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1.
Br J Clin Psychol ; 62(3): 674-688, 2023 Sep.
Article in English | MEDLINE | ID: mdl-37345385

ABSTRACT

OBJECTIVES: People with autism spectrum disorders (ASD) usually exhibit typical behaviours and thoughts that are called autistic traits. Autistic traits are widely and continuously distributed among typically developed (TD) and ASD populations. Previous studies have found that people with ASD have difficulty in following the eye gaze of social peers. However, it remains unknown whether TD adults with high or low autistic traits also differ in spontaneous gaze following and initiation in face-to-face social interactions. To fill this gap, this study used a novel and naturalistic gaze-cueing paradigm to examine this research question. DESIGN: A 4 (group: high-high, high-low, low-high or low-low autistic traits) × 3 (congruency: congruent, neutral, or incongruent) mixed-measures design was used. METHODS: Typically developed adults who were high or low in autistic traits completed a visual search task while a confederate who was high or low in autistic traits sat facing them. Critically, the match of autistic traits within a participant-confederate pair was manipulated. The confederate gazed at (congruent) or away from (incongruent) the location of the target prior to the appearance of the target. Participants were not explicitly instructed to follow the confederate's gaze. RESULTS: Autistic traits were associated with spontaneous gaze following and initiation in face-to-face social interactions. Specifically, only when both the participant and confederate were low in autistic traits did the incongruent gaze cues of confederates interfere with the participants' responses. CONCLUSIONS: Autistic traits impeded gaze following and initiation by TD adults. This study has theoretical and practical implications regarding autistic trait-induced social deficits and indicates a new approach for social skill interventions.


Subject(s)
Autism Spectrum Disorder , Autistic Disorder , Adult , Humans , Social Interaction , Interpersonal Relations , Fixation, Ocular
2.
Biomacromolecules ; 23(10): 4339-4348, 2022 Oct 10.
Article in English | MEDLINE | ID: mdl-36054822

ABSTRACT

The carboxysome is a protein-based nanoscale organelle in cyanobacteria and many proteobacteria, which encapsulates the key CO2-fixing enzymes ribulose-1,5-bisphosphate carboxylase/oxygenase (Rubisco) and carbonic anhydrase (CA) within a polyhedral protein shell. The intrinsic self-assembly and architectural features of carboxysomes and the semipermeability of the protein shell provide the foundation for the accumulation of CO2 within carboxysomes and enhanced carboxylation. Here, we develop an approach to determine the interior pH conditions and inorganic carbon accumulation within an α-carboxysome shell derived from a chemoautotrophic proteobacterium Halothiobacillus neapolitanus and evaluate the shell permeability. By incorporating a pH reporter, pHluorin2, within empty α-carboxysome shells produced in Escherichia coli, we probe the interior pH of the protein shells with and without CA. Our in vivo and in vitro results demonstrate a lower interior pH of α-carboxysome shells than the cytoplasmic pH and buffer pH, as well as the modulation of the interior pH in response to changes in external environments, indicating the shell permeability to bicarbonate ions and protons. We further determine the saturated HCO3- concentration of 15 mM within α-carboxysome shells and show the CA-mediated increase in the interior CO2 level. Uncovering the interior physiochemical microenvironment of carboxysomes is crucial for understanding the mechanisms underlying carboxysomal shell permeability and enhancement of Rubisco carboxylation within carboxysomes. Such fundamental knowledge may inform reprogramming carboxysomes to improve metabolism and recruit foreign enzymes for enhanced catalytical performance.


Subject(s)
Carbonic Anhydrases , Ribulose-Bisphosphate Carboxylase , Bacterial Proteins/metabolism , Bicarbonates , Carbon/metabolism , Carbon Dioxide/metabolism , Carbonic Anhydrases/metabolism , Hydrogen-Ion Concentration , Organelles/metabolism , Oxygenases/metabolism , Permeability , Protons , Ribulose-Bisphosphate Carboxylase/chemistry , Ribulose-Bisphosphate Carboxylase/metabolism
3.
Anal Chem ; 91(24): 15461-15468, 2019 12 17.
Article in English | MEDLINE | ID: mdl-31710204

ABSTRACT

High-purity cellulose membranes prepared via a green pathway were used to attempt to enhance their performance of glucose detection compared with that of traditional filter paper. In this work, cellulose-based strips (CBS) for the low concentration of glucose detection have been designed based on a fast, sensitive, and easy enzyme colorimetric assay from porous and high-purity cellulose membranes (CM). Different from the traditional paper-based sensors that were made of commercially available filter paper, the cellulose-based membranes matrix was fabricated by a "green" route in that cellulose was dissolved in an aqueous NaOH/urea solution, and then modified by the sodium periodate oxidation method to immobilize the glucose oxidase (GOX) and horseradish peroxidase (HRP) with Schiff-base reaction. The structure and properties of CM and CBS were characterized by scanning electron microscopy (SEM), energy-dispersive X-ray mapping (EDS), Fourier-transform infrared spectroscopy (FT-IR), X-ray photoelectron spectroscopy (XPS), etc. SEM images showed a porous, interpenetrating structure of CM, which benefited the enzyme immobilization and enzymatic reaction. When glucose solution was dropped onto the CBS, the color change from colorless to blue was only 5 min. The limit of detection (LOD) is 0.45 mM in the linear range of glucose from 1 to 11 mM. Moreover, the CBS had also been successfully used for glucose determination in real urine samples, and the color changes can be easily recorded by a simple camera to achieve the semiquantitative detection of glucose. This work provided a new design strategy for the cellulose-based functional materials which could be applied in biosensors, drug carriers, and biomedicine.


Subject(s)
Cellulose/chemistry , Colorimetry/methods , Glucose/chemistry , Reagent Strips , Blood Vessels , Glycosuria , Humans , Molecular Structure , Sensitivity and Specificity , Tears/chemistry
4.
Cell Physiol Biochem ; 52(5): 1178-1192, 2019.
Article in English | MEDLINE | ID: mdl-30990587

ABSTRACT

BACKGROUND/AIMS: Rheumatoid arthritis (RA) is a progressive, chronic, even disabling systemic autoimmune disease. Imbalance between pathogenic immune cells and immunosuppressive cells is associated with the pathogenesis and development of RA and other autoimmune diseases. As Foxp3 is also expressed on activated CD4+ cells in the presence of inflammation, the identification of Treg cells in patients with RA remains a challenge. METHODS: Comprehensive analyses were carried out by Flow cytometry. Expression of Helios, CD226, T cell immunoreceptor with Ig and ITIM domains clinical samples and healthy controls. RESULTS: We have systemically examined three potential markers, Helios, CD226 and TIGIT, that are possibly related to Treg identification, and found that Helios expression on CD4+Foxp3+cells was decreased and negatively correlated with the disease activity of RA patients, while CD226 and TIGIT both showed elevated expression levels in CD4+Foxp3+cells in RA patients and they were not associated with disease activity of RA patients. CONCLUSION: Taken together, our findings indicate that CD4+CD25hiCD127low/-Foxp3+Helios+ may represent the real Treg cell population in patients with RA.


Subject(s)
Antigens, Differentiation, T-Lymphocyte/immunology , Antigens, Differentiation/immunology , Arthritis, Rheumatoid/immunology , Forkhead Transcription Factors/immunology , Ikaros Transcription Factor/immunology , Receptors, Immunologic/immunology , T-Lymphocytes, Regulatory/immunology , Adult , Arthritis, Rheumatoid/pathology , Female , Humans , Male , Middle Aged , T-Lymphocytes, Regulatory/pathology
5.
Bioorg Med Chem Lett ; 28(23-24): 3816-3821, 2018 12 15.
Article in English | MEDLINE | ID: mdl-30342958

ABSTRACT

MMP-2/MMP-8 is established as one of the most important metalloenzymes for targeting cancer. A series of dihydropyrazothiazole derivatives (E1-E18) bearing a salicylaldehyde group linked to Pyrazole ring were designed, synthesized, and evaluated for their pharmacological activity as MMP-2/MMP-8 inhibitors. Among them, compound E17 exhibited most potent inhibitory activity (IC50 = 2.80 µM for MMP-2 and IC50 = 5.6 µM for MMP-8), compared to the positive drug CMT-1 (IC50 = 1.29 µM). Compounds (E1-E18) were scrutinized by CoMFA and CoMSIA techniques of Three-dimensional quant. structure-activity relationship (3D-QSAR), as well as a docking simulation. Moreover, treatment with compound E4 could induce MCF-7 cell apoptosis. Overall, the biological profile of E1-E18 may provide a research basis for the development of new agents against cancer.


Subject(s)
Matrix Metalloproteinase 2/metabolism , Matrix Metalloproteinase 8/metabolism , Matrix Metalloproteinase Inhibitors/chemistry , Matrix Metalloproteinase Inhibitors/pharmacology , Thiazoles/chemistry , Thiazoles/pharmacology , Antineoplastic Agents/chemistry , Antineoplastic Agents/pharmacology , Apoptosis/drug effects , Cell Line , Cell Line, Tumor , Drug Design , Humans , Molecular Docking Simulation , Neoplasms/drug therapy , Neoplasms/enzymology , Pyrazoles/chemistry , Pyrazoles/pharmacology , Quantitative Structure-Activity Relationship
6.
Bioorg Med Chem Lett ; 26(2): 677-683, 2016 Jan 15.
Article in English | MEDLINE | ID: mdl-26652482

ABSTRACT

A series of novel pyrazole-nitroimidazole derivatives had been arranged and evaluated for their EGFR/HER-2 tyrosine kinase inhibitory activity as well as their antiproliferative properties on four kinds of cancer cell lines (MCF-7, Hela, HepG2, B16-F10). The bioassay results showed most of the designed compounds exhibited potential antiproliferation activity, with the IC50 values ranging from 0.13µM to 128.06µM in four tumor cell lines. Among them, compound 5c exhibited remarkable inhibitory activity against EGFR/HER-2 tyrosine kinase with IC50 value of 0.26µM/0.51µM, respectively, comparable to the positive control erlotinib (IC50=0.41µM for HER-2 and IC50=0.20µM for EGFR) and lapatinib (IC50=0.54µM for HER-2 and IC50=0.28µM for EGFR). Molecular modeling simulation studies were performed in order to predict the biological activity of the proposed compounds and activity relationship (SAR) of these pyrazole-nitroimidazole derivatives.


Subject(s)
ErbB Receptors/antagonists & inhibitors , Nitroimidazoles/chemistry , Nitroimidazoles/pharmacology , Protein Kinase Inhibitors/chemistry , Protein Kinase Inhibitors/pharmacology , Receptor, ErbB-2/antagonists & inhibitors , Antineoplastic Agents/chemistry , Antineoplastic Agents/pharmacology , Cell Line, Tumor , Cell Proliferation/drug effects , Drug Design , ErbB Receptors/metabolism , Humans , Molecular Docking Simulation , Neoplasms/drug therapy , Neoplasms/metabolism , Pyrazoles/chemistry , Pyrazoles/pharmacology , Receptor, ErbB-2/metabolism
7.
Phys Chem Chem Phys ; 18(15): 10255-61, 2016 Apr 21.
Article in English | MEDLINE | ID: mdl-27022001

ABSTRACT

Hydrogen production from seawater and solar energy based on photoelectrochemical cells is extremely attractive due to earth-abundance of seawater and solar radiation. Herein, we report the successful fabrication of novel inorganic-organic 2D/2D WO3/g-C3N4 nanosheet arrays (WO3/g-C3N4 NSAs) grown on a FTO substrate via a facile hydrothermal growth and deposition-annealing process, and their application in natural seawater splitting. The results indicate that the WO3/g-C3N4 NSAs exhibit a photocurrent density of 0.73 mA cm(-2) at 1.23 V versus RHE under AM 1.5G (100 mW cm(-2)) illumination, which is 2-fold higher than that of WO3 NSAs. More importantly, the WO3/g-C3N4 NSA photoanode is quite stable during seawater splitting and the photocurrent density does not substantially decrease after continuous illumination for 3600 s. The remarkably enhanced performance originates primarily from the formation of the WO3/g-C3N4 heterojunction between WO3 and g-C3N4 nanosheets, which accelerates charge transfer and separation, and prolongs the lifetime of electrons as demonstrated by EIS and Mott-Schottky analyses. Finally, a possible mechanism for the improved performance was proposed and discussed.

8.
Bioorg Med Chem ; 22(15): 4312-22, 2014 Aug 01.
Article in English | MEDLINE | ID: mdl-24909678

ABSTRACT

A series of 1,3,4-thiadiazol-2-amide derivatives (6a-w) were designed and synthesized as potential inhibitors of tubulin polymerization and as anticancer agents. The in vitro anticancer activities of these compounds were evaluated against three cancer cell lines by the MTT method. Among all the designed compounds, compound 6f exhibited the most potent anticancer activity against A549, MCF-7 and HepG2 cancer cell lines with IC50 values of 0.03 µM, 0.06 µM and 0.05 µM, respectively. Compound 6f also exhibited significant tubulin polymerization inhibitory activity (IC50=1.73 µM), which was superior to the positive control. The obtained results, along with a 3D-QSAR study and molecular docking that were used for investigating the probable binding mode, could provide an important basis for further optimization of compound 6f as a novel anticancer agent.


Subject(s)
Amides/chemistry , Amides/pharmacology , Antineoplastic Agents/chemical synthesis , Tubulin Modulators/chemical synthesis , Tubulin Modulators/pharmacology , Amides/chemical synthesis , Antineoplastic Agents/chemistry , Antineoplastic Agents/pharmacology , Apoptosis/drug effects , Binding Sites , Cell Line, Tumor , Cell Proliferation/drug effects , Crystallography, X-Ray , G2 Phase Cell Cycle Checkpoints/drug effects , Hep G2 Cells , Humans , M Phase Cell Cycle Checkpoints/drug effects , MCF-7 Cells , Molecular Conformation , Molecular Docking Simulation , Protein Structure, Tertiary , Quantitative Structure-Activity Relationship , Tubulin Modulators/chemistry
9.
Water Res ; 254: 121385, 2024 May 01.
Article in English | MEDLINE | ID: mdl-38452525

ABSTRACT

The Yangtze River is the third longest river in the world with more than 6300 km, covering 0.4 billion people. However, the aquatic ecosystem of the Yangtze River has been seriously damaged in the past decades due to a rapid development of economic and industrialization along the coast. In this study, we first established a dataset of fifty elements, including nine common heavy metals (HMs) and forty-one other elements, in the Yangtze River Basin through the collection of historical data from 2000 to 2020, and then analyzed their spatiotemporal distribution characteristics. The results indicated that the Three Gorges Reservoir (TGR), a region formed by the construction of the Three Gorges Dam (TGD), may act as a sink for these elements from upstream regions. The concentrations of seven elements in surface water and 13 elements in sediment obviously increased from the upstream region of the TGR to the TGR. In addition, ten elements in the surface water and 5 elements in the sediments clearly decreased, possibly because of the interception effects of the TGD. On a timescale, Cr obviously tended to migrate from the water phase to the sediment; Pb tended to migrate from the sediment to the water phase. In the ecological risk assessment, all common HMs in surface water were supposed to have negligible risks as protecting 90 % of aquatic organisms; Cd (210.2), Hg (58.0) and As (43.1) in sediment posed high and moderate ecological risks using the methodology of the potential ecological risk index. Furthermore, Hunan Province is at considerable risk according to the sum of the potential risk index (314.8) due to Cd pollution (66.8 %). These fundamental data and results will support follow-up control strategies for elements and policies related to aquatic ecosystem protection in the Yangtze River Basin.


Subject(s)
Metals, Heavy , Water Pollutants, Chemical , Humans , Ecosystem , Rivers , Cadmium/analysis , Retrospective Studies , Environmental Monitoring , Water Pollutants, Chemical/analysis , Geologic Sediments , Metals, Heavy/analysis , Risk Assessment , Water/analysis , China
10.
J Ethnopharmacol ; 321: 117487, 2024 Mar 01.
Article in English | MEDLINE | ID: mdl-38030024

ABSTRACT

ETHNOPHARMACOLOGICAL RELEVANCE: Acute lung injury (ALI) is a life-threatening condition with high morbidity and mortality, underscoring the urgent need for novel treatments. Monochasma savatieri Franch. (LRC) is commonly used clinically to treat wind-heat cold, bronchitis, acute pneumonia and acute gastroenteritis. However, its role in the treatment of ALI and its mechanism of action are still unclear. AIM OF THE STUDY: This study aimed to demonstrate the pharmacological effects and underlying mechanisms of LRC extract, and provide important therapeutic strategies and theoretical basis for ALI. MATERIALS AND METHODS: In this study, a research paradigm of integrated pharmacology combining histopathological analysis, network pharmacology, metabolomics, and biochemical assays was used to elucidate the mechanisms underlaying the effects of LRC extract on LPS-induced ALI in BALB/c mice. RESULTS: The research findings demonstrated that LRC extract significantly alleviated pathological damage in lung tissues and inhibited apoptosis in alveolar epithelial cells, and the main active components were luteolin, isoacteoside, and aucubin. Lung tissue metabolomic and immunohistochemical methods confirmed that LRC extract could restore metabolic disorders in ALI mice by correcting energy metabolism imbalance, activating cholinergic anti-inflammatory pathway (CAP), and inhibiting TLR4/NF-κB signaling pathway. CONCLUSIONS: This study showed that LRC extract inhibited the occurrence and development of ALI inflammation by promoting the synthesis of antioxidant metabolites, balancing energy metabolism, activating CAP and suppressing the α7nAChR-TLR4/NF-κB p65 signaling pathway. In addition, our study provided an innovative research model for exploring the effective ingredients and mechanisms of traditional Chinese medicine. To the best of our knowledge, this is the first report describing the protective effects of LRC extract in LPS-induced ALI mice.


Subject(s)
Acute Lung Injury , Pneumonia , Animals , Mice , NF-kappa B/metabolism , alpha7 Nicotinic Acetylcholine Receptor/metabolism , Toll-Like Receptor 4/metabolism , Lipopolysaccharides/toxicity , Signal Transduction , Acute Lung Injury/chemically induced , Acute Lung Injury/drug therapy , Acute Lung Injury/prevention & control , Lung/pathology , Pneumonia/pathology
11.
Phytomedicine ; 130: 155345, 2024 Jul 25.
Article in English | MEDLINE | ID: mdl-38810555

ABSTRACT

BACKGROUND: Sepsis causes inflammation in response to infection, often leading to acute lung injury (ALI). Yazhicao (Commelina communis L., YZC) is widely distributed in the global tropics and has good anti-respiratory inflammatory activity; however, the protection of YZC against septic-ALI has not been established. PURPOSE: The role of YZC in septic-ALI will be investigated in this study. METHODS AND RESULTS: In this study, YZC was shown to inhibit excessive inflammation and alleviate septic-ALI. Network pharmacology predicts that Quercetin, Acacetin and Diosmetin have the potential to serve as the pharmacological substance basis of YZC in alleviating septic-ALI. The metabolomics results indicated that YZC could improve the metabolic disorders caused by septic-ALI, which were mostly concerned with energy metabolism and amino acid metabolism, with Trimethylamine (TMA)/Trimethylamine N-oxide (TMAO) being potential small molecule metabolic markers for the clinical diagnosis and treatment of septic-ALI. YZC inhibits the initiation and progression of septic-ALI by controlling the TMA/TMAO metabolites. Our results also suggest that YZC protects the intestinal barrier from damage. Furthermore, our research indicated that YZC reduces TMAO synthesis by inhibiting TMA production through remodeling the intestine microbiota. We investigated the mechanism of YZC-mediated protection against septic-ALI and showed that YZC reduced the expression of proteins associated with NLRP3 inflammatory vesicles in the lung by inhibiting the expression of NF-κB. CONCLUSION: These results show that YZC inhibits the NF-κB/NLRP3 signaling pathway by regulating metabolic and intestinal flora disorders in septic-ALI mice to reduce TMAO synthesis. This study presents a theoretical groundwork for the advancement of novel medications and clinical use of YZC to enhance septic-ALI and furnishes a theoretical rationale for regulating intestinal microbiota as a therapeutic instrument to treat sepsis and septic-ALI.


Subject(s)
Acute Lung Injury , Gastrointestinal Microbiome , Metabolomics , Methylamines , NLR Family, Pyrin Domain-Containing 3 Protein , Sepsis , Signal Transduction , Animals , Gastrointestinal Microbiome/drug effects , NLR Family, Pyrin Domain-Containing 3 Protein/metabolism , Signal Transduction/drug effects , Male , Sepsis/drug therapy , Methylamines/metabolism , Mice , Acute Lung Injury/drug therapy , Acute Lung Injury/metabolism , Mice, Inbred C57BL , Plant Extracts/pharmacology , Disease Models, Animal , Network Pharmacology
12.
J Ethnopharmacol ; 332: 118358, 2024 Oct 05.
Article in English | MEDLINE | ID: mdl-38763370

ABSTRACT

ETHNOPHARMACOLOGICAL RELEVANCE: The incidence of skin trauma is high and the repair process is complex, often leading to poor healing and other issues, which can result in significant economic and social burdens. Traditional Chinese medicine (TCM) is a valuable resource with proven effectiveness and safety in wound repair, widely utilized in clinical practice. A systematic analysis of wound healing with a focus on TCM research progress holds both academic and clinical importance. AIM OF THE REVIEW: This article reviews the research progress of TCM in promoting wound healing, and provides basic data for the development of innovative drugs that promote wound healing. MATERIALS AND METHODS: This article provides a review of the literature from the past decade and conducts a thorough analysis of various databases that contain reports on the use of TCM for wound repair. The data for this systematic research was gathered from electronic databases including CNKI, SciFinder, and PubMed. The study explores and summarizes the research findings and patterns by creating relevant charts. RESULTS: This study reviewed the mechanism of wound healing, experimental TCM methods to promote wound healing, the theory and mode of action of TCM to promote wound healing, the active ingredients of TCM that promote wound healing, the efficacy of TCM formulae to promote wound healing, and the potential toxicity of TCM and its antidotes. This study enriched the theory of TCM in promoting wound healing. CONCLUSION: Skin wound healing is a complex process that can be influenced by various internal and external factors. This article offers a theoretical foundation for exploring and utilizing TCM resources that enhance wound repair. By analyzing a range of TCM that promote wound healing, the article highlights the clinical importance and future potential of these medicines in promoting wound healing.


Subject(s)
Drugs, Chinese Herbal , Medicine, Chinese Traditional , Wound Healing , Wound Healing/drug effects , Humans , Medicine, Chinese Traditional/methods , Animals , Drugs, Chinese Herbal/pharmacology , Drugs, Chinese Herbal/therapeutic use
13.
J Ethnopharmacol ; 324: 117736, 2024 Apr 24.
Article in English | MEDLINE | ID: mdl-38242219

ABSTRACT

ETHNOPHARMACOLOGICAL RELEVANCE: The genus Physalis L. (Solanaceae) is commonly used in the treatment of dermatitis, leprosy, bronchitis, pneumonia, hepatitis and rheumatism in China and other Asian countries. AIM OF THE REVIEW: This article reviews the resources, cultivation, phytochemistry, pharmacological properties, and applications of Physalis L., and proposes further research strategies to enhance its therapeutic potential in treating various human diseases. MATERIALS AND METHODS: We conducted a systematic search of electronic databases, including CNKI, SciFinder and PubMed, using the term "Physalis L." to collect information on the resources, phytochemistry, pharmacological activities, and applications of Physalis L. in China during the past ten years (2013.1-2023.1). RESULTS: So far, a variety of chemical constituents have been isolated and identified from Physalis L. mainly including steroids, flavonoids, and so on. Various pharmacological activities were evaluated by studying different extracts of Physalis L., these activities include anti-inflammatory, antibacterial, antioxidant, antiviral, antineoplastic, and other aspects. CONCLUSION: Physalis L. occupies an important position in the traditional medical system. It is cost-effective and is a significant plant with therapeutic applications in modern medicine. However, further in-depth studies are needed to determine the medical use of this plant resources and cultivation, chemical composition, pharmacological effects and applications.


Subject(s)
Physalis , Humans , Physalis/chemistry , Medicine, Traditional , Phytotherapy , Medicine, Chinese Traditional , Anti-Inflammatory Agents/pharmacology , Anti-Inflammatory Agents/therapeutic use , Phytochemicals/pharmacology , Phytochemicals/therapeutic use , Plant Extracts/pharmacology , Plant Extracts/therapeutic use , Plant Extracts/chemistry , Ethnopharmacology
14.
J Ethnopharmacol ; 319(Pt 3): 117250, 2024 Jan 30.
Article in English | MEDLINE | ID: mdl-37832811

ABSTRACT

ETHNOPHARMACOLOGICAL RELEVANCE: Based on the theory of traditional Chinese medicine (TCM), diabetic cardiomyopathy (DCM) belongs to the category of "Xiaoke disease" according to the symptoms, and "stasis-heat" is the main pathogenesis of DCM. The Chinese medicine Anemarrhena asphodeloides Bunge (AAB), as a representative of heat-clearing and engendering fluid, is often used clinically in the treatment of DCM. Anemarrhena asphodeloides Bunge total saponins (RATS) are the main bioactive components of AAB, the modern pharmacologic effects of RATS are anti-inflammatory, hypoglycemic, and cardioprotective. However, the potential protective mechanisms of RATS against DCM remain largely undiscovered. AIM OF THE STUDY: The primary goal of this study was to explore the effect of RATS on DCM and its mechanism of action. MATERIALS AND METHODS: Streptozotocin and a high-fat diet were used to induce DCM in rats. UHPLC/Q-TOF-MS was used to determine the chemical components of RATS. The degenerative alterations and apoptotic cells in the heart were assessed by HE staining and TUNEL. Network pharmacology was used to anticipate the probable targets and important pathways of RATS. The alterations in metabolites and main metabolic pathways in heart tissue were discovered using 1 H-NMR metabolomics. Ultimately, immunohistochemistry was used to find critical pathway protein expression. RESULTS: First of all, UHPLC/Q-TOF-MS analysis showed that RATS contained 11 active ingredients. In animal experiments, we found that RATS lowered blood glucose and lipid levels in DCM rats, and alleviated cardiac pathological damage, and decreased cardiomyocyte apoptosis. Furthermore, the study found that RATS effectively reduced inflammatory factor release and the level of oxidative stress. Mechanistically, RATS downregulated the expression levels of PI3K, AKT, HIF-1α, LDHA, and GLUT4 proteins. Additionally, glycolysis was discovered to be a crucial pathway for RATS in the therapy of DCM. CONCLUSIONS: Our findings suggest that the protective effect of RATS on DCM may be attributed to the inhibition of the PI3K/AKT/HIF-1α pathway and the correction of glycolytic metabolism.


Subject(s)
Anemarrhena , Diabetes Mellitus , Diabetic Cardiomyopathies , Saponins , Animals , Diabetic Cardiomyopathies/drug therapy , Proto-Oncogene Proteins c-akt/metabolism , Phosphatidylinositol 3-Kinases/metabolism , Anemarrhena/chemistry , Saponins/pharmacology , Saponins/therapeutic use , Saponins/chemistry , Glycolysis
15.
Int J Pharm ; 646: 123459, 2023 Nov 05.
Article in English | MEDLINE | ID: mdl-37778513

ABSTRACT

Cancer is a significant public health problem in the world. The treatment methods include surgery, chemotherapy, phototherapy, and immunotherapy. Due to their respective limitations, the treatment effect is often unsatisfactory, laying hidden dangers for metastasis and recurrence. Since their exceptional biocompatibility and excellent targeting capabilities, hyaluronic acid-based biomaterials have generated great interest as drug delivery methods for tumor therapy. Moreover, modified HA can self-assemble into hydrogels or nanoparticles (NPs) for precise drug administration. This article summarizes the application of HA-based NPs in combination therapy. Ultimately, it is anticipated that this research will offer guidance for creating various HA-based NPs utilized in numerous cancer therapies.


Subject(s)
Nanoparticles , Neoplasms , Hyaluronic Acid , Cell Line, Tumor , Combined Modality Therapy , Nanoparticles/therapeutic use , Drug Delivery Systems/methods , Neoplasms/drug therapy
16.
Polymers (Basel) ; 15(21)2023 Oct 26.
Article in English | MEDLINE | ID: mdl-37959912

ABSTRACT

Deep eutectic solvents (DESs) are promising for lignin dissolution and extraction. However, they usually possess high polarity and are difficult to recycle. To overcome this drawback, a variety of switchable ionic liquids (SILs) composed of 1,8-diazabicyclo[5.4.0]undec-7-ene (DBU) and alcohols was synthesized and screened. According to the thermodynamic modeling suggestions, the selected DBU-HexOH SIL was coupled with hydrogen-bond donors to form switchable-DES (SDES) systems with moderated viscosity, conductivity, and pH while maintaining switchability. The SDESs produced a well-improved lignin and lignin model compound solubility compared with those of SILs; charging CO2 into SDES (SDESCO2) caused a further increase in solubility. The solubility (25 °C) of syringic acid, ferulic acid, and milled wood lignin in SDESCO2 reached 230.57, 452.17, and 279.12 mg/g, respectively. Such SDES-dissolved lignin can be regenerated using acetone as an anti-solvent. The SDES-regenerated lignin exhibited a well-preserved structure with no noticeable chemical modifications. Furthermore, the SDESCO2 lignin possessed a higher molecular weight (Mw = 10,340 g/mol; Mn = 7672 g/mol), improved uniformity (polydispersity index = 1.35), and a higher guaiacyl lignin unit content compared with the original milled wood lignin. The SDES system proposed in the present work could benefit the fractionation of lignin compounds and facilitate downstream industrial processes.

17.
ACS Appl Mater Interfaces ; 15(10): 12631-12642, 2023 Mar 15.
Article in English | MEDLINE | ID: mdl-36867458

ABSTRACT

It is very important to establish a sustained-release pralidoxime chloride (2-PAM) drug system with brain targeting function for the treatment of neurotoxicant poisoning. Herein, Vitamin B1 (VB1), also known as thiamine, which can specifically bind to the thiamine transporter on the surface of the blood-brain barrier, was incorporated onto the surface of MIL-101-NH2(Fe) nanoparticles with a size of ∼100 nm. Pralidoxime chloride was further loaded within the interior of the above resulted composite by soaking, and a resulting composite drug (denoted as 2-PAM@VB1-MIL-101-NH2(Fe)) with a loading capacity of 14.8% (wt) was obtained. The results showed that the drug release rate of the composite drug was increased in PBS solution with the increase of pH (2-7.4) and a maximum drug release rate of 77.5% at pH 4. Experiments on the treatment of poisoning by gavage with the nerve agent sarin in mice combined with atropine revealed that sustained release of 2-PAM from the composite drug was achieved for more than 72 h. Sustained and stable reactivation of poisoned acetylcholinesterase (AChE) was observed with an enzyme reactivation rate of 42.7% in the ocular blood samples at 72 h. By using both zebrafish brain and mouse brain as models, we found that the composite drug could effectively cross the blood-brain barrier and restore the AChE activity in the brain of poisoned mice. The composite drug is expected to be a stable therapeutic drug with brain targeting and prolonged drug release properties for nerve agent intoxication in the middle and late stages of treatment.


Subject(s)
Cholinesterase Reactivators , Nerve Agents , Poisoning , Animals , Mice , Acetylcholinesterase/metabolism , Blood-Brain Barrier/metabolism , Cholinesterase Inhibitors , Oximes , Zebrafish/metabolism , Iron
18.
Biomater Adv ; 152: 213504, 2023 Sep.
Article in English | MEDLINE | ID: mdl-37331244

ABSTRACT

As a natural polymer with good biocompatibility, gelatin hydrogel has been widely used in the field of biomedical science for a long time. However, the lack of suitable gelation temperature and mechanical properties often limit the clinical applicability in diverse and complex environments. Here, we proposed a strategy based on the Hofmeister effect that gelatin hydrogels were soaked in the appropriate concentration of sodium sulfate solution, and the change in molecular chain interactions mainly guided by kosmotropic ions resulted in a comprehensive adjustment of multiple properties. A series of gelatin hydrogels treated with different concentrations of the salt solution gave rise to microstructural changes, which brought a decrease in the number and size of pores, a wide range of gelation temperature from 32 °C to 46 °C, a stress enhancement of about 40 times stronger to 0.8345 MPa, a strain increase of about 7 times higher to 238.05 %, and a certain degree of electrical conductivity to be utilized for versatile applications. In this regard, for example, we prepared microneedles and obtained a remarkable compression (punctuation) strength of 0.661 N/needle, which was 55 times greater than those of untreated ones. Overall, by integrating various characterizations and suggesting the corresponding mechanism behind the phenomenon, this method provides a simpler and more convenient performance control procedure. This allowed us to easily modulate the properties of the hydrogel as per the intended purpose, revealing its vast potential applications such as smart sensors, electronic skin, and drug delivery.


Subject(s)
Gelatin , Hydrogels , Gelatin/chemistry , Temperature , Drug Delivery Systems
19.
Dalton Trans ; 52(33): 11526-11534, 2023 Aug 22.
Article in English | MEDLINE | ID: mdl-37540012

ABSTRACT

Regulating the structural and interfacial properties of transition metal phosphides (TMPs) by coupling carbon-based materials with large surface areas to enhance hydrogen evolution reaction (HER) performance presents significant progress for water splitting technology. Herein, we constructed a composite substrate of a three-dimensional porous graphene oxide matrix (3D-GO) embedded in nickel foam (NF) to grow a Co2P electrocatalyst. Well-defined gladiolus-like Co2P nanowire arrays tightly anchored on the substrate show enhanced electrochemical characteristics for the hydrogen evolution reaction (HER) based on the promoting roles of 3D porous reduced GO (3D-rGO) derived from 3D-GO, which promotes the dispersion of active components, improves the rate of electron transfer, and facilitates the transport of water molecules. As a result, the obtained Co2P@3D-rGO/NF electrode exhibits superior HER activity in 1.0 M KOH media, achieving overpotentials of 36.5 and 264.7 mV at current densities of 10 and 100 mA cm-2, respectively. The electrode also has a low Tafel slope of 55.5 mV dec-1, a large electrochemical surface area, and small charge-transfer resistance, further revealing its mechanism of high intrinsic activity. Moreover, the electrode exhibits excellent HER stability and durability without surface morphology and chemical state changes.

20.
J Ethnopharmacol ; 307: 116229, 2023 May 10.
Article in English | MEDLINE | ID: mdl-36773789

ABSTRACT

ETHNOPHARMACOLOGICAL RELEVANCE: Chronic obstructive pulmonary disease (COPD) is the third leading cause of death globally and thus imposes heavy economic burden on patients, their families, and society. Furthermore, COPD seriously affects the quality of life of patients. The concept of "overall regulation" of traditional Chinese medicine (TCM) plays an important role in the prevention and treatment of COPD. AIM OF THE STUDY: The objective of this review is to summarize the TCM theories, experimental methods, TCM extracts, active TCM ingredients, and TCM formulas for the treatment of COPD and reveal the effects and mechanisms of TCM treatments on COPD. MATERIALS AND METHODS: This article reviewed literature on TCM-based treatments for COPD reported from 2016 to 2021. Relevant scientific studies were obtained from databases that included PubMed, China National Knowledge Infrastructure, Web of Science, Google Scholar, The Plant List, ScienceDirect, and SciFinder. RESULTS: This review summarized TCM-based theory, experimental methods, active ingredients, and potential toxicities, the effects of TCM extracts and formulations, and their mechanisms for the treatment of COPD. Most investigators have used in vivo models of cigarette smoke combined with lipopolysaccharide induction in rats and in vitro models of cigarette smoke extract induction. The active ingredients of TCM used for the treatment of COPD in relevant studies were triterpenoids, flavonoids, phenolics, quinones, glycosides, and alkaloids. TCMs commonly used in the treatment of COPD include antipyretic drugs, tonic medicines, anticough medications, and asthma medications. TCM can treat COPD by suppressing inflammation, reducing oxidative stress, inhibiting apoptosis, and improving airway remodeling. CONCLUSIONS: This review enriches the theory of COPD treatments based on TCM, established the clinical significance and development prospects of TCM-based COPD treatments, and provided the necessary theoretical support for the further development of TCM resources for the treatment of COPD.


Subject(s)
Asthma , Drugs, Chinese Herbal , Pulmonary Disease, Chronic Obstructive , Rats , Animals , Medicine, Chinese Traditional , Quality of Life , Pulmonary Disease, Chronic Obstructive/drug therapy , Phytotherapy , Asthma/drug therapy , Drugs, Chinese Herbal/pharmacology
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