Indole-Based and Cyclopentenylindole-Based Analogues Containing Fluorine Group as Potential 18F-Labeled Positron Emission Tomography (PET) G-Protein Coupled Receptor 44 (GPR44) Tracers.

Recently, growing evidence of the relationship between G-protein coupled receptor 44 (GPR44) and the inflammation-cancer system has garnered tremendous interest, while the exact role of GPR44 has not been fully elucidated. Currently, there is a strong and urgent need for the development of non-invasive in vivo GPR44 positron emission tomography (PET) radiotracers that can be used to aid the exploration of the relationship between inflammation and tumor biologic behavior. Accordingly, the choosing and radiolabeling of existing GPR44 antagonists containing a fluorine group could serve as a viable method to accelerate PET tracers development for in vivo imaging to this purpose. The present study aims to evaluate published (2000-present) indole-based and cyclopentenyl-indole-based analogues of the GPR44 antagonist to guide the development of fluorine-18 labeled PET tracers that can accurately detect inflammatory processes. The selected analogues contained a crucial fluorine nuclide and were characterized for various properties including binding affinity, selectivity, and pharmacokinetic and metabolic profile. Overall, 26 compounds with favorable to strong binding properties were identified. This review highlights the potential of GPR44 analogues for the development of PET tracers to study inflammation and cancer development and ultimately guide the development of targeted clinical therapies.

Fabrication of pH-sensitive graphene oxide-Benazepril carrier as biosafety controlled release systems.

A novel graphene oxide (GO)-based carrier was fabricated for the controlled release of Benazepril (BENA). Freeze dried samples of GO-BENA carrier were prepared for controlled drug release at different pHs (pH = 2, 7, and 10) and release kinetics indicate BENA desorption from GO is by Fickian diffusion. The BENA yield from the carrier amounted to ~55% of the adsorbed material in a strongly acidic medium after 50 h. Binding fractions of BENA to 10 mg/L GO was determined for different solution concentrations of the drug. In vitro assays of cell proliferation (WST-1 kit), cell structural integrity (LDH kit) and flow cytometric indicators of necrosis in three different cell lines (CACO-2, SGC-7901, and primary mouse hepatic fibroblast) all demonstrated that the GO carrier had a good biocompatibility. The pH-dependent release sensitivity of the GO-based carrier suggests that it is a potential candidate for use in the controlled release of drugs in the acidic environment of the stomach.

Amplified Analysis of DNA or Proteins by TdT-generated DNAzyme.

Sensitive and specific detection of nucleic acids or proteins, which act as biomarkers, is of great importance in disease diagnosis. By combing the concept and operation of an endonuclease-assisted target-responsive amplification method and peroxidase-mimic DNAzyme generated by terminal deoxynucleotidyl transferase (TdT), a novel and facile colorimetric biosensor was developed for DNA and protein. Target DNA and thrombin were chosen as representative biomolecules. The production of cleavage fragments can only be triggered by specific target binding and the following nicking process, which do not occur spontaneously. In the signal collection part, numerous guanine-rich DNA were produced through the prolongation of cleavage fragments by TdT and formed highly effective DNAzyme with hemin. In this novel amplification method, we succeeded in realizing sensitive and specific detection of target DNA and thrombin. Under optimal conditions, target DNA can be detected as low as 1 pM, and thrombin with a detection limit of 100 pM. The method also proves the potential versatility and feasibility of TdT-generated DNAzyme in various bio-analyses.

A New Method of Biostorage and Biopreservation for Human Amputated Extremities.

OBJECTIVES: We have explored a better method to preserve and store human medically amputated large size samples. The approach involved developing a special embalming solution and procedures for biopreservation and biostorage of a large-sized sample as a whole specimen rather than dissected small parts. Evaluation of the effect of our special embalming solution and procedures on whole human amputated extremities compared with excised small tissues was conducted. Histological and morphological techniques and elemental analyses were utilized to assess the effects of our new method using the special embalming solution. METHODS: Whole remains and excised tissues (skin, muscle, saphenous nerve, and femoral artery) were immersed in a special embalming solution for 6, 12, and 24 months, respectively. Then samples from whole remains and excised tissues were paraffin embedded and Hematoxylin-Eosin staining was performed. Transmission electron microscopy was performed to detect the microstructure of the samples. At the same time, concentrations of chemical elements in the embalming solution from whole remains and excised tissues were separately determined by using inductively coupled plasma atomic emission spectrometry. RESULTS: The morphological structure of tissues was well preserved at 6 and 12 months, and few chemical elements, especially trace elements, leached into the embalming fluid. The macroelements leached into the fluid earlier than the trace elements, but there were some differences in the ultrastructure after preservation for 24 months between tissues excised before and after embalming. Over time, the types and concentrations of chemical elements in the embalming fluid increased. The trace elements in the whole remains were preserved better than those in the removed tissues, and trace elements in muscles and femoral artery were better preserved than those in the skin and saphenous nerve. CONCLUSION: The special embalming fluid can preserve fresh amputated remains well for a short time (less than 24 months), and performs better for the whole remains than excised tissues. This specific embalming fluid should be further studied to achieve higher quality preservation of different tissues for a longer period of time.