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1.
RSC Adv ; 14(22): 15408-15412, 2024 May 10.
Article in English | MEDLINE | ID: mdl-38741971

ABSTRACT

Iron-based electrochemical catalysts used to modify electrodes for biosensing have received more attention from biosensor manufacturers because of their excellent biocompatibility and low cost. In this work, a fast-ion conductor potassium ferrite (K2Fe4O7) modified glassy carbon electrode (GCE) was prepared for detecting epinephrine (EP) by electrochemical techniques. The obtained K2Fe4O7/GCE electrode exhibited not only a wide linear range over EP concentration from 2 µM to 260 µM with a detection limit of 0.27 µM (S/N = 3) but also high selectivity toward EP in the presence of common interferents ascorbic acid (AA) and uric acid (UA), as well as good reproducibility and stability.

2.
Eur J Pharmacol ; 970: 176493, 2024 May 05.
Article in English | MEDLINE | ID: mdl-38484925

ABSTRACT

Excessive activation of FGF19/fibroblast growth factor receptor 4 (FGFR4) signaling is associated with poor survival of patients with hepatocellular carcinoma (HCC). FGFR4 inhibitors show promise for HCC treatment. F30, an indazole derivative designed through computer-aided drug design targeting FGFR4, demonstrated anti-HCC activity as described in our previous studies. However, the precise molecular mechanisms underlying F30's anticancer effects remain largely unexplored. We report here that F30 could effectively induce ferroptosis in HCC cells. The concentrations of cellular ferrous iron, the peroxidation of cell membranes and the homeostasis of reduced glutathione (GSH)/oxidized glutathione disulfide (GSSG) were dysregulated by F30, thereby affecting cellular redox status. Induction of ferroptosis in HCC by F30 was inhibited by specific ferroptosis inhibitor ferrostatin-1. F30 upregulates various ferroptosis-related genes, including the heme oxygenase enzymes 1 (HMOX1), a key mediator of redox regulation. Surprisingly, F30-induced ferroptosis in HCC is dependent on HMOX1. The dysregulation of cellular ferrous iron concentrations and cell membrane peroxidation was rescued when knocking down HMOX1 with specific small interfering RNA. These findings shed light on the molecular mechanisms underlying FGFR4-targeting F30's anti-HCC effects and suggest that FGFR4 inactivation could be beneficial for HCC treatment involving ferroptosis.


Subject(s)
Carcinoma, Hepatocellular , Ferroptosis , Liver Neoplasms , Humans , Carcinoma, Hepatocellular/genetics , Liver Neoplasms/genetics , Receptor, Fibroblast Growth Factor, Type 4/genetics , Receptor, Fibroblast Growth Factor, Type 4/metabolism , Cell Line, Tumor , Cell Proliferation , Iron , Heme Oxygenase-1
3.
Colloids Surf B Biointerfaces ; 236: 113818, 2024 Apr.
Article in English | MEDLINE | ID: mdl-38417347

ABSTRACT

The feasibility of immobilized protein-based biodetection relies critically on the activity of the immobilized proteins as well as the biocompatibility of the protein surface. Although many protein immobilization strategies have been developed with satisfied detection readout signals. Non-specific interactions caused by the protein-coating surface are still of great concern since they often interfere with or affect the reliability of detection. Herein, we developed a highly efficient G protein-coupled receptor (GPCR) immobilization method by the combination of polyethylene glycol (PEG) with a self-labeling enzyme-catalyzed reaction. The immobilization relies on the covalent interaction between the fusion tag of a target GPCR (kinase domain of epidermal growth factor receptor, EGFR) and its covalent inhibitor ibrutinib, which is modified on PEGylated silica gels. Two types of GPCRs, N-methyl-D-aspartate 2 A receptor (NMDAR2A) and endothelin A receptor (ETAR), were used as examples to realize protein immobilization. The GPCR modified gels and the affinity columns packed with them have been extensively characterized, in terms of non-specific adsorptions, retention factor (k'), half peak width (W1/2), tailing factor (Tf), theoretical plates (N), and association and dissociation constants of the ligands with the receptors. The immobilized GPCRs with reduced non-specific interactions and enhanced fouling resistance, salt tolerance, and chromatographic performance were clearly observed. We believe it is the first work to introduce PEGylation in GPCR immobilization and provide comprehensive proof-of-concept studies to illustrate the improved antifouling property, salt tolerance, and chromatographic performance. This method could be generally applicable in other immobilized protein-based technology for reliable biodetection.


Subject(s)
Receptors, G-Protein-Coupled , Salt Tolerance , Reproducibility of Results , Receptors, G-Protein-Coupled/metabolism , Immobilized Proteins/chemistry , Gels
4.
BMC Med ; 22(1): 86, 2024 Feb 27.
Article in English | MEDLINE | ID: mdl-38413945

ABSTRACT

BACKGROUND: Myocardial bridging (MB) is common in patients with hypertrophic cardiomyopathy (HCM). There are sparse data on the impact of MB on myocardial fibrosis in HCM. This study was designed to evaluate the relationship between MB and myocardial fibrosis in patients with obstructive HCM. METHODS: In this cohort study, retrospective data were collected from a high-volume HCM center. Patients with obstructive HCM who underwent septal myectomy and preoperative cardiac magnetic resonance (CMR) were screened from 2011 to 2018. RESULTS: Finally, 492 patients were included in this study, with an average age of 45.7 years. Of these patients, 76 patients had MB. MB occurred mostly in the left anterior descending artery (73/76). The global extent of late gadolinium enhancement (LGE) was correlated with the degree of systolic compression (r = 0.33, p = 0.003). Multivariable linear regression analysis revealed that the degree of systolic compression was an independent risk factor for LGE (ß = 0.292, p = 0.007). The LGE fraction of basal and mid anteroseptal segments in patients with severe MB (compression ratio ≥ 80%) was significantly greater than that in patients with mild to moderate MB (compression ratio < 80%). During a median follow-up of 28 (IQR: 15-52) months, 15 patients died. Kaplan-Meier analysis did not identify differences in all-cause death (log-rank p = 0.63) or cardiovascular death (log-rank p = 0.72) between patients undergoing MB-related surgery and those without MB. CONCLUSIONS: MB with severe systolic compression was significantly associated with a high extent of fibrosis in patients with obstructive HCM. Concomitant myotomy or coronary artery bypass grafting might provide excellent survival similar to that of patients without MB. Identification of patients with severe MB and providing comprehensive management might help improve the prognosis of patients with HCM.


Subject(s)
Cardiomyopathy, Hypertrophic , Myocardial Bridging , Humans , Middle Aged , Myocardium/pathology , Contrast Media , Retrospective Studies , Cohort Studies , Myocardial Bridging/complications , Myocardial Bridging/diagnostic imaging , Myocardial Bridging/pathology , Gadolinium , Cardiomyopathy, Hypertrophic/complications , Cardiomyopathy, Hypertrophic/diagnostic imaging , Cardiomyopathy, Hypertrophic/surgery , Fibrosis , Risk Factors
5.
Ther Drug Monit ; 46(1): 42-48, 2024 02 01.
Article in English | MEDLINE | ID: mdl-37315150

ABSTRACT

BACKGROUND AND OBJECTIVE: Liver cancer is the second highest cause of cancer-related deaths worldwide. It is commonly treated with liver transplantation, where tacrolimus is typically used as an antirejection immunosuppressant. The purpose of this study was to evaluate the effect of tacrolimus time in therapeutic range (TTR) on liver cancer recurrence in liver transplant recipients and to compare the performance of TTRs calculated according to the target ranges recommended in published guidelines. METHODS: A total of 84 patients who underwent liver transplantation for liver cancer were retrospectively included. Tacrolimus TTR was calculated using linear interpolation from the date of transplantation until recurrence or the last follow-up according to target ranges recommended in the Chinese guideline and international expert consensus. RESULT: Twenty-four recipients developed liver cancer recurrence after liver transplantation. The CTTR (TTR calculated according to the Chinese guideline) for the recurrence group was significantly lower than that of the nonrecurrence group (26.39% vs. 50.27%, P < 0.001), whereas the ITTR (TTR calculated according to the international consensus) was not significantly different between the two groups (47.81% vs. 56.37%, P = 0.165). Multivariate survival analysis revealed that age, microvascular invasion, hepatocellular carcinoma, CTTR, and mean tacrolimus trough concentration were independent predictors of liver cancer recurrence after liver transplantation. CONCLUSIONS: TTR predicts liver cancer recurrence in liver transplant recipients. The range of tacrolimus concentrations recommended in the Chinese guideline was more beneficial than that recommended in the international consensus for Chinese patients undergoing liver transplantation for liver cancer.


Subject(s)
Liver Neoplasms , Liver Transplantation , Humans , Tacrolimus/therapeutic use , Retrospective Studies , Immunosuppressive Agents/therapeutic use , Liver Neoplasms/surgery , Liver Neoplasms/drug therapy
6.
Adv Mater ; 36(2): e2306724, 2024 Jan.
Article in English | MEDLINE | ID: mdl-37863645

ABSTRACT

The abundant oxygen-related defects (e.g., O vacancies, O-H) in the TiO2 electron transport layer results in high surface energy, which is detrimental to effective carrier extraction and seriously impairs the photovoltaic performance and stability of perovskite solar cells. Here, novel surface energy engineering (SEE) is developed by applying a surfactant of heptadecafluorooctanesulfonate tetraethylammonium (HFSTA) on the surface of the TiO2 . Theoretical calculations show that the HFSTA-TiO2 is less prone to form O vacancies, leading to lower surface energy, thus improving the carrier-extraction efficiency. The experimental results show that superior perovskite film is obtained due to the reduced heterogeneous nucleation sites and improved crystallization process on the modified TiO2 . Furthermore, the flexible long alkyl chains in HFSTA considerably relieve the compressive stresses at the buried interface. By combining the passivation of TiO2 , crystallization process modulation, and stress relief, a champion PCE up to 25.03% is achieved. The device without encapsulation sustains 92.2% of its initial PCE after more than 2500 h storage under air ambient with relative humidity of 25-30%. The SEE of a buried interface paves a new way toward high-efficiency, stable perovskite solar cells.

7.
Bioprocess Biosyst Eng ; 47(2): 159-168, 2024 Feb.
Article in English | MEDLINE | ID: mdl-37922017

ABSTRACT

Multiheme cytochrome c (Cyt c) can function as a redox protein on electrode to accomplish bioelectrocatalysis. However, the direct electron transfer (DET) between the redox site of Cyt c and electrode is low due to the large coupling distance. A close proximity or a connection pathway from the deeply buried active site to the protein surface can be established by modifying the electrode with carbon nanotubes (CNTs) to improve the DET. Therefore, the isolated Cyt c has been assembled or casted with CNTs by various processes to form Cyt c-CNTs bioelectrodes that can be further applied to biosensing and bioanalysis. These strategies can be transplanted to the fabrication of biofilm-CNTs based electrodes by complexing the out membrane (OM) Cyt c of natural electricigen with CNTs to realize the application of the electrochemical properties of "in vivo" Cyt c to bioelectrochemical systems (BESs). This review intends to highlight the preparation strategies of bioelectrodes that have been well studied in electrochemical biosensors and improving approaches of the DET from the CNTs surface to Cyt c in their hybrids. The efficient fabrication processes of the biofilm-CNTs based electrodes that can be considered as "in vivo" Cyt c-CNTs based electrodes for BES designs are also summarized, aiming to provide an inspiration source and a reference to the related studies of BES downstream.


Subject(s)
Alkanesulfonic Acids , Biosensing Techniques , Nanotubes, Carbon , Cytochromes c/metabolism , Nanotubes, Carbon/chemistry , Oxidation-Reduction , Electrodes
8.
J Chromatogr A ; 1715: 464606, 2024 Jan 25.
Article in English | MEDLINE | ID: mdl-38154257

ABSTRACT

Characterization of the drug-target interactions is pivotal throughout the whole procedure of drug development. Most of the current assays, particularly, chromatographic methods lack the capacity to reveal drug adsorption on the muti-target surface. To this end, we derived a reliable and workable mathematical equation for revealing drug bindings to dual targets on the heterogeneous surface starting from the mass balance equation. The derivatization relied on the correlation of drug injection amounts with their retention factors. Experimental validation was performed by determining the binding parameters of three canonical drugs on a heterogeneous surface, which was fabricated by fusing angiotensin receptor type I and type II receptors (AT1R and AT2R) at the terminuses of circularly permuted HaloTag (cpHaloTag) and immobilizing the whole fusion protein onto 6-bromohexanoic acid modified silica gel. We proved that immobilized AT1R-cpHalo-AT2R maintained the original ligand- and antibody-binding activities of the two receptors in three weeks. The association constants of valsartan, candesartan, and telmisartan to AT1R were (6.26±0.14) × 105, (9.66±0.71) × 105, and (3.17±0.03) × 105 L/mol. In the same column, their association constants to AT2R were (1.25±0.04) × 104, (2.30±0.08) × 104, and (8.51±0.06) × 103 L/mol. The patterns of the association constants to AT1R/AT2R (candesartan>valsartan>telmisartan) were in good line with the data by performing nonlinear chromatography on control columns containing immobilized AT1R or AT2R alone. This provided proof of the fact that the derivatization allowed the determination of drug bindings on the heterogeneous surface with the utilization of a single series of injections and linear regression. We reasoned that is simple enough to model the bindings of drug adsorption on commercially available adsorbents in fundamental or industrial fields, thus having the potential to become a universal method for analyzing the bindings of a drug to the heterogeneous surface containing multiple targets.


Subject(s)
Benzimidazoles , Biphenyl Compounds , Receptor, Angiotensin, Type 1 , Receptor, Angiotensin, Type 2 , Tetrazoles , Telmisartan , Receptor, Angiotensin, Type 2/metabolism , Receptor, Angiotensin, Type 1/chemistry , Valsartan , Chromatography
9.
ACS Appl Mater Interfaces ; 15(43): 50148-50154, 2023 Nov 01.
Article in English | MEDLINE | ID: mdl-37856670

ABSTRACT

Various additives have been introduced to assist in film preparation and defect passivation. Herein, fluoroiodobenzene (FIB) molecules with different numbers of F atoms were incorporated into perovskite films to optimize the film quality as well as passivate defects. Based on the calculation and experimental results, it was found that the FIB additives were inclined to exist at the bottom of the film because of the strong affinity between F atoms stemming from FIB molecules and O atoms stemming from TiO2, especially for molecules with more F atoms. By optimization of the FIB molecule, the perovskite film crystallinity was significantly improved, the carrier lifetimes were prolonged, and the charge extraction ability was also enhanced. The device with FIB with one F atom achieved a photoelectrical conversion efficiency as high as 22.89% with a Voc of 1.118 V, fill factor (FF) of 80.44%, and Jsc of 25.45 mA cm-2, which was much higher than that of the control device with an efficiency of 20.87%. Furthermore, FIB molecules with three and five F atoms also achieved higher efficiency than that of the control device. The devices with FIB molecules showed better stability than the devices without additives. The unencapsulated devices with FIB additives held 90% of their original efficiencies in an ambient environment with a temperature of 15-25 °C and a relative humidity of 20-30%, while the control device dropped to 76% after more than 1000 h.

10.
Am J Cardiol ; 206: 185-190, 2023 11 01.
Article in English | MEDLINE | ID: mdl-37708749

ABSTRACT

Obstructive hypertrophic cardiomyopathy (oHCM) and mitral valve (MV) prolapse (MVP) are the 2 conditions which could cause symptomatic heart failure and sudden cardiac death. The clinical characteristics and surgical outcomes of patients with oHCM and MVP have not been well reported. From April 2012 to February 2018, 84 patients with oHCM (28 patients with MVP and 56 gender- and age-matched patients without MVP) who underwent septal myectomy at our institution were enrolled in this study. Information on clinical characteristics and outcomes was obtained from electronic medical records and follow-up surveys. Compared with those without MVP, patients with MVP were more symptomatic (New York Heart Association class III to IV; 96% vs 77%), more often moderate-to-severe mitral regurgitation (86% vs 48%), atrial fibrillation (39% vs 11%) and higher incidence of nonsustained ventricular tachycardia (44% vs 15%). Twenty (71%) had MV repair and 8 (29%) had MV replacement. Compared with patients without MVP, those with MVP had a longer postoperative hospital stay (10.9 ± 6.4 vs 7.8 ± 2.8 days). None of the 84 study patients died during hospital or follow-up. At the most recent echocardiographic evaluation, left ventricular outflow tract gradient significantly decreased from 69.7 ± 35.4 millimeters of mercury to 7.3 ± 5.1 millimeters of mercury and the degree of mitral valve regurgitation improved from grade 2.43 ± 0.69 to grade 0.5 ± 0.69. In conclusion, MVP occurs rarely in oHCM, and was related to atrial fibrillation, ventricular arrhythmia and mitral regurgitation. Mitral valve surgery in combination with myectomy is effective and safe for patients with oHCM and MVP, relieving substantially left ventricular outflow tract gradients and mitral regurgitation.


Subject(s)
Atrial Fibrillation , Cardiomyopathy, Hypertrophic , Mercury , Mitral Valve Insufficiency , Mitral Valve Prolapse , Humans , Mitral Valve Prolapse/complications , Mitral Valve Prolapse/surgery , Mitral Valve Insufficiency/diagnosis , Mitral Valve Insufficiency/surgery , Treatment Outcome , Cardiomyopathy, Hypertrophic/complications , Cardiomyopathy, Hypertrophic/surgery
11.
Mikrochim Acta ; 190(10): 387, 2023 09 12.
Article in English | MEDLINE | ID: mdl-37700165

ABSTRACT

Food safety is a critical issue that is closely related to people's health and safety. As a simple, rapid, and sensitive detection technique, surface-enhanced Raman scattering (SERS) technology has significant potential for food safety detection. Recently, researchers have shown a growing interest in utilizing silent region molecules for SERS analysis. These molecules exhibit significant Raman scattering peaks in the cellular Raman silent region between 1800 and 2800 cm-1 avoiding overlapping with the SERS spectrum of biological matrices in the range 600-1800 cm-1, which could effectively circumvent matrix effects and improve the SERS accuracy. In this review, the application of silent region molecules-based SERS analytical technique for food safety detection is introduced, detection strategies including label-free detection and labeled detection are discussed, and recent applications of SERS analysis technology based on molecules containing alkyne and nitrile groups, as well as Prussian blue (PB) in the detection of pesticides, mycotoxins, metal ions, and foodborne pathogens are highlighted. This review aims to draw the attention to the silent region molecules-based SERS analytical technique and to provide theoretical support for its further applications in food safety detection.


Subject(s)
Mycotoxins , Pesticides , Humans , Food Safety , Alkynes , Nitriles
12.
Sci Rep ; 13(1): 13941, 2023 08 25.
Article in English | MEDLINE | ID: mdl-37626141

ABSTRACT

A drug-loaded diaphragm is an easy-to-use and effective drug delivery system that is often used to treat mouth ulcers. In this study, an ultrafine fiber film loaded with capsaicin was successfully prepared using the electrospinning technology. poly-L-lactic acid and gelatin were selected as the matrix materials to form the composite fiber, and trifluoroethanol was used as a co-solvent for poly-L-lactic acid, gelatin and capsaicin to prepare the spinning solution, which was simple to fabricate. The prepared fiber films were characterized based on their microscopic morphology and tested to derive their mechanical properties. Thereafter, the capsaicin release behavior of the film was investigated. In vitro experiments revealed certain anti-inflammatory and antibacterial abilities while animal experiments revealed that the capsaicin-loaded ultrafine fiber film could promote the healing of oral ulcers in rats. Healing of the tongue tissue in rats administered 10% capsaicin-loaded fiber film was found to be better than that in rats administered the commercial dexamethasone patch. Overall, this development strategy may prove to be promising for the development of oral ulcer patch formulations.


Subject(s)
Oral Ulcer , Animals , Rats , Oral Ulcer/drug therapy , Capsaicin , Gelatin , Motion Pictures , Particulate Matter
13.
Org Lett ; 25(27): 5151-5156, 2023 Jul 14.
Article in English | MEDLINE | ID: mdl-37394755

ABSTRACT

A rhodium(I)-catalyzed highly enantioselective ring-opening and isomerization of cyclobutanols has been developed. The reaction provides a mild, atom-economical, and redox-neutral approach for the synthesis of chiral acyclic ketones bearing a ß-tertiary stereocenter. Excellent enantioselectivities and high yields can be achieved using cyclobutanols with alkoxy substituents at the C3 position. Mechanistic studies reveal that cyclobutanol only undergoes intramolecular hydrogen migration, and the formation of a (Z)-unsaturated ketone intermediate is crucial for achieving high enantioselectivity.


Subject(s)
Rhodium , Molecular Structure , Ketones , Stereoisomerism , Isomerism , Catalysis
14.
Langmuir ; 39(29): 10259-10269, 2023 07 25.
Article in English | MEDLINE | ID: mdl-37454390

ABSTRACT

Revealing drug-protein interaction is highly important to select a drug candidate with improved drug-like properties in the early stages of drug discovery. This highlights the urgent need to develop assays that enable the analysis of drug-protein interaction with high speed. Herein, this purpose was realized by the development of an affinity chromatographic method with a two-fold higher speed than typical assays like frontal analysis and zonal elution. The method involved synthesis of a stationary phase by immobilizing poly(ADP-ribose) polymerase-1 (PARP1) onto macroporous silica gel through a one-step bioorthogonal reaction, characterization of mutual displacement interaction of two canonical drugs to the immobilized PARP1, determination of the interaction between three (iniparib, rucaparib, and olaparib) drugs and the protein, and validation of these parameters by typical frontal analysis. The numbers of binding sites on the column were (2.85 ± 0.05) × 10-7, (1.89 ± 0.71) × 10-6, and (1.49 ± 0.06) × 10-7 M for iniparib, rucaparib, and olaparib, respectively. On these sites, the association constants of the three drugs to the protein were (9.85 ± 0.56) × 104, (2.85 ± 0.34) × 104, and (1.07 ± 0.35) × 105 M-1. The determined parameters presented a good agreement with the calculation by typical frontal analyses, which indicated that the current continuous competitive frontal analysis method was reliable for determining drug-protein interaction. Application of the methods was achieved by screening tubeimosides I and II as the bioactive compounds against breast cancer in Bolbostemma paniculatum. Their mechanism may be the interference of DNA repair via down-regulating PARP1 and meiotic recombination 11 expressions, thus leading to oncogene mutations and death of cancer cells. The method was high speed since it allowed simultaneous determination of binding parameters between two drugs and a protein with a smaller number of experiments to be performed. Such a feature made the method an attractive alternative for high-speed analysis of drug-protein interaction or the other bindings in a binary system.


Subject(s)
Benzamides , Poly(ADP-ribose) Polymerase Inhibitors , Humans , Chromatography, Affinity , Binding Sites
15.
Molecules ; 28(12)2023 Jun 15.
Article in English | MEDLINE | ID: mdl-37375349

ABSTRACT

To comprehensively understand the volatile compounds and assess the aroma profiles of different types of Pyrus ussuriensis Maxim. Anli, Dongmili, Huagai, Jianbali, Jingbaili, Jinxiangshui, and Nanguoli were detected via headspace solid phase microextraction (HS-SPME) coupled with two-dimensional gas chromatography/time-of-flight mass spectrometry (GC×GC-TOFMS). The aroma composition, total aroma content, proportion and number of different aroma types, and the relative quantities of each compound were analyzed and evaluated. The results showed that 174 volatile aroma compounds were detected in various cultivars, mainly including esters, alcohols, aldehydes, and alkenes: Jinxiangshui had the highest total aroma content at 2825.59 ng/g; and Nanguoli had the highest number of aroma species detected at 108. The aroma composition and content varied among pear varieties, and the pears could be divided into three groups based on principal component analysis. Twenty-four kinds of aroma scents were detected; among them, fruit and aliphatic were the main fragrance types. The proportions of aroma types also varied among different varieties, visually and quantitatively displaying changes of the whole aroma of the different varieties of pears brought by the changes in aroma composition. This study contributes to further research on volatile compound analysis, and provides useful data for the improvement of fruit sensory quality and breeding work.


Subject(s)
Odorants , Pyrus , Volatile Organic Compounds , Odorants/analysis , Plant Breeding , Pyrus/chemistry , Pyrus/genetics , Solid Phase Microextraction/methods , Volatile Organic Compounds/analysis , Gas Chromatography-Mass Spectrometry , China
16.
Biosens Bioelectron ; 234: 115369, 2023 Aug 15.
Article in English | MEDLINE | ID: mdl-37163878

ABSTRACT

Surface-enhanced Raman spectroscopy (SERS) is an ultrasensitive technique for both detection and structural characterizations. To further exploit these advantages, we designed and fabricated a dual-functional SERS probe for specific capture and fast detection of small molecule ligands binding to target protein from a mixture of compounds such as extracts of natural products. As a proof of concept, we synthesized SiO2@Ag nanoclusters that are coated with 6-chlorohexanoic acid for covalent immobilization of serotonin transporter (5-HTT) fused with a Halo-tag through enzyme-substrate recognition. As such, we fabricated a bioconjugated SERS probe, and the synthesis, coating, protein immobilization, and affinity-based ligand binding have been characterized and verified by transmission electron microscope (TEM), X-ray photoelectron spectroscopy (XPS), and elemental mapping. By applying this probe to analyze Gardenia jasminoides extract, we have successfully identified crocin I as a compound binding to 5-HTT, which was further proved by using mass spectrometry (MS) and nuclear magnetic resonance (NMR). Taken together, we have developed a novel SERS probe by integrating the inherent strength of SERS in molecular analysis with an extended functionality of affinity-guided molecular capture, which has demonstrated the potential in drug screening of challenging systems.


Subject(s)
Biosensing Techniques , Metal Nanoparticles , Silicon Dioxide/chemistry , Biosensing Techniques/methods , Spectrum Analysis, Raman/methods , Metal Nanoparticles/chemistry
17.
Antiviral Res ; 215: 105637, 2023 07.
Article in English | MEDLINE | ID: mdl-37196902

ABSTRACT

Emerging evidence has demonstrated the critical role of long noncoding RNAs (lncRNAs) in regulating gene expression. However, the functional significance and mechanisms underlying influenza A virus (IAV)-host lncRNA interactions are still elusive. Here, we identified a functional lncRNA, LncRNA#61, as a broad anti-IAV factor. LncRNA#61 is highly upregulated by different subtypes of IAV, including human H1N1 virus and avian H5N1 and H7N9 viruses. Furthermore, nuclear-enriched LncRNA#61 can translocate from the nucleus to the cytoplasm soon after IAV infection. Forced LncRNA#61 expression dramatically impedes viral replication of various subtypes of IAV, including human H1N1 virus and avian H3N2/N8, H4N6, H5N1, H6N2/N8, H7N9, H8N4, H10N3, H11N2/N6/N9 viruses. Conversely, abolishing LncRNA#61 expression substantially favored viral replication. More importantly, LncRNA#61 delivered by the lipid nanoparticle (LNP)-encapsulated strategy shows good performance in restraining viral replication in mice. Interestingly, LncRNA#61 is involved in multiple steps of the viral replication cycle, including virus entry, viral RNA synthesis and the virus release period. Mechanistically, the four long ring arms of LncRNA#61 mainly mediate its broad antiviral effect and contribute to its inhibition of viral polymerase activity and nuclear aggregation of key polymerase components. Therefore, we defined LncRNA#61 as a potential broad-spectrum antiviral factor for IAV. Our study further extends our understanding of the stunning and unanticipated biology of lncRNAs as well as their close interaction with IAV, providing valuable clues for developing novel broad anti-IAV therapeutics targeting host lncRNAs.


Subject(s)
Influenza A Virus, H1N1 Subtype , Influenza A Virus, H5N1 Subtype , Influenza A Virus, H7N9 Subtype , Influenza, Human , RNA, Long Noncoding , Animals , Humans , Mice , Antiviral Agents/pharmacology , Host-Pathogen Interactions , Influenza A Virus, H1N1 Subtype/genetics , Influenza A Virus, H3N2 Subtype/genetics , Influenza A Virus, H5N1 Subtype/genetics , Influenza A Virus, H7N9 Subtype/genetics , RNA, Long Noncoding/genetics , RNA, Long Noncoding/pharmacology , Virus Replication
18.
Infect Dis Ther ; 12(6): 1579-1592, 2023 Jun.
Article in English | MEDLINE | ID: mdl-37140880

ABSTRACT

INTRODUCTION: Pharmacist-driven (PD) dosing and monitoring services have been shown to improve the clinical and economic outcomes in patients treated with different antibiotics, other than teicoplanin. This study investigates the impact of PD dosing and monitoring services on the clinical and economic outcomes of non-critically ill patients receiving teicoplanin treatment. METHODS: A single-center retrospective study was conducted. Patients were divided into the PD group and the non-PD (NPD) group. Primary outcomes included the achievement of target serum concentration, and a composite endpoint of all-cause mortality, intensive care unit (ICU) admission, and sepsis or septic shock development during hospitalization or within 30 days of hospital admission. The cost of teicoplanin, overall medication cost, and total cost during hospital stay were also compared. RESULTS: A total of 163 patients from January to December 2019 were included and assessed. Seventy patients were assigned to the PD group and 93 to the NPD group. The PD group had a higher percentage of patients reaching the target trough concentration (54% versus 16%, p < 0.001). Around 26% of the patients in the PD group and 50% of the patients in the NPD group met the composite endpoint during their hospital stay (p = 0.002). The PD group exhibited a significantly lower incidence of sepsis or septic shock, shorter hospital stays, reduced drug costs, and lower total expenses. CONCLUSIONS: Our study demonstrates that pharmacist-driven teicoplanin therapy can improve the clinical and economic outcomes for non-critically ill patients. TRIAL REGISTRATION: https://www.chictr.org.cn ; identifier, ChiCTR2000033521.

19.
Int J Biol Macromol ; 236: 123924, 2023 May 01.
Article in English | MEDLINE | ID: mdl-36871679

ABSTRACT

With the bioactivities of antioxidant, anti-bacteria, anti-inflammation, immune regulation, antitumor and anti-coagulation, plant and microbial polysaccharides have been widely used in foods, medicine and cosmetics. However, how structure features affect the physicochemical property and bioactivity of plant and microbial polysaccharides is still unclear. Ultrasonic degradation usually degrades or modifies plant and microbial polysaccharides with different physicochemical properties and bioactivities by affecting their chemical or spatial structures via mechanical bond breaking and cavitation effects. Therefore, ultrasonic degradation might be an effective strategy for producing bioactive plant and microbial polysaccharides and analyzing their structure-function relationship. Present review summarized the influence of ultrasonic degradation on structural feature, physicochemical property and bioactivity of plant and microbial polysaccharides. Moreover, further problems need to be paid attention to during the application of ultrasonication for plant and microbial polysaccharides degradation are also recommended. Overall, present review will provide an efficient method for producing enhanced bioactive plant and microbial polysaccharides and analyzing their structure-activity relationship based on ultrasonic degradation.


Subject(s)
Antioxidants , Ultrasonics , Chemical Phenomena , Antioxidants/pharmacology , Antioxidants/chemistry , Structure-Activity Relationship , Polysaccharides/pharmacology , Polysaccharides/chemistry
20.
Sci Rep ; 13(1): 2166, 2023 02 07.
Article in English | MEDLINE | ID: mdl-36750602

ABSTRACT

Due to the interest in the potential pharmacological application of dandelion, the chemical constituents and activities of Taraxacum mongolicum Hand.-Mazz were studied. Box-Behnken response surface methodology was employed to optimize the protocol for extraction of flavonoid from dandelion. The molecular structures of different flavonoid compounds were acquired and analyzed by liquid chromatography-mass spectrometry (LC-MS) and nuclear magnetic resonance (NMR) spectroscopy. Several major flavonoid compounds were isolated and purified, namely, hesperetin-5'-O-ß-rhamnoglucoside, hesperetin-7-glucuronide, kaempferol-3-glucoside, baicalein, hyperseroside, which were extracted for the first time from dandelion. Hesperetin-5'-O-ß-rhamnoglucoside was identified as a new type of flavonoid that had never reported in the literature. This new flavonoid has outstanding antioxidant activity, as shown by its IC50 value (8.72 mg/L) for scavenging DPPH free radicals. The determination of the structure-related antioxidant activities could be interpreted based on DFT calculations. As such, we have not only illustrated the rich flavonoid contents in Taraxacum mongolicum Hand.-Mazz, but also revealed new types of flavonoid compounds in dandelion in terms of structure and antioxidant properties.


Subject(s)
Flavonoids , Taraxacum , Flavonoids/chemistry , Antioxidants/analysis , Taraxacum/chemistry , Chromatography, Liquid , Mass Spectrometry
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