobaric hypoxia environment at 7 000 m above sea level on cardiac structure and function in rats. METHODS: A total of 96 male SD rats were randomly divided into high-altitude hypobaric hypoxia group (hypoxia group) and normobaric normoxia group (control group). Rats of hypoxia group were placed in a large cabin simulated 7 000 m high-altitude hypobaric hypoxia environment. Operating time 23 h / d, the control circadian ratio of approximately 12 h:12 h. The rats in control group were bred under normobaric normoxia. The hypoxic group was divided into 3 d, 7 d, 14 d, 28 d groups according to hypoxic time, 12 rats in each group. Changes of structure and function of heart due to hypoxia were evaluated by echocardiography and electrocardiogram. Myocardial pathological changes were analyzed by hematoxylin-eosin staining(HE). RESULTS: Compared with the control group at the same time point ①With prolonged exposure to hypobaric hypoxia, the growth ratio of body mass in rats is slower. Arterial oxygen saturation was significantly lower in both 14 d and 28 d (P<0.05). ② Left ventricular end-diastolic anterior wall thickness (LVAWD) and left ventricular end-diastolic posterior wall thickness (LVPWD) of rats in 28 d were increased significantly (P<0.05). Left ventricular end-diastolic diameter (LVIDD) and left ventricular internal dimension systole (LVIDS) of rats in 28 d were decreased significantly (P<0.05, P<0.01). Left ventricular ejection fraction (EF), fractional shortening of left ventricle (FS), pulmonary vein (PV) peak velocity and PV peak gradient of rats in 7 d were decreased significantly (P<0.05, P<0.01). ③The QRS and QT interval period were significantly prolonged in 14 d and 28 d (P<0.05, P<0.01). The ST was significantly lower in 3 d and 7 d (P<0.05, P<0.01). The amplitude of R wave gradually shifted downward in 7 d, 14 d, 28 d (P<0.05, P<0.01). ④The red blood cell (RBC), hemoglobin (HGB), red blood cell distribution width (RDW) in hypoxic group were increased significantly (P<0.01). The platelet count (PLT) count was decreased significantly in 14 d and 28 d (P<0.01). The serum creatinine (CR) was increased significantly in 14 d and 28 d (P<0.05). ⑤Pathological changes such as myocardial edema, sarcolemma condensate, focal degeneration and necrosis with inflammatory cell infiltration could be found at early stage of hypoxia. Myocardial compensatory repair such as myocardial fibroblasts proliferation was significant at end stage of hypoxia. CONCLUSION: Left ventricular systolic functions of rats were decreased significantly after exposure to high altitude hypoxia hypobaric. The left ventricular systolic functions would recovery compensatory after one week exposed to high altitude hypoxia hypobaric.


Assuntos
Altitude , Coração/fisiopatologia , Hipóxia , Animais , Masculino , Ratos , Ratos Sprague-Dawley
12.
Artigo em Inglês | MEDLINE | ID: mdl-31007700

RESUMO

Danggui Shaoyao San (DSS), a traditional Chinese medicinal prescription, was widely used to reinforce earth to activate collaterals in ancient times. Recently, many clinical studies found that DSS had a renoprotection. In this study, we evaluated the effect of DSS on unilateral ureteral obstruction- (UUO-) induced renal fibrosis in rats and investigated the mechanisms underlying the effect. Sprague Dawley (SD) rats were randomized to UUO or Sham operation. After 1 day, the rats that underwent UUO were randomized to treatment for four experimental groups (n=10 each group): Sham, UUO only, UUO+ benazepril (Bena), and UUO+DSS. After 4 weeks, we demonstrated that DSS significantly suppressed UUO-induced renal hypertrophy by gravimetric. In addition, DSS obviously prevented UUO-induced disorder in renal structure and renal function by HE and biochemistry test. We also found that DSS abrogated UUO-induced renal fibrosis by Masson's staining and collagen volume fraction (CVF) analysis; this is consistent with the western blot analysis that showed DSS abrogated the UUO-induced enhanced TGF-ß1 and weakened BMP-7. Compared with the UUO only group, rats treated with DSS exhibited significant increase in vascular density, followed by decrease in hypoxia and HIF-1α protein level through western blot and immunofluorescence analysis. Furthermore, we also determined proteins of autophagy and DSS enhanced autophagy to prevent the damage-induced by UUO. Taken together, our findings demonstrated that DSS had a renoprotection effect in ameliorating renal fibrosis possibly via attenuating tissue hypoxia and regulating autophagy.

13.
Phytomedicine ; 53: 18-27, 2019 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-30668397

RESUMO

BACKGROUND: Lung cancer is a leading cause of cancer-related death worldwide. Cisplatin-based chemotherapy is the standard treatment for lung cancer, but chemoresistance and adverse effects especially cardiotoxicity limit its efficacy. PURPOSE: The efficacy of combination treatment of dendrobine, a plant alkaloid isolated from Dendrobium nobile, with cisplatin was examined as a possible anti-non-small cell lung cancer strategy. METHODS: The cytotoxicity of dendrobine and cisplatin against A549 lung cancer cells was analyzed by MTT and colony formation assays. Apoptosis was measured by annexin V/PI double staining. Apoptosis-related proteins were assessed by western blotting and qPCR analysis. In vivo efficacy was determined using A549 xenograft in nude mice. JNK and Bim inhibition were achieved by siRNA knockdown and/or chemical inhibition. Cardiotoxicity was assessed by serum creatine phosphokinase activity assay. RESULTS: Dendrobine induced apoptotic cell death through mitochondrial-mediated pathway. Combination treatment of dendrobine with cisplatin showed enhanced cytotoxicity through stimulation of JNK/p38 stress signaling pathways and, consequently, the induction of apoptosis involving pro-apoptotic proteins Bax and Bim. In addition, dendrobine attenuated the body weight reduction and cardiotoxicity induced by cisplatin in nude mice. CONCLUSION: The combination treatment showed enhanced anticancer activity toward non-small cell lung cancer cells without aggravating the cardiotoxic effects of cisplatin suggesting that the combination strategy deserves further investigation for human lung cancer treatment.


Assuntos
Alcaloides/farmacologia , Protocolos de Quimioterapia Combinada Antineoplásica/farmacologia , Carcinoma Pulmonar de Células não Pequenas/tratamento farmacológico , Neoplasias Pulmonares/tratamento farmacológico , Sistema de Sinalização das MAP Quinases/efeitos dos fármacos , Células A549 , Alcaloides/administração & dosagem , Animais , Antineoplásicos Fitogênicos/administração & dosagem , Antineoplásicos Fitogênicos/farmacologia , Apoptose/efeitos dos fármacos , Proteínas Reguladoras de Apoptose/metabolismo , Peso Corporal/efeitos dos fármacos , Carcinoma Pulmonar de Células não Pequenas/patologia , Linhagem Celular Tumoral , Cisplatino/administração & dosagem , Cisplatino/farmacologia , Feminino , Humanos , Neoplasias Pulmonares/patologia , Camundongos Endogâmicos BALB C , Mitocôndrias/efeitos dos fármacos , Mitocôndrias/metabolismo , Ensaios Antitumorais Modelo de Xenoenxerto
14.
Neurosci Bull ; 34(6): 1058-1066, 2018 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-30225764

RESUMO

While inflammatory bowel disease (IBD) might be a risk factor in the development of brain dysfunctions, the underlying mechanisms are largely unknown. Here, mice were treated with 5% dextran sodium sulfate (DSS) in drinking water and sacrificed on day 7. The serum level of IL-6 increased, accompanied by elevation of the IL-6 and TNF-α levels in cortical tissue. However, the endotoxin concentration in plasma and brain of mice with DSS-induced colitis showed a rising trend, but with no significant difference. We also found significant activation of microglial cells and reduction in occludin and claudin-5 expression in the brain tissue after DSS-induced colitis. These results suggested that DSS-induced colitis increases systemic inflammation which then results in cortical inflammation via up-regulation of serum cytokines. Here, we provide new information on the impact of colitis on the outcomes of cortical inflammation.


Assuntos
Córtex Cerebral/patologia , Colite/induzido quimicamente , Colite/complicações , Citocinas/metabolismo , Sulfato de Dextrana/toxicidade , Encefalite/etiologia , Animais , Proteínas de Ligação ao Cálcio/metabolismo , Caspase 3/metabolismo , Claudina-5/metabolismo , Colite/patologia , Citocinas/genética , Modelos Animais de Doenças , Regulação da Expressão Gênica/efeitos dos fármacos , Camundongos , Proteínas dos Microfilamentos/metabolismo , Ocludina/metabolismo , Polissacarídeos/sangue , Polissacarídeos/toxicidade , Fatores de Tempo
15.
J Radiat Res ; 59(5): 604-615, 2018 Sep 01.
Artigo em Inglês | MEDLINE | ID: mdl-30085197

RESUMO

It remains controversial whether radical radiotherapy in patients with esophageal squamous cell carcinoma (ESCC) still requires elective nodal irradiation (ENI), or only involved-field irradiation (IFI). In this study, a meta-analysis was conducted to compare ENI and IFI in the treatment of ESCC, in order to provide guidance for clinical practice. Literature on the use of ENI and IFI in the treatment of ESCC was retrieved, and the last access date was 31 December 2017. A meta-analysis was performed to evaluate the relative advantages and disadvantages of using ENI and IFI. Ten studies, involving a total of 1348 patients, were included in this analysis; of these, 605 patients underwent radiotherapy only, and 743 underwent radiochemotherapy. There was no significant difference in the 1-, 2- or 3-year local control rates between ENI and IFI, or in the 1-, 2- or 3-year overall survival rates. However, the incidences of ≥Grade 3 acute esophagitis and pneumonia were significantly lower in the IFI group. There were no differences in the rates of ≥Grade 3 myelosuppression or of out-field recurrence or metastasis between these two groups. Thus, neither local control rates nor overall survival rates differed significantly between the ENI and IFI groups, but in the latter group, incidences of severe radiation esophagitis and pneumonia were significantly lower. IFI was not associated with an increase in out-field recurrence or metastasis.


Assuntos
Carcinoma de Células Escamosas/radioterapia , Neoplasias Esofágicas/radioterapia , Esôfago/efeitos da radiação , Linhagem Celular Tumoral , Quimiorradioterapia/métodos , Carcinoma de Células Escamosas do Esôfago , Humanos , Metástase Linfática , Metástase Neoplásica , Recidiva Local de Neoplasia , Lesões por Radiação , Radioterapia/métodos , Radioterapia Conformacional , Resultado do Tratamento
16.
Infect Drug Resist ; 11: 1105-1117, 2018.
Artigo em Inglês | MEDLINE | ID: mdl-30127628

RESUMO

Background: Sporadic studies in antimicrobial therapy have evaluated the effects of infusion rates on therapeutic and economic outcomes, and new findings may challenge the regular infusion regimen. Methods: Focusing on studies comparing the outcomes of different infusion regimens, the relevant literature was identified by searching PubMed, Web of Science, and Scopus from January 1, 2013 to March 1, 2018. Papers were finally chosen using a PRISMA flowchart. Results: Antimicrobials with the superiority of prolonged infusion to standard infusion in terms of efficacy and safety include meropenem, doripenem, imipenem, cefepime, ceftazidime, piperacillin/tazobactam, linezolid, and vancomycin. The strategy of concomitantly reducing total daily dose and prolonging infusion time may cause treatment failure (eg, imipenem). Extended infusion of piperacillin/tazobactam has pharmacoeconomic advantage over standard infusion. Prolonged infusion of voriconazole is inferior to standard infusion because of lower efficacy caused by pharmacokinetic changes. Comparable outcomes following standard infusion and continuous infusion were observed with norvancomycin and nafcillin. Factors determining whether prolonged infusion has a benefit over standard infusion include MIC of bacterial pathogens, bacterial density, diagnosis, disease severity, total daily dose, and renal function. Conclusion: To maximally preserve the effectiveness of current antimicrobials, effective interventions should be implemented to enhance the application of optimal infusion strategies. For reducing nephrotoxicity, prolonged infusion of meropenem is better than conventional infusion in neonates with Gram-negative late-onset sepsis, and continuous infusion of vancomycin is superior to intermittent infusion. For increasing efficacy, prolonged or continuous infusion of time-dependent antimicrobials (eg, meropenem, doripenem, imipenem, cefepime, ceftazidime, piperacillin/tazobactam, linezolid, and vancomycin) is an optimal choice. Nevertheless, such advantages may only be demonstrated in special clinical circumstances and special populations (eg, patients with a sequential organ failure assessment (SOFA) score≥9, respiratory tract infections, urinary or intra-abdominal infections, or infections caused by less susceptible pathogens would benefit from prolonged infusion of piperacillin/tazobactam).

17.
J Nurs Scholarsh ; 50(5): 567-576, 2018 09.
Artigo em Inglês | MEDLINE | ID: mdl-29998630

RESUMO

PURPOSE: China is a country with frequent disasters, and nurses play indispensable roles in the disaster process. The Chinese disaster nursing specialty developed with several deficiencies. This study aimed to identify the limitations in the development of disaster nursing in China and to provide a reference for the future by comparing relevant studies between China and other countries. DESIGN: A systematic literature review was conducted in English and Chinese databases to identify disaster nursing articles published from January 1, 2000, to December 31, 2016. METHODS: This study followed the systematic literature collection tactic and bibliometric method. Basic information such as country, number of publications, and discussed disaster types were described through frequency distributions. Article themes were extracted and divided into the four phases of the International Council of Nurses Framework of Disaster Nursing Competencies. FINDINGS: 1,384 articles were included in the analysis, containing 781 written in Chinese and 603 written in English (with 56 of them written by Chinese researchers). The number of Chinese disaster nursing articles and other publications increased sharply between 2007 and 2009 but dropped significantly afterwards, while the total number of articles in other countries fluctuated, with a general upward trend. Compared to other countries, there were fewer research methods used and less focus on disaster prevention and preparedness in China, an imbalanced focus on disaster types, and a lack of focus on prevention, preparedness, and recovery phases. CONCLUSIONS: In China, there is a lack of stable development of disaster nursing research, a lack of study types, and less focus on disaster prevention, preparedness, and recovery. Varied study methods and an increased focus on disaster prevention and preparedness are required in the future. CLINICAL RELEVANCE: This study analyzed the deficiencies in Chinese disaster nursing, which led to recommendations and proposed directions for future studies and a clinical focus in this field, in compliance with the United Nations guidelines for disaster management.


Assuntos
Planejamento em Desastres/organização & administração , Desastres , Pesquisa em Enfermagem/organização & administração , Bibliometria , China , Humanos , Conselho Internacional de Enfermagem
18.
Zhongguo Ying Yong Sheng Li Xue Za Zhi ; 34(1): 4-7, 2018 Jan 08.
Artigo em Chinês | MEDLINE | ID: mdl-29926650

RESUMO

OBJECTIVE: To investigate the effects of deficiency of CHL1 in inflammatory bowel disease (IBD). METHODS: Dextran Sulfate Sodium (DSS)-induced colitis model was used to study the effects of deficiency of CHL1 on the development of IBD. Ten CHL1(+/+) mice in C57/BL6 background were randomly divided into CHL1(+/+) group and DSS-induced CHL1(+/+) group. Ten CHL1(-/-) mice in C57/BL6 background were randomly divided into CHL1(-/-) group and DSS-induced CHL1(-/-) group. DSS-induced CHL1(+/+) group and DSS-induced CHL1(-/-)group were fed with 1.5% DSS for 7 days, and then drinking distilled water for 2 days. CHL1(+/+) group and CHL1(-/-) group as control group were fed with distilled water for 9 days. The changes of weight, survival, fecal blood and the change of colon length in this study were observed. RESULTS: On the 7th day, the weight of DSS-induced CHL1(-/-) group were reduced significantly, and DSS-induced CHL1(-/-) group had extreme mortality on the 9th day. The fecal blood of DSS-induced CHL1(-/-) group also had higher score than that of DSS-induced CHL1(+/+) group. In the DSS-induced CHL1(-/-) group,the length of colon was shortened obviously. CONCLUSIONS: The loss of CHL1 aggravates the development of IBD.


Assuntos
Moléculas de Adesão Celular/genética , Colite/genética , Animais , Moléculas de Adesão Celular/deficiência , Colite/induzido quimicamente , Colo/patologia , Sulfato de Dextrana , Modelos Animais de Doenças , Camundongos , Camundongos Endogâmicos C57BL , Distribuição Aleatória
19.
Am J Perinatol ; 35(10): 946-950, 2018 08.
Artigo em Inglês | MEDLINE | ID: mdl-29444533

RESUMO

OBJECTIVE: To investigate the relationship between blood glucose fluctuation and brain damage in the hypoglycemia neonates. STUDY DESIGN: A retrospective study including all neonates hospitalized due to hypoglycemia from September 2013 to August 2016 was performed. All the 58 hypoglycemia infants were divided into two groups-the brain-damaged group and the nonbrain-damaged group, according to head magnetic resonance imaging and/or amplitude-integrated electroencephalogram. Relationship between glucose variability and brain damage and whether these variation indexes could act as early indicators for hypoglycemic brain damage were investigated. RESULTS: Of the 13 brain-damaged cases, the lowest blood glucose (LBG) level was lower, while duration of hypoglycemia was longer compared with the 45 nonbrain-damaged cases (p < 0.001). The largest amplitude of glycemic excursions, standard deviation of blood glucose, and mean amplitude of glycemic excursions (MAGE) of the brain-damaged group were higher (p < 0.001). Under receiver-operating characteristic curve, values of area under the curve of MAGE were 0.892, duration of hypoglycemia was 0.921, and LBG was 0.109 (p < 0.0001). CONCLUSION: Brain damage of the hypoglycemia neonates relates not only with LBG and duration of hypoglycemia but also with the blood glucose variation indexes; MAGE and duration of hypoglycemia could act as predictors for brain damage.


Assuntos
Glicemia/análise , Lesões Encefálicas/etiologia , Lesões Encefálicas/patologia , Hipoglicemia/complicações , Lesões Encefálicas/sangue , Eletroencefalografia , Feminino , Hemoglobina A Glicada/metabolismo , Humanos , Hipoglicemia/sangue , Recém-Nascido/sangue , Imageamento por Ressonância Magnética , Masculino , Curva ROC , Estudos Retrospectivos , Fatores de Risco
20.
Front Cell Dev Biol ; 6: 169, 2018.
Artigo em Inglês | MEDLINE | ID: mdl-30619851

RESUMO

Hypoxia is the most critical factor for maintaining stemness. During embryonic development, neural stem cells (NSCs) reside in hypoxic niches, and different levels of oxygen pressure and time of hypoxia exposure play important roles in the development of NSCs. Such hypoxic niches exist in adult brain tissue, where the neural precursors originate. Hypoxia-inducible factors (HIFs) are key transcription heterodimers consisting of regulatory α-subunits (HIF-1α, HIF-2α, HIF-3α) and a constitutive ß-subunit (HIF-ß). Regulation of downstream targets determines the fate of NSCs. In turn, the stability of HIFs-α is regulated by prolyl hydroxylases (PHDs), whose activity is principally modulated by PHD substrates like oxygen (O2), α-ketoglutarate (α-KG), and the co-factors ascorbate (ASC) and ferrous iron (Fe2+). It follows that the transcriptional activity of HIFs is actually determined by the contents of O2, α-KG, ASC, and Fe2+. In normoxia, HIFs-α are rapidly degraded via the ubiquitin-proteasome pathway, in which PHDs, activated by O2, lead to hydroxylation of HIFs-α at residues 402 and 564, followed by recognition by the tumor suppressor protein von Hippel-Lindau (pVHL) as an E3 ligase and ubiquitin labeling. Conversely, in hypoxia, the activity of PHDs is inhibited by low O2 levels and HIFs-α can thus be stabilized. Hence, suppression of PHD activity in normoxic conditions, mimicking the effect of hypoxia, might be beneficial for preserving the stemness of NSCs, and it is clinically relevant as a therapeutic approach for enhancing the number of NSCs in vitro and for cerebral ischemia injury in vivo. This study will review the putative role of PHD inhibitors on the self-renewal of NSCs.

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