RESUMO
OBJECTIVES: To compare the repair effects of different doses of human umbilical cord mesenchymal stem cells (hUC-MSCs) on white matter injury (WMI) in neonatal rats. METHODS: Two-day-old Sprague-Dawley neonatal rats were randomly divided into five groups: sham operation group, WMI group, and hUC-MSCs groups (low dose, medium dose, and high dose), with 24 rats in each group. Twenty-four hours after successful establishment of the neonatal rat white matter injury model, the WMI group was injected with sterile PBS via the lateral ventricle, while the hUC-MSCs groups received injections of hUC-MSCs at different doses. At 14 and 21 days post-modeling, hematoxylin and eosin staining was used to observe pathological changes in the tissues around the lateral ventricles. Real-time quantitative polymerase chain reaction was used to detect the quantitative expression of myelin basic protein (MBP) and glial fibrillary acidic protein (GFAP) mRNA in the brain tissue. Immunohistochemistry was employed to observe the expression levels of GFAP and neuron-specific nuclear protein (NeuN) in the tissues around the lateral ventricles. TUNEL staining was used to observe cell apoptosis in the tissues around the lateral ventricles. At 21 days post-modeling, the Morris water maze test was used to observe the spatial learning and memory capabilities of the neonatal rats. RESULTS: At 14 and 21 days post-modeling, numerous cells with nuclear shrinkage and rupture, as well as disordered arrangement of nerve fibers, were observed in the tissues around the lateral ventricles of the WMI group and the low dose group. Compared with the WMI group, the medium and high dose groups showed alleviated pathological changes; the arrangement of nerve fibers in the medium dose group was relatively more orderly compared with the high dose group. Compared with the WMI group, there was no significant difference in the expression levels of MBP and GFAP mRNA in the low dose group (P>0.05), while the expression levels of MBP mRNA increased and GFAP mRNA decreased in the medium and high dose groups. The expression level of MBP mRNA in the medium dose group was higher than that in the high dose group, and the expression level of GFAP mRNA in the medium dose group was lower than that in the high dose group (P<0.05). Compared with the WMI group, there was no significant difference in the protein expression of GFAP and NeuN in the low dose group (P>0.05), while the expression of NeuN protein increased and GFAP protein decreased in the medium and high dose groups. The expression of NeuN protein in the medium dose group was higher than that in the high dose group, and the expression of GFAP protein in the medium dose group was lower than that in the high dose group (P<0.05). Compared with the WMI group, there was no significant difference in the number of apoptotic cells in the low dose group (P>0.05), while the number of apoptotic cells in the medium and high dose groups was less than that in the WMI group, and the number of apoptotic cells in the medium dose group was less than that in the high dose group (P<0.05). Compared with the WMI group, there was no significant difference in the escape latency time in the low dose group (P>0.05); starting from the third day of the latency period, the escape latency time in the medium dose group was less than that in the WMI group (P<0.05). The medium and high dose groups crossed the platform more times than the WMI group (P<0.05). CONCLUSIONS: Low dose hUC-MSCs may yield unsatisfactory repair effects on WMI in neonatal rats, while medium and high doses of hUC-MSCs have significant repair effects, with the medium dose demonstrating superior efficacy.
Assuntos
Animais Recém-Nascidos , Transplante de Células-Tronco Mesenquimais , Ratos Sprague-Dawley , Cordão Umbilical , Substância Branca , Animais , Ratos , Humanos , Cordão Umbilical/citologia , Substância Branca/patologia , Substância Branca/metabolismo , Proteína Glial Fibrilar Ácida/metabolismo , Proteína Glial Fibrilar Ácida/genética , Proteína Glial Fibrilar Ácida/análise , Células-Tronco Mesenquimais , Proteína Básica da Mielina/genética , Proteína Básica da Mielina/análise , Proteína Básica da Mielina/metabolismo , Masculino , Apoptose , Feminino , RNA Mensageiro/análise , RNA Mensageiro/metabolismoRESUMO
Aims: To investigate the effects of M-CSF on myocardial injury in mice after MI by regulating different types of cardiac macrophages through the P2X7R/NLRP3/IL-1ß signal pathway. Methods: A total of 60 C57BL/6J WT mice were used, with the Sham Group subjected to ligation without ligation through the LAD, the MI model was prepared by ligation of the LAD in the MC Group and MM Group, with the M-CSF reagent (500 µg/kg/d) being given an intraperitoneal injection for the first 5 days after surgery in the MM Group. All mice were fed in a barrier environment for 1 week. After the study, myocardial tissues were collected and IL-4, IL-6, IL-10, TNF-α, MCP-1, IFN-α, ANP, BNP, ß-MHC, Collage I, Collage III, P2X7R, NLRP3, IL-1ß, Bax, Caspase 3, C-Casp 3, Bcl-2, M1/2 macrophage, the apoptosis of cardiomyocytes, and the collagen deposition were detected. Results: The inflammatory response was significantly lower in the MM Group, the cardiomyocyte apoptosis, fibrosis, and hypertrophy were inhibited compared to the MC Group, and the levels of P2X7R, NLRP3, and IL-1ß were also statistically lower in the MM Group. Additionally, the expression of M2 macrophages increased in the MM Group while the M1 macrophages statistically decreased compared to the MC Group. Conclusion: M-CSF can significantly increase the expression of M2 macrophage and reduce the level of M1 macrophage by inhibiting the levels of NLRP3/IL-1ß-related proteins, thereby inhibiting inflammation, ameliorating reducing myocardial hypertrophy, apoptosis, and fibrosis, improve myocardial injury in mice after MI.
RESUMO
Spin polarization of two-dimensional electron gas (2DEG) at the interface of EuTiO3/SrTiO3(STO) heterostructures has been theoretical predicted and experimentally observed via x-ray magnetic circular dichroism and polarized x-ray absorption spectroscopy, which, however, is lack of magnetotransport evidence. Here, we report the fabrication of high-quality EuTiO3/STO heterostructures by depositing antiferromagnetic insulating EuTiO3thin films onto STO substrates. Shubnikov-de Haas oscillation, Hall, and magnetoresistance (MR) measurements show that the interface is not only highly conducting, with electron mobility up to5.5×103cm2V-1s-1at 1.8 K, but also shows low-field hysteretic MR effects. MR of â¼9% is observed at 1.8 K and 20 Oe, which is one order of magnitude higher than those observed in other spin-polarized 2DEG oxide systems. Moreover, the heterostructures show ferromagnetic hysteresis loops. These results demonstrate that the high-mobility 2DEG is spin polarized, whose origin is attributed to the interfacial Ti3+-3dstates due to oxygen deficiency and the exchange interactions between interfacial Eu spins and itinerant Ti-3delectrons.
RESUMO
Esophageal squamous cell carcinoma is one of the most common malignant tumors in the digestive system in China and the world. Most patients are diagnosed as locally advanced or advanced stage. Concurrent chemoradiotherapy is the standard treatment for locally advanced esophageal squamous cell carcinoma. This study intends to summarize the evidence-based medical evidence of the treatment principle of locally advanced esophageal squamous cell carcinoma, the selection of radiotherapy dose, the outline of radiotherapy target and the selection of chemotherapy scheme. As a result, the effect of radiotherapy and chemotherapy is equivalent to that of surgery for the radical treatment of esophageal squamous cell carcinoma. In the era of immunization, it is recommended to use involved field irradiation. Fluorouracil plus cisplatin regimen is the standard chemotherapy regimen. FOLFOX regimen and paclitaxel plus fluorouracil regimen are optional concurrent chemotherapy regimens. The toxic and side effects of different chemotherapy regimens are different, which can be selected according to the actual situation of patients.
RESUMO
Actin-binding proteins (ABPs), by interacting with actin, regulate the polymerization, depolymerization, bundling, and cross-linking of actin filaments, directly or indirectly, thereby mediating the maintenance of cell morphology, cell movement, and many other biological functions. Consequently, these functions of ABPs help regulate cancer cell invasion and metastasis when cancer occurs. In recent years, a variety of ABPs have been found to be abnormally expressed in various cancers, indicating that the detection and interventions of unusual ABP expression to alter this are available for the treatment of cancer. The early stages of most cancer development involve long-term chronic inflammation or repeated stimulation. This is the case for breast cancer, gastric cancer, lung cancer, prostate cancer, liver cancer, esophageal cancer, pancreatic cancer, melanoma, and colorectal cancer. This article discusses the relationship between chronic inflammation and the above-mentioned cancers, emphatically introduces relevant research on the abnormal expression of ABPs in chronic inflammatory diseases, and reviews research on the expression of different ABPs in the above-mentioned cancers. Furthermore, there is a close relationship between ABP-induced inflammation and cancer. In simple terms, abnormal expression of ABPs contributes to the chronic inflammation developing into cancer. Finally, we provide our viewpoint regarding these unusual ABPs serving as potential biomarkers for chronic inflammation-induced cancer diagnosis and therapy, and interventions to reverse the abnormal expression of ABPs represent a potential approach to preventing or treating the corresponding cancers.
Assuntos
Biomarcadores Tumorais/metabolismo , Inflamação/metabolismo , Proteínas dos Microfilamentos/metabolismo , Neoplasias/metabolismo , Actinas/metabolismo , Doença Crônica , Citoesqueleto/metabolismo , Progressão da Doença , Humanos , Inflamação/patologia , Neoplasias/diagnóstico , Neoplasias/terapia , PolimerizaçãoRESUMO
The aim was to investigate the role of the α7nAChR-mediated cholinergic anti-inflammatory pathway in vagal nerve regulated atrial fibrillation (AF).18 beagles (standard dogs for testing) were used in this study, and the effective refractory period (ERP) of atrium and pulmonary veins and AF inducibility were measured hourly during rapid atrial pacing at 800 beats/minute for 6 hours in all beagles. After cessation of 3 hours of RAP, the low-level vagal nerve stimulation (LL-VNS) group (n = 6) was given LL-VNS and injection of salinne (0.5 mL/GP) into four GPs, the methyllycaconitine (MLA, the antagonist of α7nAChR) group (n = 6) was given LL-VNS and injection of MLA into four GPs, and the Control group (n = 6) was given saline into four GPs and the right cervical vagal nerve was exposed without stimulation. Then, the levels of the tumor necrosis factor-alpha (TNF-α), interleukin-6 (IL-6), acetylcholine (ACh), STAT3, and NF-κB proteins were measured. During the first 3 hours of RAP, the ERPs gradually decreased while the dispersion of ERPs (dERPs) and AF inducibility gradually increased in all three groups. During the last 3 hours of 6 hours' RAP in this study, the ERPs in the LL-VNS group were higher, while the dERPs and AF inducibility were significantly lower when compared with the Control and MLA groups at the same time points. The levels of ACh in the serum and atrium in the LL-VNS and MLA groups were higher than in the Control group, and the levels of TNF-α and IL-6 were higher in the Control and MLA groups than in the LL-VNS group. The concentrations of STAT3 in RA and LA tissues were higher in the LL-VNS group while those of NF-κB were lower.In conclusion, the cholinergic anti-inflammatory pathway mediated by α7nACh plays an important role in low-level vagal nerve-regulated AF.
Assuntos
Aconitina/análogos & derivados , Fibrilação Atrial/fisiopatologia , Neuroimunomodulação/efeitos dos fármacos , Nervo Vago/efeitos dos fármacos , Receptor Nicotínico de Acetilcolina alfa7/antagonistas & inibidores , Acetilcolina/sangue , Aconitina/administração & dosagem , Aconitina/farmacologia , Animais , Estimulação Cardíaca Artificial/efeitos adversos , Estimulação Cardíaca Artificial/métodos , Estudos de Casos e Controles , Modelos Animais de Doenças , Cães , Átrios do Coração/inervação , Átrios do Coração/fisiopatologia , Interleucina-6/sangue , NF-kappa B/sangue , Antagonistas Nicotínicos/administração & dosagem , Antagonistas Nicotínicos/farmacologia , Veias Pulmonares/inervação , Veias Pulmonares/fisiopatologia , Período Refratário Eletrofisiológico/efeitos dos fármacos , Fator de Transcrição STAT3/sangue , Fator de Necrose Tumoral alfa/sangue , Estimulação do Nervo Vago/efeitos adversos , Estimulação do Nervo Vago/métodosRESUMO
BACKGROUND: Glutathione S-transferase omega 1 (GSTO1), as a member of the glutathione S-transferase (GST) family genes, has been discovered to be up-regulated in several cancer cell lines which exhibited strong aggressiveness. However, the function of GSTO1 on cutaneous malignant melanoma (CMM) has not been illuminated. METHODS: Outcome of expression level and prognosis of GSTO1 were obtained from Oncomine and TCGA database. The specific effects of GSTO1 on the characteristics and regulatory mechanism of CMM cells were demonstrated by cell counting kit-8, colony formation, flow cytometry, and transwell assays in vitro. Western blot was employed to analyze the expression of proliferating cell nuclear antigen (PCNA), p53 and epithelial-to-mesenchymal (EMT) related proteins. RESULTS: We observed that GSTO1 was up-regulated in CMM samples when compared with the corresponding controls. Moreover, patients in CMM with high expression of GSTO1 were more likely to have a poor prognosis. Through in vitro experiments, silenced GSTO1 resulted in inhibition of CMM cells growth and aggressiveness, increased cell apoptosis, and blocked cell cycle. Finally, the expression of PCNA, p53 and EMT-related proteins were changed due to reduction of GSTO1. CONCLUSIONS: To sum up, our outcomes exhibited that weakening GSTO1 reduced the proliferation and mobility of CMM cells, increased the apoptosis ability of CMM cells, and arrested cell cycle at G1 phase, which can be achieved by affecting the expression of PCNA, p53 and the EMT process. This discovery provided a new perspective for elucidating the mechanism of CMM, and offered theoretical support for searching clinical therapeutic targets in the future.
Assuntos
Glutationa Transferase/metabolismo , Melanoma/metabolismo , Neoplasias Cutâneas/metabolismo , Apoptose/fisiologia , Ciclo Celular/fisiologia , Linhagem Celular , Linhagem Celular Tumoral , Proliferação de Células/fisiologia , Transição Epitelial-Mesenquimal/fisiologia , Humanos , Melanoma/patologia , Prognóstico , Antígeno Nuclear de Célula em Proliferação/metabolismo , Neoplasias Cutâneas/patologia , Proteína Supressora de Tumor p53/metabolismo , Regulação para Cima/fisiologia , Melanoma Maligno CutâneoRESUMO
BACKGROUND: Radioresistance is one of the main obstacle limiting the therapeutic efficacy and prognosis of patients, the molecular mechanisms of radioresistance is still unclear. The purpose of this study was to identify the key genes and miRNAs and to explore their potential molecular mechanisms in radioresistant nasopharyngeal carcinoma. METHODS: In this study, we analysis the differentially expressed genes and microRNA based on the database of GSE48501 and GSE48502, and then employed bioinformatics to analyze the pathways and GO terms in which DEGs and DEMS target genes are involved. Moreover, Construction of protein-protein interaction network and identification of hub genes. Finally, analyzed the biological networks for validated target gene of hub miRNAs. RESULTS: A total of 373 differentially expressed genes (DEGs) and 14 differentially expressed microRNAs (DEMs) were screened out. The up-regulated gene JUN was overlap both in DEGs and publicly available studies, which was potentially targeted by three miRNAs, including hsa-miR-203, hsa-miR-24 and hsa-miR-31. Moreover, Pathway analysis showed that both up-regulated gene and DEMs target genes were enriched in TGF-beta signaling pathway, Hepatitis B, Pathways in cancer and p53 signaling pathway. Finally, we further constructed protein-protein interaction network (PPI) of DEGs and analyzed the biological networks for above mentioned common miRNAs, the result indicated that JUN was a core hub gene in PPI network, hsa-miR-24 and its target gene were significantly enriched in P53 signaling pathway. CONCLUSIONS: These results might provide new clues to improve the radiosensitivity of Nasopharyngeal Carcinoma.
Assuntos
Biologia Computacional , MicroRNAs/genética , Carcinoma Nasofaríngeo/genética , Carcinoma Nasofaríngeo/patologia , Tolerância a Radiação/genética , Bases de Dados Genéticas , Perfilação da Expressão Gênica , Ontologia Genética , Redes Reguladoras de Genes , Humanos , Mapeamento de Interação de Proteínas , Transdução de Sinais/genética , Proteína Supressora de Tumor p53/metabolismoRESUMO
BACKGROUND: Shensong Yangxin (SSYX), a traditional Chinese herbal medicine, has long been used clinically to treat arrhythmias in China. However, the mechanism of SSYX on atrial fibrillation (AF) is unknown. In this study, we tested the hypothesis that the effect of SSYX on the progression of paroxysmal AF is correlated with the regulation of autonomic nerve activity. METHODS: Eighteen mongrel dogs were randomly divided into control group (n = 6), pacing group (n = 6), and pacing + SSYX group (n = 6). The control group was implanted with pacemakers without pacing; the pacing group was implanted with pacemakers with long-term intermittent atrial pacing; the pacing + SSYX group underwent long-term intermittent atrial pacing and SSYX oral administration. RESULTS: Compared to the pacing group, the parameters of heart rate variability were lower after 8 weeks in the pacing + SSYX group (low-frequency [LF] component: 20.85 ± 3.14 vs. 15.3 ± 1.89 ms 2 , P = 0.004; LF component/high-frequency component: 1.34 ± 0.33 vs. 0.77 ± 0.15, P < 0.001). The atrial effective refractory period (AERP) was shorter and the dispersion of the AERP was higher after 8 weeks in the pacing group, while the changes were suppressed by SSYX intake. The dogs in the pacing group had more episodes and longer durations of AF than that in the pacing + SSYX group. SSYX markedly inhibited the increase in sympathetic nerves and upregulation of tumor necrosis factor-alpha and interleukin-6 expression in the pacing + SSYX group. Furthermore, SSYX suppressed the decrease of acetylcholine and α7 nicotinic acetylcholine receptor protein induced by long-term intermittent atrial pacing. CONCLUSIONS: SSYX substantially prevents atrial electrical remodeling and the progression of AF. These effects of SSYX may have association with regulating the imbalance of autonomic nerve activity and the cholinergic anti-inflammatory pathway.
Assuntos
Fibrilação Atrial/tratamento farmacológico , Fibrilação Atrial/metabolismo , Medicamentos de Ervas Chinesas/uso terapêutico , Acetilcolina/sangue , Animais , Vias Autônomas/efeitos dos fármacos , Western Blotting , Cães , Eletrofisiologia , Ensaio de Imunoadsorção Enzimática , Frequência Cardíaca/efeitos dos fármacos , Imuno-Histoquímica , Interleucina-6/sangue , Modelos Animais , Fator de Necrose Tumoral alfa/sangue , Receptor Nicotínico de Acetilcolina alfa7/sangueRESUMO
Soils were collected from Shergyla Mountain shade slope and south-facing slope in southeast Tibetan Plateau (TP) in August 2012 and they were measured for polycyclic aromatic hydrocarbons (PAHs) and organochlorine pesticides (OCPs)(including HCHs and DDTs). The concentrations of ∑16PAHs ranged from 99.3 to 1984 ng·g-1 dw, with a mean value of 1017 ng·g-1 dw. HCHs and DDTs in soils samples were in the range of 0.37-2.07 ng·g-1 dw (mean 1.15 ng·g-1 dw) and 0.70-43.9 ng·g-1 dw (mean 9.87 ng·g-1 dw), respectively. The concentrations of all measured compounds were much higher than those in central or western TP,and the PAHs concentration was even up to two orders of magnitude. The concentrations of α-HCH and DDTs in south-facing slope increased with altitude, but HCHs and DDTs in shade slope had no significant correlation with altitude. There was no consistent increasing or decreasing trend of PAHs in shade slope with altitude, and the concentrations of PAHs in south-facing slope showed a higher value in lower altitude, indicating the existence of local pollution emissions. The PAHs profile was dominated by lighter constituents (2 & 3-ring accounted for higher than 85%),inferring that the PAHs in the study area were largely influenced by long range atmospheric transport (LRAT) of pollutants. The special diagnostic ratios of PAHs suggested that PAHs were mainly produced by low temperature combustion of biomass and fossil fuels, except that two sampling sites of shade slope had been possibly influenced by oil residue. The relatively low ratios of α/γ-HCH inferred HCHs in the research area was the result of the combined contribution of the historical technical HCHs and Lindan. The ratios of p,p'-DDE/p,p'-DDT and o,p'-DDT/p,p'-DDT indicated DDTs were from the combined contribution of the historical technical DDTs and dicofol. According to the profile of PAHs, HCHs and DDTs and the meteorological conditions of Shergyla Mountain, the transport of PAHs and OCPs in the study area was mainly influenced by the Indian Monsoon.
RESUMO
Soils and grasses samples were collected from 6 typical lake catchments in the central and northern Tibetan Plateau (TP) in August 2007 and analyzed for polycyclic aromatic hydrocarbons (PAHs) and organochlorine pesticides (OCPs, including HCHs and DDTs). The concentrations of sigma16 PAHs, sigma HCHs and sigma DDTs in soil samples were in the range of 60.6-614 ng x g(-1) (mean 194 ng x g(-1)), 0.06-0.74 ng x g(-1) (mean 0.31 ng x g(-1)) and N. D. -0.17 ng x g(-1) (mean 0.07 ng x g(-1)) while those of sigma15 PAHs (excluding NAP), sigma HCHs and sigma DDTs in grasses were in the range of 262-519 ng x g(-1) (mean 327 ng x g(-1)), 0.55-3.92 ng x g(-1) (mean 2.17 ng x g(-1)) and 0.20-2.19 ng x g(-1) (mean 0.92 ng x g(-1)), respectively. All compounds were significantly lower than those in European high mountains. The biological concentration effect of grasses to soils was notable with the values of BCF ranging from 4.2 to 19.3. No significant correlations were observed between the concentrations of POPs and the content of OM/lipid, or the altitude of the sampling sites. The PAHs profile was dominated by lighter constituents (2 & 3-ring PAHs accounted for higher than 80%). The special diagnostic ratios of PAHs suggested that PAHs in the TP were mainly produced by low-temperature combustion of biomass and fossil fuels, and the relatively low ratios of alpha/gamma-HCH and high ratios of o,p'-DDT/p,p'-DDT implied that the wide applications of lindane and dicofol contributed to the OCPs contamination in the TP. According to the backward airmass trajectory models, it was deduced that the westerly wind was the main source for both central and northern sites in the TP during winter. During summer, pollutants in the central sites of the TP were mainly from the Indian subcontinent while the northern sites were also affected by Chinese inland provinces.
Assuntos
Monitoramento Ambiental , Hidrocarbonetos Clorados/análise , Resíduos de Praguicidas/análise , Poaceae/química , Hidrocarbonetos Policíclicos Aromáticos/análise , Solo/química , Altitude , DDT/análise , Hexaclorocicloexano/análise , Lagos , Poluentes do Solo/análise , TibetRESUMO
OBJECTIVE: To investigate the potential therapeutic properties of the endogenous cannabinoid N-arachidonic acid aminoethanols (anandamide, AEA) in liver fibrosis by observing its affects on proliferation of and expression of phosphorylated-Erk (pErk) in primary hepatic stellate cells (HSCs) from a mouse model of schistosome-induced liver fibrosis. METHODS: The schistosome-induced liver fibrosis model was established by attaching cercaria to the skin on the ventral side of the mouse and allowing infection to occur via direct penetration. Six weeks later, the model was confirmed by pathological analysis of liver, with Masson trichrome staining showing collagen fiber deposition around the blood vessels and hematoxylin-eosin staining showing eosinophilic granuloma formation. Primary HSCs were isolated by discontinuous density gradient centrifugation, confirmed by immunofluorescence detection of double-staining for a-smooth muscle actin and desmin (95% purity), and cultured in the presence of absence of various concentrations of AEA. Proliferative ability was evaluated by MTT assay and the expression of pErk was observed by Western blotting. RESULTS: AEA treatment inhibited the proliferation of the primary HSCs in a concentration-dependent manner (AEA: 5 mumol/L, inhibition: 7.68%; 10 mumol/L, 11.65%; 20 mumol/L, 14.70%; 40 mumol/L, 15.07%; 60 mumol/L, 18.18%; 80 mumol/L, 20.26%; 100 mumol/L, 20.17%; 120 mumol/L, 29.24%). AEA treatment increased pERK expression in both a concentration-dependent manner (AEA: 20 mumol/L, average gray value: 39.90+/-4.61; 60 mumol/L, 43.45+/-0.91; 120 mumol/L, 52.91+/-1.97; vs. negative control, all P less than 0.05) and a time-dependent manner (time: 15 min, average gray value: 85.05+/-15.80; 30 min, 103.41+/-11.89; 1 h, 118.02+/-12.24; 3 h, 109.17+/-15.69; 6 h, 100.86+/-10.55; 12 h, 71.70+/-12.87; 24 h, 34.62+/-14.85; 48 h, 22.84+/-11.73; vs. negative control, all except 48 h had P less than 0.05). CONCLUSION: AEA can suppress the proliferative capacity of primary HSCs from schistosome-induced fibrotic livers through activation of the Erk signaling pathway.
Assuntos
Células Cultivadas , Células Estreladas do Fígado , Animais , Células Estreladas do Fígado/metabolismo , Cirrose Hepática , Camundongos , FosforilaçãoRESUMO
AIM: To investigate the effects of different concentrations of Schistosoma japonicum (S. japonicum) egg antigen on fibrogenesis and apoptosis in primary hepatic stellate cells (HSCs). METHODS: A mouse model of schistosomiasis-associated liver fibrosis (SSLF) was established by infecting mice with schistosomal cercaria via the abdomen. HSCs were isolated from SSLF mice by discontinuous density gradient centrifugation, and their identity was confirmed by immunofluorescence double staining of α-smooth muscle actin (α-SMA) and desmin. The growth inhibitory effect and 50% inhibitory concentration (IC50) of S. japonicum egg antigen for primary HSCs (24 h) were determined using a cell counting kit-8 (CCK-8) assay. The expression levels of α-SMA, matrix metalloproteinase-9 (MMOL/LP-9) and tissue inhibitor of metalloproteinases-1 (TIMP-1) in HSCs in response to different concentrations of S. japonicum egg antigen were detected by Western blotting and real-time reverse transcription-polymerase chain reaction. The levels of phospho-P38 (P-P38), phospho-Jun N-terminal kinase (P-JNK) and phospho-Akt (P-AKT) in HSCs were detected by Western blotting. RESULTS: An SSLF mouse model was established, and primary HSCs were successfully isolated and cultured. S. japonicum egg antigen inhibited HSC proliferation in a concentration-dependent manner. The IC50 of the S. japonicum egg antigen was 244.53 ± 35.26 µg/mL. S. japonicum egg antigen enhanced α-SMA expression at both the mRNA and protein levels and enhanced TIMP-1 expression at the mRNA level in HSCs (P < 0.05), whereas the expression of MMOL/LP-9 was attenuated at both the mRNA and protein levels in a concentration-dependent manner (P < 0.05). A high concentration of S. japonicum egg antigen enhanced P-P38, P-JNK and P-AKT activation (P < 0.05). The changes in α-SMA and MMOL/LP-9 expression induced by S. japonicum egg antigen were closely correlated with P-P38 and P-JNK activation (P < 0.05). The attenuation of MMOL/LP-9 was also correlated with P-AKT activation (P < 0.05), but the increase in α-SMA expression was not. TIMP-1 expression was not correlated with P-P38, P-JNK or P-AKT activation. CONCLUSION: S. japonicum egg antigen promotes fibrogenesis, activates the P38/JNK mitogen-activated protein kinase and AKT/PI3K signaling pathways and inhibits proliferation in primary HSCs isolated from SSLF mice in a concentration-dependent manner.
Assuntos
Antígenos de Helmintos/imunologia , Proliferação de Células , Proteínas de Helminto/imunologia , Células Estreladas do Fígado/parasitologia , Cirrose Hepática/parasitologia , Fígado/parasitologia , Óvulo/imunologia , Schistosoma japonicum/patogenicidade , Esquistossomose Japônica/parasitologia , Actinas/metabolismo , Animais , Apoptose , Biomarcadores/metabolismo , Células Cultivadas , Cercárias , Desmina/metabolismo , Modelos Animais de Doenças , Células Estreladas do Fígado/imunologia , Células Estreladas do Fígado/metabolismo , Células Estreladas do Fígado/patologia , Proteínas Quinases JNK Ativadas por Mitógeno/metabolismo , Fígado/imunologia , Fígado/metabolismo , Fígado/patologia , Cirrose Hepática/imunologia , Cirrose Hepática/metabolismo , Cirrose Hepática/patologia , Masculino , Metaloproteinase 9 da Matriz/metabolismo , Camundongos , Camundongos Endogâmicos BALB C , Fosforilação , Proteínas Proto-Oncogênicas c-akt/metabolismo , Schistosoma japonicum/crescimento & desenvolvimento , Schistosoma japonicum/imunologia , Esquistossomose Japônica/imunologia , Esquistossomose Japônica/metabolismo , Esquistossomose Japônica/patologia , Inibidor Tecidual de Metaloproteinase-1/metabolismo , Proteínas Quinases p38 Ativadas por Mitógeno/metabolismoRESUMO
OBJECTIVE: To observe the effects of Xuesetong Soft Capsules, Notoginseng total saponin) on angiogenesis and vascular endothelial growth factor (VEGF) mRNA expression in ischemic myocardium of rats with myocardial infarction. METHODS: The left coronary artery of rats was ligated to establish the animal model of acute myocardial infarction. Rats were randomly divided into Xuesetong Soft Capsule, Shexiangbaoxin Pill (positive control), model (negative control) and sham operation groups. After 6 weeks, microvessel count (MVC), microvessel density (MVD) and VEGF mRNA expression in ischemic myocardium were evaluated. RESULTS: MVC and MVD in the myocardial infarct border area in model, Shexiangbaoxin Pill and Xuesetong Soft Capsule groups significantly increased compared with those of the sham operation group (P < 0.05). MVC and MVD in the myocardial infarct border area in Xuesetong Soft Capsule and Shexiangbaoxin Pill groups significantly increased compared with those of the model group (P < 0.05). No significant differences between Xuesetong Soft Capsule and Shexiangbaoxin Pill groups were observed (P > 0.05). The model group showed significantly higher VEGF mRNA expression than that in the sham operation group (P < 0.05). Xuesetong Soft Capsule and Shexiangbaoxin Pill groups showed significantly higher VEGF mRNA expression than that of the model group (P < 0.05). No significant difference between Xuesetong Soft Capsule and the Shexiangbaoxin Pill groups was observed (P > 0.05). CONCLUSION: Xuesetong Soft Capsules promote angiogenesis in ischemic myocardium after myocardial infarction and the mechanism may be associated with VEGF mRNA expression.
Assuntos
Infarto do Miocárdio/tratamento farmacológico , Miocárdio/metabolismo , Neovascularização Patológica/tratamento farmacológico , Saponinas/administração & dosagem , Fator A de Crescimento do Endotélio Vascular/genética , Animais , Modelos Animais de Doenças , Medicamentos de Ervas Chinesas , Expressão Gênica/efeitos dos fármacos , Humanos , Masculino , Infarto do Miocárdio/genética , Infarto do Miocárdio/metabolismo , Neovascularização Patológica/genética , Neovascularização Patológica/metabolismo , Ratos , Ratos Wistar , Fator A de Crescimento do Endotélio Vascular/metabolismoRESUMO
OBJECTIVE: To analyze the impact of mortality by age and causes of death on life expectancy at birth among residents of Liaoning province. METHODS: The study included mortality data of urban and rural residents in two periods (1973 - 1975 and 2004 - 2005). Both Abridged Life Table and Arriaga method were used to calculate and to decompose life expectancy changes by age and causes of death. RESULTS: From 1975 - 2005, the life expectancy increased by 4.68 years in urban residents and 4.91 for rural residents with a higher increment among females than males. Most part of the increase (76.27% and 82.81% for urban and rural male, 58.76% and 62.13% for urban and rural female) in life expectancy within the last 30 years could be explained by the decrease of mortality in the populations at age 0 - 4 and 55 - 74. Diseases related to respiratory system and infectious disease were contributing the most to the gap in life expectancy between the two periods. Mortality of heart disease was a negative contributor to the changes in life expectancy among both rural and urban residents while the mortalities of cerebro-vascular diseases and malignant tumors were the negative contributors for rural residents. CONCLUSION: The increase of life expectancy in the last 30 years was mainly resulted from the decrease of mortality on both respiratory and infectious diseases. Control of chronic diseases is the key point to increase the life expectancy among the residents of Liaoning province.
Assuntos
Expectativa de Vida , China , Feminino , Humanos , Tábuas de Vida , Masculino , População Rural , População UrbanaRESUMO
Enhanced cardiac sympathetic afferent reflex (CSAR) contributes to sympathetic activation in renovascular hypertension. The study was to determine whether c-Src in paraventricular nucleus (PVN) is involved in the enhanced CSAR and sympathetic activation in hypertensive rats induced by two-kidney one-clip (2K1C). At the end of the fourth week after 2K1C surgery, renal sympathetic nerve activity (RSNA) was recorded in anesthetized rats with baroreceptor denervation and vagotomy. The CSAR was evaluated by the RSNA response to epicardial application of capsaicin. In the PVN, c-Src activity was higher in 2K1C rats than sham-operated (Sham) rats while c-Src expression was not. Epicardial application of capsaicin or PVN microinjection of angiotensin II (Ang II) increased c-Src activity more in 2K1C than Sham rats. PVN microinjection of selective Src family kinase inhibitor 4-Amino-5-(4-chlorophenyl)-7-(t-butyl) pyrazol [3,4-D] pyrimidine (PP2) or 2,3-Dihydro-N,N-dimethyl-2-oxo-3-[(4,5,6,7-tetrahydro-1 H-indol-2-yl)methylene]-1 H-indole-5-sulfonamide (SU6656) abolished the CSAR and decreased RSNA more in 2K1C than Sham rats. The Ang II-induced RSNA and CSAR enhancement was abolished by PP2 or SU6656 pretreatment in 2K1C and Sham rats. NAD(P)H oxidase activity and superoxide anion level in PVN were higher in 2K1C rats, which was attenuated by PP2 but increased by epicardial application of capsaicin or PVN microinjection of Ang II. The effects of capsaicin or Ang II were abolished by PP2. These results indicate that c-Src in the PVN is involved in the enhanced CSAR and sympathetic activation in renovascular hypertension, and mediates the excitatory effects of Ang II in the PVN on the CSAR and sympathetic activity via NAD(P)H oxidase-derived generation of superoxide anions.
Assuntos
Hipertensão Renovascular/fisiopatologia , Neurônios Aferentes/fisiologia , Núcleo Hipotalâmico Paraventricular/metabolismo , Proteínas Tirosina Quinases/metabolismo , Reflexo/fisiologia , Sistema Nervoso Simpático/fisiologia , Angiotensina II/farmacologia , Animais , Pressão Sanguínea/efeitos dos fármacos , Pressão Sanguínea/fisiologia , Proteína Tirosina Quinase CSK , Capsaicina/farmacologia , Modelos Animais de Doenças , Hipertensão Renovascular/metabolismo , Indóis/farmacologia , Masculino , NADPH Oxidases/metabolismo , Neurônios Aferentes/efeitos dos fármacos , Núcleo Hipotalâmico Paraventricular/efeitos dos fármacos , Proteínas Tirosina Quinases/antagonistas & inibidores , Pirimidinas/farmacologia , Ratos , Ratos Sprague-Dawley , Espécies Reativas de Oxigênio/metabolismo , Reflexo/efeitos dos fármacos , Sulfonamidas/farmacologia , Superóxidos/metabolismo , Sistema Nervoso Simpático/efeitos dos fármacos , Quinases da Família srcRESUMO
Bone marrow stromal cells (BMSCs) are strong candidates for cell therapy against human autoimmune diseases. Intravenous administration of syngenic BMSCs to EAMG-model rats effectively ameliorated the disease, partially through a TGF-beta-dependent mechanism. The proliferative ability of T or B cells from EAMG rats was inhibited by BMSCs at proper cocultured ratios. And the imbalance of Th1, Th2, Th17 and Treg cell subsets accompanied with the development of EAMG was corrected by the administration of BMSCs. These results provide further insights into the pathogenesis of MG, EAMG, and other immune-mediated diseases, and support a potential role for BMSCs in their treatment.
Assuntos
Transplante de Medula Óssea/métodos , Miastenia Gravis Autoimune Experimental/cirurgia , Células Estromais/transplante , Linfócitos T Auxiliares-Indutores/metabolismo , Linfócitos T Reguladores/metabolismo , Fator de Crescimento Transformador beta/metabolismo , Animais , Linfócitos B/imunologia , Linfócitos B/metabolismo , Peso Corporal , Proliferação de Células , Técnicas de Cocultura/métodos , Citocinas/metabolismo , Modelos Animais de Doenças , Feminino , Imunoglobulinas/metabolismo , Miastenia Gravis Autoimune Experimental/imunologia , Peptídeos/imunologia , Ratos , Ratos Endogâmicos Lew , Receptores Colinérgicos/imunologia , Células Estromais/imunologia , Linfócitos T Auxiliares-Indutores/classificação , Linfócitos T Auxiliares-Indutores/imunologia , Linfócitos T Reguladores/imunologia , Fatores de Tempo , Fator de Crescimento Transformador beta/imunologiaRESUMO
Steady-state radiolysis experiments were performed to gain insight into the kinetics and mechanisms of nitrobenzene (NB) degradation in aqueous solutions. The degradation of NB under gamma-ray irradiation followed pseudo-first-order kinetics, and the pseudo first-order rate constant and the initial G value of NB decomposition were functionally related to both the initial NB concentration and the irradiation dose rate. Under oxidative conditions, complete mineralization of NB was achieved, whereas no total organic carbon reduction was observed under reductive conditions. The radiolytic products of NB under various conditions were identified using FTIR and GC-MS analyses. The mechanisms behind the radiolytic degradation of NB under both oxidative and reductive conditions were proposed schematically in light of the degradation products observed. In addition, calculations based on ab initio molecular orbital and density functional theory provided support for the proposed mechanisms and the preferred pathways among all the possible reactions.
Assuntos
Raios gama , Nitrobenzenos/química , Poluição Química da Água/prevenção & controle , Água/química , Cromatografia Líquida de Alta Pressão , Cromatografia Gasosa-Espectrometria de Massas , Cinética , Estrutura Molecular , Oxirredução/efeitos da radiação , Espectroscopia de Infravermelho com Transformada de FourierRESUMO
The radiation-induced degradation of acetochlor was investigated in this work. In a mixed solvent composed of acetonitrile and water at a ratio of 20/80 in volume, the acetochlor degradation rate was proportional to the radiation dose rate and acetochlor concentration. The acetochlor degradation efficiency was higher under alkali conditions and lower under acidic conditions. The contribution to the acetochlor degradation by the radicals was in the order of: e(aq)->.OH>H.. The quantum efficiency ratios of .OH, e(aq)- and H. for the degradation of acetochlor were calculated as 1:3:1.
Assuntos
Radioisótopos de Cobalto/química , Raios gama , Herbicidas/química , Toluidinas/química , Cromatografia Líquida de Alta Pressão , Herbicidas/efeitos da radiação , Concentração de Íons de Hidrogênio , Cinética , Espectrofotometria Ultravioleta , Toluidinas/efeitos da radiaçãoRESUMO
The reductive degradation of nitrobenzene (NB) by zero-valent iron was investigated. Experimental results showed that the degradation of NB was influenced by pH and NB concentration. The optimum pH value was found to be 3.0 for the reductive degradation of NB in the tested pH ranges of 3.0-12.0. The formation rate of aniline, a major reductive product of NB, followed zero-order kinetics at various pH levels. Furthermore, GC/MS analysis showed that aniline, azobenzene and azoxybenzene were the reductive products of NB by zero-valent iron. With the analysis of the products with GC/MS and FTIR, possible reductive pathways of NB by zero-valent iron were suggested.