Objective: To observe the effect of Xiaoyu Zhixue tablet (消瘀止血片,XYZXT) on the expression of platelet membrane glycoproteins in patients with hemorrhagic thrombopathy, and to explore its possible mechanism. Method...Objective: To observe the effect of Xiaoyu Zhixue tablet (消瘀止血片,XYZXT) on the expression of platelet membrane glycoproteins in patients with hemorrhagic thrombopathy, and to explore its possible mechanism. Methods: The total of 148 patients with hemorrhagic thrombopathy were randomly divided into two groups, the traditional Chinese medicicne (TCM) group (n=98) treated with XYZXT and the Western medicine (WM) group (n=50) treated with adrenosin, vitamins C, K and P, both for 6 months. The therapeutic effect and the recovery rate of platelet aggregation in the two groups were observed. And platelet membrane glycoprotein (GP) Ⅰb/Ⅸ, GPⅡb/Ⅲa complexes, GPⅠb, GPⅡb, GP Ⅲa and P-selectin were analyzed by flow cytometry in both groups before and after treatment and also in 34 normal healthy subjects. Results: The total effective rate of hemostasis was 89. 8% in TCM group and 54. 0% in the WM group (x2=45.83, P<0.01), and the recovery rate of platelet aggregation was 72.4% and 4.0% respectively (x2=62.06, P<0.01). The fluorescence intensity of GP Ⅰ b/Ⅸ, GPⅡb/Ⅲa complexes, GPⅠb, GPⅢa and P-selectin were lower in both groups before treatment than those in the healthy subjects. Expression of above-mentioned marks was elevated in TCM group after 6 months' therapy, which was insignificantly different as compared with the healthy subjects (P>0.05) and higher than those in the WM group (P<0.05). Conclusion: One of the mechanisms in treating hemorrhagic thrombopathy with XYZXT is that it could regulate the expression of GP Ⅰb/Ⅸ, GPⅡ b/Ⅲa complexes, GPⅠb, GPⅢa and P-selectin at the level of receptor protein.展开更多
To investigate the role of platelet membrane glycoprotein （GP） Ib/Ⅸ/Ⅴ complex and its subunit GP Ibα in patients with hemorrhagic thrombopathy （HT）, the expressions of GP Ib/Ⅸ/Ⅴ complex and GP Ibα,defined as...To investigate the role of platelet membrane glycoprotein （GP） Ib/Ⅸ/Ⅴ complex and its subunit GP Ibα in patients with hemorrhagic thrombopathy （HT）, the expressions of GP Ib/Ⅸ/Ⅴ complex and GP Ibα,defined as mean fluorescence intensity （MFI）, were assessed by flow cytometry. The maximum aggregation of platelet was determined by turbidity method. These indicators were compared among 68 HT patients with the presenting complaint of hemorrhage, 33 well-controlled HT patients and 32 normal healthy subjects. The results showed that the MFI of GP Ib/Ⅸ /Ⅴ complex and GP Ibα was markedly lower in HT patients with current hemorrhage than that in the healthy subjects, with difference being statistically significant （P〈0.05）. There was no significant difference in the expressions of GP Ib/ Ⅸ/ Ⅴ complex and GP Ibα between well-controlled HT patients and normal healthy subjects （P〉0.05）. It was concluded that the expression of GP Ib/Ⅸ /Ⅴ complex, the receptor of thrombin and von Willebrand factor, was down-regulated in HT patients with current hemorrhage, which might result in the dysfunction of platelet aggregation and recurrence of HT.展开更多
AIM： To evaluate whether intratumoral expression of measles virus fusogenic membrane glycoproteins H and F （MV-FMG）, encoded by an adenovirus vector Ad.MV-HI F, alone or in combination with local coexpression of cy...AIM： To evaluate whether intratumoral expression of measles virus fusogenic membrane glycoproteins H and F （MV-FMG）, encoded by an adenovirus vector Ad.MV-HI F, alone or in combination with local coexpression of cytokines （IL-2, IL-12, IL-18, IL-21 or GM-CSF）, can serve as a platform for inducing tumor-specific immune responses in colon cancer.METHODS： We used confocal laser scanning microscopy and flow cytometry to analyze cell-cell fusion after expression of MV-FMG by dye colocalization. In a syngeneic bilateral subcutaneous MC38 and Colon26 colon cancer model in C57BL/6 and BALB/c mice, we assessed the effect on both the directly vector-treated tumor as well as the contralateral, not directly vector- treated tumor. We assessed the induction of a tumorspecific cytotoxic T lymphocyte （CTL） response with a lactate dehydrogenase （LDH） release assay.RESULTS： We demonstrated in vitro that transduction of MC38 and Colon26 cells with Ad.MV-H/F resulted in dye colocalization, indicative of cell-cell fusion, in addition, in the syngeneic bilateral tumor model we demonstrated a significant regression of the directly vector-inoculated tumor upon intratumoral expression of MV-FMG alone or in combination with the tested cytokines. We observed the highest anti-neoplastic efficacy with MV-FMG and lL-21 coexpression. The degree of tumor regression of the not directly vector-treated tumor correlated with the anti-neoplastic response of the directly vector-treated tumor. This regression was mediated by a tumor-specific CTL response.CONCLUSION： Our data indicate that intratumoral expression of measles virus fusogenic membrane glycoproteins is a promising tool both for direct tumor treatment as well as for tumor vaccination approaches that can be further enhanced by cytokine coexpression.展开更多
To explore the correlation between the C807T polymorphism of platelet membrane glycoprotein Ⅰa （GP Ⅰa） gene and aspirin resistance in Chinese people, 200 patients with high-risk of atherosclerosis took aspirin （1...To explore the correlation between the C807T polymorphism of platelet membrane glycoprotein Ⅰa （GP Ⅰa） gene and aspirin resistance in Chinese people, 200 patients with high-risk of atherosclerosis took aspirin （100 mg/d） for 7 days. Platelet aggregation function was detected using adenosine diphosphate （ADP） and arachidonic acid （AA） before and after the administration of aspirin. Then the subjects were divided into three groups according to the results of platelet aggregation function： an aspirin resistant （AR） group, an aspirin semi-responder （ASR） group and an aspirin-sensitive （AS） group. Platelet GP Ⅰa gene 807CT polymorphism was examined by means of polymerase chain reaction-sequence specific primers （PCR-SSP）. The results showed that T allelic frequency in AR group and ASR group were higher that of AS group （P〈0.005）, and the prevalence of genotypes （TT＋TC） of these two groups was significantly higher than that in AS group （P〈0.05）. Platelet GP Ⅰa T allele was significantly associated with aspirin resistance as revealed by multiple logistic regression （OR=3.76, 95% CI： 2.87-9.58）. The results suggest that inherited platelet GP Ⅰa variations may have an important impact on aspirin resistance and the presence of GP Ⅰa T allele may be a marker of genetic susceptibility to aspirin resistance.展开更多
The redistribution of platelet membrane glycoprotein IV (GPIV) and the release of intracellular Q-granule thrombospondin (TSP) were examined and the inhibition of 5-thromboglobulin (&TG) and platelet factor 4 (PF4...The redistribution of platelet membrane glycoprotein IV (GPIV) and the release of intracellular Q-granule thrombospondin (TSP) were examined and the inhibition of 5-thromboglobulin (&TG) and platelet factor 4 (PF4) in patients with chronic myelogenous leukemia (CML) was observed and quantitation of β-TG and PF4 in sera was conducted. GPIV in inactive platelet from CML was 36080±17010 molecules/platelet as compared with 13190±4810 from the controls (P<0,01), No abnormality was found in the distribution of platelet membrane GPIb and GPIIb/III.(P>0. 05). The GPIV redistribution on active platelet membrane induced thrombin (1U/ml) from CML and healthy donors was 44320132310 and 228001 12700 molecules/platelet respectively (P<0. 01 ). The difference in the release of intracellular Q-granule TSP between CML and the control group was not found (P>0.05). There was no direct correlation between GPIV expression and TSP binding after platelet activation. The high leveIs of β-TG and PF4 in sera inhibited release of intracellular a-granule TSP in vitro. These results indicate that the abnormality of platelet membrane GPIV is a common marker in CML, therefore the specific increase of platelet GPIV in patients with CML may be a useful tool for the diagnosis and monitoring of the platelet dysfunction. The release of interna1 TSP pools is hindered by either β-TG or PF4 in sera.展开更多
The interaction of p-opioid receptor （MOPr） with the neuronal membrane glycoprotein M6a is known to facilitate MOPr endocytosis in human embryonic kidney 293 （HEK293） cells. To further study the role of M6a in the...The interaction of p-opioid receptor （MOPr） with the neuronal membrane glycoprotein M6a is known to facilitate MOPr endocytosis in human embryonic kidney 293 （HEK293） cells. To further study the role of M6a in the post-endocytotic sorting of MOPr, we investigated the agonist-induced co-internalization of MOPr and M6a and protein targeting after internalization in HEK293 cells that co-expressed HA-tagged MOPr and Myc-tagged M6a. ,We found that M6a, MOPr, and Rab 11, a marker for recycling endosomes, co-localized in endocytotic vesicles, indicating that MOPr and M6a are primarily targeted to recycling endosomes after endocytosis. Furthermore, co-expression of M6a augmented the post-endocytotic sorting of 6-opioid receptors into the recycling pathway, indicating that M6a might have a more general role in opioid receptor post-endocytotic sorting. The enhanced post-endocytotic sorting of MOPr into the recycling pathway was accompanied by a decrease in agonist-induced receptor down-regulation of M6a in co-expressing cells. We tested the physiological relevance of these findings in primary cultures of cortical neurons and found that co-expression of M6a markedly increased the translocation of MOPrsfrom the plasma membrane to intracellular vesicles at steady state and significantly enhanced both constitutive and agonist-induced receptor endocytosis. In conclusion, our results strongly indicate that M6a modulates MOPr endocytosis and post-endocytotic sorting and has an important role in receptor regulation.展开更多
The Lassa virus(LASV)is endemic in West Africa and causes severe hemorrhagic Lassa fever in humans.The glycoprotein complex(GPC)of LASV is highly glycosylation-modified,with 11 N-glycosylation sites.All 11 N-linked gl...The Lassa virus(LASV)is endemic in West Africa and causes severe hemorrhagic Lassa fever in humans.The glycoprotein complex(GPC)of LASV is highly glycosylation-modified,with 11 N-glycosylation sites.All 11 N-linked glycan chains play critical roles in GPC cleavage,folding,receptor binding,membrane fusion,and immune evasion.In this study,we focused on the first glycosylation site because its deletion mutant(N79Q)results in an unexpected enhanced membrane fusion,whereas it exerts little effect on GPC expression,cleavage,and receptor binding.Meanwhile,the pseudotype virus bearing GPC_(N79Q)was more sensitive to the neutralizing antibody 37.7H and was attenuated in virulence.Exploring the biological functions of the key glycosylation site on LASV GPC will help elucidate the mechanism of LASV infection and provide strategies for the development of attenuated vaccines against LASV infection.展开更多
Gal alpha(1, 3) Gal (gal epitope) is a carbohydrate epitope and synthesized in large amount by alpha(1, 3) galactosyltransferase [alpha(1, 3) GT] enzyme on the cells of lower mammalian animals such as pigs and mice. H...Gal alpha(1, 3) Gal (gal epitope) is a carbohydrate epitope and synthesized in large amount by alpha(1, 3) galactosyltransferase [alpha(1, 3) GT] enzyme on the cells of lower mammalian animals such as pigs and mice. Human has no gal epitope due to the inactivation of alpha(1, 3) GT gene but produces a large amount of antibodies (anti-Gal) which recognize Gal alpha(1, 3) Gal structures specifically. In this study, a replication-deficient recombinant adenoviral vector Ad5sGT containing pig alpha(1, 3) GT cDNA was constructed and characterized. Adenoviral vector-mediated transfer of pig alpha(1, 3) GT gene into human tumor cells such as malignant melanoma A375, stomach cancer SGC-7901, and lung cancer SPC-A-1 was reported for the first time. Results showed that Gal epitope did not increase the sensitivity of human tumor cells to human complement-mediated lysis, although human complement activation and the binding of human IgG and IgM natural antibodies to human tumor cells were enhanced significantly after Ad5sGT transduction. Appearance of gal epitope on the human tumor cells changed the expression of cell surface carbohydrates reacting with Ulex europaeus I (UEA I) lectins, Vicia villosa agglutinin (VVA), Arachis hypogaea agglutinin (PNA), and Glycine max agglutinin (SBA) to different degrees. In addition, no effect of gal epitope on the growth in vitro of human tumor cells was observed in MTT assay.展开更多
Shu Xin Yi Mai Capsules (舒心益脉胶囊) combined with western medicine was used in the routine treatment of 22 cases who successfully received coronary artery introducing therapy (Chinese-western medicine group),and th...Shu Xin Yi Mai Capsules (舒心益脉胶囊) combined with western medicine was used in the routine treatment of 22 cases who successfully received coronary artery introducing therapy (Chinese-western medicine group),and the results was compared with the 26 cases treated routinely with simple western medicine in the control group (western medicine group).It was found that both the recurrence rate of angina pectoris and the incidence rate of recurrent stricture in the Chinese-western medicine group were significantly lower than that in the control group (both P<0.05).There was no significant difference between the two groups in expression of platelet activating molecules CD62P (a-granular membrane protein),CD63 (lysosome intact membrane protein) and CD41 (glucoprotein IIb) before the treatment,but with a significant difference after the treatment (P<0.05).展开更多
A novel SARS-related coronavirus(SARS-CoV-2)has recently emerged as a serious pathogen that causes high morbidity and substantial mortality.However,the mechanisms by which SARS-CoV-2 evades host immunity remain poorly...A novel SARS-related coronavirus(SARS-CoV-2)has recently emerged as a serious pathogen that causes high morbidity and substantial mortality.However,the mechanisms by which SARS-CoV-2 evades host immunity remain poorly understood.Here,we identified SARS-CoV-2 membrane glycoprotein M as a negative regulator of the innate immune response.We found that the M protein interacted with the central adaptor protein MAVS in the innate immune response pathways.This interaction impaired MAVS aggregation and its recruitment of downstream TRAF3,TBK1,and IRF3,leading to attenuation of the innate antiviral response.Our findings reveal a mechanism by which SARS-CoV-2 evades the innate immune response and suggest that the M protein of SARSCoV-2 is a potential target for the development of SARS-CoV-2 interventions.展开更多
Objective： To investigate the effect of Xiaoyu Zhixue Tablet （消瘀止血片, XYZXT） on the expression of platelet membrane glycoprotein （GP） Ⅰ b/Ⅸ/Ⅴ complex and GP Ⅰ b α in patients with chronic renal failure ...Objective： To investigate the effect of Xiaoyu Zhixue Tablet （消瘀止血片, XYZXT） on the expression of platelet membrane glycoprotein （GP） Ⅰ b/Ⅸ/Ⅴ complex and GP Ⅰ b α in patients with chronic renal failure （CRF） in early metaphase. Methods： Fifty-one patients with CRF in early metaphase （treated group） were treated with XYZXT, 3 months as the course of treatment for 2 courses. The previous therapies remained unchanged. Flow cytometry was used to assess the expression of platelet GP Ⅰb/Ⅸ/Ⅴ complex and GP Ⅰb α in patients with CRF, and turbidity method was used to determine the platelet maximum aggregation rate （MAR）, meanwhile the renal function was measured. The final data were compared with those before the treatment, and with those in the normal control group （31 healthy subjects）. Results： Compared with the normal control group, expressions of GP Ⅰ b/Ⅸ/Ⅴ complex and GPⅠb α, and platelet MAR in CRF patients were significantly lower （P=0.007,P=0.001,P=0.009） before the treatment; after the treatment with XYZXT, the above indexes in CRF patients were remarkably increased （P=0.033,P=0.026, P=0.045）, but still lower than those in the normal control group, however, it was not statistically significant. Conclusion： （1） The expression of GP Ⅰ b/Ⅸ/Ⅴ complex in CRF patients of early metaphase was decreased, which lead to platelet aggregation dysfunction. This might be one of the reasons for the hemorrhagic trend in CRF. （2） XYZXT was able to upgrade expressions of GP Ⅰb/Ⅸ/Ⅴ complex and GPⅠb α in CRF patients, improve platelet function and clown-regulate platelet activation in patients with CRF.展开更多
文摘Objective: To observe the effect of Xiaoyu Zhixue tablet (消瘀止血片,XYZXT) on the expression of platelet membrane glycoproteins in patients with hemorrhagic thrombopathy, and to explore its possible mechanism. Methods: The total of 148 patients with hemorrhagic thrombopathy were randomly divided into two groups, the traditional Chinese medicicne (TCM) group (n=98) treated with XYZXT and the Western medicine (WM) group (n=50) treated with adrenosin, vitamins C, K and P, both for 6 months. The therapeutic effect and the recovery rate of platelet aggregation in the two groups were observed. And platelet membrane glycoprotein (GP) Ⅰb/Ⅸ, GPⅡb/Ⅲa complexes, GPⅠb, GPⅡb, GP Ⅲa and P-selectin were analyzed by flow cytometry in both groups before and after treatment and also in 34 normal healthy subjects. Results: The total effective rate of hemostasis was 89. 8% in TCM group and 54. 0% in the WM group (x2=45.83, P<0.01), and the recovery rate of platelet aggregation was 72.4% and 4.0% respectively (x2=62.06, P<0.01). The fluorescence intensity of GP Ⅰ b/Ⅸ, GPⅡb/Ⅲa complexes, GPⅠb, GPⅢa and P-selectin were lower in both groups before treatment than those in the healthy subjects. Expression of above-mentioned marks was elevated in TCM group after 6 months' therapy, which was insignificantly different as compared with the healthy subjects (P>0.05) and higher than those in the WM group (P<0.05). Conclusion: One of the mechanisms in treating hemorrhagic thrombopathy with XYZXT is that it could regulate the expression of GP Ⅰb/Ⅸ, GPⅡ b/Ⅲa complexes, GPⅠb, GPⅢa and P-selectin at the level of receptor protein.
基金supported by a grant from the National Natural Science Foundation of China (No. 30572441).
文摘To investigate the role of platelet membrane glycoprotein （GP） Ib/Ⅸ/Ⅴ complex and its subunit GP Ibα in patients with hemorrhagic thrombopathy （HT）, the expressions of GP Ib/Ⅸ/Ⅴ complex and GP Ibα,defined as mean fluorescence intensity （MFI）, were assessed by flow cytometry. The maximum aggregation of platelet was determined by turbidity method. These indicators were compared among 68 HT patients with the presenting complaint of hemorrhage, 33 well-controlled HT patients and 32 normal healthy subjects. The results showed that the MFI of GP Ib/Ⅸ /Ⅴ complex and GP Ibα was markedly lower in HT patients with current hemorrhage than that in the healthy subjects, with difference being statistically significant （P〈0.05）. There was no significant difference in the expressions of GP Ib/ Ⅸ/ Ⅴ complex and GP Ibα between well-controlled HT patients and normal healthy subjects （P〉0.05）. It was concluded that the expression of GP Ib/Ⅸ /Ⅴ complex, the receptor of thrombin and von Willebrand factor, was down-regulated in HT patients with current hemorrhage, which might result in the dysfunction of platelet aggregation and recurrence of HT.
基金grants from Deutsche Forschungsgemeinschaft, Wilhelm Sander-Stiftung, and Forschungsfrderung Ruhr-Universitt Bochum Medizinische Fakultt to OW
文摘AIM： To evaluate whether intratumoral expression of measles virus fusogenic membrane glycoproteins H and F （MV-FMG）, encoded by an adenovirus vector Ad.MV-HI F, alone or in combination with local coexpression of cytokines （IL-2, IL-12, IL-18, IL-21 or GM-CSF）, can serve as a platform for inducing tumor-specific immune responses in colon cancer.METHODS： We used confocal laser scanning microscopy and flow cytometry to analyze cell-cell fusion after expression of MV-FMG by dye colocalization. In a syngeneic bilateral subcutaneous MC38 and Colon26 colon cancer model in C57BL/6 and BALB/c mice, we assessed the effect on both the directly vector-treated tumor as well as the contralateral, not directly vector- treated tumor. We assessed the induction of a tumorspecific cytotoxic T lymphocyte （CTL） response with a lactate dehydrogenase （LDH） release assay.RESULTS： We demonstrated in vitro that transduction of MC38 and Colon26 cells with Ad.MV-H/F resulted in dye colocalization, indicative of cell-cell fusion, in addition, in the syngeneic bilateral tumor model we demonstrated a significant regression of the directly vector-inoculated tumor upon intratumoral expression of MV-FMG alone or in combination with the tested cytokines. We observed the highest anti-neoplastic efficacy with MV-FMG and lL-21 coexpression. The degree of tumor regression of the not directly vector-treated tumor correlated with the anti-neoplastic response of the directly vector-treated tumor. This regression was mediated by a tumor-specific CTL response.CONCLUSION： Our data indicate that intratumoral expression of measles virus fusogenic membrane glycoproteins is a promising tool both for direct tumor treatment as well as for tumor vaccination approaches that can be further enhanced by cytokine coexpression.
文摘To explore the correlation between the C807T polymorphism of platelet membrane glycoprotein Ⅰa （GP Ⅰa） gene and aspirin resistance in Chinese people, 200 patients with high-risk of atherosclerosis took aspirin （100 mg/d） for 7 days. Platelet aggregation function was detected using adenosine diphosphate （ADP） and arachidonic acid （AA） before and after the administration of aspirin. Then the subjects were divided into three groups according to the results of platelet aggregation function： an aspirin resistant （AR） group, an aspirin semi-responder （ASR） group and an aspirin-sensitive （AS） group. Platelet GP Ⅰa gene 807CT polymorphism was examined by means of polymerase chain reaction-sequence specific primers （PCR-SSP）. The results showed that T allelic frequency in AR group and ASR group were higher that of AS group （P〈0.005）, and the prevalence of genotypes （TT＋TC） of these two groups was significantly higher than that in AS group （P〈0.05）. Platelet GP Ⅰa T allele was significantly associated with aspirin resistance as revealed by multiple logistic regression （OR=3.76, 95% CI： 2.87-9.58）. The results suggest that inherited platelet GP Ⅰa variations may have an important impact on aspirin resistance and the presence of GP Ⅰa T allele may be a marker of genetic susceptibility to aspirin resistance.
文摘The redistribution of platelet membrane glycoprotein IV (GPIV) and the release of intracellular Q-granule thrombospondin (TSP) were examined and the inhibition of 5-thromboglobulin (&TG) and platelet factor 4 (PF4) in patients with chronic myelogenous leukemia (CML) was observed and quantitation of β-TG and PF4 in sera was conducted. GPIV in inactive platelet from CML was 36080±17010 molecules/platelet as compared with 13190±4810 from the controls (P<0,01), No abnormality was found in the distribution of platelet membrane GPIb and GPIIb/III.(P>0. 05). The GPIV redistribution on active platelet membrane induced thrombin (1U/ml) from CML and healthy donors was 44320132310 and 228001 12700 molecules/platelet respectively (P<0. 01 ). The difference in the release of intracellular Q-granule TSP between CML and the control group was not found (P>0.05). There was no direct correlation between GPIV expression and TSP binding after platelet activation. The high leveIs of β-TG and PF4 in sera inhibited release of intracellular a-granule TSP in vitro. These results indicate that the abnormality of platelet membrane GPIV is a common marker in CML, therefore the specific increase of platelet GPIV in patients with CML may be a useful tool for the diagnosis and monitoring of the platelet dysfunction. The release of interna1 TSP pools is hindered by either β-TG or PF4 in sera.
文摘The interaction of p-opioid receptor （MOPr） with the neuronal membrane glycoprotein M6a is known to facilitate MOPr endocytosis in human embryonic kidney 293 （HEK293） cells. To further study the role of M6a in the post-endocytotic sorting of MOPr, we investigated the agonist-induced co-internalization of MOPr and M6a and protein targeting after internalization in HEK293 cells that co-expressed HA-tagged MOPr and Myc-tagged M6a. ,We found that M6a, MOPr, and Rab 11, a marker for recycling endosomes, co-localized in endocytotic vesicles, indicating that MOPr and M6a are primarily targeted to recycling endosomes after endocytosis. Furthermore, co-expression of M6a augmented the post-endocytotic sorting of 6-opioid receptors into the recycling pathway, indicating that M6a might have a more general role in opioid receptor post-endocytotic sorting. The enhanced post-endocytotic sorting of MOPr into the recycling pathway was accompanied by a decrease in agonist-induced receptor down-regulation of M6a in co-expressing cells. We tested the physiological relevance of these findings in primary cultures of cortical neurons and found that co-expression of M6a markedly increased the translocation of MOPrsfrom the plasma membrane to intracellular vesicles at steady state and significantly enhanced both constitutive and agonist-induced receptor endocytosis. In conclusion, our results strongly indicate that M6a modulates MOPr endocytosis and post-endocytotic sorting and has an important role in receptor regulation.
基金the National Key Research and Development Program(2022YFC2303300,2018YFA0507204)the Strategic Priority Research Program of the Chinese Academy of Sciences(XDB0490000)the Na-tional Natural Science Foundation of China(82172273,31670165).
文摘The Lassa virus(LASV)is endemic in West Africa and causes severe hemorrhagic Lassa fever in humans.The glycoprotein complex(GPC)of LASV is highly glycosylation-modified,with 11 N-glycosylation sites.All 11 N-linked glycan chains play critical roles in GPC cleavage,folding,receptor binding,membrane fusion,and immune evasion.In this study,we focused on the first glycosylation site because its deletion mutant(N79Q)results in an unexpected enhanced membrane fusion,whereas it exerts little effect on GPC expression,cleavage,and receptor binding.Meanwhile,the pseudotype virus bearing GPC_(N79Q)was more sensitive to the neutralizing antibody 37.7H and was attenuated in virulence.Exploring the biological functions of the key glycosylation site on LASV GPC will help elucidate the mechanism of LASV infection and provide strategies for the development of attenuated vaccines against LASV infection.
基金National..973" project, the Special Funds for Major State Bacsic Reseaxch of China (G1999053905) and NationalNatural Science Fou
文摘Gal alpha(1, 3) Gal (gal epitope) is a carbohydrate epitope and synthesized in large amount by alpha(1, 3) galactosyltransferase [alpha(1, 3) GT] enzyme on the cells of lower mammalian animals such as pigs and mice. Human has no gal epitope due to the inactivation of alpha(1, 3) GT gene but produces a large amount of antibodies (anti-Gal) which recognize Gal alpha(1, 3) Gal structures specifically. In this study, a replication-deficient recombinant adenoviral vector Ad5sGT containing pig alpha(1, 3) GT cDNA was constructed and characterized. Adenoviral vector-mediated transfer of pig alpha(1, 3) GT gene into human tumor cells such as malignant melanoma A375, stomach cancer SGC-7901, and lung cancer SPC-A-1 was reported for the first time. Results showed that Gal epitope did not increase the sensitivity of human tumor cells to human complement-mediated lysis, although human complement activation and the binding of human IgG and IgM natural antibodies to human tumor cells were enhanced significantly after Ad5sGT transduction. Appearance of gal epitope on the human tumor cells changed the expression of cell surface carbohydrates reacting with Ulex europaeus I (UEA I) lectins, Vicia villosa agglutinin (VVA), Arachis hypogaea agglutinin (PNA), and Glycine max agglutinin (SBA) to different degrees. In addition, no effect of gal epitope on the growth in vitro of human tumor cells was observed in MTT assay.
文摘Shu Xin Yi Mai Capsules (舒心益脉胶囊) combined with western medicine was used in the routine treatment of 22 cases who successfully received coronary artery introducing therapy (Chinese-western medicine group),and the results was compared with the 26 cases treated routinely with simple western medicine in the control group (western medicine group).It was found that both the recurrence rate of angina pectoris and the incidence rate of recurrent stricture in the Chinese-western medicine group were significantly lower than that in the control group (both P<0.05).There was no significant difference between the two groups in expression of platelet activating molecules CD62P (a-granular membrane protein),CD63 (lysosome intact membrane protein) and CD41 (glucoprotein IIb) before the treatment,but with a significant difference after the treatment (P<0.05).
基金supported by the National Key Research and Development Project of China(2020YFC0841000)the Strategic Priority Research Program(XDB29010302)+2 种基金the National Natural Science Foundation of China(31800732)the Key Research Programs of Frontier Sciences funded by the Chinese Academy of Sciencesthe Special Research Assistant Grant Program of the Chinese Academy of Sciences.
文摘A novel SARS-related coronavirus(SARS-CoV-2)has recently emerged as a serious pathogen that causes high morbidity and substantial mortality.However,the mechanisms by which SARS-CoV-2 evades host immunity remain poorly understood.Here,we identified SARS-CoV-2 membrane glycoprotein M as a negative regulator of the innate immune response.We found that the M protein interacted with the central adaptor protein MAVS in the innate immune response pathways.This interaction impaired MAVS aggregation and its recruitment of downstream TRAF3,TBK1,and IRF3,leading to attenuation of the innate antiviral response.Our findings reveal a mechanism by which SARS-CoV-2 evades the innate immune response and suggest that the M protein of SARSCoV-2 is a potential target for the development of SARS-CoV-2 interventions.
基金the National Natural Science Foundation of China(No.30572441)
文摘Objective： To investigate the effect of Xiaoyu Zhixue Tablet （消瘀止血片, XYZXT） on the expression of platelet membrane glycoprotein （GP） Ⅰ b/Ⅸ/Ⅴ complex and GP Ⅰ b α in patients with chronic renal failure （CRF） in early metaphase. Methods： Fifty-one patients with CRF in early metaphase （treated group） were treated with XYZXT, 3 months as the course of treatment for 2 courses. The previous therapies remained unchanged. Flow cytometry was used to assess the expression of platelet GP Ⅰb/Ⅸ/Ⅴ complex and GP Ⅰb α in patients with CRF, and turbidity method was used to determine the platelet maximum aggregation rate （MAR）, meanwhile the renal function was measured. The final data were compared with those before the treatment, and with those in the normal control group （31 healthy subjects）. Results： Compared with the normal control group, expressions of GP Ⅰ b/Ⅸ/Ⅴ complex and GPⅠb α, and platelet MAR in CRF patients were significantly lower （P=0.007,P=0.001,P=0.009） before the treatment; after the treatment with XYZXT, the above indexes in CRF patients were remarkably increased （P=0.033,P=0.026, P=0.045）, but still lower than those in the normal control group, however, it was not statistically significant. Conclusion： （1） The expression of GP Ⅰ b/Ⅸ/Ⅴ complex in CRF patients of early metaphase was decreased, which lead to platelet aggregation dysfunction. This might be one of the reasons for the hemorrhagic trend in CRF. （2） XYZXT was able to upgrade expressions of GP Ⅰb/Ⅸ/Ⅴ complex and GPⅠb α in CRF patients, improve platelet function and clown-regulate platelet activation in patients with CRF.
