Displaying publications 1 - 20 of 122 in total

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  1. Wang S, Yang J, Kuang X, Li H, Du H, Wu Y, et al.
    J Ethnopharmacol, 2024 May 23;326:117913.
    PMID: 38360380 DOI: 10.1016/j.jep.2024.117913
    ETHNOPHARMACOLOGICAL RELEVANCE: Kaempferia galanga Linn. is an aromatic medicinal herb with extensively applied in India, China, Malaysia and other South Asia countries for thousands of years. It has been mentioned to treat abdominal tumors. Ethyl cinnamate (EC), one of the main chemical constituents of the rhizome of K. galanga, exhibited nematocidal, sedative and vasorelaxant activities. However, its anti-angiogenic activity, and anti-tumor effect have not been investigated.

    AIM OF THE STUDY: To investigate the anti-angiogenic mechanism of EC and its anti-tumor effect by suppressing angiogenesis.

    MATERIALS AND METHODS: The in vitro anti-angiogenic effect was evaluated using HUVECs model induced by VEGF and zebrafish model in vivo. The influence of the EC on phosphorylation of VEGFR2 and its downstream signaling pathways were evaluated by western blotting assay. Molecule docking technology was conducted to explore the interaction between EC and VEGFR2. SPR assay was used for detecting the binding affinity between EC and VEGFR2. To further investigate the molecular mechanism of EC on anti-angiogenesis, VEGFR2 knockdown in HUVECs and examined the influence of the EC. Anti-tumor activity of EC was evaluated using colony formation assay and apoptosis assay. The inhibitory effect of EC on tumor growth was explored using HT29 colon cancer xenograft model.

    RESULTS: EC obviously inhibited proliferation, migration, invasion and tube formation of VEGF-induced HUVECs. EC also induced apoptosis of HUVECs. Moreover, it inhibited the development of vessel formation in zebrafish. Further investigations demonstrated that EC could suppress the phosphorylation of VEGFR2, and its downstream signaling pathways were altered in VEGF-induced HUVECs. EC formed a hydrogen bond to bind with the ATP binding site of the VEGFR2, and EC-VEGFR2 interaction was shown in SPR assay. The suppressive effect of EC on angiogenesis was abrogated after VEGFR2 knockdown in HUVECs. EC inhibited the colon cancer cells colony formation and induced apoptosis. In addition, EC suppressed tumor growth in colon cancer xenograft model, and no detectable hepatotoxicity and nephrotoxicity. In addition, it inhibited the phosphorylation of VEGFR2, and its downstream signal pathways in tumor.

    CONCLUSIONS: EC could inhibit tumor growth in colon cancer by suppressing angiogenesis via VEGFR2 signaling pathway, and suggested EC as a promising candidate for colon cancer treatment.

    Matched MeSH terms: Vascular Endothelial Growth Factor A/metabolism
  2. Siervo M, Hussin AM, Calella P, Ashor A, Shannon OM, Mendes I, et al.
    J Nutr, 2024 Feb;154(2):469-478.
    PMID: 38048992 DOI: 10.1016/j.tjnut.2023.12.002
    BACKGROUND: Aging and vitamin D deficiency have been associated with reduced nitric oxide (NO) synthesis and impaired endothelial function (EF) but the evidence in humans remains weak.

    OBJECTIVES: Two independent cross-sectional studies were designed to evaluate the association between age, sex, and plasma vitamin D concentrations with physiological and biochemical biomarkers of NO synthesis and EF in young and older healthy participants (Study 1) and in overweight and obese postmenopausal females (Study 2).

    METHODS: In Study 1, 40 young (20-49 y) and older (50-75 y) males and females (10 participants per age and sex group) were included. Resting blood pressure and ear-to-finger peripheral pulse wave velocity (PWV) were measured. A stable-isotopic method was used to determine whole-body NO production. Plasma 25-hydroxyvitamin D (25(OH)D), nitrate, nitrite, and asymmetric dimethylarginine (ADMA) concentrations were determined. In Study 2, 80 older overweight and obese females (age 61.2 ± 6.2 y, body mass index 29.5 ± 4.4 kg/m2) were recruited. Postocclusion reactive hyperemia (PORH) and peripheral PWV were measured. Plasma concentrations of 25(OH)D, nitrate, cyclic guanosine monophosphate, 3-nitrotyrosine (3-NT), endothelin-1, vascular endothelial growth factor, and ADMA were determined.

    RESULTS: In Study 1, whole-body NO production was significantly greater in young compared with older participants (0.61 ± 0.30 μmol·h-1·kg-1 compared with 0.39 ± 0.10 μmol·h-1·kg-1, P = 0.01) but there was no evidence of a sex difference (P = 0.81). Plasma 25(OH)D concentration was not associated with PWV (r = 0.18, P = 0.28) or whole-body NO production (r = -0.20, P = 0.22). Plasma ADMA concentration was associated positively with age (r = 0.35, P = 0.03) and negatively with whole-body NO production (r = -0.33, P = 0.04). In Study 2, age was associated with lower PORH (r = -0.28, P = 0.02) and greater ADMA concentrations (r = 0.22, P = 0.04). Plasma 25(OH)D concentration was inversely associated with 3-NT concentrations (r = -0.31, P = 0.004).

    CONCLUSIONS: Older age was associated with lower whole-body NO production. Plasma vitamin D concentrations were not associated with NO production or markers of EF but showed a weak, significant correlation with oxidative stress in postmenopausal overweight females.

    Matched MeSH terms: Vascular Endothelial Growth Factor A
  3. Sudhakaran G, Chandran A, Sreekutty AR, Madesh S, Pachaiappan R, Almutairi BO, et al.
    Molecules, 2023 Jul 12;28(14).
    PMID: 37513223 DOI: 10.3390/molecules28145350
    Diabetes Mellitus is a metabolic disease that leads to microvascular complications like Diabetic retinopathy (DR), a major cause of blindness worldwide. Current medications for DR are expensive and report multiple side effects; therefore, an alternative medication that alleviates the disease condition is required. An interventional approach targeting the vascular endothelial growth factor (VEGF) remains a treatment strategy for DR. Anti-VEGF medicines are being investigated as the main therapy for managing vision-threatening complications of DR, such as diabetic macular oedema. Therefore, this study investigated the effect of flavonoid naringenin (NG) from citrus fruits on inhibiting early DR in zebrafish. When exposed to 130 mM glucose, the zebrafish larvae developed a hyperglycaemic condition accompanied by oxidative stress, cellular damage, and lipid peroxidation. Similarly, when adult zebrafish were exposed to 4% Glucose, high glucose levels were observed in the ocular region and massive destruction in the retinal membrane. High glucose upregulated the expression of VEGF. In comparison, the co-exposure to NG inhibited oxidative stress and cellular damage and restored the glutathione levels in the ocular region of the zebrafish larvae. NG regressed the glucose levels and cellular damage along with an inhibition of macular degeneration in the retina of adult zebrafish and normalized the overexpression of VEGF as a promising strategy for treating DR. Therefore, intervention of NG could alleviate the domestication of alternative medicine in ophthalmic research.
    Matched MeSH terms: Vascular Endothelial Growth Factor A/metabolism
  4. Cilwyn-Shalitha B, Sasidharan S
    Microsc Microanal, 2023 Jun 09;29(3):1153-1167.
    PMID: 37749670 DOI: 10.1093/micmic/ozad023
    The present study investigated the effects of Polyalthia longifolia leaf extract against the growth of HeLa cell xenograft tumor in nude mice and its underlying mechanism. The nude mice xenografted with HeLa cells were treated with 5% DMSO (vehicle control), 20 mg/kg/body weight of etoposide (positive control), and 500 and 1000 mg/kg/body weight of leaf extract, respectively. Antitumor activity was evaluated with apoptosis, proliferation, and angiogenesis using microscopic-based histological and immunohistochemical microanalyses. The tumor tissue histological and immunohistochemical analyses showed that the HeLa tumor cell death was associated with apoptosis and decreased (p < 0.05) expression of Ki-67 in tumor tissues. The extract also inhibits tumor angiogenesis by downregulating (p < 0.05) the expression of VEGF and CD31 in tumor tissues after treatment for 35 days. Conclusively, the P. longifolia leaf extract effectively inhibited HeLa cell xenograft growth in nude mice. The possible mechanism was related to induction of apoptosis, inhibition of tumor HeLa cell proliferation by decreasing the Ki-67 protein expression, and prevention of tumor angiogenesis by reducing VEGF and CD31 protein expression in HeLa cells.
    Matched MeSH terms: Vascular Endothelial Growth Factor A
  5. Abdul Ghani NA, Abdul Nasir NA, Lambuk L, Sadikan MZ, Agarwal R, Ramli N
    Graefes Arch Clin Exp Ophthalmol, 2023 Jun;261(6):1587-1596.
    PMID: 36622408 DOI: 10.1007/s00417-022-05965-3
    PURPOSE: Angiogenesis in diabetic retinopathy (DR) is associated with increased retinal expression of angiopoietin-2 (Ang-2) and protein kinase C (PKC). Tocotrienol-rich fraction (TRF) has been shown to reduce the expression vascular endothelial growth factor (VEGF) in several experimental models. However, its effect against other angiogenic markers such as Ang-2 and PKC in rat model of diabetes remains unknown. Therefore, we investigated the effect of TRF on the retinal vascular changes and Ang-2 and PKC expressions in rats with streptozotocin (STZ)-induced DR.

    METHODS: Sprague-Dawley rats were divided into normal control rats (N) which received vehicle, and diabetic rats which either received vehicle (DV) or 100 mg/kg of TRF (DT). Diabetes was induced with intraperitoneal injection of STZ (60 mg/kg body weight). Treatments were given orally, once daily, for 12 weeks after confirmation of hyperglycaemia. Fundus photographs were captured at baseline, 6- and 12-week post-STZ injection and average diameter of retinal veins and arteries were measured. At 12-week post-STZ injection, rats were euthanised, and retinae were collected for measurement of Ang-2 and PKC gene and protein expressions.

    RESULTS: Retinal venous and arterial diameters were significantly greater in DV compared to DT at week 12 post-STZ injection (p vascular diameter of rats with STZ-induced DR.

    Matched MeSH terms: Vascular Endothelial Growth Factor A/genetics; Vascular Endothelial Growth Factor A/metabolism
  6. Nursyafiqah MT, Siti-Azrin AH, Yaacob NM, Wan-Nor-Asyikeen WA, Zunaina E
    Trop Med Int Health, 2023 Apr;28(4):300-307.
    PMID: 36787961 DOI: 10.1111/tmi.13862
    OBJECTIVE: Intravitreal ranibizumab is one of the anti-vascular endothelial growth factors used for the treatment of diabetic macular oedema, not always successfully. We aimed to identify the factors affecting the changes of central macular thickness after induction treatment with intravitreal ranibizumab, to predict the treatment effect and facilitate early treatment decisions.

    METHODS: Cross-sectional study involving a retrospective record review of diabetic macular oedema patients who received an induction treatment of three monthly 0.5 mg intravitreal ranibizumab injections between 2016 and 2019. Central macular thickness was measured at baseline and 3 months post-treatment. Linear regression was applied to identify the factors associated with the changes of central macular thickness.

    RESULTS: A total of 153 diabetic macular oedema patients were involved in this study. Their mean age was 57.5 ± 7.7 years, 54.9% were female. The mean change of central macular thickness from baseline to 3 months after completed induction treatment of intravitreal ranibizumab was 155.5 ± 137.8 μm. Factors significantly associated with changes of central macular thickness were baseline central macular thickness [b = 0.73; 95% (CI): 0.63, 0.84; p = <0.001] and presence of subretinal fluid [b = 35.43; 95% CI: 3.70, 67.16; p = 0.029].

    CONCLUSION: Thicker baseline central macular thickness and presence of subretinal fluid were the factors significantly associated with greater changes of central macular thickness in diabetic macular oedema patients after receiving three injections of intravitreal ranibizumab.

    Matched MeSH terms: Vascular Endothelial Growth Factor A/therapeutic use
  7. Edirisinghe ST, Weerasekera M, De Silva DK, Devmini MT, Pathmaperuma S, Wijesinghe GK, et al.
    Asian Pac J Cancer Prev, 2023 Jan 01;24(1):267-274.
    PMID: 36708576 DOI: 10.31557/APJCP.2023.24.1.267
    BACKGROUND: The incidence of oral squamous cell carcinoma (OSCC) is very high in South Asia and Vascular endothelial growth factor (VEGF) is one of the key factors essential for cancer growth. The importance of VEGF-A and VEGF Receptor 2(VEGFR-2) in oral cancer pathophysiology is yet to be decided. Vascular Endothelial Growth Factor A (VEGF-A) is the main factor concerned in angiogenesis in tumors, but its role in Oral Squamous Cell Carcinoma (OSCC) is still debatable. Our study aimed to determine the role of VEGF-A and VEGFR-2 in OSCC.

    METHODS: Blood from 30 patients with primary OSCC and 1:1 age-sex-matched controls was subjected to qPCR and ELISA to detect VEGF-A gene expression and serum level. Tumors of the 30 patients were investigated for VEGF Receptor-2 (VEGFR-2) expression and were analyzed using Image J software version 1.52 for DAB percentage (DAB-P) area and optical density (OD).

    RESULTS: VEGF-A relative gene expression among patients was 2.43-fold higher compared to the healthy control group. Well-differentiated had a 1.98-fold increment, while poorly differentiated had a 3.58-fold increment. Serum VEGF-A was significantly elevated among the patients compared to controls (458.7 vs 253.2, p=0.0225). Poorly differentiated had a higher serum VEGF concentration (1262.0±354.7pg/ml) compared with other two. Mean VEGFR-2 DAB-P level in OSCC was 42.41±5.61(p=0.15). Well-differentiated had a DAB-P of 41.20±5.32 while poorly differentiated had DAB-P 46.21±3.78. The mean OD in OSCC was 0.54±0.16. VEGFR-2 OD in well and poorly differentiated OSCC were 0.48±0.12 and 0.68±0.17, respectively.

    CONCLUSIONS: VEGF-A gene expression, serum levels, and tissue VEGFR-2 levels correlated linearly with the stage and grade of the tumor. This study justifies the value of VEGF-A as a potential biomarker in OSCC in early detection of OSCC. More studies are needed to accept the use of VEGF-A.

    Matched MeSH terms: Vascular Endothelial Growth Factor A/genetics; Vascular Endothelial Growth Factor A/metabolism
  8. Yong PH, New SY, Azzani M, Wu YS, Chia VV, Ng ZX
    Endocr Regul, 2023 Jan 01;58(1):26-39.
    PMID: 38345496 DOI: 10.2478/enr-2024-0004
    Hyperglycemia in diabetes mediates the release of angiogenic factors, oxidative stress, hypoxia, and inflammation, which in turn stimulate angiogenesis. Excessive angiogenesis can cause diabetic retinopathy, diabetic neuropathy, and diabetic nephropathy. All of these complications are debilitating, which may lead to an increased susceptibility to lower-limb amputations due to ulcerations and infections. In addition, microvascular alterations, segmental demyelination, and endoneurial microangiopathy may cause progressive deterioration ultimately leading to kidney failure and permanent blindness. Some medicinal plants have potent anti-angiogenic, antioxidant or anti-inflammatory properties that can ameliorate angiogenesis in diabetes. The purpose of this systematic review is to demonstrate the potential of medicinal plants in ameliorating the neovascularization activities in diabetes. Manuscripts were searched from PubMed, Science Direct, and Scopus databases, and Google Scholar was used for searching additional papers. From 1862 manuscripts searched, 1854 were excluded based on inclusion and exclusion criteria and 8 were included into this systematic review, whereas the required information was extracted and summarized. All identified medicinal plants decreased the high blood glucose levels in diabetes, except the aqueous extract of Lonicerae japonicae flos (FJL) and Vasant Kusumakar Ras. They also increased the reduced body weight in diabetes, except the aqueous extract of FL and total lignans from Fructus arctii. However, methanolic extract of Tinospora cordifolia and Vasant Kusumakar Ras were not tested for their ability to affect the body weight. Besides, all medicinal plants identified in this systematic review decreased the vascular endothelial growth factor (VEGF) protein expression and vasculature activity demonstrated by histopathological examination indicating promising anti-angiogenic properties. All medicinal plants identified in this systematic review have a potential to ameliorate neovascularization activities in diabetes by targeting the mechanistic pathways related to oxidative stress, inflammation, and angiogenesis.
    Matched MeSH terms: Vascular Endothelial Growth Factor A
  9. Guo HF, Mohd Ali R, Abd Hamid R, Chang SK, Rahman MH, Zainal Z, et al.
    Int J Low Extrem Wounds, 2022 Dec;21(4):544-554.
    PMID: 33241700 DOI: 10.1177/1534734620971066
    Our previous study has demonstrated that epidermal growth factor (EGF) with tocotrienol-rich fraction (TRF) cream formulation accelerating postburn wound healing with deep partial-thickness burn in rats. Current study was conducted to determine the gene expression levels related to burn wound healing process. A total of 180 Sprague-Dawley rats were randomly divided into 6 groups: untreated control, treated with Silverdin cream, base cream, base cream with 0.00075% EGF, base cream with 3% TRF or base cream with 0.00075% EGF, and 3% TRF, respectively. Burn wounds were created and the above-mentioned creams were applied once daily. Six animals from each group were sacrificed on days 3, 7, 11, 14, and 21 postburn. RNA was extracted from wound tissues and quantitative real-time polymerase chain reaction was performed to analyze the 9 wound healing-related genes against time postburn. Results demonstrated that topically applied EGF + TRF formulation downregulated the expression levels of IL-6 (interluekin-6), TNF-α (tumor necrosis factor-α) and iNOS (inducible nitric oxide synthase) throughout the whole healing process. TGF-β1 (transforming growth factor-β) and VEGF-A (vascular endothelial growth factor-A) were reduced on day 14 postburn. On the contrary, increased expression of Collagen-1 in the early stage of wound healing was observed with no effects on epidemal growth factor receptor (EGFR). The results showed beneficial application of EGF + TRF cream in the treatment of burn wound since it accelerated wound healing by relieving oxidative stress, decreasing inflammation, and promoting proper tissue modelling in the burn wound.
    Matched MeSH terms: Vascular Endothelial Growth Factor A
  10. ElFar OA, Billa N, Lim HR, Chew KW, Cheah WY, Munawaroh HSH, et al.
    Bioengineered, 2022 Jun;13(6):14681-14718.
    PMID: 35946342 DOI: 10.1080/21655979.2022.2100863
    Arthrospira platensis (A. platensis) aqueous extract has massive amounts of natural products that can be used as future drugs, such as C-phycocyanin, allophycocyanin, etc. This extract was chosen because of its high adaptability, which reflects its resolute genetic composition. The proactive roles of cyanobacteria, particularly in the medical field, have been discussed in this review, including the history, previous food and drug administration (FDA) reports, health benefits and the various dose-dependent therapeutic functions that A. platensis possesses, including its role in fighting against lethal diseases such as cancer, SARS-CoV-2/COVID-19, etc. However, the remedy will not present its maximal effect without the proper delivery to the targeted place for deposition. The goal of this research is to maximize the bioavailability and delivery efficiency of A. platensis constituents through selected sites for effective therapeutic outcomes. The solutions reviewed are mainly on parenteral and tablet formulations. Moreover, suggested enteric polymers were discussed with minor composition variations applied for better storage in high humid countries alongside minor variations in the polymer design were suggested to enhance the premature release hindrance of basic drugs in low pH environments. In addition, it will open doors for research in delivering active pharmaceutical ingredients (APIs) in femtoscale with the use of various existing and new formulations.Abbrevations: SDGs; Sustainable Development Goals, IL-4; Interleukin-4, HDL; High-Density Lipoprotein, LDL; Low-Density Lipoprotein, VLDL; Very Low-Density Lipoprotein, C-PC; C-Phycocyanin, APC; Allophycocyanin, PE; Phycoerythrin, COX-2; Cyclooxygenase-2, RCTs; Randomized Control Trials, TNF-α; Tumour Necrosis Factor-alpha, γ-LFA; Gamma-Linolenic Fatty Acid, PGs; Polyglycans, PUFAs: Polyunsaturated Fatty Acids, NK-cell; Natural Killer Cell, FDA; Food and Drug Administration, GRAS; Generally Recognized as Safe, SD; Standard Deviation, API; Active Pharmaceutical Ingredient, DW; Dry Weight, IM; Intramuscular, IV; Intravenous, ID; Intradermal, SC; Subcutaneous, AERs; Adverse Event Reports, DSI-EC; Dietary Supplement Information Executive Committee, cGMP; Current Good Manufacturing Process, A. platensis; Arthrospira platensis, A. maxima; Arthrospira maxima, Spirulina sp.; Spirulina species, Arthrospira; Spirulina, Tecuitlatl; Spirulina, CRC; Colorectal Cancer, HDI; Human Development Index, Tf; Transferrin, TfR; Transferrin Receptor, FR; Flow Rate, CPP; Cell Penetrating Peptide, SUV; Small Unilamenar Vesicle, LUV; Large Unilamenar Vesicle, GUV; Giant Unilamenar Vesicle, MLV; Multilamenar Vesicle, COVID-19; Coronavirus-19, PEGylated; Stealth, PEG; Polyethylene Glycol, OSCEs; Objective Structured Clinical Examinations, GI; Gastrointestinal Tract, CAP; Cellulose Acetate Phthalate, HPMCP, Hydroxypropyl Methyl-Cellulose Phthalate, SR; Sustained Release, DR; Delay Release, Poly(MA-EA); Polymethyl Acrylic Co-Ethyl Acrylate, f-DR L-30 D-55; Femto-Delay Release Methyl Acrylic Acid Co-Ethyl Acrylate Polymer, MW; Molecular Weight, Tg; Glass Transition Temperature, SN2; Nucleophilic Substitution 2, EPR; Enhance Permeability and Retention, VEGF; Vascular Endothelial Growth Factor, RGD; Arginine-Glycine-Aspartic Acid, VCAM-1; Vascular Cell Adhesion Molecule-1, P; Coefficient of Permeability, PES; Polyether Sulfone, pHe; Extracellular pH, ζ-potential; Zeta potential, NTA; Nanoparticle Tracking Analysis, PB; Phosphate Buffer, DLS; Dynamic Light Scattering, AFM; Atomic Force Microscope, Log P; Partition Coefficient, MR; Molar Refractivity, tPSA; Topological Polar Surface Area, C log P; Calculated Partition Coefficient, CMR; Calculated Molar Refractivity, Log S; Solubility Coefficient, pka; Acid Dissociation Constant, DDAB; Dimethyl Dioctadecyl Ammonium Bromide, DOPE; Dioleoylphosphatidylethanolamine, GDP; Good Distribution Practice, RES; Reticuloendothelial System, PKU; Phenylketonuria, MS; Multiple Sclerosis, SLE; Systemic Lupus Erythematous, NASA; National Aeronautics and Space Administration, DOX; Doxorubicin, ADRs; Adverse Drug Reactions, SVM; Support Vector Machine, MDA; Malondialdehyde, TBARS; Thiobarbituric Acid Reactive Substances, CRP; C-Reactive Protein, CK; Creatine Kinase, LDH; Lactated Dehydrogenase, T2D; Type 2 Diabetes, PCB; Phycocyanobilin, PBP; Phycobiliproteins, PEB; Phycoerythrobilin, DPP-4; Dipeptidyl Peptidase-4, MTT; 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyl-2H-tetrazolium bromide, IL-2; Interleukin-2, IL-6; Interleukin-6, PRISMA; Preferred Reporting Items for Systematic Reviews and Meta-Analyses, STATA; Statistics, HepG2; Hepatoblastoma, HCT116; Colon Cancer Carcinoma, Kasumi-1; Acute Leukaemia, K562; Chronic Leukaemia, Se-PC; Selenium-Phycocyanin, MCF-7; Breast Cancer Adenocarcinoma, A375; Human Melanoma, RAS; Renin-Angiotensin System, IQP; Ile-Gln-Pro, VEP; Val-Glu-Pro, Mpro; Main Protease, PLpro; Papin-Like Protease, BMI; Body Mass Index, IC50; Inhibitory Concentration by 50%, LD50; Lethal Dose by 50%, PC12 Adh; Rat Pheochromocytoma Cells, RNS; Reactive Nitrogen Species, Hb1Ac; hemoglobin A1c.
    Matched MeSH terms: Vascular Endothelial Growth Factor A/metabolism
  11. Sakamoto T, Shimura M, Kitano S, Ohji M, Ogura Y, Yamashita H, et al.
    Graefes Arch Clin Exp Ophthalmol, 2022 Feb;260(2):477-487.
    PMID: 34477927 DOI: 10.1007/s00417-021-05308-8
    PURPOSE: The MERCURY study aimed to evaluate the effects on visual acuity and psychological symptoms, and safety, of ranibizumab and subsequent treatment in patients with diabetic macular oedema (DME) and impaired visual acuity (VA). We report data from the prespecified 12-month interim analysis.

    METHODS: This was a 24-month, phase 4, open-label, single-arm, prospective, observational study conducted at 20 specialised retinal centres in Japan. Participants were 209 patients with DME and impaired VA, not previously treated with either intravitreal or systemic anti-vascular endothelial growth factor (anti-VEGF) agents, who initiated ranibizumab 0.5 mg per investigator discretion. Following ranibizumab administration, patients were treated per routine clinical practice. Other treatments were allowed. The main outcome measure was the mean change in best-corrected VA (BCVA) in logarithmic minimum angle of resolution (logMAR) from baseline to month 12. An exploratory objective was to assess patients' psychological status using the Hospital Anxiety and Depression Scale (HADS).

    RESULTS: The mean ± standard deviation BCVA at baseline was 0.43 ± 0.39 logMAR. The mean number of injections of ranibizumab and anti-VEGF agents from baseline to month 11 was 3.2 ± 2.0 and 3.6 ± 2.4, respectively. The BCVA change from baseline to 12 months was - 0.08 ± 0.34 logMAR (p = 0.011), showing a significant improvement; the HADS-anxiety score also decreased significantly (p = 0.001) and the depression score decreased numerically (p = 0.080).

    CONCLUSION: MERCURY study data confirm the effectiveness of real-world treatment initiated with ranibizumab in Japanese patients with DME. In addition, treatment was able to positively influence anxiety via VA improvement.

    Matched MeSH terms: Vascular Endothelial Growth Factor A
  12. Chuar PF, Ng YT, Phang SCW, Koay YY, Ho JI, Ho LS, et al.
    Nutrients, 2021 Oct 25;13(11).
    PMID: 34836025 DOI: 10.3390/nu13113770
    Diabetic peripheral neuropathy (DPN) is the most common microvascular complication of diabetes that affects approximately half of the diabetic population. Up to 53% of DPN patients experience neuropathic pain, which leads to a reduction in the quality of life and work productivity. Tocotrienols have been shown to possess antioxidant, anti-inflammatory, and neuroprotective properties in preclinical and clinical studies. This study aimed to investigate the effects of tocotrienol-rich vitamin E (Tocovid SuprabioTM) on nerve conduction parameters and serum biomarkers among patients with type 2 diabetes mellitus (T2DM). A total of 88 patients were randomized to receive 200 mg of Tocovid twice daily, or a matching placebo for 12 months. Fasting blood samples were collected for measurements of HbA1c, renal profile, lipid profile, and biomarkers. A nerve conduction study (NCS) was performed on all patients at baseline and subsequently at 2, 6, 12 months. Patients were reassessed after 6 months of washout. After 12 months of supplementation, patients in the Tocovid group exhibited highly significant improvements in conduction velocity (CV) of both median and sural sensory nerves as compared to those in the placebo group. The between-intervention-group differences (treatment effects) in CV were 1.60 m/s (95% CI: 0.70, 2.40) for the median nerve and 2.10 m/s (95% CI: 1.50, 2.90) for the sural nerve. A significant difference in peak velocity (PV) was also observed in the sural nerve (2.10 m/s; 95% CI: 1.00, 3.20) after 12 months. Significant improvements in CV were only observed up to 6 months in the tibial motor nerve, 1.30 m/s (95% CI: 0.60, 2.20). There were no significant changes in serum biomarkers, transforming growth factor beta-1 (TGFβ-1), or vascular endothelial growth factor A (VEGF-A). After 6 months of washout, there were no significant differences from baseline between groups in nerve conduction parameters of all three nerves. Tocovid at 400 mg/day significantly improve tibial motor nerve CV up to 6 months, but median and sural sensory nerve CV in up to 12 months of supplementation. All improvements diminished after 6 months of washout.
    Matched MeSH terms: Vascular Endothelial Growth Factor A/blood
  13. Alomari G, Al-Trad B, Hamdan S, Aljabali AAA, Al Zoubi MS, Al-Batanyeh K, et al.
    IET Nanobiotechnol, 2021 Jul;15(5):473-483.
    PMID: 34694755 DOI: 10.1049/nbt2.12026
    This study examines the effect of nanoparticles with zinc oxides (ZnONPs) on diabetic nephropathy, which is the primary cause of mortality for diabetic patients with end-stage renal disease. Diabetes in adult male rats was induced via intraperitoneal injection of streptozotocin. ZnONPs were intraperitoneally administered to diabetic rats daily for 7 weeks. Diabetes was associated with increases in blood glucose level, 24-h urinary albumin excretion rate, glomerular basement membrane thickness, renal oxidative stress markers, and renal mRNA or protein expression of transforming growth factor-β1, fibronectin, collagen-IV, tumour necrosis factor-α and vascular endothelial growth factor-A. Moreover, the expression of nephrin and podocin, and the mRNA expression of matrix metalloproteinase-9 were decreased in the diabetic group. These changes were not detected in the control group and were significantly prevented by ZnONP treatment. These results provide evidence that ZnONPs ameliorate the renal damage induced in a diabetic rat model of nephropathy through improving renal functionality; inhibiting renal fibrosis, oxidative stress, inflammation and abnormal angiogenesis; and delaying the development of podocyte injury. The present findings may help design the clinical application of ZnONPs for protection against the development of diabetic nephropathy.
    Matched MeSH terms: Vascular Endothelial Growth Factor A
  14. Nahar N, Mohamed S, Mustapha NM, Lau S, Ishak NIM, Umran NS
    Naunyn Schmiedebergs Arch Pharmacol, 2021 Mar;394(3):457-467.
    PMID: 33047165 DOI: 10.1007/s00210-020-01989-w
    Diabetes mellitus (DM) often causes ocular disorders leading to vision loss. Metformin is commonly prescribed for type 2 diabetes. This study assessed the effect of metformin on hyperglycemic histopathological eye abnormalities and some possible pathways involved. Male rats were divided into 3 groups (N = 6), namely, healthy control, hyperglycemic non-treated control, and hyperglycemic rats treated with 200 mg/kg metformin. Two weeks after diabetes induction by an intraperitoneal streptozotocin (60 mg streptozotocin (STZ)/kg) injection, the rats develop ocular abnormalities, and metformin (200 mg/kg) treatment was administered daily. Rats underwent dilated retinal digital ophthalmoscope examination and graded for diabetic retinopathy. Rats were sacrificed at 12 weeks, and the cornea, lens, sclera, ciliary body, iris, conjunctiva, retinal, and optic nerve were examined histologically. Rats' fasting blood glucose and body weight were monitored. Serum tumor necrosis factor-α (TNF-α), vascular endothelial growth factor (VEGF), claudin-1, and glutathione/malondialdehyde ratios were analyzed. Metformin significantly attenuated diabetes-related histopathological ocular deteriorations in the cornea, lens, sclera, ciliary body, iris, conjunctiva, retina, and optic nerve partly by restoring serum TNF-α, VEGF, claudin-1, and glutathione/malondialdehyde ratios without significantly affecting the fasting blood glucose levels or body weight in these hyperglycemic rats. Metformin attenuated hyperglycemia-associated histopathological eye deteriorations, possibly partly by ameliorating vascular leakage, oxidative stress, inflammation, and neovascularization, without affecting the fasting blood glucose levels or body weights in these STZ-induced diabetic rats.
    Matched MeSH terms: Vascular Endothelial Growth Factor A/blood
  15. Rezvanian M, Ng SF, Alavi T, Ahmad W
    Int J Biol Macromol, 2021 Feb 28;171:308-319.
    PMID: 33421467 DOI: 10.1016/j.ijbiomac.2020.12.221
    Previously we developed and characterized a novel hydrogel film wound dressing containing Sodium Alginate and Pectin loaded with Simvastatin with multi-functional properties. This study investigated the in-vivo efficacy of the developed wound dressing on type I diabetic wound model. Experiments were performed on male Wistar rats for the period of 21-days. Animals developed diabetes after intraperitoneal injection (50 mg/kg) of Streptozotocin then randomly divided into different groups. On days 7, 14, and 21 of post-wounding, animals were euthanized and the wounds tissue were harvested for analysis. The wound healing rate, hematology and histological analysis, hydroxyproline assay, and Vascular Endothelial Growth Factor A measurements were noted. The results revealed that the wound dressing healed the wounded area significantly (p 
    Matched MeSH terms: Vascular Endothelial Growth Factor A/biosynthesis
  16. Koay YY, Tan GCJ, Phang SCW, Ho JI, Chuar PF, Ho LS, et al.
    Nutrients, 2021 Jan 18;13(1).
    PMID: 33477404 DOI: 10.3390/nu13010258
    Diabetic kidney disease (DKD) is a debilitating complication of diabetes, which develops in 40% of the diabetic population and is responsible for up to 50% of end-stage renal disease (ESRD). Tocotrienols have shown to be a potent antioxidant, anti-inflammatory, and antifibrotic agent in animal and clinical studies. This study evaluated the effects of 400 mg tocotrienol-rich vitamin E supplementation daily on 59 DKD patients over a 12-month period. Patients with stage 3 chronic kidney disease (CKD) or positive urine microalbuminuria (urine to albumin creatinine ratio; UACR > 20-200 mg/mmol) were recruited into a randomized, double-blind, placebo-controlled trial. Patients were randomized into either intervention group (n = 31) which received tocotrienol-rich vitamin E (Tocovid SupraBioTM; Hovid Berhad, Ipoh, Malaysia) 400 mg daily or a placebo group which received placebo capsules (n = 28) for 12 months. HbA1c, renal parameters (i.e., serum creatinine, eGFR, and UACR), and serum biomarkers were collected at intervals of two months. Tocovid supplementation significantly reduced serum creatinine levels (MD: -4.28 ± 14.92 vs. 9.18 ± 24.96), p = 0.029, and significantly improved eGFR (MD: 1.90 ± 5.76 vs. -3.29 ± 9.24), p = 0.011 after eight months. Subgroup analysis of 37 patients with stage 3 CKD demonstrated persistent renoprotective effects over 12 months; Tocovid improved eGFR (MD: 4.83 ± 6.78 vs. -1.45 ± 9.18), p = 0.022 and serum creatinine (MD: -7.85(20.75) vs. 0.84(26.03), p = 0.042) but not UACR. After six months post washout, there was no improvement in serum creatinine and eGFR. There were no significant changes in the serum biomarkers, TGF-β1 and VEGF-A. Our findings verified the results from the pilot phase study where tocotrienol-rich vitamin E supplementation at two and three months improved kidney function as assessed by serum creatinine and eGFR but not UACR.
    Matched MeSH terms: Vascular Endothelial Growth Factor A/blood
  17. Han H, Yang Y, Wu Z, Liu B, Dong L, Deng H, et al.
    Biomed Pharmacother, 2021 Jan;133:110999.
    PMID: 33227710 DOI: 10.1016/j.biopha.2020.110999
    Abnormal angiogenesis is associated with intraocular diseases such as proliferative diabetic retinopathy and neovascular age-related macular degeneration, and current therapies for these eye diseases are not satisfactory. The purpose of this study was to determine whether capilliposide B (CPS-B), a novel oleanane triterpenoid saponin derived from Lysimachia capillipes Hemsl, can inhibit vascular endothelial growth factor (VEGF)-induced angiogenesis signaling events and cellular responses in primary human retinal microvascular endothelial cells (HRECs). Our study revealed that the capilliposide B IC50 for HRECs was 8.5 μM at 72 h and that 1 μM capilliposide B specifically inhibited VEGF-induced activation of VEGFR2 and its downstream signaling enzymes Akt and Erk. In addition, we discovered that this chemical effectively blocked VEGF-stimulated proliferation, migration and tube formation of the HRECs, suggesting that capilliposide B is a promising prophylactic for angiogenesis-associated diseases such as proliferative diabetic retinopathy.
    Matched MeSH terms: Vascular Endothelial Growth Factor A/pharmacology*
  18. Md Yusof K, Rosli R, Abdullah M, A Avery-Kiejda K
    Cancers (Basel), 2020 Nov 06;12(11).
    PMID: 33172072 DOI: 10.3390/cancers12113290
    Lymphatic vessels are regarded as the "forgotten" circulation. Despite this, growing evidence has shown significant roles for the lymphatic circulation in normal and pathological conditions in humans, including cancers. The dissemination of tumor cells to other organs is often mediated by lymphatic vessels that serve as a conduit and is often referred to as tumor-associated lymphangiogenesis. Some of the most well-studied lymphangiogenic factors that govern tumor lymphangiogenesis are the vascular endothelial growth factor (VEGF-C/D and VEGFR-2/3), neuroplilin-2 (NRP2), fibroblast growth factor (FGF), and hepatocyte growth factor (HGF), to name a few. However, recent findings have illustrated that non-coding RNAs are significantly involved in regulating gene expression in most biological processes, including lymphangiogenesis. In this review, we focus on the regulation of growth factors and non-coding RNAs (ncRNAs) in the lymphatic development in normal and cancer physiology. Then, we discuss the lymphangiogenic factors that necessitate tumor-associated lymphangiogenesis, with regards to ncRNAs in various types of cancer. Understanding the different roles of ncRNAs in regulating lymphatic vasculature in normal and cancer conditions may pave the way towards the development of ncRNA-based anti-lymphangiogenic therapy.
    Matched MeSH terms: Vascular Endothelial Growth Factor A
  19. Maki MAA, Cheah SC, Bayazeid O, Kumar PV
    Sci Rep, 2020 10 15;10(1):17468.
    PMID: 33060727 DOI: 10.1038/s41598-020-74467-1
    Galectin-3 (Gal-3) is a carbohydrate-binding protein, that promotes angiogenesis through mediating angiogenic growth factors such as vascular endothelial growth factor (VEGF) and fibroblast growth factor (FGF). There is strong evidence confirming FGF involvement in tumor growth and progression by disrupting cell proliferation and angiogenesis. In this study, we investigated the effect of β-cyclodextrin:everolimus:FGF-7 inclusion complex (Complex) on Caco-2 cell migration, cell motility and colony formation. In addition, we examined the inhibitory effect of the Complex on the circulating proteins; Gal-3 and FGF-7. Swiss Target Prediction concluded that Gal-3 and FGF are possible targets for β-CD. Results of the chemotaxis cell migration assay on Caco-2 cell line revealed that the Complex has higher reduction in cell migration (78.3%) compared to everolimus (EV) alone (58.4%) which is possibly due to the synergistic effect of these molecules when used as a combined treatment. Moreover, the Complex significantly decreased the cell motility in cell scratch assay, less than 10% recovery compared to the control which has ~ 45% recovery. The Complex inhibited colony formation by ~ 75% compared to the control. Moreover, the Complex has the ability to inhibit Gal-3 with minimum inhibitory concentration of 33.46 and 41 for β-CD and EV, respectively. Additionally, β-CD and β-CD:EV were able to bind to FGF-7 and decreased the level of FGF-7 more than 80% in cell supernatant. This confirms Swiss Target Prediction result that predicted β-CD could target FGF. These findings advance the understanding of the biological effects of the Complex which reduced cell migration, cell motility and colony formation and it is possibly due to inhibiting circulating proteins such as; Gal-3 and FGF-7.
    Matched MeSH terms: Vascular Endothelial Growth Factor A/metabolism
  20. Subbiah D, Hashim H, Chew FLM
    Ocul Immunol Inflamm, 2020 Oct 02;28(7):1149-1151.
    PMID: 31509457 DOI: 10.1080/09273948.2019.1648834
    We present five cases of choroidal neovascularization secondary to pediatric Best disease which were treated with two different doses of intravitreal ranibizumab. Optical coherence tomography was used for monitoring of the cases. Three cases had subretinal fibrosis at presentation and two out of these 3 cases required repeat intravitreal ranibizumab at one year follow-up due to recurrence of subfoveal subretinal fluid.
    Matched MeSH terms: Vascular Endothelial Growth Factor A/antagonists & inhibitors
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