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1.
Pathol Oncol Res ; 29: 1611114, 2023.
Artigo em Inglês | MEDLINE | ID: mdl-37465317

RESUMO

Aim: To observe the efficacy of the low dose apatinib plus deep hyperthermia as third-line or later treatment for patients with human epidermal growth factor receptor 2 (HER-2) negative advanced gastric cancer. Methods: 80 eligible patients with HER-2 negative advanced gastric cancer admitted to Jingjiang People's Hospital Affiliated with Yangzhou University-from March 2021 to March 2022 were selected, and they were divided into the control group (n = 40, apatinib) and experimental group (n = 40, apatinib plus deep hyperthermia) on the basis of random number table method. The levels of serum carcinoembryonic antigen (CEA), carbohydrate antigen 199 (CA199), and vascular endothelial growth factor (VEGF) were monitored, and the efficacy of the two groups was analyzed by referring to Karnofsky performance status (KPS), overall survival (OS) and disease control rate (DCR) before and after treatment. Results: The levels of CEA, CA199, and VEGF in both groups were lower after treatment than before (p < 0.05), and lower (CEA: 8.85 ± 1.36 vs. 12.87 ± 1.23, CA199: 34.19 ± 4.68 vs. 50.11 ± 5.73, VEGF: 124.8 ± 18.03 vs. 205.9 ± 19.91) in the experimental group than in the control group (p < 0.05). The DCR and KPS of the patients in the experimental group were significantly higher (DCR: 62.50% vs. 40.00%; KPS: 83.25 ± 1.15 vs. 76.25 ± 1.17) than in the control group (p < 0.05). In survival analysis, patients with control group had shorter OS than the experimental group. (median 5.65 vs. 6.50 months; hazard ratio [HR], 1.63 [95% confidence interval (CI) 1.02-2.60], p = 0.0396). Conclusion: The application of low-dose apatinib plus deep hyperthermia for patients with HER-2 negative gastric cancer who failed second-line treatment should be a promising option.


Assuntos
Antineoplásicos , Hipertermia Induzida , Neoplasias Gástricas , Humanos , Neoplasias Gástricas/tratamento farmacológico , Neoplasias Gástricas/induzido quimicamente , Fator A de Crescimento do Endotélio Vascular , Antineoplásicos/uso terapêutico , Antígeno Carcinoembrionário
2.
Phytomedicine ; 109: 154551, 2023 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-36610119

RESUMO

BACKGROUND: The significant clinical efficacy of Xuanfei Baidu Decoction (XFBD) is proven in the treatment of patients with coronavirus disease 2019 (COVID-19) in China. However, the mechanisms of XFBD against acute lung injury (ALI) are still poorly understood. METHODS: In vivo, the mouse model of ALI was induced by IgG immune complexes (IgG-IC), and then XFBD (4g/kg, 8g/kg) were administered by gavage respectively. 24 h after inducing ALI, the lungs were collected for histological and molecular analysis. In vitro, alveolar macrophages inflammation models induced by IgG-IC were performed and treated with different dosage of XFBD-containing serum to investigate the protective role and molecular mechanisms of XFBD. RESULTS: The results revealed that XFBD mitigated lung injury and significantly downregulated the production of pro-inflammatory mediators in lung tissues and macrophages upon IgG-IC stimulation. Notably, XFBD attenuated C3a and C5a generation, inhibited the expression of C3aR and C5aR and suppressed the activation of JAK2/STAT3/SOCS3 and NF-κB signaling pathway in lung tissues and macrophages induced by IgG-IC. Moreover, in vitro experiments, we verified that Colivelin TFA (CAF, STAT3 activator) and C5a treatment markedly elevated the IgG-IC-triggered inflammatory responses in macrophages and XFBD weakened the effects of CAF or C5a. CONCLUSION: XFBD suppressed complement overactivation and ameliorated IgG immune complex-induced acute lung injury by inhibiting JAK2/STAT3/SOCS3 and NF-κB signaling pathway. These data contribute to understanding the mechanisms of XFBD in COVID-19 treatment.


Assuntos
Lesão Pulmonar Aguda , COVID-19 , Animais , Humanos , Camundongos , Lesão Pulmonar Aguda/tratamento farmacológico , Lesão Pulmonar Aguda/metabolismo , Complexo Antígeno-Anticorpo/metabolismo , COVID-19/patologia , Tratamento Farmacológico da COVID-19 , Imunoglobulina G , Janus Quinase 2/metabolismo , Lipopolissacarídeos , Pulmão/patologia , NF-kappa B/metabolismo , Transdução de Sinais , Proteína 3 Supressora da Sinalização de Citocinas/metabolismo , Proteínas Supressoras da Sinalização de Citocina/metabolismo
3.
Front Pharmacol ; 12: 735079, 2021.
Artigo em Inglês | MEDLINE | ID: mdl-34744719

RESUMO

Chronic pancreatitis (CP) is a progressive fibro-inflammatory syndrome. The damage of acinar cells is the main cause of inflammation and the activation of pancreatic stellate cells (PSCs), which can thereby possibly further aggravate the apoptosis of more acinar cells. Saikosaponind (SSd), a major active ingredient derived from Chinese medicinal herb bupleurum falcatum, which exerted multiple pharmacological effects. However, it is not clear whether SSd protects pancreatic injury of CP via regulating the apoptosis of pancreatic acinar cells. This study systematically investigated the effect of SSd on pancreatic injury of CP in vivo and in vitro. The results revealed that SSd attenuate pancreatic damage, decrease the apoptosis and suppress the phosphorylation level of MAPK family proteins (JNK1/2, ERK1/2, and p38 MAPK) significantly in the pancreas of CP rats. In addition, SSd markedly reduced the apoptosis and inflammation of pancreatic acinar AR42J cells induced by cerulein, a drug induced CP, or Conditioned Medium from PSCs (PSCs-CM) or the combination of PSCs-CM and cerulein. Moreover, SSd significantly inhibited the activated phosphorylation of JNK1/2, ERK1/2, and p38 MAPK induced by cerulein or the combination of PSCs-CM and cerulein in AR42J cells. Furthermore, SSd treatment markedly decreased the protein levels of p-JNK and p-p38 MAPK caused by PSCs-CM alone. In conclusion, SSd ameliorated pancreatic injury, suppressed AR42J inflammation and apoptosis induced by cerulein, interrupted the effect of PSCs-CM on AR42J cells inflammation and apoptosis, possibly through MAPK pathway.

4.
Int Immunopharmacol ; 99: 107986, 2021 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-34303280

RESUMO

Albiziae Cortex (AC) is a well-known traditional Chinese medicine with sedative-hypnotic effects and neuroprotective ability. However, the bioactive components of AC responsible for the neuro-protective actitivity remain unknown. Here, we investigated the anti-neuroinflammatory effects of (-)-syringaresinol (SYR) extracted from AC in microglia cells and wild-type mice. As a result, (-)-SYR significantly reduced lipopolysaccharide (LPS)-induced production of interleukin - 6 (IL-6), tumor necrosis factor α (TNF-α), interleukin -1 beta (IL-1ß), cycloxygenase-2 (COX-2), and nitric oxide (NO) in BV2 microglia cells. (-)-SYR also significantly reduced M1 marker CD40 expression and increased M2 marker CD206 expression. Moreover, we found that (-)-SYR inhibited LPS-induced NF-κB activation by suppressing the translocation of NF-κB p65 into the nucleus in a concentration-dependent manner. Meanwhile, estrogen receptor ß (ERß) was found to be implied in the anti-inflammatory activity of (-)-SYR in BV2 microglia. In vivo experiments revealed that administration of (-)-SYR in mice significantly reduced microglia/astrocytes activation and mRNA levels of proinflammatory mediators. Taken together, our data indicated that (-)-SYR exerted the anti-neuroinflammatory effects by inhibiting NF-κB activation and modulation of microglia polarization, and via interaction with ERß. The anti-neuroinflammatory activity of (-)-SYR may provide a new therapeutic avenue for the treatment of brain diseases associated with inflammation.


Assuntos
Receptor beta de Estrogênio/metabolismo , Furanos/farmacologia , Lignanas/farmacologia , Microglia/metabolismo , Albizzia/química , Animais , Anti-Inflamatórios/uso terapêutico , Sobrevivência Celular/efeitos dos fármacos , Citocinas/metabolismo , Receptor beta de Estrogênio/antagonistas & inibidores , Furanos/química , Lignanas/química , Lipopolissacarídeos/farmacologia , Sistema de Sinalização das MAP Quinases/efeitos dos fármacos , Ativação de Macrófagos/efeitos dos fármacos , Masculino , Camundongos , Camundongos Endogâmicos C57BL , Microglia/efeitos dos fármacos , Doenças Neuroinflamatórias/tratamento farmacológico , Proteína Oncogênica v-akt/metabolismo , Fator de Transcrição RelA/metabolismo
5.
Front Pharmacol ; 12: 679557, 2021.
Artigo em Inglês | MEDLINE | ID: mdl-34177589

RESUMO

Pancreatic fibrosis is a pathological characteristic of chronic pancreatitis (CP) and pancreatic cancer. Chaihu Guizhi Ganjiang Decoction (CGGD) is a traditional Chinese medicine, which is widely used in the clinical treatment of digestive diseases. However, the potential anti-fibrosis mechanism of CGGD in treating CP remains unclear. Here, we conducted a series of experiments to examine the effect of CGGD on the CP rat model and primary isolated pancreatic stellate cells (PSCs). The results revealed that CGGD attenuated pancreatic damage, decreased collagen deposition, and inhibited PSC activation in the pancreas of CP rats. However, compared with the CP group, CGGD had no effect on body weight and serum amylase and lipase. In addition, CGGD suppressed autophagy by downregulating Atg5, Beclin-1, and LC3B and facilitated phosphorylation of mTOR and JNK in pancreatic tissues and PSCs. Moreover, the CGGD-containing serum also decreased LC3B or collagen I expression after rapamycin (mTOR inhibitor) or SP600125 (JNK inhibitor) treatment in PSCs. In conclusion, CGGD attenuated pancreatic fibrosis and PSC activation, possibly by suppressing autophagy of PSCs through the JNK/mTOR signaling pathway.

6.
Artigo em Inglês | MEDLINE | ID: mdl-32188155

RESUMO

Access to green space (GS) is vital for children's health and development, including during daycare. In Japan, deregulation to alleviate daycare shortages has created a new category of so-called unlicensed daycare centers (UDCs) that often lack dedicated GS. UDCs rely on surrounding GS, including parks, temples and university grounds, but reports of conflicts highlight the precarity of children's well-being in a rapidly aging country. Knowledge about GS access in Japanese UDCs remains scarce. Our mail-back survey (n = 173) of UDCs and online survey (n = 3645) of parents investigated threats to GS access during daycare across 14 Japanese cities. Results suggest that UDCs use a variety of GS and aim to provide daily access. Caregivers are vital in mediating children's access, but locally available GS diversity, quality and quantity as well as institutional support were perceived as lacking. Parents did not rank GS high among their priorities when selecting daycare providers, and showed limited awareness of conflicts during GS visits. Implications of this study include the need for caregivers and parents to communicate and collaborate to improve GS access, and the importance of strong public investment into holistically improving GS diversity, quality and quantity from the perspective of public health and urban planning.


Assuntos
Creches , Proteção da Criança , Meio Ambiente , Criança , Pré-Escolar , Cidades , Feminino , Humanos , Japão , Masculino , Características de Residência , Inquéritos e Questionários
7.
Chin J Integr Med ; 26(8): 599-603, 2020 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-29181733

RESUMO

OBJECTIVE: To investigate the effect of Modified Xiaochaihu Decoction (MXD, ) on collagen degradation in rats with chronic pancreatitis (CP). METHODS: Rats were injected dibutyltin dichloride (DBTC, 7 mg/kg of body weight) into the right caudal vein to induce CP model. Thirty heallhy male Wistar rats were randomly divided into three groups by a random number table: the control, the model and the treatment groups. Rats of treatment group were administered MXD (10 g/kg of body weight) orally once daily starting from the day post-model establishment. Pancreatic tissues were harvested after 28-day feeding and fibrosis was evaluated by picro-sirius red staining. The contents of collagen type I and III were detected using enzymelinked immunosorbent assay (ELISA), the expression of matrix metalloproteinase 13 (MMP13) and tissue inhibitor of metalloproteinase 1 (TIMP1) was analyzed by Western blot and real-time polymerase chain reaction (PCR). RESULTS: The fibrosis scoring of pancreatic tissues, the concentrations of collagen type I and III, the expression levels of MMP13 and TIMP1 proteins and mRNA in the model group were all increased compared with the control group (P<0.05). After treatment with MXD, the fibrosis scoring of pancreatic tissues, the concentrations of collagen type I and III, the expression levels of MMP13 proteins and mRNA in the teatment group were all decreased compared with the model group (P<0.05), but there were no significant differences in the expression levels of TIMP1 proteins and mRNA (P>0.05). CONCLUSIONS: MXD could promote collagen degradation and reverse pancreatic fibrosis in CP rats via a mechanism involve up-regulation of MMP13 expression.


Assuntos
Medicamentos de Ervas Chinesas/farmacologia , Colágenos Fibrilares/metabolismo , Metaloproteinase 13 da Matriz/metabolismo , Pancreatite Crônica/tratamento farmacológico , Inibidor Tecidual de Metaloproteinase-1/metabolismo , Animais , Modelos Animais de Doenças , Fibrose/tratamento farmacológico , Masculino , Ratos , Ratos Wistar , Regulação para Cima
8.
Biomed Pharmacother ; 118: 109275, 2019 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-31382128

RESUMO

Pancreatic cancer is a digestive tract malignancy that poses a serious threat to human health. Compounds derived from traditional Chinese medicines have been an important source of anticancer drugs and adjuvant agents to regulate the tumor immune microenvironment in patients with pancreatic cancer. In this study, icariin was purified from Herba Epimedii using macropores, and its bioactivity against pancreatic cancer was also investigated. We found that icariin has direct inhibitory and immunomodulatory effects on tumor cells. In vitro experiments showed that icariin can inhibit the migration and proliferation of Panc02 pancreatic cancer cells and induce apoptosis. Our in vivo experiments show that icariin inhibits the development of mouse pancreatic cancer by inhibiting tumor-infiltrating M2 macrophages and polymorphonuclear myeloid-derived suppressor cells (MDSCs) (PMN-MDSCs). In addition, icariin inhibits the polarization of RAW 264.7 cells into M2 macrophages by inhibiting the expression of ARG1 and MRC1 and downregulating the IL4-STAT6 signaling pathway. In conclusion, the inhibitory effect of icariin on pancreatic cancer can not only directly affect tumor cells but also inhibit tumor development by regulating the tumor immune microenvironment.


Assuntos
Medicamentos de Ervas Chinesas/química , Flavonoides/isolamento & purificação , Flavonoides/farmacologia , Resinas Vegetais/química , Microambiente Tumoral/imunologia , Adsorção , Animais , Apoptose/efeitos dos fármacos , Linhagem Celular Tumoral , Movimento Celular/efeitos dos fármacos , Polaridade Celular/efeitos dos fármacos , Proliferação de Células/efeitos dos fármacos , Progressão da Doença , Regulação para Baixo/efeitos dos fármacos , Flavonoides/química , Macrófagos/efeitos dos fármacos , Macrófagos/patologia , Camundongos , Camundongos Endogâmicos C57BL , Células Supressoras Mieloides/patologia , Neutrófilos/patologia , Porosidade , Células RAW 264.7 , Fator de Transcrição STAT6/metabolismo , Transdução de Sinais/efeitos dos fármacos , Baço/patologia , Microambiente Tumoral/efeitos dos fármacos
9.
Chin J Nat Med ; 17(5): 355-362, 2019 May 20.
Artigo em Inglês | MEDLINE | ID: mdl-31171270

RESUMO

Modified Da-chai-hu Decoction (MDD), a traditional Chinese medicinal formulation, which was empirically generated from Da-chai-hu decoction, has been utilized to treat severe acute pancreatitis (SAP) for decades. The aim of the present study was to explore its potential organprotective mechanism in SAP. In the present study, rat SAP model was induced by retrograde injection of 3.5% sodium taurocholate into the biliopancreatic duct, MDD (23.35 g/kg body weight, twelve times the clinical dose) were orally given at 2 h before and 10 h after injection. At 12 h after model induction, blood was taken from vena cava for analysis of amylase, diamine oxidase (DAO), pulmonary surfactant protein-A (SP-A), and C-reactive protein (CRP). Histopathological change of pancreas, ileum and lung was assayed by H&E staining, myeloperoxidase (MPO) activity were determinated using colorimetric assay, and the expressions of occludin and nuclear factor-κB (NF-κB) were detected by real-time RT-PCR and western blot, respectively. In addition, the tissue concentrations of tumor necrosis factor-α (TNF-α), interleukin-1ß (IL-1ß), and monocyte chemoattractant protein-1 (MCP-1) were measured by enzyme-linked immunosorbent assay (ELISA). The results showed that in SAP rats, MDD significantly alleviated histopathological damage, depressed the MPO activity and the concentrations of TNF-α, IL-1ß, and MCP-1 of pancreas, ileum and lung, and reduced the serum levels of amylase [(3283.4 ± 585.5) U·L-1vs (5626.4 ± 795.1)U·L-1], DAO [(1100.1 ± 334.3) U·L-1vs (1666.4 ± 525.3) U·L-1] and CRP [(7.6 ± 1.2) µg·mL-1vs (17.8 ± 3.8) µg·mL-1]. However, the serum SP-A concentration [(106.1 ± 16.6) pg·mL-1vs (90.1 ± 14.9) pg·mL-1] was elevated when treated SAP rats with MDD. Furthermore, MDD increased the occludin expression and reduced the NF-κB expression in pancreas, ileum and lung of SAP rats. Our findings suggested that MDD administration was an effective therapeutic approach for SAP treatment. It could up-regulate occludin expression to protect intercellular tight junction and down-regulate NF-κB expression to inhibit inflammatory reaction of pancreas, ileum and lung.


Assuntos
NF-kappa B/metabolismo , Ocludina/metabolismo , Pancreatite Necrosante Aguda/tratamento farmacológico , Pancreatite Necrosante Aguda/patologia , Extratos Vegetais/uso terapêutico , Animais , Biomarcadores/sangue , Biomarcadores/metabolismo , Bupleurum , Citocinas/metabolismo , Modelos Animais de Doenças , Íleo/efeitos dos fármacos , Íleo/metabolismo , Íleo/patologia , Pulmão/efeitos dos fármacos , Pulmão/metabolismo , Pulmão/patologia , Masculino , NF-kappa B/genética , Ocludina/genética , Pâncreas/efeitos dos fármacos , Pâncreas/metabolismo , Pâncreas/patologia , Pancreatite Necrosante Aguda/induzido quimicamente , Ratos Wistar , Ácido Taurocólico/toxicidade
10.
Am J Chin Med ; 47(3): 675-689, 2019.
Artigo em Inglês | MEDLINE | ID: mdl-30966770

RESUMO

Pancreatic cancer cells overexpress the insulin receptor (IR) and the insulin-like growth factor-1 receptor (IGF1R). Activating these receptors, insulin and insulin-like growth factor-1 increase the growth and glycolysis of pancreatic cancer cells. The high glycolysis in pancreatic cancer cells increases whole-body energy expenditure and is therefore involved in the pathogenesis of cancer cachexia. The antagonism of IR and IGF1R may sabotage pancreatic cancer cells and attenuate cancer cachexia. Previous studies have shown that the intracellular regulating system of IR/IGF1R may be functionally interrelated to another intracellular system whose master regulator is hypoxia-inducible factor-1 (HIF-1). In this study, we investigated how the IR/IGF1R and HIF-1 systems are interrelated in pancreatic cancer cells. We also investigated whether a phytochemical, penta-O-galloyl- ß -D-glucose ( ß -PGG), antagonizes IR/IGF1R, sabotages pancreatic cancer cells and alleviates cancer cachexia. We found in MiaPaCa2 pancreatic cancer cells that IR/IGF1R activation increased both the α -subunit of HIF-1 and caveolin-1. This result suggests that IR/IGF1R, HIF-1 α , and caveolin-1 may constitute a feed-forward loop to mediate the effect of IR/IGF1R activation. ß -PGG inhibited IR/IGF1R activity and decreased glycolytic enzymes in MiaPaCa2 and Panc-1 pancreatic cancer cells. When MiaPaCa2 cells were transplanted in athymic mice, their growth was inhibited by ß -PGG or by a HIF-1 α inhibitor, rhein. ß -PGG and rhein also decreased glycolytic enzymes in the tumor grafts and reduced liver gluconeogenesis, skeletal-muscle proteolysis and fat lipolysis in the tumor carriers. Cancer-induced body-weight loss, however, was prevented by ß -PGG but not rhein. In conclusion, ß -PGG combats pancreatic cancer cells and cures cancer cachexia.


Assuntos
Caquexia/tratamento farmacológico , Taninos Hidrolisáveis/farmacologia , Taninos Hidrolisáveis/uso terapêutico , Neoplasias Pancreáticas/metabolismo , Animais , Caquexia/etiologia , Caveolina 1/metabolismo , Glicólise , Humanos , Subunidade alfa do Fator 1 Induzível por Hipóxia/metabolismo , Masculino , Camundongos Endogâmicos BALB C , Transplante de Neoplasias , Neoplasias Pancreáticas/complicações , Receptor IGF Tipo 1 , Receptor de Insulina/antagonistas & inibidores , Receptor de Insulina/metabolismo , Receptores de Somatomedina/antagonistas & inibidores , Receptores de Somatomedina/metabolismo , Células Tumorais Cultivadas
11.
Sci Rep ; 9(1): 3222, 2019 03 01.
Artigo em Inglês | MEDLINE | ID: mdl-30824734

RESUMO

Sargentodoxa cuneata is a tropical plant used in traditional Chinese medicine to treat intestinal inflammation. In this study, 3, 4-dihydroxyphenylethyl alcohol glycoside (DAG) was purified from the stem of S. cuneata using macroporous resins and its bioactivity was also investigated. The adsorption/desorption of DAG on macroporous resins was investigated systematically. HPD300 resin was selected as the most suitable medium for DAG purification. Further dynamic absorption/desorption experiments on the HPD300 column were conducted to obtain the optimal parameters. To obtain more than 95% DAG, a second stage procedure was developed to purify the DAG using SiliaSphere C18 with 8% v/v acetonitrile through elution at low pressure. Further investigation showed that DAG pretreatment significantly reversed the shortening of colon length, the increase in the disease activity index (DAI) scores and histological damage in the colon. Moreover, DAG greatly increased SOD and GPx activities, significantly decreased MPO and MDA activities and reduced the levels of pro-inflammatory cytokines in the colon. Free radical scavenging activities of DAG were assessed using DPPH, with an IC50 value of 17.03 ug/mL. Additionally, DAG suppressed ROS and proinflammatory cytokine production in LPS-stimulated RAW 264.7 macrophages by suppressing activation of the ERK1/2 and NF-κB pathways. The results were indicative of the antioxidant and anti-inflammatory properties of DAG. When viewed together, these findings indicated that DAG can be used to expand future pharmacological research and to potentially treat colitis.


Assuntos
Colite/prevenção & controle , Glicosídeos/farmacologia , Preparações de Plantas/farmacologia , Ranunculales/química , Animais , Colite/induzido quimicamente , Colite/metabolismo , Citocinas/metabolismo , Sulfato de Dextrana , MAP Quinases Reguladas por Sinal Extracelular/metabolismo , Glutationa Peroxidase/metabolismo , Glicosídeos/isolamento & purificação , Macrófagos/efeitos dos fármacos , Macrófagos/metabolismo , Masculino , Metoxi-Hidroxifenilglicol/análogos & derivados , Metoxi-Hidroxifenilglicol/química , Camundongos , Camundongos Endogâmicos BALB C , NF-kappa B/metabolismo , Preparações de Plantas/isolamento & purificação , Substâncias Protetoras/isolamento & purificação , Substâncias Protetoras/farmacologia , Células RAW 264.7 , Transdução de Sinais/efeitos dos fármacos , Superóxido Dismutase/metabolismo
12.
Chem Biol Interact ; 300: 18-26, 2019 Feb 25.
Artigo em Inglês | MEDLINE | ID: mdl-30611790

RESUMO

Chronic pancreatitis is characterized by pancreatic fibrosis, associated with excessive activation of pancreatic stellate cells (PSCs) and increased expression of transforming growth factor-ß1 (TGF-ß1). Recently, our studies have shown that autophagy inhibitor could inhibit PSCs activation and reduce collagen secretion. Saikosaponin d (SSd), the major active component of bupleurum falcatum (a medicinal plant), has anti-fibrosis effects in liver. However, it is unclear whether SSd has a role in pancreatic fibrosis. This study aimed to investigate the effect of SSd on the autophagy and activation of PSCs in vivo and in vitro. In vivo, a rat chronic pancreatitis model was induced by intravenous injection of dibutyltin dichloride. SSd was administered at a dose of 2.0 mg/kg body weight per day by gavage. After 4 weeks, the pancreas was collected for histological and molecular analysis. In vitro, PSCs were isolated and cultured for treatment with different dosages of SSd. The results showed that SSd inhibited PSCs autophagy and activation while also reducing extracellular matrix (ECM) formation and pancreatic damage. SSd inhibited autophagy through activating the PI3K/Akt/mTOR pathway. SSd also promoted degradation of ECM with an increasing ratio of MMPs/TIMPs and suppressed the TGF-ß1/Smads pathway. From these results, we concluded that SSd prevents pancreatic fibrosis by reducing autophagy of PSCs through PI3K/Akt/mTOR pathway, which has crosstalk with the TGF-ß1/Smads pathway.


Assuntos
Autofagia/efeitos dos fármacos , Ácido Oleanólico/análogos & derivados , Pâncreas/efeitos dos fármacos , Saponinas/farmacologia , Transdução de Sinais/efeitos dos fármacos , Animais , Células Cultivadas , Matriz Extracelular/metabolismo , Fibrose , Masculino , Metaloproteinases da Matriz/metabolismo , Ácido Oleanólico/farmacologia , Ácido Oleanólico/uso terapêutico , Compostos Orgânicos de Estanho/toxicidade , Pâncreas/metabolismo , Pâncreas/patologia , Células Estreladas do Pâncreas/citologia , Células Estreladas do Pâncreas/efeitos dos fármacos , Células Estreladas do Pâncreas/metabolismo , Pancreatite Crônica/induzido quimicamente , Pancreatite Crônica/patologia , Pancreatite Crônica/prevenção & controle , Pancreatite Crônica/veterinária , Fosfatidilinositol 3-Quinases/metabolismo , Proteínas Proto-Oncogênicas c-akt/metabolismo , Ratos , Ratos Wistar , Saponinas/uso terapêutico , Proteínas Smad/metabolismo , Serina-Treonina Quinases TOR/metabolismo , Fator de Crescimento Transformador beta1/metabolismo
13.
J Chin Med Assoc ; 81(5): 437-443, 2018 May.
Artigo em Inglês | MEDLINE | ID: mdl-29129515

RESUMO

BACKGROUND: The pathogenesis of chronic pancreatitis (CP) is a complex process of interaction between tissue injury and repair, which involves microcirculatory disturbance. Amygdalin, an effective component extracted from Semen Persicae (a kind of Chinese herbal medicine), can decrease blood viscosity and improve microcirculation. In this study, we investigated the therapeutic effects of amygdalin on pancreatic fibrosis in rats with CP. METHODS: The rat CP model was induced by injecting dibutyltin dichloride (DBTC) into the right caudal vein. Amygdalin was administrated via the penile vein at a dose of 10 mg/(kg d) from the next day, after the induction of CP, once a day for the previous 3 days, and then once every 2 days, until the end of the experiment. Body weight was observed every 7 days. Pancreatic blood flow and histopathological changes were assessed at 28 days. The activation of pancreatic stellate cells (PSCs) was estimated by the expression of α-smooth muscle actin (α-SMA). At the same time, the expression of platelet-derived growth factor-BB (PDGF-BB), transforming growth factor ß-1 (TGFß-1), endothelin-1 (ET-1), and calcitonin gene-related peptide (CGRP) of pancreatic tissues were detected. RESULTS: Treatment of CP rats with amygdalin improved body weight and pancreatic blood flow, as well as alleviated pancreatic fibrosis and acinar destruction, accompanied by the down-regulation of the expressions of α-SMA, PDGF-BB, TGFß-1, and ET-1, and the up-regulation of the CGRP's expression. CONCLUSION: Amygdalin could reduce the production of pro-fibrotic cytokines, inhibit the activation of PSCs, and attenuate pancreatic fibrosis in a rat with CP. The mechanism probably includes improving microcirculatory disturbance by regulating the production of ET-1 and CGRP.


Assuntos
Amigdalina/farmacologia , Peptídeo Relacionado com Gene de Calcitonina/genética , Endotelina-1/genética , Regulação da Expressão Gênica/efeitos dos fármacos , Microcirculação/efeitos dos fármacos , Pâncreas/efeitos dos fármacos , Pancreatite Crônica/tratamento farmacológico , Actinas/genética , Amigdalina/uso terapêutico , Animais , Becaplermina/genética , Fibrose , Masculino , Pâncreas/irrigação sanguínea , Pâncreas/patologia , Células Estreladas do Pâncreas/fisiologia , Ratos , Ratos Wistar
15.
J Environ Manage ; 153: 33-9, 2015 Apr 15.
Artigo em Inglês | MEDLINE | ID: mdl-25646674

RESUMO

Three new baffle flow constructed wetlands (CWs), namely the baffle horizontal flow CW (Z1), baffle vertical flow CW (Z2) and baffle hybrid flow CW (Z3), along with one traditional horizontal subsurface flow CW (Z4) were designed to test the removal efficiency of nitrogen (N) and phosphorus (P) from the septic tank effluent under varying hydraulic retention times (HRTs). Results showed that the optimal HRT was two days for maximal removal of N and P from the septic tank effluent among the four CWs. At this HRT, the Z1, Z2, Z3 and Z4 CWs removed, respectively, 49.93, 58.50, 46.01 and 44.44% of TN as well as 87.82, 93.23, 95.97 and 91.30% of TP. Our study further revealed that the Z3 CW was the best design for overall removal of N and P from the septic tank effluent due to its hybrid flow directions with better oxygen supply inside the CW system.


Assuntos
Esgotos/análise , Eliminação de Resíduos Líquidos/métodos , Poluentes Químicos da Água/metabolismo , Áreas Alagadas , Zingiberales/metabolismo , Nitrogênio/metabolismo , Fósforo/metabolismo
16.
Environ Monit Assess ; 186(9): 5353-62, 2014 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-24802588

RESUMO

Groundwater is connected to the landscape above and is thus affected by the overlaying land uses. This study evaluated the impacts of land uses upon groundwater quality using trilinear analysis. Trilinear analysis is a display of experimental data in a triangular graph. Groundwater quality data collected from agricultural, septic tank, forest, and wastewater land uses for a 6-year period were used for the analysis. Results showed that among the three nitrogen species (i.e., nitrate and nitrite (NO(x)), dissolved organic nitrogen (DON), and total organic nitrogen (TON)), NO(x) had a high percentage and was a dominant species in the groundwater beneath the septic tank lands, whereas TON was a major species in groundwater beneath the forest lands. Among the three phosphorus species, namely the particulate phosphorus (PP), dissolved ortho phosphorus (PO4(3-)) and dissolved organic phosphorus (DOP), there was a high percentage of PP in the groundwater beneath the septic tank, forest, and agricultural lands. In general, Ca was a dominant cation in the groundwater beneath the septic tank lands, whereas Na was a dominant cation in the groundwater beneath the forest lands. For the three major anions (i.e., F(-), Cl(-), and SO4(2-)), F(-) accounted for <1% of the total anions in the groundwater beneath the forest, wastewater, and agricultural lands. Impacts of land uses on groundwater Cd and Cr distributions were not profound. This study suggests that trilinear analysis is a useful technique to characterize the relationship between land use and groundwater quality.


Assuntos
Monitoramento Ambiental/métodos , Água Subterrânea/química , Poluentes Químicos da Água/análise , Agricultura/estatística & dados numéricos , Agricultura Florestal/estatística & dados numéricos , Nitratos/análise , Nitrogênio/análise , Fósforo/análise , Árvores , Urbanização/tendências
17.
Bioresour Technol ; 146: 656-662, 2013 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-23982062

RESUMO

In this study, the enzyme activities and their relationships to domestic wastewater purification are investigated in four different types of subsurface-flow constructed wetlands (CWs), namely the traditional horizontal subsurface-flow, horizontal baffled subsurface-flow, vertical baffled subsurface-flow, and composite baffled subsurface-flow CWs. Results showed that the urease activity in the composite baffled subsurface-flow CW was significantly higher than in the other three CWs, while the phosphatase activity in the vertical baffled subsurface-flow CW were higher than in the other three CWs. There were significant and very significant correlations between the activities of urease and the removal rates of TN and NH4(+)-N for the horizontal baffled flow, horizontal subsurface flow, and composite baffled subsurface flow CWs. This study suggests that the activity of urease in the root zones of those three CWs is an important indicator for N purification from wastewaters.


Assuntos
Biodegradação Ambiental , Enzimas/química , Áreas Alagadas , Amônia/química , Nitrogênio/análise , Nitrogênio/química , Nitrogênio/isolamento & purificação , Fósforo/análise , Fósforo/química , Raízes de Plantas/metabolismo , Análise de Regressão , Fatores de Tempo , Urease/metabolismo , Eliminação de Resíduos Líquidos/métodos , Águas Residuárias , Água/química , Poluentes Químicos da Água/isolamento & purificação , Purificação da Água/métodos , Zingiberales/metabolismo
18.
Int J Phytoremediation ; 13(7): 692-701, 2011 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-21972496

RESUMO

Vertical-flow constructed wetland (VFCW) is an effective alternative for removal of nutrients, heavy metals, and organic pollutants from wastewaters. This study investigated the uptake and removal of total phosphorus (TP) by Cyperus alternifolius from domestic wastewaters in the simulated VFCWs, The total of eight simulated VFCW treatments, including two different substrates, two different wet-to-dry ratios, and with and without C. alternifolius species (2 x 2 x 2 = 8), were utilized for an operation period of two years in this study. Results show that about 1.1 to 1.4 times more TP was removed from the influent with the presence of C. alternifolius as compared to without this plant species. A linear correlation existed between the aboveground biomass and its TP content. An increase in total biomass by 1000 g would result in an increase in TP accumulation in the aboveground biomass by 4.9 g. Large amounts of TP were removed by the substrate adsorption as compared to those by the aboveground biomass. Results suggest that, although substrate adsorption played a major role in TP removal, C. alternifolius uptake was an alternative pathway for further removal of TP from wastewaters in the VFCWs.


Assuntos
Cyperus/metabolismo , Fósforo/metabolismo , Eliminação de Resíduos Líquidos/métodos , Poluentes Químicos da Água/metabolismo , Purificação da Água/métodos , Áreas Alagadas , Adsorção , Biodegradação Ambiental , Biomassa , China , Componentes Aéreos da Planta/metabolismo , Estações do Ano , Fatores de Tempo
19.
Arch Environ Contam Toxicol ; 55(2): 210-7, 2008 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-18175159

RESUMO

Constructed wetland (CW) is a promising technique for removal of pollutants from wastewater and agricultural runoff. The performance of a CW to remove pollutants, however, hinges on the use of suitable substrate materials. This study examined the physicochemical properties and phosphorus (P) sorption capacities of nine different CW substrate materials using both batch experiments and the Freundlich as well as the Langmuir isotherm. The nine substrate materials used in this study were turf, topsoil, gravel, midsized sand (MSS), blast furnace slag (BFS), coal burn slag (CBS), blast furnace artificial slag (BFAS), coal burn artificial slag (CBAS), and midsized artificial sand (MSAS). Experimental data showed that sorption of P increased with initial solution P concentrations for all nine substrate materials. The maximum P sorption capacity of the substrate materials estimated by Langmuir isotherm was in the following order: turf (4243 mg/kg substrate) > BFAS (2116 mg/kg substrate) > BFS (1598 mg/kg substrate) > CBS (1449 mg/kg substrate) > top soil (1396 mg/kg substrate) > CBAS (1194 mg/kg substrate) > MSAS (519 mg/kg substrate) > gravel (494 mg/kg substrate) > MSS (403 mg/kg substrate). The specific gravity of eight substrate materials (except gravel) had very significant negative correlations with the P sorption, whereas the particle diameter of D(60) and uniformity coefficient (K(60)) had positive correlations with the P sorption. The cation exchange capacity, organic matter, available ferrous, and exchangeable aluminum of the eight substrate materials also had very significant positive correlations with the P sorption, while the pH of the substrate materials showed a very significant negative correlation with the P sorption. Our study further suggests that turf and CBAS are the two relatively ideal substrate materials suitable for removal of P from a CW system.


Assuntos
Recuperação e Remediação Ambiental , Fósforo/química , Áreas Alagadas , Resíduos Industriais , Cinética , Eliminação de Resíduos , Solo , Poluição da Água
20.
J Environ Sci (China) ; 18(4): 665-9, 2006.
Artigo em Inglês | MEDLINE | ID: mdl-17078543

RESUMO

The integrated wetland systems were constructed by combining horizontal-flow and vertical-flow bed, and their purification efficiencies for septic tank effluent were detected when the hydraulic retention time (HRT) was 1 d, 3 d, 5 d under different seasons. The results showed that the removal efficiencies of the organics, phosphorus were steady in the hybrid systems, but the removal efficiency of total nitrogen was not steady due to high total nitrogen concentration in the septic tank effluent. The average removal rates of COD (chemical oxygen demand) were 89%, 87%, 83%, and 86% in summer, autumn, winter and spring, respectively, and it was up to 88%, 85%, 73%, and 74% for BOD5 (5 d biochemical oxygen demand) removal rate in four seasons. The average removal rates of TP (total phosphorous) could reach up to 97%, 98%, 95%, 98% in four seasons, but the removal rate of TN (total nitrogen) was very low. The results of this study also indicated that the capability of purification was the worst in winter. Cultivating with plants could improve the treated effluent quality from the hybrid systems. The results of the operation of the horizontal-flow and vertical-flow cells (hybrid systems) showed that the removal efficiencies of the organics, TP and TN in horizontal-flow and vertical-flow cells were improved significantly with the extension of HRT under the same season. The removal rate of 3 d HRT was obviously higher than that of 1 d HRT, and the removal rate of 5 d HRT was better than that of 3 d HRT, but the removal efficiency was not very obvious with the increment of HRT. Therefore, 3 d HRT might be recommended in the actual operation of the hybrid systems for economic and technical reasons.


Assuntos
Biodegradação Ambiental , Esgotos , Eliminação de Resíduos Líquidos/métodos , Purificação da Água/métodos , Nitrogênio/análise , Nitrogênio/metabolismo , Oxigênio/metabolismo , Fósforo/metabolismo , Estações do Ano , Fatores de Tempo , Movimentos da Água
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