Objective To explore the complement deposition levels on blood cell surfaces in patients with paroxysmal nocturnal hemoglobinuria(PNH)and evaluate their association with clinical manifestations.Methods This study enro...Objective To explore the complement deposition levels on blood cell surfaces in patients with paroxysmal nocturnal hemoglobinuria(PNH)and evaluate their association with clinical manifestations.Methods This study enrolled patients with PNH,who had not been treated with complement inhibitors and appeared at Peking Union Medical College Hospital from February 2021 to February 2023.The clinical information of participants was retrospectively recorded,and peripheral blood samples were collected.Gender-and age-matched normal controls(NC)were recruited accordingly.展开更多
Hydrogen sulfide,which can be generated in the central nervous system from the sulfhydryl-containing amino acid,L-cysteine,by cystathionine-β-synthase,may exert protective effects in experimental subarachnoid hemorrh...Hydrogen sulfide,which can be generated in the central nervous system from the sulfhydryl-containing amino acid,L-cysteine,by cystathionine-β-synthase,may exert protective effects in experimental subarachnoid hemorrhage;however,the mechanism underlying this effect is unknown.This study explored the mechanism using a subarachnoid hemorrhage rat model induced by an endovascular perforation technique.Rats were treated with an intraperitoneal injection of 100 mM L-cysteine(30μL)30 minutes after subarachnoid hemorrhage.At 48 hours after subarachnoid hemorrhage,hematoxylin-eosin staining was used to detect changes in prefrontal cortex cells.L-cysteine significantly reduced cell edema.Neurological function was assessed using a modified Garcia score.Brain water content was measured by the wet-dry method.L-cysteine significantly reduced neurological deficits and cerebral edema after subarachnoid hemorrhage.Immunofluorescence was used to detect the number of activated microglia.Reverse transcription-polymerase chain reaction(RT-PCR)was used to detect the levels of interleukin 1β and CD86 mRNA in the prefrontal cortex.L-cysteine inhibited microglial activation in the prefrontal cortex and reduced the mRNA levels of interleukin 1βand CD86.RT-PCR and western blot analysis of the complement system showed that L-cysteine reduced expression of the complement factors,C1q,C3αand its receptor C3aR1,and the deposition of C1q in the prefrontal cortex.Dihydroethidium staining was applied to detect changes in reactive oxygen species,and immunohistochemistry was used to detect the number of NRF2-and HO-1-positive cells.L-cysteine reduced the level of reactive oxygen species in the prefrontal cortex and the number of NRF2-and HO-1-positive cells.Western blot assays and immunohistochemistry were used to detect the protein levels of CHOP and GRP78 in the prefrontal cortex and the number of CHOP-and GRP78-positive cells.L-cysteine reduced CHOP and GRP78 levels and the number of CHOP-and GRP78-positive cells.The cystathionine-β-synthase inhibitor,aminooxyacetic acid,significantly reversed the above neuroprotective effects of L-cysteine.Taken together,L-cysteine can play a neuroprotective role by regulating neuroinflammation,complement deposition,oxidative stress and endoplasmic reticulum stress.The study was approved by the Animals Ethics Committee of Shandong University,China on February 22,2016(approval No.LL-201602022).展开更多
文摘Objective To explore the complement deposition levels on blood cell surfaces in patients with paroxysmal nocturnal hemoglobinuria(PNH)and evaluate their association with clinical manifestations.Methods This study enrolled patients with PNH,who had not been treated with complement inhibitors and appeared at Peking Union Medical College Hospital from February 2021 to February 2023.The clinical information of participants was retrospectively recorded,and peripheral blood samples were collected.Gender-and age-matched normal controls(NC)were recruited accordingly.
基金supported by the National Natural Science Foundation of China,Nos.81873768 and 81671213(to ZW),81571284 and 81874083(to GL)the Key Research and Development Foundation of Shandong Province of China,No.2017GSF218091(to ZW)+2 种基金the Natural Science Foundation of Shandong Province of China,No.ZR2016HM33(to DXL)the Shandong Medical and Health Science and Technology Development Plan Project of China,No.2017WS068(to QH)the Taishan Scholars of Shandong Province of China,No.ts201511093(to GL)
文摘Hydrogen sulfide,which can be generated in the central nervous system from the sulfhydryl-containing amino acid,L-cysteine,by cystathionine-β-synthase,may exert protective effects in experimental subarachnoid hemorrhage;however,the mechanism underlying this effect is unknown.This study explored the mechanism using a subarachnoid hemorrhage rat model induced by an endovascular perforation technique.Rats were treated with an intraperitoneal injection of 100 mM L-cysteine(30μL)30 minutes after subarachnoid hemorrhage.At 48 hours after subarachnoid hemorrhage,hematoxylin-eosin staining was used to detect changes in prefrontal cortex cells.L-cysteine significantly reduced cell edema.Neurological function was assessed using a modified Garcia score.Brain water content was measured by the wet-dry method.L-cysteine significantly reduced neurological deficits and cerebral edema after subarachnoid hemorrhage.Immunofluorescence was used to detect the number of activated microglia.Reverse transcription-polymerase chain reaction(RT-PCR)was used to detect the levels of interleukin 1β and CD86 mRNA in the prefrontal cortex.L-cysteine inhibited microglial activation in the prefrontal cortex and reduced the mRNA levels of interleukin 1βand CD86.RT-PCR and western blot analysis of the complement system showed that L-cysteine reduced expression of the complement factors,C1q,C3αand its receptor C3aR1,and the deposition of C1q in the prefrontal cortex.Dihydroethidium staining was applied to detect changes in reactive oxygen species,and immunohistochemistry was used to detect the number of NRF2-and HO-1-positive cells.L-cysteine reduced the level of reactive oxygen species in the prefrontal cortex and the number of NRF2-and HO-1-positive cells.Western blot assays and immunohistochemistry were used to detect the protein levels of CHOP and GRP78 in the prefrontal cortex and the number of CHOP-and GRP78-positive cells.L-cysteine reduced CHOP and GRP78 levels and the number of CHOP-and GRP78-positive cells.The cystathionine-β-synthase inhibitor,aminooxyacetic acid,significantly reversed the above neuroprotective effects of L-cysteine.Taken together,L-cysteine can play a neuroprotective role by regulating neuroinflammation,complement deposition,oxidative stress and endoplasmic reticulum stress.The study was approved by the Animals Ethics Committee of Shandong University,China on February 22,2016(approval No.LL-201602022).
