Publications by authors named "Wenjun Zou"

58 Publications

TEC kinase stabilizes PLK4 to promote liver cancer metastasis.

Cancer Lett 2021 Oct 9. Epub 2021 Oct 9.

School of Biomedical Sciences, The University of Hong Kong, Pokfulam, Hong Kong, China; State Key Laboratory of Liver Research (The University of Hong Kong), The University of Hong Kong, Pokfulam, Hong Kong, China. Electronic address:

Aberrated PLK4 expression has been reported in different malignancies and causes centrosome amplification, aneuploidy, and genomic instability. However, the mechanism by which PLK4 is regulated in carcinogenesis remains not fully characterised. Here, we showed that PLK4 was overexpressed in human HCC and overexpression of PLK4 predicted poorer patient prognosis. Unexpectedly, we found that induced expression of PLK4 promotes, but knockdown of PLK4 inhibits, HCC cell migration and invasion. Mechanistically, we found that TEC tyrosine kinase, which also promotes HCC cell migration, stabilizes PLK4 by phosphorylation. TEC directly phosphorylates PLK4 at tyrosine 86 residue, which not only stabilizes the protein but also enhances PLK4-mediated HCC cell invasion. Further investigation by transcriptome sequencing indicated that PLK4 promotes the phosphorylation of focal adhesion kinase to regulate the focal adhesion pathway in HCC cell migration. Taken together, our results demonstrated that PLK4 plays an important role in HCC metastasis and revealed for the first time the mechanism by which PLK4 promotes HCC metastasis via TEC phosphorylation.
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http://dx.doi.org/10.1016/j.canlet.2021.08.038DOI Listing
October 2021

A Comprehensive Review of Genus : Traditional Uses, Chemical Constituents and Medical Applications.

Front Pharmacol 2021 20;12:750165. Epub 2021 Sep 20.

School of Pharmacy, Southwest Medical University, Luzhou, China.

Genus (family: Rosaceae) comprises nearly 148 species, distributed widely across the temperate and subtropical regions of the Northern Hemisphere. L. () has been used as a hemostatic and scald treating medicine in China for a long time. Numerous studies have demonstrated that plant extracts or monomers from exhibit several pharmacological effects, such as anti-cancer, anti-virus, anti-inflammation, anti-bacteria, neuroprotective and hepatoprotective effects. The other species of genus are also being studied by researchers worldwide. Scop. (), as an edible wild plant, is a common ingredient of the Mediterranean diet, and its young shoots and leaves are often mixed with traditional vegetables and consumed as salad. Reports on genus available in the current literature were collected from Google Scholar, Web of Science, Springer, and PubMed. The Plant List (http://www.theplantlist.org./tpl1.1/search?q=Sanguisorba), International Plant Name Index (https://www.ipni.org/?q=Sanguisorba) and Kew Botanical Garden (http://powo.science.kew.org/) were used for obtaining the scientific names and information on the subspecies and cultivars. In recent years, several and experiments have been conducted to reveal the active components and effective monomers of and . To date, more than 270 compounds have been isolated and identified so far from the species belonging to genus . Numerous reports on the chemical constituents, pharmacologic effects, and toxicity of genus are available in the literature. This review provides a comprehensive understanding of the current traditional applications of plants, which are supported by a large number of scientific experiments. Owing to these promising properties, this species is used in the treatment of various diseases, including influenza virus infection, inflammation, Alzheimer's disease, type 2 diabetes and leukopenia caused by bone marrow suppression. Moreover, the rich contents and biological effects of and facilitate these applications in dietary supplements and cosmetics. Therefore, the purpose of this review is to summarize the recent advances in the traditional uses, chemical constituents, pharmacological effects and clinical applications of genus . The present comprehensive review may provide new insights for the future research on genus .
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http://dx.doi.org/10.3389/fphar.2021.750165DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8488092PMC
September 2021

The Clinical Efficacy and Safety of 11 Commonly Used Treatment Strategies Improving Arrhythmia of CHD in China: A Network Meta-Analysis.

Front Pharmacol 2021 20;12:741716. Epub 2021 Sep 20.

College of Pharmacy, Chengdu University of Traditional Chinese Medicine, Chengdu, China.

Arrhythmia which as a common complication of CHD, has a high incidence. At present, more and more anti-arrhythmic drugs are used in clinical practice. However, which drug has the best efficacy and high safety is still unknown. Therefore, we decided to use NMA to solve this problem. We searched CNKI, Wanfang database, VIP database, Pubmed, Embase and Cochrane libraries, and collected all RCTs of arrhythmia of CHD, and used RevMan (5.3) and Stata (13.0) to carry out this NMA. The primary outcome indicator of this study is efficiency; the secondary outcome indicator is the incidence of adverse reactions. A total of 134 RCTs, 13,951 patients, and 11 treatment strategies were included in this NMA. The results show that all treatment strategies can effectively improve the arrhythmia of patients. Among them, PMA+AM, AM+AT, AM+WG have higher effective rates, and PMA+AM, WG+ME, SC+ME have better safety. The effectiveness and safety of the treatment strategies which combined TCM and chemical drugs, are significantly better than that of using chemical drugs alone. The treatment strategy of combination of multiple drugs usually has higher efficiency and safety. PMA+AM seems to be the most recommended treatment strategy. In addition, the rational combination of TCM and chemical drugs may provide potential benefit. : https://www.crd.york.ac.uk/PROSPERO/, identifier CRD42021229693.
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http://dx.doi.org/10.3389/fphar.2021.741716DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8488134PMC
September 2021

Comparative Efficacy and Safety of Thrombopoietin Receptor Agonists in Adults With Thrombocytopenia: A Systematic Review and Network Meta-analysis of Randomized Controlled Trial.

Front Pharmacol 2021 28;12:704093. Epub 2021 Jul 28.

Laboratory of Chinese Materia Medica, Department of Pharmacology, School of Pharmacy, Southwest Medical University, Luzhou, China.

Thrombopoietin receptor agonists (TPO-RAs) play a crucial role in stimulating thrombopoiesis. However, conventional meta-analyses have shown inconsistent results regarding the efficacy of thrombopoietin receptor agonists versus placebo. Therefore, we performed a network meta-analysis to assess the effects of five TPO-RAs indirect comparison. For this network meta-analysis, we considered randomized trials that included any of the following interventions: avatrombopag, lusutrombopag, eltrombopag, romiplostim, recombinant human thrombopoietin (rhTPO). We searched the , , , , and databases for randomized controlled clinical trials from inception to January 31, 2021. We use randomized controlled clinical trials of TPO-RAs for treatment of immune thrombocytopenia in adults. The primary outcome was the number of patients achieving platelet response which was defined as the achievement of a platelet count of more than 30 or 50 cells × 10/L in the absence of rescue therapy, and the secondary outcome was the therapy-related serious adverse events and incidence of bleeding episodes. To obtain the estimates of efficacy and safety outcomes, we performed a random-effects network meta-analysis. These estimates were presented as odds ratios with 95% confidence intervals. We use surface under the cumulative ranking probabilities to rank the comparative effects and safety of all drugs against the placebo. In total, 2,207 patients were analyzed in 20 clinical trials. All preparations improved the point estimates of platelet response when compared with the placebo. Avatrombopag and lusutrombopag had the best platelet response compared to the placebo, the former had a non-significant advantage compared to the latter [odds ratio (OR) = 1.91 (95% confidence interval: 0.52, 7.05)]. The treatments were better than eltrombopag, romiplostim, rituximab, and rhTPO + rituximab, with corresponding ORs of 3.10 (1.01, 9.51), 9.96 (2.29, 43.29), 33.09 (8.76, 125.02), and 21.31 (3.78, 119.98) for avatrombopag and 1.62 (0.63, 4.17), 5.21 (1.54, 17.62), 17.34 (5.15, 58.36), and 11.16 (2.16, 57.62) for lusutrombopag. Regarding bleeding, the placebo group had the highest probability of bleeding, whereas lusutrombopag had the lowest risk of bleeding when compared to the placebo. Adverse events were slightly higher in patients receiving rituximab than in those receiving placebo or other treatments. Overall, this meta-analysis showed that avatrombopag may yield the highest efficacy because it has the most favorable balance of benefits and acceptability.
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http://dx.doi.org/10.3389/fphar.2021.704093DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8355583PMC
July 2021

Therapeutic effect of berberine on chronic atrophic gastritis based on plasma and urine metabolisms.

Eur J Pharmacol 2021 Oct 12;908:174335. Epub 2021 Jul 12.

College of Pharmacy, Chengdu University of Traditional Chinese Medicine, Chengdu, China; Department of Pharmacy, Chinese PLA General Hospital, Beijing, China. Electronic address:

The purpose of this study was to investigate the therapeutic effect of berberine (BBR) on chronic atrophic gastritis (CAG) and its potential mechanism. The effects of BBR on gastric histopathology, serum biochemical indexes and inflammatory factors in CAG rats were assessed. Moreover, plasma and urine metabolomics based on ultra high performance liquid chromatography-quadrupole-time-of-flight mass spectrometer (UHPLC-Q-TOF/MS) were used to identify potential metabolic markers and possible pathways of BBR in the treatment of CAG. The results showed that BBR could significantly improve the pathological characteristics of gastric tissue, alleviate the serum biochemical indexes and reduce the mRNA expression of nuclear factor-κB, tumor necrosis factor-α, Cyclooxygenase-2, monocyte chemoattractant protein-1, Interleukin-17A and I interferon-γ. The results of metabolomic analysis show that the therapeutic effect of BBR on CAG may be related to the regulation of 15 metabolic markers and 12 metabolic pathways, which may be the potential mechanism for the treatment of CAG. This study provides new insights for elucidating the mechanism of BBR improving CAG.
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http://dx.doi.org/10.1016/j.ejphar.2021.174335DOI Listing
October 2021

Monitoring intraocular proangiogenic and profibrotic cytokines within 7 days after adjunctive anti-vascular endothelial growth factor therapy for proliferative diabetic retinopathy.

Acta Ophthalmol 2021 Jul 14. Epub 2021 Jul 14.

Department of Ophthalmology, The First Affiliated Hospital of Nanjing Medical University, Nanjing, China.

Purpose: To monitor the intraocular proangiogenic and profibrotic cytokine profiles within 7 days after intravitreous injection of conbercept (IVC) for patients with proliferative diabetic retinopathy (PDR).

Methods: This prospective, randomized controlled, consecutive, comparative study included 157 eyes with PDR. Participant eyes underwent sham IVC or IVC and subsequent vitrectomy at days 2, 3, 4, 5, 6, 7 postinjection. The intraocular cytokines profiles were measured using beaded assay methods.

Results: After IVC, the vascular endothelial growth factor (VEGF)-A level in PDR vitreous decreased rapidly by approximately 10 times at day 2 (p = 0.00001) and kept at a low level at days 3, 4, 5, 6, 7 (p < 0.001, each compared with IVC-sham group). Similar tendency of the change in VEGF-A was observed in aqueous humour. The level of placenta growth factor (PIGF) in aqueous humour decreased 2 days after IVC whereas returned to baseline level after 5 days. The vitreous profibrotic cytokines, tissue growth factor (TGF)-β1, TGF-β2, TGF-β3 and connective tissue growth factor did not increase after IVC in each group.

Conclusion: We observed a remarkable and rapid decrease in intraocular VEGF-A, temporal decrease in PIGF from day 2 to day 4, increase in VEGF-C and VEGF-D from day 2 onwards, but no profibrotic switch in PDR eyes after IVC. The findings might suggest that ideal vitrectomy timing might be around 3 days after IVC.
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http://dx.doi.org/10.1111/aos.14957DOI Listing
July 2021

Datasets for gravelly soil liquefaction case histories.

Data Brief 2021 Jun 28;36:107104. Epub 2021 Apr 28.

College of Civil Engineering and Architecture, China Three Gorges University, China.

This data article provides summarized information on the liquefaction case histories of gravelly soil from 17 earthquakes. 234 historical cases based on the shear wave velocity test and dynamic penetration test are carefully compiled and corrected according to the data processing procedures recommended in the related research article [1]. All necessary information that helps develop the corresponding deterministic or probabilistic prediction models for gravelly soil liquefaction, including earthquake name and time, site name and its location, moment magnitude (M), peak ground acceleration, epicentral distance, bracketed duration, fines content, gravel content, average particle size, normalized dynamic penetration test blow count or normalized shear wave velocity, groundwater table, depth of gravelly soil deposit, total and effective overburden stress, the thickness of the impermeable capping layer, the thickness of the unsaturated zone between the groundwater table and capping layer, cyclic stress ratio for M = 7.5, and liquefaction information, are given for the datasets.
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http://dx.doi.org/10.1016/j.dib.2021.107104DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8138722PMC
June 2021

Berberine Attenuates Chronic Atrophic Gastritis Induced by MNNG and Its Potential Mechanism.

Front Pharmacol 2021 25;12:644638. Epub 2021 Mar 25.

Department of Pharmacy, Chinese PLA General Hospital, Beijing, China.

The purpose of this study was to investigate the therapeutic effect of berberine (BBR) on MNNG-induced chronic atrophic gastritis (CAG) and the possible mechanism of BBR through TGF-β1/PI3K signal pathway. GES-1 were pretreated with MNNG for 2 h before BBR treatment in all procedures. Cell viability was quantified by cell counting kit-8, and GES-1 morphology and proliferation were detected by high content screening (HCS) assay. The rat model of CAG was established by MNNG, and the therapeutic effect of BBR on stomach histopathology and serum supernatant were analyzed . In addition, the possible mechanism of BBR was further discussed, and the expression of related genes and proteins in TGF-β1/PI3K signal pathway was detected. The results showed that BBR could significantly improve the survival rate and morphological changes of GES-1, improve the gastric tissue injury of CAG rats, and reduce the expression of G-17 and inflammatory factors IL-8, TNF-α, IL-6 and IL-1β. In addition, BBR down-regulated the expression of TGF-β1 axis-related signals such as TGF-β1, PI3K, p-Akt/Akt, p-mTOR/mTOR and P70S6K, and promoted the expression of PTEN, LC3-II and Beclin-1. In Conclusion, BBR can improve CAG which may be closely related to TGF-β1/PI3K signal pathway.
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http://dx.doi.org/10.3389/fphar.2021.644638DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8026873PMC
March 2021

Dioscin and diosgenin: Insights into their potential protective effects in cardiac diseases.

J Ethnopharmacol 2021 Jun 11;274:114018. Epub 2021 Mar 11.

College of Pharmacy, Chengdu University of Traditional Chinese Medicine, Chengdu, 611137, China. Electronic address:

Background And Ethnopharmacological Relevance: Dioscin and diosgenin derived from plants of the genus Dioscoreaceae such as D. nipponica and D. panthaica Prain et Burk. Were utilized as the main active ingredients of traditional herbal medicinal products for coronary heart disease in the former Soviet Union and China since 1960s. A growing number of research showed that dioscin and diosgenin have a wide range of pharmacological activities in heart diseases.

Aim Of The Study: To summarize the evidence of the effectiveness of dioscin and diosgenin in cardiac diseases, and to provide a basis and reference for future research into their clinical applications and drug development in the field of cardiac disease.

Methods: Literatures in this review were searched in PubMed, ScienceDirect, Google Scholar, China National Knowledge Infrastructure (CNKI) and Web of Science. All eligible studies are analyzed and summarized in this review.

Results: The pharmacological activities and therapeutic potentials of dioscin and diosgenin in cardiac diseases are similar, can effectively improve hypertrophic cardiomyopathy, arrhythmia, myocardial I/R injury and cardiotoxicity caused by doxorubicin. But the bioavailability of dioscin and diosgenin may be too low as a result of poor absorption and slow metabolism, which hinders their development and utilization.

Conclusion: Dioscin and diosgenin need further in-depth experimental research, clinical transformation and structural modification or research of new preparations before they can be expected to be developed into new therapeutic drugs in the field of cardiac disease.
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http://dx.doi.org/10.1016/j.jep.2021.114018DOI Listing
June 2021

Case Report: Acute Retinal Necrosis after Intravitreal Ranibizumab for Exudative Macular Degeneration.

Optom Vis Sci 2021 03;98(3):206-211

Significance: Acute retinal necrosis (ARN) may occur after intravitreal ranibizumab (IVR) treatment for patients with exudative age-related macular degeneration (AMD). Awareness of this unusual but devastating complication after IVR is needed. Early identification may help provide timely antiviral treatment and prevent irreversible visual loss.

Purpose: This study aimed to report a case of ARN after IVR in a patient with exudative AMD.

Case Report: A 67-year-old male patient complained of blurred vision in his left eye for 1 month. The patient was diagnosed with exudative AMD after detailed ophthalmic clinical evaluations. He received IVR once in his left eye. Three days after IVR, he developed varicella-zoster virus-associated ARN, which was treated with systemic and intravitreal antiviral therapy. Because of progressive inflammation, the patient underwent 25G pars plana vitrectomy with silicone oil tamponade. Seven months later, the patient was administered intravitreal aflibercept once in his left eye. Three months after intravitreal aflibercept, he underwent removal of silicone oil, and retinal detachment occurred 2 weeks after the surgery because of low IOP, and the patient eventually discontinued treatment.

Conclusions: This study reports the first case of varicella-zoster virus-associated ARN after IVR. Early ARN may be very difficult to distinguish from intraocular inflammation after IVR. Therefore, early detection of viral DNA in the intraocular fluid using polymerase chain reaction is recommended. Immediate antiviral treatment may be beneficial to prevent severe visual loss.
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http://dx.doi.org/10.1097/OPX.0000000000001649DOI Listing
March 2021

Key factors influencing earthquake-induced liquefaction and their direct and mediation effects.

PLoS One 2021 17;16(2):e0246387. Epub 2021 Feb 17.

Medical College, China Three Gorges University, Yichang, Hubei, China.

Many factors impact earthquake-induced liquefaction, and there are complex interactions between them. Therefore, rationally identifying the key factors and clarifying their direct and indirect effects on liquefaction help to reduce the complexity of the predictive model and improve its predictive performance. This information can also help researchers understand the liquefaction phenomenon more clearly. In this paper, based on a shear wave velocity (Vs) database, 12 key factors are quantitatively identified using a correlation analysis and the maximum information coefficient (MIC) method. Subsequently, the regression method combined with the MIC method is used to construct a multiple causal path model without any assumptions based on the key factors for clarifying their direct and mediation effects on liquefaction. The results show that earthquake parameters produce more important influences on the occurrence of liquefaction than soil properties and site conditions, whereas deposit type, soil type, and deposit age produce relatively small impacts on liquefaction. In the multiple causal path model, the influence path of each factor on liquefaction becomes very clear. Among the key factors, in addition to the duration of the earthquake and Vs, other factors possess multiple mediation paths that affect liquefaction; the thickness of the critical layer and thickness of the unsaturated zone between the groundwater table and capping layer are two indirect-only mediators, and the fines content and thickness of the impermeable capping layer induce suppressive effects on liquefaction. In addition, the constructed causal model can provide a logistic regression model and a structure of the Bayesian network for predicting liquefaction. Five-fold cross-validation is used to compare and verify their predictive performances.
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http://journals.plos.org/plosone/article?id=10.1371/journal.pone.0246387PLOS
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7888622PMC
August 2021

Zuojin Pill ameliorates chronic atrophic gastritis induced by MNNG through TGF-β1/PI3K/Akt axis.

J Ethnopharmacol 2021 May 29;271:113893. Epub 2021 Jan 29.

Department of Pharmacy, Chinese PLA General Hospital, Beijing, China. Electronic address:

Ethnopharmacological Relevance: Zuojin Pill (ZJP) is a classic prescription composed of Coptis chinensis and Tetradium ruticarpum (A.Juss.) T.G.Hartley, which is often used in the treatment of digestive system diseases.

Aim Of This Study: The purpose of this study was to explore the therapeutic effect and potential mechanism of ZJP on chronic atrophic gastritis (CAG) induced by MNNG.

Materials And Methods: The GES-1 and rat model of CAG was established by MNNG. Detection of cell viability, morphological changes and proliferation of GES-1 by CCK-8 and high content screening (HCS) assay. G-17, IL-8 and TNF-α in rat serum were detected by ELISA kit. The expression of related mRNA and protein on TGF-β1/PI3K/Akt signal axis were detected by RT-PCR and Western blot.

Results: The results showed that ZJP could significantly improve the GES-1 damage induced by MNNG and improve the gastric histomorphology of CAG rats. The intervention of ZJP could significantly reduce the content of G-17 and inflammatory factors IL-8, TNF- α, IL-6 and IL-1β, inhibit the expression of TGF-β1, PI3K and their downstream signals p-Akt, p-mTOR, P70S6K, and promote the expression level of PTEN, LC3-II and Beclin-1.

Conclusion: ZJP has a good therapeutic effect on CAG induced by MNNG, which may be closely related to the inhibition of TGF-β1/PI3K/Akt signal pathway.
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http://dx.doi.org/10.1016/j.jep.2021.113893DOI Listing
May 2021

ASK1/p38‑mediated NLRP3 inflammasome signaling pathway contributes to aberrant retinal angiogenesis in diabetic retinopathy.

Int J Mol Med 2021 02 24;47(2):732-740. Epub 2020 Dec 24.

Department of Ophthalmology, The Affiliated Wuxi No. 2 People's Hospital of Nanjing Medical University, Wuxi, Jiangsu 214002, P.R. China.

Diabetic retinopathy (DR) is the leading cause of blindness among the working‑age population in several countries. Despite the available treatments, some patients are diagnosed at the late stages of the disease when treatment is more difficult. Hence, it is crucial that novel targets are identified in order to improve the clinical therapy of DR. In the present study, an animal model of DR and a cell model using primary human retinal microvascular endothelial cells exposed to high glucose were constructed to examine the association between apoptosis signal‑regulating kinase 1 (ASK1)/p38 and NLR family pyrin domain containing 3 (NLRP3) in DR. The results revealed that DR induced inflammatory response and microvascular cell proliferation. NLRP3 contributed to DR‑mediated inflammatory development and progression, which promoted the expression of inflammatory‑related cytokines. In addition, NLRP3 promoted the tube formation of retinal microvascular endothelial cells and angiogenesis. Moreover, further research indicated that the NLRP3‑mediated aberrant retinal angiogenesis in DR was regulated by ASK1 and p38. It was thus suggested that ASK1/p38 may be novel target for the treatment of DR.
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http://dx.doi.org/10.3892/ijmm.2020.4833DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7797434PMC
February 2021

Tubeimoside II inhibits TGF-β1-induced metastatic progression of human retinoblastoma cells through suppressing redoxosome-dependent EGFR activation.

Chem Biol Interact 2021 Feb 4;335:109367. Epub 2021 Jan 4.

Sydney Pharmacy School, The University of Sydney, Sydney, NSW, 2006, Australia.

Metastasis is the leading cause of death in retinoblastoma (Rb) patients. Tubeimoside II (TBMS II) is a compound enriched in the Traditional Chinese Medicine (TCM) Tu Bei Mu. It has been shown to induce cytotoxicity of several types of tumors; however, littler is known about its effect on Rb. This study investigated the influence of TBMS II on TGF-β1-induced metastasis of human retinoblastoma Y-79 and WERI-Rb-1 cells. The data showed that TBMS II significantly inhibited epithelial-mesenchymal transition (EMT), cell adhesion, migration and invasion via reducing TGF-β1-induced oxidative stress in Rb cells. Further findings revealed that TBMS II exerted its inhibitory effect against TGF-β1-induced metastatic progression of Rb cells via suppressing redoxosome-dependent EGFR activation including EGFR phosphorylation and oxidation, and the activation of such signaling attenuated TBMS II's effect. Our study reveals that TBMS II impacts on TGF-β1-induced metastatic progression of Rb cells, and this information may contribute to better understanding the therapeutic potentials of TBMS II on metastatic Rb.
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http://dx.doi.org/10.1016/j.cbi.2021.109367DOI Listing
February 2021

Association of Low Leptin with Poor 3-Month Prognosis in Ischemic Stroke Patients with Type 2 Diabetes.

Clin Interv Aging 2020 9;15:2353-2361. Epub 2020 Dec 9.

Department of Biochemistry, Medical College of Georgia, Augusta, GA, USA.

Background: Leptin, an adipokine, has effects on the cardiovascular system with both protective and harmful role. This study aimed to assess the relationship between leptin and 3-month prognosis in ischemic stroke patients with type 2 diabetes.

Patients And Methods: As a prospective single-center observational study, we collected consecutive first-ever acute ischemia stroke with type 2 diabetes mellitus from February 2019 to February 2020. Serum samples were obtained at admission, and leptin serum levels were tested by the ELISA method. Logistic regression models were used to assess leptin's prognostic value to predict the functional outcome and mortality within three months.

Results: Finally, two hundred and eleven patients were included, and the mean leptin serum level was 16.8 (SD. 6.9) ng/mL. At admission, 53.6% of those included patients (N=113) were defined as severe stroke (NIH Stroke Scale [NIHSS]>5). In multivariable models adjusted for other factors, leptin levels<11.6ng/mL (lowest quartile, Q1) related to severe stroke and the risk increased 175% (odds ratios [OR] =2.75; 95% confidence interval [CI]=2.13-3.38; P=0.002). Serum leptin levels on admission in patients with poor outcomes and nonsurvivors were significantly reduced (P<0.001 and P<0.001). Leptin levels <11.6ng/mL (lowest quartile, Q1) related to a higher risk of poor functional impairment (OR=5.13; 95% CI =3.25-6.86; P<0.001) and mortality (OR=3.19; 95% CI =2.03-4.25; P<0.001).

Conclusion: The data shows that leptin serum level is a useful prognostic biomarker in ischemic stroke patients with type 2 diabetes, and this relationship is negative.
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http://dx.doi.org/10.2147/CIA.S279535DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7734075PMC
April 2021

Elucidation of the molecular mechanism of Sanguisorba Officinalis L. against leukopenia based on network pharmacology.

Biomed Pharmacother 2020 Dec 1;132:110934. Epub 2020 Nov 1.

Department of Pharmacology, School of Pharmacy, Southwest Medical University, Luzhou, Sichuan, 646000, China; Institute of Cardiovascular Research, The Key Laboratory of Medical Electrophysiology, Ministry of Education of China, Medical Key Laboratory for Drug Discovery and Druggability Evaluation of Sichuan Province, Luzhou Key Laboratory of Activity Screening and Druggability Evaluation for Chinese Materia Medica, Luzhou 646000, China. Electronic address:

Leukopenia is the most common hallmark of hematopoietic diseases in clinic. Sanguisorba Officinalis L., a traditional Chinese medicine, has long been used for alleviating leukopenia. However, its associated mechanism still remains unknown. In this study, a network pharmacology approach was used to elucidate the underlying mechanisms of Sanguisorba Officinalis L. against leukopenia. Firstly, 12 active compounds of Sanguisorba Officinalis L. were identified through TCMSP database with absorption, distribution, metabolism, excretion (ADME) screening, and UHPLC-MS analysis. Then, 258 leukopenia related targets of the identified active compounds were predicted via the Swiss Target Prediction database, GeneCards database and DisGeNET database, respectively. After taking the intersection of two related targets, 72 common targets were selected. Among them, 8 core targets (VEGFA, HSP90AA1, EGFR, PTGS2, MTOR, ESR1, ERBB2, MDM2) of Sanguisorba Officinalis L. against leukopenia were obtained through the topological analysis. Meanwhile, both the GO and KEGG pathway analysis reveal that the core targets are mainly enriched in PI3K-Akt, HIF-1, VEGF and estrogen signaling pathways. In addition, molecular docking simulation was performed to explore the binding ability between the 12 active compounds of Sanguisorba Officinalis L. with 8 core targets. Furthermore, a myelosuppressive mice model was established to evaluate the protective effect of Sanguisorba Officinalis L. against leukopenia. The results showed that the ethanol extract of Sanguisorba Officinalis L. significantly raised the number of peripheral white blood cells. Overall, this study provides an insight into the underlying mechanisms of Sanguisorba Officinalis L. against leukopenia, which lays a theoretical foundation for the further experimental verification and clinical application.
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http://dx.doi.org/10.1016/j.biopha.2020.110934DOI Listing
December 2020

Prevalence of persistent vegetative state compared to recovery, disability, and death in subjects with severe traumatic brain injury: A meta-analysis.

Int J Clin Pract 2021 Apr 23;75(4):e13835. Epub 2020 Nov 23.

Department of Anesthesiology, Sichuan Bayi Rehabilitation Center of Chengdu University of TCM, Chengdu, Sichuan, China.

Background: The persistent vegetative state has drawn considerable attention since it is the poorest result apart from mortality in subjects with severe traumatic brain injury. This meta-analysis was performed to evaluate its prevalence compared to recovery, disability, and death 6 months post severe traumatic brain injury.

Methods: A systematic-literature search up to May 2020 was performed and 19 studies were detected with 10 368 subjects. They contained data about the subject's status 6 months post severe traumatic brain injury (recovery, disability, persistent vegetative state, and death). Odds ratio (OR) with 95% confidence intervals (CIs) was calculated comparing the prevalence of persistent vegetative state to that of recovery, disability, and death; 6 months post severe traumatic brain injury using the dichotomous method with a random- or fixed-effect model.

Results: Significantly higher prevalence was found of recovery (OR, 0.08; 95% CI, 0.03-0.20, P < .001); disability (OR, 0.09; 95% CI, 0.06-0.15, P < .001); and death (OR, 0.07; 95% CI, 0.04-0.11, P < .001) compared to the prevalence of persistent vegetative state. The prevalence of persistent vegetative state was variable over time. Also, the prevalence of persistent vegetative states in developing countries was much higher than in developed countries.

Conclusions: However, persistent vegetative state is the poorest result apart from mortality in subjects with severe traumatic brain injury. Its prevalence is lower than the recovery, disability, and death even in developing counties with its lower healthcare services. The prevalence was variable over time and higher in developing countries. This relationship forces us to recommend improving healthcare services to the extent that a persistent vegetative state could be avoided as much as possible.
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http://dx.doi.org/10.1111/ijcp.13835DOI Listing
April 2021

Clinical Efficacy and Safety of Eight Traditional Chinese Medicine Combined with Entecavir in the Treatment of Chronic Hepatitis B Liver Fibrosis in Adults: A Network Meta-Analysis.

Evid Based Complement Alternat Med 2020 30;2020:7603410. Epub 2020 Sep 30.

College of Pharmacy, Chengdu University of Traditional Chinese Medicine, Chengdu 611137, China.

Background: Traditional Chinese medicine (TCM) is used as an adjuvant drug for the treatment of chronic hepatitis B liver fibrosis and is used frequently. We still do not know which TCM has the best curative effect as an adjuvant drug. Therefore, we decided to use network meta-analysis to solve this problem.

Methods: We used the RevMan software (5.3) and Stata software (13.0) to achieve this network meta-analysis (NMA). The primary outcomes of this study were HA, LN, PCIII, and IV-C; the secondary outcomes of this study were AST, ALT, and HBV-DNA negative conversion rate, and the Cochrane risk-of-bias tool was used to assess the quality of the included studies. For all outcomes, the scissors funnel plot, Egger test, and Begg test were used to detect publication bias, and sensitivity analysis was used to investigate the stability of the results. And the meta-regression was used to explore the source of heterogeneity.

Results: A total of 34 articles were included in this study. The study involved a total of 3199 patients, of which 1578 were assigned to the control group and 1621 patients were assigned to the experimental group. The number of men and women is roughly equal, and the average age is about 43 years old. In addition, nine treatment strategies were involved in this study. The combination of TCM and entecavir can significantly improve the patients' HA, LN, PCIII, IV-C, AST, ALT, and HBV-DNA negative conversion rates. The comprehensive evaluation results showed that FHC combined with entecavir has more advantages than other treatment strategies.

Conclusion: For improving the HBV-DNA negative conversion rates, adding TCM to the therapeutic strategies does not seem to show absolute superiority. Finally, FHC combined with entecavir is the best therapeutic strategy.
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http://dx.doi.org/10.1155/2020/7603410DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7545414PMC
September 2020

An investigation of the pharmacological applications used for the Ancient Egyptian systemic model 'ra-ib' compared with modern Traditional Chinese Medicine.

J Ethnopharmacol 2021 Jan 3;265:113115. Epub 2020 Sep 3.

LU-European Center for Chinese Medicine and Natural Compounds, Institute of Biology, Leiden University, Sylviusweg 72, 2333 BE, Leiden, the Netherlands; SU BioMedicine, Post Bus 546, 2300 AM, Leiden, the Netherlands; Shenzhen HUAKAI TCM and Natural Medicine Research Center, NO. 2, Boya Building, Zone A, Dawang Cultural and Creative Industrial Park, Wutong Mountain, No. 197, Kengbei Village, Luohu District, Shenzhen, 518114, China. Electronic address:

Ethnopharmacological Relevance: Ancient Egyptian texts only offer glimpses into their conceptual understandings of the inner-body and illness manifestation. Explanations of how prescribed materia medica were believed to work are rare and obscure, often resulting in modern approximations for ancient terminology such as 'ra-ib'-an ancient Egyptian classification predominantly translated as 'stomach'-leading to misunderstandings of historical texts, and therefore their use of pharmacology.

Aim Of The Study: To investigate the ra-ib and the explanatory models of illness from the Egyptian perspective, and to explore the link between these and the prescribed selection of materia medica. To then compare the conceptual mechanics of these treatment strategies with those of another non-Western tradition-namely Traditional Chinese Medicine (TCM)-to provide further insight into potential conceptual frameworks.

Materials And Methods: We conducted a case study of a unit of Ancient Egyptian texts focusing on the ra-ib. Totalling 34 prescriptions, the first stage lexicographically analysed the texts using cognitive linguistic and translation theories to produce our new understanding. This enabled our comparison of the mechanics of materia medica usage within these texts with those found in TCM outlined by the Pharmacopoeia of the Peoples Republic of Pharmacopeia of the People's Republic of China 2015 for the relevant ingredients.

Results: the study demonstrated that-rather than denoting the organ 'stomach'-ra-ib instead constitutes a system running from the mouth, downward to the anus. This is best translated as 'inner thoroughfare', and changes the way in which we attempt to understand potential motivations in the selection of ingredients. By exploring common themes in the use of eleven securely translated ingredients from the Egyptian corpus and the Pharmacopoeia of the People's Republic of China-representing a modern traditional system which understands the body via a series of interconnected systems-we were able to highlight certain themes which might be 'universal' to system-based traditions; this provided new insights into the Egyptian motivations for treatment selection.

Conclusions: Having gained the ancient view of the body and illness, cultural comparisons are important for providing further potential insights and clarifications of a discontinued historical healing tradition. The new understanding of the ra-ib from our study greatly changes the way in which we understand the dynamics of Egyptian ethnopharmacological source material from this period.
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http://dx.doi.org/10.1016/j.jep.2020.113115DOI Listing
January 2021

Centrosomal protein TAX1BP2 inhibits centrosome-microtubules aberrations induced by hepatitis B virus X oncoprotein.

Cancer Lett 2020 11 19;492:147-161. Epub 2020 Aug 19.

School of Biomedical Sciences, Hong Kong; State Key Laboratory of Liver Research (The University of Hong Kong), The University of Hong Kong, 21 Sassoon Road, Pokfulam, Hong Kong. Electronic address:

Liver cancer (hepatocellular carcinoma, HCC) is one of the most prevalent cancers worldwide. Several etiological factors of HCC, including hepatitis B or hepatitis C virus infection, liver cirrhosis and aflatoxin B1 intake has been identified. HBx, which is an oncogenic protein encoded by the hepatitis B virus, is strongly associated with hepatocarcinogenesis. Using stable HBx-expressing cell, we showed that HBx induced chromosome gain, with amplification of centrosomes numbers and deregulation of centrosome ultrastructure. To dissect the mechanism for chromosome instability, our result revealed that HBx contributed to a hyperactive centrosome-microtubule dynamics by accelerating microtubule nucleation and polymerization. Further investigations suggested that HBx interacted with a centrosome linker protein TAX1BP2, which has previously been shown to function as an intrinsic block of centrosome amplification and a tumour suppressor in HCC. Restoring TAX1BP2 was able to block HBx-mediated centrosome amplification and abolish the HBx-mediated centrosome aberration, thereby suppressing chromosome instability. Thus, we demonstrate here a mechanism by which HBx deregulates centrosome-microtubule dynamics through interacting with TAX1BP2, which underlines the possibility of restoration of TAX1BP2 to rescue cells from chromosome instability.
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http://dx.doi.org/10.1016/j.canlet.2020.08.005DOI Listing
November 2020

Clinical efficacy and safety of Tanreqing injection combined with antibiotics versus antibiotics alone in the treatment of pulmonary infection patients after chemotherapy with lung cancer: A systematic review and meta-analysis.

Phytother Res 2021 Jan 11;35(1):122-137. Epub 2020 Aug 11.

Department of Pharmacy, Chinese PLA General Hospital, Beijing, China.

This study aimed to evaluate the efficacy and safety of Tanreqing injection (TRQi) in the treatment of pulmonary infection after chemotherapy in patients with lung cancer. Cochrane Library, PubMed, Web of Science, EMbase, CNKI, VMIS, Wan-Fang, and CBM databases were comprehensively searched from established to March 2020. randomized controlled trials (RCTs) of TRQi were selected. The evaluation manual of Cochrane RCT was used to evaluate the methodological quality of all included studies, Stata 13.0 and Review Manager 5.3 software was used for meta-analysis. This study is registered with PROSPERO (CRD42020175533). Eighteen RCTs with a total of 1,438 patients were met the inclusion criteria. Meta-analysis showed that compared with antibiotics alone, TRQi plus antibiotics could significantly improve the clinical efficacy, defervescence time, lung rale disappearance time, cough disappearance time, and average hospitalization time, reduce white blood cell, C-reactive protein, and procalcitonin levels, and adverse reactions. However, due to the small sample size and low quality of the study, more rigorous and more RCTs are needed for further verification. In conclusion, this study provides useful evidence for the efficacy and safety of TRQi combined with antibiotics in the treatment of pulmonary infection after chemotherapy with lung cancer.
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http://dx.doi.org/10.1002/ptr.6790DOI Listing
January 2021

Combination Compositions Composed of l-Glutamine and Si-Jun-Zi-Tang Might Be a Preferable Choice for 5-Fluorouracil-Induced Intestinal Mucositis: An Exploration in a Mouse Model.

Front Pharmacol 2020 17;11:918. Epub 2020 Jun 17.

School of Pharmacy, Chengdu University of Traditional Chinese Medicine, Chengdu, China.

Intestinal mucositis is a common toxicity of many anti-neoplastic therapies that negatively influences health, the quality of life, economic outcomes, and even the success of cancer treatment. Unfortunately, there is presently no optimal medicine that is able to effectively manage this condition. l-glutamine is one of the most frequently used agent in practice among the limited treatment choices due to its safety and inexpensiveness despite there being a lack of evidence. Previous studies indicated that l-glutamine may alleviate mucositis and mucosal atrophy but failed to improve patients' macroscopic conditions, such as the occurrence of diarrhea. A compound glutamine capsule (G-SJZ), composed of l-glutamine and the traditional Chinese herbal formula Si-Jun-Zi-Tang, has been used in China for 23 years to treat many types of gastrointestinal diseases, including gastrointestinal reactions induced by radiotherapy and chemotherapy. However, the exact effect of G-SJZ on intestinal mucositis is unclear, and moreover, whether l-glutamine combined with Si-Jun-Zi-Tang is more effective than l-glutamine alone have not been studied. In the current study, we explored the effects of G-SJZ and l-glutamine in a mouse model of intestinal mucositis induced by 5-fluorouracil (5-Fu). The results revealed that pretreatment with G-SJZ ameliorated the physical manifestations of weight loss and the severity of diarrhea following continuous 5-Fu injections in mice. Likewise, the histopathological damage and the destruction of villus and crypt structures in the intestinal mucosa as well as the increase in circulating intestinal injury markers caused by 5-Fu were reversed with G-SJZ pretreatment. Furthermore, the protective effect of G-SJZ was accompanied by modulations in the immunohistochemical expression of tight junction proteins. Interestingly, although treatment with a dose of l-glutamine alone that was equivalent to the dose in G-SJZ also showed a protective effect, it did not appear to be as strong as treatment with G-SJZ. Si-Jun-Zi-Tang in G-SJZ may compensate for the deficiencies of l-glutamine in this model which seems not to be related to the regulation of tight junction proteins. Our study is the first to suggest that the combined use of l-glutamine and Si-Jun-Zi-Tang might be more effective than l-glutamine alone despite exact mechanism still needs further study. Because of the limited number of therapeutic agents, G-SJZ is likely to be a preferable choice for intestinal mucositis.
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http://dx.doi.org/10.3389/fphar.2020.00918DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7313676PMC
June 2020

Modulation of Donor Alkyl Terminal Chains with the Shifting Branching Point Leads to the Optimized Morphology and Efficient All-Small-Molecule Organic Solar Cells.

ACS Appl Mater Interfaces 2020 Jun 19;12(22):25100-25107. Epub 2020 May 19.

CAS Key Laboratory of Nanosystem and Hierarchical Fabrication, CAS Center for Excellence in Nanoscience, National Center for Nanoscience and Technology, Beijing 100190, China.

Terminal group modification is one of the most influential factors for small-molecular donors compared with their polymer counterparts, resulting in an opportunity to optimize the morphology of all-small-molecule organic solar cells (ASM-OSCs). In this article, we report three novel small-molecular donors with branching points at the 1-, 2-, and 3-positions in alkyl terminal chains, called , , and , respectively. Using IDIC-4Cl as the acceptor, the subtle branching position shift achieves a dramatic disparity in photovoltaic parameters, as indicated by the short circuit current () changing from 4.9 to 20.1 to 14.2 mA cm and the fill factor varying from 33.9 to 71.3 to 67.0% for , , and , respectively. The best device performance of 12.40% is obtained by the :IDIC-4Cl system, which not only ranks among the top values reported to date but also exhibits low energy loss in systems that use IDIC as acceptors. The notable device performance based on is attributed to the optimized phase morphology caused by the strong molecular crystallinity and suitable intermolecular interaction with IDIC-4Cl. These results demonstrate that suitably tuning the branching position of terminal groups could promote the high performance of ASM-OSCs.
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http://dx.doi.org/10.1021/acsami.0c03977DOI Listing
June 2020

p38 promoted retinal micro-angiogenesis through up-regulated RUNX1 expression in diabetic retinopathy.

Biosci Rep 2020 05;40(5)

Department of Ophthalmology, The Affiliated Wuxi No. 2 People's Hospital of Nanjing Medical University, Zhongshan Road 68, Wuxi 214002, Jiangsu, China.

Diabetic retinopathy (DR) is the most common microvascular complication of diabetes and is characterized by visible microvascular alterations including retinal ischemia-reperfusion injury, inflammation, abnormal permeability, neovascularization and macular edema. Despite the available treatments, some patients present late in the course of the disease when treatment is more difficult. Hence, it is crucial that the new targets are found and utilized in the clinical therapy of DR. In the present study, we constructed a DR animal model and a model in HRMECs to investigate the relationship between p38 and RUNX1 in retinal micro-angiogenesis in diabetic retinopathy. We found that p38 could promote retinal micro-angiogenesis by up-regulating RUNX1 expression in diabetic retinopathy. This suggested that the p38/ RUNX1 pathway could become a new retinal micro-angiogenesis target in DR treatment.
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http://dx.doi.org/10.1042/BSR20193256DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7201564PMC
May 2020

Role of Xingnaojing Injection in treating acute cerebral hemorrhage: A systematic review and meta-analysis.

Medicine (Baltimore) 2020 Apr;99(15):e19648

School of Pharmacy, Chengdu University of Traditional Chinese Medicine, Chengdu, China.

Background: Xingnaojing injection (XNJi) is widely used for acute cerebral hemorrhage. However, the efficacy of XNJi for acute cerebral hemorrhage has not been comprehensively proved by systematic analysis yet. Therefore, it is essential to evaluate the efficacy and safety of XNJi in an evidence-based method.

Methods: Six databases were searched with XNJi used for acute cerebral hemorrhage in randomized controlled trials (RCTs). Meta-analysis was performed by Review Manager 5.3. The efficacy rate, brain edema, cerebral hematoma, neurological deficit score, hs-crp, Glasgow Coma Scale (GCS), and activities of daily living (ADL) were systematically evaluated. The Cochrane risk of bias was used to evaluate the methodological quality of eligible studies.

Results: This study is registered with PROSPERO (CRD42018098737). Twenty-nine studies with a total of 2638 patients were included in this meta-analysis. Compared with conventional treatment, XNJi got higher efficacy rate (OR = 3.37, 95% CI [2.65, 4.28], P < .00001). Moreover, XNJi showed significant enhancement of efficacy rate via subgroup analysis in course and dosage. In addition, XNJi demonstrated significant improvement in Chinese stroke scale (CSS) and National Institutes of Health Stroke Scale (NHISS) (mean difference [MD] = -4.74, 95% CI [-5.89, -3.60], P < .00001; MD = -4.45, 95% CI [-5.49, -3.41], P < .00001), GCS (MD = 2.72, 95% CI [2.09, 3.35], P < .00001). It also remarkably decreased the level of hs-crp (MD = -6.50, 95% CI [-7.79, -5.21], P < .00001), enhanced ADL (MD = 20.38, 95% CI [17.98, 22.79], P < .00001), and alleviated hematoma and edema (MD = -2.53, 95% CI [-4.75, -0.31] P < .05; MD = -1.74 95% CI [-2.42, -1.07] P < .00001) compared with conventional treatment.

Conclusion: XNJi is effective in treating acute cerebral hemorrhage with significant improvement of CSS, NHISS and impairment of hs-crp, hematoma, and edema compared with conventional treatment. Moreover, XNJi got remarkable efficacy at the dose of 20, 30, 60 mL and from 7 to 28 days. No serious adverse reactions occurred. These results were mainly based on small-sample and low-quality studies. Therefore, more rigorous, large-scale RCTs were further needed to confirm its efficacy, safety, and detailed characteristic of application.
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http://dx.doi.org/10.1097/MD.0000000000019648DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7220447PMC
April 2020

FoxM1 affects adhesive, migratory, and invasive abilities of human retinoblastoma Y-79 cells by targeting matrix metalloproteinase 2.

Acta Biochim Biophys Sin (Shanghai) 2020 Mar;52(3):294-301

Save Sight Institute, University of Sydney, Sydney, New South Wales 2000, Australia.

Forkhead box protein M1 (FoxM1) is an important transcription factor involved in various pathological processes including tumor metastasis. The changes of adhesive, migratory, and invasive abilities are considered as crucial events in tumor metastasis progression. In this study, we aimed to investigate the correlation between FoxM1 and retinoblastoma (Rb) metastasis and to explore the detailed mechanism. Wound healing, cell adhesion, and invasion assays showed that FoxM1 overexpression induced epithelial-mesenchymal transition in Y-79 cells and inhibited adhesion and subsequently promoted metastasis of Y-79 cells, while FoxM1 knockdown showed the opposite effects. A luciferase reporter assay and chromatin immunoprecipitation assay provided evidence that FoxM1 promoted matrix metalloproteinase 2 (MMP2) transcription by directly binding to and promoting MMP2 promoter. MMP2 knockdown by siRNA transfection attenuated cell metastasis of Y-79 cells induced by FoxM1 overexpression. Furthermore, the FoxM1-binding site mapped between -1167 and -1161 bp of the MMP2 promoter was identified. Our results suggested that the FoxM1-MMP2 axis plays an important role in Rb metastasis, which may be a novel target for designing therapeutic regimen to control Rb metastasis.
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http://dx.doi.org/10.1093/abbs/gmz160DOI Listing
March 2020

Therapeutic effects of higenamine combined with [6]-gingerol on chronic heart failure induced by doxorubicin via ameliorating mitochondrial function.

J Cell Mol Med 2020 04 19;24(7):4036-4050. Epub 2020 Feb 19.

Department of Pharmacy, The Fifth Medical Center of PLA General Hospital, Beijing, China.

Higenamine (HG) is a natural benzylisoquinoline alkaloid isolated from Aconitum with positive inotropic and chronotropic effects. This study aimed to investigate the possible cardioprotective effects of HG combined with [6]-gingerol (HG/[6]-GR) against DOX-induced chronic heart failure (CHF) by comprehensive approaches. DOX-induced cardiotoxicity model in rats and H9c2 cells was established. Therapeutic effects of HG/[6]-GR on haemodynamics, serum indices and histopathology of cardiac tissue were analysed. Cell mitochondrial energy phenotype and cell mitochondrial fuel flex were measured by a Seahorse XFp analyser. Moreover, UHPLC-Q-TOF/MS was performed to explore the potential metabolites affecting the therapeutic effects and pathological process of CHF. To further investigate the potential mechanism of HG/[6]-GR, mRNA and protein expression levels of RAAS and LKB1/AMPK/Sirt1-related pathways were detected. The present data demonstrated that the therapeutic effects of HG/[6]-GR combination on CHF were presented in ameliorating heart function, down-regulation serum indices and alleviating histological damage of heart tissue. Besides, HG/[6]-GR has an effect on increasing cell viability of H9c2 cells, ameliorating DOX-induced mitochondrial dysfunction and elevating mitochondrial OCR and ECAR value. Metabolomics analyses showed that the therapeutic effect of HG/[6]-GR combination is mainly associated with the regulation of fatty acid metabolites and energy metabolism pathways. Furthermore, HG/[6]-GR has an effect on down-regulating RAAS pathway-related molecules and up-regulating LKB1/AMPKα/Sirt1-related pathway. The present work demonstrates that HG/[6]-GR prevented DOX-induced cardiotoxicity via the cardiotonic effect and promoting myocardial energy metabolism through the LKB1/AMPKα/Sirt1 signalling pathway, which promotes mitochondrial energy metabolism and protects against CHF.
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http://dx.doi.org/10.1111/jcmm.15041DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7171398PMC
April 2020

Antitumor Effects of Trimethylellagic Acid Isolated From L. on Colorectal Cancer Angiogenesis Inhibition and Apoptosis Induction.

Front Pharmacol 2019 28;10:1646. Epub 2020 Jan 28.

Department of Pharmacology, School of Pharmacy, Southwest Medical University, Luzhou, China.

Previous studies have demonstrated that tannin could inhibit the proliferation and angiogenesis of cancer cells. However, the mechanism(s) associated with its antitumor effect remains unclear. Here, we investigated the effects of 3,3',4'-trimethylellagic acid (TMEA), a tannin compound isolated from L., on the proliferation, angiogenesis, and apoptosis in cancer cells, as well as the underlying mechanism(s) related to its antitumor activity. TMEA was isolated from L. by silica gel column chromatography. Molecular docking was carried out to assess active pocket binding between TMEA and vascular endothelial growth factor receptor 2 (VEGFR2). The antiangiogenic effect of TMEA on the migration and tube formation was detected in HUVECs by wound healing and tube formation assays, respectively. The antitumor effects of TMEA on the cell proliferation were determined in HepG2, A549, and SW620 cells by MTS assay and on the tumor growth of SW620 xenografts bearing in nude mice . The mRNA expression of Bcl-2, Bax, caspase-3, VEGF, PI3K, and mTOR were measured by qRT-PCR and protein expression of Bcl-2, Bax, caspase-3, VEGF, PI3K, and mTOR by Western blotting, and the protein expression of Bcl-2, Bax, caspase-3 and CD31 were detected by immunohistochemical analysis , respectively. The results showed that TMEA combined with VEGFR2 in the functional pockets of Asn223A, Gly922A, and Leu840A and inhibited the proliferation, migration, tube formation, and expression of VEGF and its downstream signaling mediators in HUVECs. TMEA also significantly inhibited the proliferation of HepG2, A549, and SW620 cancer cells , and suppressed the growth of SW620 tumors . Moreover, TMEA upregulated the expression of proapoptotic factors Bax and caspase-3 and downregulated the expression of antiapoptotic factors CD31 and Bcl-2 in cancer cells and/or tumor tissues. The data indicate that TMEA executes its anticancer activity by inducing apoptosis and inhibiting angiogenesis in cancer cells and tumor growth . The underlying anticancer mechanism is associated with the apoptotic and VEGF/PI3K/AKT/mTOR pathways.
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http://dx.doi.org/10.3389/fphar.2019.01646DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6997556PMC
January 2020

A de novo nonsense mutation in the N-terminal of ligand-binding domain of NR2F1 gene provoked a milder phenotype of BBSOAS.

Ophthalmic Genet 2020 02 3;41(1):88-89. Epub 2020 Feb 3.

Department of Ophthalmology, The Affiliated Wuxi No.2 People's Hospital of Nanjing Medical University, Wuxi, China.

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http://dx.doi.org/10.1080/13816810.2020.1719520DOI Listing
February 2020

ASK1 induces retinal microvascular endothelial cell apoptosis through ER stress-associated pathway.

Int J Clin Exp Pathol 2019 1;12(4):1324-1332. Epub 2019 Apr 1.

Department of Ophthalmology, Shanghai First People's Hospital of Nanjing Medical University Shanghai, China.

Diabetic retinopathy (DR) is a major microvascular complication in patients with diabetes mellitus; it can cause a variety of eye problems in a high percentage of diabetic patients. The purpose of this study was to determine the role of apoptosis signal-regulating kinase 1 (ASK1) in the regulation of the endoplasmic reticulum (ER) stress-associated apoptosis pathway in microvascular endothelial cells. For studies, a streptozotocin (STZ)-induced diabetes model was used to assess apoptosis in retinal tissues. Apoptotic cell death was determined by TUNEL assay. For studies, a high glucose (HG)-induced retinal microvascular endothelial cell injury model was generated to evaluate apoptosis. Apoptotic rates were measured by flow cytometry and apoptosis-related proteins were detected by western blotting. We found that retinal microvascular endothelial cell apoptosis was increased in both animal and cell models. HG-induced apoptosis primarily occurred in an ER stress-dependent manner. HG-induced apoptosis was alleviated by inhibiting ASK1 with shRNA or a specific inhibitor, NQDI-1. TUNEL and western blot assays showed that ASK1 promoted the expression of ER stress-related proteins that are the master regulators of DR. Our study suggests that ASK1 functions as a promoter of DR through the ER stress-induced apoptosis pathway, and it may be a therapeutic target for DR.
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http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6947079PMC
April 2019
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