Background:Amanita poisoning as a foodborne disease has raised concerning mortality issues.Reducing the interval between mushroom ingestion and medical intervention could greatly influence the outcomes of Amanita pois...Background:Amanita poisoning as a foodborne disease has raised concerning mortality issues.Reducing the interval between mushroom ingestion and medical intervention could greatly influence the outcomes of Amanita poisoning patients,while treatment is highly dependent on a confirmed diagnosis.To this end,we developed an early detection-guided intervention strategy by optimizing diagnostic process with performingα-amanitin detection,and further explored whether this strategy influenced the progression of Amanita poisoning.Methods:This study was a retrospective analysis of 25 Amanita poisoning patients.Thirteen patients in the detection group were diagnosed mainly based onα-amanitin detection,and 12 patients were diagnosed essentially on the basis of mushroom consumption history,typical clinical patterns and mushroom identification(conventional group).Amanita poisoning patients received uniform therapy,in which plasmapheresis was executed once confirming the diagnosis of Amanita poisoning.We compared the demographic baseline,clinical and laboratory data,treatment and outcomes between the two groups,and further explored the predictive value ofα-amanitin concentration in serum.Results:Liver injury induced by Amanita appeared worst at the fourth day and alanine aminotransferase(ALT)rose higher than aspartate aminotransferase(AST).The mortality rate was 7.7%(1/13)in the detection group and 50.0%(6/12)in the conventional group(P=0.030),since patients in the detection group arrived hospital much earlier and received plasmapheresis at the early stage of disease.The early detection-guided intervention helped alleviate liver impairment caused by Amanita and decreased the peak AST as well as ALT.However,the predictive value ofα-amanitin concentration in serum was still considered limited.Conclusions:In the management of mushroom poisoning,consideration should be given to the rapid detection ofα-amanitin in suspected Amanita poisoning patients and the immediate initiation of medical treatment upon a positive toxin screening result.展开更多
Colorectal cancer(CRC) is often diagnosed at an advanced stage when tumor cell dissemination has taken place. Chemo-and targeted therapies provide only a limited increase of overall survival for these patients. The ma...Colorectal cancer(CRC) is often diagnosed at an advanced stage when tumor cell dissemination has taken place. Chemo-and targeted therapies provide only a limited increase of overall survival for these patients. The major reason for clinical outcome finds its origin in therapy resistance. Escape mechanisms to both chemo-and targeted therapy remain the main culprits. Here, we evaluate major resistant mechanisms and elaborate on potential new therapies. Amongst promising therapies is α-amanitin antibodydrug conjugate targeting hemizygous p53 loss. It becomes clear that a dynamic interaction with the tumor microenvironment exists and that this dictates therapeutic outcome. In addition, CRC displays a limited response to checkpoint inhibitors, as only a minority of patients with microsatellite instable high tumors is susceptible. In this review, we highlight new developments with clinical potentials to augment responses to checkpoint inhibitors.展开更多
BACKGROUND： Evolutionary novelties, be they morphological or biochemical, fascinate both scientists and non-scientists alike. These types of adaptations can significantly impact the biodiversity of the organisms in w...BACKGROUND： Evolutionary novelties, be they morphological or biochemical, fascinate both scientists and non-scientists alike. These types of adaptations can significantly impact the biodiversity of the organisms in which they occur. While much work has been invested in the evolution of novel morphological traits, substantially less is known about the evolution of biochemical adaptations. METHODS： In this review, we present the results of literature searches relating to one such biochemical adaptation： α- amanitin tolerance/resistance in the genus Drosophila. RESULTS： Amatoxins, including α-amanitin, are one of several toxin classes found in Amanita mushrooms. They act by binding to RNA polymerase Ⅱ and inhibiting RNA transcription. Although these toxins are lethal to most eukaryotic organisms, 17 mushroom-feeding Drosophila species are tolerant of natural concentrations of amatoxins and can develop in toxic mushrooms. The use of toxic mushrooms allows these species to avoid infection by parasitic nematodes and lowers competition. Their amatoxin tolerance is not due to mutations that would inhibit α-amanitin from binding to RNA polymerase Ⅱ. Furthermore, the mushroom-feeding flies are able to detoxify the other toxin classes that occur in their mushroom hosts. In addition, resistance has evolved independently in several D. melanogaster strains. Only one of the strains exhibits resistance due to mutations in the target of the toxin. CONCLUSIONS： Given our current understanding of the evolutionary relationships among the mushroom-feeding flies, it appears that amatoxin tolerance evolved multiple times. Furthermore, independent lines of evidence suggest that multiple mechanisms confer α-amanitin tolerance/resistance in Drosophila.展开更多
The transcription reactions in vitro of yeast ADHl and PHO5 gene promoters are investigated by means of a yeast crude nuclear extract. Using specific RNA probes, the transcription products of these 2 promoters have be...The transcription reactions in vitro of yeast ADHl and PHO5 gene promoters are investigated by means of a yeast crude nuclear extract. Using specific RNA probes, the transcription products of these 2 promoters have been first obtained. A low concentration of α-amanitin is highly inhibitory. The transcription of the PHO5 gene was initiated in vitro at or near the sites used in vim. The transcription products increase with the amount of the template and reach the maximum at certain concentrations of the template. The deletion of the yeast promoter sequences abolishes the reaction.展开更多
基金This project was supported by a grant from the Foundation of Key Discipline Construction of Zhejiang Province for Traditional Chinese Medicine (2017-XKA36).
文摘Background:Amanita poisoning as a foodborne disease has raised concerning mortality issues.Reducing the interval between mushroom ingestion and medical intervention could greatly influence the outcomes of Amanita poisoning patients,while treatment is highly dependent on a confirmed diagnosis.To this end,we developed an early detection-guided intervention strategy by optimizing diagnostic process with performingα-amanitin detection,and further explored whether this strategy influenced the progression of Amanita poisoning.Methods:This study was a retrospective analysis of 25 Amanita poisoning patients.Thirteen patients in the detection group were diagnosed mainly based onα-amanitin detection,and 12 patients were diagnosed essentially on the basis of mushroom consumption history,typical clinical patterns and mushroom identification(conventional group).Amanita poisoning patients received uniform therapy,in which plasmapheresis was executed once confirming the diagnosis of Amanita poisoning.We compared the demographic baseline,clinical and laboratory data,treatment and outcomes between the two groups,and further explored the predictive value ofα-amanitin concentration in serum.Results:Liver injury induced by Amanita appeared worst at the fourth day and alanine aminotransferase(ALT)rose higher than aspartate aminotransferase(AST).The mortality rate was 7.7%(1/13)in the detection group and 50.0%(6/12)in the conventional group(P=0.030),since patients in the detection group arrived hospital much earlier and received plasmapheresis at the early stage of disease.The early detection-guided intervention helped alleviate liver impairment caused by Amanita and decreased the peak AST as well as ALT.However,the predictive value ofα-amanitin concentration in serum was still considered limited.Conclusions:In the management of mushroom poisoning,consideration should be given to the rapid detection ofα-amanitin in suspected Amanita poisoning patients and the immediate initiation of medical treatment upon a positive toxin screening result.
基金Supported by the National Natural Science Foundation of China,No.81620108030
文摘Colorectal cancer(CRC) is often diagnosed at an advanced stage when tumor cell dissemination has taken place. Chemo-and targeted therapies provide only a limited increase of overall survival for these patients. The major reason for clinical outcome finds its origin in therapy resistance. Escape mechanisms to both chemo-and targeted therapy remain the main culprits. Here, we evaluate major resistant mechanisms and elaborate on potential new therapies. Amongst promising therapies is α-amanitin antibodydrug conjugate targeting hemizygous p53 loss. It becomes clear that a dynamic interaction with the tumor microenvironment exists and that this dictates therapeutic outcome. In addition, CRC displays a limited response to checkpoint inhibitors, as only a minority of patients with microsatellite instable high tumors is susceptible. In this review, we highlight new developments with clinical potentials to augment responses to checkpoint inhibitors.
文摘BACKGROUND： Evolutionary novelties, be they morphological or biochemical, fascinate both scientists and non-scientists alike. These types of adaptations can significantly impact the biodiversity of the organisms in which they occur. While much work has been invested in the evolution of novel morphological traits, substantially less is known about the evolution of biochemical adaptations. METHODS： In this review, we present the results of literature searches relating to one such biochemical adaptation： α- amanitin tolerance/resistance in the genus Drosophila. RESULTS： Amatoxins, including α-amanitin, are one of several toxin classes found in Amanita mushrooms. They act by binding to RNA polymerase Ⅱ and inhibiting RNA transcription. Although these toxins are lethal to most eukaryotic organisms, 17 mushroom-feeding Drosophila species are tolerant of natural concentrations of amatoxins and can develop in toxic mushrooms. The use of toxic mushrooms allows these species to avoid infection by parasitic nematodes and lowers competition. Their amatoxin tolerance is not due to mutations that would inhibit α-amanitin from binding to RNA polymerase Ⅱ. Furthermore, the mushroom-feeding flies are able to detoxify the other toxin classes that occur in their mushroom hosts. In addition, resistance has evolved independently in several D. melanogaster strains. Only one of the strains exhibits resistance due to mutations in the target of the toxin. CONCLUSIONS： Given our current understanding of the evolutionary relationships among the mushroom-feeding flies, it appears that amatoxin tolerance evolved multiple times. Furthermore, independent lines of evidence suggest that multiple mechanisms confer α-amanitin tolerance/resistance in Drosophila.
文摘The transcription reactions in vitro of yeast ADHl and PHO5 gene promoters are investigated by means of a yeast crude nuclear extract. Using specific RNA probes, the transcription products of these 2 promoters have been first obtained. A low concentration of α-amanitin is highly inhibitory. The transcription of the PHO5 gene was initiated in vitro at or near the sites used in vim. The transcription products increase with the amount of the template and reach the maximum at certain concentrations of the template. The deletion of the yeast promoter sequences abolishes the reaction.
