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Esteban Vera Pingitore María Silvina Juárez Tomás Birgitt Wiese 《Drug development and industrial pharmacy》2015,41(6):942-952
Context: The administration of pharmabiotics is a promising alternative to antimicrobial drugs for the treatment and/or prevention of female urogenital infections.Objective: To design pharmabiotic formulations including bioactive ingredients of microbial origin combined with non-microbial substances and then to evaluate the stability of the combinations during freeze-drying and storage.Materials and methods: Different formulations including Lactobacillus gasseri CRL 1263, Lactobacillus salivarius CRL 1328, salivaricin CRL 1328 (a bacteriocin) and non-microbial compounds (lactose, inulin and ascorbic acid) were assayed, and the ingredients were freeze-dried together or separately. The formulations were stored in gelatin capsules at 4?°C for 360?d.Results: The viability of lactobacilli was affected to different extents depending on the strains and on the formulations assayed. L. salivarius and ascorbic acid were successfully combined only after the freeze-drying process. Salivaricin activity was not detected in formulations containing L. gasseri. However, when combined with ascorbic acid, lactose, inulin or L. salivarius, the bacteriocin maintained its activity for 360?d. The selected microorganisms proved to be compatible for their inclusion in multi-strain formulations together with lactose, inulin and ascorbic acid. Salivaricin could be included only in a L. salivarius CRL 1328 single-strain formulation together with non-microbial substances.Conclusions: This study provides new insights into the design of urogenital pharmabiotics combining beneficial lactobacilli, salivaricin CRL 1328 and compounds with different functionalities. 相似文献
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Priyadarshi Chakraborty Yiming Tang Tomoya Yamamoto Yifei Yao Tom Guterman Shai Zilberzwige-Tal Nofar Adadi Wei Ji Tal Dvir Ayyalusamy Ramamoorthy Guanghong Wei Ehud Gazit 《Advanced materials (Deerfield Beach, Fla.)》2020,32(9):1906043
Self-assembled peptide hydrogels represent the realization of peptide nanotechnology into biomedical products. There is a continuous quest to identify the simplest building blocks and optimize their critical gelation concentration (CGC). Herein, a minimalistic, de novo dipeptide, Fmoc-Lys(Fmoc)-Asp, as an hydrogelator with the lowest CGC ever reported, almost fourfold lower as compared to that of a large hexadecapeptide previously described, is reported. The dipeptide self-assembles through an unusual and unprecedented two-step process as elucidated by solid-state NMR and molecular dynamics simulation. The hydrogel is cytocompatible and supports 2D/3D cell growth. Conductive composite gels composed of Fmoc-Lys(Fmoc)-Asp and a conductive polymer exhibit excellent DNA binding. Fmoc-Lys(Fmoc)-Asp exhibits the lowest CGC and highest mechanical properties when compared to a library of dipeptide analogues, thus validating the uniqueness of the molecular design which confers useful properties for various potential applications. 相似文献
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Dr. Yahu A. Liu Dr. Qihui Jin Qiang Ding Dr. Xueshi Hao Tingting Mo Shanshan Yan Dr. Yefen Zou Dr. Zhihong Huang Xiaoyue Zhang Wenqi Gao Dr. Tom Y.-H. Wu Chun Li Dr. Badry Bursalaya Dr. Michael Di Donato Dr. You-Qing Zhang Lisa Deaton Dr. Weijun Shen Dr. Brandon Taylor Anwesh Kamireddy Dr. George Harb Dr. Jing Li Dr. Yong Jia Dr. Andrew M. Schumacher Dr. Bryan Laffitte Dr. Richard Glynne Dr. Shifeng Pan Dr. Peter McNamara Dr. Valentina Molteni Dr. Jon Loren 《ChemMedChem》2020,15(16):1562-1570
Loss of β-cell mass and function can lead to insufficient insulin levels and ultimately to hyperglycemia and diabetes mellitus. The mainstream treatment approach involves regulation of insulin levels; however, approaches intended to increase β-cell mass are less developed. Promoting β-cell proliferation with low-molecular-weight inhibitors of dual-specificity tyrosine-regulated kinase 1A (DYRK1A) offers the potential to treat diabetes with oral therapies by restoring β-cell mass, insulin content and glycemic control. GNF4877, a potent dual inhibitor of DYRK1A and glycogen synthase kinase 3β (GSK3β) was previously reported to induce primary human β-cell proliferation in vitro and in vivo. Herein, we describe the lead optimization that lead to the identification of GNF4877 from an aminopyrazine hit identified in a phenotypic high-throughput screening campaign measuring β-cell proliferation. 相似文献
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Alexander J.Stirk Benjamin H.Wilson Christopher A.O’Keefe Hazem Amame Kelong Zhu Robert W.Schurko Stephen J.Loeb 《Nano Research》2021,14(2):417-422
The concept of“robust dynamics”describes the incorporation of mechanically interlocked molecules(MIMs)into metal-organic framework(MOF)materials such that large amplitude motions(e.g.,rotation or translation of a macrocycle)can occur inside the free volume pore of the MOF.To aid in the preparation of such materials,reticular synthesis was used herein to design rigid molecular building blocks with predetermined ordered structures starting from the well-known MOF NOTT-101.New linkers were synthesized that have a T-shape,based on a triphenylene tetra-carboxylate strut,and their incorporation into Cu(II)-based MOFs was investigated.The single-crystal structures of three new MOFs,UWCM-12(fof),β-UWCM-13(loz),UWCM-14(lil),with naked T-shaped linkers were determined;β-UWCM-13 is the first reported example of the loz topology.A fourth MOF,UWDM-14(lil)is analogous to UWCM-14(lil)but contains a[2]rotaxane linker.Variable-temperature,2H solid-state NMR was used to probe the dynamics of a 24-membered macrocycle threaded onto the MOF skeleton. 相似文献