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1.
Front Pharmacol ; 15: 1272087, 2024.
Article in English | MEDLINE | ID: mdl-38694923

ABSTRACT

Chrysanthemi indic Flos (CIF) has been commonly consumed for the treatment of inflammation and related skin diseases. However, the potential bioactive components responsible for its anti-inflammatory and sensitive skin (SS) improvement activities, and the correlated mechanisms of action still remain unknown. In this work, it was firstly found that the CIF extract (CIFE) displayed arrestive free radical scavenging activity on DPPH and ABTS radicals, with no significant difference with positive control Trolox (p > 0.05). Then, compared to the negative group, CIFE markedly decreased the productions of the pro-inflammatory cytokines (IL-1ß, IL-6, PEG2, TNF-α, IFN-γ, NO) in LPS induced RAW264.7 cells in a dose-dependent manner (p < 0.01). Besides, CIFE strongly inhibited the COX-2 and hyaluronidase (HAase) with the IC50 values of 1.06 ± 0.01 µg/mL and 12.22 ± 0.39 µg/mL, indicating higher inhibitory effect than positive control of aspirin of 6.33 ± 0.05 µg/mL (p < 0.01), and comparable inhibitory effect with indometacin of 0.60 ± 0.03 µg/mL, and ascorbic acid of 11.03 ± 0.41 µg/mL (p > 0.05), respectively. Furthermore, kinetic assays with Lineweaver-Burk plot (Michaelis Menten equation) suggested that CIFE reversibly inhibited the COX-2 and HAase, with a mixed characteristics of competitive and non-competitive inhibition. Thereafter, multi-target affinity ultrafiltration liquid chromatography-mass spectrometry (UF-LC/MS) method was employed to fast fish out the potential COX-2 and HAase in CIFE. Herein, 13 components showed various affinity binding degrees to the COX-2 and HAase, while those components with relative binding affinity (RBA) value higher than 3.0, such as linarin and chlorogenic acid isomers, were deemed to be the most bioactive components for the anti-inflammatory and SS improvement activities of CIFE. Finally, the interaction mechanism, including binding energy, inhibition constant, docking sites, and the key amino acids involved in hydrogen bonds between the potential ligands and COX-2/HAase were simulated and confirmed with the molecule docking analysis. In summary, this study showcased the prominent anti-inflammatory and SS improvement activities of CIF, which would provide further insights on this functional medicinal plant to be a natural anti-SS remedy.

2.
Cell Rep Med ; 5(2): 101418, 2024 Feb 20.
Article in English | MEDLINE | ID: mdl-38340726

ABSTRACT

The continual emergence of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) variants of concern (VOCs) poses a major challenge to vaccines and antiviral therapeutics due to their extensive evasion of immunity. Aiming to develop potent and broad-spectrum anticoronavirus inhibitors, we generated A1-(GGGGS)7-HR2m (A1L35HR2m) by introducing an angiotensin-converting enzyme 2 (ACE2)-derived peptide A1 to the N terminus of the viral HR2-derived peptide HR2m through a long flexible linker, which showed significantly improved antiviral activity. Further cholesterol (Chol) modification at the C terminus of A1L35HR2m greatly enhanced the inhibitory activities against SARS-CoV-2, SARS-CoV-2 VOCs, SARS-CoV, and Middle East respiratory syndrome coronavirus (MERS-CoV) pseudoviruses, with IC50 values ranging from 0.16 to 5.53 nM. A1L35HR2m-Chol also potently inhibits spike-protein-mediated cell-cell fusion and the replication of authentic Omicron BA.2.12.1, BA.5, and EG.5.1. Importantly, A1L35HR2m-Chol distributed widely in respiratory tract tissue and had a long half-life (>10 h) in vivo. Intranasal administration of A1L35HR2m-Chol to K18-hACE2 transgenic mice potently inhibited Omicron BA.5 and EG.5.1 infection both prophylactically and therapeutically.


Subject(s)
Middle East Respiratory Syndrome Coronavirus , Animals , Mice , Administration, Intranasal , Mice, Transgenic , Peptides/pharmacology , SARS-CoV-2/genetics , Antiviral Agents/pharmacology , Antiviral Agents/therapeutic use
3.
Nat Commun ; 15(1): 1125, 2024 Feb 06.
Article in English | MEDLINE | ID: mdl-38321032

ABSTRACT

Congenital vertebral malformation, affecting 0.13-0.50 per 1000 live births, has an immense locus heterogeneity and complex genetic architecture. In this study, we analyze exome/genome sequencing data from 873 probands with congenital vertebral malformation and 3794 control individuals. Clinical interpretation identifies Mendelian etiologies in 12.0% of the probands and reveals a muscle-related disease mechanism. Gene-based burden test of ultra-rare variants identifies risk genes with large effect sizes (ITPR2, TBX6, TPO, H6PD, and SEC24B). To further investigate the biological relevance of the genetic association signals, we perform single-nucleus RNAseq on human embryonic spines. The burden test signals are enriched in the notochord at early developmental stages and myoblast/myocytes at late stages, highlighting their critical roles in the developing spine. Our work provides insights into the developmental biology of the human spine and the pathogenesis of spine malformation.


Subject(s)
Musculoskeletal Abnormalities , Spine , Humans , Spine/abnormalities , Musculoskeletal Abnormalities/genetics , Alleles , Exome , T-Box Domain Proteins/genetics
4.
Cell Rep Methods ; 4(1): 100687, 2024 Jan 22.
Article in English | MEDLINE | ID: mdl-38211594

ABSTRACT

Leveraging protein structural information to evaluate pathogenicity has been hindered by the scarcity of experimentally determined 3D protein. With the aid of AlphaFold2 predictions, we developed the structure-informed genetic missense mutation assessor (SIGMA) to predict missense variant pathogenicity. In comparison with existing predictors across labeled variant datasets and experimental datasets, SIGMA demonstrates superior performance in predicting missense variant pathogenicity (AUC = 0.933). We found that the relative solvent accessibility of the mutated residue contributed greatly to the predictive ability of SIGMA. We further explored combining SIGMA with other top-tier predictors to create SIGMA+, proving highly effective for variant pathogenicity prediction (AUC = 0.966). To facilitate the application of SIGMA, we pre-computed SIGMA scores for over 48 million possible missense variants across 3,454 disease-associated genes and developed an interactive online platform (https://www.sigma-pred.org/). Overall, by leveraging protein structure information, SIGMA offers an accurate structure-based approach to evaluating the pathogenicity of missense variants.


Subject(s)
Computational Biology , Mutation, Missense , Virulence , Proteins/genetics , Mutation
6.
Phytochem Anal ; 35(2): 239-253, 2024 Mar.
Article in English | MEDLINE | ID: mdl-37779216

ABSTRACT

INTRODUCTION: Scutellaria baicalensis Georgi, a traditional Chinese medicine, is widely applied to treat various diseases among people, especially in East Asia. However, the specific active compounds in S. baicalensis aqueous extracts (SBAEs) responsible for the hypoglycemic and hypolipidemic properties as well as their potential mechanisms of action remain unclear. OBJECTIVES: This work aimed to explore the potential hypoglycemic and hypolipidemic compounds from SBAE and their potential mechanisms of action. METHODOLOGY: The in vitro inhibitory tests against lipase and α-glucosidase, and the effects of SBAE on glucose consumption and total triglyceride content in HepG2 cells were first performed to evaluate the hypoglycemic and hypolipidemic effects. Then, affinity ultrafiltration liquid chromatography-mass spectrometry (LC-MS) screening strategy with five drug targets, including α-glucosidase, α-amylase, protein tyrosine phosphatase 1B (PTP1B), lipase and 3-hydroxy-3-methylglutaryl-coenzyme A reductase (HMGCR) was developed to screen out the potential active constituents from SBAE, and some representative active compounds were further validated. RESULTS: SBAE displayed noteworthy hypoglycemic and hypolipidemic properties, and 4, 10, 4, 8, and 8 potential bioactive components against α-amylase, α-glucosidase, PTP1B, HMGCR, and lipase were initially screened out, respectively. The interaction network was thus constructed between the potential bioactive compounds screened out and their corresponding drug targets. Among them, baicalein, wogonin, and wogonoside were revealed to possess remarkable hypoglycemic and hypolipidemic effects. CONCLUSION: The potential hypolipidemic and hypoglycemic bioactive compounds in SBAE and their mode of action were initially explored through ligand-target interactions by combining affinity ultrafiltration LC-MS strategy with five drug targets.


Subject(s)
Scutellaria baicalensis , Ultrafiltration , Humans , alpha-Glucosidases , Hypoglycemic Agents/pharmacology , Lipase , alpha-Amylases
7.
CNS Neurosci Ther ; 30(4): e14526, 2024 04.
Article in English | MEDLINE | ID: mdl-37990346

ABSTRACT

OBJECTIVE: The purpose of this study was to identify significant prognostic factors associated with facial paralysis after vestibular schwannoma (VS) surgery and develop a novel nomogram for predicting facial nerve (FN) outcomes. METHODS: Retrospective data were retrieved from 355 patients who underwent microsurgery via the retrosigmoid approach for VS between December 2017 and December 2022. Univariate and multivariate logistic regression analysis were used to construct a radiographic features-based nomogram to predict the risk of facial paralysis after surgery. RESULTS: Following a thorough screening process, a total of 185 participants were included. The univariate and multivariate logistic regression analysis revealed that tumor size (p = 0.005), fundal fluid cap (FFC) sign (p = 0.014), cerebrospinal fluid cleft (CSFC) sign (p < 0.001), and expansion of affected side of internal auditory canal (IAC) (p = 0.033) were independent factors. A nomogram model was constructed based on these indicators. When applied to the validation cohort, the nomogram demonstrated good discrimination and favorable calibration. Then we generated a web-based calculator to facilitate clinical application. CONCLUSION: Tumor size, FFC and CSFC sign, and the expansion of the IAC, serve as good predictors of postoperative FN outcomes. Based on these factors, the nomogram model demonstrates good predictive performance.


Subject(s)
Facial Paralysis , Neuroma, Acoustic , Humans , Neuroma, Acoustic/diagnostic imaging , Neuroma, Acoustic/surgery , Facial Nerve/diagnostic imaging , Facial Nerve/surgery , Retrospective Studies , Facial Paralysis/diagnostic imaging , Facial Paralysis/etiology , Nomograms
8.
Comput Struct Biotechnol J ; 23: 157-164, 2024 Dec.
Article in English | MEDLINE | ID: mdl-38144945

ABSTRACT

In the field of metastatic skeletal oncology imaging, the role of artificial intelligence (AI) is becoming more prominent. Bone metastasis typically indicates the terminal stage of various malignant neoplasms. Once identified, it necessitates a comprehensive revision of the initial treatment regime, and palliative care is often the only resort. Given the gravity of the condition, the diagnosis of bone metastasis should be approached with utmost caution. AI techniques are being evaluated for their efficacy in a range of tasks within medical imaging, including object detection, disease classification, region segmentation, and prognosis prediction in medical imaging. These methods offer a standardized solution to the frequently subjective challenge of image interpretation.This subjectivity is most desirable in bone metastasis imaging. This review describes the basic imaging modalities of bone metastasis imaging, along with the recent developments and current applications of AI in the respective imaging studies. These concrete examples emphasize the importance of using computer-aided systems in the clinical setting. The review culminates with an examination of the current limitations and prospects of AI in the realm of bone metastasis imaging. To establish the credibility of AI in this domain, further research efforts are required to enhance the reproducibility and attain robust level of empirical support.

9.
Front Pharmacol ; 14: 1298049, 2023.
Article in English | MEDLINE | ID: mdl-38027025

ABSTRACT

Rodgersia podophylla A. Gray (R. podophylla) is a traditional Chinese medicine with various pharmacological effects. However, its antioxidant and anti-hyperuricemia components and mechanisms of action have not been explored yet. In this study, we first assessed the antioxidant potential of R. podophylla with 2,2-diphenyl-1-picrylhydrazyl (DPPH), 2,2'-azino-bis(3-ethylbenzothiazoline-6-sulfonic acid) (ABTS) and ferric ion reducing antioxidant power (FRAP) assays. The results suggested that the ethyl acetate (EA) fraction of R. podophylla not only exhibited the strongest DPPH, ABTS radical scavenging and ferric-reducing activities, but also possessed the highest total phenolic and total flavonoid contents among the five fractions. After that, the potential superoxide dismutase (SOD) and xanthine oxidase (XOD) ligands from the EA fraction were quickly screened and identified through the bio-affinity ultrafiltration liquid chromatography-mass spectrometry (UF-LC-MS). Accordingly, norbergenin, catechin, procyanidin B2, 4-O-galloylbergenin, 11-O-galloylbergenin, and gallic acid were considered to be potential SOD ligands, while gallic acid, 11-O-galloylbergenin, catechin, bergenin, and procyanidin B2 were recognized as potential XOD ligands, respectively. Moreover, these six ligands effectively interacted with SOD in molecular docking simulation, with binding energies (BEs) ranging from -6.85 to -4.67 kcal/mol, and the inhibition constants (Ki) from 9.51 to 379.44 µM, which were better than the positive controls. Particularly, catechin exhibited a robust binding affinity towards XOD, with a BE value of -8.54 kcal/mol and Ki value of 0.55 µM, which surpassed the positive controls. In conclusion, our study revealed that R. podophylla possessed remarkable antioxidant and anti-hyperuricemia activities and that the UF-LC-MS method is suitable for screening potential ligands for SOD and XOD from medicinal plants.

10.
Article in English | MEDLINE | ID: mdl-37718529

ABSTRACT

BACKGROUND: In recent years, many semiconductor materials with unique band structures have been used as Pt counter electrode (CE) substitutes for dye-sensitized solar cells (DSSCs), which makes the photoelectric properties of DSSCs possible to be modulated by electric field, magnetic field, and light field. In this work, La0.67(Ca Ba)0.33MnO3 (LCBMO) thin film is employed to act as CE in DSSCs. METHOD: The experimental results indicate that short-circuit current density and photoelectric conversion efficiency present better stability when applying an external magnetic field to the DSSCs. Furthermore, both the exchange current density (J0) and limit diffusion current density (Jlim) are largely enhanced by an external magnetic field. J0 increases from -0.51 mA•cm-2 to -0.65 mA•cm-2, and Jlim increases from 0.2 mA•cm-2 to 0.3 mA•cm-2 when applying a magnetic field of 0.25 T. RESULT: The fitting results of the impedance test verify that the magnetic field reduces the value of Rct. CONCLUSION: Both magnetic-field enhancing catalytic activity and CMR effect jointly promote the increase of photocurrent and finally improve the photovoltaic effect in DSSCs.

11.
Adv Sci (Weinh) ; 10(30): e2303414, 2023 Oct.
Article in English | MEDLINE | ID: mdl-37668266

ABSTRACT

Sb2 S3 is rapidly developed as light absorber material for solar cells due to its excellent photoelectric properties. However, the use of the organic hole transport layer of Spiro-OMeTAD and gold (Au) in Sb2 S3 solar cells imposes serious problems in stability and cost. In this work, low-cost molybdenum (Mo) prepared by magnetron sputtering is demonstrated to serve as a back electrode in superstrate structured Sb2 S3 solar cells for the first time. And a multifunctional layer of Se is inserted between Sb2 S3 /Mo interface by evaporation, which plays vital roles as: i) soft loading of high-energy Mo particles with the help of cottonlike-Se layer; ii) formation of surficial Sb2 Se3 on Sb2 S3 layer, and then reducing hole transportation barrier. To further alleviate the roll-over effect, a pre-selenide Mo target and consequentially form a MoSe2 is skillfully sputtered, which is expected to manipulate the band alignment and render an enhanced holes extraction. Impressively, the device with an optimized Mo electrode achieves an efficiency of 5.1%, which is one of the highest values among non-noble metal electrode based Sb2 S3 solar cells. This work sheds light on the potential development of low-cost metal electrodes for superstrate Sb2 S3 devices by carefully designing the back contact interface.

12.
Heliyon ; 9(8): e18776, 2023 Aug.
Article in English | MEDLINE | ID: mdl-37560633

ABSTRACT

Recently GeSe has developed as a promising light harvesting material by enjoying to its optical and electrical features as well as earth-abundant and low-toxic constituent elements. Nevertheless, the power conversion efficiency of GeSe-based solar cells yet lags far behind the Shockley-Queisser limit. In this work, we systematically designed, simulated and analyzed the highly efficient GeSe thin-film solar cells by SCAPS-1D. The influence of thickness and defect density of light harvest material, GeSe/CdS interface defect density, electron transport layer (ETL), electrode work function and hole transport layer (HTL) on the device output are carefully analyzed. By optimizing the parameters (thickness, defect, concentration, work function, ETL and HTL), an impressive PCE of 17.98% is delivered along with Jsc of 37.11 mA/cm2, FF of 75.53%, Voc of 0.61 V. This work offers theoretical guidance for the design of highly efficient GeSe thin film solar cells.

13.
Sensors (Basel) ; 23(12)2023 Jun 15.
Article in English | MEDLINE | ID: mdl-37420792

ABSTRACT

Tungsten heavy alloys (WHAs) are an extremely hard-to-machine material extensively used in demanding applications such as missile liners, aerospace, and optical molds. However, the machining of WHAs remains a challenging task as a result of their high density and elastic stiffness which lead to the deterioration of the machined surface roughness. This paper proposes a brand-new multi-objective dung beetle algorithm. It does not take the cutting parameters (i.e., cutting speed, feed rate, and depth of cut) as the optimization objects but directly optimizes cutting forces and vibration signals monitored using a multi-sensor (i.e., dynamometer and accelerometer). The cutting parameters in the WHA turning process are analyzed through the use of the response surface method (RSM) and the improved dung beetle optimization algorithm. Experimental verification shows that the algorithm has better convergence speed and optimization ability compared with similar algorithms. The optimized forces and vibration are reduced by 9.7% and 46.47%, respectively, and the surface roughness Ra of the machined surface is reduced by 18.2%. The proposed modeling and optimization algorithms are anticipated to be powerful to provide the basis for the parameter optimization in the cutting of WHAs.


Subject(s)
Coleoptera , Tungsten , Animals , Algorithms , Alloys , Feces
14.
Spine J ; 23(9): 1358-1364, 2023 09.
Article in English | MEDLINE | ID: mdl-37209967

ABSTRACT

BACKGROUND CONTEXT: Pedicle screws are widely used in spinal surgeries. Pedicle screw fixation has shown better clinical effects than other techniques by providing steady fixation from the posterior arch to the vertebral body. However, there are several concerns about the impact of pedicle screw instrumentation insertion on vertebral development in young children, including early closure of the neurocentral cartilage (NCC). The effect of pedicle screw insertion in an early age on further growth of the upper thoracic spine is still unclear. PURPOSE: This study aimed to evaluate the impact of pedicle screw insertion on further growth of the upper thoracic vertebra and spinal canal. STUDY DESIGN: A retrospective case study. PATIENT SAMPLE: Twenty-eight patients. OUTCOME MEASUREMENTS: X-ray and CT parameters including length, height and area of the vertebrae and spinal canal were manually measured. METHODS: Twenty-eight patients who underwent pedicle screw fixation (T1-T6) before the age of 5 years from March 2005 to August 2019 at Peking Union Medical College Hospital were recruited, and records were retrospectively reviewed. Vertebral body and spinal canal parameters were measured at instrumented and adjacent noninstrumented levels and compared using statistical methods. RESULTS: Ninety-seven segments met the inclusion criteria (average age at instrumentation 44.57 months, range from 23-60 months). Thirty-nine segments had no screws, and 58 had at least one screw. There was no significant difference between the preoperative and final follow-up values of the measurement of vertebral body parameters. No significant difference was observed between the growth rates in levels with or without screws in pedicle length, vertebral body diameter, or spinal canal parameters. CONCLUSION: Pedicle screw instrumentation in the upper thoracic spine does not cause a negative effect on the development of the vertebral body and spinal canal in children younger than 5 years old.


Subject(s)
Pedicle Screws , Spinal Fusion , Child , Humans , Child, Preschool , Infant , Pedicle Screws/adverse effects , Retrospective Studies , Thoracic Vertebrae/diagnostic imaging , Thoracic Vertebrae/surgery , Spinal Canal , Radiography , Spinal Fusion/methods , Treatment Outcome
15.
Food Chem ; 418: 135950, 2023 Aug 30.
Article in English | MEDLINE | ID: mdl-36989642

ABSTRACT

In recent years, microbial volatile organic compounds (mVOCs) produced by microbial metabolism have attracted more and more attention because they can be used to detect food early contamination and flaws. So far, many analytical methods have been reported for the determination of mVOCs in food, but few integrated review articles discussing these methods are published. Consequently, mVOCs as indicators of food microbiological contamination and their generation mechanism including carbohydrate, amino acid, and fatty acid metabolism are introduced. Meanwhile, a detailed summary of the mVOCs sampling methods such as headspace, purge trap, solid phase microextraction, and needle trap is presented, and a systematic and critical review of the analytical methods (ion mobility spectrometry, electronic nose, biosensor, and so on) of mVOCs and their application in the detection of food microbial contamination is highlighted. Finally, the future concepts that can help improve the detection of food mVOCs are prospected.


Subject(s)
Volatile Organic Compounds , Amino Acids , Electronic Nose , Ion Mobility Spectrometry , Solid Phase Microextraction/methods , Volatile Organic Compounds/analysis , Food Microbiology
16.
Mol Biol Rep ; 50(4): 3493-3502, 2023 Apr.
Article in English | MEDLINE | ID: mdl-36781610

ABSTRACT

BACKGROUND: Water scarcity has become one of the most prevalent environmental factors adversely affecting plant growth and development. Different species have developed multiple ways of drought resistance. Saposhnikovia divaricata is a commonly used traditional herb in East Asia. However, limited information is available on the drought response of this herb and further clarification of underlying molecular mechanism remains a challenge. METHODS AND RESULTS: In this study, a comparative transcriptome analysis was firstly conducted to identify the major pathways and candidate genes involved in the drought adaptive response of S. divaricata. The seedlings of S. divaricata were subjected to progressive drought by withholding water for 16 days followed by 8 days of rehydration. Transcriptome analysis identified a total of 89,784 annotated unigenes. The number of differentially expressed genes (DEGs) gradually increased with the deepening of drought and decreased after rehydration. Gene Ontology enrichment analysis and Kyoto Encyclopedia of Genes and Genomes pathway analysis suggested genes related to oxidoreductase activity, carbohydrate metabolism, plant hormone signaling pathway and secondary metabolism were important in drought response of S. divaricata. Specific genes involved in reactive oxygen species scavenging system (POD, Cu/Zn-SOD, APX), abscisic acid and jasmonic acid signaling pathway (PYL4, PP2Cs, JAR1, JAZ) and phenylpropanoid biosynthesis (4CL, CCR, CAD) underwent dynamic alterations under drought and rehydration. Finally, the expression pattern of 12 selected DEGs from the transcriptomic profiling was validated by real-time quantitative PCR. CONCLUSION: Our study laid a foundation for understanding the stress response of S. divaricata and other Apiaceae family plant at molecular level.


Subject(s)
Apiaceae , Transcriptome , Transcriptome/genetics , Droughts , Gene Expression Profiling , Fluid Therapy , Apiaceae/genetics , Gene Expression Regulation, Plant/genetics , Stress, Physiological/genetics
17.
J Cancer Res Clin Oncol ; 149(10): 7895-7903, 2023 Aug.
Article in English | MEDLINE | ID: mdl-36809501

ABSTRACT

BACKGROUND AND PURPOSE: Nucleic acid aptamers are a novel molecular recognition tool that is functionally similar to antibodies but superior to antibodies in terms of thermal stability, structural modification, preparation, and cost, and therefore hold great promise for molecular detection. However, due to the limitations of a single aptamer in molecular detection, the multiple aptamer combination for bioanalysis has received much attention. Here, we reviewed the progress of tumor precision detection based on the combination of multiple nucleic acid aptamers and optical methods and discussed its challenges and prospects. METHODS: The relevant literature in PubMed was collected and reviewed. RESULTS: The combination of two or more aptamers with modern nanomaterials and analytical methods allows the fabrication of various detection systems for the simultaneous detection of different structural domains of a substance and/or different substances, including soluble tumor markers, tumor cell surface and intracellular markers, circulating tumor cells, and other tumor-related biomolecules, which has great potential for application in efficient and precise tumor detection. CONCLUSION: The combination of multiple nucleic acid aptamers provides a new approach for the precise detection of tumors and will play an important role in precision medicine for tumors.


Subject(s)
Aptamers, Nucleotide , Nanostructures , Neoplastic Cells, Circulating , Nucleic Acids , Humans , Nucleic Acids/chemistry , Biomarkers, Tumor/metabolism
18.
EMBO Mol Med ; 15(1): e16373, 2023 01 11.
Article in English | MEDLINE | ID: mdl-36511116

ABSTRACT

The pathological retinal angiogenesis often causes blindness. Current anti-angiogenic therapy for proliferative retinopathy targets the vascular endothelial growth factor (VEGF), but many patients do not radically benefit from this therapy. Herein, we report that circulating prostaglandin (PG) F2α metabolites were increased in type 2 diabetic patients with proliferative retinopathy, and the PGF2α receptor (Ptgfr) was upregulated in retinal endothelial cells (ECs) from a mouse model of oxygen-induced retinopathy (OIR). Further, disruption of the PTGFR receptor in ECs attenuated OIR in mice. PGF2α promoted the proliferation and tube formation of human retinal microvascular endothelial cells (HRMECs) via the release of ELR+ CXC chemokines, such as CXCL8 and CXCL2. Mechanistically, the PGF2α /PTGFR axis potentiated ELR+ CXC chemokine expression in HRMECs through the Gq /CAMK2G/p38/ELK-1/FOS pathway. Upregulated FOS-mediated ELR+ CXC chemokine expression was observed in retinal ECs from PDR patients. Moreover, treatment with PTGFR inhibitor lessened the development of OIR in mice in a CXCR2-dependent manner. Therefore, inhibition of PTGFR may represent a new avenue for the treatment of retinal neovascularization, particularly in PDR.


Subject(s)
Chemokines, CXC , Retinal Diseases , Humans , Mice , Animals , Chemokines, CXC/physiology , Endothelial Cells/metabolism , Vascular Endothelial Growth Factor A/metabolism , Neovascularization, Pathologic/pathology , Retinal Diseases/pathology , Oxygen , Mice, Inbred C57BL , Placenta Growth Factor
19.
Food Chem ; 404(Pt A): 134515, 2023 Mar 15.
Article in English | MEDLINE | ID: mdl-36240559

ABSTRACT

Andrographis paniculata (Burm. F.) Nees (AP) was a typical plant resource that has the concomitant function of both foodstuff and medicine, while the action mechanisms of its immune regulation, anti-inflammatory and anti-viral effects and the specific components remain unclear. In this work, a screening approach combining bio-affinity ultrafiltration with liquid chromatography mass spectrometry (UF-LC/MS) was hired to screen potential bioactive compounds from AP. The crude extract of AP exerted COX-2 and ACE2 inhibitory effects by other bioassays. Meanwhile, a total of eleven ligands targeting COX-2, IL-6 and ACE2 were screened out. Thereinto, two compounds including andrographolide and 14-deoxy-11,12-didehydroandrographolide exhibited strong binding affinities to COX-2, IL-6 and ACE2 by UF-LC/MS and molecular docking analysis. This is the first report to apply UF-LC/MS approach to rapidly screen out multi-target ligands from AP, and further decipher corresponding mechanisms, which could be beneficial to expedite the search for new multi-target bioactive compounds in other natural products or foods.


Subject(s)
Andrographis , Diterpenes , Andrographis/chemistry , Andrographis/metabolism , Ultrafiltration/methods , Andrographis paniculata , Chromatography, High Pressure Liquid/methods , Cyclooxygenase 2/metabolism , Molecular Docking Simulation , Angiotensin-Converting Enzyme 2 , Interleukin-6 , Plant Extracts/pharmacology , Plant Extracts/chemistry
20.
Sci Bull (Beijing) ; 67(3): 263-269, 2022 Feb 15.
Article in English | MEDLINE | ID: mdl-36546075

ABSTRACT

The use of organic hole transport layer (HTL) Spiro-OMeTAD in various solar cells imposes serious stability and cost problems, and thus calls for inorganic substitute materials. In this work, a novel inorganic MnS film prepared by thermal evaporation has been demonstrated to serve as a decent HTL in high-performance Sb2(S, Se)3 solar cells, providing a cost-effective all-inorganic solution. A low-temperature air-annealing process for the evaporated MnS layer was found to result in a significant positive effect on the power conversion efficiency (PCE) of Sb2(S, Se)3 solar cells, due to its better-matched energy band alignment after partial oxidation. Impressively, the device with the optimized MnS HTL has achieved an excellent PCE of about 9.24%, which is the highest efficiency among all-inorganic Sb2(S, Se)3 solar cells. Our result has revealed that MnS is a feasible substitute for organic HTL in Sb-based solar cells to achieve high PCE, low cost, and high stability.

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