Cancer is a global health problem and one of the leading causes of mortality.Immune checkpoint inhibitors have revolutionized the field of oncology,emerging as a powerful treatment strategy.A key pathway that has garn...Cancer is a global health problem and one of the leading causes of mortality.Immune checkpoint inhibitors have revolutionized the field of oncology,emerging as a powerful treatment strategy.A key pathway that has garnered considerable attention is programmed cell death-1(PD-1)/programmed cell death-ligand 1(PD-L1).The interaction between PD-L1 expressed on tumor cells and PD-1 reduces the innate immune response and thus compromises the capability of the body’s immune system.Furthermore,it controls the phenotype and functionality of innate and adaptive immune components.A range of monoclonal antibodies,including avelumab,atezolizumab,camrelizumab,dostarlimab,durvalumab,sinitilimab,toripalimab,and zimberelimab,have been developed for targeting the interaction between PD-1 and PD-L1.These agents can induce a broad spectrum of autoimmune-like complications that may affect any organ system.Recent studies have focused on the effect of various natural compounds that inhibit immune checkpoints.This could contribute to the existing arsenal of anticancer drugs.Several bioactive natural agents have been shown to affect the PD-1/PD-L1 signaling axis,promoting tumor cell apoptosis,influencing cell proliferation,and eventually leading to tumor cell death and inhibiting cancer progression.However,there is a substantial knowledge gap regarding the role of different natural compounds targeting PD-1 in the context of cancer.Hence,this review aims to provide a common connection between PD-1/PD-L1 blockade and the anticancer effects of distinct natural molecules.Moreover,the primary focus will be on the underlying mechanism of action as well as the clinical efficacy of bioactive molecules.Current challenges along with the scope of future research directions targeting PD-1/PD-L1 interactions through natural substances are also discussed.展开更多
The rare ginsenoside Compound K (C-K) is attracting more attention because of its good physiological activity and urgent need. There are many pathways to obtain ginsenoside C-K, including chemical and biological met...The rare ginsenoside Compound K (C-K) is attracting more attention because of its good physiological activity and urgent need. There are many pathways to obtain ginsenoside C-K, including chemical and biological methods. Among these, the conversion of PPD-type ginsenosides by enzymatic hydrolysis is a trend due to its high efficiency and mild conditions. For effectively extracting from the other panaxadiol saponins, the conversion process for ginsenoside C-K was investigated using snailases in this study. The univariate experimental design and response surface methodology were used to determine the optimal hydrolysis conditions for the conversion of ginsenoside Rbl into ginsenoside C-K by snailases. The optimum conditions were as follows: pH 5,12, temperature 51 ℃, ratio of snailase/substrate 0.21, and reaction time 48 h. On the basis of these parameters, the addition of 1.0 mmol· L- 1 ferric ion was found to significantly improve the enzymolysis ofsnailases for the first time. With the above conditions, the maximum conversion rate reached 89.7%, suggesting that the process can obviously increase the yield of ginsenoside C-K. The bioassay tests indicated that the ginsenoside C-K showed anti-tumor activity in a series of tumor cell lines. Based on these results, we can conclude that the process of rare ginsenoside C- K production by enzymolysis with snailase is feasible, efficient, and suitable for the industrial production and application.展开更多
Acid-catalyzed dehydration of alcohols has been widely employed for the synthesis of alkenes. However, activated alcohols when employed as substrates in dehydration reactions are often pla-gued by the lack of alkene s...Acid-catalyzed dehydration of alcohols has been widely employed for the synthesis of alkenes. However, activated alcohols when employed as substrates in dehydration reactions are often pla-gued by the lack of alkene selectivity. In this work, the reaction system can be significantly improved through enhancing the performance of Lewis acid catalysts in the dehydration of activated alcohols by combining with a Lewis base. Observations of the reaction mechanism revealed that the Lewis base component might have changed the reaction rate order. Although both the principal and side reaction rates decreased, the effect was markedly more observed on the latter reaction. Therefore, the selectivity of the dehydration reaction was improved. On the basis of this observation, a new route to synthesize 2-cinnamyl-1,3-dicarbonyl compounds was developed by using 2-aryl-3,4- di-hydropyran as a starting substrate in the presence of a Lewis acid/Lewis base combined catalyst system.展开更多
A compound disinfectant, which consisted of didecyldimethylammonium chloride (DDAC), ortho-dichlorobenzene (1,2-dichlorobenzene, ODB), and chlorocresol (4-chloro-3-methylphenol, CC), and its component chemicals were i...A compound disinfectant, which consisted of didecyldimethylammonium chloride (DDAC), ortho-dichlorobenzene (1,2-dichlorobenzene, ODB), and chlorocresol (4-chloro-3-methylphenol, CC), and its component chemicals were individually tested for effectiveness against bovine herpes virus type 1 (BHV-1). DDAC, DDAC+ODB, DDAC+CC, and DDAC+ODB+CC showed effectiveness against BHV-1 at room temperature. However, ODB, CC, and ODB+CC showed no virucidal effects. The effects of all disinfectants tested were decreased at low temperature. DDAC showed disinfectant effects at a dilution of 1/800 and DDAC+ODB, DDAC+CC, and DDAC+ODB+CC at dilutions of 1/800 and 1/1600 at low temperature in the presence of 2% fetal bovine serum (FBS) but ODB, CC, and ODB+CC showed no virucidal effects. At low temperature and in the presence of 10% FBS, DDAC, DDAC+ODB, and DDAC+CC showed disinfectant effects at dilutions of 1/800, whereas ODB, CC, and ODB+CC showed no virucidal effects. DDAC+ ODB+CC was more effective (at 1/800 and 1/1600) than the other disinfectants under these conditions. In conclusion, a combination of three disinfectant components (DDAC+ODB+CC), enhanced the disinfectant effects at low temperature and in organic matter contamination.展开更多
基金support provided by the Department of Science and Technology,Science and Engineering Research Board(DST-SERB),the Anusandhan National Research Foundation(ANRF),State University Research Excellence(SERB-SURE),Ministry of Science and Technology,Govt.of India(SUR/2022/001353).
文摘Cancer is a global health problem and one of the leading causes of mortality.Immune checkpoint inhibitors have revolutionized the field of oncology,emerging as a powerful treatment strategy.A key pathway that has garnered considerable attention is programmed cell death-1(PD-1)/programmed cell death-ligand 1(PD-L1).The interaction between PD-L1 expressed on tumor cells and PD-1 reduces the innate immune response and thus compromises the capability of the body’s immune system.Furthermore,it controls the phenotype and functionality of innate and adaptive immune components.A range of monoclonal antibodies,including avelumab,atezolizumab,camrelizumab,dostarlimab,durvalumab,sinitilimab,toripalimab,and zimberelimab,have been developed for targeting the interaction between PD-1 and PD-L1.These agents can induce a broad spectrum of autoimmune-like complications that may affect any organ system.Recent studies have focused on the effect of various natural compounds that inhibit immune checkpoints.This could contribute to the existing arsenal of anticancer drugs.Several bioactive natural agents have been shown to affect the PD-1/PD-L1 signaling axis,promoting tumor cell apoptosis,influencing cell proliferation,and eventually leading to tumor cell death and inhibiting cancer progression.However,there is a substantial knowledge gap regarding the role of different natural compounds targeting PD-1 in the context of cancer.Hence,this review aims to provide a common connection between PD-1/PD-L1 blockade and the anticancer effects of distinct natural molecules.Moreover,the primary focus will be on the underlying mechanism of action as well as the clinical efficacy of bioactive molecules.Current challenges along with the scope of future research directions targeting PD-1/PD-L1 interactions through natural substances are also discussed.
基金Supported by the National Natural Science Foundation of China(21476182,21776227,21776228)Shaanxi Key Laboratory of Degradable Biomedical Materials Program(2014SZS07-K04,2014SZS07-P05,15JS106,2014SZS07-Z01,2014SZS07-Z02,2016SZSj-35,2014SZS07-K03)Shaanxi R&D Center of Biomaterials and Fermentation Engineering Program(2015HBGC-04)
文摘The rare ginsenoside Compound K (C-K) is attracting more attention because of its good physiological activity and urgent need. There are many pathways to obtain ginsenoside C-K, including chemical and biological methods. Among these, the conversion of PPD-type ginsenosides by enzymatic hydrolysis is a trend due to its high efficiency and mild conditions. For effectively extracting from the other panaxadiol saponins, the conversion process for ginsenoside C-K was investigated using snailases in this study. The univariate experimental design and response surface methodology were used to determine the optimal hydrolysis conditions for the conversion of ginsenoside Rbl into ginsenoside C-K by snailases. The optimum conditions were as follows: pH 5,12, temperature 51 ℃, ratio of snailase/substrate 0.21, and reaction time 48 h. On the basis of these parameters, the addition of 1.0 mmol· L- 1 ferric ion was found to significantly improve the enzymolysis ofsnailases for the first time. With the above conditions, the maximum conversion rate reached 89.7%, suggesting that the process can obviously increase the yield of ginsenoside C-K. The bioassay tests indicated that the ginsenoside C-K showed anti-tumor activity in a series of tumor cell lines. Based on these results, we can conclude that the process of rare ginsenoside C- K production by enzymolysis with snailase is feasible, efficient, and suitable for the industrial production and application.
基金supported by the National Natural Science Foundation of China (21173089 and 21373093)the Fundamental Research Funds for the Central Universities of China (2014ZZGH019)the Cooperative Innovation Center of Hubei Province
文摘Acid-catalyzed dehydration of alcohols has been widely employed for the synthesis of alkenes. However, activated alcohols when employed as substrates in dehydration reactions are often pla-gued by the lack of alkene selectivity. In this work, the reaction system can be significantly improved through enhancing the performance of Lewis acid catalysts in the dehydration of activated alcohols by combining with a Lewis base. Observations of the reaction mechanism revealed that the Lewis base component might have changed the reaction rate order. Although both the principal and side reaction rates decreased, the effect was markedly more observed on the latter reaction. Therefore, the selectivity of the dehydration reaction was improved. On the basis of this observation, a new route to synthesize 2-cinnamyl-1,3-dicarbonyl compounds was developed by using 2-aryl-3,4- di-hydropyran as a starting substrate in the presence of a Lewis acid/Lewis base combined catalyst system.
文摘A compound disinfectant, which consisted of didecyldimethylammonium chloride (DDAC), ortho-dichlorobenzene (1,2-dichlorobenzene, ODB), and chlorocresol (4-chloro-3-methylphenol, CC), and its component chemicals were individually tested for effectiveness against bovine herpes virus type 1 (BHV-1). DDAC, DDAC+ODB, DDAC+CC, and DDAC+ODB+CC showed effectiveness against BHV-1 at room temperature. However, ODB, CC, and ODB+CC showed no virucidal effects. The effects of all disinfectants tested were decreased at low temperature. DDAC showed disinfectant effects at a dilution of 1/800 and DDAC+ODB, DDAC+CC, and DDAC+ODB+CC at dilutions of 1/800 and 1/1600 at low temperature in the presence of 2% fetal bovine serum (FBS) but ODB, CC, and ODB+CC showed no virucidal effects. At low temperature and in the presence of 10% FBS, DDAC, DDAC+ODB, and DDAC+CC showed disinfectant effects at dilutions of 1/800, whereas ODB, CC, and ODB+CC showed no virucidal effects. DDAC+ ODB+CC was more effective (at 1/800 and 1/1600) than the other disinfectants under these conditions. In conclusion, a combination of three disinfectant components (DDAC+ODB+CC), enhanced the disinfectant effects at low temperature and in organic matter contamination.