The extensive research on public ethics in the local administration is more than necessary. This paper identifies the basic values of and the challenges to Macedonian Legal System in this area, and explains the key et...The extensive research on public ethics in the local administration is more than necessary. This paper identifies the basic values of and the challenges to Macedonian Legal System in this area, and explains the key ethical aspects, which should be implemented in practice by civil servants, who increasingly have to learn how to perform in accordance with ethical values. In this paper I will analyze the ethical values of civil servants laid down by the Organization for Economic Co-operation and Development (OECD) and the Civil Servants Agency in Macedonia, upon which the ethical principles for civil servants in the local administration units are intended to be set. This paper deals with the ethics of civil servants, assessment of best practices, and evaluation of positive and negative indicators. The paper concludes with a few recommendations for the next steps in this process; and some criteria for the consideration of future developments are suggested.展开更多
Objective: To assess the inhibitory effects of local injection of liposomal adriamycin (LADR) on the proliferation of lymph node metastases in rabbits bearing VX2 carcinoma in the mammary gland. Methods:Thirty female ...Objective: To assess the inhibitory effects of local injection of liposomal adriamycin (LADR) on the proliferation of lymph node metastases in rabbits bearing VX2 carcinoma in the mammary gland. Methods:Thirty female New Zealand white rabbits were divided into 3 groups, with 10 in each. VX2 tumor mass suspensions were injected into the breast tissues of rabbits. Treatment initiated once the axillary lymph node reached 5 mm in the maximum diameter. Group 1 received a sham treatment. Group 2 received a subcutaneous injection of LADR adjacent to tumor. Group 3 received an intravenous injection of free ADR (FADR) at the same dose and concentration to group 2. The breast tumors and axillary lymph nodes were resected after the treatment was repeated 3 times. The tumor and node sizes before and after treatment were measured. PCNA mRNA expressions in breast tumors and axillary nodes were determined using RT-PCR. Results: The mean growth ratios of lymph nodes after treatment were 3. 70, 1. 55, and 2. 89,respectively, in groups 1,2, and 3. The slowest node growth was observed in animals of group 2, with significant differences from group 1 (P<0. 001) and group 3 (P = 0. 002). The relative values of PCNA mRNA expression in lymph nodes were 0. 541, 0. 329,and 0. 450, respectively, in groups 1,2, and 3. Group 2 exhibited a significantly reduced PCNA mRNA expression in metastatic lymph node, as compared to group 1 (P<0. 001) and group 3 (P = 0. 004). Intravenous FADR injection effectively lowered the mRNA expressions of PCNA in breast tumors, which were not apparently altered after local LADR injection. Conclusion: Local injection of LADR holds a strong inhibitory effect on the proliferation of metastatic tumor cells in lymph nodes and appears to be an effective method for the treatment of lymphatic metastases of breast cancer.展开更多
The aim of this study was to identify the potential antibacterial effects of gatifloxacin on periodontal pathogens including Aggregatibacter actinomycetemcomitans, Porphyromonas gingi-valis, and Prevotella intermedia....The aim of this study was to identify the potential antibacterial effects of gatifloxacin on periodontal pathogens including Aggregatibacter actinomycetemcomitans, Porphyromonas gingi-valis, and Prevotella intermedia. The minimum inhibitory concentrations (MIC) of gatifloxacin and its bactericidal effects were investigated. Gatifloxacin inhibited the growth of all three kinds of periodontopathic bacteria tested in broth. The MIC value of 2.5 nM was found to be the most effective in inhibiting A. actinomycetemcomitans. An adenosine triphosphate biolumi-nescence assay revealed that gatifloxacin exhibited bactericidal effects on the tested bacteria in a time-dependent manner. The safety of gatifloxacin in mammalian cells was evaluated by assessing the viability of normal human dermal fibroblast (NHDF) cells treated with gatifloxacin. Almost all NHDF cells survived after 2-d culture, while 81% of the cells survived after 4-d culture when treated with 1.0 × 10<sup>3</sup> nM gatifloxacin. These results indicate that gatifloxacin is a possible drug for local administration to prevent periodontal infection.展开更多
Colorectal cancer causes the third most common type of malignant tumors with high morbidity and mortality.Chemotherapy is currently one of the most effective and common treatments for colorectal cancer.However,the poo...Colorectal cancer causes the third most common type of malignant tumors with high morbidity and mortality.Chemotherapy is currently one of the most effective and common treatments for colorectal cancer.However,the poor water solubility of some chemotherapeutics,untargeted drug delivery,and the undesirable systemic side effects of conventional treatment remain the major issues for colorectal cancer chemotherapy.Fortunately,drug delivery systems(DDS)based on biomaterials have been widely investigated and found to be capable of resolving those issues with good performance.Therefore,the main goal of this review is to summarize and discuss the progress and potential advantages of different DDS for colorectal cancer chemotherapy.We not only reviewed the nanocarriers used to improve the solubility of chemotherapeutics,including liposomes,micelles,and nanoparticles,but also discussed targeted DDS based on specific ligand-receptor recognition and tumor microenvironmental stimulus responses.Furthermore,locally administered systems based on hydrogels and microspheres,which have been shown to increase drug accumulation at the tumor site while decreasing systemic toxicity,were also emphasized.DDS provides a good option for improving the efficacy of chemotherapy in the treatment of colorectal cancer.展开更多
Enzyme-catalysis self-assembled oligopeptide hydrogel holds great interest in drug delivery,which has merits of biocompatibility,biodegradability and mild gelation conditions.However,its application for protein delive...Enzyme-catalysis self-assembled oligopeptide hydrogel holds great interest in drug delivery,which has merits of biocompatibility,biodegradability and mild gelation conditions.However,its application for protein delivery is greatly limited by inevitable degradation of enzyme on the encapsulated proteins leading to loss of protein activity.Moreover,for the intracellularly acted proteins,cell membrane as a primary barrier hinders the transmembrane delivery of proteins.The internalized proteins also suffer from acidic and enzymatic degradation in endosomes and lysosomes.We herein develop a proteasemanipulated hybrid nanogel/nanofiber hydrogel for localized delivery of intracellularly acted proteins.The embedded polymeric nanogels(CytoC/aNGs)preserve activity of cytochrome c(CytoC)that is an intracellular activator for cell apoptosis as a model protein against proteolysis,and do not affect the gelation properties of the protease-catalysis assembled hydrogels.The injectable hydrogel(CytoC/aNGs/Gel)serves as a reservoir to enhance intratumoral retention and realize sustainable release of CytoC/aNGs.The released CytoC/aNGs increase cellular uptake of CytoC and enhance its intracellular delivery to its target site,cytoplasm,resulting in favorable apoptosis-inducing and cytotoxic effects.We show that a single local administration of CytoC/aNGs/Gel efficiently inhibit the tumor growth in the breast tumor mouse model.展开更多
文摘The extensive research on public ethics in the local administration is more than necessary. This paper identifies the basic values of and the challenges to Macedonian Legal System in this area, and explains the key ethical aspects, which should be implemented in practice by civil servants, who increasingly have to learn how to perform in accordance with ethical values. In this paper I will analyze the ethical values of civil servants laid down by the Organization for Economic Co-operation and Development (OECD) and the Civil Servants Agency in Macedonia, upon which the ethical principles for civil servants in the local administration units are intended to be set. This paper deals with the ethics of civil servants, assessment of best practices, and evaluation of positive and negative indicators. The paper concludes with a few recommendations for the next steps in this process; and some criteria for the consideration of future developments are suggested.
基金Supported by the grants provided by the National Natural Science Foundation of China (No. 30600597)Natural Science Foundation of Shaanxi Province [No. 2005K09-G10(4)Science Technology Development Foundation of Xi'an (No. GG06167)
文摘Objective: To assess the inhibitory effects of local injection of liposomal adriamycin (LADR) on the proliferation of lymph node metastases in rabbits bearing VX2 carcinoma in the mammary gland. Methods:Thirty female New Zealand white rabbits were divided into 3 groups, with 10 in each. VX2 tumor mass suspensions were injected into the breast tissues of rabbits. Treatment initiated once the axillary lymph node reached 5 mm in the maximum diameter. Group 1 received a sham treatment. Group 2 received a subcutaneous injection of LADR adjacent to tumor. Group 3 received an intravenous injection of free ADR (FADR) at the same dose and concentration to group 2. The breast tumors and axillary lymph nodes were resected after the treatment was repeated 3 times. The tumor and node sizes before and after treatment were measured. PCNA mRNA expressions in breast tumors and axillary nodes were determined using RT-PCR. Results: The mean growth ratios of lymph nodes after treatment were 3. 70, 1. 55, and 2. 89,respectively, in groups 1,2, and 3. The slowest node growth was observed in animals of group 2, with significant differences from group 1 (P<0. 001) and group 3 (P = 0. 002). The relative values of PCNA mRNA expression in lymph nodes were 0. 541, 0. 329,and 0. 450, respectively, in groups 1,2, and 3. Group 2 exhibited a significantly reduced PCNA mRNA expression in metastatic lymph node, as compared to group 1 (P<0. 001) and group 3 (P = 0. 004). Intravenous FADR injection effectively lowered the mRNA expressions of PCNA in breast tumors, which were not apparently altered after local LADR injection. Conclusion: Local injection of LADR holds a strong inhibitory effect on the proliferation of metastatic tumor cells in lymph nodes and appears to be an effective method for the treatment of lymphatic metastases of breast cancer.
文摘The aim of this study was to identify the potential antibacterial effects of gatifloxacin on periodontal pathogens including Aggregatibacter actinomycetemcomitans, Porphyromonas gingi-valis, and Prevotella intermedia. The minimum inhibitory concentrations (MIC) of gatifloxacin and its bactericidal effects were investigated. Gatifloxacin inhibited the growth of all three kinds of periodontopathic bacteria tested in broth. The MIC value of 2.5 nM was found to be the most effective in inhibiting A. actinomycetemcomitans. An adenosine triphosphate biolumi-nescence assay revealed that gatifloxacin exhibited bactericidal effects on the tested bacteria in a time-dependent manner. The safety of gatifloxacin in mammalian cells was evaluated by assessing the viability of normal human dermal fibroblast (NHDF) cells treated with gatifloxacin. Almost all NHDF cells survived after 2-d culture, while 81% of the cells survived after 4-d culture when treated with 1.0 × 10<sup>3</sup> nM gatifloxacin. These results indicate that gatifloxacin is a possible drug for local administration to prevent periodontal infection.
基金financial support from the National Natural Science Foundation of China(Nos.U21A20417,31930067,and 31800797)the Sichuan Science and Technology Program(Nos.2022YFS0333 and 2022YFS0203)+1 种基金the 1·3·5 project for disciplines of excellence,West China Hospital,Sichuan University(No.ZYGD18002)the Post-Doctor Research Project,West China Hospital,Sichuan University(No.2018HXBH066)。
文摘Colorectal cancer causes the third most common type of malignant tumors with high morbidity and mortality.Chemotherapy is currently one of the most effective and common treatments for colorectal cancer.However,the poor water solubility of some chemotherapeutics,untargeted drug delivery,and the undesirable systemic side effects of conventional treatment remain the major issues for colorectal cancer chemotherapy.Fortunately,drug delivery systems(DDS)based on biomaterials have been widely investigated and found to be capable of resolving those issues with good performance.Therefore,the main goal of this review is to summarize and discuss the progress and potential advantages of different DDS for colorectal cancer chemotherapy.We not only reviewed the nanocarriers used to improve the solubility of chemotherapeutics,including liposomes,micelles,and nanoparticles,but also discussed targeted DDS based on specific ligand-receptor recognition and tumor microenvironmental stimulus responses.Furthermore,locally administered systems based on hydrogels and microspheres,which have been shown to increase drug accumulation at the tumor site while decreasing systemic toxicity,were also emphasized.DDS provides a good option for improving the efficacy of chemotherapy in the treatment of colorectal cancer.
基金supported by the National Key Research and Development Program of China(No.2019YFA0905200)the National Natural Science Foundation of China(No.81971730,No.81503012)+1 种基金the Natural Science Foundation of Jiangsu Province of China for Excellent Young Scholars(No.BK20190084)the Young Elite Scientists Sponsorship Program by CAST(China)
文摘Enzyme-catalysis self-assembled oligopeptide hydrogel holds great interest in drug delivery,which has merits of biocompatibility,biodegradability and mild gelation conditions.However,its application for protein delivery is greatly limited by inevitable degradation of enzyme on the encapsulated proteins leading to loss of protein activity.Moreover,for the intracellularly acted proteins,cell membrane as a primary barrier hinders the transmembrane delivery of proteins.The internalized proteins also suffer from acidic and enzymatic degradation in endosomes and lysosomes.We herein develop a proteasemanipulated hybrid nanogel/nanofiber hydrogel for localized delivery of intracellularly acted proteins.The embedded polymeric nanogels(CytoC/aNGs)preserve activity of cytochrome c(CytoC)that is an intracellular activator for cell apoptosis as a model protein against proteolysis,and do not affect the gelation properties of the protease-catalysis assembled hydrogels.The injectable hydrogel(CytoC/aNGs/Gel)serves as a reservoir to enhance intratumoral retention and realize sustainable release of CytoC/aNGs.The released CytoC/aNGs increase cellular uptake of CytoC and enhance its intracellular delivery to its target site,cytoplasm,resulting in favorable apoptosis-inducing and cytotoxic effects.We show that a single local administration of CytoC/aNGs/Gel efficiently inhibit the tumor growth in the breast tumor mouse model.