Cardamonin is a natural chalcone that has been extensively investigated for its anticancer activity.However,its clinical relevance is still not explicit,limiting its progression into clinical trials and highlighting a...Cardamonin is a natural chalcone that has been extensively investigated for its anticancer activity.However,its clinical relevance is still not explicit,limiting its progression into clinical trials and highlighting a persistent gap between preclinical evidence and practical application.This review aims to assess the readiness of cardamonin to progress from laboratory research to clinical application as an anticancer agent by examining both scientific evidence and translational challenges.Preclinical pharmacokinetic and pharmacodynamic data suggest that cardamonin’s therapeutic potential as an anticancer agent is hindered by its poor oral bioavailability.Although its molecular targets remain undefined,evidence indicates that cardamonin can inhibit various signaling pathways,including nuclear factor kappa-light-chain-enhancer of activated B cells,mammalian target of rapamycin,signal transducer and activator of transcription 3,and Wnt/β-catenin.The lack of in vivo toxicity studies creates uncertainty regarding the balance between its therapeutic benefits and potential adverse effects when moving from laboratory research to human trials.Despite these limitations,cardamonin has,however,demonstrated antiproliferative,anti-metastatic,and chemosensitizing effects,mainly against breast,colorectal,and ovarian cancers.Nevertheless,exploring its combination with standard chemotherapeutic agents may offer a promising foundation for advancing cardamonin into clinical trials.展开更多
Objective: To evaluate the value of oral Gd-DTPA as a negative contrast agent during magnetic resonance cholangiopancreatography (MRCP) to eliminate the high signals of the gastrointestinal tract. Methods: To select t...Objective: To evaluate the value of oral Gd-DTPA as a negative contrast agent during magnetic resonance cholangiopancreatography (MRCP) to eliminate the high signals of the gastrointestinal tract. Methods: To select the optimal concentration of oral Gd-DTPA for MRCP, a phantom study was performed followed by clinical trial in 15 cases undergoing MRCP before and after oral Gd-DTPA (in a total volume of 250 ml 1∶5 diluted Gd-DTPA, 1.488 g/L). MRCP images were acquired using two-dimensional single slice fast spin-echo (SSTSE) sequence and half-Fourier acquisition single slice fast spin-echo (HASTE) sequence. Results: The phantom study showed that the 1∶5 diluted oral Gd-DTPA was best in decreasing the signal intensity both in T2-weighted imaging (59.5%) and in HASTE sequence (82.45%). The high signal intensity of the stomach and intestinal fluid was completely suppressed in all the cases. The depictions of the common bile duct and pancreatic duct were markedly improved by using the oral contrast agent (P<0.05). Conclusion: Oral Gd-DTPA is effective and safe for eliminating the high signal of the gastrointestinal tract to improve the depiction of the biliary system by MRCP.展开更多
In order to study the effect of anti-HABs agents on Penaeus chinensis, the toxicity experiments on clay, Ca(ClO)2, FeCl3, and AlCl3 to Penaeus chinensis are carried out. The results show that: (1) the clay isn't t...In order to study the effect of anti-HABs agents on Penaeus chinensis, the toxicity experiments on clay, Ca(ClO)2, FeCl3, and AlCl3 to Penaeus chinensis are carried out. The results show that: (1) the clay isn't toxic to Penaeus chinensis; (2) Ca(ClO)2 has no toxicity to Penaeus chinensis at low levels, but has acute and chronic toxicity at high levels; (3) Penaeus chinensis can accumulate Fe and Al. The toxic effect needs further study.展开更多
The effect of the Chinese herbal compound (CHC) on solid sarcoma 180 (S180) in Swiss mice was studied either alone or in combination with 5-fluorouracil (5FU), cyclophosphamide (CYT) or mitomycin C (MMC). The prelimin...The effect of the Chinese herbal compound (CHC) on solid sarcoma 180 (S180) in Swiss mice was studied either alone or in combination with 5-fluorouracil (5FU), cyclophosphamide (CYT) or mitomycin C (MMC). The preliminary results indicated that combination treatment seemed to possess better antitumor activity than chemotherapy alone. The treatment with CHC alone however had neither an obvious antitumor effect in tumor bearing mice nor toxicity in normal mice. These results show that CHC may stimulate organs of the immune system such as the spleen to be im-munomodulators and enhance the antitumor activity of some chemotherapeutic agents.展开更多
Effects of angiotensin Ⅱ and other six vasoactive agents on tissue blood flow of Yoahida rat ascites hepatoma AH109A and normal liver were measured by the hydrogen clearance method. The mean blood flow in the tumor p...Effects of angiotensin Ⅱ and other six vasoactive agents on tissue blood flow of Yoahida rat ascites hepatoma AH109A and normal liver were measured by the hydrogen clearance method. The mean blood flow in the tumor peripheral part under normal tension was 11. 9±8. 2ml/ min/100g tissue and was not influenced by tumor size. Tumor blood flow was more significantly increased in infusion angiotensin Ⅱthan 0.5mg/ ml methoxamine, however, normal liver blood flow of tumor-bearing rats was unchanged in contrast to an Increase seen in the tumor. A pronounced reduction of tumor blood flow was found after administration of epinephrine, norepinephrin and ethylphenylephrine. In addition, metaraminol and phenyleprine as well as 1. 0 and 2. 5mg/ ml methoxamine were not found to significantly change blood flow of the tumor.展开更多
A new series of 12-benzyl matrinic amide/ethanamide derivatives were synthesized from matrinine（1）and evaluated for their anti-HCV activity,taking compound 2 as the lead.SAR revealed that the introduction of a suita...A new series of 12-benzyl matrinic amide/ethanamide derivatives were synthesized from matrinine（1）and evaluated for their anti-HCV activity,taking compound 2 as the lead.SAR revealed that the introduction of a suitable substituent at the N’-end of matrinic amide might greatly enhance the potency.Among them,matrinic acid 17 and N’-substituted matrinic amides 18a-d exhibited promising potency with low micromolar EC50 values ranging from 1.03μmol/L to 7.54 μmol/L,and better therapeutic window with SI from 66 to 132.Moreover,compound 17 displayed an excellent PK and safety profile in vivo,demonstrating good drug-like characteristics.Thus,it has been selected for further investigation,with an advantage of decreased chances of inducing drug-resistance mutations.展开更多
Leishmaniases and chronic inflammatory diseases are the cause of millions of deaths in the world each year.The treatment of leishmaniasis is facing serious drawbacks particularly due to the limited number of effective...Leishmaniases and chronic inflammatory diseases are the cause of millions of deaths in the world each year.The treatment of leishmaniasis is facing serious drawbacks particularly due to the limited number of effective medicines,the resistance,and the toxicity of available drugs.On the other hand,many drugs are used for the management of inflammatory disorders.However,the most commonly prescribed although efficient is highly toxic with multiples side effects.New leads compounds for the development of new anti-leishmanial and anti-inflammatory drugs are needed.Over the past decade,several studies on the potential of endophytes to produce bioactive metabolites have been reported.We are presenting in the present review the status of research from 2000 to 2019 on the anti-leishmanial and anti-inflammatory metabolites isolated from endophytes from diverse habitats.An emphasis was put on existing gaps in the literature to inspire and guide future investigations.We hope that this review will help accelerate the drug discovery against leishmaniases and inflammation-associated disorders.展开更多
In the MAS, system goal task can be decomposed into many transactions, which will be achieved by special agents distributed in different physical space. Due to complex coupling relations among transactions, transactio...In the MAS, system goal task can be decomposed into many transactions, which will be achieved by special agents distributed in different physical space. Due to complex coupling relations among transactions, transactions may form Waiting-Circle resulting in deadlock. Concerning the problem, this paper proposes two theorems developed for Waiting-Circle detection in transaction set and ensures the implement of goal task decomposition result. Furthermore, Circle-First Search is put forward to search all of the Waiting-Circle, which prnvide the basic guideline for decomposing goal task again and eliminate Waiting-Circle.展开更多
In open normative multi-agent communities,an agent is not usually and explicitly given the norms of the host agents.Thus,when it is not able to adapt the communities's norms,it is totally deprived of accessing res...In open normative multi-agent communities,an agent is not usually and explicitly given the norms of the host agents.Thus,when it is not able to adapt the communities's norms,it is totally deprived of accessing resources and services from the host.Such circumstance severely affects its performance resulting in failure to achieve its goal.Consequently,this study attempts to overcome this deficiency by proposing a technique that enables an agent to detect the host's potential norms via self-enforcement and update its norms even in the absence of sanctions from a third-party.The authors called this technique as the potential norms detection technique(PNDT).The PNDT consists of five components: Agent's belief base; observation process; potential norms mining algorithm(PNMA);verification process; and updating process.The authors demonstrate the operation of the PNMA algorithm by testing it on a typical scenario and analyzing the results on several perspectives.The tests' results show that the PNDT performs satisfactorily albeit the success rate depends on the environment variables settings.展开更多
Gram-negative bacteria have become the main pathogens and cause serious clinical problems with increased morbidity and mortality. However, the slow discovery of new antimicrobial agents is unable to meet the need for ...Gram-negative bacteria have become the main pathogens and cause serious clinical problems with increased morbidity and mortality. However, the slow discovery of new antimicrobial agents is unable to meet the need for the treatment of bacterial infections caused by drug-resistant strains. The interaction of L12 and L10 is essential for ribosomal function and protein synthesis. In this study, a yeast two-hybrid system was established to successfully detect the interaction between L12 and L10 proteins from gram-negative bacteria Escherichia coli, which allows us to screen compounds that specifically disrupt this interaction. With this system, we identified two compounds IMB-84 and IMB-87 that block L12-L10 interaction and show bactericidal activity against E. coli. We used glutathione-S-transferase(GST) pull-down and surface plasmon resonance(SPR) assays to demonstrate that these compounds disrupt L12-L10 interaction in vitro and the target of compounds was further confirmed by the overexpression of target proteins. Moreover, protein synthesis and elongation factor G-dependent GTPase activities are inhibited by two compounds. Therefore, we have identified two antibacterial agents that disrupt L12-L10 interaction by using yeast two-hybrid system.展开更多
Multi-agent systems for a certain application area can be modeled at multiple levels of abstraction.Interlevel relations are a means to relate models from different abstraction levels.Three dimensions of abstraction o...Multi-agent systems for a certain application area can be modeled at multiple levels of abstraction.Interlevel relations are a means to relate models from different abstraction levels.Three dimensions of abstraction often occurring are the process abstraction,temporal abstraction,and agent cluster abstraction dimension.In this paper a unifying formalization is presented that can be used as a framework to specify interlevel relations for any of such dimensions.The approach is illustrated by showing how a variety of different types of abstraction relations between multi-agent system models can be formally specified in a unified manner.展开更多
Twenty-six novel tricyclic sophoridinic and matrinic derivatives containing a common chlorinated benzene fragment were designed, synthesized and evaluated for their anti-ebolavirus(EBOV)activities. Structure–activity...Twenty-six novel tricyclic sophoridinic and matrinic derivatives containing a common chlorinated benzene fragment were designed, synthesized and evaluated for their anti-ebolavirus(EBOV)activities. Structure–activity relationship analysis indicated:(i) 12 N-dichlorobenzyl motif was beneficial for the activity;(ii) the chiral configuration at C5 atom might not affect the activity much. Among the target compounds, compound 7d exhibited the most potent potency against EBOV with an IC_(50) value of 5.29 μmol/L and an SI value of over 37.8. Further in vivo anti-EBOV assay of 7d identified its high effectiveness, and in vivo anti-MARV assay of 7d suggested its inspiring broad-spectrum anti-filovirus activity. The results provided powerful information on further strategic optimization and development of this kind of compounds against filoviruses.展开更多
基金Supported by Malaysian Ministry of Higher Education through the Fundamental Research Grant Scheme,No.FP103-2019.
文摘Cardamonin is a natural chalcone that has been extensively investigated for its anticancer activity.However,its clinical relevance is still not explicit,limiting its progression into clinical trials and highlighting a persistent gap between preclinical evidence and practical application.This review aims to assess the readiness of cardamonin to progress from laboratory research to clinical application as an anticancer agent by examining both scientific evidence and translational challenges.Preclinical pharmacokinetic and pharmacodynamic data suggest that cardamonin’s therapeutic potential as an anticancer agent is hindered by its poor oral bioavailability.Although its molecular targets remain undefined,evidence indicates that cardamonin can inhibit various signaling pathways,including nuclear factor kappa-light-chain-enhancer of activated B cells,mammalian target of rapamycin,signal transducer and activator of transcription 3,and Wnt/β-catenin.The lack of in vivo toxicity studies creates uncertainty regarding the balance between its therapeutic benefits and potential adverse effects when moving from laboratory research to human trials.Despite these limitations,cardamonin has,however,demonstrated antiproliferative,anti-metastatic,and chemosensitizing effects,mainly against breast,colorectal,and ovarian cancers.Nevertheless,exploring its combination with standard chemotherapeutic agents may offer a promising foundation for advancing cardamonin into clinical trials.
文摘Objective: To evaluate the value of oral Gd-DTPA as a negative contrast agent during magnetic resonance cholangiopancreatography (MRCP) to eliminate the high signals of the gastrointestinal tract. Methods: To select the optimal concentration of oral Gd-DTPA for MRCP, a phantom study was performed followed by clinical trial in 15 cases undergoing MRCP before and after oral Gd-DTPA (in a total volume of 250 ml 1∶5 diluted Gd-DTPA, 1.488 g/L). MRCP images were acquired using two-dimensional single slice fast spin-echo (SSTSE) sequence and half-Fourier acquisition single slice fast spin-echo (HASTE) sequence. Results: The phantom study showed that the 1∶5 diluted oral Gd-DTPA was best in decreasing the signal intensity both in T2-weighted imaging (59.5%) and in HASTE sequence (82.45%). The high signal intensity of the stomach and intestinal fluid was completely suppressed in all the cases. The depictions of the common bile duct and pancreatic duct were markedly improved by using the oral contrast agent (P<0.05). Conclusion: Oral Gd-DTPA is effective and safe for eliminating the high signal of the gastrointestinal tract to improve the depiction of the biliary system by MRCP.
基金Supported by National Natural Scientific Foundation (40025614 and 39790110)Knowledge Innovation Project of Chinese Academy of Sciences (KZCX2-206)
文摘In order to study the effect of anti-HABs agents on Penaeus chinensis, the toxicity experiments on clay, Ca(ClO)2, FeCl3, and AlCl3 to Penaeus chinensis are carried out. The results show that: (1) the clay isn't toxic to Penaeus chinensis; (2) Ca(ClO)2 has no toxicity to Penaeus chinensis at low levels, but has acute and chronic toxicity at high levels; (3) Penaeus chinensis can accumulate Fe and Al. The toxic effect needs further study.
文摘The effect of the Chinese herbal compound (CHC) on solid sarcoma 180 (S180) in Swiss mice was studied either alone or in combination with 5-fluorouracil (5FU), cyclophosphamide (CYT) or mitomycin C (MMC). The preliminary results indicated that combination treatment seemed to possess better antitumor activity than chemotherapy alone. The treatment with CHC alone however had neither an obvious antitumor effect in tumor bearing mice nor toxicity in normal mice. These results show that CHC may stimulate organs of the immune system such as the spleen to be im-munomodulators and enhance the antitumor activity of some chemotherapeutic agents.
文摘Effects of angiotensin Ⅱ and other six vasoactive agents on tissue blood flow of Yoahida rat ascites hepatoma AH109A and normal liver were measured by the hydrogen clearance method. The mean blood flow in the tumor peripheral part under normal tension was 11. 9±8. 2ml/ min/100g tissue and was not influenced by tumor size. Tumor blood flow was more significantly increased in infusion angiotensin Ⅱthan 0.5mg/ ml methoxamine, however, normal liver blood flow of tumor-bearing rats was unchanged in contrast to an Increase seen in the tumor. A pronounced reduction of tumor blood flow was found after administration of epinephrine, norepinephrin and ethylphenylephrine. In addition, metaraminol and phenyleprine as well as 1. 0 and 2. 5mg/ ml methoxamine were not found to significantly change blood flow of the tumor.
基金supported by the National Natural Science Foundation of China (Nos. 21472246 and 81321004)the Beijing Natural Science Foundation (No. 7152097)National Mega-Project for Innovation Drugs (No. 2012ZX09103101-037)
文摘A new series of 12-benzyl matrinic amide/ethanamide derivatives were synthesized from matrinine（1）and evaluated for their anti-HCV activity,taking compound 2 as the lead.SAR revealed that the introduction of a suitable substituent at the N’-end of matrinic amide might greatly enhance the potency.Among them,matrinic acid 17 and N’-substituted matrinic amides 18a-d exhibited promising potency with low micromolar EC50 values ranging from 1.03μmol/L to 7.54 μmol/L,and better therapeutic window with SI from 66 to 132.Moreover,compound 17 displayed an excellent PK and safety profile in vivo,demonstrating good drug-like characteristics.Thus,it has been selected for further investigation,with an advantage of decreased chances of inducing drug-resistance mutations.
文摘Leishmaniases and chronic inflammatory diseases are the cause of millions of deaths in the world each year.The treatment of leishmaniasis is facing serious drawbacks particularly due to the limited number of effective medicines,the resistance,and the toxicity of available drugs.On the other hand,many drugs are used for the management of inflammatory disorders.However,the most commonly prescribed although efficient is highly toxic with multiples side effects.New leads compounds for the development of new anti-leishmanial and anti-inflammatory drugs are needed.Over the past decade,several studies on the potential of endophytes to produce bioactive metabolites have been reported.We are presenting in the present review the status of research from 2000 to 2019 on the anti-leishmanial and anti-inflammatory metabolites isolated from endophytes from diverse habitats.An emphasis was put on existing gaps in the literature to inspire and guide future investigations.We hope that this review will help accelerate the drug discovery against leishmaniases and inflammation-associated disorders.
基金Sponsored by the High-Tech Research and Development Program of China (Grant No. 2001AA412210)Spaceflight Support Technology Fund Project (Grant No. 2001-HT-HGDO1)
文摘In the MAS, system goal task can be decomposed into many transactions, which will be achieved by special agents distributed in different physical space. Due to complex coupling relations among transactions, transactions may form Waiting-Circle resulting in deadlock. Concerning the problem, this paper proposes two theorems developed for Waiting-Circle detection in transaction set and ensures the implement of goal task decomposition result. Furthermore, Circle-First Search is put forward to search all of the Waiting-Circle, which prnvide the basic guideline for decomposing goal task again and eliminate Waiting-Circle.
文摘In open normative multi-agent communities,an agent is not usually and explicitly given the norms of the host agents.Thus,when it is not able to adapt the communities's norms,it is totally deprived of accessing resources and services from the host.Such circumstance severely affects its performance resulting in failure to achieve its goal.Consequently,this study attempts to overcome this deficiency by proposing a technique that enables an agent to detect the host's potential norms via self-enforcement and update its norms even in the absence of sanctions from a third-party.The authors called this technique as the potential norms detection technique(PNDT).The PNDT consists of five components: Agent's belief base; observation process; potential norms mining algorithm(PNMA);verification process; and updating process.The authors demonstrate the operation of the PNMA algorithm by testing it on a typical scenario and analyzing the results on several perspectives.The tests' results show that the PNDT performs satisfactorily albeit the success rate depends on the environment variables settings.
基金supported by the National Natural Science Foundation of China (Grant nos.81370089,81529003,81621064 and 81361138020)the Foundation for Innovative Research Groups and the Funds for International Cooperation and Exchange between China–Sweden and CAMS Initiative for Innovative Medicine (2016-12M-3-014)
文摘Gram-negative bacteria have become the main pathogens and cause serious clinical problems with increased morbidity and mortality. However, the slow discovery of new antimicrobial agents is unable to meet the need for the treatment of bacterial infections caused by drug-resistant strains. The interaction of L12 and L10 is essential for ribosomal function and protein synthesis. In this study, a yeast two-hybrid system was established to successfully detect the interaction between L12 and L10 proteins from gram-negative bacteria Escherichia coli, which allows us to screen compounds that specifically disrupt this interaction. With this system, we identified two compounds IMB-84 and IMB-87 that block L12-L10 interaction and show bactericidal activity against E. coli. We used glutathione-S-transferase(GST) pull-down and surface plasmon resonance(SPR) assays to demonstrate that these compounds disrupt L12-L10 interaction in vitro and the target of compounds was further confirmed by the overexpression of target proteins. Moreover, protein synthesis and elongation factor G-dependent GTPase activities are inhibited by two compounds. Therefore, we have identified two antibacterial agents that disrupt L12-L10 interaction by using yeast two-hybrid system.
文摘Multi-agent systems for a certain application area can be modeled at multiple levels of abstraction.Interlevel relations are a means to relate models from different abstraction levels.Three dimensions of abstraction often occurring are the process abstraction,temporal abstraction,and agent cluster abstraction dimension.In this paper a unifying formalization is presented that can be used as a framework to specify interlevel relations for any of such dimensions.The approach is illustrated by showing how a variety of different types of abstraction relations between multi-agent system models can be formally specified in a unified manner.
基金supported by the National Natural Science Foundation of China (Nos. 81673307 and 81321004)CAMS Innovation Fund for Medical Sciences (2016–I2M–3–009)
文摘Twenty-six novel tricyclic sophoridinic and matrinic derivatives containing a common chlorinated benzene fragment were designed, synthesized and evaluated for their anti-ebolavirus(EBOV)activities. Structure–activity relationship analysis indicated:(i) 12 N-dichlorobenzyl motif was beneficial for the activity;(ii) the chiral configuration at C5 atom might not affect the activity much. Among the target compounds, compound 7d exhibited the most potent potency against EBOV with an IC_(50) value of 5.29 μmol/L and an SI value of over 37.8. Further in vivo anti-EBOV assay of 7d identified its high effectiveness, and in vivo anti-MARV assay of 7d suggested its inspiring broad-spectrum anti-filovirus activity. The results provided powerful information on further strategic optimization and development of this kind of compounds against filoviruses.
