Your browser doesn't support javascript.
loading
Show: 20 | 50 | 100
Results 1 - 20 de 190
Filter
Add more filters

Country/Region as subject
Publication year range
1.
Cell ; 187(13): 3445-3459.e15, 2024 Jun 20.
Article in English | MEDLINE | ID: mdl-38838668

ABSTRACT

Understanding cellular force transmission dynamics is crucial in mechanobiology. We developed the DNA-based ForceChrono probe to measure force magnitude, duration, and loading rates at the single-molecule level within living cells. The ForceChrono probe circumvents the limitations of in vitro single-molecule force spectroscopy by enabling direct measurements within the dynamic cellular environment. Our findings reveal integrin force loading rates of 0.5-2 pN/s and durations ranging from tens of seconds in nascent adhesions to approximately 100 s in mature focal adhesions. The probe's robust and reversible design allows for continuous monitoring of these dynamic changes as cells undergo morphological transformations. Additionally, by analyzing how mutations, deletions, or pharmacological interventions affect these parameters, we can deduce the functional roles of specific proteins or domains in cellular mechanotransduction. The ForceChrono probe provides detailed insights into the dynamics of mechanical forces, advancing our understanding of cellular mechanics and the molecular mechanisms of mechanotransduction.


Subject(s)
Mechanotransduction, Cellular , Single Molecule Imaging , Animals , Humans , Mice , Biomechanical Phenomena , Cell Adhesion , DNA/chemistry , DNA/metabolism , Focal Adhesions/metabolism , Integrins/metabolism , Microscopy, Atomic Force/methods , Single Molecule Imaging/methods , Cell Line , Cell Survival , Base Pairing , Calibration
2.
Nat Methods ; 20(11): 1780-1789, 2023 Nov.
Article in English | MEDLINE | ID: mdl-37798478

ABSTRACT

Extracellular matrix (ECM) rigidity serves as a crucial mechanical cue impacting diverse biological processes. However, understanding the molecular mechanisms of rigidity sensing has been limited by the spatial resolution and force sensitivity of current cellular force measurement techniques. Here we developed a method to functionalize DNA tension probes on soft hydrogel surfaces in a controllable and reliable manner, enabling molecular tension fluorescence microscopy for rigidity sensing studies. Our findings showed that fibroblasts respond to substrate rigidity by recruiting more force-bearing integrins and modulating integrin sampling frequency of the ECM, rather than simply overloading the existing integrin-ligand bonds, to promote focal adhesion maturation. We also demonstrated that ECM rigidity positively regulates the pN force of T cell receptor-ligand bond and T cell receptor mechanical sampling frequency, promoting T cell activation. Thus, hydrogel-based molecular tension fluorescence microscopy implemented on a standard confocal microscope provides a simple and effective means to explore detailed molecular force information for rigidity-dependent biological processes.


Subject(s)
Hydrogels , Integrins , Ligands , Focal Adhesions/chemistry , Microscopy, Fluorescence , Receptors, Antigen, T-Cell , Cell Adhesion
3.
Opt Express ; 32(4): 6329-6341, 2024 Feb 12.
Article in English | MEDLINE | ID: mdl-38439338

ABSTRACT

Phase-shifting interferometry (PSI) requires accurate phase shifts between interferograms for realizing high-accuracy phase retrieval. This paper presents an adaptive PSI through synchronously capturing phase shifts measurement interferograms and phase measurement interferograms, in which the former is a series of spatial carrier frequency phase-shifting interferograms generated by an additional assembly and the phase shifts are calculated with the single-spectrum phase shifts measurement algorithm (SS-PSMA), the latter is employed for phase retrieval with an adaptive phase-shifting digital holography algorithm (PSDHA) based on complex amplitude recovery. In addition to exhibiting excellent reliability, high-accuracy phase retrieval (0.02 rad), and short calculation time (<25 ms), the proposed adaptive PSDHA is suitable for various interferograms with different fringe shapes and numbers. Importantly, both simulation analysis and experimental result demonstrate that this adaptive PSI based on PSDHA can effectively eliminate phase-shifting errors caused by phase shifter and external disturbance, ensuring high-accuracy phase shifts measurement and phase retrieval, meanwhile significantly reducing phase-shifting interferograms acquisition time and phase retrieval calculation time.

4.
Acta Radiol ; 65(1): 91-98, 2024 Jan.
Article in English | MEDLINE | ID: mdl-37722764

ABSTRACT

BACKGROUND: Magnetic resonance imaging (MRI) is effective in diagnosing deltoid ligament (DL) injury but its sensitivity in chronic cases is low. Additional diagnostic signs are required to reduce the risk of a false negative diagnosis. PURPOSE: To evaluate the added diagnostic value of bone marrow edema at the ligament insertion (BMELI) of DL to the MRI assessment of chronic DL injury. MATERIAL AND METHODS: One hundred patients who consecutively came to our institution between November 2018 and December 2021 and underwent arthroscopic surgery for chronic ankle instability (CAI) were enrolled in the present study. Preoperative MR images were retrospectively reviewed by two orthopedic surgeons to evaluate the sensitivity, specificity and interobserver reliability of three MRI signs in diagnosing chronic DL injury, namely, abnormal ligamentous morphological characteristics (ALMC), BMELI and medial clear space (MCS). RESULTS: Taking arthroscopy as the reference standard, there were 34 patients with and 66 without DL injury. ALMC had 64.71% (22/34; 46.47-79.70) sensitivity and 83.33% (55/66; 71.71-91.00) specificity, BMELI had 70.59% (24/34; 52.33-84.29) sensitivity and 95.45% (63/66; 86.44-98.82) specificity and MCS had 26.47% (9/34; 13.51-44.65) sensitivity and 92.42% (61/66; 82.50-97.18) specificity. Compared with ALMC, BMELI had similar efficacy in superficial cases (P = 0.06) and greater efficacy in deep cases (P = 0.04). All three signs showed good interobserver agreement (kappa values all above 0.7). CONCLUSION: BMELI can reliably indicate concomitant injury to the DL in CAI patients. Using BMELI as a sign of chronic DL injury when ALMC is unclear may reduce the risk of a false negative diagnosis.


Subject(s)
Ankle Injuries , Joint Instability , Lateral Ligament, Ankle , Humans , Ankle Joint/diagnostic imaging , Ankle Joint/surgery , Reproducibility of Results , Retrospective Studies , Bone Marrow/pathology , Ankle Injuries/diagnostic imaging , Ankle Injuries/surgery , Ankle Injuries/complications , Lateral Ligament, Ankle/injuries , Magnetic Resonance Imaging/methods , Ligaments, Articular/diagnostic imaging , Ligaments, Articular/pathology , Joint Instability/diagnostic imaging , Joint Instability/surgery , Arthroscopy
5.
Nano Lett ; 23(12): 5562-5572, 2023 06 28.
Article in English | MEDLINE | ID: mdl-37289965

ABSTRACT

Macrophages are a type of immune cell that helps eliminate pathogens and diseased cells. Recent research has shown that macrophages can sense mechanical cues from potential targets to perform effective phagocytosis, but the mechanisms behind it remain unclear. In this study, we used DNA-based tension probes to study the role of integrin-mediated forces in FcγR-mediated phagocytosis. The results showed that when the phagocytic receptor FcγR is activated, the force-bearing integrins create a "mechanical barrier" that physically excludes the phosphatase CD45 and facilitates phagocytosis. However, if the integrin-mediated forces are physically restricted at lower levels or if the macrophage is on a soft matrix, CD45 exclusion is significantly reduced. Moreover, CD47-SIRPα "don't eat me" signaling can reduce CD45 segregation by inhibiting the mechanical stability of the integrin barrier. These findings demonstrate how macrophages use molecular forces to identify physical properties and combine them with biochemical signals from phagocytic receptors to guide phagocytosis.


Subject(s)
Integrins , Receptors, IgG , Integrins/metabolism , Phagocytosis , Macrophages/metabolism , Signal Transduction , Carrier Proteins
6.
Bioorg Chem ; 130: 106256, 2023 01.
Article in English | MEDLINE | ID: mdl-36371822

ABSTRACT

The novel Palmatine (PLT)-based supramolecular salt palmatine-sulfosalicylic acid (PLT-SSA) was designed and synthesized, and its structures was determined by the single crystal X-ray diffraction. It is found that PLT-SSA exhibited enhancing thermodynamic stability, fluorescence intensity and emission lifetime in crystal state, which indicated that these structures and aromatic rings may give more overlap between the host-guest units and give rise to a long-lived charge-separated state. In addition, the dyeing properties and toxicity of these protoberberine alkaloid (BBC and PLTCl) and their supramolecular salts will be developed in this work used as yellow dyes for development multifunctional fabrics.


Subject(s)
Berberine Alkaloids , Alkaloids/pharmacology , Alkaloids/chemistry , Coloring Agents , Thermodynamics , Berberine Alkaloids/chemistry , Berberine Alkaloids/pharmacology
7.
Knee Surg Sports Traumatol Arthrosc ; 31(5): 2015-2022, 2023 May.
Article in English | MEDLINE | ID: mdl-36175528

ABSTRACT

PURPOSE: To compare the clinical and magnetic resonance imaging (MRI) results after arthroscopic deltoid ligament (DL) repair versus DL nonrepair in patients with rotational ankle instability. METHODS: All patients with rotational ankle instability were enrolled in this retrospective cohort study. Clinical evaluation was performed by the American Orthopedic Foot and Ankle Society (AOFAS) score, Karlsson Ankle Functional Score (KAFS), and Tegner activity score preoperatively and at a minimum follow-up of 2 years. MRI at follow-up was performed to evaluate the DL morphology. RESULTS: A total of 50 patients were enrolled in this study. Among them, 24 patients received DL repair (the repair group), whereas 26 patients did not (the nonrepair group). No significant difference was found in the AOFAS score (98 ± 4 vs. 97 ± 4; n.s.), KAFS (94 ± 7 vs. 93 ± 9; n.s.), or Tegner activity score (5 ± 2 vs. 5 ± 1; n.s.) between the repair group and the nonrepair group at the final follow-up. However, the repair group had a significantly shorter return-to-sport time than the nonrepair group (4.6 ± 1.6 mo vs. 6.0 ± 2.5 mo; p = 0.03). Comparison of the postoperative deltoid ligament showed that the repair group had a lower signal intensity than the nonrepair group. CONCLUSION: Arthroscopic treatment of rotational ankle instability revealed good to excellent clinical results. However, patients who underwent DL repair had a significantly earlier return to sports as well as a lower signal intensity of DL than those who did not undergo DL repair. LEVEL OF EVIDENCE: Level III.


Subject(s)
Joint Instability , Lateral Ligament, Ankle , Humans , Lateral Ligament, Ankle/surgery , Ankle , Retrospective Studies , Arthroscopy/methods , Ligaments , Joint Instability/surgery
8.
J Perianesth Nurs ; 38(5): 799-803, 2023 10.
Article in English | MEDLINE | ID: mdl-37330722

ABSTRACT

PURPOSE: To investigate the incidence and risk factors of hypoxemia in the postanesthesia care unit (PACU) after general anesthesia in children. DESIGN: A retrospective observational study. METHODS: Elective surgical patients (N = 3,840 patients) treated in a pediatric hospital were divided into a hypoxemia group and a nonhypoxemia group according to the presence of hypoxemia following transport to the PACU. The clinical data of the 3,840 patients were compared between these two groups to evaluate factors that were linked to the development of postoperative hypoxemia. Factors that showed a statistically significant difference (P < .05) in single-factor tests were then examined in multivariate regression analyses to identify hypoxemia risk factors. FINDINGS: In our study group of 3,840 patients, 167 (4.35%) patients developed hypoxemia, with an incidence of 4.35%. Univariate analysis indicated that age, weight, anesthesia method, and operation type were significantly associated with hypoxemia. Logistic regression analysis indicated that operation type was associated with hypoxemia. CONCLUSIONS: Surgery type is a primary risk factor for pediatric hypoxemia in the PACU following general anesthesia. Patients undergoing oral surgery are more prone to hypoxemia and should be more intensively monitored to ensure timely treatment if required.


Subject(s)
Anesthesia, General , Postoperative Complications , Humans , Child , Postoperative Complications/therapy , Anesthesia, General/adverse effects , Hypoxia/epidemiology , Hypoxia/etiology , Hypoxia/therapy , Risk Factors , Anesthesia Recovery Period
9.
Anal Chem ; 94(11): 4570-4575, 2022 03 22.
Article in English | MEDLINE | ID: mdl-35257583

ABSTRACT

Mechanical forces have profound effects on the morphology and migration of cells in a two-dimensional environment. However, cells in vivo mostly migrate in three-dimensional space while physically constrained, and the mechanism by which cellular dynamic forces drive migration in this confined environment is unclear. Here, we present a method of fabricating microfluidic chips with integrated DNA-based tension probes to measure spatiotemporal variations in integrin-mediated force exerted during confined cell migration. Using this developed device, we measured the spatial locations, magnitudes, and temporal characteristics of integrin-ligand tension signals in motile cells in different microchannels and found that cells exerted less force and underwent increasingly transitory integrin-ligand interactions when migrating in confined spaces. This study demonstrates that the described method provides insights into understanding the migratory machinery of cells in geometrically confined environment that better mimics physiological conditions.


Subject(s)
DNA , Integrins , Cell Movement , DNA Probes , Ligands
10.
Biochem Biophys Res Commun ; 606: 80-86, 2022 05 28.
Article in English | MEDLINE | ID: mdl-35339756

ABSTRACT

Lung cancer remains the most common fatal malignant disease, and the 5-year survival rate of patients with metastasis is merely 6%. In this research, the platinum nanocluster (short for nano-Pt) was used for optical imaging without the help of other fluorescent probes and possess targeted antitumor activity as well as low systemic toxicity. The endocytic pathway and distribution of nano-Pt in non-small cell lung cancer NSCLC H1299 cells was explored by the means of quantitative and qualitative tests. Furthermore, the targeting capability and antitumor efficiency of nano-Pt was detected by intravital imaging experiment and antitumor experiment. The research implies that nano-Pt entered H1299 cells dominatingly through macropinocytosis and clathrin-dependent endocytosis pathway, and has significant antitumor efficiency, targeting properties and reliable safety for mouse tumor, indicating this nano-Pt has great potential for clinical diagnosis and therapy of NSCLC H1299 cells.


Subject(s)
Carcinoma, Non-Small-Cell Lung , Lung Neoplasms , Animals , Carcinoma, Non-Small-Cell Lung/drug therapy , Carcinoma, Non-Small-Cell Lung/pathology , Cell Line, Tumor , Endocytosis , Humans , Lung Neoplasms/pathology , Mice , Platinum
11.
Acta Neuropathol ; 144(5): 861-879, 2022 11.
Article in English | MEDLINE | ID: mdl-36053316

ABSTRACT

Parkinson's disease (PD) is a movement disorder characterized by the early loss of nigrostriatal dopaminergic pathways producing significant network changes impacting motor coordination. Recently three motor stages of PD have been proposed (a silent period when nigrostriatal loss begins, a prodromal motor period with subtle focal manifestations, and clinical PD) with evidence that motor cortex abnormalities occur to produce clinical PD[8]. We directly assess structural changes in the primary motor cortex and corticospinal tract using parallel analyses of longitudinal clinical and cross-sectional pathological cohorts thought to represent different stages of PD. 18F-FP-CIT positron emission tomography and subtle motor features identified patients with idiopathic rapid-eye-movement sleep behaviour disorder (n = 8) that developed prodromal motor signs of PD. Longitudinal diffusion tensor imaging before and after the development of prodromal motor PD showed higher fractional anisotropy in motor cortex and corticospinal tract compared to controls, indicating adaptive structural changes in motor networks in concert with nigrostriatal dopamine loss. Histological analyses of the white matter underlying the motor cortex showed progressive disorientation of axons with segmental replacement of neurofilaments with α-synuclein, enlargement of myelinating oligodendrocytes and increased density of their precursors. There was no loss of neurons in the motor cortex in early or late pathologically confirmed motor PD compared to controls, although there were early cortical increases in neuronal neurofilament light chain and myelin proteins in association with α-synuclein accumulation. Our results collectively provide evidence of a direct impact of PD on primary motor cortex and its output pathways that begins in the prodromal motor stage of PD with structural changes confirmed in early PD. These adaptive structural changes become considerable as the disease advances potentially contributing to motor PD.


Subject(s)
Motor Cortex , Parkinson Disease , White Matter , Cross-Sectional Studies , Diffusion Tensor Imaging , Dopamine , Humans , Motor Cortex/metabolism , Parkinson Disease/pathology , Prodromal Symptoms , White Matter/pathology , alpha-Synuclein/metabolism
12.
J Nanobiotechnology ; 20(1): 359, 2022 Aug 02.
Article in English | MEDLINE | ID: mdl-35918698

ABSTRACT

The conversion of tumor-promoting M2 macrophage phenotype to tumor-suppressing M1 macrophages is a promising therapeutic approach for cancer treatment. However, the tumor normally provides an abundance of M2 macrophage stimuli, which creates an M2 macrophage-dominant immunosuppressive microenvironment. In our study, docetaxel (DTX) as chemotherapeutic modularity was loaded into M1 macrophage-derived exosomes (M1-Exo) with M1 proinflammatory nature to establish DTX-M1-Exo drug delivery system. We found that DTX-M1-Exo induced naïve M0 macrophages to polarize to M1 phenotype, while failed to repolarize to M2 macrophages upon Interleukin 4 restimulation due to impaired mitochondrial function. This suggests that DTX-M1-Exo can achieve long-term robust M1 activation in immunosuppressive tumor microenvironment. The in vivo results further confirmed that DTX-M1-Exo has a beneficial effect on macrophage infiltration and activation in the tumor tissues. Thus, DTX-M1-Exo is a novel macrophage polarization strategy via combined chemotherapy and immunotherapy to achieve great antitumor therapeutic efficacy.


Subject(s)
Exosomes , Neoplasms , Docetaxel/pharmacology , Exosomes/genetics , Humans , Immunotherapy , Macrophages , Neoplasms/pathology , Tumor Microenvironment
13.
Chemistry ; 27(50): 12884-12889, 2021 Sep 06.
Article in English | MEDLINE | ID: mdl-34133047

ABSTRACT

Chiral phosphoric acid-catalyzed couplings of C-alkynyl N,N'-di-(tert-butoxycarbonyl)-aminals with ß-naphthols led to chiral propargylamines in moderate to high yields with high to excellent enantioselectivity, in which the reactions underwent sequential chiral phosphoric acid-catalyzed in situ formation of N-(tert-butoxycarbonyl)-imines (N-Boc-imines) from the aminals, and 1,2-addition of ß-naphthols to the N-Boc-imines. Chiral 1,2-dihydronaphtho[2,1-b]furans and naphtho[2,1-b]furans were prepared with satisfactory results when 10 mol% AgOAc and 20 mol% 2,6-lutidine or 1.2 equiv. of 1,8-diazabicyclo[5.4.0]undec-7-ene (DBU) were added to the resulting chiral propargylamines solution, respectively.

14.
J Obstet Gynaecol Res ; 47(9): 3034-3046, 2021 Sep.
Article in English | MEDLINE | ID: mdl-34109708

ABSTRACT

BACKGROUND: Preeclampsia (PE) is a serious obstetric complication. Recent studies point out that the functions of long intergenic noncoding RNA 00473 (linc00473), miR-424-5p, and Wnt/ß-catenin signaling pathway were involved in the invasion and migration of extravillous trophoblast. Here, we investigated the role and mechanism of linc00473 in HTR-8/SVneo trophoblastic cell line and its role in PE. METHOD: The expression levels of linc00473 and miR-424-5p in placental tissues and the transfection efficiency of miR-424-5p were detected by quantitative real-time polymerase chain reaction (qRT-PCR). HTR-8/SVneo cell invasion and proliferation were determined by transwell and Cell Counting Kit-8 (CCK-8) assays. The protein expressions of wnt3a, p-GSK3ß, GSK3ß, active ß-catenin, and total ß-catenin were detected by Western blot. The apoptosis and migration of HTR-8/SVneo cells were detected by flow cytometry and wound healing assays. The targeting relationships between linc00473, miR-424-5p, and wnt3a were predicted by ENCORI database and TargetScan V7.2 and were determined using dual-luciferase reporter assay. RESULTS: The expression level of linc00473 was low and miR-424-5p was high in placenta of PE patients. Linc00473 can target miR-424-5p, while miR-424-5p target wnt3a. High expression of linc00473 and wnt3a promoted cell proliferation, migration, invasion, and inhibited cell apoptosis. However, miR-424-5p mimic inhibited HTR-8/SVneo cells proliferation, migration, invasion, while promoted cell apoptosis, partially reversed the effect of linc00473, while wnt3a overexpression partially counteracted the effect of miR-424-5p mimic. CONCLUSION: Linc00473 mediates the regulation of Wnt/ß-catenin signaling pathway by miR-424-5p to affect the invasion and migration ability of trophoblastic cell line HTR-8/SVneo. It indicated that linc00473 is involved in PE and could be a therapeutic target.


Subject(s)
MicroRNAs , RNA, Long Noncoding , Cell Line , Cell Movement , Female , Humans , MicroRNAs/genetics , Placenta , Pregnancy , RNA, Long Noncoding/genetics , RNA, Long Noncoding/metabolism , Signal Transduction , Trophoblasts , Wnt3A Protein , beta Catenin
15.
Knee Surg Sports Traumatol Arthrosc ; 29(5): 1510-1515, 2021 May.
Article in English | MEDLINE | ID: mdl-32725448

ABSTRACT

PURPOSE: The angle between the anterior talofibular ligament (ATFL) and the posterior talofibular ligament (PTFL) is increased in patients with chronic ATFL injury. This study aimed to compare the AFTL-PTFL angle before versus after ankle lateral stabilization surgery, and to evaluate whether the ATFL-PTFL angle correlates with the ligament injury severity. METHODS: This retrospective study included 48 patients with mechanical ankle instability treated between 2016 and 2018. After arthroscopic evaluation, all patients underwent ankle lateral stabilization surgery comprising ligament repair (n = 28) or reconstruction (n = 20). The ATFL-PTFL angle was measured in the axial plane on pre- and postoperative MRI. Comparisons were made of the pre- versus postoperative ATFL-PTFL angles, and the ATFL-PTFL angle of the repair versus reconstruction groups. Receiver operating characteristic (ROC) curve analysis was used to assess the diagnostic performance of the ATFL-PTFL angle in selecting the surgical technique. RESULTS: The postoperative ATFL-PTFL angle was significantly decreased compared with preoperatively. The ATFL-PTFL angle was significantly smaller in the repair group than the reconstruction group preoperatively and postoperatively. The area under the ROC curve was 0.741 (P < 0.01). The optimal cutoff point for the selection of ligament reconstruction was an ATFL-PTFL angle of 89.4° (sensitivity 0.85, specificity 0.61). CONCLUSION: The ATFL-PTFL angle decreases after ankle lateral stabilization surgery. The ATFL-PTFL angle is related to the severity of the ATFL injury. Ankle lateral ligament reconstruction should be considered when the ATFL-PTFL angle is > 89.4°. LEVEL OF EVIDENCE: Level III.


Subject(s)
Ankle Injuries/surgery , Ankle Joint/surgery , Joint Instability/surgery , Lateral Ligament, Ankle/physiopathology , Lateral Ligament, Ankle/surgery , Adolescent , Adult , Ankle Joint/diagnostic imaging , Ankle Joint/physiopathology , Arthroplasty/methods , Female , Humans , Lateral Ligament, Ankle/diagnostic imaging , Magnetic Resonance Imaging/methods , Male , Middle Aged , Postoperative Period , ROC Curve , Plastic Surgery Procedures/methods , Retrospective Studies , Young Adult
16.
Molecules ; 26(19)2021 Sep 29.
Article in English | MEDLINE | ID: mdl-34641449

ABSTRACT

We discovered SW033291 in a high throughput chemical screen aimed at identifying 15-prostaglandin dehydrogenase (15-PGDH) modulators. The compound exhibited inhibitory activity in in vitro biochemical and cell-based assays of 15-PGDH activity. We subsequently demonstrated that this compound, and several analogs thereof, are effective in in vivo mouse models of bone marrow transplant, colitis, and liver regeneration, where increased levels of PGE2 positively potentiate tissue regeneration. To better understand the binding of SW033291, we carried out docking studies for both the substrate, PGE2, and an inhibitor, SW033291, to 15-PGDH. Our models suggest similarities in the ways that PGE2 and SW033291 interact with key residues in the 15-PGDH-NAD+ complex. We carried out molecular dynamics simulations (MD) of SW033291 bound to this complex, in order to understand the dynamics of the binding interactions for this compound. The butyl side chain (including the sulfoxide) of SW033291 participates in crucial binding interactions that are similar to those observed for the C15-OH and the C16-C20 alkyl chain of PGE2. In addition, interactions with residues Ser138, Tyr151, and Gln148 play key roles in orienting and stabilizing SW033291 in the binding site and lead to enantioselectivity for the R-enantiomer. Finally, we compare the binding mode of (R)-S(O)-SW033291 with the binding interactions of published 15-PGDH inhibitors.


Subject(s)
Hydroxyprostaglandin Dehydrogenases/antagonists & inhibitors , Pyridines/chemistry , Pyridines/pharmacology , Thiophenes/chemistry , Thiophenes/pharmacology , Binding Sites , Humans , Molecular Dynamics Simulation
17.
BMC Genomics ; 21(1): 81, 2020 Jan 28.
Article in English | MEDLINE | ID: mdl-31992199

ABSTRACT

BACKGROUND: Zanthoxylum armatum (Z. armatum) is a highly economically important tree that presents a special numbing taste. However, the underlying regulatory mechanism of the numbing taste remains poorly understood. Thus, the elucidation of the key genes associated with numbing taste biosynthesis pathways is critical for providing genetic information on Z. armatumand the breeding of high-quality germplasms of this species. RESULTS: Here, de novo transcriptome assembly was performed for the five major organs of Z. armatum, including the roots, stems, leaf buds, mature leaves and fruits. A total of 111,318 unigenes were generated with an average length of 1014 bp. Additionally, a large number of SSRs were obtained to improve our understanding of the phylogeny and genetics of Z. armatum. The organ-specific unigenes of the five major samples were screened and annotated via GO and KEGG enrichment analysis. A total of 53 and 34 unigenes that were exclusively upregulated in fruit samples were identified as candidate unigenes for terpenoid biosynthesis or fatty acid biosynthesis, elongation and degradation pathways, respectively. Moreover, 40 days after fertilization (Fr4 stage) could be an important period for the accumulation of terpenoid compounds during the fruit development and maturation of Z. armatum. The Fr4 stage could be a key point at which the first few steps of the fatty acid biosynthesis process are promoted, and the catalysis of subsequent reactions could be significantly induced at 62 days after fertilization (Fr6 stage). CONCLUSIONS: The present study realized de novo transcriptome assembly for the five major organs of Z. armatum. To the best of our knowledge, this study provides the first comprehensive analysis revealing the genes underlying the special numbing taste of Z. armatum. The assembled transcriptome profiles expand the available genetic information on this species and will contribute to gene functional studies, which will aid in the engineering of high-quality cultivars of Z. armatum.


Subject(s)
Fatty Acids/metabolism , Gene Expression Regulation, Plant , Lipid Metabolism , Terpenes/metabolism , Transcriptome , Zanthoxylum/genetics , Zanthoxylum/metabolism , Biosynthetic Pathways , Computational Biology/methods , Microsatellite Repeats , Molecular Sequence Annotation , Organ Specificity
18.
Bioorg Chem ; 94: 103346, 2020 01.
Article in English | MEDLINE | ID: mdl-31645277

ABSTRACT

Many natural or synthetic chalcones have potential anti-tumor activity. Here, we synthesized two series of chalcone analogues containing a thieno[2,3-d]pyrimidin-2-yl group and evaluated for their cytotoxic activity towards cultured human lung cancer A549 and colorectal HCT-116 cells. Among them, compound 8d was the most cytotoxic against HCT-116 cells, with an IC50 value of 2.65 µM. Analyses of the phenotypic changes induced by this compound found a dose-dependent accumulation of HCT-116 cells in sub-G1 phase, indicating that compound 8d might induce apoptosis. Furthermore, we found that 8d triggered mitochondrial membrane potential depolarization, promoted reactive oxygen species formation in HCT-116 cells, and increased the percentage of early and late apoptotic cells. Finally, immunoblotting indicated that 8d increased PARP-1 and caspases 3, 7 and 9 cleavage. These data suggest that compound 8d induces apoptosis via the mitochondrial death pathway.


Subject(s)
Antineoplastic Agents/chemical synthesis , Antineoplastic Agents/pharmacology , Chalcones/chemical synthesis , Chalcones/pharmacology , Pyrimidines/chemistry , A549 Cells , Antineoplastic Agents/chemistry , Apoptosis/drug effects , Cell Proliferation/drug effects , Chalcones/chemistry , HCT116 Cells , Humans , Membrane Potential, Mitochondrial/drug effects , Mitochondria/drug effects , Oxidative Stress/drug effects
19.
Knee Surg Sports Traumatol Arthrosc ; 28(12): 3987-3993, 2020 Dec.
Article in English | MEDLINE | ID: mdl-32322948

ABSTRACT

PURPOSE: To compare clinical function after knot anchor versus knotless anchor repair of the anterior talofibular ligament (ATFL) in patients with chronic lateral ankle instability. METHODS: All patients who underwent arthroscopic surgical ATFL repair using knot or knotless suture anchors were included in this study. Functional scores (American Orthopedic Foot and Ankle Society (AOFAS), Karlsson score and Tegner activity scores) and magnetic resonance imaging (MRI) were used to evaluate the ankle with a follow-up of at least 2 years. RESULTS: A total of 52 patients with chronic ankle instability were included in this study. Among these patients, 23 patients underwent one knot anchor repair procedure (Group A), and the other 29 patients underwent one knotless anchor repair procedure (Group B). At the final follow-up, there were no significant differences between Group A and Group B regarding the AOFAS score (89 ± 9 vs 84 ± 11; ns), Karlsson score (82 ± 14 vs 75 ± 18; ns), or Tegner activity score (4 ± 1 vs 4 ± 2; ns). There also were no significant differences in the mean ATFL signal-noise ratio (SNR) value (7.5 ± 4.4 vs 7.3 ± 2.9; ns) or ATFL angle (82° ± 7° vs 84° ± 9°; ns) between the groups. CONCLUSION: When compared with knot repair, knotless repair of the lateral ankle ligament produced similar functional outcomes. LEVEL OF EVIDENCE: III.


Subject(s)
Ankle Joint/surgery , Arthroscopy/methods , Joint Instability/surgery , Lateral Ligament, Ankle/surgery , Suture Anchors , Suture Techniques , Adult , Ankle Joint/diagnostic imaging , Female , Humans , Joint Instability/diagnostic imaging , Lateral Ligament, Ankle/diagnostic imaging , Lysholm Knee Score , Magnetic Resonance Imaging , Male , Retrospective Studies , Young Adult
20.
Knee Surg Sports Traumatol Arthrosc ; 28(1): 221-226, 2020 Jan.
Article in English | MEDLINE | ID: mdl-31165905

ABSTRACT

PURPOSE: To compare the function and activity level after one-anchor repair versus two-anchor repair of the anterior talofibular ligament (ATFL) in patients with chronic lateral ankle instability. METHODS: All patients who underwent arthroscopic surgical ATFL repair using suture anchors were included in this study. The American Orthopedic Foot and Ankle Society (AOFAS) score, Karlsson Ankle Functional Score (Karlsson score) and Tegner activity score were used to evaluate ankle function at a follow-up of a minimum of 2 years. A magnetic resonance imaging (MRI) scan was performed to evaluate the repaired ATFL. RESULTS: A total of 51 patients with chronic ankle instability were included in this study. Among them, 20 patients accepted a one-anchor repair procedure (one-anchor group), and the other 31 patients accepted a two-anchor repair procedure (two-anchor group). At the final follow-up, there was no significant difference in the AOFAS score between the one-anchor group and the two-anchor group (90 ± 9 vs 91 ± 10; ns). However, the mean Karlsson score of the two-anchor group (88 ± 12) was significantly higher than that of the one-anchor group (80 ± 14) (p = 0.04). There was a significant difference in activity level as measured by the Tegner activity score (5 ± 1 vs 4 ± 1; p < 0.001) between the two-anchor group and the one-anchor group after surgery. Patients in the two-anchor group (68%) had a significantly higher percentage of sport participation compared to those in the one-anchor group (30%) (p = 0.01). CONCLUSION: Compared with a one-anchor repair, a two-anchor repair of the lateral ankle ligament produced better functional outcomes. Arthroscopic ATFL repair with two anchors provided a minimally invasive technique with a higher rate of return to sports than repair with one anchor. The present study showed its clinical relevance by maintaining the advantage of ATFL repair using two anchors regarding the clinical function. LEVEL OF EVIDENCE: III.


Subject(s)
Ankle Joint/surgery , Arthroscopy/instrumentation , Joint Instability/surgery , Lateral Ligament, Ankle/surgery , Suture Anchors , Suture Techniques/instrumentation , Adult , Ankle Joint/diagnostic imaging , Ankle Joint/physiopathology , Arthroscopy/methods , Female , Follow-Up Studies , Humans , Joint Instability/diagnostic imaging , Lateral Ligament, Ankle/diagnostic imaging , Lysholm Knee Score , Magnetic Resonance Imaging , Male , Middle Aged , Recovery of Function , Treatment Outcome
SELECTION OF CITATIONS
SEARCH DETAIL