We sought to investigate the effects of telmisartan on high-fat diet-induced hypertension and to explore the possible underlying mechanisms. Rats receiving high-fat diet were randomly divided into two groups, the tel-...We sought to investigate the effects of telmisartan on high-fat diet-induced hypertension and to explore the possible underlying mechanisms. Rats receiving high-fat diet were randomly divided into two groups, the tel- misartan group （n = 9） and the high-fat diet group （n = 10）. The control group consisted of age-matched rats on a regular diet （n = 10）. At the end of the treatment, the body weight, blood pressure, insulin sensitivity and serum adiponectin levels of all rats were examined, and their visceral fat was extracted and weighed. Our results showed that telmisartan improved insulin resistance and dyslipidemia and increased serum adiponectin levels. Telmisar- tan also lowered both systolic blood pressure and diastolic blood pressure, and decreased the accumulation of perirenal fat associated with high-fat diet. Furthermore, telmisartan increased adiponectin mRNA expression in the perirenal fat. Correlation analysis showed that both systolic blood pressure and diastolic blood pressure were positively correlated with perirenal fat. These effects of telmisartan may be mediated through decreases in perirenal fat and contributed to the improvement of perirenal fat function. Our findings suggested a strong link between perirenal fat and high-fat diet-induced hypertension, and identified telmisartan as a potential drug for the treatment of obesity-related hypertension.展开更多
ABSTRACT:Although radiotherapy(RT)can induce immunogenic cell death(ICD),the endogenous resistance of tumor cells to X-rays and the immunosuppressive microenvironment has suppressed its therapeutic effect,which can ea...ABSTRACT:Although radiotherapy(RT)can induce immunogenic cell death(ICD),the endogenous resistance of tumor cells to X-rays and the immunosuppressive microenvironment has suppressed its therapeutic effect,which can easily lead to tumor recurrence and metastasis after RT.Herein,we prepared a glutathione(GSH)-responsive system called AHD,by loading Aurora-A inhibitor alisertib(Ali)and iron protoporphyrin Ⅸ chloride(Hemin),for X-raytriggered continuous reactive oxygen species(ROS)generation to sensitize breast cancer senescence immunotherapy.AHD accumulates at the tumor tissue through the enhanced permeability and retention(EPR)effect,shows high specificity for the tumor microenvironment with overexpressed GSH,and rapidly releases Ali and Hemin.Under external X-ray irradiation,tumor cells produce H_(2)O_(2),and AHD activates Hemin to catalyze the chemical kinetics process of H_(2)O_(2),continuously generating hydroxyl radicals(·OH).Meanwhile,AHD can also induce tumor cell senescence by up-regulating P21 and P16 expressions.In vitro and in vivo experimental results show that the cascade ROS generation induced by the AHD system can trigger extensive ICD in tumor cells,alleviate the immunosuppressive microenvironment after RT,activate the anti-tumor immune ability of CD8^(+)T cells.Therefore,AHD can be used as a tumor immunomodulator to enhance radioimmunotherapy and has great potential for clinical translation.展开更多
The induction of tumor carbonyl stress is reported to efficiently revert immune suppression in the tumor microenvironment and enhance cancer immunotherapy.However,low oxygen concentration due to inherent tumor hypoxia...The induction of tumor carbonyl stress is reported to efficiently revert immune suppression in the tumor microenvironment and enhance cancer immunotherapy.However,low oxygen concentration due to inherent tumor hypoxia limits its catalytic effect.Herein,an injectable thermosensitive hydrogel system(named APH)is developed for co-loading of near-infrared(NIR)aggregation-induced emission(AIE)nanoparticles and plasma amine oxidase(PAO)for boosting carbonyl stress and enhancing antitumor immunity.Upon 808 nm NIR laser irradiation,the AIE nanoparticles trigger a mild-temperature(around 45℃)photothermal effect in the tumor site,which significantly relieves tumor hypoxia and promotes the catalytic effect of released PAO to inhibit the growth of Myeloid-derived suppressor cells.Remarkably,the synergistic therapeutic effect of APH is verified through a significant inhibitory effect on the distant tumor,enhanced immune memory,and effective suppression of postoperative recurrence,rechallenge,and metastasis.Overall,the combined effect of AIE-mediated photothermal therapy and carbonyl stress by APH upon NIR irradiation therapy can significantly activate cancer immunotherapy,making it a promising treatment approach for cancer treatment.展开更多
基金supported by the Natural Science Foundation of China(No.30871042)
文摘We sought to investigate the effects of telmisartan on high-fat diet-induced hypertension and to explore the possible underlying mechanisms. Rats receiving high-fat diet were randomly divided into two groups, the tel- misartan group （n = 9） and the high-fat diet group （n = 10）. The control group consisted of age-matched rats on a regular diet （n = 10）. At the end of the treatment, the body weight, blood pressure, insulin sensitivity and serum adiponectin levels of all rats were examined, and their visceral fat was extracted and weighed. Our results showed that telmisartan improved insulin resistance and dyslipidemia and increased serum adiponectin levels. Telmisar- tan also lowered both systolic blood pressure and diastolic blood pressure, and decreased the accumulation of perirenal fat associated with high-fat diet. Furthermore, telmisartan increased adiponectin mRNA expression in the perirenal fat. Correlation analysis showed that both systolic blood pressure and diastolic blood pressure were positively correlated with perirenal fat. These effects of telmisartan may be mediated through decreases in perirenal fat and contributed to the improvement of perirenal fat function. Our findings suggested a strong link between perirenal fat and high-fat diet-induced hypertension, and identified telmisartan as a potential drug for the treatment of obesity-related hypertension.
基金financial support from the Key Laboratory of Birth Defects and Stem Cell Biobank of Guangxi(No.GXWCHZDKF-2023-09).
文摘ABSTRACT:Although radiotherapy(RT)can induce immunogenic cell death(ICD),the endogenous resistance of tumor cells to X-rays and the immunosuppressive microenvironment has suppressed its therapeutic effect,which can easily lead to tumor recurrence and metastasis after RT.Herein,we prepared a glutathione(GSH)-responsive system called AHD,by loading Aurora-A inhibitor alisertib(Ali)and iron protoporphyrin Ⅸ chloride(Hemin),for X-raytriggered continuous reactive oxygen species(ROS)generation to sensitize breast cancer senescence immunotherapy.AHD accumulates at the tumor tissue through the enhanced permeability and retention(EPR)effect,shows high specificity for the tumor microenvironment with overexpressed GSH,and rapidly releases Ali and Hemin.Under external X-ray irradiation,tumor cells produce H_(2)O_(2),and AHD activates Hemin to catalyze the chemical kinetics process of H_(2)O_(2),continuously generating hydroxyl radicals(·OH).Meanwhile,AHD can also induce tumor cell senescence by up-regulating P21 and P16 expressions.In vitro and in vivo experimental results show that the cascade ROS generation induced by the AHD system can trigger extensive ICD in tumor cells,alleviate the immunosuppressive microenvironment after RT,activate the anti-tumor immune ability of CD8^(+)T cells.Therefore,AHD can be used as a tumor immunomodulator to enhance radioimmunotherapy and has great potential for clinical translation.
基金National Natural Science Foundation of China,Grant/Award Number:82002779Guangxi Natural Science Foundation,Grant/Award Number:2023GXNSFBA026137China Postdoctoral Science Foundation,Grant/Award Number:2022M710853。
文摘The induction of tumor carbonyl stress is reported to efficiently revert immune suppression in the tumor microenvironment and enhance cancer immunotherapy.However,low oxygen concentration due to inherent tumor hypoxia limits its catalytic effect.Herein,an injectable thermosensitive hydrogel system(named APH)is developed for co-loading of near-infrared(NIR)aggregation-induced emission(AIE)nanoparticles and plasma amine oxidase(PAO)for boosting carbonyl stress and enhancing antitumor immunity.Upon 808 nm NIR laser irradiation,the AIE nanoparticles trigger a mild-temperature(around 45℃)photothermal effect in the tumor site,which significantly relieves tumor hypoxia and promotes the catalytic effect of released PAO to inhibit the growth of Myeloid-derived suppressor cells.Remarkably,the synergistic therapeutic effect of APH is verified through a significant inhibitory effect on the distant tumor,enhanced immune memory,and effective suppression of postoperative recurrence,rechallenge,and metastasis.Overall,the combined effect of AIE-mediated photothermal therapy and carbonyl stress by APH upon NIR irradiation therapy can significantly activate cancer immunotherapy,making it a promising treatment approach for cancer treatment.
