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991.
《Endocrine practice》2023,29(7):560-565
ObjectiveType 2 diabetes mellitus (T2DM) affects 25% of adults over age 65. Nevertheless, few clinical trials include patients over age 75.MethodsThis case series reports retrospective data on a cohort of 85 patients aged 80 and over (mean 88.1, range 80-104) with T2DM, managed by a single endocrinologist. The practice’s computerized data base was searched for all patients 80 years of age and older with a diagnosis of T2DM.ResultsThe major observations were the significant decrease in the use of agents associated with hypoglycemia (sulfonylureas and insulin), and the beneficial and well-tolerated use of glucagon like peptide-1 receptor analogues (GLP-1 RA). The mean A1c in the entire cohort dropped from 7.6% to 6.6% over a mean of 9 months. Nearly one-half of the cohort were treated with GLP1-RA, reflecting studies demonstrating the safety and efficacy of this class of drugs in less elderly patients. At presentation, 75% were on sulfonylurea and/or insulin; this number was reduced to 27%. Furthermore, none of the patients required short-acting (bolus) insulin to achieve the individualized A1c target.ConclusionPatients with T2DM aged 80 and over respond well to GLP1-RA drugs, drastically reducing the need for agents associated with hypoglycemia. The important question, which will require larger and prospective studies, is whether the lowering of A1c, as shown in this paper, and the use of GLP-1 RA specifically, are associated with improved morbidity and mortality in the very elderly. 相似文献
992.
Guanghui Zong Melissa Hirsch Collin Mondrik Zhijian Hu Wei Q. Shi 《Bioorganic & medicinal chemistry letters》2017,27(12):2752-2756
Ipomoeassin F is a plant-derived macrocyclic glycolipid with single-digit nanomolar IC50 values against cancer cell growth. In previous structure–activity relationship studies, we have demonstrated that certain modifications around the fucoside moiety did not cause significant cytotoxicity loss. To further elucidate the effect of the fucoside moiety on the biological activity, we describe here the design and synthesis of several fucose-truncated monosaccharide analogues of ipomoeassin F. Subsequent biological evaluation strongly suggests that the 6-membered ring of the fucoside moiety is essential to the overall conformation of the molecule, thereby influencing bioactivity. 相似文献
993.
994.
L. A. Fonina A. A. Az’muko V. N. Kalikhevich M. L. Lewit Z. A. Ardemasova S. A. Gur’yanov R. G. Belevskaya M. A. Efremov E. M. Treshchalina A. A. Mikhailova 《Russian Journal of Bioorganic Chemistry》2008,34(4):404-408
The Val-Val-Tyr-Pro-Asp bone marrow peptide (MP-5) and its analogue (MP-5-Lys) were synthesized. Fluorescent derivatives, Ftc-MP-5 and MP-5-Lys(Ftc), were prepared. The iological activity of MP-5 and MP-5-Lys was studied in vitro and in vivo. The MP-5 peptide caused 60–84% inhibition of growth of the following mouse cancers: lymphatic leukemia P388, melanoma B-16, and cervical carcinoma CUC-5. These peptides also restored functional activity of T-lymphocytes that was inhibited by metabolic products of the HL-60 leukemic cell line. MP-5-Lys(Ftc) was shown to preserve the functional properties of MP-5 towards T-lymphocytes, but Ftc-MP-5 was practically inactive. 相似文献
995.
Estimation of an effective soil water potential at the root surface of transpiring plants 总被引:7,自引:3,他引:4
HAMLYN G. JONES 《Plant, cell & environment》1983,6(8):671-674
Abstract. A simple method is described for estimating an average of 'effective' soil water potential at the root surface for transpiring plants. The method is based on measurements of leaf water potential and leaf conductance to water vapour in stressed plants and in well-watered controls, and uses the simple Ohm's law analogue for water flow in the soil-plant system. The technique is applied to data for field-grown apple trees and to previously published data for wheat and cowpea. 相似文献
996.
A. E. Medvedev V. Glover 《Biochemistry (Moscow) Supplemental Series B: Biomedical Chemistry》2007,1(3):192-197
Criteria for the evaluation of the functional importance of endogenous analogues of pharmacological drugs are proposed. These include opposite changes in their content in opposite pathophysiological or physiological states, accompanied by corresponding changes in the functional activity of enzymes sensitive to changes in their level, and the regulation of target enzymes by physiological concentrations of such endogenous compounds. The applicability of these criteria has been demonstrated using tribulin, the endogenous family of inhibitors of monoamine oxidases. 相似文献
997.
《Bioorganic & medicinal chemistry letters》2020,30(2):126819
Twenty-nine nucleoside analogues have been synthesized and evaluated in a cell based assay for their ability to activate the human Stimulator of Interferon Genes (hSTING), a key protein of the innate immune defense. Some 6-O-alkyl nucleoside analogues activate hSTING without associated cytotoxicity. SAR and combination studies were performed to decipher possible activation mechanism. The described nucleoside hSTING activators represent first-in-class modulators of the innate immune defense; a highly relevant target for antiviral, antibacterial, anticancer or Alzheimer’s disease treatments and may present advantages over other types of hSTING activators. 相似文献
998.
Atish Barua Pritha Choudhury Joy Krishna Maity Sukhendu Bikash Mandal Suvra Mandal 《Free radical research》2019,53(1):57-67
Therapeutic efficacy of nucleoside analogues (NAs) like Gemcitabine, 5-fluorouracil in cancer treatment is already well established. Most of the known NAs are highly toxic to normal cells due to its non-specific action; thus searching for non-toxic NAs are still going on. For that purpose we have synthesised nine different NAs by alteration of their structural and functional groups. The aim of present study is to investigate the therapeutic potential of NAs against mice bearing breast adenocarcinoma cells at IC50 dose for 10 days treatment schedule. Results of the present study showed that, among the seven nucleoside analogues, NA-7 and NA-9 showed maximum therapeutic efficacy in controlling cancer cells by inhibiting cell proliferation and inducing apoptosis without any adverse effects to normal host cells. Additionally, NAs significantly decreased the tumour burden and enhanced survivability of host through generation of reactive oxygen species in tumour cells. These ultimately led to DNA damage, depolarisation of mitochondrial membrane potential and apoptosis in tumour cells. To find out the molecular mechanisms, we showed that administration of NA-7 and NA-9, down- regulating the expression of Bcl-2, cyclin D1, C-myc, P-21 and up-regulating the expression of P-53, Cyt-c, Bax, caspase-3 and caspase-9. The results suggest that NA-7 and NA-9 exhibits significant antitumor activity than 5-fluorouracil by modulating the cell cycle checkpoints and inducing apoptosis in Ehrlich ascites carcinoma (EAC)-bearing mice. Additionally, NA-7 and NA-9 did not show any clastogenic effect on bone marrow cells at sub-lethal dose. Thus, the present study clearly suggested therapeutic benefit of NAs by augmenting anticancer efficacy and diminishing toxicity to the host. 相似文献
999.
Broadbridge Robert J. Sharma Ram P. 《International journal of peptide research and therapeutics》1999,6(5-6):335-341
Summary Phosphorylation reactions are key meditors in a variety of biochemical signal processes. Research into the selective inhibition
of protein tyrosine kinases to generate anticancer agents has madeO-phosphotyrosyl analogues important pharmacological tools. The simple procedures reported here involving the formation of
interative peptide libraries together with the development of a selective and sensitive bead-binding assay have made it possible
to rapidly screen peptides incorporatingO-phosphotyrosyl surrogates (includingO-phospho-2,3,5,6-tetrafluorotyrosine, 4-(phosphono)hydroxymethyl-phenylalanine and 4-(phosphono)fluoromethyl-phenylalanine)
for their potential to inhibit the protein tyrosine kinase p56lck. These procedures can be easily adapted to combinatorical peptide libraries. 相似文献
1000.
Ma Wenli Mosberg Henry I. 《International journal of peptide research and therapeutics》1999,6(2-3):179-183
Summary A straightforward approach for the synthesis of several new, aryl-substituted derivatives of the conformationally constrained
phenylalanine analogue 1,2,3,4-tetrahydroisoquinoline-3-carboxylic acid (Tic) is described. Tic, nitrosubstituted at the 6
or 7 position, was prepared by base-catalyzed cyclization of diethyl acetamidomalonate with α,α-dibromo-4-nitro-o-xylene followed by decarboxylation and deacylation under refluxing conditions in aqueous HCl. Catalytic hydrogenation of
nitro-Tic in the presence of 10% Pd/C afforded amino-Tic, which was then converted to iodo-Tic by a modified Sandmeyer reaction.
Both amino-Tic and iodo-Tic can easily be transformed to other substituents. 相似文献