To study the effects of oestrogcn on ischemia-induced neurogenesis in the hippocampal dentate gyms, thirty-two adult male rats were randomly divided into four groups: the control surgery group with eestrogen administ...To study the effects of oestrogcn on ischemia-induced neurogenesis in the hippocampal dentate gyms, thirty-two adult male rats were randomly divided into four groups: the control surgery group with eestrogen administration (SE), the control surgery group with normal saline administration (SN), the middle cerebral artery occlusion (MCAO) group with oestrogen administration (ME) and the MCAO group with normal saline administration (MN). The MCAO rats were occluded for 90 rain by an intraluminal filament and then recirculated. After 1, 3, 12, 24 and 28 h of MCAO, the rats of the four groups were killed to investigate the infarct volume, apoptosis and neurogenesis. The cerebral infarct volume in the ME group was significantly smaller than that of the MN group (P 〈 0.05). No significant cell loss was seen in the dentate gyms. Cerebral ischemia led to increased neurogenosis, which is independent of cell death in the ipsilateral dentate gyrus(P 〈 0.05). BrdU-pesitive cells in the ipsilateral dentate gyms of the ME group were significantly increased when compared with those of the MN group(P 〈 0.05). In the SE group, BrdU-positive cells in both the ipsilateral and contralateral dentate gyms, were increased when compared with those of the SN group ( P 〈 0.05 ). We concluded that ocstregen plays an important role in neurogenesis, which is independent of ischemia-induced by MCAO in the hippocampal dentate gyms of rats.展开更多
Programmed cell death (PCD) during secondary xylem differentiation in Eucommia ulmoides Oliv. was examined using electron microscopy and by investigation of DNA fragmentation and degradation of caspase-like proteases ...Programmed cell death (PCD) during secondary xylem differentiation in Eucommia ulmoides Oliv. was examined using electron microscopy and by investigation of DNA fragmentation and degradation of caspase-like proteases (CLPs). DNA ladders were detected in developing secondary xylem by gel electrophoresis. DNA fragmentation was further confirmed by using the TdT-mediated dUTP nick-end labeling (TUNEL) method. Western blotting analysis showed that CLPs (caspase-8- and caspase-3-like proteases) and PARP (poly (ADP-ribose) polymerase) were degraded during secondary xylem differentiation. The results thus indicated that secondary xylem differentiation in E ulmoides was a typical process of PCD and the degradation of CLPs might be a constitutive PCD event during secondary xylem differentiation.展开更多
Programmed cell death (PCD) of the nucellar cells at the micropylar end is involved in pollen chamber morphogenesis in Ginkgo biloba L. A development-course observation of the morphological changes in the nucellar cel...Programmed cell death (PCD) of the nucellar cells at the micropylar end is involved in pollen chamber morphogenesis in Ginkgo biloba L. A development-course observation of the morphological changes in the nucellar cells undergoing PCD to form pollen chamber was performed. During the PCD, the nucellar cells degraded their cellular components through an orderly progression. Through the vactiolation, the cytosol was engulfed by the enlarging vacuole, leaving out various organelles, which remained morphologically integrated. As the vacuolation continued, the vacuole collapsed with the breakage of the tonoplast and the cytosol disappeared completely. Organelles were subsequently destroyed. Ultimately, nucellar cells digested away all of their cytoplasm, leaving with cell walls. They became collapsed as the nucellus developed. Intracellular membranes were strikingly changed, playing a role in leading to cell death. Some of these noticeable changes were the appearance of multivesicular body, multicycle-like membranes, membrane-bounded bodies containing some organelles, tonoplast rupture and numerous vesicles. The dehiscence of the apical epidermis, resulting in the opening, appeared to have followed two different pathways with one involving a specific epidermal cell autolysis and the other by detachment from middle lamella of two neighboring epidermal cells without cell autolysis. The specific epidermal cells had been dead prior to the dehiscence of the apical epidermis, which marked the sites of the dehiscence followed. In view of the changes in the cellular morphology, a process of nucellar cell PCD in the course of the pollen chamber formation was demonstrated.展开更多
Upon encountering the antigen (Ag), the immune system can either develop a specific immune response or enter a specific state of unresponsiveness, tolerance. The response of B cells to their specific Ag can be activat...Upon encountering the antigen (Ag), the immune system can either develop a specific immune response or enter a specific state of unresponsiveness, tolerance. The response of B cells to their specific Ag can be activation and proliferation, leading to the immune response, or anergy and activation-induced cell death (AICD), leading to tolerance. AICD in B lymphocytes is a highly regulated event initiated by crosslinking of the B cell receptor (BCR). BCR engagement initiates several signaling events such as activation of PLCr, Ras, and PI3K, which generally speaking, lead to survival. However, in the absence of survival signals (CD40 or IL-4R engagement), BCR crosslinking can also promote apoptotic signal transduction pathways such as activation of effector caspases, expression of pro-apoptotic genes, and inhibition of pro-survival genes. The complex interplay between survival and death signals determines the B cell fate and, consequently, the immune response.展开更多
Cyanea nozakii Kishinouye (C. nozakii), a giant cnidarian of the class Scyphomedusae, order Semaeostomeae and family Cyaneidae, is widely distributed in the East China Sea, the Yellow Sea and the Bohai Sea, and is a...Cyanea nozakii Kishinouye (C. nozakii), a giant cnidarian of the class Scyphomedusae, order Semaeostomeae and family Cyaneidae, is widely distributed in the East China Sea, the Yellow Sea and the Bohai Sea, and is abundant from late summer to early autumn. Venom produced by C. nozakii during mass agglomerations can contaminate seawater resulting in death of the halobios and seriously damage commercial fisheries. Swimmers and fishermen commonly suffer painful stings from this j ellyfish, resulting in local edema, tingling, breathing difficulties, depressed blood pressure and even death. Such effects arise from the complex mixture of biologically active molecules that make up jellyfish venom. In the present study, the hemolytic activity of venom from tentacles of C. nozakii and factors affecting its activity were assayed. The HUso (defined as the amount of protein required to lyse 50% of erythrocytes) of the venom against dove and chicken erythrocytes was 34 and 59 gg/mL, respectively. Carboxylmethyl chitosan and glycerol could increase hemolytic activity at concentrations greater than 0.06% and 0.2 mol/L, respectively.展开更多
Gastric cancer is the second most common cancer worldwide and the second most common cause of cancer-related deaths. Despite complete resection of gastric cancer and lymph node dissection, as well as improvements in c...Gastric cancer is the second most common cancer worldwide and the second most common cause of cancer-related deaths. Despite complete resection of gastric cancer and lymph node dissection, as well as improvements in chemotherapy and radiotherapy, there are still 700 000 gastric cancer-related deaths per year worldwide and more than 80% of patients with advanced gastric cancer die of the disease or recurrent disease within 1 year after diagnosis. None of the treatment modalities we have been applying today can influence the overall survival rates:at present, the overall 5-year relative survival rate for gastric cancer is about 28%. Cellular metaplasia due to chronic inflammation, injury and repair are the most documented processes for neoplasia. It appears that chronic inflammation stimulates tumor development and plays a critical role in initiating, sustaining and advancing tumor growth. It is also evident that not all inflammation is tumorigenic. Additional mutations can be acquired, and this leads to the cancer cell gaining a further growth advantage and acquiring a more malignant phenotype. Intestinalization of gastric units, which is called "intestinal metaplasia"; phenotypic antralization of fundic units, which is called "spasmolytic polypeptide-expressing metaplasia"; and the development directly from the stem/progenitor cellzone are three pathways that have been described for gastric carcinogenesis. Also, an important factor for the development of gastrointestinal cancers is peritumoral stroma. However, the initiating cellular event in gastric metaplasia is still controversial. Understanding gastric carcinogenesis and its precursor lesions has been under intense investigation, and our paper attempts to highlight recent progress in this field of cancer research.展开更多
Objective To investigate the expression of programmed cell death 5 (PDCD5) in tissues of normal human prostate (NP), benign prostatic hyperplasia (BPH), and prostate cancer (PCa) in order to assess the clinica...Objective To investigate the expression of programmed cell death 5 (PDCD5) in tissues of normal human prostate (NP), benign prostatic hyperplasia (BPH), and prostate cancer (PCa) in order to assess the clinical role of PDCD5 in PCa. Methods PDCD5 expression was determined by EnVision immunohistochemical staining in forma-lin-fixed and paraffin-embedded specimens obtained from 12 subjects with NP, 22 with BPH, and 22 with PCa. In addition, PCa cases were classified as low/middle-risk (Gleason sumS7) and high-risk (Gleason sum〉7) on the basis of Gleason grade. Positive expression rates and intensity of PDCD5 protein were observed under light microscope and analyzed with computer imaging technique. Expression of PDCD5 was compared among different prostatic tissues. Results The expression of PDCD5 was significantly lower in tissue of PCa than in tissues of NP and BPH (P〈0.01). However, there was no significant difference in PDCD5 expression between tissues of NP and BPH. In addition, the expression of PDCD5 was further downregulated with the increase of Gleason sum in PCa. Conclusions By downregulating apoptosis, low PDCD5 expression may play an important role in the occurrence and development of PCa. PDCD5 is supposed to have a potential clinical value to be a new predictor of progression and target of gene therapy in PCa.展开更多
Cancer is one of the most serious issues in human life.Blocking programmed cell death protein 1 and programmed death ligand-1(PD-L1)pathway is one of the great innovations in the last few years,a few numbers of inhibi...Cancer is one of the most serious issues in human life.Blocking programmed cell death protein 1 and programmed death ligand-1(PD-L1)pathway is one of the great innovations in the last few years,a few numbers of inhibitors can be able to block it.(2-Methyl-3-biphenylyl)methanol derivative is one of them.Here,the quantitative structure-activity relationship(QSAR)established twenty(2-methyl-3-biphenylyl)methanol derivatives as the programmed death ligand-1 inhibitors.Density functional theory at the B3LPY/6-31+G(d,p)level was employed to study the chemical structure and properties of the chosen compounds.Highest occupied molecular orbital energy EHOMO,lowest unoccupied molecular orbital energy ELUMO,total energy ET,dipole moment DM,absolute hardnessη,absolute electronegativityχ,softness S,electrophilicityω,energy gap?E,etc.,were observed and determined.Principal component analysis(PCA),multiple linear regression(MLR)and multiple nonlinear regression(MNLR)analysis were carried out to establish the QSAR.The proposed quantitative models and interpreted outcomes of the compounds were based on statistical analysis.Statistical results of MLR and MNLR exhibited the coefficient R^2 was 0.661 and 0.758,respectively.Leave-one-out cross-validation,r_m^2 metric,r_m^2 test,and"Golbraikh&Tropsha’s criteria"analyses were applied for the validation of MLR and MNLR,which indicate two models are statistically significant and well stable with data variation in the external validation towards PD-L1.The obtained results showed that the MNLR model predicts the bioactivity more accurately than MLR,and it may be helpful and supporting for evaluation of the biological activity of PD-L1 inhibitors.展开更多
AIM: To investigate the effects of 5-Fluorouracil (5-FU) on modulation of pro-inflammatory and anti-inflammatory cytokines in acute pancreatitis and the mechanism of it in the treatment of acute pancreatitis. METH...AIM: To investigate the effects of 5-Fluorouracil (5-FU) on modulation of pro-inflammatory and anti-inflammatory cytokines in acute pancreatitis and the mechanism of it in the treatment of acute pancreatitis. METHODS: Male Sprague Dawley rats were assigned to 3 Groups: Group A, sham operated rats as controls (n = 7); Group B, acute pancreatitis induced by ductal injection with 5% sodium cholate at a volume of 1.0 mL/kg without any other treatment; Group C, after the pancreatitis was induced as in Group B, the rats were injected intravenously with 5-FU 40 mg/kg. The animals in Groups B and C were killed at 2, 6 and 24 h after operation (n = 7), and blood samples were taken for measurement of tumor necrosis factor-α (TNF-α), interleukin-1 (IL-1), interleukin-6 (IL-6) (by bioassay), and interleukin-10 (IL-10), transforming growth factor-β (TGF-β) (by ELISA). The wet weight of pancreatic tissue, serum amylase levels and white blood cells were also measured. RESULTS: Four rats in Group B and one in Group C died after pancreatitis was induced. Both pro-inflammatory cytokines (TNF-α, IL-1, IL-6) at the 2 and 6 h period and the anti-inflammatory cytokines (IL-10, TGF-β) at 24 h increased significantly (P 〈 0.05) in rats of Group B. After treatment with 5-FU, TNF-α, IL-1, and IL-6 in serum of rats of Group C were inhibited at 2 and 6 h after operation (P 〈 0.05), and IL-IO, TGF-13 were inhibited at 24 h compared to Group B (P 〈 0.05). Obvious improvements in the severity of the acute pancreatitis, including the amylase levels, wet weight of pancreatic tissue and neutrophil counts, were also observed after treatment with 5-FU. CONCLUSION: 5-FU is an anti-metabolic and immunosuppressive agent which can minimize the abnormal immune o/tokine response and relieve the pathophysiological disorders associated with experimental acute pancreatitis.展开更多
文摘To study the effects of oestrogcn on ischemia-induced neurogenesis in the hippocampal dentate gyms, thirty-two adult male rats were randomly divided into four groups: the control surgery group with eestrogen administration (SE), the control surgery group with normal saline administration (SN), the middle cerebral artery occlusion (MCAO) group with oestrogen administration (ME) and the MCAO group with normal saline administration (MN). The MCAO rats were occluded for 90 rain by an intraluminal filament and then recirculated. After 1, 3, 12, 24 and 28 h of MCAO, the rats of the four groups were killed to investigate the infarct volume, apoptosis and neurogenesis. The cerebral infarct volume in the ME group was significantly smaller than that of the MN group (P 〈 0.05). No significant cell loss was seen in the dentate gyms. Cerebral ischemia led to increased neurogenosis, which is independent of cell death in the ipsilateral dentate gyrus(P 〈 0.05). BrdU-pesitive cells in the ipsilateral dentate gyms of the ME group were significantly increased when compared with those of the MN group(P 〈 0.05). In the SE group, BrdU-positive cells in both the ipsilateral and contralateral dentate gyms, were increased when compared with those of the SN group ( P 〈 0.05 ). We concluded that ocstregen plays an important role in neurogenesis, which is independent of ischemia-induced by MCAO in the hippocampal dentate gyms of rats.
文摘Programmed cell death (PCD) during secondary xylem differentiation in Eucommia ulmoides Oliv. was examined using electron microscopy and by investigation of DNA fragmentation and degradation of caspase-like proteases (CLPs). DNA ladders were detected in developing secondary xylem by gel electrophoresis. DNA fragmentation was further confirmed by using the TdT-mediated dUTP nick-end labeling (TUNEL) method. Western blotting analysis showed that CLPs (caspase-8- and caspase-3-like proteases) and PARP (poly (ADP-ribose) polymerase) were degraded during secondary xylem differentiation. The results thus indicated that secondary xylem differentiation in E ulmoides was a typical process of PCD and the degradation of CLPs might be a constitutive PCD event during secondary xylem differentiation.
文摘Programmed cell death (PCD) of the nucellar cells at the micropylar end is involved in pollen chamber morphogenesis in Ginkgo biloba L. A development-course observation of the morphological changes in the nucellar cells undergoing PCD to form pollen chamber was performed. During the PCD, the nucellar cells degraded their cellular components through an orderly progression. Through the vactiolation, the cytosol was engulfed by the enlarging vacuole, leaving out various organelles, which remained morphologically integrated. As the vacuolation continued, the vacuole collapsed with the breakage of the tonoplast and the cytosol disappeared completely. Organelles were subsequently destroyed. Ultimately, nucellar cells digested away all of their cytoplasm, leaving with cell walls. They became collapsed as the nucellus developed. Intracellular membranes were strikingly changed, playing a role in leading to cell death. Some of these noticeable changes were the appearance of multivesicular body, multicycle-like membranes, membrane-bounded bodies containing some organelles, tonoplast rupture and numerous vesicles. The dehiscence of the apical epidermis, resulting in the opening, appeared to have followed two different pathways with one involving a specific epidermal cell autolysis and the other by detachment from middle lamella of two neighboring epidermal cells without cell autolysis. The specific epidermal cells had been dead prior to the dehiscence of the apical epidermis, which marked the sites of the dehiscence followed. In view of the changes in the cellular morphology, a process of nucellar cell PCD in the course of the pollen chamber formation was demonstrated.
文摘Upon encountering the antigen (Ag), the immune system can either develop a specific immune response or enter a specific state of unresponsiveness, tolerance. The response of B cells to their specific Ag can be activation and proliferation, leading to the immune response, or anergy and activation-induced cell death (AICD), leading to tolerance. AICD in B lymphocytes is a highly regulated event initiated by crosslinking of the B cell receptor (BCR). BCR engagement initiates several signaling events such as activation of PLCr, Ras, and PI3K, which generally speaking, lead to survival. However, in the absence of survival signals (CD40 or IL-4R engagement), BCR crosslinking can also promote apoptotic signal transduction pathways such as activation of effector caspases, expression of pro-apoptotic genes, and inhibition of pro-survival genes. The complex interplay between survival and death signals determines the B cell fate and, consequently, the immune response.
基金Supported by the National Natural Science Foundation of China(Nos.41376004,41406152)the Key R&D program of Shandong Province(Nos.2015GSF115022,2015GSF115034)the China Postdoctoral Science Foundation(No.2013M531654)
文摘Cyanea nozakii Kishinouye (C. nozakii), a giant cnidarian of the class Scyphomedusae, order Semaeostomeae and family Cyaneidae, is widely distributed in the East China Sea, the Yellow Sea and the Bohai Sea, and is abundant from late summer to early autumn. Venom produced by C. nozakii during mass agglomerations can contaminate seawater resulting in death of the halobios and seriously damage commercial fisheries. Swimmers and fishermen commonly suffer painful stings from this j ellyfish, resulting in local edema, tingling, breathing difficulties, depressed blood pressure and even death. Such effects arise from the complex mixture of biologically active molecules that make up jellyfish venom. In the present study, the hemolytic activity of venom from tentacles of C. nozakii and factors affecting its activity were assayed. The HUso (defined as the amount of protein required to lyse 50% of erythrocytes) of the venom against dove and chicken erythrocytes was 34 and 59 gg/mL, respectively. Carboxylmethyl chitosan and glycerol could increase hemolytic activity at concentrations greater than 0.06% and 0.2 mol/L, respectively.
文摘Gastric cancer is the second most common cancer worldwide and the second most common cause of cancer-related deaths. Despite complete resection of gastric cancer and lymph node dissection, as well as improvements in chemotherapy and radiotherapy, there are still 700 000 gastric cancer-related deaths per year worldwide and more than 80% of patients with advanced gastric cancer die of the disease or recurrent disease within 1 year after diagnosis. None of the treatment modalities we have been applying today can influence the overall survival rates:at present, the overall 5-year relative survival rate for gastric cancer is about 28%. Cellular metaplasia due to chronic inflammation, injury and repair are the most documented processes for neoplasia. It appears that chronic inflammation stimulates tumor development and plays a critical role in initiating, sustaining and advancing tumor growth. It is also evident that not all inflammation is tumorigenic. Additional mutations can be acquired, and this leads to the cancer cell gaining a further growth advantage and acquiring a more malignant phenotype. Intestinalization of gastric units, which is called "intestinal metaplasia"; phenotypic antralization of fundic units, which is called "spasmolytic polypeptide-expressing metaplasia"; and the development directly from the stem/progenitor cellzone are three pathways that have been described for gastric carcinogenesis. Also, an important factor for the development of gastrointestinal cancers is peritumoral stroma. However, the initiating cellular event in gastric metaplasia is still controversial. Understanding gastric carcinogenesis and its precursor lesions has been under intense investigation, and our paper attempts to highlight recent progress in this field of cancer research.
文摘Objective To investigate the expression of programmed cell death 5 (PDCD5) in tissues of normal human prostate (NP), benign prostatic hyperplasia (BPH), and prostate cancer (PCa) in order to assess the clinical role of PDCD5 in PCa. Methods PDCD5 expression was determined by EnVision immunohistochemical staining in forma-lin-fixed and paraffin-embedded specimens obtained from 12 subjects with NP, 22 with BPH, and 22 with PCa. In addition, PCa cases were classified as low/middle-risk (Gleason sumS7) and high-risk (Gleason sum〉7) on the basis of Gleason grade. Positive expression rates and intensity of PDCD5 protein were observed under light microscope and analyzed with computer imaging technique. Expression of PDCD5 was compared among different prostatic tissues. Results The expression of PDCD5 was significantly lower in tissue of PCa than in tissues of NP and BPH (P〈0.01). However, there was no significant difference in PDCD5 expression between tissues of NP and BPH. In addition, the expression of PDCD5 was further downregulated with the increase of Gleason sum in PCa. Conclusions By downregulating apoptosis, low PDCD5 expression may play an important role in the occurrence and development of PCa. PDCD5 is supposed to have a potential clinical value to be a new predictor of progression and target of gene therapy in PCa.
基金the Natural Science Foundation of Jiangsu Province(BK20181128)333 Project of Jiangsu Province(BRA2016518)Jiangsu Provincial Medical Youth Talent(QNRC2016626)。
文摘Cancer is one of the most serious issues in human life.Blocking programmed cell death protein 1 and programmed death ligand-1(PD-L1)pathway is one of the great innovations in the last few years,a few numbers of inhibitors can be able to block it.(2-Methyl-3-biphenylyl)methanol derivative is one of them.Here,the quantitative structure-activity relationship(QSAR)established twenty(2-methyl-3-biphenylyl)methanol derivatives as the programmed death ligand-1 inhibitors.Density functional theory at the B3LPY/6-31+G(d,p)level was employed to study the chemical structure and properties of the chosen compounds.Highest occupied molecular orbital energy EHOMO,lowest unoccupied molecular orbital energy ELUMO,total energy ET,dipole moment DM,absolute hardnessη,absolute electronegativityχ,softness S,electrophilicityω,energy gap?E,etc.,were observed and determined.Principal component analysis(PCA),multiple linear regression(MLR)and multiple nonlinear regression(MNLR)analysis were carried out to establish the QSAR.The proposed quantitative models and interpreted outcomes of the compounds were based on statistical analysis.Statistical results of MLR and MNLR exhibited the coefficient R^2 was 0.661 and 0.758,respectively.Leave-one-out cross-validation,r_m^2 metric,r_m^2 test,and"Golbraikh&Tropsha’s criteria"analyses were applied for the validation of MLR and MNLR,which indicate two models are statistically significant and well stable with data variation in the external validation towards PD-L1.The obtained results showed that the MNLR model predicts the bioactivity more accurately than MLR,and it may be helpful and supporting for evaluation of the biological activity of PD-L1 inhibitors.
文摘AIM: To investigate the effects of 5-Fluorouracil (5-FU) on modulation of pro-inflammatory and anti-inflammatory cytokines in acute pancreatitis and the mechanism of it in the treatment of acute pancreatitis. METHODS: Male Sprague Dawley rats were assigned to 3 Groups: Group A, sham operated rats as controls (n = 7); Group B, acute pancreatitis induced by ductal injection with 5% sodium cholate at a volume of 1.0 mL/kg without any other treatment; Group C, after the pancreatitis was induced as in Group B, the rats were injected intravenously with 5-FU 40 mg/kg. The animals in Groups B and C were killed at 2, 6 and 24 h after operation (n = 7), and blood samples were taken for measurement of tumor necrosis factor-α (TNF-α), interleukin-1 (IL-1), interleukin-6 (IL-6) (by bioassay), and interleukin-10 (IL-10), transforming growth factor-β (TGF-β) (by ELISA). The wet weight of pancreatic tissue, serum amylase levels and white blood cells were also measured. RESULTS: Four rats in Group B and one in Group C died after pancreatitis was induced. Both pro-inflammatory cytokines (TNF-α, IL-1, IL-6) at the 2 and 6 h period and the anti-inflammatory cytokines (IL-10, TGF-β) at 24 h increased significantly (P 〈 0.05) in rats of Group B. After treatment with 5-FU, TNF-α, IL-1, and IL-6 in serum of rats of Group C were inhibited at 2 and 6 h after operation (P 〈 0.05), and IL-IO, TGF-13 were inhibited at 24 h compared to Group B (P 〈 0.05). Obvious improvements in the severity of the acute pancreatitis, including the amylase levels, wet weight of pancreatic tissue and neutrophil counts, were also observed after treatment with 5-FU. CONCLUSION: 5-FU is an anti-metabolic and immunosuppressive agent which can minimize the abnormal immune o/tokine response and relieve the pathophysiological disorders associated with experimental acute pancreatitis.