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1.
FASEB J ; 38(11): e23697, 2024 Jun 15.
Article in English | MEDLINE | ID: mdl-38842874

ABSTRACT

Diabetic retinopathy (DR) is characterized by chronic, low-grade inflammation. This state may be related to the heightened production of neutrophil extracellular traps (NETs) induced by high glucose (HG). Human cathelicidin antimicrobial peptide (LL37) is an endogenous ligand of G protein-coupled chemoattractant receptor formyl peptide receptor 2 (FPR2), expressed on neutrophils and facilitating the formation and stabilization of the structure of NETs. In this study, we detected neutrophils cultured under different conditions, the retinal tissue of diabetic mice, and fibrovascular epiretinal membranes (FVM) samples of patients with proliferative diabetic retinopathy (PDR) to explore the regulating effect of LL37/FPR2 on neutrophil in the development of NETs during the process of DR. Specifically, HG or NG with LL37 upregulates the expression of FPR2 in neutrophils, induces the opening of mitochondrial permeability transition pore (mPTP), promotes the increase of reactive oxygen species and mitochondrial ROS, and then leads to the rise of NET production, which is mainly manifested by the release of DNA reticular structure and the increased expression of NETs-related markers. The PI3K/AKT signaling pathway was activated in neutrophils, and the phosphorylation level was enhanced by FPR2 agonists in vitro. In vivo, increased expression of NETs markers was detected in the retina of diabetic mice and in FVM, vitreous fluid, and serum of PDR patients. Transgenic FPR2 deletion led to decreased NETs in the retina of diabetic mice. Furthermore, in vitro, inhibition of the LL37/FPR2/mPTP axis and PI3K/AKT signaling pathway decreased NET production induced by high glucose. These results suggested that FPR2 plays an essential role in regulating the production of NETs induced by HG, thus may be considered as one of the potential therapeutic targets.


Subject(s)
Antimicrobial Cationic Peptides , Cathelicidins , Diabetic Retinopathy , Extracellular Traps , Mice, Inbred C57BL , Neutrophils , Receptors, Formyl Peptide , Diabetic Retinopathy/metabolism , Diabetic Retinopathy/pathology , Extracellular Traps/metabolism , Animals , Receptors, Formyl Peptide/metabolism , Receptors, Formyl Peptide/genetics , Humans , Neutrophils/metabolism , Mice , Antimicrobial Cationic Peptides/metabolism , Male , Receptors, Lipoxin/metabolism , Receptors, Lipoxin/genetics , Diabetes Mellitus, Experimental/metabolism , Signal Transduction , Reactive Oxygen Species/metabolism , Female , Middle Aged
2.
Environ Res ; 241: 117639, 2024 Jan 15.
Article in English | MEDLINE | ID: mdl-37972811

ABSTRACT

In this study, CuFe2O4/CuS composite photocatalysts were successfully synthesized for the activation of peroxynomosulfate to remove ciprofloxacin from wastewater. The structural composition and morphology of the materials were analyzed by XRD, SEM, TEM, and Raman spectroscopy. The electrochemical properties of the samples were tested by an electrochemical workstation. The band gap of the samples was calculated by DFT and compared with the experimental values. The effects of different catalysts, oxidant PMS concentrations, and coexisting ions on the experiments were investigated. The reusability and stability of the photocatalysts were also investigated. The mechanism of the photocatalytic degradation process was proposed based on the free radical trapping experiment. The results show that the p-p heterojunction formed between the two contact surfaces of the CuFe2O4 nanoparticle and CuS promoted the charge transfer between the interfaces and inhibited the recombination of electrons and holes. CuFe2O4-5/CuS photocatalyst has the best catalytic activity, and the removal rate of ciprofloxacin is 93.7%. The intermediates in the degradation process were tested by liquid chromatography-mass spectrometry (LC-MS), and the molecular structure characteristics of ciprofloxacin were analyzed by combining with DFT calculations. The possible degradation pathways of pollutants were proposed. This study reveals the great potential of the photocatalyst CuFe2O4/CuS in the activation of PMS for the degradation of ciprofloxacin wastewater.


Subject(s)
Wastewater , Water Pollutants, Chemical , Peroxides/chemistry , Ciprofloxacin , Water Pollutants, Chemical/chemistry , Oxidants
3.
J Sci Food Agric ; 104(10): 5660-5674, 2024 Aug 15.
Article in English | MEDLINE | ID: mdl-38415843

ABSTRACT

Zinc, a crucial trace element is vital for the growth and development of humans. It is frequently described as 'the flower of life' and 'the source of intelligence'. Zinc supplements play a pivotal role in addressing zinc deficiency by serving as a vital source of this essential micronutrients, effectively replenishing depleted zinc levels in the body. In this paper, we first described the biological behavior of zinc in the human body and briefly described the physiological phenomena associated with zinc levels. The benefits and drawbacks of various zinc supplement forms are then discussed, with emphasis on the most recent zinc supplement formulations. Finally, the application of zinc supplements in food, medicine, and animal husbandry is further summarized. © 2024 Society of Chemical Industry.


Subject(s)
Dietary Supplements , Zinc , Dietary Supplements/analysis , Zinc/administration & dosage , Animals , Humans , Trace Elements/analysis
4.
Bioorg Chem ; 130: 106259, 2023 01.
Article in English | MEDLINE | ID: mdl-36375351

ABSTRACT

Natural products have been an important database for anti-cancer drug development. However, low water solubility and poor biocompatibility limit the efficacy of natural products. Carbon dots (CDs), as an emerging 0D material, have unique properties in bioimaging, water solubility and biocompatibility. Here, we prepared three pentacyclic triterpenoids (PTs) included glycyrrhetinic acid (GA), ursolic acid (UA) and oleanolic acid (OA), which have anticancer activity but poor water solubility, as raw materials into CDs to improve disadvantages. Our data indicated that the active surface groups of all three CDs were largely preserved and were able to excite green fluorescence. Their carboxyl edges not only exhibited excellent water solubility, but also specifically targeted tumor cell mitochondria due to high sensitivity to ROS-induced damage and high internal oxidative stress. In cancer cells, the PT-CDs induced cell death through three pathways (apoptosis, ferroptosis, and autophagy), which is essentially the same way their raw materials induce death, but the effect was much stronger than raw materials. Notably, functionalized PT-CDs also exhibited extremely low toxicity. In summary, PT-CDs not only have improved water solubility and biocompatibility, but also retain the structure of their raw materials well and exert better efficacy, which provides new ideas for the development of anti-cancer natural product drugs.


Subject(s)
Antineoplastic Agents , Quantum Dots , Triterpenes , Humans , Apoptosis/drug effects , Autophagy/drug effects , Biological Products , Carbon/pharmacology , Carbon/chemistry , Ferroptosis/drug effects , Mitochondria/drug effects , Neoplasms/drug therapy , Triterpenes/pharmacology , Triterpenes/chemistry , Water , Quantum Dots/chemistry , Antineoplastic Agents/chemistry , Antineoplastic Agents/pharmacology , Drug Delivery Systems/methods
5.
J Chem Phys ; 159(21)2023 Dec 07.
Article in English | MEDLINE | ID: mdl-38047515

ABSTRACT

The research and development of absorbing materials with high absorbing capacity, wide effective absorption bandwidth, and lightweight has always been interesting. In this research, a facile hydrothermal method was used to prepare MnFe2O4, and the grain size of MnFe2O4 decreased with increasing hydrothermal temperature. When the size of MnFe2O4 nanoparticles is less than 10 nm, its quantum size effect and surface effect make its electromagnetic microwave absorption performance greatly optimized. When the thickness of MnFe2O4-110 °C is 2.57 mm, the minimum reflection loss (RLmin) is -35.28 dB. Based on this, light porous diatomite and a three-dimensional polyaniline network are introduced. Diatomite is used as the base material to effectively reduce the agglomeration of MnFe2O4 quantum dots. The relatively high surface area introduced by a three-dimensional network of polyaniline promotes the orientation, interfacial polarization, multiple relaxation, and impedance matching, thereby generating further dielectric loss. Additionally, the magnetic properties of manganese ferrite and the strong electrical conductivity of polyaniline play an appropriate complementary role in electromagnetic wave absorption. The RLmin of MnFe2O4/PANI/diatomite is -56.70 dB at 11.12 GHz with an absorber layer thickness of 2.57 mm. The effective frequency bandwidth (RL < -10 dB) ranges from 9.21 to 18.00 GHz. The absorption mechanism indicates that the high absorption intensity is the result of the synergistic effect of impedance matching, conduction losses, polarization losses, and magnetic losses.

6.
Article in English | MEDLINE | ID: mdl-38091059

ABSTRACT

BACKGROUND: To find out the incidence and risk factors of opaque bubble layer (OBL) in eyes with myopia and myopic astigmatism following femtosecond laser-assisted in situ keratomileusis (FS-LASIK) and small incision lenticule extraction (SMILE). METHODS: A total of 1076 eyes from 569 patients who had FS-LASIK or SMILE were included in the retrospective research. For each kind of surgery, eyes were separated into two groups: "OBL" groups and "no OBL" groups. In the FS-LASIK group, eyes that developed OBL were split into "hard OBL" and "soft OBL" groups. The incidence and size of OBL were analyzed after watching the surgical procedure videotaped during the operation and taking screenshots. Surgical parameters, including sphere, cylinder, keratometry, corneal thickness, flap thickness, cap thickness, lenticule thickness, and visual acuity, were compared. RESULTS: In the FS-LASIK surgery, the incidence of OBL was 63.2% (347 eyes). A thicker central corneal thickness (CCT) was the only independent risk factor affecting the OBL area (ß = 0.126, P = 0.019). One hundred and thirty of these eyes had hard OBL, and the flap thickness of these eyes was thinner than that of those with soft OBL (P = 0.027). In the SMILE group, 26.6% (140 eyes) developed OBL. A higher flat keratometry (K) and a thicker residual stromal thickness (RST) were risk factors affecting the OBL area (ß = 0.195, P = 0.024; ß = 0.281, P = 0.001). CONCLUSION: The incidence of OBL differs between the FS-LASIK surgery and the SMILE surgery. There are differences in the factors influencing OBL between the two surgeries.

7.
BMC Ophthalmol ; 23(1): 176, 2023 Apr 24.
Article in English | MEDLINE | ID: mdl-37095443

ABSTRACT

BACKGROUND: To evaluate the prevalence and associated health and lifestyle factors of myopic maculopathy (MM) in a northern Chinese industrial city. METHODS: The cross-sectional Kailuan Eye Study included subjects who participated in the longitudinal Kailuan Study in 2016. Ophthalmologic and general examinations were performed on all the participants. MM was graded based on fundus photographs using the International Photographic Classification and Grading System. The prevalence of MM was evaluated. Univariate and multiple logistic regression were adopted to evaluated risk factors of MM. RESULTS: The study included 8330 participants with gradable fundus photographs for MM and ocular biometry data. The prevalence of MM was 1.11% (93/8330; 95% confidence interval [CI] 0.89-1.33%). Diffuse chorioretinal atrophy, patchy chorioretinal atrophy, macular atrophy, and plus lesions were observed in 72 (0.9%), 15 (0.2%), 6 (0.007%), and 32 eyes (0.4%), respectively. MM was more common in eyes with longer axial length (OR 4.517; 95%CI 3.273 to 6.235) and in participants with hypertension (OR 3.460; 95%CI 1.152 to 10.391), and older age (OR 1.084; 95%CI 1.036 to 1.134). CONCLUSIONS: The MM was present in 1.11% of the northern Chinese individuals 21 years or older and the associate factors include longer axial length, older age, and hypertension.


Subject(s)
Macular Degeneration , Myopia, Degenerative , Retinal Degeneration , Retinal Diseases , Humans , Visual Acuity , Prevalence , Cross-Sectional Studies , China/epidemiology , Life Style , Atrophy
8.
Phytother Res ; 2023 Jun 16.
Article in English | MEDLINE | ID: mdl-37326338

ABSTRACT

Cancer cells consume considerable glucose quantities and majorly employ glycolysis for ATP generation. This metabolic signature (the Warburg effect) allows cancer cells to channel glucose to biosynthesis to support and maintain their dramatic growth along with proliferation. Currently, our understanding of the metabolic and mechanistic implications of the Warburg effect along with its relationship with biosynthesis remains unclear. Herein, we illustrate that the tumor repressor p53 mediate Magnolol (MAG) triggers colon cancer cell apoptosis. And MAG regulates the glycolytic and oxidative phosphorylation steps through transcriptional modulation of its downstream genes TP53-induced glycolysis modulator and biosynthesis of cytochrome c oxidase, attenuating cell proliferation and tumor growth in vivo and in vitro. Meanwhile, we show that MAG cooperates with its own intestinal microflora characteristic metabolites to repress tumors, especially remarkably declined kynurenine (Kyn)/tryptophan (Trp) ratio. Besides, strong relationships of MAG influenced genes, microbiota, as well as metabolites, were explored. Therefore, we established that p53-microbiota-metabolites function as a mechanism, which enable therapy approaches against metabolism-implicated colorectal cancer, in particular MAG as a prospective candidate for treating colorectal cancer.

9.
Pharmacol Res ; 181: 106257, 2022 07.
Article in English | MEDLINE | ID: mdl-35569708

ABSTRACT

Cardiac fibrosis is a pathogenic factor of many cardiovascular diseases (CVD), which seriously affects people's life and health, causing huge economic losses.Therefore, it is very significant to find an effective treatment for myocardial fibrosis. Adipokines are mainly derived from adipose tissue and have an prominent regulatory effect on glucose and lipid metabolism, inflammation, immune response and cardiovascular function. Adipose tissue is composed of a variety of cell types, including adipocytes, endothelial cells, macrophages and smooth muscle cells. Adipokines mainly include adiponectin, leptin, resistin, visfatin and omentin, which are synthesized and secreted by adipocytes. More and more evidence shows that adipokines can regulate the progress of cardiac fibrosis. This scientific review provides new ideas for targeting adipokines in the treatment of myocardial fibrosis and provides strategies for the development of new, safe, and effective pharmacological antagonists against myocardial fibrosis based on adipokines activity.


Subject(s)
Adipokines , Endothelial Cells , Adipokines/metabolism , Adiponectin/metabolism , Adipose Tissue/metabolism , Endothelial Cells/metabolism , Fibrosis , Humans , Leptin , Obesity/metabolism
10.
Pharmacol Res ; 177: 106013, 2022 03.
Article in English | MEDLINE | ID: mdl-34856333

ABSTRACT

Ferroptosis is a type of lipid peroxidation-induced cell death that can be regulated in various ways, from changing the activity of antioxidant enzymes to the levels of transcription factors. The p53 tumor suppressor gene is the "guardian of the genome" and is involved in controlling cell survival and division under various pressures. In addition to its effects on apoptosis, autophagy, and cell cycle, p53, through the way of transcription dependent or independent two-way, also regulates the biological processes of tumor cell sensitivity to ferroptosis, including the metabolism of amino acids, nicotinamide adenine dinucleotide phosphate, and lipid peroxidation, as well as the biosynthesis of glutathione, phospholipids, NADPH and coenzyme Q10. As reviewed here, we summarized the metabolic network of p53 and its signaling pathway in regulating ferroptosis and elucidated possible factors and potential clinical application of p53 regulating ferroptosis. This review will provide a basis for further understanding the role of p53 in tumor ferroptosis and new strategies for cancer therapeutic avenues.


Subject(s)
Ferroptosis , Neoplasms , Apoptosis , Humans , Lipid Peroxidation , NADP/metabolism , Neoplasms/drug therapy , Neoplasms/genetics , Neoplasms/metabolism , Tumor Suppressor Protein p53/genetics , Tumor Suppressor Protein p53/metabolism
11.
J Nanobiotechnology ; 20(1): 485, 2022 Nov 19.
Article in English | MEDLINE | ID: mdl-36402976

ABSTRACT

Currently, tumor treatments are characterized by intelligence, diversity and personalization, but the therapeutic reagents used are often limited in clinical efficacy due to problems with water solubility, targeting, stability and multidrug resistance. To remedy these shortcomings, the application of multifunctional nanotechnology in the biomedical field has been widely studied. Synthetic melanin nanoparticles (MNPs) surfaces which contain highly reactive chemical groups such as carboxyl, hydroxyl and amine groups, can be used as a reaction platform on which to graft different functional components. In addition, MNPs easily adhere to substrate surface, and serve as a secondary reaction platform to modify it. The multifunctionality and intrinsic biocompatibility make melanin-like nanoparticles promising as a multifunctional and powerful nanoplatform for oncological applications. This paper first reviews the preparation methods, polymerization mechanisms and physicochemical properties of melanin including natural melanin and chemically synthesized melanin to guide scholars in MNP-based design. Then, recent advances in MNPs especially synthetic polydopamine (PDA) melanin for various medical oncological applications are systematically and thoroughly described, mainly focusing on bioimaging, photothermal therapy (PTT), and drug delivery for tumor therapy. Finally, based on the investigated literature, the current challenges and future directions for clinical translation are reasonably discussed, focusing on the innovative design of MNPs and further elucidation of pharmacokinetics. This paper is a timely and comprehensive and detailed study of the progress of MNPs in tumor therapy, especially PTT, and provides ideas for the design of personalized and customizable oncology nanomedicines to address the heterogeneity of the tumor microenvironment.


Subject(s)
Nanoparticles , Neoplasms , Humans , Melanins/chemistry , Photothermal Therapy , Nanoparticles/therapeutic use , Nanoparticles/chemistry , Nanomedicine , Neoplasms/drug therapy , Tumor Microenvironment
12.
Pharmacol Res ; 170: 105756, 2021 08.
Article in English | MEDLINE | ID: mdl-34237440

ABSTRACT

Chronic Cerebral Hypoperfusion(CCH)-induced vascular dementia(VD) is a common neurodegenerative disease which seriously affects the patient's quality of life. Therefore, it is critical to find an effective treatment of VD. Autophagy is a natural regulated mechanism that can remove dysfunctional proteins and organelles, however, over-activation or under-activation can of autophagy can induce the apoptosis of cells. Although autophagy plays a role in the central nervous system is unquestionable, the effects of autophagy in the ischemic brain are still controversial. Some autophagy regulators have been tested, suggesting that both activation and inhibition of autophagy can improve the cognitive function. This article reviews the role of autophagy in CCH-induced VD to discuss whether autophagy has the potential to become a target for drug development and provides several potential compounds for treating vascular dementia.


Subject(s)
Autophagy/drug effects , Biological Products/therapeutic use , Brain/drug effects , Dementia, Vascular/drug therapy , Animals , Apoptosis/drug effects , Apoptosis Regulatory Proteins/metabolism , Autophagy-Related Proteins/metabolism , Biological Products/adverse effects , Brain/metabolism , Brain/pathology , Cerebrovascular Circulation , Dementia, Vascular/metabolism , Dementia, Vascular/pathology , Dementia, Vascular/physiopathology , Humans , Signal Transduction
13.
Pak J Pharm Sci ; 32(3 Special): 1415-1418, 2019 May.
Article in English | MEDLINE | ID: mdl-31551223

ABSTRACT

To evaluate the clinical efficacy of combined therapy of Zushima tablet and western medicine in treatment of rheumatoid arthritis and analyze the MRI test results. A total of 170 patients who had been treated for rheumatoid arthritis at our hospital from August 2016 and June 2018, were enrolled as research objects. They were randomly divided into control group and research group, with 85 patients in each group. The patients in the control group were treated with western medicine, while patients in the research group were treated with combined therapy of Zushima tablet and western medicine. The clinical efficacies of two groups were compared. results showed that the overall effective rate of the research group was higher than that of the control group (p<0.05). Various clinical symptoms including joint swelling, joint tenderness, duration of morning stiffness for both groups before and after treatment were recorded, and results showed that the improvement of the research group was significantly better than that of the control group (p<0.05). Application of combined therapy of Zushima tablet and western medicine in treatment of rheumatoid arthritis could lead to favorable effects and improvement of the patients' clinical symptoms.


Subject(s)
Antirheumatic Agents/therapeutic use , Arthritis, Rheumatoid/drug therapy , Drugs, Chinese Herbal/therapeutic use , Adult , Arthritis, Rheumatoid/diagnostic imaging , Female , Humans , Magnetic Resonance Imaging , Male , Methotrexate/therapeutic use , Middle Aged , Naproxen/therapeutic use , Prednisolone/therapeutic use , Sulfasalazine/therapeutic use , Tablets , Treatment Outcome , Western World
14.
Bioorg Med Chem Lett ; 28(7): 1257-1261, 2018 04 15.
Article in English | MEDLINE | ID: mdl-29534926

ABSTRACT

A novel series of N-aryl-N'-pyrimidin-4-yl ureas has been optimized to afford potent and selective inhibitors of the EGFR L858R/T790M. The most representative compound 28 showed high activity against EGFR L858R/T790M kinase (IC50 = 4 nM) and 22-fold selectivity against wild type EGFR. Moreover, compound 28 potently inhibited EGFR L858R/T790M phosphorylation (IC50 = 41 nM) and cellular proliferation (IC50 = 37 nM) in the H1975 cell line, while being significantly less toxic to A431 cells. Further, compound 28 exhibited a great selectivity in a mini-panel of kinases.


Subject(s)
Antineoplastic Agents/pharmacology , Drug Discovery , Protein Kinase Inhibitors/pharmacology , Urea/pharmacology , Antineoplastic Agents/chemical synthesis , Antineoplastic Agents/chemistry , Cell Line, Tumor , Cell Proliferation/drug effects , Dose-Response Relationship, Drug , Drug Screening Assays, Antitumor , ErbB Receptors/antagonists & inhibitors , ErbB Receptors/genetics , ErbB Receptors/metabolism , Humans , Molecular Docking Simulation , Molecular Structure , Mutation , Phosphorylation/drug effects , Protein Kinase Inhibitors/chemical synthesis , Protein Kinase Inhibitors/chemistry , Structure-Activity Relationship , Urea/analogs & derivatives , Urea/chemistry
15.
Zhongguo Zhong Yao Za Zhi ; 42(10): 1825-1829, 2017 May.
Article in Zh | MEDLINE | ID: mdl-29090537

ABSTRACT

Longgu is the fossil of ancient mammals which was used as a common kind of mineral medicine. Longgu is always used to treat neurological diseases. Currently, the quality standard of Longgu is incomplete. Moreover, because of the non-renewable nature of the resource and the increase of national protection of fossils, the clinical application of Longgu is facing a series of problems. As the discovery of the ingredient and the development of forging technology researchers launched to search the substitutes of Longgu. The article summarizes the usage and the study of Longgu, in order that we can discuss the modern usage and substitutability of Longgu.


Subject(s)
Fossils , Mammals , Medicine, Chinese Traditional , Nervous System Diseases/therapy , Animals , Humans , Research
16.
Br J Radiol ; 96(1148): 20220051, 2023 Aug.
Article in English | MEDLINE | ID: mdl-37227804

ABSTRACT

OBJECTIVE: To investigate the correlation between the risk of breast cancer for high-risk females and the density and background parenchymal enhancement (BPE) on contrast-enhanced spectral mammography (CESM). METHODS: Females at high-risk, without breast cancer history and received CESM from July 2016 to December 2017 were retrospectively enrolled. The longest follow-up time was 4.5 years, and patients who developed breast cancer with maximized follow-up time were classified as cancer cohort, while females who did not develop breast cancer were categorized as control cohort. These two cohorts were one-to-one matched in age, family and/or genetic history of breast cancer, menopausal status and BRCA status. The density and BPE at CESM imaging were assessed. Conditional logistic regression was applied to evaluate the relationship between imaging features and breast cancer risk. RESULTS: During the follow-up interval, 90 women at high-risk without history of breast cancer were newly diagnosed. Compared with minimal BPE, increasing BPE levels were associated with the risk of breast cancer among high-risk females in a time interval of 4.5 years (mild: odds ratio [OR]=3.2, p = 0.001; moderate: OR = 4.0, p = 0.002; marked: OR = 11.2, p < 0.001). In addition, females with mild, moderate or marked BPE were four times more likely to be diagnosed with breast cancer than females with minimal BPE in a time interval of 4.5 years (OR = 4.0, p < 0.001). CONCLUSION: Qualitative CESM BPE assessment may be useful in the prediction of breast cancer risk among high-risk females. ADVANCES IN KNOWLEDGE: • Qualitative CESM BPE assessment may be useful in the prediction of breast cancer risk among high-risk women during the follow-up period of 4.5 years. • The significance of breast density as an independent risk factor is not fully established for high-risk women during the follow-up period of 4.5 years.


Subject(s)
Breast Neoplasms , Female , Humans , Breast Neoplasms/diagnostic imaging , Retrospective Studies , Breast/diagnostic imaging , Mammography/methods , Breast Density , Magnetic Resonance Imaging/methods
17.
Phytomedicine ; 109: 154600, 2023 Jan.
Article in English | MEDLINE | ID: mdl-36610144

ABSTRACT

BACKGROUND: There is no doubt that Alzheimer's disease (AD) is one of the greatest threats facing mankind today. Within the next few decades, Acetylcholinesterase inhibitors (AChEIs) will be the most widely used treatment for Alzheimer's disease. The withdrawal of the first generation AChEIs drug Tacrine (TAC)/ Cognex from the market as a result of hepatotoxicity has always been an interesting case study. Rosmarinic acid (RA) is a natural compound of phenolic acids that has pharmacological activity for inhibiting Alzheimer's disease, as well as liver protection. PURPOSE AND STUDY DESIGN: In this study, we determined that RA can reduce the hepatotoxicity of TAC, and both of them act synergistically to inhibit the progression of AD in mice. METHODS: In addition to the wild type mice (WT) group, the 6-month-old APP/PS1 (APPswe/PSEN1dE9) double-transgenic (Tg) mice were randomly divided into 6 groups: Tg group, TAC group, RA group, TAC+Silymarin (SIL) group, TAC+RA-L (Rosmarinic Acid Low Dose) goup and TAC+RA-H (Rosmarinic Acid High Dose) group. A series of experiments were carried out, including open field test, Morris water maze test, Hematoxylin - Eosin (HE) staining, Nissl staining, biochemical analysis, immunofluorescence analysis, western blotting analysis and so on. RESULTS: RA combined with TAC could enter the brain tissue of AD mice, and the combination of drugs could better improve the cognitive behavior and brain pathological damage of AD mice, reduce the expression of A ß oligomer, inhibit the deposition of A ß, inhibit the activity of AChE and enhance the level of Ach in hippocampus. Both in vivo and in vitro experiments showed that RA could alleviate the hepatotoxicity or liver injury induced by TAC. The Western blot analysis of the liver of AD mice showed that RA combined with TAC might inhibit the apoptosis of Bcl-2/Bax, reduce the programmed apoptosis mediated by caspase-3 and reduce the burden of liver induced by TAC, could inhibit the development of liver apoptosis by alleviating the hepatotoxicity of TAC and inhibiting the phosphorylation of JNK. CONCLUSION: The potential drug combination that combines rosmarinic acid with tacrine could reduce tacrine's hepatotoxicity as well as enhance its therapeutic effect on Alzheimer's disease.


Subject(s)
Alzheimer Disease , Chemical and Drug Induced Liver Injury , Mice , Animals , Alzheimer Disease/metabolism , Tacrine/pharmacology , Tacrine/therapeutic use , Acetylcholinesterase/metabolism , Mice, Transgenic , Disease Models, Animal , Amyloid beta-Peptides , Rosmarinic Acid
18.
ACS Appl Mater Interfaces ; 14(2): 2464-2477, 2022 Jan 19.
Article in English | MEDLINE | ID: mdl-35045602

ABSTRACT

Nanomedicine, constructed from therapeutics, presents an advantage in drug delivery for cancer therapies. However, nanocarrier-based treatment systems have problems such as interbatch variability, multicomponent complexity, poor drug delivery, and carrier-related toxicity. To solve these issues, the natural molecule honokiol (HK), an anticancer agent in a phase I clinical trial (CTR20170822), was used to form a self-assembly nanoparticle (SA) through hydrogen bonding and hydrophobicity. The preparation of SA needs no molecular precursors or excipients in aqueous solution, and 100% drug-loaded SA exhibited superior tumor-targeting ability due to the enhanced permeability and retention (EPR) effect. Moreover, SA significantly enhanced the antitumor immunity relative to free HK, and the mechanism has notable selectivity to the p53 pathway. Furthermore, SA exhibited excellent physiological stability and inappreciable toxicity. Taken together, this supramolecular self-assembly strategy provides a safe and "molecular economy" model for rational design of clinical therapies and is expected to promote targeted therapy of HK, especially in colorectal cancer patients with obvious p53 status.


Subject(s)
Antineoplastic Agents, Phytogenic/pharmacology , Biocompatible Materials/pharmacology , Biphenyl Compounds/pharmacology , Colorectal Neoplasms/therapy , Immunotherapy , Lignans/pharmacology , Small Molecule Libraries/pharmacology , Tumor Suppressor Protein p53/antagonists & inhibitors , Animals , Antineoplastic Agents, Phytogenic/chemical synthesis , Antineoplastic Agents, Phytogenic/chemistry , Biocompatible Materials/chemical synthesis , Biocompatible Materials/chemistry , Biphenyl Compounds/chemical synthesis , Biphenyl Compounds/chemistry , Colorectal Neoplasms/immunology , Female , Humans , Lignans/chemical synthesis , Lignans/chemistry , Macromolecular Substances/chemical synthesis , Macromolecular Substances/chemistry , Materials Testing , Mice , Mice, Inbred BALB C , Mice, Nude , Molecular Structure , Neoplasms, Experimental/immunology , Neoplasms, Experimental/therapy , Small Molecule Libraries/chemical synthesis , Small Molecule Libraries/chemistry , Tumor Cells, Cultured , Tumor Suppressor Protein p53/immunology
19.
Biophys J ; 100(6): 1383-91, 2011 Mar 16.
Article in English | MEDLINE | ID: mdl-21402019

ABSTRACT

We identify a connection between the structural features of mass-action networks and the robustness of their steady-state fluxes against rate constant variations. We find that in all positive steady states of so-called injective networks-networks that arise, for example, in metabolic and gene regulation contexts-there are certain firm bounds on the flux control coefficients. In particular, the control coefficient of the flux of a reaction, with respect to variation in its own rate constant, is delimited in a precise way. Moreover, for each pair of reactions, the flux of at least one of them must have a precisely delimited control coefficient with respect to variation in the rate constant of the other. The derived bounds can, however, be violated in noninjective networks, so for them a more pronounced lack of robustness could be exhibited. These results, which indicate a mechanism by which some degree of robustness is induced in the injective setting, also shed light on how robustness might evolve.


Subject(s)
Models, Biological , Models, Chemical , Kinetics , Metabolic Networks and Pathways
20.
Ann Palliat Med ; 10(9): 9398-9405, 2021 Sep.
Article in English | MEDLINE | ID: mdl-34628865

ABSTRACT

BACKGROUND: A peripherally inserted central catheter (PICC) effectively reduces frequent vein punctures in cancer patients. With increasing clinical applications, PICC-associated infections are attracting increasing attention. In this study, we retrospectively analyzed PICC-associated infections in chemotherapy patients treated at our hospital in recent years to identify risk factors for PICC-associated infections and the preventive effect of a self-efficacy intervention program. METHODS: Using a convenience sampling method, we selected 159 cancer patients who received chemotherapy through a PICC at our hospital between July 2017 and December 2018, and the patients were randomly divided to an observation group (n=79) and a control group (n=80) using a random number table. The control group received conventional intervention, and the observation group received a self-efficacy intervention. We analyzed self-efficacy scores before and after the intervention, the complication rate, the infection rate, pathogens identified, and risk factors for PICC-associated infections. RESULTS: Among the 159 chemotherapy patients, 26 (16.35%) experienced PICC-associated infections in this finished trial. Univariate analysis showed that sex, puncture site, and steroid use were unrelated to PICC-associated infections (P>0.05), whereas PICC indwelling time, white blood cell (WBC) count, a history of diabetes, and immunity were significantly related to PICC-associated infections (P<0.05). The self-efficacy score improved after the intervention in both groups, especially in the observation group (P<0.05). The incidence of complications such as catheter infection, catheter blockage, and catheter displacement was significantly lower in the observation group than in the control group (16. 67% vs. 88.10%; P<0.05). CONCLUSIONS: The self-efficacy intervention improves self-management and reduces complications in cancer patients receiving chemotherapy through a PICC. PICC indwelling time, WBC count, a history of diabetes, and immunity are independent risk factors for PICC-associated infections; thus, measures should be implemented to prevent infections. TRIAL REGISTRATION: Chinese Clinical Trial Registry ChiCTR2100050651.


Subject(s)
Catheterization, Central Venous , Self Efficacy , Catheterization, Central Venous/adverse effects , Catheters , Humans , Retrospective Studies , Risk Factors
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