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1.
Cell Biochem Funct ; 42(4): e4061, 2024 Jun.
Article En | MEDLINE | ID: mdl-38812287

Curcumin is a strong substance derived from turmeric, a popular spice, renowned for its antioxidant and anti-inflammatory abilities. The study delved deeply into a thorough examination of various sources to evaluate the impact of both regular curcumin and nano-formulated curcumin on elements that impact physical performance, including muscular strain, discomfort, swelling, and oxidative tension. While engaging in exercise, the body experiences a rise in reactive oxygen species and inflammation. As a result, it is important to ensure a proper balance between internal and external sources of antioxidants to maintain stability in the skeletal muscle. Without this balance, there is a risk of muscle soreness, damage, and ultimately, a decline in exercise performance. Curcumin possesses the ability to enhance physical performance and reduce the symptoms of muscle fatigue and injury by virtue of its antioxidative and anti-inflammatory properties. Including curcumin supplements appears to have advantageous effects on various aspects of exercise, such as enhancing performance, assisting with recovery, lessening muscle damage and discomfort, and lowering levels of inflammation and oxidative stress. However, a thorough assessment is necessary to precisely gauge the healing advantages of curcumin in enhancing exercise ability and reducing recovery time.


Antioxidants , Curcumin , Exercise , Curcumin/pharmacology , Curcumin/chemistry , Humans , Antioxidants/pharmacology , Oxidative Stress/drug effects , Animals , Nanoparticles/chemistry , Muscle, Skeletal/drug effects , Muscle, Skeletal/metabolism , Anti-Inflammatory Agents/pharmacology , Anti-Inflammatory Agents/chemistry
2.
Front Pharmacol ; 15: 1366683, 2024.
Article En | MEDLINE | ID: mdl-38495098

Introduction: Depression is a complex psychiatric disorder with substantial societal impact. While current antidepressants offer moderate efficacy, their adverse effects and limited understanding of depression's pathophysiology hinder the development of more effective treatments. Amidst this complexity, the role of neuroinflammation, a recognized but poorly understood associate of depression, has gained increasing attention. This study investigates hydroxytyrosol (HT), an olive-derived phenolic antioxidant, for its antidepressant and anti-neuroinflammatory properties based on mitochondrial protection. Methods: In vitro studies on neuronal injury models, the protective effect of HT on mitochondrial ultrastructure from inflammatory damage was investigated in combination with high-resolution imaging of mitochondrial substructures. In animal models, depressive-like behaviors of chronic restraint stress (CRS) mice and chronic unpredictable mild stress (CUMS) rats were examined to investigate the alleviating effects of HT. Targeted metabolomics and RNA-Seq in CUMS rats were used to analyze the potential antidepressant pathways of HT. Results: HT protected mitochondrial ultrastructure from inflammatory damage, thus exerting neuroprotective effects in neuronal injury models. Moreover, HT reduced depressive-like behaviors in mice and rats exposed to CRS and CUMS, respectively. HT's influence in the CRS model included alleviating hippocampal neuronal damage and modulating cytokine production, mitochondrial dysfunction, and brain-derived neurotrophic factor (BDNF) signaling. Targeted metabolomics in CUMS rats revealed HT's effect on neurotransmitter levels and tryptophan-kynurenine metabolism. RNA-Seq data underscored HT's antidepressant mechanism through the BDNF/TrkB signaling pathways, key in nerve fiber functions, myelin formation, microglial differentiation, and neural regeneration. Discussion: The findings underscore HT's potential as an anti-neuroinflammatory treatment for depression, shedding light on its antidepressant effects and its relevance in nutritional psychiatry. Further investigations are warranted to comprehensively delineate its mechanisms and optimize its clinical application in depression treatment.

3.
Sci Rep ; 14(1): 5353, 2024 Mar 04.
Article En | MEDLINE | ID: mdl-38438493

The development of algorithms and the spread of digital infrastructure have contributed significantly to the productivity of the digital economy. Data has come to be known as the "oil of the digital economy". At the same time, data has begun to participate more deeply in the production activities of the global sports industry chain, and the international discussion on how to protect the rights of sports event data has been increasing. Based on the configurational theory and fuzzy-set qualitative comparative analysis, this study discusses the factors affecting the protection of sports event data rights. The study found three configuration paths for achieving high enterprise data protection effectiveness and two for achieving low enterprise data protection effectiveness. The results of this study provide theoretical support for governments to address the issue of sports event data rights. They will also facilitate the safe use of data in sports, promote the global sports industry and humanitarian action development, and contribute to international sustainable development.

4.
PLoS One ; 18(11): e0292914, 2023.
Article En | MEDLINE | ID: mdl-37971991

The amount of data in the globe is increasing at an exponential rate, and the role of digital technology and data elements in the modern growth of China's sports business is becoming more significant. Disputes over sports data rights have grown in the international arena, with a special focus on how to preserve the sports data rights of key stakeholders. This study begins from the standpoint of stakeholders, constructs a tripartite evolutionary game model of the government, sports enterprises, and the public around the issue of sports data rights protection, investigates the behavioral evolutionary characteristics of each stakeholder and its stabilization strategies, simulates and analyzes the evolutionary stabilization strategies of the stakeholders in various situations using MATLAB, and proposes a compatible institution. According to the findings of this study, the cost of sports data governance, the cost of sports data sharing, the degree of sports data compliance use, the government incentive system, and the government regulation mechanism are the important elements impacting each stakeholder's behavioral decision-making. Based on the foregoing, the study proposes corresponding institutional strategies for governments to respond to the issue of sports data rights, which will be more conducive to the safe use of data for development and humanitarian action, as well as contribute to global sustainable development.


Government , Sustainable Development , Biological Evolution , Motivation , Health Facilities , China , Game Theory
6.
Materials (Basel) ; 16(9)2023 Apr 24.
Article En | MEDLINE | ID: mdl-37176220

In recent years, numerous studies have explored the benefits of utilizing prestressed carbon fiber-reinforced polymer (CFRP) for strengthening concrete structures. However, research on the reinforcement of prestressed CFRP on full-scale hollow RC box girders, particularly damaged bridges, remains limited. In this study, both experiments and finite element analysis (FEA) were performed to investigate the flexural behavior of full-scale hollow RC box girders with varying degrees of damage, which were strengthened using CFRP with different levels of prestress. The adhesive behavior of the CFRP-concrete interface was considered in the FEA. Numerical simulations were conducted to assess the flexural behaviors of the girders, including failure modes, yield and ultimate loads, and deflections. The results revealed that the application of prestressed CFRP efficiently increased the yield and ultimate loads of the box girders. Specifically, when the degree of damage of the hollow box girder was less than 23%, the flexural bearing capacity of the repaired girder could be recovered after being strengthened with two prestressed CFRP strips measuring 50 mm in width and 3 mm in thickness. However, the risk of premature debonding at the CFRP-concrete interface increased when the prestressing level of CFRP and degree of damage of hollow RC box girders exceeded 35% and 40%, respectively. These findings suggest that the use of prestressed CFRP may be a promising method for repairing damaged hollow RC box girders, but careful consideration of the degree of damage and prestressing level would be necessary to ensure the effectiveness and safety of the repair.

7.
Exp Cell Res ; 425(1): 113538, 2023 04 01.
Article En | MEDLINE | ID: mdl-36871856

Breast cancer has become the highest incidence of cancer in women. It was extensively and deeply studied by biologists and medical workers worldwide. However, the meaningful results in lab researches cannot be realized in clinical, and a part of new drugs in clinical experiments do not obtain as good results as the preclinical researches. It is urgently that promote a kind of breast cancer research models that can get study results closer to the physiological condition of the human body. Patient-derived models (PDMs) originating from clinical tumor, contain primary elements of tumor and maintain key clinical features of tumor. So they are promising research models to facilitate laboratory researches translate to clinical application, and predict the treatment outcome of patients. In this review, we summarize the establishment of PDMs of breast cancer, reviewed the application of PDMs in clinical translational researches and personalized precision medicine with breast cancer as an example, to improve the understanding of PDMs among researchers and clinician, facilitate them to use PDMs on a large scale of breast cancer researches and promote the clinical translation of laboratory research and new drug development.


Breast Neoplasms , Humans , Female , Breast Neoplasms/drug therapy , Breast Neoplasms/genetics , Breast Neoplasms/pathology , Research , Precision Medicine/methods , Xenograft Model Antitumor Assays
8.
Molecules ; 28(5)2023 Feb 25.
Article En | MEDLINE | ID: mdl-36903407

It is interesting and meaningful to explore fluorescent probes for novel rapid detection methods. In this study, we discovered a natural fluorescence probe, bovine serum albumin (BSA), for the assay of ascorbic acid (AA). Due to clusterization-triggered emission (CTE), BSA has the character of clusteroluminescence. AA shows an obvious fluorescence quenching effect on BSA, and the quenching effect increases with increasing concentrations of AA. After optimization, a method for the rapid detection of AA is established by the AA-caused fluorescence quenching effect. The fluorescence quenching effect reaches saturation after 5 min of incubation time and the fluorescence is stable within more than one hour, suggesting a rapid and stable fluorescence response. Moreover, the proposed assay method shows good selectivity and a wide linear range. To further study the mechanisms of AA-caused fluorescence quenching effect, some thermodynamic parameters are calculated. The main intermolecular force between BSA and AA is electrostatic, presumably leading to the inhibiting CTE process of BSA. This method also shows acceptable reliability for the real vegetable sample assay. In summary, this work will not only provide an assay strategy for AA, but also open an avenue for the application expansion of CTE effect of natural biomacromolecules.


Ascorbic Acid , Vegetables , Ascorbic Acid/analysis , Reproducibility of Results , Spectrometry, Fluorescence/methods , Fluorescent Dyes , Serum Albumin, Bovine , Limit of Detection
9.
Theriogenology ; 199: 1-10, 2023 Mar 15.
Article En | MEDLINE | ID: mdl-36731281

Endometrial receptivity is a critical process for the successful establishment of pregnancy in ruminants. However, the biological role of long non-coding RNAs (lncRNAs) in the development of endometrial receptivity is poorly understood. In this study, we performed RNA-seq analysis of immortalised goat endometrial epithelial cells (gEECs) treated with interferon-τ (IFNT). Transcriptome profiles showed that 8069 high-confidence putative lncRNAs, including 6498 intronic lncRNA transcripts, 1078 lincRNAs and 493 antisense lncRNAs were identified in gEECs with or without IFNT treatment. Functional clustering analysis was performed by using cis and trans lncRNAs prediction. GO and KEGG analyses revealed that differentially expressed lncRNAs may regulate tissue remodelling and immune responses. Subsequently, six of the 21 differentially expressed antisense lncRNAs were validated using qRT-PCR. Through functional screening and co-expression analysis of lncRNAs in gEECs, we identified that ISG15-AS was mainly expressed in the luminal and glandular epithelium on days 5 and 15 and was strongly upregulated on day 18 of pregnancy in vivo. Similarly, ISG15-AS was abundant in the nucleus and cytoplasm, and was significantly upregulated after treatment with IFNT in gEECs. In addition, ISG15 is an IFNT-responsive gene, that displayed an evident increase in vivo and in vitro. Moreover, sense ISG15 was significantly upregulated following ISG15-AS silencing. The key genes related to ISGylation and endometrial receptivity in gEECs dramatically increased after ISG15-AS inhibition. Collectively, our results indicate that a novel antisense lncRNA, ISG15-AS, may be important in regulating endometrial receptivity through ISGylation.


RNA, Long Noncoding , Animals , Female , Pregnancy , Endometrium , Epithelial Cells/physiology , Epithelium , Goats/genetics , RNA, Long Noncoding/genetics , Cytokines/genetics , Ubiquitins/genetics
10.
Drug Resist Updat ; 68: 100947, 2023 05.
Article En | MEDLINE | ID: mdl-36812747

Trastuzumab is a humanized monoclonal antibody, and has been clinical employed to treat human epidermal growth factor receptor 2 (HER2) positive breast cancer. However, drug resistance to trastuzumab remains a challenge due to the generally uncharacterized interactive immune responses within the tumor tissue. In this study, by means of single-cell sequencing, we identified a novel podoplanin-positive (PDPN+) cancer-associated fibroblasts (CAFs) subset, which was enriched in trastuzumab resistant tumor tissues. Furthermore, we found that PDPN+ CAFs promote resistance to trastuzumab in HER2+ breast cancer by secreting immunosuppressive factors indoleamine 2,3-dioxygenase 1 (IDO1) as well as tryptophan 2,3-dioxygenase 2 (TDO2), thereby suppressing antibody-dependent cell-mediated cytotoxicity (ADCC), which was mediated by functional NK cells. A dual inhibitor IDO/TDO-IN-3 simultaneously targeting IDO1 and TDO2 showed a promising effect on reversing PDPN+ CAFs-induced suppression of NK cells mediated ADCC. Collectively, a novel subset of PDPN+ CAFs was identified in this study, which induced trastuzumab resistance in breast cancer of HER2+ status via inhibiting ADCC immune response mediated by NK cells, hinting that PDPN+ CAFs could be a novel target of treatment to increase the sensitivity of HER2+ breast cancer to trastuzumab.


Breast Neoplasms , Cancer-Associated Fibroblasts , Humans , Female , Trastuzumab/pharmacology , Trastuzumab/therapeutic use , Breast Neoplasms/drug therapy , Breast Neoplasms/genetics , Breast Neoplasms/metabolism , Antibody-Dependent Cell Cytotoxicity , Receptor, ErbB-2/genetics , Killer Cells, Natural/metabolism , Cell Line, Tumor , Membrane Glycoproteins/pharmacology , Membrane Glycoproteins/therapeutic use
11.
J Environ Manage ; 326(Pt B): 116776, 2023 Jan 15.
Article En | MEDLINE | ID: mdl-36435122

Antibiotics are emerging pollutants largely considered to have a lower risk based on persistent, bioaccumulative, toxic (PBT) risk assessments. However, an increasing number of studies have illustrated that antibiotics are responsible for the global increase in antimicrobial resistance (AMR), which suggests that the risk of antibiotics has been largely underestimated by using PBT risk assessment. Here, we designed an integrated innovation risk assessment framework of persistent, bioaccumulative, toxic, and resistance (PBTR) that accounts for antibiotic resistance to better represent the antibiotic environmental risk. This novel antibiotic risk assessment framework was further verified via application to 39 target antibiotics in the 23 drinking water sources of the lower Yangtze River (LYR), China, during the normal and flood seasons. In contrast with the PBT assessment, single toxicity assessment and single resistance assessment, in the PBTR assessment, 7 of 39 target antibiotics with bacterial insensitivity were observed to represent a more prominent risk, as were the sites sampled during the flood season with low concentrations but high pollution loads, which confirmed that the sensitivity of PBTR risk assessment was instructive. The PBTR risk assessment for the screened priority antibiotics contributes not only representative data but also an innovative approach for identifying resistance risks. Using the positive matrix factorization (PMF) model, the sources of priority antibiotics can be predicted and thus supported the corresponding policy. Overall, this study first constructed a PBTR risk assessment framework, then applied it to facilitate the accurate management of antibiotic pollution at the basin level.


Drinking Water , Water Pollutants, Chemical , Drinking Water/analysis , Environmental Monitoring , Anti-Bacterial Agents/pharmacology , Anti-Bacterial Agents/analysis , Water Pollutants, Chemical/analysis , Rivers , Risk Assessment , China
12.
Environ Pollut ; 318: 120865, 2023 Feb 01.
Article En | MEDLINE | ID: mdl-36521718

Coexisting of microplastics (MPs) and residual herbicides has received substantial attention due to concerns about the pollutant vector effect. Here, the widely used amide herbicides were examined for their sorption behaviors on the priority biodegradable and nondegradable MPs identified in intensive agriculture. The fitting results indicated that the interactions between napropamide (Nap)/acetochlor (Ace) and the MPs, i.e., poly (butyleneadipate-co-terephthalate) microplastic (PBATM), polyethylene microplastic (PEM), and polypropylene microplastic (PPM), may be dominated by hydrophobic absorptive partitioning on the heterogeneous surfaces. Additionally, chemisorption cannot be ignored for the sorption of Nap/Ace on the biodegradable MPs. The sorption capacities of Nap/Ace on the MPs followed the order of PBATM > PEM > PPM. The differences in sorption capacity which varied by the MP colors were not significant. The hydrophobicity of the herbicides and the MPs, the rubber regions, surface O-functional groups, benzene ring structures and large specific surface area of the biodegradable MPs played key roles in the better performance in sorbing amide herbicides. Moreover, MPs, especially biodegradable MPs, might lead to a higher vector effect for residual amide herbicides than some other common environmental media. This study may provide baseline insights into the great potential of biodegradable MPs to serve as carriers of residual amide herbicides in intensive agrosystems.


Plastics , Water Pollutants, Chemical , Plastics/chemistry , Microplastics/chemistry , Amides , Adsorption , Polypropylenes , Polyethylene , Agriculture , Water Pollutants, Chemical/analysis
13.
Front Oncol ; 12: 898156, 2022.
Article En | MEDLINE | ID: mdl-35814401

Sorafenib is one of the few effective first-line drugs approved for the treatment of advanced hepatocellular carcinoma (HCC). However, the development of drug resistance is common among individuals with HCC. Recent evidence indicated that the anticancer activity of sorafenib mainly relies on the induction of ferroptosis. Furthermore, in our study, genes that suppress ferroptosis, especially GPX4 and DHODH, were enriched in sorafenib-resistant cells and primary tissues and were associated with poor prognosis of HCC patients who received sorafenib treatment. Therefore, a new ferroptosis inducer comprising a multiplex small interfering RNA (multi-siRNA) capable of simultaneously silencing GPX4 and DHODH was created. Then, exosomes with high multi-siRNA loading and HCC-specific targeting were established by fusing the SP94 peptide and the N-terminal RNA recognition motif (RRM) of U1-A with the exosomal membrane protein Lamp2b. The results from the in vitro and in vivo experiments indicate that this tumor-targeting nano-delivery system (ExoSP94-lamp2b-RRM-multi-siRNA) could enhance sorafenib-induced ferroptosis and overcome sorafenib resistance. Taken together, HCC-targeted exosomes (ExoSP94-Lamp2b-RRM) could specifically deliver multi-siRNA to HCC tissues, enhance sorafenib-induced ferroptosis by silencing GPX4 and DHODH expression and consequently increase HCC sensitivity to sorafenib, which opens a new avenue for clinically overcoming sorafenib resistance from the perspective of ferroptosis.

14.
Polymers (Basel) ; 14(14)2022 Jul 20.
Article En | MEDLINE | ID: mdl-35890715

The advantages of using prestressed carbon fiber reinforced polymer (CFRP) for strengthening and retrofitting structures have been reported in recent years. In this regard, most of the studies on prestressed CFRP technique have been carried out in the laboratory test with small-scale and no damage (reinforced concrete) RC beam. However, the real structures that need to be retrofitted in service are often degraded or damaged due to early cracking. This paper aims at studying the effect of prestressed CFRP method on full-scale and damaged RC beams. The damaged levels of four full-scale damaged hollow RC beams taken from an old bridge were evaluated. One damaged beam was tested to check the residual capacity, and the other three were strengthened with prestressed composite strengthened CFRP and steel-carbon fiber reinforced polymer (SCFRP). The flexural behavior of non-strengthened and prestressed strengthened beams was investigated. During the experiments, the failure modes, deflection, yield and ultimate load, strains of concrete, steel reinforcements, and SCFRP were measured and analyzed. The results showed that the stiffness at the elastic stage was increased by 64.9%, 66.9%, and 67.1% after strengthened by SCFRP with 30%, 40%, and 60% prestressing level. Moreover, the ultimate load of damaged hollow RC beams were improved by 19.53%, 21.82%, and 31.9%, respectively. The flexural behavior of the severely damaged RC beam with strength reduction coefficient of 0.65 can be recovered after being strengthened by SCFRP with 40% prestressing levels. Meanwhile, SCFRP-concrete interface debonding failure occurred when the prestressing level exceed 60%, and the characteristics of brittle failure became more evident with increased prestressing level of the SCFRP.

15.
Materials (Basel) ; 15(13)2022 Jul 04.
Article En | MEDLINE | ID: mdl-35806805

The durability of reinforced concrete (RC) beams strengthened with carbon fiber-reinforced polymer (CFRP) is a worldwide concern in structural engineering. As an important part of the strengthened beam, the performance of the CFRP-concrete interface under hygrothermal environments is a delicate problem. In this paper, the fatigue behavior of CFRP-strengthened RC beams is analyzed by a theoretical model. In the model, CFRP-concrete interface degradation under hygrothermal environments is involved. Since interface debonding and rebar fracture induced by intermediate cracking are two typical failure modes, the damage models of rebar and the CFRP-concrete interface are established. Based on the theoretical model, the failure mode of CFRP-strengthened RC beams can be predicted, and fatigue life can be determined. The results showed that IC debonding is more likely to occur under hygrothermal environments. The accurate prediction of failure modes is essential for fatigue life prediction.

16.
Environ Sci Pollut Res Int ; 29(50): 76365-76377, 2022 Oct.
Article En | MEDLINE | ID: mdl-35668251

The inundated area of dam and dike-break floods includes various types of land and factories that release considerable amounts of pollutants into floods, causing serious water pollution and further endangering human health. Many pollution sources and factors affect the water pollution risk in inundated areas. Accurate assessment of the water pollution risk for dam and dike-break floods enables people to take measures in advance to reduce public health problems. The existing evaluation methods cannot effectively analyze the water pollution risk for dam and dike-break floods because partial or all pollution sources and influencing factors are ignored. The main factors affecting flood water quality were summarized into point source (PS), non-point source (NPS), flood depth, velocity, duration, and temperature. The water pollution risk caused by NPSs and PSs were quantified, as well as the impact of all main factors on water pollution risk. The evaluation model proposed for water pollution risk in inundated areas of dam and dike-break floods considers all pollution sources and influencing factors. The WPR was proposed to represent the water pollution risk value. The dam-break flood of Luhun Reservoir was simulated to verify the feasibility of the evaluation model. We concluded that (1) WPR varied with space and time in the inundated area and was seriously affected by PS in local areas; (2) the annual average WPR of different land use types from high to low were construction land, cropland, urban, water, rural area, woodland, and grassland. The evaluation model can be used to evaluate the water pollution risk for dam and dike-break floods at macro and micro scales. People can use this method to evaluate the impact, range, and degree of specific pollution sources or pollutants in the inundated area, thus allowing for measures to be taken in advance to reduce associated damages.


Environmental Pollutants , Floods , Humans , Water Pollution , Water Quality
17.
Materials (Basel) ; 15(12)2022 Jun 13.
Article En | MEDLINE | ID: mdl-35744244

The bonding interface between the CFRP and the steel plate is the weak link of CFRP-strengthened steel structures. This paper studies the bond-slip relationship of the CFRP-steel interface by experiments and numerical tests. First, a series of double-strap experiments on a CFRP-strengthened steel plate are carried out. The results show that the maximum shear stress of the bonding interface of the Q345B specimen is larger than that of the X100 specimen. The initial slip and maximum slip become larger as the thickness of the bonding interface becomes larger. Finite element analysis of the above tests is carried out; we introduce the maximum stress criterion to simulate the bonding interface, which assumes that when the nominal stress of the material reaches the maximum nominal stress of damage, the material begins to damage. The FE model established has proved very effective for analyzing the bond characteristics of CFRP-strengthened steel plates. Finally, a verification test was carried out, using an FE analysis to verify the accuracy of the modified equations; the results prove that the results of the modified equations are in good agreement with the numerical results and experiment results, which verifies the effectiveness of the equations.

18.
Bioorg Chem ; 116: 105321, 2021 11.
Article En | MEDLINE | ID: mdl-34500305

Hyperuricemia is a principal factor mediating gout and kidney damage, and xanthine oxidase (XOD) is a key enzyme in the pathogenesis of hyperuricemia. In this context, a series of geniposide derivatives were designed and synthesized, and antihyperuricemic and nephroprotective effects of all derivatives was evaluated in vitro and in vivo. Compound 2e emerged as the most potent XOD inhibitor, with an IC50 value of 6.67 ± 0.46 µM. Simultaneously, cell viability, ROS generation, and SOD levels assay showed that compound 2e could repair the damage of HKC cells by inhibiting the oxidative stress response. The results of the study indicated compound 2e significantly decreased uric acid levels by inhibiting the XOD activity, and repaired kidney damage by inhibiting the expression of TLR4/TLR2/MyD88/NF-κB and NALP3/ASC/caspase-1 signaling pathways. Enzyme inhibition kinetics suggested that compound 2e functioned via reversible mixed competitive inhibition. Moreover, a molecular docking study was performed to gain insight into the binding mode of compound 2e with XOD. These results suggest that geniposide derivatives were potential to be developed into a novel medicine to reveal healthy benefits in natural prevention and reduction risk of hyperuricemia and kidney damage.


Drug Design , Enzyme Inhibitors/pharmacology , Gout Suppressants/pharmacology , Hyperuricemia/drug therapy , Iridoids/pharmacology , Xanthine Oxidase/antagonists & inhibitors , Dose-Response Relationship, Drug , Enzyme Inhibitors/chemical synthesis , Enzyme Inhibitors/chemistry , Gout Suppressants/chemical synthesis , Gout Suppressants/chemistry , Humans , Hyperuricemia/metabolism , Iridoids/chemical synthesis , Iridoids/chemistry , Molecular Structure , Structure-Activity Relationship , Xanthine Oxidase/metabolism
19.
Theranostics ; 11(16): 7767-7778, 2021.
Article En | MEDLINE | ID: mdl-34335963

Background: Lipid droplets (LDs) establish a considerable number of contact sites with mitochondria to enable energy transfer and communication. In this study, we developed a fluorescent biosensor to image LD-mitochondria interactions at the nanoscale and further explored the function of LD-mediated matrix transmission in processes involving multi-organelle interactions. Methods: A fluorescent probe called C-Py (C21H19N3O2, 7-(diethylamino) coumarin-3-vinyl-4-pyridine acetonitrile) was designed and synthesized. Colocalization of C-Py and the commercial LD stain Nile Red was analyzed in HeLa cells. The fluorescence stability and signal to background ratio of C-Py under structured illumination microscopy (SIM) were compared to those of the commercial probe BODIPY493/503. The cytotoxicity of C-Py was assessed using CCK-8 assays. The uptake pattern of C-Py in HeLa cells was then observed under various temperatures, metabolic levels, and endocytosis levels. Contact sites between LDs and various organelles, such as mitochondria, nuclei, and cell membrane, were imaged and quantitated using SIM. Physical changes to the contact sites between LDs and mitochondria were monitored after lipopolysaccharide induction. Results: A LD-targeted fluorescent biosensor, C-Py, with good specificity, low background signal, excellent photostability, low cytotoxicity, and high cellular permeability was developed for tracking LD contact sites with multiple organelles using SIM. Using C-Py, the subcellular distribution and dynamic processes of LDs in living cells were observed under SIM. The formation of contact sites between LDs and multiple organelles was visualized at a resolution below ~200 nm. The number of LD-mitochondria contact sites formed was decreased by lipopolysaccharide treatment inducing an inflammatory environment. Conclusions: C-Py provides strategies for the design of ultra-highly selective biosensors and a new tool for investigating the role and regulation of LDs in living cells at the nanoscale.


Lipid Droplets/metabolism , Mitochondria/metabolism , Single Molecule Imaging/methods , Biosensing Techniques/methods , Fluorescent Dyes/chemical synthesis , Fluorescent Dyes/metabolism , HeLa Cells , Humans , Lipid Metabolism/physiology
20.
Theriogenology ; 169: 47-55, 2021 Jul 15.
Article En | MEDLINE | ID: mdl-33933757

Follicular atresia is primarily caused by granulosa cell (GC) apoptosis, although the mechanisms are largely unknown. Ufmylation is a recently identified ubiquitin-like post-translational modifier that plays an important role in cell proliferation and apoptosis. The purpose of this study was to investigate the effects of Ufmylation on GC apoptosis during goat follicular atresia. Ubiquitin-fold modifier 1 (UFM1) and its target DDRGK domain containing 1 (DDRGK1) proteins were identified in granulosa cells (GCs) isolated from all stages of preantral follicles and from healthy (HF), early atretic (EF) and progressed atretic (PF) antral follicles. The expression levels were higher in GCs derived from antral atretic follicles than healthy follicles. Although the viability of GCs was not affected after overexpression of UFM1, siRNA-mediated UFM1 silencing significantly inhibited GC proliferation and induced apoptosis. Notably, components of the ufmylation pathway were significantly upregulated in GCs induced by the ER stress agent tunicamycin (Tm) and thapsigargin (Tg), but not affected by oxidative stress inducer H2O2. Furthermore, UFM1 silencing markedly increased the apoptosis of GCs upon Tg treatment by stimulating the ER stress-related gene expression. Our results provide evidence that UFM1 and its target DDRGK1 are expressed in the goat GCs during follicular development and atresia, and ufmylation may play an important role in the prevention of ER stress but not oxidative stress-induced GCs apoptosis.


Follicular Atresia , Goats , Animals , Apoptosis , Female , Granulosa Cells/metabolism , Hydrogen Peroxide/metabolism , Oxidative Stress
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