Publications by authors named "Liying Tang"

45 Publications

Characteristics of TCM Constitution and Related Biomarkers for Mild Cognitive Impairment.

Neuropsychiatr Dis Treat 2021 20;17:1115-1124. Epub 2021 Apr 20.

Department of Acupuncture and Moxibustion, The First Affiliated Hospital of Guangxi University of Chinese Medicine, Nanning, 530023, People's Republic of China.

Introduction: The incidence of Alzheimer's disease is on the rise, early detection of cognitive impairment of the elderly is very important. In traditional Chinese medicine, constitution is related to the susceptibility of the human body to diseases. Based on the theory of constitution of traditional Chinese medicine (TCM), the human population can be classified into 9 constitutions. However, little is known about the characteristics of medical constitution and related biomarkers in subjects with mild cognitive impairment (MCI).

Methods: We measured the TCM Constitution of 214 subjects by using the Constitution in Chinese Medicine Questionnaire (CCMQ). MMSE and MoCA were used to assess cognitive function. The subjects were divided into mild cognitive impairment group (MCI, n = 152) and normal control group (NC, n = 62). The levels of serum Hcy and serum/urine 8-iso-PGF 2α were determined.

Results: 1) It was found that there was a significant difference in constitution types between MCI and NC. There were significant differences in MMSE and MoCA score, serum Hcy and serum/urine 8-iso-PGF 2a levels between the two groups. 2) In logistic regression analysis, the variables with statistical significance were TCM Constitution of Yang-Deficient, Phlegm-Dampness, Blood-Stasis and abnormal increase of Hcy (OR>1). 3) The MoCA scores had a positive correlation with the MMSE. A statistically significant inverse association was found between serum Hcy, blood and urine 8-iso-PGF 2a and scores of cognitive assessment in MCI.

Conclusion: Constitution types (Yang-Deficient, Phlegm-Dampness and Blood-Stasis) and abnormal serum Hcy elevation can be used as risk factors for MCI. MoCA scores can serve to detect MCI at early stage. Serum/urine 8-iso-PGF 2α has a certain relationship with MCI. Higher levels of serum/urine 8-iso-PGF 2α are more likely to be associated with MCI risk.
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http://dx.doi.org/10.2147/NDT.S290692DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8068505PMC
April 2021

Casein Kinase 2-Interacting Protein-1 Alleviates High Glucose-Reduced Autophagy, Oxidative Stress, and Apoptosis in Retinal Pigment Epithelial Cells via Activating the p62/KEAP1/NRF2 Signaling Pathway.

J Ophthalmol 2021 11;2021:6694050. Epub 2021 Feb 11.

Department of Geriatrics, Beijing Chaoyang Hospital, Capital Medical University, Beijing 100043, China.

Background: Casein kinase 2-interacting protein-1 (CKIP-1) has been proved to be associated with complications of diabetes. Diabetic retinopathy is a main diabetic complication which usually leads to blindness. The current study aims to investigate the role of CKIP-1 in high glucose-treated retinal pigment epithelial (RPE) cells which is a component of blood-retinal barriers.

Methods: The RPE cells, ARPE-19, are treated with high glucose to mimic the diabetic stimulation. CKIP-1 was overexpressed in ARPE-19 cells to evaluate its effects on autophagy, oxidative stress, and apoptosis induced by high glucose treatment, using Western blot, immunofluorescence, and flow cytometry assays, respectively.

Results: CKIP-1 was expressed at a lower level in high glucose-treated cells than in normal glucose cells. Overexpression of CKIP-1 enhanced the Nrf2 translocation to the nucleus. Furthermore, high glucose-induced autophagy, oxidative stress, and apoptosis were inhibited after overexpression of CKIP-1. Also, CKIP-1 regulates the p62/Keap1/Nrf2 signaling, which might be the potential mechanism in this model.

Conclusion: In conclusion, CKIP-1 may be a potential therapeutic target that protects RPE cells from injury and subsequent diabetic retinopathy induced by high glucose.
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http://dx.doi.org/10.1155/2021/6694050DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7892229PMC
February 2021

Withaferin A protects against hyperuricemia induced kidney injury and its possible mechanisms.

Bioengineered 2021 12;12(1):589-600

Department of Geriatrics, Beijing Chaoyang Hospital Affiliated to Capital Medical University , Beijing, China.

The study was designed to explore the effects of Withaferin A (WFA) on hyperuricemia-induced kidney injury and its action mechanism. Potassium oxonate (PO) was employed to establish the hyperuricemic mouse model. The pathological changes of renal tissue were evaluated by hematoxylin-eosin and masson trichrome staining. The levels of creatinine, blood urea nitrogen (BUN), uric acid (UA) and xanthine oxidase (XOD) were detected using corresponding commercial kits. Expressions of collagen-related and apoptosis-associated proteins in renal tissues were, respectively, evaluated by immunofluorescence and western blotting. Cell apoptosis was detected by TUNEL assay, and transporter expressions using western blotting. Followed by WFA, NRK-52E cells were treated with UA before evaluation of apoptosis and fibrosis. Results indicated that WFA ameliorated renal damage, improved kidney function, and decreased levels of creatinine, BUN, UA, and XOD in PO-induced hyperuricemic mice. Furthermore, WFA significantly prevented renal fibrosis and increased the expression of collagen-related proteins. Similarly, WFA markedly inhibited renal apoptosis, accompanied by changes of apoptosis-related proteins. Importantly, expression of transporters responsible for the secretion of organic anion transporter 1 (OAT1), OAT3, ATP-binding cassette subfamily G member 2 (ABCG2) was remarkably enhanced whereas that of urate transporter 1 (URAT1) and glucose transporter 9 (GLUT9) was reduced in renal tissues of mice with hyperuricemia. study revealed that WFA notably ameliorated UA-induced cell fibrosis and apoptosis. Taken together, WFA improves kidney function by decreasing UA via regulation of XOD and transporter genes in renal tubular cells.
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http://dx.doi.org/10.1080/21655979.2021.1882761DOI Listing
December 2021

Role of CD4+ T Helper Cells in the Development of BAC-Induced Dry Eye Syndrome in Mice.

Invest Ophthalmol Vis Sci 2021 01;62(1):25

Department of Ophthalmology, Xiang'an Hospital of Xiamen University, Fujian Provincial Key Laboratory of Ophthalmology and Visual Science, Eye Institute of Xiamen University, School of Medicine, Xiamen University, Xiamen, Fujian, China.

Purpose: To evaluate the role of CD4+ T helper cells in benzalkonium chloride (BAC)-induced ocular surface disorder in C57BL/6 mice.

Methods: Topical 0.075% BAC was applied twice daily in C57BL/6 mice for 7 consecutive days; PBS-treated and untreated mice served as controls. Adoptive transfer of CD4+ T cells isolated from the BAC-treated mice or PBS-treated mice into nude mice was conducted to identify the roles of CD4+ T cells, with untreated nude mice as controls. Oregon green dextran staining, PAS staining, and the phenol red cotton test were carried out in these two models. The gene and protein levels of T-bet, IFN-γ, RORγt, and IL-17 were detected by quantitative RT-PCR and ELISA, respectively. The activation and subsets of CD4+ T cells were identified by double immunofluorescent staining and flow cytometry.

Results: An increase in CD4+CD69+, CD4+IFN-γ+, and CD4+IL-17+ cells was induced by BAC in C57BL/6 mice. IFN-γ, IL-17, Th1, Th17, and the transcription factors T-bet and RORγt were increased in BAC-treated mice compared with control mice. In addition, ocular surface damage, including corneal barrier dysfunction, goblet cell loss, and decreased tear production, was induced by BAC. Interestingly, adoptive transfer of CD4+ T cells isolated from BAC-treated mice into nude mice resulted in ocular surface manifestations similar to those of direct topical BAC treatment of C57BL/6 mice, including increased CD4+ T cells, IFN-γ, IL-17, and ocular surface disorders.

Conclusions: Topical application of BAC induced a dry-eye-like ocular surface disorder partly through the CD4+ T cell-mediated inflammatory response.
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http://dx.doi.org/10.1167/iovs.62.1.25DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7838551PMC
January 2021

Comparison of Treatment Effect and Tolerance of the Topical Application of Mizoribine and Cyclosporine A in a Mouse Dry Eye Model.

Transl Vis Sci Technol 2020 12 15;9(13):22. Epub 2020 Dec 15.

Department of Ophthalmology, Xiang'an Hospital of Xiamen University, Fujian Provincial Key Laboratory of Ophthalmology and Visual Science, Eye Institute of Xiamen University, School of Medicine, Xiamen University, Xiamen, Fujian, China.

Purpose: To compare the treatment effects and tolerability of a topical application of mizoribine (MZR) and cyclosporine A (CsA) eye drops (Restasis; Allergan, Inc., Irvine, CA, USA) in a mouse dry eye model.

Methods: C57BL/6 mice subjected to desiccating stress (DS) were treated with 0.05% MZR in phosphate-buffered saline (PBS) or Restasis eye drops four times a day for 5 days. Untreated mice served as control. Tear secretion, Oregon green dextran staining, and the conjunctival goblet cell quantity were evaluated. The apoptosis and matrix metalloproteinase 9 (MMP-9) in the ocular surface, conjunctival CD4, and T helper-related cytokines were verified. The ocular tolerance of these two drugs was evaluated by observing the mice's behavioral changes.

Results: Topical administrations of MZR or Restasis both increased tear production, maintained goblet cell density, and improved corneal barrier function. Both MZR and Restasis suppressed the expression of MMP-9 and apoptosis in the ocular surface. Meanwhile, both MZR and Restasis decreased the infiltration of CD4 T cells, reversed the production of interferon-γ, interleukin (IL)-17A, and IL-13 in conjunctiva under DS. The abovementioned efficacies between these two eye drops were not statistically significant. However, the number of scratching and wiping behaviors in the MZR-treated group was significantly less than in the Restasis-treated group.

Conclusions: MZR (0.05% in PBS) could be a good competitive product for Restasis because of the comparable treatment effect in dry eye diseases and better ocular tolerability in ocular itch and pain.

Translational Relevance: This study provided an immunosuppressive agent comparable to Restasis for the treatment of dry eye disease.
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http://dx.doi.org/10.1167/tvst.9.13.22DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7745621PMC
December 2020

Efficacy and Safety of Eye Drops Atomization Treatment for Meibomian Gland Dysfunction-Related Dry Eye Disease: A Randomized, Double-Blinded, Placebo-Controlled Clinical Trial.

J Clin Med 2020 Dec 12;9(12). Epub 2020 Dec 12.

Department of Ophthalmology, Xiang'an Hospital of Xiamen University, Fujian Provincial Key Laboratory of Ophthalmology and Visual Science, Xiamen 361102, China.

Purpose: To evaluate the efficacy and safety of eye drops (a Chinese traditional medicine) atomization treatment in meibomian gland dysfunction (MGD)-related dry eye disease (DED) patients.

Methods: A total of 240 eligible patients diagnosed with MGD-related DED were assigned either eye drops or placebo for atomization once daily for four weeks in a multi-center, randomized, double-blind, placebo-controlled clinical study. Primary outcome evaluations used included eye symptom score (using the Chinese Dry Eye Questionnaire), meibum quality, and tear break-up time (TBUT), while safety evaluations included adverse events (AEs), visual acuity, and intraocular pressure monitoring. Indicators were measured at baseline as well as one week, two weeks, and four weeks after treatment.

Results: Primary outcome measures of the group were improved compared with their placebo counterparts following four-week treatment. Eye symptom scores were significantly reduced relative to the baseline in the group (mean ± standard error of the mean, 9.00 ± 0.61) compared with the placebo group (6.29 ± 0.55; = 0.0018). Reduction in meibum quality score in the group (0.91 ± 0.10) was also significantly higher compared with the placebo group (0.57 ± 0.10; = 0.0091), while TBUT in the treatment group (6.30 ± 0.22) was also longer than in the latter (5.60 ± 0.24; = 0.0192). No medication-related adverse events were observed.

Conclusions: Atomization treatment with eye drops is both clinically and statistically effective for the treatment of mild to moderate MGD-related DED patients. This approach is generally safe and was tolerated well by patients.
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http://dx.doi.org/10.3390/jcm9124022DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7763017PMC
December 2020

IL-1/IL-1R signaling induced by all-trans-retinal contributes to complement alternative pathway activation in retinal pigment epithelium.

J Cell Physiol 2021 May 9;236(5):3660-3674. Epub 2020 Oct 9.

Fujian Provincial Key Laboratory of Ophthalmology and Visual Science, School of Medicine, Eye Institute of Xiamen University, Xiamen University, Xiamen, China.

The underlying mechanisms of complement activation in Stargardt disease type 1 (STGD1) and age-related macular degeneration (AMD) are not fully understood. Overaccumulation of all-trans-retinal (atRAL) has been proposed as the pathogenic factor in both diseases. By incubating retinal pigment epithelium (RPE) cells with atRAL, we showed that C5b-9 membrane attack complexes (MACs) were generated mainly through complement alternative pathway. An increase in complement factor B (CFB) expression as well as downregulation of complement regulatory proteins CD46, CD55, CD59, and CFH were observed in RPE cells after atRAL treatment. Furthermore, interleukin-1β production was provoked in both atRAL-treated RPE cells and microglia/macrophages. Coincubation of RPE cells with interleukin-1 receptor antagonist (IL1Ra) and atRAL ameliorated complement activation and downregulated CFB expression by attenuating both p38 and c-Jun N-terminal kinase (JNK) signaling pathways. Our findings demonstrate that atRAL induces an autocrine/paracrine IL-1/IL-1R signaling to promote complement alternative pathway activation in RPE cells and provide a novel perspective on the pathomechanism of macular degeneration.
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http://dx.doi.org/10.1002/jcp.30103DOI Listing
May 2021

Identification of the Gene Family in Pomegranate ( L.) and Functional Analysis of .

Int J Mol Sci 2020 Sep 10;21(18). Epub 2020 Sep 10.

Zhengzhou Fruit Research Institute, Chinese Academy of Agricultural Sciences, Zhengzhou 450009, China.

Sucrose, an important sugar, is transported from source to sink tissues through the phloem, and plays important role in the development of important traits in plants. However, the gene family is still not well characterized in pomegranate. In this study, we first identified the pomegranate sucrose transporter ( gene family from the whole genome. Then, the phylogenetic relationship of genes, gene structure and their promoters were analyzed. Additionally, their expression patterns were detected during the development of the seed. Lastly, genetic transformation and cytological observation were used to study the function of . A total of ten pomegranate genes were identified from the whole genome of pomegranate 'Tunisia'. The promoter region of all the pomegranate genes contained myeloblastosis (MYB) elements. Four of the genes, , , and , were differentially expressed during seed development. We further noticed that was expressed most prominently in the stem parts in transgenic plants compared to other tissue parts (leaves, flowers and silique). The cells in the xylem vessels were small and lignin content was lower in the transgenic plants as compared to wild plants. In general, our result suggests that the MYB cis-elements in the promoter region might regulate expression to control the structure of xylem, thereby affecting seed hardness in pomegranate.
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http://dx.doi.org/10.3390/ijms21186608DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7554910PMC
September 2020

Farfarae Flos: A review of botany, traditional uses, phytochemistry, pharmacology, and toxicology.

J Ethnopharmacol 2020 Oct 8;260:113038. Epub 2020 Jun 8.

Institute of Chinese Materia Medica, China Academy of Chinese Medical Science, Beijing, 100700, China. Electronic address:

Ethnopharmacological Relevance: Farfarae Flos (FF; dried flower buds of Tussilago farfara L.), a widely used traditional Chinese medicine (TCM), is also known as "Kuandonghua" (Chinese: ). It has a wide range of pharmacological effects and has long been used to treat various respiratory conditions including cough, asthma, and acute or chronic bronchitis.

Aims: This study reviews the current advances in the research on the botany, ethnopharmacology, phytochemistry, pharmacology, and toxicology of Farfarae Flos. Prospects for future investigation and application of this herb are also discussed.

Materials And Methods: Information on FF was collected from both published materials (such as ancient and modern books, Ph.D. and M. Sc. dissertations, monographs on medicinal plants, and pharmacopoeia) and electronic databases (such as CNKI, SciFinder, WanFang data, PubMed, ScienceDirect, Web of Science, Taylor&Francis, ACS Publications, Wiley, Springer, Europe PMC, EBSCOhost, J-STAGE, and Google Scholar).

Results: Approximately 175 chemical compounds, including terpenoids, organic acids, flavonoids, alkaloids, chromones, volatile oils, and other compounds, have been isolated from FF. This TCM has been reported to produce pharmacological effects on the respiratory, cardiovascular, and digestive systems, and exert antioxidant, anti-inflammatory, and neuroprotective activities. FF is safe in the traditional dose range, but the potential toxicity due to the emergence of pyrrolidine alkaloids needs to be paid more attention.

Conclusions: FF is a commonly used TCM with pharmacological activities mainly on the respiratory system. This study suggests that the further expansion of the pharmacological effect of FF and in-depth study of its prescription need to be concerned about. The investigations of the role of more active substances and the pharmacokinetics of the hepatotoxic components of FF will help to maximize the therapeutic potential and promote its popularization and application. Meanwhile, it is important to pay attention to pursue research on the similarities and differences between the leaves and the flower buds to find their respective advantages and make rational use of T. farfara L.

Resources:
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http://dx.doi.org/10.1016/j.jep.2020.113038DOI Listing
October 2020

Traditional Chinese Medicine of Angelicae Pubescentis Radix: A Review of Phytochemistry, Pharmacology and Pharmacokinetics.

Front Pharmacol 2020 18;11:335. Epub 2020 Mar 18.

Institute of Chinese Materia Medica, China Academy of Chinese Medical Science, Beijing, China.

Angelicae Pubescentis Radix (APR) is a widely used antirheumatic Chinese medicinal herb known as "Duhuo" in China. It has the effects of dispelling wind and removing dampness, diffusing impediment, and relieving pain, and is mainly indicated for rheumatic arthritis with pain in the lower back and knees, and headache. To the best of our knowledge, an attempt is made to provide an up-to-date review on these aspects based on published materials, including ancient and modern books; Master's and doctoral theses; monographs on medicinal plants; the pharmacopoeia of different countries, websites for publication of patent and electronic databases, such as SCI finder, PubMed, Web of Science, ACS, Science Direct, Wiley, Springer, Taylor, CNKI, and Google Scholar. APR, which has a good clinical effect, has been used for traditional Chinese medicine more than 2000 years. Since 1957, a variety of chemical constituents have been reported from the medicinal plants of this herb, mostly coumarins and volatile oil. In the past 30 years, numerous studies have shown that the extracts and compounds isolated from APR showed effective analgesic and anti-inflammatory actions, also showing well effects on central nervous system, effects on cardiovascular system and deworming activity. In addition, we also present and discuss the botany, traditional medicinal use, pharmacokinetics, toxicity, quality control, future trends and prospects of APR. All this information suggest that future research of APR should be supplemented in the area of pharmacology and toxicology to provide further insight on the clinical use and quality control.
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http://dx.doi.org/10.3389/fphar.2020.00335DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7094754PMC
March 2020

High-fat diet induces dry eye-like ocular surface damages in murine.

Ocul Surf 2020 04 28;18(2):267-276. Epub 2020 Feb 28.

Department of Ophthalmology, Xiang'an Hospital of Xiamen University, Xiamen University Affiliated Xiamen Eye Center, Eye Institute of Xiamen University, Fujian Provincial Key Laboratory of Ophthalmology and Visual Science, School of Medicine, Xiamen University, Xiamen, China. Electronic address:

Purpose: A high-fat diet leads to dysfunction in multiple systems of the body. Herein we investigate the effects of a high-fat diet on the ocular surface using a murine model.

Methods: Four-week-old male C57BL/6 mice were fed with a standard-fat diet (10 kcal% fat, SFD) or a high-fat diet (60 kcal% fat, HFD) for 1 or 3 months. Phenol red thread test was used to detect tear production, oregon green dextran (OGD) staining was performed to assess corneal epithelial permeability, and PAS staining was conducted to ascertain the presence of conjunctival goblet cells. Squamous metaplasia in the ocular surface and corneal epithelial barrier function were detected by immunofluorescent staining, zymography and Western blot analysis. Oxidative stress related protein expression was evaluated by immunostaining and Western blot analysis. Corneal and conjunctival cell apoptosis was determined by TUNEL assay and caspase-3 expression.

Results: A HFD induced obvious ocular surface damages, including decreased tear production, notable OGD staining and distinct goblet cell loss. It also resulted in corneal epithelial barrier dysfunction and significant squamous metaplasia of the corneal and conjunctival epithelia. The HFD also upregulated key factors that regulate oxidative stress in the ocular surface, and upregulated cell apoptosis in ocular surface epithelial cells.

Conclusions: A HFD induces dry eye-like ocular surface damages in mice via the activation of oxidative stress and an induction of apoptosis in the cells of the ocular surface.
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http://dx.doi.org/10.1016/j.jtos.2020.02.009DOI Listing
April 2020

Keratocytes promote corneal neovascularization through VEGFr3 induced by PPARα-inhibition.

Exp Eye Res 2020 04 21;193:107982. Epub 2020 Feb 21.

Eye Institute of Xiamen University, Fujian Provincial Key Laboratory of Ophthalmology and Visual Science, Medical College, Xiamen University, Xiamen, Fujian, China. Electronic address:

As the peroxisome proliferator - activated receptor alpha (PPARα) agonist, fenofibrate has been widely used to be a good lipid-regulating drug in the clinical application. In this study, we investigated the mechanism by which keratocytes inhibit the corneal neovascularization (CNV) through PPARα - activation. To do this, the CNV model was established by alkali burn, followed by being divided into three groups including control, fenofibrate and vehicle group. The expression of VEGFr3, MMP13 and PPARα in corneas of normal mouse and alkali-burned mouse was determined via quantitative RT- PCR (qRT-PCR) and Western blot analysis (WB). The CNV area was observed under a slit lamp microscope. The location of PPARα expression in the corneas was determined via immunohistochemistry. In cultured primary keratocytes, the effect of fenofibrate on PPARα, VEGFr3 and MMP13 expression was determined by qRT-PCR and WB. Besides, PPARα knockout (PPARα-/-) mouse CNV and keratocytes model were established to further confirm the effect of PPARα on VEGFr3 and MMP13 expression. We found that PPARα was expressed in epithelium, stroma and endothelium of the normal cornea, however, with relatively low level in the corneal stroma. Meanwhile, its expression was decreased markedly in the cornea during the stage of CNV formation. After treatment of fenofibrate, PPARα expression was promoted and the expression of VEGFr3 and MMP13 was inhibited in both CNV mice model and primary keratocytes, and CNV areas were decreased in CNV mice model. However, the results in PPARα-/- CNV and keratocytes model were opposite. Our results suggest that keratocytes could promote the expression of VEGFr3 and MMP13, and CNV formation through PPARα downregulation.
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http://dx.doi.org/10.1016/j.exer.2020.107982DOI Listing
April 2020

Hyperlipidemia Affects Tight Junctions and Pump Function in the Corneal Endothelium.

Am J Pathol 2020 03 13;190(3):563-576. Epub 2020 Jan 13.

Department of Ophthalmology, Xiang'an Hospital of Xiamen University, Fujian Provincial Key Laboratory of Ophthalmology and Visual Science, Eye Institute of Xiamen University, School of Medicine, Xiamen University, Xiamen, China; Xiamen University Affiliated Xiamen Eye Center, Xiamen, China. Electronic address:

Hyperlipidemia impacts on various diseases, such as atherosclerosis, hypertension, and diabetes mellitus. However, its influence, if any, on ocular tissues is largely unknown. Herein, we developed hyperlipidemic murine models by feeding 4-week-old male wild-type mice with a high-fat diet and apolipoprotein E knockout (ApoE) mice with a high-fat diet or standard diet to investigate the corneal endothelial change under hyperlipidemic conditions. Oil Red O staining showed an accumulation of lipid droplets in corneal endothelial cells (CECs) of hyperlipidemic mice. Other manifestations included a reduced cell density and distorted cell morphology, a disruption of the endothelial cell tight junctions and adhesion junctions, a reduced number of surface microvilli, down-regulation of Na-K-ATPase expression and function, activation of oxidative stress, changes in mitochondrial ultrastructure, and increased apoptosis. CEC recovery after injury, moreover, was diminished in hyperlipidemic mice; and high palmitate levels were found in the aqueous humor. In vitro hyperlipemia model, moreover, was found to be associated with dose-dependent CEC cytotoxicity, altered cell morphology, reduced pump function, and an induction of oxidative stress, leading to functional and pathologic changes in the corneal endothelium.
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http://dx.doi.org/10.1016/j.ajpath.2019.11.008DOI Listing
March 2020

Integrated UPLC-Q/TOF-MS Technique and MALDI-MS to Study of the Efficacy of YiXinshu Capsules Against Heart Failure in a Rat Model.

Front Pharmacol 2019 6;10:1474. Epub 2019 Dec 6.

Institute of Chinese Materia Medica, China Academy of Chinese Medical Sciences, Beijing, China.

Yixinshu Capsules (YXSC) are widely used in Chinese medicine for the treatment of cardiovascular diseases. However, the therapeutic mechanisms of action are not well understood. In this study, a metabonomic approach based on integrated UPLC-Q/TOF-MS technique and MALDI-MS was utilized to explore potential metabolic biomarkers that may help increase the understanding of heart failure (HF) and in order to assess the potential mechanisms of YXSC against HF. Plasma metabolic profiles were analyzed by UPLC-Q/TOF-MS with complementary hydrophilic interaction chromatography and reversed-phase liquid chromatography. Moreover, time-course analysis at the 2nd, 4th, and 10th week after permanent occlusion was conducted. In an effort to identify a more reliable potential metabolic marker, common metabolic markers of the 2nd, 4th, and 10th week were selected through multivariate data analysis. Furthermore, MALDI-MS was applied to identify metabolic biomarkers in the blood at apoptotic positions of heart tissues. The results showed that HF appeared at the fourth week after permanent occlusion based on echocardiographic assessment. Clear separations were observed between the sham and model group by loading plots of orthogonal projection to latent structure discrimination analysis (OPLS-DA) at different time points after permanent occlusion. Potential markers of interest were extracted from the combining S-plots, variable importance for the projections values (VIP > 1), and t-test ( < 0.05). Twenty-one common metabolic markers over the course of the development and progression of HF after permanent occlusion were identified. These were determined to be mainly related to disturbances in fatty acids, phosphatidylcholine, bile acids, amino acid metabolism, and pyruvate metabolism. Of the metabolic markers, 16 metabolites such as palmitoleic acid, arachidonic acid, and lactic acid showed obvious changes ( < 0.05) and a tendency for returning to baseline values in YXSC-treated HF rats at the 10th week. Moreover, four biomarkers, including palmitoleic acid, palmitic acid, arachidonic, acid and lactic acid, were further validated at the apoptotic position of heart tissue using MALDI-MS, consistent to the variation trends in the plasma. Taken in concert, our proposed strategy may contribute to the understanding of the complex pathogenesis of ischemia-induced HF and the potential mechanism of YXSC.
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http://dx.doi.org/10.3389/fphar.2019.01474DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6910235PMC
December 2019

MicroRNA-495 serves as a diagnostic biomarker in patients with sepsis and regulates sepsis-induced inflammation and cardiac dysfunction.

Eur J Med Res 2019 Nov 26;24(1):37. Epub 2019 Nov 26.

Department of Burns Surgery, The First Affiliated Hospital of Wenzhou Medical University, Nanbaixiang Street, Wenzhou, 325000, Zhejiang, People's Republic of China.

Background: Sepsis leads to severe inflammatory and cardiac dysfunction. This study aimed to explore the clinical value of miR-495 in sepsis, as well as its role in sepsis-induced inflammation and cardiac dysfunction.

Methods: 105 sepsis patients were recruited; receiver operating characteristic (ROC) curve was plotted to assess the diagnostic value of miR-495 in sepsis. A model of sepsis in rats was created via performing cecal ligation and puncture (CLP). After modeling, the cardiac function, including left ventricular systolic pressure (LVSP), left ventricular end diastolic pressure (LVEDP) and maximum rate of rise/fall of left ventricle pressure (± dp/dt), and serum cardiac troponin I (CTn-I), creative kinase isoenzyme MB (CK-MB) were detected. The blood cytokines levels including TNF-α, IL-6, IL-1β were also measured. Quantitative real-time PCR (qRT-PCR) was used for the measurement of the expression level of miR-495.

Results: MiR-495 was significantly downregulated in sepsis patients, especially patients who suffered from septic shock (SS). MiR-495 expression was negatively associated with Scr, WBC, CRP, PCT, APACHE II score and SOFA score. MiR-495 could distinguish patients with SS from non-SS patients. MiR-495 and SOFA score were better indictors for the occurrence of cardiac dysfunction in sepsis patients. In CLP-induced sepsis model. CLP rats experienced deterioration of LVSP, LVEDP, ± dp/dt, and had a rise in serum CTn-I, CK-MB, TNF-α, IL-6 and IL-1β, which were improved by miR-495 agomir injection.

Conclusions: MiR-495 might be a potential diagnostic biomarker for sepsis patients, and overexpression of miR-495 alleviated sepsis-induced inflammation and cardiac dysfunction.
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http://dx.doi.org/10.1186/s40001-019-0396-3DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6878688PMC
November 2019

Studies on bacterial cellulose/poly(vinyl alcohol) hydrogel composites as tissue-engineered corneal stroma.

Biomed Mater 2020 04 30;15(3):035022. Epub 2020 Apr 30.

Department of Ophthalmology, Xiang'an Hospital of Xiamen University, Xiamen University Affiliated Xiamen Eye Center, Eye Institute of Xiamen University, School of Medicine, Xiamen University, Xiamen, People's Republic of China. Fujian Provincial Key Laboratory of Ophthalmology and Visual Science, Xiamen, People's Republic of China.

Corneal transplantation is currently the major solution in the treatment of severe corneal diseases. However, it is restricted due to the limited number of corneal donors. A tissue-engineered cornea is a potential substitute which could help overcome this limitation. This research envisages the development of a novel tissue-engineered corneal stroma consisting of bacterial cellulose (BC)/poly(vinyl alcohol) (PVA) hydrogel composites for reconstructing the cornea. It was found that the properties of BC/PVA were better suited for use as a corneal stroma material than the BC hydrogel. The human corneal stromal cells (hCSCs) were used to evaluate the cytotoxicity of the materials, wherein BC/PVA displayed excellent biocompatibility with these cells. Furthermore, in the in vivo studies, the BC/PVA was transplanted intrastromally in rabbits. After four weeks, the cornea remained almost transparent, and without obvious inflammation, sensitization or neovascularization, as confirmed by the clinical and histological examinations. Our results demonstrate that BC/PVA was well-tolerated in the rabbit cornea, and may be a potential substitute for corneal stroma.
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http://dx.doi.org/10.1088/1748-605X/ab56caDOI Listing
April 2020

PTEN inhibition attenuates endothelial cell apoptosis in coronary heart disease via modulating the AMPK-CREB-Mfn2-mitophagy signaling pathway.

J Cell Physiol 2020 05 25;235(5):4878-4889. Epub 2019 Oct 25.

Department of Geriatrics, Beijing Chaoyang Hospital Affiliated to Capital Medical University, Beijing, China.

Atherosclerosis (AS) is a major pathogenic factor in patients with cardiovascular diseases, and endothelial dysfunction (ED) plays a primary role in the occurrence and development of AS. In our study, we attempted to evaluate the role of phosphatase and tensin homolog (PTEN) in endothelial cell apoptosis under oxidized low-density lipoprotein (ox-LDL) stimulation and identify the associated mechanisms. The results of our study demonstrated that ox-LDL induced human umbilical vein endothelial cell (HUVEC) death via mitochondrial apoptosis, as evidenced by reduced mitochondrial potential, increased mitochondria permeability transition pore opening, cellular calcium overload, and caspase-9/-3 activation. In addition, ox-LDL also suppressed cellular energy production via downregulating the mitochondrial respiratory complex. Moreover, ox-LDL impaired HUVECs migration. Western blot analysis showed that PTEN expression was upregulated after exposure to ox-LDL and knockdown of PTEN could attenuate ox-LDL-mediated endothelial cell damage. Furthermore, we found that ox-LDL impaired mitophagy activity, whereas PTEN deletion could improve mitophagic flux and this effect relied on the activity of the AMP-activated protein kinase (AMPK)-cAMP-response element-binding protein (CREB)-Mitofusin-2 (Mfn2) axis. When the AMPK-CREB-Mfn2 pathway was inhibited, PTEN deletion-associated HUVECs protection was significantly reduced, suggesting that the AMPK-CREB-Mfn2-mitophagy axis is required for PTEN deletion-mediated endothelial cell survival under ox-LDL. Taken together, our results indicate that ox-LDL-induced endothelial cell damage is associated with PTEN overexpression, and inhibition of PTEN could promote endothelial survival via activating the AMPK-CREB-Mfn2-mitophagy signaling pathway.
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http://dx.doi.org/10.1002/jcp.29366DOI Listing
May 2020

Resting-state functional magnetic resonance imaging (fMRI) and functional connectivity density mapping in patients with corneal ulcer.

Neuropsychiatr Dis Treat 2019 5;15:1833-1844. Epub 2019 Jul 5.

Department of Ophthalmology, The First Affiliated Hospital of Nanchang University, Jiangxi Province Clinical Ophthalmology Institute, Nanchang, Jiangxi 330006, People's Republic of China.

Purpose: To investigate alternations in spontaneous brain activities reflected by functional connectivity density (FCD) in patients with corneal ulcer (CU) using resting-state functional connectivity (rsFC).

Methods: We recruited 24 patients with CU (12 males, 12 females), and 24 healthy controls (HCs; 12 males, 12 females) matched for age, gender and education status. Functional magnetic resonance imaging examinations were performed on all subjects in a resting state and the following parameters determined: rsFC, long-range FCD (longFCD) and short-range FCD (IFCD). Receiver operating characteristic (ROC) curves were then used to differentiate patients with CU from HCs.

Results: Compared with HCs, CU patients showed significantly reduced rsFC values in the right cerebellum posterior lobe gyrus, right middle frontal gyrus/inferior frontal gyrus/superior frontal gyrus and left inferior parietal lobule/precuneus. Significantly reduced longFCD values were found in the right hippocampus/inferior temporal gyrus and the left inferior temporal gyrus. Moreover, compared with HCs, IFCD values were significantly reduced in the left inferior temporal gyrus/middle temporal gyrus, left limbic lobe/medial frontal gyrus, and left precuneus/limbic lobe, but were significantly increased in the right insula/superior temporal gyrus, left superior temporal gyrus/inferior frontal gyrus/insula, right superior temporal gyrus/postcentral gyrus, and left precentral gyrus.

Conclusions: Patients with CU exhibited alterations in spontaneous brain activities in several brain areas. These novel findings may help to reveal the neuropathological mechanisms underlying CU.

This study provides a direction for further exploration of underlying neural mechanisms of CU and facilitate the clinical diagnosis and treatment of CU.
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http://dx.doi.org/10.2147/NDT.S210658DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6617566PMC
July 2019

A Metabonomics Investigation into the Therapeutic Effects of BuChang NaoXinTong Capsules on Reversing the Amino Acid-Protein Interaction Network of Cerebral Ischemia.

Oxid Med Cell Longev 2019 20;2019:7258624. Epub 2019 Mar 20.

Institute of Chinese Materia Medica, China Academy of Chinese Medical Sciences, Beijing 100700, China.

Background: Amino acids (AAs) in cerebrospinal fluid (CSF) play a pivotal role in cerebral ischemia (CI). BuChang NaoXinTong Capsules (BNC) are widely prescribed in Chinese medicine for the treatment of cerebrovascular and cardiovascular diseases.

Methods: In order to investigate the therapeutic effects and pharmacological mechanisms of BNC on reversing CI from a system level, an amino acid-protein interaction imbalanced network of CI containing metabolites of AAs, key regulatory enzymes, and proteins was constructed for the first time. Furthermore, a novel method for detecting the ten AAs in CSF was developed by UPLC-QQQ-MS in an effort to validate the imbalanced networks and the therapeutic effects of BNC via analysis of metabolites.

Results: Based on a middle cerebral artery occlusion (MCAO) rat model, the dynamic levels of amino acids in CSF 3, 6, 12, and 24 h after MCAO were analyzed. Up to 24 h, the accumulated nine AA biomarkers were found to significantly change in the MCAO group compared to the sham group and exhibited an obvious tendency for returning to baseline values after BNC treatment. In addition, based on the imbalanced network of CI, four key enzymes that regulate the generation of BNC-mediated AA biomarkers were selected and validated using an enzyme-linked immunosorbent assay and western blotting. Finally, aromatic-L-amino-acid decarboxylase (AADC) was found to be one of the putative targets for BNC-mediated protection against CI.

Conclusion: This study provides new strategies to explore the mechanism of cerebral ischemia and help discover the potential mechanism of BNC.
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http://dx.doi.org/10.1155/2019/7258624DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6446104PMC
August 2019

A review of the phytochemistry and pharmacological activities of Magnoliae officinalis cortex.

J Ethnopharmacol 2019 May 25;236:412-442. Epub 2019 Feb 25.

Institute of Chinese Materia Medica, China Academy of Chinese Medical Science, Beijing 100700, China. Electronic address:

Ethnopharmacological Relevance: Magnoliae Officinalis Cortex (the dried bark of Magnolia officinalis), a widely used traditional Chinese medicine, is also known as 'Houpo' (Chinese: ). Magnoliae Officinalis Cortex has a wide range of pharmacological effects and has been used to treat conditions such as abdominal distention, vomiting, diarrhea, food accumulation, Qi stagnation, constipation, phlegm and fluid retention and cough resulting from asthma.

Aims Of The Review: The present paper reviews advances in research relating to the botany, ethnopharmacology, phytochemistry, pharmacology and toxicology of Magnoliae Officinalis Cortex. Prospects for future investigation and application of this herb are also discussed.

Materials And Methods: Information on Magnoliae Officinalis Cortex was obtained from published materials, including ancient and modern books; PhD and MSc dissertations; monographs on medicinal plants; the pharmacopoeia of different countries and electronic databases, such as SCI finder, PubMed, Web of Science, ACS, Science Direct, Wiley, Springer, Taylor, AGRIS, Europe PMC, EBSCO host, CNKI, WanFang DATA, J-STAGE and Google Scholar.

Results: More than 200 chemical compounds have been isolated from Magnoliae Officinalis Cortex, including lignans, phenylethanoid glycosides, phenolic glycosides, alkaloids, steroids and essential oils. The plant has been reported to have pharmacological effects on the digestive system, nervous system and cardiovascular and cerebrovascular systems, as well as antibacterial, anti-tumour, analgesic, anti-inflammatory and anti-oxidative effects.

Conclusions: Magnoliae Officinalis Cortex is an essential traditional Chinese medicine with pharmacological activities that mainly affect the digestive system, nervous system and cardiovascular and cerebrovascular systems. This review summarises its botany, ethnopharmacology, phytochemistry, pharmacology and toxicology. These information suggest that we should focus on the development of new drugs related to Magnoliae Officinalis Cortex, including specific constituents, so that Magnoliae Officinalis Cortex can exert greater therapeutic potential. Meanwhile, it is important to pay attention to the rational use of Magnolia resources, avoiding over-harvesting which could lead to lack of resources. We should also pursue research on Magnolia substitutes and develop resources such as Magnoliae Officinalis Flos and Magnolia Leaf.
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http://dx.doi.org/10.1016/j.jep.2019.02.041DOI Listing
May 2019

Sleep Deprivation Induces Dry Eye Through Inhibition of PPARα Expression in Corneal Epithelium.

Invest Ophthalmol Vis Sci 2018 11;59(13):5494-5508

Eye Institute of Xiamen University, Fujian Provincial Key Laboratory of Ophthalmology and Visual Science, Medical College, Xiamen University, Xiamen, Fujian, China.

Purpose: To determine if sleep deprivation induces dry eye through altering peroxisome proliferator-activated receptor alpha (PPARα) expression in mice.

Methods: The "stick over water" sleep deprivation-induced dry eye (SDE) model evaluated PPARα involvement in inducing this condition. Scanning electron microscopy (SEM) examined microvilli morphology in superficial corneal epithelial cells (SCECs) in SDE and PPARα-/- mice. Quantitative RT-PCR (qRT-PCR) and Western blot (WB) or immunostaining evaluated PPARα, carnitine palmitoyl transferase 1α (CPT1α), and transient receptor potential vanilloid 6 (TRPV6) expression levels and Ezrin phosphorylation status. Hematoxylin-eosin and Oil Red O staining characterized meibomian gland morphology and corneal lipid accumulation, respectively. Phenol red cotton threads measured tear production. In cultured corneal epithelial sheets, qRT-PCR, WB, and SEM determined the individual effects of fenofibrate and MK886 (PPARα agonist and antagonist, respectively) on PPARα, TRPV6 expression, and SCEC microvilli morphology.

Results: Corneal epithelial lipid accumulation, microvilli morphologic changes, and decreased tear production were associated with marked declines in PPARα, CPT1α, and TRPV6 expression levels as well as Ezrin phosphorylation status, whereas meibomian glands were unaltered in SDE mice. These effects of SDE mice mimicked those in their nonstressed PPARα-/-counterpart. Topical application of fenofibrate reversed these effects in SDE corneas. In cultured corneal epithelial sheets, fenofibrate increased PPARα and TRPV6 gene and protein expression levels and restored microvilli morphology, whereas MK886 attenuated these changes.

Conclusions: Sleep deprivation induces dry eye through abnormal SCEC microvilli morphology, which is caused by sequential downregulation of PPARα, TRPV6 expression, and Ezrin phosphorylation status in mice.
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http://dx.doi.org/10.1167/iovs.18-24504DOI Listing
November 2018

Determination of Bitterness of Based on Electronic Tongue Technology and Discovery of the Key Compounds of Bitter Substances.

Molecules 2018 Dec 19;23(12). Epub 2018 Dec 19.

Institute of Chinese Materia Medica, China Academy of Chinese Medical Science, No.16 Nanxiaojie, Dongzhimennei Ave., Beijing 100700, China.

(AH), the dry aerial segments of (Burm.f.) Nees, is a common herbal remedy with bitter properties in traditional Chinese medicine (TCM) theory. Although bitterness is one of the features representing Chinese medicine, it has not been implemented as an index to assess the quality and efficacy of TCM because of peoples' subjectivity to taste. In this study, 30 batches of AH with different commercial classifications (leaves, stems, or mixtures of both) were collected. Bitterness of AH was quantified by electronic tongue technology. Meanwhile, chemical compositions were characterized through establishing high-performance liquid chromatography fingerprints. The result indicated that the radar curves of the bitterness from different AH commercial classifications displayed different taste fingerprint information. Based on six taste factors, a Principal Component Analysis (PCA) score three-dimensional (3D) plot exhibited a clear grouping trend (R²X, 0.912; Q², 0.763) among the three different commercial classifications. Six compounds (Peaks 2, 3, 4, 6, 7, 8) with positive correlation to bitterness were discovered by a Spearman correlation analysis. Peaks 2, 6, 7, 8 were identified as andrographolide, neoandrographolide, 14-deoxyandrographolide, and dehydroandrographolide, respectively. The electronic tongue can be used to distinguish AH samples with different commercial classifications and for quality evaluation.
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http://dx.doi.org/10.3390/molecules23123362DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6321225PMC
December 2018

Effects of diesel exhaust particles on the condition of mouse ocular surface.

Ecotoxicol Environ Saf 2018 Nov 1;163:585-593. Epub 2018 Aug 1.

Eye Institute & Affiliated Xiamen Eye Center, Xiamen University Medical College, Xiamen 361102, China; Fujian Provincial Key Laboratory of Ophthalmology and Visual Science, Xiamen 361102, China. Electronic address:

In order to evaluate the effects of diesel exhaust particles (DEP) on the ocular surface, different concentrations (100 and 1000 μg/ml) of DEP eye drops were administered on the mouse ocular surface for a period of 28 days. After DEP treatment, the corneal epithelial permeability to Oregon Green Dextran was studied, which increased proportionally with time. Also, the number of corneal epithelial cell layers significantly increased, which was accompanied with a high Ki67 expression. On the other hand, the number of goblet cells in the conjunctival fornix were reduced, and apoptotic cells were detected in the corneal and conjunctival epithelium by TUNEL assay in the DEP treated group, along with increased Caspase 3/8 expression. Furthermore, the number of CD4 positive cells significantly increased in the conjunctiva, while NF-κB p65 (phospho S536) expression was elevated in the cornea and also the conjunctiva. Our data revealed that the topical administration of DEP on the ocular surface in mouse disrupted the organized structure of the ocular surface and induced an inflammation of the cornea and conjunctiva.
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http://dx.doi.org/10.1016/j.ecoenv.2018.07.101DOI Listing
November 2018

0.005% Preservative-Free Latanoprost Induces Dry Eye-Like Ocular Surface Damage via Promotion of Inflammation in Mice.

Invest Ophthalmol Vis Sci 2018 07;59(8):3375-3384

Eye Institute of Xiamen University & Fujian Provincial Key Laboratory of Ophthalmology and Visual Science, Xiamen University, Xiamen, Fujian, China.

Purpose: To investigate the side effects of preservative-free 0.005% latanoprost on the murine ocular surface.

Methods: We applied 0.005% latanoprost or vehicle in mice in two patterns for 14 to 28 days. Tear production was measured by phenol red cotton test, and corneal epithelial barrier function was assessed by Oregon-green-dextran (OGD) staining. Periodic acid-Schiff (PAS) staining was used to quantify conjunctival goblet cells (GCs). The expression of matrix metalloproteinase (MMP)-3 and -9, occludin-1 and zonula occludens (ZO)-1 in corneal epithelium was assessed by immunofluorescent staining and/or quantitative real-time PCR (qRT-PCR). Inflammation in conjunctiva was assessed by activation of P38 and NF-κB, infiltration of CD4+ T cells, and production inflammatory cytokines including TNF-α, IL-1β, IFN-γ, IL-17A, and IL-13. Apoptosis in ocular surface was assessed by TUNEL and immunofluorescent staining for activated caspase-3 and -8. Cell viability assay was performed in human corneal epithelial cells.

Results: Topical latanoprost treatment decreased tear production, induced conjunctival GC loss, disrupted the corneal epithelial barrier, and promoted cell apoptosis in the ocular surface. Topical latanoprost treatment increased the expression of MMP-3 and -9, and decreased the expression of ZO-1 and occludin-1 in the corneal epithelium. Topical application of latanoprost promoted activation of P38-NF-κB signaling and production of TNF-α and IL-1β in conjunctiva. Topical application of latanoprost increased CD4+ T cells infiltration, with increased production of IFN-γ and IL-17A and decreased production of IL-13 in conjunctiva.

Conclusion: 0.005% latanoprost induced dry eye-like ocular surface damage via promotion of inflammation in mice.
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http://dx.doi.org/10.1167/iovs.18-24013DOI Listing
July 2018

Trichosanthis Fructus: botany, traditional uses, phytochemistry and pharmacology.

J Ethnopharmacol 2018 Oct 26;224:177-194. Epub 2018 May 26.

State Key Laboratory of Generic Manufacture Technology of Chinese Traditional Medicine, Shandong 276006, China. Electronic address:

Ethnopharmacological Relevance: Trichosanthis Fructus (ripe fruits of Trichosanthes kirilowii Maxim. and Trichosanthes rosthornii Harms) is an essential traditional Chinese medicine to treat thoracic obstruction, angina, cardiac failure, myocardial infarction, pulmonary heart disease, some cerebral ischaemic diseases, etc. The present report reviews the advancements in research on the botany, traditional uses, phytochemistry and pharmacology of Trichosanthis Fructus. Finally, perspectives on future research and its possible directions are discussed.

Aim Of The Study: This review provides up-to-date information about the botany, traditional uses, phytochemistry, pharmacology, toxicity and quality control of Trichosanthis Fructus and discusses the perspectives on future research and possible directions of this traditional Chinese Medicine and its origin plants.

Materials And Methods: The information on Trichosanthes kirilowii Maxim. and Trichosanthes rosthornii Harms was collected from published scientific materials, including books; monographs on medicinal plants; pharmacopoeia and electronic databases such as SCI finder, PubMed, Web of Science, ACS, Science Direct, Wiley, Springer, Taylor, CNKI and Google Scholar.

Results: Approximately 162 compounds, including terpenoids, phytosterols, flavonoids, nitrogenous compounds and lignans, have been isolated and identified from Trichosanthes kirilowii Maxim. and Trichosanthes rosthornii Harms. Numerous studies have shown that the extracts and compounds isolated from these two plants exhibit pharmacological activities, including protection against myocardial ischaemia, calcium antagonist, endothelial cell protection, anti-hypoxic, anti-platelet aggregation, expectorant, anti-inflammatory, cytotoxic and antioxidant.

Conclusions: Trichosanthis Fructus is an essential traditional Chinese medicine with pharmacological activities that mainly affect the cardiovascular system. This review summarises its botany, traditional uses, phytochemistry and pharmacology. Future research is needed to clarify the different uses of the seeds, pericarps and fruits. Quality control of investigations of the fruits should be improved, and the potential uses of the flesh, leaves and twigs should be further explored.
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http://dx.doi.org/10.1016/j.jep.2018.05.034DOI Listing
October 2018

oxLDL-mediated cellular senescence is associated with increased NADPH oxidase p47phox recruitment to caveolae.

Biosci Rep 2018 06 12;38(3). Epub 2018 Jun 12.

Department of Geriatrics, Beijing Chaoyang Hospital Affiliated to Capital Medical University, Beijing 100043, China

Atherosclerosis develops as a consequence of inflammation and cell senescence. In critical factors involved in the atherosclerotic changes, reactive oxygen species (ROS) generation is considered a leading cause. While NADPH oxidases, particularly NOX2, are the main sources of ROS, how they are regulated in the disease is incompletely understood. In addition, how caveolae, the membrane structure implicated in oxLDL deposition under vascular endothelia, is involved in the oxLDL-mediated ROS production remains mostly elusive. We report here that macrophages exposed to oxLDL up-regulate its caveolin-1 expression, and the latter in turn up-regulates NOX2 p47phox level. This combination effect results in increased cellular senescence. Interestingly, oxLDL treatment causes the p47phox residing in the cytosol to translocate to the caveolae. Immunoprecipitation assays confirms that cavelin-1 is in high degree association with p47phox. These results suggest caveolin-1 may serve as the membrane target for p47phox and as a switch for ROS production following oxLDL exposure. Our results reveal a previously unknown molecular event in oxLDL-mediated cellular ageing, and may provide a target for clinical intervention for atherosclerosis.
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http://dx.doi.org/10.1042/BSR20180283DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC5997791PMC
June 2018

NR4A1 contributes to high-fat associated endothelial dysfunction by promoting CaMKII-Parkin-mitophagy pathways.

Cell Stress Chaperones 2018 07 22;23(4):749-761. Epub 2018 Feb 22.

Department of Geriatrics, Beijing Chaoyang Hospital Affiliated to Capital Medical University, Beijing, 100043, China.

Parkin-related mitophagy is vital for endothelial cell viability and the development of atherosclerosis, although the upstream regulatory factor underlying Parkin-mediated mitophagy in endothelial apoptosis and atherosclerosis progression remains unknown. In the present study, we demonstrated that nuclear receptor subfamily 4 group A member 1 (NR4A1) is actually expressed in aortic endothelial cells (AECs) under oxidized low-density lipoprotein (ox-LDL) treatment in vitro or isolated from high-fat treated mice in vivo. Higher NR4A1 levels were associated with AEC apoptosis, mitochondrial dysfunction, and energy disorder. At the molecular level, ox-LDL stimulation increased NR4A1 expression, which evoked Parkin-mediated mitophagy. Excessive mitophagy overtly consumed mitochondrial mass, leading to an energy shortage and mitochondrial dysfunction. However, loss of NR4A1 protected AECs against ox-LDL induced apoptosis by inhibiting excessive mitophagy. Furthermore, we also identified that NR4A1 regulated Parkin activation via post-transcriptional modification by Ca2/calmodulin-dependent protein kinase II (CaMKII). Activated CaMKII via NR4A1 induced the phosphorylated activation of Parkin. In summary, our data support the role of NR4A1/CaMKII/Parkin/mitophagy in AEC apoptosis and atherosclerosis formation and provide new insights into treating atherosclerosis with respect to endothelial viability, mitophagy, and NR4A1.
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http://dx.doi.org/10.1007/s12192-018-0886-1DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6045535PMC
July 2018

Botany, Phytochemistry, Pharmacology and Toxicity of Strychnos nux-vomica L.: A Review.

Am J Chin Med 2018 3;46(1):1-23. Epub 2018 Jan 3.

* Institute of Chinese Materia Medica, China Academy of Chinese Medical Science, No. 16 Nanxiaojie, Dongzhimennei Ave., Beijing 100700, P. R. China.

Strychnos nux-vomica L. belongs to the genus Strychnos of the family Loganiaceae and grows in Sri Lanka, India and Australia. The traditional medicinal component is its seed, called Nux vomica. This study provides a relevant and comprehensive review of S. nux-vomica L., including its botany, ethnopharmacology, phytochemistry, pharmacology and toxicology, thus providing a foundation for future studies. Up to the present day, over 84 compounds, including alkaloids, iridoid glycosides, flavonoid glycosides, triterpenoids, steroids and organic acids, among others, have been isolated and identified from S. nux-vomica. These compounds possess an array of biological activities, including effects on the nervous system, analgesic and anti-inflammatory actions, antitumor effects, inhibition of the growth of pathogenic microorganisms and regulation of immune function. Furthermore, toxicity and detoxification methods are preliminarily discussed toward the end of this review. In further research on S. nux-vomica, bioactivity-guided isolation strategies should be emphasized. Its antitumor effects should be investigated further and in vivo animal experiments should be performed alongside in vitro testing. The pharmacological activity and toxicology of strychnine [Formula: see text]-oxide and brucine [Formula: see text]-oxide should be studied to explore the detoxification mechanism associated with processing more deeply.
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http://dx.doi.org/10.1142/S0192415X18500015DOI Listing
June 2018

Simultaneous Determination of Seven Anthraquinone Aglycones of Crude and Processed Semen Cassiae Extracts in Rat Plasma by UPLC-MS/MS and Its Application to a Comparative Pharmacokinetic Study.

Molecules 2017 Oct 28;22(11). Epub 2017 Oct 28.

Institute of Chinese Materia Medica, China Academy of Chinese Medical Science, No. 16 Nanxiaojie, Dongzhimennei Ave., Beijing 100700, China.

Semen cassiae is the ripe seed of L. or L. of the family Leguminosae. In traditional Chinese medicine, the two forms of Semen cassiae are raw Semen cassiae (R-SC) and parched Semen cassiae (P-SC). To clarify the processing mechanism of Semen cassiae, the pharmacokinetics of R-SC and P-SC extracts were examined. A simple, rapid, sensitive ultra-high-performance liquid chromatography-tandem mass spectroscopy (UPLC-MS/MS) method was developed and validated for the simultaneous determination of seven anthraquinone aglycones of Semen cassiae (aurantio-obtusin, obtusifolin, questin, 2-hydroxyemodin-1-methyl-ether, rhein, emodin, 1,2,7-trimethoxyl-6,8-dihydroxy-3-methylanthraquinone) to compare the pharmacokinetics of raw and parched Semen cassiae in rat plasma. Compared with the R-SC group, C and AUC tended to be higher in the P-SC group. In particular, C values for aurantio-obtusin, obtusifolin, questin, 2-hydroxyemodin-1-methyl-ether and rhein were significantly higher in the P-SC group ( < 0.05). Meanwhile, T and MRT tended to be lower in the P-SC group. Specifically, T for aurantio-obtusin and 2-hydroxyemodin-1-methyl-ether and MRT for obtusifolin and rhein were significantly higher in the P-SC group ( < 0.05).
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http://dx.doi.org/10.3390/molecules22111803DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6150312PMC
October 2017

Application of near-infrared spectroscopy for the rapid quality assessment of Radix Paeoniae Rubra.

Spectrochim Acta A Mol Biomol Spectrosc 2017 Aug 20;183:75-83. Epub 2017 Apr 20.

Institute of Chinese Materia Medica, China Academy of Chinese Medical Sciences, Dong Nei Nan Xiao Jie 16, Beijing 100700, China. Electronic address:

Near-infrared (NIR) spectroscopy with multivariate analysis was used to quantify gallic acid, catechin, albiflorin, and paeoniflorin in Radix Paeoniae Rubra, and the feasibility to classify the samples originating from different areas was investigated. A new high-performance liquid chromatography method was developed and validated to analyze gallic acid, catechin, albiflorin, and paeoniflorin in Radix Paeoniae Rubra as the reference. Partial least squares (PLS), principal component regression (PCR), and stepwise multivariate linear regression (SMLR) were performed to calibrate the regression model. Different data pretreatments such as derivatives (1st and 2nd), multiplicative scatter correction, standard normal variate, Savitzky-Golay filter, and Norris derivative filter were applied to remove the systematic errors. The performance of the model was evaluated according to the root mean square of calibration (RMSEC), root mean square error of prediction (RMSEP), root mean square error of cross-validation (RMSECV), and correlation coefficient (r). The results show that compared to PCR and SMLR, PLS had a lower RMSEC, RMSECV, and RMSEP and higher r for all the four analytes. PLS coupled with proper pretreatments showed good performance in both the fitting and predicting results. Furthermore, the original areas of Radix Paeoniae Rubra samples were partly distinguished by principal component analysis. This study shows that NIR with PLS is a reliable, inexpensive, and rapid tool for the quality assessment of Radix Paeoniae Rubra.
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http://dx.doi.org/10.1016/j.saa.2017.04.034DOI Listing
August 2017