BACKGROUND： Previous studies have indicated preventive acupuncture and moxibustion at the Guanyuan point have positive effects on the immune system of menopausal rats. OBJECTIVE： To observe the effects of preventive...BACKGROUND： Previous studies have indicated preventive acupuncture and moxibustion at the Guanyuan point have positive effects on the immune system of menopausal rats. OBJECTIVE： To observe the effects of preventive acupuncture or moxibustion at the Guanyuan point on interleukin-2 （IL-2） and its receptor （IL-2R mRNA） levels in hypothalamus, serum, and uterus of menopausal rats. DESIGN： Randomized control animal experiment. SETTING： School of Acupuncture and Moxibustion, Beijing University of Chinese Medicine. MATERIALS： This study was performed at the Laboratory of Beijing University of Chinese Medicine from November 2004 to July 2005. The vaginal smear method was used to determine the estrus cycle of 9.5-month-old Sprague Dawley （SD） female rats. Three continuous estrus cycles were measured, and 160 rats with estrus cycle disorder, weighing （300 _＋ 20） g, were included in this study. The rats were randomly divided into four groups： preventive acupuncture group （n =48）, preventive moxibustion group （n =48）, model groups （n =48）, and 10-month-old group （n =16）. Sixteen 3.5-month-old healthy SD female rats, weighing （240 ± 20） g, were also assigned to the young group. All rats were clean grade and were purchased from the Laboratory Animal Center, Beijing University of Chinese Medicine. The experiment was in accordance with animal ethics standards. METHODS： Acupuncture was applied to the preventive acupuncture group at 10 months of age. The needle was inserted upward and perpendicularly two fen to a point that was two fen below the Guanyuan point. The rats freely moved around during needle retention （20 minutes）. Acupuncture was administered twice a week and continued for eight weeks. A moxa cone （small） moxibustion was applied to the preventive moxibustion group at 10 months of age. The rats were caught gently and kept at the same position as the preventive acupuncture group. The moxa cone was ignited and held to the Guanyuan point directly. Only one moxa cone was used each time. After moxibustion, the local skin turned slightly red. Moxibustion was used twice a week and continued for eight weeks. Nothing except gently catching and lying was administered to the model group and the young group. MAIN OUTCOME MEASURES： Radioimmunoassay, in situ hybridization, and similar methods were employed to detect IL-2 in serum and the uterus, as well as IL-2R mRNA expression in the hypothalamus and uterus arcuate nuclei, of the preventive acupuncture group, preventive moxibustion group, model groups （at 12, 14, and 16 months）, 10 month old group （at 10 months）, and the young group （at 4 months）. RESULTS： All 176 rats were included in the final analysis. （1） IL-2R mRNA： IL-2R mRNA expression decreased significantly in the uterus of 12-, 14-, and 16-month-old model groups and in the hypothalamus of 14- and 16-month-old model groups （P 〈 0.05-0.01）. Compared to the same month-aged model groups, the expression of IL-2R mRNA increased significantly in the hypothalamus and uterus of 16-month-old preventive acupuncture or moxibustion groups （P 〈 0.05-0.01）.（2） IL-2：IL-2 in serum of 12- and 14-month-old model groups and in the uterus of 12-, 14-, and 16-month-old model groups decreased significantly compared to the young group （P 〈 0.05-0.01）. IL-2 serum levels increased significantly in the 16-month-old group with preventive moxibustion; in addition, IL-2 expression levels increased significantly in the uterus of the 12-month-old group with preventive moxibustion, as well as the 12- and 16-month-old groups with preventive acupuncture （P 〈 0.05-0.01）. CONCLUSION： As a rat ages and becomes menopausal, IL-2R mRNA expression in the hypothalamus and uterus, as well as IL-2 levels in the serum and uterus, decrease. However, preventive acupuncture and preventive moxibustion can repress the decrease to some extent. This effect is even greater in the late stages of menopause （16-month-old rats）.展开更多
Objective： To investigate the difference of peripheral blood sIL-2R before and after chemotherapy in breast cancer patients, and evaluate the clinical value of the sIL-2R in breast cancer＇s diagnosis and therapy. Me...Objective： To investigate the difference of peripheral blood sIL-2R before and after chemotherapy in breast cancer patients, and evaluate the clinical value of the sIL-2R in breast cancer＇s diagnosis and therapy. Methods： The peripheral blood sIL-2R levels of the breast cancer patients with or without chemotherapy were detected by ELISA. The healthy persons were made as the control group. Results： The sIL-2R levels of the breast cancer patients were higher than that of the control group（P（0.05）; the sIL-2R＇s levels in I^II stage breast cancer were lower than that in Ill^IV stage breast cancer （P（0.05）; the sIL-2R levels of the patients before chemotherapy were higher than that of the patients undergone chemotherapy（P（0.05）; The level of the patient with chemotherapy was still higher than that of the control group （P（0.05）; the sIL-2R levels of the patients whose chemotherapies were noneffective were higher than that of the patients received effective chemotherapies （P（0.05）. There was no significant difference between the group with ER（＋） or PR（＋） and the group with ER（-） or PR（-）（P〉0.05）. Conclusion： The breast cancer patients have the high sIL-2R levels. There is a close relationship between the cancer incidence and the patients, immune situation. The level of sIL-2R could be a clinical index which can be used for evaluating the cancer degree, because the higher levels of sIL-2R can indicate that the immune ability of patient is worse. There is a significant difference between the sIL-2R levels of the patients before chemotherapy and that of the patients undergone chemotherapy.展开更多
Background: Cytokines are mediators of diseases. Expression levels in the blood could be of clinical relevance. Objective: sIL-2Rα is used as a marker for different malignancies in human medicine. The aim of this stu...Background: Cytokines are mediators of diseases. Expression levels in the blood could be of clinical relevance. Objective: sIL-2Rα is used as a marker for different malignancies in human medicine. The aim of this study was to show if sIL-2Rα is detectable and if there is any correlation to different diseases in dogs. Methods: For this purposes sIL-2Rα concentrations in the blood were measured in healthy dogs, in dogs with different non-neoplastic diseases and benign tumors and in dogs with malignant tumors. Serum levels of sIL-2Rα were measured by using a human specific enzyme linked immunosorbent assay (ELISA). Results: Measurement of sIL-2Rα was successful in most of the samples. Dogs with diseases have significantly increased serum levels of sIL-2Rα compared to healthy controls. sIL-2Rα serum levels are higher in patients with non-neoplastic diseases and benign tumors than in those with malignant neoplasia. There is a strong correlation between sIL-2Rα and leukocyte count. Conclusion: Measurements of sIL-2Rα in serum may be helpful in detecting stages and grades of inflammation in the progression of disease. sIL-2Rα could actually not be used as an indicator for malignant diseases in dogs like in humans. The strong correlation between sIL-2Rα and the leukocyte count indicates the inflammatory response to the disease. This could be helpful in giving a prognosis in some cases, because the inflammatory reaction is of prognostic relevance in different diseases including malignant and non-malignant neoplasia. Although the results of our research studies were very promising, further studies should be performed with a canine ELISA.展开更多
Plasma levels of soluble interleukin-2 receptor (sIL-2R) in patients with chronic active hepatitis B (CAHB) or severe hepatitis B (SHB) were measured quantitatively by 'sandwich' ELISA with monoclonal antibodi...Plasma levels of soluble interleukin-2 receptor (sIL-2R) in patients with chronic active hepatitis B (CAHB) or severe hepatitis B (SHB) were measured quantitatively by 'sandwich' ELISA with monoclonal antibodies in order to explore the change of sIL-2R levels, its clinical significance,and its relation to liver damage. The results showed that the plasma sIL-2R levels in patients with CAHB and SHB were much higher than those in normal controls (P < 0. 01 ), and the level ofplasma sIL-2R in patients with SHB was greatly higher than that in patients with CAHB. These results suggest that there is close relation between plasma level of sIL-2R, the clinical types of hepatitis B,and the severity of liver damage. In addition, there is no significant difference in plasma levels of sIL-2R between acute severe hepatitis B (ASHB), subacute severe hepatitis B (SASHB), and chronic severe hepatitis B (CSHB). No relation was found between sIL-2R level and hepatitis B virusreplication activity.展开更多
Esophageal squamous cell carcinoma(ESCC),a malignancy of the digestive system,is highly prevalent and the primary cause of cancer-related deaths worldwide due to the lack of early diagnostic biomarkers and effective t...Esophageal squamous cell carcinoma(ESCC),a malignancy of the digestive system,is highly prevalent and the primary cause of cancer-related deaths worldwide due to the lack of early diagnostic biomarkers and effective therapeutic targets.Dysregulated ribonucleotide reductase(RNR)expression has been confirmed to be causally linked to tumorigenesis.This study demonstrated that ribonucleotide reductase small subunit M2(RRM2)is significantly upregulated in ESCC tissue and that its expression is negatively correlated with clinical outcomes.Mechanistically,HuR promotes RRM2 mRNA stabilization by binding to the adenine/uridine(AU)-rich elements(AREs)within the 3′UTR,resulting in persistent overexpression of RRM2.Furthermore,bifonazole is identified as an inhibitor of HuR via computational screening and molecular docking analysis.Bifonazole disrupts HuR-ARE interactions by competitively binding to HuR at F65,R97,I103,and R153 residues,resulting in reduced RRM2 expression.Furthermore,bifonazole exhibited antitumor effects on ESCC patient-derived xenograft(PDX)models by decreasing RRM2 expression and the dNTP pool.In summary,this study reveals the interaction network among HuR,RRM2,and bifonazole and demonstrated that bifonazole is a potential therapeutic compound for ESCC through inhibition of the HuR/RRM2 axis.展开更多
基金the National Nature Science Foundation of China, No. 90209026Natural Science Foundation of Beijing, No. 7052037
文摘BACKGROUND： Previous studies have indicated preventive acupuncture and moxibustion at the Guanyuan point have positive effects on the immune system of menopausal rats. OBJECTIVE： To observe the effects of preventive acupuncture or moxibustion at the Guanyuan point on interleukin-2 （IL-2） and its receptor （IL-2R mRNA） levels in hypothalamus, serum, and uterus of menopausal rats. DESIGN： Randomized control animal experiment. SETTING： School of Acupuncture and Moxibustion, Beijing University of Chinese Medicine. MATERIALS： This study was performed at the Laboratory of Beijing University of Chinese Medicine from November 2004 to July 2005. The vaginal smear method was used to determine the estrus cycle of 9.5-month-old Sprague Dawley （SD） female rats. Three continuous estrus cycles were measured, and 160 rats with estrus cycle disorder, weighing （300 _＋ 20） g, were included in this study. The rats were randomly divided into four groups： preventive acupuncture group （n =48）, preventive moxibustion group （n =48）, model groups （n =48）, and 10-month-old group （n =16）. Sixteen 3.5-month-old healthy SD female rats, weighing （240 ± 20） g, were also assigned to the young group. All rats were clean grade and were purchased from the Laboratory Animal Center, Beijing University of Chinese Medicine. The experiment was in accordance with animal ethics standards. METHODS： Acupuncture was applied to the preventive acupuncture group at 10 months of age. The needle was inserted upward and perpendicularly two fen to a point that was two fen below the Guanyuan point. The rats freely moved around during needle retention （20 minutes）. Acupuncture was administered twice a week and continued for eight weeks. A moxa cone （small） moxibustion was applied to the preventive moxibustion group at 10 months of age. The rats were caught gently and kept at the same position as the preventive acupuncture group. The moxa cone was ignited and held to the Guanyuan point directly. Only one moxa cone was used each time. After moxibustion, the local skin turned slightly red. Moxibustion was used twice a week and continued for eight weeks. Nothing except gently catching and lying was administered to the model group and the young group. MAIN OUTCOME MEASURES： Radioimmunoassay, in situ hybridization, and similar methods were employed to detect IL-2 in serum and the uterus, as well as IL-2R mRNA expression in the hypothalamus and uterus arcuate nuclei, of the preventive acupuncture group, preventive moxibustion group, model groups （at 12, 14, and 16 months）, 10 month old group （at 10 months）, and the young group （at 4 months）. RESULTS： All 176 rats were included in the final analysis. （1） IL-2R mRNA： IL-2R mRNA expression decreased significantly in the uterus of 12-, 14-, and 16-month-old model groups and in the hypothalamus of 14- and 16-month-old model groups （P 〈 0.05-0.01）. Compared to the same month-aged model groups, the expression of IL-2R mRNA increased significantly in the hypothalamus and uterus of 16-month-old preventive acupuncture or moxibustion groups （P 〈 0.05-0.01）.（2） IL-2：IL-2 in serum of 12- and 14-month-old model groups and in the uterus of 12-, 14-, and 16-month-old model groups decreased significantly compared to the young group （P 〈 0.05-0.01）. IL-2 serum levels increased significantly in the 16-month-old group with preventive moxibustion; in addition, IL-2 expression levels increased significantly in the uterus of the 12-month-old group with preventive moxibustion, as well as the 12- and 16-month-old groups with preventive acupuncture （P 〈 0.05-0.01）. CONCLUSION： As a rat ages and becomes menopausal, IL-2R mRNA expression in the hypothalamus and uterus, as well as IL-2 levels in the serum and uterus, decrease. However, preventive acupuncture and preventive moxibustion can repress the decrease to some extent. This effect is even greater in the late stages of menopause （16-month-old rats）.
文摘Objective： To investigate the difference of peripheral blood sIL-2R before and after chemotherapy in breast cancer patients, and evaluate the clinical value of the sIL-2R in breast cancer＇s diagnosis and therapy. Methods： The peripheral blood sIL-2R levels of the breast cancer patients with or without chemotherapy were detected by ELISA. The healthy persons were made as the control group. Results： The sIL-2R levels of the breast cancer patients were higher than that of the control group（P（0.05）; the sIL-2R＇s levels in I^II stage breast cancer were lower than that in Ill^IV stage breast cancer （P（0.05）; the sIL-2R levels of the patients before chemotherapy were higher than that of the patients undergone chemotherapy（P（0.05）; The level of the patient with chemotherapy was still higher than that of the control group （P（0.05）; the sIL-2R levels of the patients whose chemotherapies were noneffective were higher than that of the patients received effective chemotherapies （P（0.05）. There was no significant difference between the group with ER（＋） or PR（＋） and the group with ER（-） or PR（-）（P〉0.05）. Conclusion： The breast cancer patients have the high sIL-2R levels. There is a close relationship between the cancer incidence and the patients, immune situation. The level of sIL-2R could be a clinical index which can be used for evaluating the cancer degree, because the higher levels of sIL-2R can indicate that the immune ability of patient is worse. There is a significant difference between the sIL-2R levels of the patients before chemotherapy and that of the patients undergone chemotherapy.
文摘Background: Cytokines are mediators of diseases. Expression levels in the blood could be of clinical relevance. Objective: sIL-2Rα is used as a marker for different malignancies in human medicine. The aim of this study was to show if sIL-2Rα is detectable and if there is any correlation to different diseases in dogs. Methods: For this purposes sIL-2Rα concentrations in the blood were measured in healthy dogs, in dogs with different non-neoplastic diseases and benign tumors and in dogs with malignant tumors. Serum levels of sIL-2Rα were measured by using a human specific enzyme linked immunosorbent assay (ELISA). Results: Measurement of sIL-2Rα was successful in most of the samples. Dogs with diseases have significantly increased serum levels of sIL-2Rα compared to healthy controls. sIL-2Rα serum levels are higher in patients with non-neoplastic diseases and benign tumors than in those with malignant neoplasia. There is a strong correlation between sIL-2Rα and leukocyte count. Conclusion: Measurements of sIL-2Rα in serum may be helpful in detecting stages and grades of inflammation in the progression of disease. sIL-2Rα could actually not be used as an indicator for malignant diseases in dogs like in humans. The strong correlation between sIL-2Rα and the leukocyte count indicates the inflammatory response to the disease. This could be helpful in giving a prognosis in some cases, because the inflammatory reaction is of prognostic relevance in different diseases including malignant and non-malignant neoplasia. Although the results of our research studies were very promising, further studies should be performed with a canine ELISA.
文摘Plasma levels of soluble interleukin-2 receptor (sIL-2R) in patients with chronic active hepatitis B (CAHB) or severe hepatitis B (SHB) were measured quantitatively by 'sandwich' ELISA with monoclonal antibodies in order to explore the change of sIL-2R levels, its clinical significance,and its relation to liver damage. The results showed that the plasma sIL-2R levels in patients with CAHB and SHB were much higher than those in normal controls (P < 0. 01 ), and the level ofplasma sIL-2R in patients with SHB was greatly higher than that in patients with CAHB. These results suggest that there is close relation between plasma level of sIL-2R, the clinical types of hepatitis B,and the severity of liver damage. In addition, there is no significant difference in plasma levels of sIL-2R between acute severe hepatitis B (ASHB), subacute severe hepatitis B (SASHB), and chronic severe hepatitis B (CSHB). No relation was found between sIL-2R level and hepatitis B virusreplication activity.
基金funded by National Natural Science Foundation of China(grant numbers:81872335,82303891 and 82303119)The Central Plains Science and Technology Innovation Leading Talents(No.224200510015,China)+1 种基金Key scientific research project plan of colleges and universities in Henan Province(grant number:24A310025,China)Science and Technology Project of Henan Province(No.242102310414,China).
文摘Esophageal squamous cell carcinoma(ESCC),a malignancy of the digestive system,is highly prevalent and the primary cause of cancer-related deaths worldwide due to the lack of early diagnostic biomarkers and effective therapeutic targets.Dysregulated ribonucleotide reductase(RNR)expression has been confirmed to be causally linked to tumorigenesis.This study demonstrated that ribonucleotide reductase small subunit M2(RRM2)is significantly upregulated in ESCC tissue and that its expression is negatively correlated with clinical outcomes.Mechanistically,HuR promotes RRM2 mRNA stabilization by binding to the adenine/uridine(AU)-rich elements(AREs)within the 3′UTR,resulting in persistent overexpression of RRM2.Furthermore,bifonazole is identified as an inhibitor of HuR via computational screening and molecular docking analysis.Bifonazole disrupts HuR-ARE interactions by competitively binding to HuR at F65,R97,I103,and R153 residues,resulting in reduced RRM2 expression.Furthermore,bifonazole exhibited antitumor effects on ESCC patient-derived xenograft(PDX)models by decreasing RRM2 expression and the dNTP pool.In summary,this study reveals the interaction network among HuR,RRM2,and bifonazole and demonstrated that bifonazole is a potential therapeutic compound for ESCC through inhibition of the HuR/RRM2 axis.
