Objective Combination immunotherapy strategies targeting OX40,a co-stimulatory molecule that can enhance antitumor immunity by modulating the proliferation,differentiation,and effector function of tumor-infiltrating T...Objective Combination immunotherapy strategies targeting OX40,a co-stimulatory molecule that can enhance antitumor immunity by modulating the proliferation,differentiation,and effector function of tumor-infiltrating T cells,have attracted much attention for their excellent therapeutic effects.In this study,we aimed to evaluate the antitumor efficacy of combined anti-OX40 and hepatitis B core viruslike particles(HBc VLPs)therapy using a mouse colon cancer model.Methods Humanized B-h OX40 mice were injected subcutaneously with MC38 colon tumor cells and treated with HBc VLPs+anti-h OX40 antibody.Tumor growth was monitored.Flow cytometric analysis was performed to evaluate the populations of T cell subsets in the tumors.Results The combination of anti-OX40 with HBc VLPs resulted in a significant delay in tumor growth,suggesting that a potent antitumor immunity was induced by the combination therapy.Further studies revealed that HBc VLPs+anti-OX40 treatment induced a significant increase in effector T cells(Teffs)and a significant decrease in regulatory T cells(Tregs)in the tumor microenvironment(TME),which accounted for the synergistic antitumor effect of anti-OX40 in combination with HBc VLPs.Conclusion Combination therapy of anti-h OX40 and HBc VLPs provides synergistic antitumor activity in colon cancer-bearing mice,which may represent a potential design strategy for cancer immunotherapy.展开更多
Blastomycosis, the systemic fungal infection of humans and animals, has presented a diagnostic challenge to clinicians and laboratory personnel for many years. Our laboratory has been concentrating on attempting to de...Blastomycosis, the systemic fungal infection of humans and animals, has presented a diagnostic challenge to clinicians and laboratory personnel for many years. Our laboratory has been concentrating on attempting to develop antigenic reagents from the yeast phase of various isolates of Blastomyces dermatitidis and to evaluate these lysate antigens with regard to antibody detection in blastomycosis. The aim of this current study was to evaluate yeast phase antigens prepared from four dog isolates of B. dermatitidis and to evaluate their efficacy, when used individually or in combination, for antibody detection in sera from dogs with blastomycosis. Mean absorbance values using the ELISA to assay 24 serum specimens (Trial 1) ranged from 0.588 with an individual lysate antigen to 0.992 when three reagents were combined. Eight of the lysates exhibited mean absorbance values ranging from 0.992 to 0.915 with 7 out of 8 being lysate antigen combinations. Mean absorbance values with the other 6 lysates ranged from 0.899 to 0.588. In Trial 2, the 6 most sensitive reagents from Trial 1 were assayed against 10 highly reactive dog sera. The results of Trial 2 showed that 5 antigen combinations detected antibody to a greater degree than the individual lysate antigen. Combinations of northern and southern antigens were able to detect antibody in serum specimens from either of these geographical regions. Comparative studies are continuing to further evaluate various lysate antigen combinations for antibody detection in blastomycosis.展开更多
Objective:To explore the therapeutic effect of combination of Zhuanyindan (ZYD, 转阴丹, a self-made Chinese herbal preparation) and hormone in treating male infertility with positive antisperm antibody and its influen...Objective:To explore the therapeutic effect of combination of Zhuanyindan (ZYD, 转阴丹, a self-made Chinese herbal preparation) and hormone in treating male infertility with positive antisperm antibody and its influence on nitric oxide (NO) level. Methods:Eighty-two patients were randomly divided (according to the digital list) into the WM group (n = 20, treated with prednisone), the TCM group (n=28, treated with ZYD) and the ICWM group (n=34, treated with prednisone plus ZYD). The clinical effect, negative converting rate of antisperm antibody, changes of NO level in semen and various parameters of sperm motion before and after treatment were observed. Results: The total effective rate in the ICWM group was 88.2%, that in theTCM group 75. 0% and in the WM group 65. 0%. Significant difference was seen in the ICWM and TCM group before and after treatment in NO level, sperm motion parameters, including linear motion speed, linearity, propulsion, whip frequency, sperm vitality and mean moving angle, and quality of semen ( P < 0. 05 or P < 0. 01). In the WM group, significant difference in comparison before and after treatment was seen in NO level, propulsion, whip frequency, mean moving angle and quality of semen, including vitality and survival rate (P<0. 01). Conclusion: Combination of Chinese herbs and hormone could lower the NO level in semen and improve the quality of sperm.Original article on CJITWM (Chin) 2004 ;23 (3): 223展开更多
Osteoporosis and osteopenia are major health issues that mainly affect elderly people,women after menopause and immobilized patients.Our previous studies have proved that sclerostin antibody(Scl-Ab)can dramatically en...Osteoporosis and osteopenia are major health issues that mainly affect elderly people,women after menopause and immobilized patients.Our previous studies have proved that sclerostin antibody(Scl-Ab)can dramatically enhance bone formation and reduce bone resorption in a severe osteoporosis rat model with the combination of ovariectomy(OVX)and hindlimb immobilization(HLS).However,the mechanism in the cellular level is unclear.The objective of this study is to assess the effect of Scl-Ab on osteocytic morphology change in a combined OVX and HLS rat model via quantification of long-and short-axis and the ratio and osteocyte volume in midshaft cortical bone.Four-month-old virgin female SD rats were divided into 7 groups(n=11 per group):Sham+Veh,Sham+HLS+Veh,Sham+HLS+Scl-Ab,OVX+Veh,OVX+Scl-Ab,OVX+HLS+Veh,OVX+HLS+Scl-Ab.HLS was performed 2 weeks after sham or OVX surgery;and treatment was initiated at the time of HLS.Scl-Ab(25 mg/kg)or vehicle was subcutaneously injected twice per week for 5 weeks.Femurs were harvested at the end of study and embedded in PMMA and polished for SEM imaging.Cortical bone mid shaft osteocyte number per bone area was quantified under 1K magnification;the ratios between long axis and short axis of osteocytes were quantified under 2K magnification;osteocyte dendrite number and surface area were quantified under 5K magnification.Osteocyte dendrites width was quantified using 10K magnification.All the quantification was done by ImageJ.We have reported that multiple morphological and structural changes in osteocytes,including a decreased osteocyte density and reduced osteocyte dendrite number in HLS,OVX or the combination group and Scl-Ab’s ability to abolish these unfavorable alterations.We continued our SEM analysis on osteocytes and discovered that the oval shape of osteocyte under HLS,OVX or HLS+OVX has been distorted toward a spindle-like shape,with relatively longer long axis and shorter short axis,assuming osteocyte has a perfect spheroid shape.The ratio between long-and short-axis showed an increased trend in OVX and HLS condition,but Scl-Ab inhibited these increases(P<0.001,P<0.01,respectively).The volume decreased in HLS,OVX group,but Scl-Ab maintained osteocytes’volume in HLS condition(P<0.001).It indicates that cortical bone responds to HLS and/or OVX and Scl-Ab treatment via multiple cellular mechanisms,including density of osteocyte,dendrite number and osteocyte shape.The change of osteocyte shape may imply an altered cytoskeleton system within osteocyte and a subsequent disruption of mechanosensing ability for osteocyte,which lead to bone loss macroscopically.These data suggest Scl-Ab’s therapeutic potential could be related with its ability to maintain osteocyte’s morphologic and structural changes induced by OVX,HLS or both.展开更多
In this study,we have examined the effects of exposure to high temperature, carbon inonoxideor a combination of both conditions in a model system,the rat and in industrial workers.In the rat liver, HSP70 mRNA and HSP7...In this study,we have examined the effects of exposure to high temperature, carbon inonoxideor a combination of both conditions in a model system,the rat and in industrial workers.In the rat liver, HSP70 mRNA and HSP70 synthesis were measured by dot hybridization and western blot. The results showed that after a heat stress HSP70 mRNA and its product, HSP70 increased significantly and there was a synergism in the combined effects of high temperature and carbon monoxide exposure on the induction of HSP70 mRNA and HSP70 synthesis. Heat played a major role in this induction. The presence of antibodies to human HSP27, HSP60, HSP70,HSC73, HSP89 αand β in workers exposed to heat, carbon monoxide was also measured by western blot using purified HSPs as antigens. Plasma free amino acids were measured in the saine group of workers. The incidence of antibodies to HSP27 and HSP70 Was significantly higher in the workers working in an environment with extreme heat, and high carbon monoxide ernission than in a control group. The carbon monoxide exposed group showed the highest incidence of antibodies to HSPs. Although our previous results indicated that workers had an insufficient protein intake,plasma free amino acids tended to increase, especially in methionine and tryptophan two kinds of amino acids which are absent from the main stress protein, HSP70.These results suggest that the major problems that these workers may face are how to facilitate the use of plasma free amino acids and reduce the inhibition of synthesis of normal proteins when they are exposed to occupational harmful factors.These resultsalso add new information on the measurement of HSPs as a potential biomonitor to assess whether organisms are experiencing metabolic stress within their environment.展开更多
Combined liver and kidney transplantation(CLKT)is indicated in patients with failure of both organs,or for the treatment of end-stage chronic kidney disease(ESKD)caused by a genetic defect in the liver.The aim of the ...Combined liver and kidney transplantation(CLKT)is indicated in patients with failure of both organs,or for the treatment of end-stage chronic kidney disease(ESKD)caused by a genetic defect in the liver.The aim of the present review is to provide the most up-to-date overview of the rare conditions as indications for CLKT.They are major indications for CLKT in children.However,in some of them(e.g.,atypical hemolytic uremic syndrome or primary hyperoxaluria),CLKT may be required in adults as well.Primary hyperoxaluria is divided into three types,of which type 1 and 2 lead to ESKD.CLKT has been proven effective in renal function replacement,at the same time preventing recurrence of the disease.Nephronophthisis is associated with liver fibrosis in 5%of cases and these patients are candidates for CLKT.In alpha 1-antitrypsin deficiency,hereditary C3 deficiency,lecithin cholesterol acyltransferase deficiency and glycogen storage diseases,glomerular or tubulointerstitial disease can lead to chronic kidney disease.Liver transplantation as a part of CLKT corrects underlying genetic and consequent metabolic abnormality.In atypical hemolytic uremic syndrome caused by mutations in the genes for factor H,successful CLKT has been reported in a small number of patients.However,for this indication,CLKT has been largely replaced by eculizumab,an anti-C5 antibody.CLKT has been well established to provide immune protection of the transplanted kidney against donor-specific antibodies against class I HLA,facilitating transplantation in a highly sensitized recipient.展开更多
基金supported by National Major Science and Technology Projects of China 2017ZX10105015-001-002。
文摘Objective Combination immunotherapy strategies targeting OX40,a co-stimulatory molecule that can enhance antitumor immunity by modulating the proliferation,differentiation,and effector function of tumor-infiltrating T cells,have attracted much attention for their excellent therapeutic effects.In this study,we aimed to evaluate the antitumor efficacy of combined anti-OX40 and hepatitis B core viruslike particles(HBc VLPs)therapy using a mouse colon cancer model.Methods Humanized B-h OX40 mice were injected subcutaneously with MC38 colon tumor cells and treated with HBc VLPs+anti-h OX40 antibody.Tumor growth was monitored.Flow cytometric analysis was performed to evaluate the populations of T cell subsets in the tumors.Results The combination of anti-OX40 with HBc VLPs resulted in a significant delay in tumor growth,suggesting that a potent antitumor immunity was induced by the combination therapy.Further studies revealed that HBc VLPs+anti-OX40 treatment induced a significant increase in effector T cells(Teffs)and a significant decrease in regulatory T cells(Tregs)in the tumor microenvironment(TME),which accounted for the synergistic antitumor effect of anti-OX40 in combination with HBc VLPs.Conclusion Combination therapy of anti-h OX40 and HBc VLPs provides synergistic antitumor activity in colon cancer-bearing mice,which may represent a potential design strategy for cancer immunotherapy.
文摘Blastomycosis, the systemic fungal infection of humans and animals, has presented a diagnostic challenge to clinicians and laboratory personnel for many years. Our laboratory has been concentrating on attempting to develop antigenic reagents from the yeast phase of various isolates of Blastomyces dermatitidis and to evaluate these lysate antigens with regard to antibody detection in blastomycosis. The aim of this current study was to evaluate yeast phase antigens prepared from four dog isolates of B. dermatitidis and to evaluate their efficacy, when used individually or in combination, for antibody detection in sera from dogs with blastomycosis. Mean absorbance values using the ELISA to assay 24 serum specimens (Trial 1) ranged from 0.588 with an individual lysate antigen to 0.992 when three reagents were combined. Eight of the lysates exhibited mean absorbance values ranging from 0.992 to 0.915 with 7 out of 8 being lysate antigen combinations. Mean absorbance values with the other 6 lysates ranged from 0.899 to 0.588. In Trial 2, the 6 most sensitive reagents from Trial 1 were assayed against 10 highly reactive dog sera. The results of Trial 2 showed that 5 antigen combinations detected antibody to a greater degree than the individual lysate antigen. Combinations of northern and southern antigens were able to detect antibody in serum specimens from either of these geographical regions. Comparative studies are continuing to further evaluate various lysate antigen combinations for antibody detection in blastomycosis.
文摘Objective:To explore the therapeutic effect of combination of Zhuanyindan (ZYD, 转阴丹, a self-made Chinese herbal preparation) and hormone in treating male infertility with positive antisperm antibody and its influence on nitric oxide (NO) level. Methods:Eighty-two patients were randomly divided (according to the digital list) into the WM group (n = 20, treated with prednisone), the TCM group (n=28, treated with ZYD) and the ICWM group (n=34, treated with prednisone plus ZYD). The clinical effect, negative converting rate of antisperm antibody, changes of NO level in semen and various parameters of sperm motion before and after treatment were observed. Results: The total effective rate in the ICWM group was 88.2%, that in theTCM group 75. 0% and in the WM group 65. 0%. Significant difference was seen in the ICWM and TCM group before and after treatment in NO level, sperm motion parameters, including linear motion speed, linearity, propulsion, whip frequency, sperm vitality and mean moving angle, and quality of semen ( P < 0. 05 or P < 0. 01). In the WM group, significant difference in comparison before and after treatment was seen in NO level, propulsion, whip frequency, mean moving angle and quality of semen, including vitality and survival rate (P<0. 01). Conclusion: Combination of Chinese herbs and hormone could lower the NO level in semen and improve the quality of sperm.Original article on CJITWM (Chin) 2004 ;23 (3): 223
文摘Osteoporosis and osteopenia are major health issues that mainly affect elderly people,women after menopause and immobilized patients.Our previous studies have proved that sclerostin antibody(Scl-Ab)can dramatically enhance bone formation and reduce bone resorption in a severe osteoporosis rat model with the combination of ovariectomy(OVX)and hindlimb immobilization(HLS).However,the mechanism in the cellular level is unclear.The objective of this study is to assess the effect of Scl-Ab on osteocytic morphology change in a combined OVX and HLS rat model via quantification of long-and short-axis and the ratio and osteocyte volume in midshaft cortical bone.Four-month-old virgin female SD rats were divided into 7 groups(n=11 per group):Sham+Veh,Sham+HLS+Veh,Sham+HLS+Scl-Ab,OVX+Veh,OVX+Scl-Ab,OVX+HLS+Veh,OVX+HLS+Scl-Ab.HLS was performed 2 weeks after sham or OVX surgery;and treatment was initiated at the time of HLS.Scl-Ab(25 mg/kg)or vehicle was subcutaneously injected twice per week for 5 weeks.Femurs were harvested at the end of study and embedded in PMMA and polished for SEM imaging.Cortical bone mid shaft osteocyte number per bone area was quantified under 1K magnification;the ratios between long axis and short axis of osteocytes were quantified under 2K magnification;osteocyte dendrite number and surface area were quantified under 5K magnification.Osteocyte dendrites width was quantified using 10K magnification.All the quantification was done by ImageJ.We have reported that multiple morphological and structural changes in osteocytes,including a decreased osteocyte density and reduced osteocyte dendrite number in HLS,OVX or the combination group and Scl-Ab’s ability to abolish these unfavorable alterations.We continued our SEM analysis on osteocytes and discovered that the oval shape of osteocyte under HLS,OVX or HLS+OVX has been distorted toward a spindle-like shape,with relatively longer long axis and shorter short axis,assuming osteocyte has a perfect spheroid shape.The ratio between long-and short-axis showed an increased trend in OVX and HLS condition,but Scl-Ab inhibited these increases(P<0.001,P<0.01,respectively).The volume decreased in HLS,OVX group,but Scl-Ab maintained osteocytes’volume in HLS condition(P<0.001).It indicates that cortical bone responds to HLS and/or OVX and Scl-Ab treatment via multiple cellular mechanisms,including density of osteocyte,dendrite number and osteocyte shape.The change of osteocyte shape may imply an altered cytoskeleton system within osteocyte and a subsequent disruption of mechanosensing ability for osteocyte,which lead to bone loss macroscopically.These data suggest Scl-Ab’s therapeutic potential could be related with its ability to maintain osteocyte’s morphologic and structural changes induced by OVX,HLS or both.
文摘In this study,we have examined the effects of exposure to high temperature, carbon inonoxideor a combination of both conditions in a model system,the rat and in industrial workers.In the rat liver, HSP70 mRNA and HSP70 synthesis were measured by dot hybridization and western blot. The results showed that after a heat stress HSP70 mRNA and its product, HSP70 increased significantly and there was a synergism in the combined effects of high temperature and carbon monoxide exposure on the induction of HSP70 mRNA and HSP70 synthesis. Heat played a major role in this induction. The presence of antibodies to human HSP27, HSP60, HSP70,HSC73, HSP89 αand β in workers exposed to heat, carbon monoxide was also measured by western blot using purified HSPs as antigens. Plasma free amino acids were measured in the saine group of workers. The incidence of antibodies to HSP27 and HSP70 Was significantly higher in the workers working in an environment with extreme heat, and high carbon monoxide ernission than in a control group. The carbon monoxide exposed group showed the highest incidence of antibodies to HSPs. Although our previous results indicated that workers had an insufficient protein intake,plasma free amino acids tended to increase, especially in methionine and tryptophan two kinds of amino acids which are absent from the main stress protein, HSP70.These results suggest that the major problems that these workers may face are how to facilitate the use of plasma free amino acids and reduce the inhibition of synthesis of normal proteins when they are exposed to occupational harmful factors.These resultsalso add new information on the measurement of HSPs as a potential biomonitor to assess whether organisms are experiencing metabolic stress within their environment.
文摘Combined liver and kidney transplantation(CLKT)is indicated in patients with failure of both organs,or for the treatment of end-stage chronic kidney disease(ESKD)caused by a genetic defect in the liver.The aim of the present review is to provide the most up-to-date overview of the rare conditions as indications for CLKT.They are major indications for CLKT in children.However,in some of them(e.g.,atypical hemolytic uremic syndrome or primary hyperoxaluria),CLKT may be required in adults as well.Primary hyperoxaluria is divided into three types,of which type 1 and 2 lead to ESKD.CLKT has been proven effective in renal function replacement,at the same time preventing recurrence of the disease.Nephronophthisis is associated with liver fibrosis in 5%of cases and these patients are candidates for CLKT.In alpha 1-antitrypsin deficiency,hereditary C3 deficiency,lecithin cholesterol acyltransferase deficiency and glycogen storage diseases,glomerular or tubulointerstitial disease can lead to chronic kidney disease.Liver transplantation as a part of CLKT corrects underlying genetic and consequent metabolic abnormality.In atypical hemolytic uremic syndrome caused by mutations in the genes for factor H,successful CLKT has been reported in a small number of patients.However,for this indication,CLKT has been largely replaced by eculizumab,an anti-C5 antibody.CLKT has been well established to provide immune protection of the transplanted kidney against donor-specific antibodies against class I HLA,facilitating transplantation in a highly sensitized recipient.
