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1.
CNS Neurosci Ther ; 30(9): e70002, 2024 Sep.
Article in English | MEDLINE | ID: mdl-39252462

ABSTRACT

AIMS: This study aims to investigate the safety, tolerability, efficacy, and pharmacokinetics of Pynegabine as an add-on therapy in the treatment of focal epilepsy. METHODOLOGY: This is a protocol phase-IIa, randomized, double-blinded, placebo-controlled, multicenter study in patients with focal epilepsy from multiple centers in China who have been treated with at least 2 ASMs without effective control. The study involves an 8-week run-in period with stable use of previous medications. Patients are then randomized to receive either Pynegabine or a placebo. Sentinel administration is performed initially, and subsequent patients are randomized based on safety assessments. Three dose cohorts (15, 20, and 25 mg/d) are established. Efficacy is assessed through various measures, including seizure frequency, CGI score, PGI score, HAMA score, HAMD score, MoCA scale score, QOLIE-31 scale score, and 12 h-EEG score. Safety evaluations, PK blood samples, concomitant medications, and adverse events are also recorded. CONCLUSION: Data from the study will be used to evaluate the safety, tolerability, efficacy, and pharmacokinetics of Pynegabine tablets as add-on therapy for focal epilepsy.


Subject(s)
Anticonvulsants , Epilepsies, Partial , Humans , Double-Blind Method , Epilepsies, Partial/drug therapy , Anticonvulsants/pharmacokinetics , Anticonvulsants/administration & dosage , Anticonvulsants/therapeutic use , Male , Female , Adult , Middle Aged , Young Adult , Drug Therapy, Combination , Treatment Outcome , Dose-Response Relationship, Drug , Adolescent , Administration, Oral , Tablets , Aged , Carbamates , Propylamines
2.
Anal Chem ; 96(35): 14108-14115, 2024 Sep 03.
Article in English | MEDLINE | ID: mdl-39167423

ABSTRACT

In electrochemical analysis, developing biosensors that can resist the nonspecific adsorption of interfering biomolecules in human serum remains a huge challenge, which depends on the design of efficient antifouling materials. Herein, 3-aminopropyldimethylamine oxide (APDMAO) biomimetic zwitterions were prepared as antifouling interfaces. Among them, the unique positive and negative charges (N+-O-) of APDMAO promoted its hydrogen bonding with water molecules, forming a firm hydration barrier that endowed it with strong and stable antifouling performance. Meanwhile, its inherent amino groups could copolymerize with the biomimetic adhesive dopamine to form a thin layer of quinone intermediates, providing conditions for the subsequent binding of aptamers and signal probes. Importantly, the biomimetic APDMAO with functional groups and one-step oxidation characteristics solved the challenges of zwitterionic synthesis and modification, as well as improved biocompatibility of the sensing interface, thereby expanding the application potential of zwitterions as antifouling materials in sensing analysis. Thiol-containing alpha-fetoprotein (AFP) aptamers modified with methylene blue (MB) were coupled under controllable potential, greatly reducing the incubation time, which promoted the productization application of biosensors. In addition, the ratio sensing strategy using MB as internal standard factors and concanavalin-silver nanoparticles (ConA-Ag NPs) as signal probes was introduced to reduce background and instrument interferences, thus improving detection accuracy. On this basis, the proposed antifouling electrochemical biosensor achieved sensitive and accurate AFP detection over a wide dynamic range (10 fg/mL-10 ng/mL), with a low detection limit of 3.41 fg/mL (3σ/m). This work provides positive insights into the development of zwitterionic antifouling materials and clinical detection of liver cancer markers in human serum.


Subject(s)
Biosensing Techniques , Electrochemical Techniques , alpha-Fetoproteins , Humans , alpha-Fetoproteins/analysis , Biosensing Techniques/methods , Electrochemical Techniques/methods , Limit of Detection , Biofouling/prevention & control , Aptamers, Nucleotide/chemistry , Propylamines/chemistry , Polymers/chemistry
3.
ACS Nano ; 18(34): 23537-23552, 2024 Aug 27.
Article in English | MEDLINE | ID: mdl-39133543

ABSTRACT

Numerous small biomolecules exist in the human body and play roles in various biological and pathological processes. Small molecules are believed not to induce intrafibrillar mineralization alone. They are required to work in synergy with noncollagenous proteins (NCPs) and their analogs, e.g. polyelectrolytes, for inducing intrafibrillar mineralization, as the polymer-induced liquid-like precursor (PILP) process has been well-documented. In this study, we demonstrate that small charged molecules alone, such as sodium tripolyphosphate, sodium citrate, and (3-aminopropyl) triethoxysilane, could directly mediate fibrillar mineralization. We propose that small charged molecules might be immobilized in collagen fibrils to form the polyelectrolyte-like collagen complex (PLCC) via hydrogen bonds. The PLCC could attract CaP precursors along with calcium and phosphate ions for inducing mineralization without any polyelectrolyte additives. The small charged molecule-mediated mineralization process was evidenced by Cryo-TEM, AFM, SEM, FTIR, ICP-OES, etc., as the PLCC exhibited both characteristic features of collagen fibrils and polyelectrolyte with increased charges, hydrophilicity, and density. This might hint at one mechanism of pathological biomineralization, especially for understanding the ectopic calcification process.


Subject(s)
Sodium Citrate , Sodium Citrate/chemistry , Sodium Citrate/metabolism , Animals , Humans , Citrates/chemistry , Collagen/chemistry , Collagen/metabolism , Calcinosis/metabolism , Calcinosis/pathology , Propylamines/chemistry
4.
Enzyme Microb Technol ; 180: 110501, 2024 Oct.
Article in English | MEDLINE | ID: mdl-39197217

ABSTRACT

L-phosphinothricin (L-PPT) is the most popular broad-spectrum and highly effective herbicide. Transaminases (TAs) play a pivotal role in asymmetric synthesis of L-PPT, yet encounter the challenge of unfavorable reaction equilibrium. In this study, the novel dual transaminases cascade system (DTCS) was introduced to facilitate the synthesis of L-PPT. The specific amine transaminase BdATA, originating from Bradyrhizobium diazoefficiens ZJY088, was screened and identified. It exhibited remarkable activity, good stability, and required only 2.5 equivalents of isopropylamine to transform pyruvate effectively. By coupling BdATA with previously reported SeTA to construct the DTCS for pyruvate removal in situ, the L-PPT yield escalated from 37.37 % to 85.35 %. Three advantages of the DTCS were presented: the removal of pyruvate alleviated by-product inhibition, the use of isopropylamine reduced reliance on excess L-alanine, and no demand for expensive cofactors like NAD(P)H. It demonstrated an innovative idea for addressing the challenges associated with transaminase-mediated synthesis of L-PPT.


Subject(s)
Aminobutyrates , Pyruvic Acid , Transaminases , Transaminases/metabolism , Aminobutyrates/metabolism , Pyruvic Acid/metabolism , Bradyrhizobium/enzymology , Herbicides , Bacterial Proteins/metabolism , Amines/metabolism , Propylamines/chemistry
5.
Int J Biol Macromol ; 277(Pt 2): 134185, 2024 Oct.
Article in English | MEDLINE | ID: mdl-39074694

ABSTRACT

Critical-size bone defect repair presents multiple challenges, such as osteogenesis, vascularization, and neurogenesis. Current biomaterials for bone repair need more consideration for the above functions. Organic-inorganic composites combined with bioactive ions offer significant advantages in bone regeneration. In our work, we prepared an organic-inorganic composite material by blending polylactic acid (PLA) with 3-aminopropyltriethoxysilane (APTES)-modified magnesium silicate (A-M2S) and fabricated it by 3D printing. With the increase of A-M2S proportion, the hydrophilicity and mineralization ability showed an enhanced trend, and the compressive strength and elastic modulus were increased from 15.29 MPa and 94.61 MPa to 44.30 MPa and 435.77 MPa, respectively. Furthermore, A-M2S/PLA scaffolds not only exhibited good cytocompatibility of bone marrow mesenchymal stem cells (BMSCs), human umbilical vein endothelial cells (HUVECs), and Schwann cells (SCs), but also effectively promoted osteogenesis, angiogenesis, and neurogenesis in vitro. After implanting 10% A-M2S/PLA scaffolds in vivo, the scaffolds showed the most effective repair of cranium defects compared to the blank and control group (PLA). Additionally, they promoted the secretion of proteins related to bone regeneration and neurovascular formation. These results provided the basis for expanding the application of A-M2S and PLA in bone tissue engineering and presented a novel concept for neurovascularized bone repair.


Subject(s)
Bone Regeneration , Human Umbilical Vein Endothelial Cells , Magnesium Silicates , Mesenchymal Stem Cells , Osteogenesis , Polyesters , Printing, Three-Dimensional , Tissue Scaffolds , Bone Regeneration/drug effects , Tissue Scaffolds/chemistry , Polyesters/chemistry , Humans , Human Umbilical Vein Endothelial Cells/drug effects , Mesenchymal Stem Cells/drug effects , Mesenchymal Stem Cells/cytology , Osteogenesis/drug effects , Animals , Magnesium Silicates/chemistry , Tissue Engineering/methods , Biocompatible Materials/chemistry , Biocompatible Materials/pharmacology , Schwann Cells/drug effects , Schwann Cells/cytology , Silanes/chemistry , Silanes/pharmacology , Neurogenesis/drug effects , Propylamines/chemistry , Propylamines/pharmacology , Neovascularization, Physiologic/drug effects
6.
J Environ Sci (China) ; 146: 39-54, 2024 Dec.
Article in English | MEDLINE | ID: mdl-38969461

ABSTRACT

To improve the selective separation performance of silica nanofibers (SiO2 NFs) for cesium ions (Cs+) and overcome the defects of Prussian blue nanoparticles (PB NPs), PB/SiO2-NH2 NFs were prepared to remove Cs+ from water. Among them, 3-aminopropyltriethoxysilane (APTES) underwent an alkylation reaction with SiO2, resulting in the formation of a dense Si-O-Si network structure that decorated the surface of SiO2 NFs. Meanwhile, the amino functional groups in APTES combined with Fe3+ and then reacted with Fe2+ to form PB NPs, which anchored firmly on the aminoated SiO2 NFs surface. In our experiment, the maximum adsorption capacity of PB/SiO2-NH2 NFs was 111.38 mg/g, which was 31.5 mg/g higher than that of SiO2 NFs. At the same time, after the fifth cycle, the removal rate of Cs+ by PB/SiO2-NH2 NFs adsorbent was 75.36% ± 3.69%. In addition, the adsorption isotherms and adsorption kinetics of PB/SiO2-NH2 NFs were combined with the Freundlich model and the quasi-two-stage fitting model, respectively. Further mechanism analysis showed that the bond between PB/SiO2-NH2 NFs and Cs+ was mainly a synergistic action of ion exchange, electrostatic adsorption and membrane separation.


Subject(s)
Cesium , Ferrocyanides , Nanofibers , Nanoparticles , Water Pollutants, Chemical , Water Purification , Ferrocyanides/chemistry , Nanofibers/chemistry , Water Pollutants, Chemical/chemistry , Cesium/chemistry , Adsorption , Water Purification/methods , Nanoparticles/chemistry , Silicon Dioxide/chemistry , Kinetics , Propylamines/chemistry , Silanes
7.
J Environ Manage ; 365: 121603, 2024 Aug.
Article in English | MEDLINE | ID: mdl-38963967

ABSTRACT

Water treatment has turned out to be more important in most societies due to the expansion of most economies and to advancement of industrialization. Developing efficient materials and technologies for water treatment is of high interest. Thin film nanocomposite membranes are regarded as the most effective membranes available for salts, hydrocarbon, and environmental pollutants removal. These membranes improve productivity while using less energy than conventional asymmetric membranes. Here, the polyvinylidene fluoride (PVDF) membranes have been successfully modified via dip single-step coating by silica-aminopropyl triethoxysilane/trimesic acid/melamine nanocomposite (Si-APTES-TA-MM). The developed membranes were evaluated for separating the emulsified oil/water mixture, the surface wettability of the membrane materials is therefore essential. During the conditioning step, that is when the freshwater was introduced, the prepared membrane reached a flux of about 27.77 L m-2 h-1. However, when the contaminated water was introduced, the flux reached 18 L m-2 h-1, alongside an applied pressure of 400 kPa. Interestingly, during the first 8 h of the filtration test, the membrane showed 90 % rejection for ions including Mg2+, and SO42- and ≈100 % for organic pollutants including pentane, isooctane, toluene, and hexadecane. Also, the membrane showed 98 % rejection for heavy metals including strontium, lead, and cobalt ions. As per the results, the membrane could be recommended as a promising candidate to be used for a mixture of salt ions, hydrocarbons, and mixtures of heavy metals from wastewater.


Subject(s)
Membranes, Artificial , Silanes , Water Pollutants, Chemical , Water Purification , Water Purification/methods , Silanes/chemistry , Water Pollutants, Chemical/chemistry , Metals/chemistry , Oils/chemistry , Propylamines/chemistry , Salts/chemistry , Hydrophobic and Hydrophilic Interactions , Ions , Polyvinyls/chemistry
8.
Sci Rep ; 14(1): 15178, 2024 07 10.
Article in English | MEDLINE | ID: mdl-38987553

ABSTRACT

The evolution of endovascular therapies, particularly in the field of intracranial aneurysm treatment, has been truly remarkable and is characterized by the development of various stents. However, ischemic complications related to thrombosis or downstream emboli pose a challenge for the broader clinical application of such stents. Despite advancements in surface modification technologies, an ideal coating that fulfills all the desired requirements, including anti-thrombogenicity and swift endothelialization, has not been available. To address these issues, we investigated a new coating comprising 3-aminopropyltriethoxysilane (APTES) with both anti-thrombogenic and cell-adhesion properties. We assessed the anti-thrombogenic property of the coating using an in vitro blood loop model by evaluating the platelet count and the level of the thrombin-antithrombin (TAT) complex, and investigating thrombus formation on the surface using scanning electron microscopy (SEM). We then assessed endothelial cell adhesion on the metal surfaces. In vitro blood tests revealed that, compared to a bare stent, the coating significantly inhibited platelet reduction and thrombus formation; more human serum albumin spontaneously adhered to the coated surface to block thrombogenic activation in the blood. Cell adhesion tests also indicated a significant increase in the number of cells adhering to the APTES-coated surfaces compared to the numbers adhering to either the bare stent or the stent coated with an anti-fouling phospholipid polymer. Finally, we performed an in vivo safety test by implanting coated stents into the internal thoracic arteries and ascending pharyngeal arteries of minipigs, and subsequently assessing the health status and vessel patency of the arteries by angiography over the course of 1 week. We found that there were no adverse effects on the pigs and the vascular lumens of their vessels were well maintained in the group with APTES-coated stents. Therefore, our new coating exhibited both high anti-thrombogenicity and cell-adhesion properties, which fulfill the requirements of an implantable stent.


Subject(s)
Cell Adhesion , Coated Materials, Biocompatible , Propylamines , Silanes , Stents , Thrombosis , Silanes/chemistry , Silanes/pharmacology , Animals , Cell Adhesion/drug effects , Humans , Stents/adverse effects , Swine , Coated Materials, Biocompatible/chemistry , Coated Materials, Biocompatible/pharmacology , Propylamines/pharmacology , Propylamines/chemistry , Adsorption , Thrombosis/prevention & control , Fibrinolytic Agents/pharmacology , Fibrinolytic Agents/chemistry , Blood Platelets/drug effects , Blood Platelets/metabolism , Human Umbilical Vein Endothelial Cells/drug effects , Endothelial Cells/drug effects , Endothelial Cells/metabolism
9.
Int J Pharm ; 662: 124487, 2024 Sep 05.
Article in English | MEDLINE | ID: mdl-39029634

ABSTRACT

In the current study, a tumor microenvironment responsive (TME-responsive) copper peroxide-mesoporous silica core-shell structure with H2O2 self-supplying ability was fabricated for targeted ferroptosis/chemotherapy against metastatic breast cancer. At the first stage, copper peroxide nanodot was synthesized and subsequently coated with mesoporous organosilica shell. After (3-Aminopropyl) triethoxysilane (APTMS) functionalization of the organosilica shell, doxorubicin (DOX) was loaded in the mesoporous structure of the nanoparticles and then, heterofunctional COOH-PEG-Maleimide was decorated on the surface through EDC/NHS chemistry. Afterward, thiol-functionalized AS1411 aptamer was conjugated to the maleimide groups of the PEGylated nanoparticles. In vitro study illustrated ROS generation of the system in the treated 4 T1 cell. Cellular uptake and cytotoxicity experiments showed enhanced internalization and cytotoxicity of the targeted system comparing to non-targeted one. The in vivo study on ectopic 4 T1 tumor induced in Female BALB/c mice showed ideal therapeutic effect of Apt-PEG-Silica-DOT@DOX with approximately 90 % tumor suppression in comparison with 50 % and 25 % tumor suppression for PEG-Silica-DOT@DOX and PEG-Silica-DOT. Moreover, Apt-PEG-Silica-DOT@DOX provide favorable characteristics for biosafety issues concerning the rate of survival and loss of body weight. The prepared platform could serve as a multifunctional system with smart behavior in drug release, tumor accumulation and capable for ferroptosis/chemotherapy against breast cancer.


Subject(s)
Breast Neoplasms , Doxorubicin , Ferroptosis , Mice, Inbred BALB C , Nanoparticles , Silicon Dioxide , Animals , Female , Doxorubicin/administration & dosage , Doxorubicin/pharmacology , Ferroptosis/drug effects , Silicon Dioxide/chemistry , Silicon Dioxide/administration & dosage , Breast Neoplasms/drug therapy , Breast Neoplasms/pathology , Nanoparticles/administration & dosage , Nanoparticles/chemistry , Cell Line, Tumor , Mice , Polyethylene Glycols/chemistry , Polyethylene Glycols/administration & dosage , Antibiotics, Antineoplastic/administration & dosage , Antibiotics, Antineoplastic/pharmacokinetics , Humans , Porosity , Peroxides/chemistry , Peroxides/administration & dosage , Silanes/chemistry , Silanes/administration & dosage , Drug Carriers/chemistry , Tumor Microenvironment/drug effects , Copper/chemistry , Copper/administration & dosage , Propylamines/chemistry , Propylamines/administration & dosage
10.
Int J Biol Macromol ; 275(Pt 2): 133130, 2024 Aug.
Article in English | MEDLINE | ID: mdl-38945703

ABSTRACT

The aging of paper seriously threatens the service life of cultural heritage documents. Bacterial cellulose (BC), which has a good fiber aspect ratio and is rich in hydroxyl groups, is suitable for strengthening aged paper. However, a single BC added was not ideal for paper restoration, since only strengthening was not able to resist the persistent acidification of ancient book. In this work, BC was functionalized by 3-aminopropyltriethoxysilane (APTES) to develop the interface bonding with aged paper. Fourier transform infrared (FTIR), X-ray diffraction (XRD), nuclear magnetic resonance (NMR) and elemental analysis identified the successful amino-silanization of BC. The modification parameters were optimized as the concentration of APTES of 5 wt%, the reaction time of 4 h, and the reaction temperature of 80 °C based on a considerable improvement in the strength properties without obvious appearance impact on reinforced papers. Moreover, the pH value of the repaired paper was achieved at 8.03, ensuring the stability of the anti-aging effect. The results confirmed that APTES-BC had great potential applications in ancient books conservation.


Subject(s)
Cellulose , Paper , Silanes , Cellulose/chemistry , Silanes/chemistry , Propylamines/chemistry , Hydrogen-Ion Concentration , X-Ray Diffraction , Temperature , Spectroscopy, Fourier Transform Infrared
11.
Int J Biol Macromol ; 274(Pt 1): 133414, 2024 Aug.
Article in English | MEDLINE | ID: mdl-38925183

ABSTRACT

A facial strategy of co-deposition is proposed to enhance the interfacial bonding in wood fiber (WF)/polylactic acid (PLA) composites. Dopamine or tannic acid (TA) was co-deposited with 3-aminopropyltriethoxysilane (APTES) onto the WF surface to create active coatings. These coatings were formed through Michael addition and Schiff base reactions and effectively attached to the WF through a combination of hydrogen and covalent bonding. Such active coatings facilitated the connection between WF and PLA through both covalent bonds and physical entanglements, thereby enhancing the interfacial interactions and compatibility between the two components. The co-deposition of TA with APTES was found to be more effective than with dopamine, leading to a dramatic improvement in the tensile strength and elongation at break of the composites by 33.4 % and 185.9 %, respectively. This work offers a facile method to prepare high performance plant fiber reinforced PLA composites, thereby broadening the potential applications of PLA.


Subject(s)
Polyesters , Tensile Strength , Wood , Polyesters/chemistry , Wood/chemistry , Silanes/chemistry , Tannins/chemistry , Materials Testing , Propylamines/chemistry
12.
J Nanobiotechnology ; 22(1): 347, 2024 Jun 19.
Article in English | MEDLINE | ID: mdl-38898529

ABSTRACT

BACKGROUND: Silica nanoparticles (SNPs) have immense potential in biomedical research, particularly in drug delivery and imaging applications, owing to their stability and minimal interactions with biological entities such as tissues or cells. RESULTS: With synthesized and characterized cyanine-dye-doped fluorescent SNPs (CSNPs) using cyanine 3.5, 5.5, and 7 (Cy3.5, Cy5.5, and Cy7). Through systematic analysis, we discerned variations in the surface charge and fluorescence properties of the nanoparticles contingent on the encapsulated dye-(3-aminopropyl)triethoxysilane conjugate, while their size and shape remained constant. The fluorescence emission spectra exhibited a redshift correlated with increasing dye concentration, which was attributed to cascade energy transfer and self-quenching effects. Additionally, the fluorescence signal intensity showed a linear relationship with the particle concentration, particularly at lower dye equivalents, indicating a robust performance suitable for imaging applications. In vitro assessments revealed negligible cytotoxicity and efficient cellular uptake of the nanoparticles, enabling long-term tracking and imaging. Validation through in vivo imaging in mice underscored the versatility and efficacy of CSNPs, showing single-switching imaging capabilities and linear signal enhancement within subcutaneous tissue environment. CONCLUSIONS: This study provides valuable insights for designing fluorescence imaging and optimizing nanoparticle-based applications in biomedical research, with potential implications for targeted drug delivery and in vivo imaging of tissue structures and organs.


Subject(s)
Carbocyanines , Fluorescent Dyes , Nanoparticles , Optical Imaging , Silicon Dioxide , Silicon Dioxide/chemistry , Nanoparticles/chemistry , Carbocyanines/chemistry , Animals , Mice , Optical Imaging/methods , Fluorescent Dyes/chemistry , Humans , Silanes/chemistry , Particle Size , Propylamines , Benzothiazoles
13.
Molecules ; 29(11)2024 May 24.
Article in English | MEDLINE | ID: mdl-38893361

ABSTRACT

A versatile family of quaternary propargylamines was synthesized employing the KA2 multicomponent reaction, through the single-step coupling of a number of amines, ketones, and terminal alkynes. Sustainable synthetic procedures using transition metal catalysts were employed in all cases. The inhibitory activity of these molecules was evaluated against human monoaminoxidase (hMAO)-A and hMAO-B enzymes and was found to be significant. The IC50 values for hMAO-B range from 152.1 to 164.7 nM while the IC50 values for hMAO-A range from 765.6 to 861.6 nM. Furthermore, these compounds comply with Lipinski's rule of five and exhibit no predicted toxicity. To understand their binding properties with the two target enzymes, key interactions were studied using molecular docking, all-atom molecular dynamics (MD) simulations, and MM/GBSA binding free energy calculations. Overall, herein, the reported family of propargylamines exhibits promise as potential treatments for neurodegenerative disorders, such as Parkinson's disease. Interestingly, this is the first time a propargylamine scaffold bearing an internal alkyne has been reported to show activity against monoaminoxidases.


Subject(s)
Alkynes , Molecular Docking Simulation , Molecular Dynamics Simulation , Monoamine Oxidase Inhibitors , Monoamine Oxidase , Pargyline , Alkynes/chemistry , Alkynes/pharmacology , Monoamine Oxidase/metabolism , Monoamine Oxidase/chemistry , Monoamine Oxidase Inhibitors/chemistry , Monoamine Oxidase Inhibitors/pharmacology , Monoamine Oxidase Inhibitors/chemical synthesis , Humans , Pargyline/chemistry , Pargyline/analogs & derivatives , Pargyline/pharmacology , Propylamines/chemistry , Structure-Activity Relationship , Molecular Structure
14.
Spectrochim Acta A Mol Biomol Spectrosc ; 319: 124542, 2024 Oct 15.
Article in English | MEDLINE | ID: mdl-38823241

ABSTRACT

Enzyme-induced in-situ fluorescence is crucial for the development of biosensing mechanisms and correlative spectroscopic analysis. Inspired by simple p-aminophenol (AP)-controlled synthesis and the specific catalytic reaction of 4-aminophenyl phosphate (APP) triggered by alkaline phosphatase (ALP), our research proposed a strategy to prepare carbon dots (CDs) as fluorescent signals for ALP detection using AP and 3-aminopropyltrimethoxysilane (APTMS) as the precursors. The further constructed ratiometric fluorescence sensor reduced the detection limit of ALP to 0.075 µU/mL by a significant margin. Considering the need for point-of-care testing (POCT), we chose agarose for the preparation of portable hydrogel sensors so that even untrained personnel can quickly achieve semi-quantitative visual detection of ALP using colorimetric cards. These results demonstrate the practical applicability of ratiometric fluorescence sensing hydrogel pillar arrays, which are important for high-sensitivity, visualization, and portable rapid enzyme activity assays.


Subject(s)
Alkaline Phosphatase , Biosensing Techniques , Hydrogels , Spectrometry, Fluorescence , Alkaline Phosphatase/metabolism , Alkaline Phosphatase/analysis , Biosensing Techniques/methods , Spectrometry, Fluorescence/methods , Hydrogels/chemistry , Limit of Detection , Silanes/chemistry , Quantum Dots/chemistry , Carbon/chemistry , Propylamines/chemistry , Colorimetry/methods , Humans
15.
Sci Rep ; 14(1): 12035, 2024 05 27.
Article in English | MEDLINE | ID: mdl-38802518

ABSTRACT

Colonoscopy is the standard procedure for screening, and surveillance of colorectal cancer, including the treatment for colonic lesions. Colonic spasm is an important problem from colonoscopy that affects both surgeons and patients. The spasm also might be the cause of longer cecal intubation time, difficulty of the procedure, and increased pain. Previous reports indicated that antispasmodic agents can decrease such symptoms. Therefore, we conducted this study to investigate the cecal intubation time of antispasmodic agents. A single blinded randomized controlled trial was conducted from 01/11/2020 to 31/08/2021. One hundred four patients were allocated to antispasmodic agent group and control group, in 1:1 ratio. The efficacy of median (range) cecal intubation time showed similar results of 5 (2, 14) and 5 (2, 15) minutes with no statistically significant difference. The mean scores of all domains i.e., pain, spasm, cleanliness, and difficulty were better in the antispasmodic agent group about 2.6 (1.4), 1.8 (0.8), 2.4 (0.9), and 2.0 (0.9), respectively, than control group but there were spasm and cleanliness showed statistically significant difference. Moreover, the satisfaction scores showed better efficacy in decreased spasm, decreased difficulty, and increased cleanliness than control group. Prescribing of antispasmodic drugs before colonoscopy might be the choice of treatment for the patients. The antispasmodic drugs will be beneficial to both of the patient and the doctor.


Subject(s)
Colonoscopy , Parasympatholytics , Simethicone , Humans , Colonoscopy/methods , Male , Female , Middle Aged , Simethicone/administration & dosage , Parasympatholytics/therapeutic use , Aged , Adult , Single-Blind Method , Propylamines
16.
Colloids Surf B Biointerfaces ; 239: 113975, 2024 Jul.
Article in English | MEDLINE | ID: mdl-38762934

ABSTRACT

Early and accurate cancer diagnosis is crucial for improving patient survival rates. Luminescent nanoparticles have emerged as a promising tool in fluorescence bioimaging for cancer diagnosis. To enhance diagnostic accuracy, ligands promoting endocytosis into cancer cells are commonly incorporated onto nanoparticle surfaces. Folic acid (FA) is one such ligand, known to specifically bind to folate receptors (FR) overexpressed in various cancer cells such as cervical and ovarian carcinoma. Therefore, surface modification of luminescent nanoparticles with FA can enhance both luminescence efficiency and diagnostic accuracy. In this study, luminescent europium-doped hydroxyapatite (EuHAp) nanocrystals were prepared via hydrothermal method and subsequently modified with (3-Aminopropyl)triethoxysilane (APTES) followed by FA to target FR-positive human cervical adenocarcinoma cell line (HeLa) cells. The sequential grafting of APTES and then FA formed a robust covalent linkage between the nanocrystals and FA. Rod-shaped FA-modified EuHAp nanocrystals, approximately 100 nm in size, exhibited emission peaks at 589, 615, and 650 nm upon excitation at 397 nm. Despite a reduction in photoluminescence intensity following FA modification, fluorescence microscopy revealed a remarkable 120-fold increase in intensity compared to unmodified EuHAp, attributed to the enhanced uptake of FA-modified EuHAp. Additionally, confocal microscope observations confirmed the specificity and the internalization of FA-modified EuHAp nanocrystals in HeLa cells. In conclusion, the modification of EuHAp nanocrystals with FA presents a promising strategy to enhance the diagnostic potential of cancer bioimaging probes.


Subject(s)
Durapatite , Europium , Folic Acid , Nanoparticles , Humans , Folic Acid/chemistry , Europium/chemistry , Nanoparticles/chemistry , HeLa Cells , Durapatite/chemistry , Luminescence , Microscopy, Fluorescence , Propylamines/chemistry , Particle Size , Luminescent Agents/chemistry
17.
Analyst ; 149(12): 3317-3324, 2024 Jun 10.
Article in English | MEDLINE | ID: mdl-38742381

ABSTRACT

In this work, the release of giant liposome (∼100 µm in diameter) content was imaged by shadow electrochemiluminescence (ECL) microscopy. Giant unilamellar liposomes were pre-loaded with a sucrose solution and allowed to sediment at an ITO electrode surface immersed in a solution containing a luminophore ([Ru(bpy)3]2+) and a sacrificial co-reactant (tri-n-propylamine). Upon polarization, the electrode exhibited illumination over its entire surface thanks to the oxidation of ECL reagents. However, as soon as liposomes reached the electrode surface, dark spots appeared and then spread over time on the surface. This observation reflected a blockage of the electrode surface at the contact point between the liposome and the electrode surface, followed by the dilution of ECL reagents after the rupture of the liposome membrane and release of its internal ECL-inactive solution. Interestingly, ECL reappeared in areas where it initially faded, indicating back-diffusion of ECL reagents towards the previously diluted area and thus confirming liposome permeabilization. The whole process was analyzed qualitatively and quantitatively within the defined region of interest. Two mass transport regimes were identified: a gravity-driven spreading process when the liposome releases its content leading to ECL vanishing and a diffusive regime when ECL recovers. The reported shadow ECL microscopy should find promising applications for the imaging of transient events such as molecular species released by artificial or biological vesicles.


Subject(s)
Electrodes , Luminescent Measurements , Luminescent Measurements/methods , Liposomes/chemistry , Electrochemical Techniques/methods , Electrochemical Techniques/instrumentation , Propylamines/chemistry , Unilamellar Liposomes/chemistry , Sucrose/chemistry , Tin Compounds
18.
Analyst ; 149(13): 3615-3624, 2024 Jun 24.
Article in English | MEDLINE | ID: mdl-38775016

ABSTRACT

Mycophenolate mofetil (MpM) is a medication used to prevent the rejection of transplanted organs, particularly in kidney, heart, and liver transplant surgeries. It is extremely important to be conscious that MpM can raise the risk of severe infections and some cancers if it exceeds the recommended dose while lower doses will result in organ rejections. So, it is essential to monitor the dosage of MpM in real time in the micromolar range. In this work, we have synthesized 3-aminopropyltriethoxysilane (APTES) functionalized nickel cobaltite (NiCo2O4) and this amino functionalization was chosen to enhance the stability and electrochemical activity of NiCo2O4. The enhanced activity of NiCo2O4 was used for developing an electrochemical sensor for the detection of MpM. APTES functionalized NiCo2O4 was coated on carbon cloth and used as the working electrode. Surface functionalization with APTES on NiCo2O4 was aimed at augmenting the adsorption/interaction of MpM due to its binding properties. The developed sensor showed a very low detection limit of 1.23 nM with linear ranges of 10-100 nM and 1-100 µM and its practical applicability was examined using artificial samples of blood serum and cerebrospinal fluid, validating its potential application in real-life scenarios.


Subject(s)
Carbon , Immunosuppressive Agents , Limit of Detection , Mycophenolic Acid , Nanostructures , Nickel , Sea Urchins , Wearable Electronic Devices , Animals , Nickel/chemistry , Mycophenolic Acid/blood , Mycophenolic Acid/chemistry , Mycophenolic Acid/analysis , Immunosuppressive Agents/blood , Immunosuppressive Agents/analysis , Immunosuppressive Agents/chemistry , Carbon/chemistry , Sea Urchins/chemistry , Nanostructures/chemistry , Electrochemical Techniques/methods , Electrochemical Techniques/instrumentation , Propylamines/chemistry , Humans , Cobalt/chemistry , Electrodes , Silanes
19.
Int J Biol Macromol ; 269(Pt 1): 132021, 2024 Jun.
Article in English | MEDLINE | ID: mdl-38697441

ABSTRACT

Challenges in enzyme and product recovery are currently intriguing in modern biotechnology. Coping enzyme stability, shelf life and efficiency, nanomaterials-based immobilization were epitomized of industrial practice. Herein, a α-amylase from Geobacillus thermoleovorans was purified and bound effectively on to a modified 3-Aminopropyltriethoxysilane (APTES)-Fe3O4 nanoparticle. It was revealed that the carrier-bound enzyme catalysis (pH 8 and 60 °C) was significant in contrast to the free enzyme (pH 7.5 and 55 °C). Furthermore, Zn2+ and Cu2+ were shown to cause inhibitory effects in both enzyme states. Unlike chloroform, toluene, benzene, and butanol, minimal effects were observed with ethanol, acetone, and hexane. The bound enzyme retained 27.4 % of its initial activity after being stored for 36 days. In addition, the reusability of the bound enzyme showed a gradual decline in activity after the first cycle; however, after 13 cycles, its residual activity at 53 % was observed. These data proved significant enough to use this enzyme for industrial starch and analogous substrate bio-processing.


Subject(s)
Enzyme Stability , Enzymes, Immobilized , Propylamines , alpha-Amylases , Enzymes, Immobilized/chemistry , Enzymes, Immobilized/metabolism , alpha-Amylases/chemistry , alpha-Amylases/metabolism , Propylamines/chemistry , Silanes/chemistry , Geobacillus/enzymology , Temperature , Hydrogen-Ion Concentration , Biocatalysis , Catalysis , Magnetite Nanoparticles/chemistry , Starch/chemistry
20.
J Gastrointest Surg ; 28(4): 451-457, 2024 Apr.
Article in English | MEDLINE | ID: mdl-38583895

ABSTRACT

PURPOSE: Postoperative serum hyperamylasemia (POH) is a part of the new, increasingly highlighted, definition for postpancreatectomy pancreatitis (PPAP). This study aimed to analyze whether the biochemical changes of PPAP are differently associated with postoperative complications after distal pancreatectomy (DP) compared with pancreatoduodenectomy (PD). The textbook outcome (TO) was used as a summary measure to capture real-world data. METHODS: The data were retrospectively extracted from a prospective clinical database. Patients with POH, defined as levels above our institution's upper limit of normal on postoperative day 1, after DP and the corresponding propensity score-matched cohort after PD were evaluated on postoperative complications by using logistic regression analyses. RESULTS: We analyzed 723 patients who underwent PD and DP over a period of 9 years. After propensity score matching, 384 patients (192 patients in each group) remained. POH was observed in 78 (41.1%) and 74 (39.4%) after PD and DP correspondingly. There was a significant increase of postoperative complications in the PD group: Clavien-Dindo classification system ≥3 (P < .01 vs P = .71), clinically relevant postoperative pancreatic fistula (P < .001 vs P = .2), postpancreatectomy hemorrhage (P < .001 vs P = .11), and length of hospital stay (P < .001 vs P = .69) if POH occurred compared with in the DP group. TO was significantly unlikely in cases with POH after PD compared with DP (P > .001 vs P = .41). Furthermore, POH was found to be an independent predictor for missing TO after PD (odds ratio [OR], 0.29; 95% CI, 0.14-0.60; P < .001), whereas this was not observed in patients after DP (OR, 0.53; 95% CI, 0.21-1.33; P = .18). CONCLUSION: As a part of the definition for PPAP, POH is a predictive indicator associated with postoperative complications after PD but not after DP.


Subject(s)
Hyperamylasemia , Pancreatitis , Propylamines , Humans , Pancreatectomy/adverse effects , Pancreaticoduodenectomy/adverse effects , Hyperamylasemia/complications , Propensity Score , Retrospective Studies , Prospective Studies , Pancreatic Fistula/epidemiology , Pancreatic Fistula/etiology , Postoperative Complications/epidemiology , Postoperative Complications/etiology , Pancreatitis/complications
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