Triple-negative breast cancer(TNBC) is defined by the lack of immunohistochemical expression of the estrogen and progesterone receptors and human epidermal growth factor receptor 2(EGFR2). Most TNBC has a basal-like m...Triple-negative breast cancer(TNBC) is defined by the lack of immunohistochemical expression of the estrogen and progesterone receptors and human epidermal growth factor receptor 2(EGFR2). Most TNBC has a basal-like molecular phenotype by gene expression profiling and shares clinical and pathological features with hereditary BRCA1 related breast cancers. This review evaluates the activity of available chemotherapy and targeted agents in TNBC. A systematic review of PubM ed and conference databases was carried out to identify randomised clinical trials reporting outcomes in women with TNBC treated with chemotherapy and targeted agents. Our review identified TNBC studies of chemotherapy and targeted agents with different mechanisms of action, including induction of synthetic lethality and inhibition of angiogenesis, growth and survival pathways. TNBC is sensitive to taxanes and anthracyclins. Platinum agents are effective in TNBC patients with BRCA1 mutation, either alone or in combination with poly adenosine diphosphate polymerase 1 inhibitors. Combinations of ixabepilone and capecitabine have added to progression-free survival(PFS) without survival benefit in metastatic TNBC. Antiangiogenic agents, tyrosine kinase inhibitors and EGFR inhibitorsin combination with chemotherapy produced only modest gains in PFS and had little impact on survival. TNBC subgroups respond differentially to specific targeted agents. In future, the treatment needs to be tailored for a specific patient, depending on the molecular characteristics of their malignancy. TNBC being a chemosensitive entity, combination with targeted agents have not produced substantial improvements in outcomes. Appropriate patient selection with rationale combinations of targeted agents is needed for success.展开更多
聚腺苷二磷酸核糖聚合酶[poly(ADP-ribose)polymerase,PARP]抑制剂与乳腺癌易感基因1(breast cancer susceptibility gene 1,BRCA1)/BRCA2突变介导的合成致死理论,为抗癌药物的研发提供了新的方向。这是一种通过抑制肿瘤细胞DNA损伤修复...聚腺苷二磷酸核糖聚合酶[poly(ADP-ribose)polymerase,PARP]抑制剂与乳腺癌易感基因1(breast cancer susceptibility gene 1,BRCA1)/BRCA2突变介导的合成致死理论,为抗癌药物的研发提供了新的方向。这是一种通过抑制肿瘤细胞DNA损伤修复,从而杀伤肿瘤细胞的安全而有效的新型治疗方式。自研究证实PARP抑制剂可引起乳腺癌细胞的合成致死效应以来,已研发出许多选择性和敏感性均较好的PARP抑制剂,且大部分已进入临床试验阶段。尽管PARP抑制剂单药在BRCA1/BRCA2突变的乳腺癌和卵巢癌中可发挥治疗效应,但目前的PARP抑制剂在临床应用时,仍是与其他化疗药物或放射治疗联合使用。本综述对已报道的PARP抑制剂联合常用化疗药物治疗肿瘤的研究进展进行小结。展开更多
Background Poly（ADP-ribose） polymerase （PARP） plays an important role in cell survival and death. However, the mechanisms involved are not fully understood. Therefore, we investigated the effect of inhibition of P...Background Poly（ADP-ribose） polymerase （PARP） plays an important role in cell survival and death. However, the mechanisms involved are not fully understood. Therefore, we investigated the effect of inhibition of PARP on acute myocardial infarction （AMI） at different time points in rats. Methods AMI was induced in rats by ligating the left anterior descending coronary artery. One group received 3-aminobenzamide （3-AB, a kind of PARP inhibitor） （30 mg/kg） by intraperitoneal injection. The changes of ultramicrostructure of cardiocytes in infarction region were noted, PARP cleavage was measured by Western blotting, and expressions of protein of PARP and apoptosis inducing factor （AIF） were measured by immunohistochemical staining after treatment with 3-AB for 2 hours, 4 hours, 6 hours, 1 week, 4 weeks and 8 weeks. Results Few damages to the ultramicrostructure of cardiocytes were observed after treatment with 3-AB. PARP cleavage was detected as early as 4 hours and markedly increased by 6 hours following AMI without 3-AB, but was not found until 6 hours following AMI treated with 3-AB. There were significant differences between 3-AB and AMI groups at the same time points. The expression of PARP was observed gradually increased, but that of AIF was suppressed for 6 hours after treatment of 3-AB, compared with AMI groups in positive cells at the same time points. There was significantly less cleavage of PARP and more PARP expression in 3-AB treated group compared with AMI and control groups at all matched time points. Conclusions Our results suggest that 3-AB inhibits degradation of PARP, increases the expression of PARP protein, and suppresses the expression of AIF protein. Inhibition of PARP activity may protect cardiocytes in rats with AMI and reduce apoptosis.展开更多
Background Poly （ADP-ribose） polymerase （PARP） has been proposed to play an important role in the pathogenesis of heart ischaemia/reperfusion （I/R） injury. 3,4-dihydro-5-[4-（1-piperidinyl）butoxy]-l（2H）-isoqu...Background Poly （ADP-ribose） polymerase （PARP） has been proposed to play an important role in the pathogenesis of heart ischaemia/reperfusion （I/R） injury. 3,4-dihydro-5-[4-（1-piperidinyl）butoxy]-l（2H）-isoquinolinone （DPQ）, a potent PARP inhibitor, has cardiac protective effects. Because the underlying mechanisms are not understood, we investigated the effect of DPQ on heart I/R injury and its mechanisms. Methods Studies were performed with I/R rats＇ hearts. DPQ was used to inhibit the activation of PARP. Cardiac function and cellular apoptosis were assessed. The activation of PARP, transcription factor nuclear factor-kappaB （NF-KB）, intercellular adhesion molecule-1 （ICAM-1）, cyclooxygenase-2 （COX-2） and matrix metalloproteinase-9 （MMP-9） were evaluated. We also evaluated expression of Akt and two of its downstream targets, glycogen synthase kinase-313 （GSK- 3β） and forkhead transcription factor FOXO3a. Results Administration of DPQ significantly decreased the activation of PARP and cellular apoptosis from （35±5）% to （20±4）% and simultaneously improved the cardiac function. DPQ reduced the expressions of NF-KB, ICAM-1, COX-2 and MMP-9 in rat heart and facilitated the activations of phosphor-Akt, phosphor-GSK-3β and phosphor-FOXO3a. Conclusion The protective effects of DPQ were associated with the suppression of inflammation and the activation of the Akt signalling pathways suggesting that the inhibition of poly （ADP-ribose） polymerase reduced heart I/R injury in rats.展开更多
Background:Metastatic triple-negative breast cancer(mTNBC)is an aggressive histological subtype with poor prognosis.Several first-line treatments are currently available for mTNBC.This study conducted a network meta-a...Background:Metastatic triple-negative breast cancer(mTNBC)is an aggressive histological subtype with poor prognosis.Several first-line treatments are currently available for mTNBC.This study conducted a network meta-analysis to compare these first-line regimens and to determine the regimen with the best efficacy.Methods:A systematic search of PubMed,EMBASE,the Cochrane Central Register of Controlled Bases,and mi-nutes of major conferences was performed.Progression-free survival(PFS),overall survival(OS),and objective response rate(ORR)were analyzed via network meta-analysis using the R software(R Core Team,Vienna,Austria).The efficacy of the treatment regimens was compared using hazard ratios and 95%confidence intervals.Results:A total of 29 randomized controlled trials involving 4607 patients were analyzed.The ranking was based on the surface under the cumulative ranking curve.Network meta-analysis results showed that cisplatin combined with nab-paclitaxel or paclitaxel was superior to docetaxel plus capecitabine in terms of PFS and ORR.For programmed death-ligand 1(PD-L1)and breast cancer susceptibility gene(BRCA)mutation-positive tumors,atezolizumab/pembrolizumab combined with nab-paclitaxel and talazoparib was superior to docetaxel plus capecitabine.No significant difference was observed among the treatments in Os.Neutropenia,diarrhea,and fatigue were common serious adverse events.Conclusion:Cisplatin combined with nab-paclitaxel or paclitaxel is the preferred first-line treatment for mTNBC.For PD-L1 and BRCA mutation-positive tumors,atezolizumab/pembrolizumab combined with nab-paclitaxel and talazoparib is an effective treatment option,Neutropenia,diarrhea,and fatigue are frequently occurring serious adverseevents.展开更多
PARP inhibitors(PARPi)are a kind of cancer therapy that targets poly(ADP-ribose)polymerase.PARPi is the first clinically approved drug to exert synthetic lethality by obstruct-ing the DNA single-strand break repair pr...PARP inhibitors(PARPi)are a kind of cancer therapy that targets poly(ADP-ribose)polymerase.PARPi is the first clinically approved drug to exert synthetic lethality by obstruct-ing the DNA single-strand break repair process.Despite the significant therapeutic effect in pa-tients with homologous recombination(HR)repair deficiency,innate and acquired resistance to PARPi is a main challenge in the clinic.In this review,we mainly discussed the underlying mechanisms of PARPi resistance and summarized the promising solutions to overcome PARPi resistance,aiming at extending PARPi application and improving patient outcomes.展开更多
BACKGROUND Poly(ADP-ribose)polymerase inhibitors(PARPis)are approved as first-line therapies for breast cancer gene(BRCA)-positive,human epidermal growth factor receptor 2-negative locally advanced or metastatic breas...BACKGROUND Poly(ADP-ribose)polymerase inhibitors(PARPis)are approved as first-line therapies for breast cancer gene(BRCA)-positive,human epidermal growth factor receptor 2-negative locally advanced or metastatic breast cancer.They are also effective for new and recurrent ovarian cancers that are BRCA-or homologous recombination deficiency(HRD)-positive.However,data on these mutations and PARPi use in the Middle East are limited.AIM To assess BRCA/HRD prevalence and PARPi use in patients in the Middle East with breast/ovarian cancer.METHODS This was a single-center retrospective study of 57 of 472 breast cancer patients tested for BRCA mutations,and 25 of 65 ovarian cancer patients tested for HRD.These adult patients participated in at least four visits to the oncology service at our center between August 2021 and May 2023.Data were summarized using descriptive statistics and compared using counts and percentages.Response to treatment was assessed using Response Evaluation Criteria in Solid Tumors criteria.RESULTS Among the 472 breast cancer patients,12.1%underwent BRCA testing,and 38.5%of 65 ovarian cancer patients received HRD testing.Pathogenic mutations were found in 25.6%of the tested patients:26.3%breast cancers had germline BRCA(gBRCA)mutations and 24.0%ovarian cancers showed HRD.Notably,40.0%of gBRCA-positive breast cancers and 66.0%of HRD-positive ovarian cancers were Middle Eastern and Asian patients,respectively.PARPi treatment was used in 5(33.3%)gBRCA-positive breast cancer patients as first-line therapy(n=1;7-months progression-free),for maintenance(n=2;>15-months progression-free),or at later stages due to compliance issues(n=2).Four patients(66.6%)with HRD-positive ovarian cancer received PARPi and all remained progression-free.CONCLUSION Lower testing rates but higher BRCA mutations in breast cancer were found.Ethnicity reflected United Arab Emirates demographics,with breast cancer in Middle Eastern and ovarian cancer in Asian patients.展开更多
Background Poly（ADP-ribose） polymerase （PARP） plays an important role in the death of retinal capillary cells in diabetic retinopathy （DR） partly via its regulation of nuclear factor kappa B （NF-κB）. The curr...Background Poly（ADP-ribose） polymerase （PARP） plays an important role in the death of retinal capillary cells in diabetic retinopathy （DR） partly via its regulation of nuclear factor kappa B （NF-κB）. The current study investigated the effect of the regimen of Gaoshan Hongjingtian （RG） on the mechanism of PARP regulation of NF-κB, and demonstrated the possible impact of the RG and Gaoshan Hongjingtian （Rhodiola sachalinensis, RS） on diabetic retinopathy. Methods Wistar rats were made diabetic by administering streptozotocin. They were then assigned to three groups at random. After 2 months, the three groups of these diabetic rats were treated with RS or RG, or untreated. Analyses of expression levels of PARP, NF-κB, and intercellular adhesion molecule-1 （ICAM-1） in the retinas of rats in different groups were performed by Western blotting and immunohistochemical assays, and mRNA levels of NF-κB and ICAM-1 were determined by real-time polymerase chain reaction （PCR）. In addition, the basement membranes of capillaries in the rats＇ retinas were observed using electron microscopy, and diabetes-induced capillary degeneration （ghost pericytes and acellular capillaries） were quantitated. Results From the third month after the injection of streptozotocin, the diabetic rats were given daily RG, RS or tap water separately. The diabetic rats failed to gain weight compared with normal age-matched rats, whereas their glycated hemoglobin levels were significantly increased. After 5 months, the mRNA levels of NF-KB and ICAM-1 and the protein expression of PARP, NF-κB, and ICAM-1 were significantly increased in the retinas of diabetic rats in the untreated group compared with the nondiabetic controls. After 8 months, the number of degenerated retinal capillaries （ghost pericytes and acellular capillaries） was significantly increased in the diabetic rats in the untreated group compared with normal age-matched rats. RG and RS inhibited diabetes-induced over-expression of PARP, NF-KB, a展开更多
文摘Triple-negative breast cancer(TNBC) is defined by the lack of immunohistochemical expression of the estrogen and progesterone receptors and human epidermal growth factor receptor 2(EGFR2). Most TNBC has a basal-like molecular phenotype by gene expression profiling and shares clinical and pathological features with hereditary BRCA1 related breast cancers. This review evaluates the activity of available chemotherapy and targeted agents in TNBC. A systematic review of PubM ed and conference databases was carried out to identify randomised clinical trials reporting outcomes in women with TNBC treated with chemotherapy and targeted agents. Our review identified TNBC studies of chemotherapy and targeted agents with different mechanisms of action, including induction of synthetic lethality and inhibition of angiogenesis, growth and survival pathways. TNBC is sensitive to taxanes and anthracyclins. Platinum agents are effective in TNBC patients with BRCA1 mutation, either alone or in combination with poly adenosine diphosphate polymerase 1 inhibitors. Combinations of ixabepilone and capecitabine have added to progression-free survival(PFS) without survival benefit in metastatic TNBC. Antiangiogenic agents, tyrosine kinase inhibitors and EGFR inhibitorsin combination with chemotherapy produced only modest gains in PFS and had little impact on survival. TNBC subgroups respond differentially to specific targeted agents. In future, the treatment needs to be tailored for a specific patient, depending on the molecular characteristics of their malignancy. TNBC being a chemosensitive entity, combination with targeted agents have not produced substantial improvements in outcomes. Appropriate patient selection with rationale combinations of targeted agents is needed for success.
文摘聚腺苷二磷酸核糖聚合酶[poly(ADP-ribose)polymerase,PARP]抑制剂与乳腺癌易感基因1(breast cancer susceptibility gene 1,BRCA1)/BRCA2突变介导的合成致死理论,为抗癌药物的研发提供了新的方向。这是一种通过抑制肿瘤细胞DNA损伤修复,从而杀伤肿瘤细胞的安全而有效的新型治疗方式。自研究证实PARP抑制剂可引起乳腺癌细胞的合成致死效应以来,已研发出许多选择性和敏感性均较好的PARP抑制剂,且大部分已进入临床试验阶段。尽管PARP抑制剂单药在BRCA1/BRCA2突变的乳腺癌和卵巢癌中可发挥治疗效应,但目前的PARP抑制剂在临床应用时,仍是与其他化疗药物或放射治疗联合使用。本综述对已报道的PARP抑制剂联合常用化疗药物治疗肿瘤的研究进展进行小结。
基金This research was supported by grants from Natural Science Foundation of Heilongjiang Province （No. D2007-23）, Post-doctoral Foundation of Heilongjiang Province （No. LRB-06-288） and Department of Education of Heilongjiang Province （No. 11531210）.
文摘Background Poly（ADP-ribose） polymerase （PARP） plays an important role in cell survival and death. However, the mechanisms involved are not fully understood. Therefore, we investigated the effect of inhibition of PARP on acute myocardial infarction （AMI） at different time points in rats. Methods AMI was induced in rats by ligating the left anterior descending coronary artery. One group received 3-aminobenzamide （3-AB, a kind of PARP inhibitor） （30 mg/kg） by intraperitoneal injection. The changes of ultramicrostructure of cardiocytes in infarction region were noted, PARP cleavage was measured by Western blotting, and expressions of protein of PARP and apoptosis inducing factor （AIF） were measured by immunohistochemical staining after treatment with 3-AB for 2 hours, 4 hours, 6 hours, 1 week, 4 weeks and 8 weeks. Results Few damages to the ultramicrostructure of cardiocytes were observed after treatment with 3-AB. PARP cleavage was detected as early as 4 hours and markedly increased by 6 hours following AMI without 3-AB, but was not found until 6 hours following AMI treated with 3-AB. There were significant differences between 3-AB and AMI groups at the same time points. The expression of PARP was observed gradually increased, but that of AIF was suppressed for 6 hours after treatment of 3-AB, compared with AMI groups in positive cells at the same time points. There was significantly less cleavage of PARP and more PARP expression in 3-AB treated group compared with AMI and control groups at all matched time points. Conclusions Our results suggest that 3-AB inhibits degradation of PARP, increases the expression of PARP protein, and suppresses the expression of AIF protein. Inhibition of PARP activity may protect cardiocytes in rats with AMI and reduce apoptosis.
基金This study was supported by grants from the Natural Science Foundation of Shandong Province, China （No.ZR2010HM069） and the Technology Development Projects of Taian City （No. 20093077）.
文摘Background Poly （ADP-ribose） polymerase （PARP） has been proposed to play an important role in the pathogenesis of heart ischaemia/reperfusion （I/R） injury. 3,4-dihydro-5-[4-（1-piperidinyl）butoxy]-l（2H）-isoquinolinone （DPQ）, a potent PARP inhibitor, has cardiac protective effects. Because the underlying mechanisms are not understood, we investigated the effect of DPQ on heart I/R injury and its mechanisms. Methods Studies were performed with I/R rats＇ hearts. DPQ was used to inhibit the activation of PARP. Cardiac function and cellular apoptosis were assessed. The activation of PARP, transcription factor nuclear factor-kappaB （NF-KB）, intercellular adhesion molecule-1 （ICAM-1）, cyclooxygenase-2 （COX-2） and matrix metalloproteinase-9 （MMP-9） were evaluated. We also evaluated expression of Akt and two of its downstream targets, glycogen synthase kinase-313 （GSK- 3β） and forkhead transcription factor FOXO3a. Results Administration of DPQ significantly decreased the activation of PARP and cellular apoptosis from （35±5）% to （20±4）% and simultaneously improved the cardiac function. DPQ reduced the expressions of NF-KB, ICAM-1, COX-2 and MMP-9 in rat heart and facilitated the activations of phosphor-Akt, phosphor-GSK-3β and phosphor-FOXO3a. Conclusion The protective effects of DPQ were associated with the suppression of inflammation and the activation of the Akt signalling pathways suggesting that the inhibition of poly （ADP-ribose） polymerase reduced heart I/R injury in rats.
文摘Background:Metastatic triple-negative breast cancer(mTNBC)is an aggressive histological subtype with poor prognosis.Several first-line treatments are currently available for mTNBC.This study conducted a network meta-analysis to compare these first-line regimens and to determine the regimen with the best efficacy.Methods:A systematic search of PubMed,EMBASE,the Cochrane Central Register of Controlled Bases,and mi-nutes of major conferences was performed.Progression-free survival(PFS),overall survival(OS),and objective response rate(ORR)were analyzed via network meta-analysis using the R software(R Core Team,Vienna,Austria).The efficacy of the treatment regimens was compared using hazard ratios and 95%confidence intervals.Results:A total of 29 randomized controlled trials involving 4607 patients were analyzed.The ranking was based on the surface under the cumulative ranking curve.Network meta-analysis results showed that cisplatin combined with nab-paclitaxel or paclitaxel was superior to docetaxel plus capecitabine in terms of PFS and ORR.For programmed death-ligand 1(PD-L1)and breast cancer susceptibility gene(BRCA)mutation-positive tumors,atezolizumab/pembrolizumab combined with nab-paclitaxel and talazoparib was superior to docetaxel plus capecitabine.No significant difference was observed among the treatments in Os.Neutropenia,diarrhea,and fatigue were common serious adverse events.Conclusion:Cisplatin combined with nab-paclitaxel or paclitaxel is the preferred first-line treatment for mTNBC.For PD-L1 and BRCA mutation-positive tumors,atezolizumab/pembrolizumab combined with nab-paclitaxel and talazoparib is an effective treatment option,Neutropenia,diarrhea,and fatigue are frequently occurring serious adverseevents.
文摘PARP inhibitors(PARPi)are a kind of cancer therapy that targets poly(ADP-ribose)polymerase.PARPi is the first clinically approved drug to exert synthetic lethality by obstruct-ing the DNA single-strand break repair process.Despite the significant therapeutic effect in pa-tients with homologous recombination(HR)repair deficiency,innate and acquired resistance to PARPi is a main challenge in the clinic.In this review,we mainly discussed the underlying mechanisms of PARPi resistance and summarized the promising solutions to overcome PARPi resistance,aiming at extending PARPi application and improving patient outcomes.
文摘BACKGROUND Poly(ADP-ribose)polymerase inhibitors(PARPis)are approved as first-line therapies for breast cancer gene(BRCA)-positive,human epidermal growth factor receptor 2-negative locally advanced or metastatic breast cancer.They are also effective for new and recurrent ovarian cancers that are BRCA-or homologous recombination deficiency(HRD)-positive.However,data on these mutations and PARPi use in the Middle East are limited.AIM To assess BRCA/HRD prevalence and PARPi use in patients in the Middle East with breast/ovarian cancer.METHODS This was a single-center retrospective study of 57 of 472 breast cancer patients tested for BRCA mutations,and 25 of 65 ovarian cancer patients tested for HRD.These adult patients participated in at least four visits to the oncology service at our center between August 2021 and May 2023.Data were summarized using descriptive statistics and compared using counts and percentages.Response to treatment was assessed using Response Evaluation Criteria in Solid Tumors criteria.RESULTS Among the 472 breast cancer patients,12.1%underwent BRCA testing,and 38.5%of 65 ovarian cancer patients received HRD testing.Pathogenic mutations were found in 25.6%of the tested patients:26.3%breast cancers had germline BRCA(gBRCA)mutations and 24.0%ovarian cancers showed HRD.Notably,40.0%of gBRCA-positive breast cancers and 66.0%of HRD-positive ovarian cancers were Middle Eastern and Asian patients,respectively.PARPi treatment was used in 5(33.3%)gBRCA-positive breast cancer patients as first-line therapy(n=1;7-months progression-free),for maintenance(n=2;>15-months progression-free),or at later stages due to compliance issues(n=2).Four patients(66.6%)with HRD-positive ovarian cancer received PARPi and all remained progression-free.CONCLUSION Lower testing rates but higher BRCA mutations in breast cancer were found.Ethnicity reflected United Arab Emirates demographics,with breast cancer in Middle Eastern and ovarian cancer in Asian patients.
基金This study was supported by a grant from the National Natural Science Foundation of China （No. 81072844）.
文摘Background Poly（ADP-ribose） polymerase （PARP） plays an important role in the death of retinal capillary cells in diabetic retinopathy （DR） partly via its regulation of nuclear factor kappa B （NF-κB）. The current study investigated the effect of the regimen of Gaoshan Hongjingtian （RG） on the mechanism of PARP regulation of NF-κB, and demonstrated the possible impact of the RG and Gaoshan Hongjingtian （Rhodiola sachalinensis, RS） on diabetic retinopathy. Methods Wistar rats were made diabetic by administering streptozotocin. They were then assigned to three groups at random. After 2 months, the three groups of these diabetic rats were treated with RS or RG, or untreated. Analyses of expression levels of PARP, NF-κB, and intercellular adhesion molecule-1 （ICAM-1） in the retinas of rats in different groups were performed by Western blotting and immunohistochemical assays, and mRNA levels of NF-κB and ICAM-1 were determined by real-time polymerase chain reaction （PCR）. In addition, the basement membranes of capillaries in the rats＇ retinas were observed using electron microscopy, and diabetes-induced capillary degeneration （ghost pericytes and acellular capillaries） were quantitated. Results From the third month after the injection of streptozotocin, the diabetic rats were given daily RG, RS or tap water separately. The diabetic rats failed to gain weight compared with normal age-matched rats, whereas their glycated hemoglobin levels were significantly increased. After 5 months, the mRNA levels of NF-KB and ICAM-1 and the protein expression of PARP, NF-κB, and ICAM-1 were significantly increased in the retinas of diabetic rats in the untreated group compared with the nondiabetic controls. After 8 months, the number of degenerated retinal capillaries （ghost pericytes and acellular capillaries） was significantly increased in the diabetic rats in the untreated group compared with normal age-matched rats. RG and RS inhibited diabetes-induced over-expression of PARP, NF-KB, a
