Displaying publications 1 - 20 of 24 in total

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  1. Zhao L, Ashraf MA
    West Indian Med J, 2015 12;64(5):506-513.
    PMID: 27400164 DOI: 10.7727/wimj.2016.179
    Background: The main reason for biomaterial related refractory infections is biofilm formation caused by bacterial adhesion on the surface of materials. Silver-hydroxyapatite (Ag/HA) nanocomposite coating can inhibit the formation of biofilm, but its mechanism is not clear.

    Material and method: In order to clarify the mechanism, the amounts of biofilm on the Ag/HA composite coating and HA coating were determined, the release rates of silver nanoparticles in simulated body fluid (SBF) were detected by atomic absorption spectrometry, and the expression values of atlE, fbe, sap, iapB genes of Staphylococcus aureus were studied when they grew on Ag/HA composite coating and HA coating.

    Results: The amount of the biofilm on the Ag/HA composite coating was significantly less than that on the HA coating, and the bacterial adhesion was decreased. The silver nanoparticles were released continuously in SBF and the release rate decreased gradually with time. The expression values of atlE, fbe and sap were high in the initial stage of adhesion and the expression value of iapB was high in the colonies-gathering stage in the control group, but they were all significantly inhibited in the presence of Ag.

    Conclusion: These results indicated that the main antibacterial effect of Ag/HA composite coating was achieved by the release of silver nanoparticles. The addition of Ag inhibited the expression of genes related to biofilm formation, which in turn inhibited the formation of biofilms. This provided theoretical support for the clinical application of Ag/HA composite coating.

  2. Jia Y, Zhao L
    Eur J Med Chem, 2021 Nov 15;224:113741.
    PMID: 34365130 DOI: 10.1016/j.ejmech.2021.113741
    Bacterial infection is amongst the most common diseases in community and hospital settings. Fluoroquinolones, exerting the antibacterial activity through binding to type II bacterial topoisomerase enzymes, DNA gyrase and topoisomerase IV, are mainstays of chemotherapy. At present, fluoroquinolones are the most valuable antibacterial agents used popularly. However, the emergence of more virulent and resistant pathogens by the development of either mutated DNA-binding proteins or efflux pump mechanism for fluoroquinolones results in an urgent demand to develop new fluoroquinolones to withstand the drug resistance and to obtain a broader spectrum of activity. This review aims to outline the recent advances of fluoroquinolone derivatives with antibacterial potential and to summarize the structure-activity relationship (SAR) so as to provide an insight for rational design of more active candidates, covering articles published between January 2018 and June 2021.
  3. Zhao L, Yang L, Ahmad K
    Hum Exp Toxicol, 2023;42:9603271221146780.
    PMID: 36607234 DOI: 10.1177/09603271221146780
    OBJECTIVES: Kaempferol (KMF), has beneficial effects against hepatic lipid accumulation. In this study, we aimed to investigate molecular mechanism underlying the protective effect of KMF on lipid accumulation.

    METHODS: HepG2 cells were treated with different concentrations of KMF and 0.5 mM palmitate (PA) for 24  h. The mRNA and protein levels of genes involved in lipid metabolism were evaluated using real-time PCR and western blot. The expression of Nrf2 was silenced using siRNA.

    RESULTS: Data indicated that KMF (20 μM) reversed PA-induced increased triglyceride (TG) levels and total lipid content. These effects were accompanied by down-regulation of the mRNA and protein levels of lipogenic genes (FAS, ACC and SREBP1), and up-regulation of genes related to fatty acid oxidation (CPT-1, HADHα and PPARα). Kaempferol significantly decreased the levels of the oxidative stress markers (ROS and MDA) and enhanced the activities of antioxidant enzymes SOD and GPx in PA-challenged cells. Luciferase analysis showed that KMF increased the transactivation of Nrf2 in hepatocytes. The results also revealed that KMF-mediated activation of Nrf2 target genes was suppressed by Nrf2 siRNA. Furthermore, Nrf2 siRNA abolished the KMF-induced reduction in ROS and MDA levels in PA treated cells. In addition, the inhibitory effect of KMF on TG levels and the mRNA and protein levels of FAS, ACC and SREPB-1 were significantly abolished by Nrf2 inhibition. Nrf2 inhibition also suppressed the KMF-induced activation of genes involved in β oxidation (CPT-1 and PPAR-α).

    CONCLUSION: The results suggest that KMF protects HepG2 cells from PA-induced lipid accumulation via activation of the Nrf2 signaling pathway.

  4. Lau YS, Zhao L, Zhang C, Li H, Han R
    Life Sci, 2020 Jul 10.
    PMID: 32659370 DOI: 10.1016/j.lfs.2020.118069
    AIM: Up-regulation of inflammasome proteins was reported in dystrophin-deficient muscles. However, it remains to be determined whether inflammasome activation plays a role in the pathogenesis of Duchenne muscular dystrophy. This study was therefore set out to investigate whether genetic disruption of the inflammasome pathway impacts the disease progression in mdx mice.

    MAIN METHODS: Mice deficient in both dystrophin and ASC (encoded by Pycard [PYD And CARD Domain Containing]) were generated. The impact of ASC deficiency on muscular dystrophy of mdx mice were assessed by measurements of serum cytokines, Western blot, real-time PCR and histopathological staining.

    KEY FINDINGS: The pro-inflammatory cytokines such as TNF-α, IL-6, KC/GRO and IL-10 were markedly increased in the sera of 8-week-old mdx mice compared to WT. Western blotting showed that P2X7, caspase-1, ASC and IL-18 were upregulated. Disruption of ASC and dystrophin expression in the mdx/ASC-/- mice was verified by Western blot analysis. Histopathological analysis did not find significant alterations in the muscular dystrophy phenotype in mdx/ASC-/- mice as compared to mdx mice.

    SIGNIFICANCE: Taken together, our results show that disruption of the central adaptor ASC of the inflammasome is insufficient to alleviate muscular dystrophy phenotype in mdx mice.

  5. Li H, Zhao L, Lau YS, Zhang C, Han R
    Oncogene, 2021 01;40(1):177-188.
    PMID: 33110234 DOI: 10.1038/s41388-020-01523-5
    Colorectal cancer is the third leading cause of cancer-related deaths in the United States and the third most common cancer in men and women. Around 20% colon cancer cases are closely linked with colitis. Both environmental and genetic factors are thought to contribute to colon inflammation and tumor development. However, the genetic factors regulating colitis and colon tumorigenesis remain elusive. Since reactive oxygen species (ROS) is vitally involved in tissue inflammation and tumorigenesis, here we employed a genome-wide CRISPR knockout screening approach to systemically identify the genetic factors involved in the regulation of oxidative stress. Next generation sequencing (NGS) showed that over 600 gRNAs including the ones targeting LGALS2 were highly enriched in cells survived after sublethal H2O2 challenge. LGALS2 encodes the glycan-binding protein Galectin 2 (Gal2), which is predominantly expressed in the gastrointestinal tract and downregulated in human colon tumors. To examine the role of Gal2 in colitis, we employed the dextran sodium sulfate (DSS)-induced acute colitis model in mice with (WT) or without Lgals2 (Gal2-KO) and showed that Gal2 deficiency ameliorated DSS-induced colitis. We further demonstrated that Gal2-KO mice developed significantly larger tumors than WT mice using Azoxymethane (AOM)/dextran sodium sulfate (DSS)-induced colorectal cancer model. We found that STAT3 phosphorylation was significantly increased in Gal2-deficient tumors as compared to those in WT mice. Gal2 overexpression decreased the proliferation of human colon tumor epithelial cells and blunted H2O2-induced STAT3 phosphorylation. Overall, our results demonstrate that Gal2 plays a suppressive role in colon tumor growth and highlights the therapeutic potential of Gal2 in colon cancer.
  6. Shao K, Ma R, Zhao L, Wang K, Kamber J
    Front Psychol, 2022;13:1039108.
    PMID: 36389586 DOI: 10.3389/fpsyg.2022.1039108
    Female-entrepreneurship plays a significantly important role in rural areas of China today. In fact, it is a driving force behind inclusive economic development of the country as a whole. However, notably very little literature out there has focused on the impact of how widespread usage of information technology tools affects the mothers entrepreneurship in the outskirt regions. Here, in this paper, the authors attempt to explore the finer details of such an impact by utilizing the data from the 2017 China Integrated Social Survey; along with the IV-Probit model to explore the transmission mechanism. Interestingly enough, it was discovered that Internet applications and tools do indeed increase entrepreneurship among women with children by a roughly 7.88%. In addition, this paper finds that the utilization of such "InfoTech" promote a continuous progress in entrepreneurship among those women with children who endeavor to start a self-managed enterprise in the less developed areas. Lastly, when looking the analysis of the transmission mechanism, this paper found that the role of Internet-usage in promoting rural mothers entrepreneurship was mainly through three factors - the gender equality effect, the information learning effect, and the financing effect. This accumulated data will be thoroughly presented here in the ensuing sections.
  7. Zhao X, Zhu M, Guo X, Wang H, Sui B, Zhao L
    Environ Sci Pollut Res Int, 2019 May;26(14):13746-13754.
    PMID: 30008165 DOI: 10.1007/s11356-018-2270-1
    The soil organic carbon accumulation in soda saline-alkaline soil and the humus composition changes with application of aluminum sulfate and rice straw were investigated by the controlled simulative experiments in laboratory. For evaluating the amelioration effect, organic carbon content and humus composition in soda saline-alkaline soil were investigated with different application amounts of rice straw and aluminum sulfate. Potassium dichromate oxidation titration (exogenous heat) method and Kumada method were used to analyze the contents of organic carbon and humus composition, respectively. The transformation of soil organic matter in the saline-alkali soil during the amelioration has been clarified in this paper. The results demonstrated that the contents of soil organic carbon were significantly increased (13-92%) with different application amounts of rice straw and aluminum sulfate. The contents of free fraction and combined fraction of humus and their compositions (humic acid and fulvic acid) were increased with different application amounts of rice straw. The free fraction of humus was increased more dramatically. Due to aluminum sulfate application, free fraction of humus and humic acid (HA) was transformed to combined fraction partially. Free HA was changed to be P type with rice straw application. With aluminum sulfate application, free form of HA was changed from type P to type Rp. For rice straw application, combined HA only was transferred within the area of type A. Aluminum sulfate addition had no significant effect on the type of combined form of HA. With the same amount of rice straw application, the contents of soil organic carbon were increased by increasing the amount of aluminum sulfate application. Both rice straw and aluminum sulfate applications could reduce the humification degree of free and combined fraction of HA. According to the types of HA, it could be concluded that humus became younger and renewed due to the application of rice straw and aluminum sulfate.
  8. Kim HS, Wu Y, Lin SJ, Deerochanawong C, Zambahari R, Zhao L, et al.
    Curr Med Res Opin, 2008 Jul;24(7):1951-63.
    PMID: 18547466 DOI: 10.1185/03007990802138731
    BACKGROUND: Data on achieving National Cholesterol Education Program Adult Treatment Panel III (ATP III) goals in Asia are limited.

    OBJECTIVE: To examine treatment patterns, goal attainment, and factors influencing treatment among patients in 6 Asian countries who were taking statins.

    METHODS: A retrospective cohort study was conducted in China, Korea, Malaysia, Singapore, Taiwan, and Thailand, where 437 physicians (41% cardiologists) recruited adults with hypercholesterolemia newly initiated on statin monotherapy.

    RESULTS: Of 2622 patients meeting inclusion and exclusion criteria, approximately 66% had coronary heart disease (CHD)/diabetes mellitus, 24% had no CHD but > or =2 risk factors, and 10% had no CHD and <2 risk factors. Most patients ( approximately 90%) received statins at medium or lower equipotency doses. Across all cardiovascular risk categories, 48% of patients attained ATP III targets for low-density lipoprotein cholesterol (LDL-C), including 38% of those with CHD/diabetes (goal: <100 mg/dL), 62% of those without CHD but with > or =2 risk factors (goal: <130 mg/dL), and 81% of those without CHD and <2 risk factors (goal: <160 mg/dL). Most patients who achieved goals did so within the first 3 months. Increasing age (odds ratio (OR)=1.015 per 1-year increment; 95% confidence interval (CI)=1.005-1.206; p=0.0038) and initial statin potency (OR=2.253; 95% CI=1.364-3.722; p=0.0015) were directly associated with goal attainment, whereas increased cardiovascular risk (OR=0.085; 95% CI=0.053-0.134; p<0.0001 for CHD/diabetes mellitus at baseline compared with <2 risk factors,) and baseline LDL-C (OR=0.990; 95% CI=0.987-0.993); p<0.0001 per 1-mg/dL increment) were inversely associated with LDL-C goal achievement. Limitations of this study include potential differences in treatment settings and cardiovascular risk factors between different countries and centers. In addition, the effects on cholesterol goal achievement of concomitant changes in lifestyle were not assessed.

    CONCLUSION: LDL-C goal attainment is low in Asians, particularly those with CHD/diabetes. More effective patient monitoring, treatments, including combining regimens and dose titration, and adherence to these treatments along with therapeutic lifestyle counseling may facilitate goal attainment.

  9. Xomphoutheb T, Jiao S, Guo X, Mabagala FS, Sui B, Wang H, et al.
    Sci Rep, 2020 04 20;10(1):6574.
    PMID: 32313140 DOI: 10.1038/s41598-020-63567-7
    An appropriate tillage method must be implemented by maize growers to improve phosphorus dynamics in the soil in order to increase phosphorus uptake by plant. The objective of this study was to investigate the effects of tillage systems on phosphorus and its fractions in rhizosphere and non-rhizosphere soils under maize. An experimental field was established, with phosphate fertilizers applied to four treatment plots: continuous rotary tillage (CR), continuous no-tillage (CN), plowing-rotary tillage (PR), and plowing-no tillage (PN). Under the different tillage methods, the available P was increased in the non-rhizosphere region. However, the concentration of available P was reduced in the rhizosphere soil region. The soil available P decreased with the age of the crop until the maize reached physiological maturity. The non-rhizosphere region had 132.9%, 82.5%, 259.8%, and 148.4% more available P than the rhizosphere region under the CR, PR, CN, and PN treatments, respectively. The continuous no-tillage method (CN) improved the uptake of soil phosphate by maize. The concentrations of Ca2-P, Ca8-P, Fe-P, Al-P and O-P at the maturity stage were significantly lower than other seedling stages. However, there was no significant relationship between total P and the P fractions. Therefore, a continuous no-tillage method (CN) can be used by farmers to improve phosphorus availability for spring maize. Soil management practices minimizing soil disturbance can be used to impove phosphorus availability for maize roots, increase alkaline phosphatase activity in the rhizosphere soil and increase the abundance of different phosphorus fractions.
  10. Zhao L, Yu M, Sun M, Xue X, Wang T, Cao W, et al.
    Molecules, 2017 Nov 10;22(11).
    PMID: 29125569 DOI: 10.3390/molecules22111935
    A reliable, rapid analytical method was established for the characterization of constituents of the ethanol extract of geopropolis (EEGP) produced by Malaysian stingless bees-Heterotrigona itama-by combining ultra-high-performance liquid chromatography with quadruple time-of-flight mass spectrometry (UHPLC-Q-TOF/MS). Based on known standards, the online METLIN database, and published literature, 28 compounds were confirmed. Phenolic acids, flavones, triterpenes and phytosterol were identified or tentatively identified using characteristic diagnostic fragment ions. The results indicated that terpenoids were the main components of EEGP, accompanied by low levels of phenolic acids, flavonoids, and phytosterol. Two major components were further purified by preparative high-performance liquid chromatography (PHPLC) and identified by nuclear magnetic resonance (NMR) as 24(E)-cycloart-24-ene-26-ol-3-one and 20-hydroxy-24-dammaren-3-one. These two triterpenes, confirmed in this geopropolis for the first time, are potential chemical markers for the identification of geopropolis from Malaysian stingless bees, H. itama.
  11. Kang K, Nanda S, Lam SS, Zhang T, Huo L, Zhao L
    Environ Res, 2020 07;186:109480.
    PMID: 32302869 DOI: 10.1016/j.envres.2020.109480
    Microwave assisted hydrothermal treatment (MHTC) was compared with torrefaction in terms of carbonization efficiency and physicochemical characteristics of char products. The utilization of produced char was optimized for composite solid biofuel production. The results show that MHTC significantly improved the binding capability of the microwave hydrochar (MHC) particles during co-densification with unprocessed biomass and coal. One possible contributor to the improved binding is the pseudo lignin formed during the MHTC, which led to a better interlocking of the feedstock particles and promoted the solid bridge formation. Composite pellet prepared with 80 wt% of torrefaction char (TC-120), 10 wt% of microwave hydrochar (MHC-30), and 10 wt% of Coal-04 showed a higher heating value of 24.54 MJ/kg and energy density of 26.43 GJ/m3, which is significantly higher than that of the raw cotton stalk pellet (16.77 MJ/kg and 18.76 GJ/m3, respectively), showing great promise as a solid biofuel. The moisture resistance and oxidation reactivity are also significantly improved. The results demonstrate that MHCs provides dual functionalities in acting as binder and fuel promoter in the production of composite biofuel. This study can provide new insight into the unique functions of MHC during fuel application, which demonstrates the great potential of applying MHTC in energy recovery from lignocellulosic biomass.
  12. Shi C, Zhao L, Atoni E, Zeng W, Hu X, Matthijnssens J, et al.
    mSystems, 2020 Sep 29;5(5).
    PMID: 32994288 DOI: 10.1128/mSystems.00640-20
    Aedes mosquitoes can efficiently transmit many pathogenic arboviruses, placing a great burden on public health worldwide. In addition, they also carry a number of insect-specific viruses (ISVs), and it was recently suggested that some of these ISVs might form a stable species-specific "core virome" in mosquito populations. However, little is known about such a core virome in laboratory colonies and if it is present across different developmental stages. In this study, we compared the viromes in eggs, larvae, pupae, and adults of Aedes albopictus mosquitoes collected from a lab colony and compared each to the virome of different developmental stages collected in the field. The virome in lab-derived A. albopictus was very stable across all stages, consistent with a vertical transmission route of these viruses, and formed a possible "vertically transmitted core virome." The different stages of field-collected A. albopictus mosquitoes also contained this stable vertically transmitted core virome, as well as another set of viruses (e.g., viruses distantly related to Guadeloupe mosquito virus, Hubei virga-like virus 2, and Sarawak virus) shared by mosquitoes across different stages, which might represent an "environment-derived core virome." To further study this core set of ISVs, we screened 48 publicly available SRA viral metagenomic data sets of mosquitoes belonging to the genus Aedes, showing that some of the identified ISVs were identified in the majority of SRAs and providing further evidence supporting the core-virome concept.IMPORTANCE Our study revealed that the virome was very stable across all developmental stages of both lab-derived and field-collected Aedes albopictus The data representing the core virome in lab A. albopictus proved the vertical transmission route of these viruses, forming a "vertically transmitted core virome." Field mosquitoes also contained this stable vertically transmitted core virome as well as additional viruses, which probably represented "environment-derived core virome" and which therefore were less stable over time and geography. By further screening publicly available SRA viral metagenomic data sets from mosquitoes belonging to the genus Aedes, some of the identified core ISVs were shown to be present in the majority of SRAs, such as Phasi Charoen-like phasivirus and Guadeloupe mosquito virus. How these core ISVs influence the biology of the mosquito host and arbovirus infection and evolution deserves to be further explored.
  13. Liu J, Yinchai W, Siong TC, Li X, Zhao L, Wei F
    PLoS One, 2022;17(12):e0278819.
    PMID: 36508410 DOI: 10.1371/journal.pone.0278819
    Deep Residual Networks (ResNets) are prone to overfitting in problems with uncertainty, such as intrusion detection problems. To alleviate this problem, we proposed a method that combines the Adaptive Neuro-fuzzy Inference System (ANFIS) and the ResNet algorithm. This method can make use of the advantages of both the ANFIS and ResNet, and alleviate the overfitting problem of ResNet. Compared with the original ResNet algorithm, the proposed method provides overlapped intervals of continuous attributes and fuzzy rules to ResNet, improving the fuzziness of ResNet. To evaluate the performance of the proposed method, the proposed method is realized and evaluated on the benchmark NSL-KDD dataset. Also, the performance of the proposed method is compared with the original ResNet algorithm and other deep learning-based and ANFIS-based methods. The experimental results demonstrate that the proposed method is better than that of the original ResNet and other existing methods on various metrics, reaching a 98.88% detection rate and 1.11% false alarm rate on the KDDTrain+ dataset.
  14. Liu J, Yinchai W, Siong TC, Li X, Zhao L, Wei F
    Sci Rep, 2022 Dec 01;12(1):20770.
    PMID: 36456582 DOI: 10.1038/s41598-022-23765-x
    For generating an interpretable deep architecture for identifying deep intrusion patterns, this study proposes an approach that combines ANFIS (Adaptive Network-based Fuzzy Inference System) and DT (Decision Tree) for interpreting the deep pattern of intrusion detection. Meanwhile, for improving the efficiency of training and predicting, Pearson Correlation analysis, standard deviation, and a new adaptive K-means are used to select attributes and make fuzzy interval decisions. The proposed algorithm was trained, validated, and tested on the NSL-KDD (National security lab-knowledge discovery and data mining) dataset. Using 22 attributes that highly related to the target, the performance of the proposed method achieves a 99.86% detection rate and 0.14% false alarm rate on the KDDTrain+ dataset, a 77.46% detection rate on the KDDTest+ dataset, which is better than many classifiers. Besides, the interpretable model can help us demonstrate the complex and overlapped pattern of intrusions and analyze the pattern of various intrusions.
  15. Zhao L, Wu HY, Xie D, Mo LM, Yang FF, Gao Y, et al.
    Trop Biomed, 2023 Dec 01;40(4):439-443.
    PMID: 38308831 DOI: 10.47665/tb.40.4.009
    The study of children who experienced with febrile seizures(FS) as a result of COVID-19 infection to gain insight into the clinical characteristics and prognosis of neurological damage, with the aim of improving prevention, diagnosis, and the treatment of neurological complications. This study investigated the clinical features of 53 children with FS who were admitted to Sanya Women and Children's Hospital from December 1, 2022, to January 31, 2023. The results indicated that the duration of convulsion in the case and control group was 7.90±8.91 and 2.67±1.23 (minutes) respectively. The analysis reveals that convulsions occurred within 24 hours in 39 cases (95.12%) of the case group, and in 8 cases (66.7%) of the control group. The difference was statistically significant (P<0.05). Additionally, the case group presented lower counts of WBC and NEU compared to the control group (p<0.05). The findings indicate that convulsions manifest at earlier stages of COVID-19 in children and the last longer than in the control group. It is therefore crucial for healthcare workers to remain attentive to patients with COVID-19 who report fever within 24 hours, and act promptly to implement preventive measures, particularly in cases of prolonged fever. It is essential to integrate the clinical manifestation, particularly convulsions, and the continuous numerical changes of inflammatory factors to assess COVID-19 linked with febrile seizures. In addition, larger-scale multi-center and systematic research are necessary to aid clinicians in monitoring neuropathological signals and biological targets, enabling more equitable diagnosis and treatment plans.
  16. Jiang Y, Zhao L, Ma J, Yang Y, Zhang B, Xu J, et al.
    Phytomedicine, 2024 Jan;123:155229.
    PMID: 38006804 DOI: 10.1016/j.phymed.2023.155229
    BACKGROUND: Triphala (TLP), as a Chinese Tibetan medicine composing of Emblica officinalis, Terminalia chebula and Terminalia bellirica (1.2:1.5:1), exhibited hepatoprotective, hypolipidemic and gut microbiota modulatory effects. Nonetheless, its roles in prevention of high-fat diet (HFD)-induced nonalcoholic fatty liver disease (NAFLD) and the related mechanistic insights involving the interplay of gut microbiota and hepatic inflammation are not known.

    PURPOSE: The present study seeks to determine if TLP would prevent HFD-induced NAFLD in vivo and its underlying mechanisms from the perspectives of gut microbiota, metabolites, and hepatic inflammation.

    METHODS: TLP was subjected to extraction and chemo-profiling, and in vivo evaluation in HFD-fed rats on hepatic lipid and inflammation, intestinal microbiota, short-chain fatty acids (SCFAs) and permeability, and body weight and fat content profiles.

    RESULTS: The TLP was primarily constituted of gallic acid, corilagin and chebulagic acid. Orally administered HFD-fed rats with TLP were characterized by the growth of Ligilactobacillus and Akkermansia, and SCFAs (acetic/propionic/butyric acid) secretion which led to increased claudin-1 and zonula occludens-1 expression that reduced the mucosal permeability to migration of lipopolysaccharides (LPS) into blood and liver. Coupling with hepatic cholesterol and triglyceride lowering actions, the TLP mitigated both inflammatory (ALT, AST, IL-1β, IL-6 and TNF-α) and pro-inflammatory (TLR4, MYD88 and NF-κB P65) activities of liver, and sequel to histopathological development of NAFLD in a dose-dependent fashion.

    CONCLUSION: TLP is promisingly an effective therapy to prevent NAFLD through modulating gut microbiota, mucosal permeability and SCFAs secretion with liver fat and inflammatory responses.

  17. Zhao L, Wang Q, Cui X, Li H, Zhao L, Wang Z, et al.
    Anal Chem, 2024 Feb 06;96(5):1913-1921.
    PMID: 38266028 DOI: 10.1021/acs.analchem.3c04062
    2D nanosheets (NSs) have been widely used in drug-related applications. However, a comprehensive investigation into the cytotoxicity mechanism linked to the redox activity is lacking. In this study, with cytochrome c (Cyt c) as the model biospecies, the cytotoxicity of 2D NSs was evaluated systematically based on their redox effect with microfluidic techniques. The interface interaction, dissolution, and redox effect of 2D NSs on Cyt c were monitored with pulsed streaming potential (SP) measurement and capillary electrophoresis (CE). The relationship between the redox activity of 2D NSs and the function of Cyt c was evaluated in vitro with Hela cells. The results indicated that the dissolution and redox activity of 2D NSs can be simultaneously monitored with CE under weak interface interactions and at low sample volumes. Both WS2 NSs and MoS2 NSs can reduce Cyt c without significant dissolution, with reduction rates measured at 6.24 × 10-5 M for WS2 NSs and 3.76 × 10-5 M for MoS2 NSs. Furthermore, exposure to 2D NSs exhibited heightened reducibility, which prompted more pronounced alterations associated with Cyt c dysfunction, encompassing ATP synthesis, modifications in mitochondrial membrane potential, and increased reactive oxygen species production. These observations suggest a positive correlation between the redox activity of 2D NSs and their redox toxicity in Hela cells. These findings provide valuable insight into the redox properties of 2D NSs regarding cytotoxicity and offer the possibility to modify the 2D NSs to reduce their redox toxicity for clinical applications.
  18. Qiu R, Zhang L, Hu Z, Du Y, Zheng X, Zhang Z, et al.
    Plant Dis, 2022 Oct 03.
    PMID: 36190300 DOI: 10.1094/PDIS-03-22-0677-PDN
    Anisomeles indica (L.) Kuntze is a perennial erect herb that belongs to the genus Epimeredi, family Labiatae (Hsieh et al., 2008). This herb is distributed in several southern provinces such as Yunnan, Sichuan and Guizhou in China, and it is also exported to Southeast Asian countries such as Singapore and Malaysia (Li., 2010; Yao et al., 2019). Due to its market potential and broad development prospects, the herb has been cultivated in Yunnan. In August 2021, virus-like symptoms on leaves, including shrinking, mosaic, and yellow mottling(Fig S1. A) appeared on approximately 80% of A. indica in the experimental fields of the Kunming Institute of Botany, Chinese Academy of Science, in Kunming, Yunnan. To unveil the possible viral agents associated with the disease symptoms, leaf samples were collected from 5 plants for transmission electron microscopy (TEM) analysis using negative staining (Zhang et al., 2016). Rhabditiform-shaped particles around 300 × 18 nm (Fig S1. C) were observed, which resemble those of tobamoviruses. To identify the exact virus, total RNA was extracted from the 20 leaf samples using the RNA-easy Isolation Reagent (Vazyme, Nanjing, China), followed by reverse transcription (RT)-PCR with a degenerate tobamovirus primer pair (Li et al., 2014). A 480-bp amplicon was obtained from each sample and cloned into the pMD18-T vector for Sanger sequencing (Takara, Dalian, China). BLASTn-analysis revealed that the 20 amplicons were identical and shared 100% nucleotide sequence identity with tobacco mosaic virus (TMV) isolate Bei Cang Zhu from Atractylodes lancea (acc. no. KU198186) One sequence was deposited in the GenBank under the accession number OK489807. ELISA testing with TMV-specific antibody (Agdia, USA) produced positive results for all of the 20 leaf samples. In order to understand the difference between TMV isolates from A. indica and those form other host plants, the sequences of movement protein (MP, 807 bp) and RNA-dependent RNA polymerase (RdRp, 3351 bp) of TMV were also obtained from one of the TMV infected samples using the target gene special primers (Tab. S1), and submitted to GenBank under the accession number OM3662406 (MP) and OM366242 (RdRp). BLASTn-analysis revealed that the amplicon of MP shared 97.75% nucleotide sequence identity with TMV isolate Henan 9-2-2017 from sweet potato (MN186255.1) and RdRp shared 97.43% nucleotide sequence identity with TMV isolate SXFQ from Solanum lycopersicum (JX993906.1). Phylogenetic analysis indicated that the isolate of A. indica grouped with several TMV isolates (e.g., tomato, AF103779.1 and tobacco, HE818449.1) from Northern China. The virus was successfully transmitted onto healthy A.indica plants (n = 5) upon mechanical inoculation as the plants not only developed foliar distortion symptoms but also tested positive for TMV by RT-PCR with the CP-specific primers (Tab. S1). Taken together, our results demonstrated that the diseased A. indica plants were infected with TMV. To our knowledge, this is the first report of TMV infected A. indica (L.) Kuntze in China. Symptomatic phenotype-based field surveys on some plantations in Yunnan Province indicated that the disease incidence ranged from 70% to 90%, resulting in significant loss of production of A. indica. It is necessary to monitor the viruses in the fields and find effective methods to protect TMV in the A. indica (L.) Kuntze industry.
  19. Choy KW, Mustafa MR, Lau YS, Liu J, Murugan D, Lau CW, et al.
    Biochem Pharmacol, 2016 09 15;116:51-62.
    PMID: 27449753 DOI: 10.1016/j.bcp.2016.07.013
    Endoplasmic reticulum (ER) stress in endothelial cells often leads to endothelial dysfunction which underlies the pathogenesis of cardiovascular diseases. Paeonol, a major phenolic component extracted from Moutan Cortex, possesses various medicinal benefits which have been used extensively in traditional Chinese medicine. The present study investigated the protective mechanism of paeonol against tunicamycin-induced ER stress in isolated mouse aortas and human umbilical vein endothelial cells (HUVECs). Vascular reactivity in aorta was measured using a wire myograph. The effects of paeonol on protein expression of ER stress markers, reactive oxygen species (ROS) production, nitric oxide (NO) bioavailability and peroxisome proliferator-activated receptor δ (PPARδ) activity in the vascular wall were assessed by Western blot, dihydroethidium fluorescence (DHE) or lucigenin enhanced-chemiluminescence, 4-amino-5-methylamino-2',7'-difluorofluorescein (DAF-FM DA) and dual luciferase reporter assay, respectively. Ex vivo treatment with paeonol (0.1μM) for 16h reversed the impaired endothelium-dependent relaxations in C57BJ/6J and PPARδ wild type (WT) mouse aortas following incubation with tunicamycin (0.5μg/mL). Elevated ER stress markers, oxidative stress and reduction of NO bioavailability induced by tunicamycin in HUVECs, C57BJ/6J and PPARδ WT mouse aortas were reversed by paeonol treatment. These beneficial effects of paeonol were diminished in PPARδ knockout (KO) mouse aortas. Paeonol increased the expression of 5' adenosine monophosphate-activated protein kinase (AMPK) and PPARδ expression and activity while restoring the decreased phosphorylation of eNOS. The present study delineates that paeonol protects against tunicamycin-induced vascular endothelial dysfunction by inhibition of ER stress and oxidative stress, thus elevating NO bioavailability via the AMPK/PPARδ signaling pathway.
  20. Zhang X, Zhao L, Xiang S, Sun Y, Wang P, Chen JJ, et al.
    J Ethnopharmacol, 2023 May 10;307:116243.
    PMID: 36791927 DOI: 10.1016/j.jep.2023.116243
    ETHNOPHARMACOLOGICAL RELEVANCE: Yishen Tongluo formula (YSTLF) is formulated based on traditional Chinese medicine theory for the treatment of Diabetic kidney disease (DKD) and has been shown to be effective in improving the symptoms of DKD according to the clinical observation.

    AIM OF THE STUDY: To explore the effect of YSTLF on DKD and figure out whether its effects were due to the regulation Sirt6/TGF-β1/Smad2/3 pathway and promoting degradation of TGF-β1.

    MATERIALS AND METHODS: The extract of YSTLF at 1, 2.5 and 5 g/kg was orally administered to C57BLKS/J (db/db) mice for 8 weeks and db/db mice were given valsartan as a positive control. The littermate db/m and db/db mice were given vehicle as the control and model group, respectively. Blood urea nitrogen and serum creatinine were detected and the urinary albumin excretion, urea albumin creatinine ratio was calculated. The histopathological change of renal tissues in each group was determined. Simultaneously, the levels of fibrosis-related proteins and messenger RNA (mRNA) in kidney and high glucose (HG)-induced SV40-MES-13 cells were detected. The roles of YSTLF in regulating of Sirt6/TGF-β1/Smad2/3 signaling pathway were investigated in HG-stimulated SV40-MES-13 cells and validated in db/db mice. Furthermore, the effect of YSTLF on TGF-β1 degradation was investigated in HG-stimulated SV40-MES-13 cells.

    RESULTS: YSTLF significantly improved the renal function in DKD mice. YSTLF dose-dependently attenuated pathological changes and suppressed the expression of type I collagen, alpha smooth muscle actin, type IV collagen, and fibronectin in vitro and in vivo, resulting in ameliorating of renal fibrosis. YSTLF positively regulated Sirt6 expression, while inhibited the activating of TGF-β1/Smad2/3 signaling pathway. TGF-β1 was steady expressed in HG-stimulated SV40-MES-13 cells, whereas was continuously degraded under YSTLF treatment.

    CONCLUSIONS: YSTLF significantly ameliorates renal damages and fibrosis may via regulating Sirt6/TGF-β1/Smad2/3 signaling pathway as well as promoting the degradation of TGF-β1.

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