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Fulltext An Intrinsic Mitochondrial Pathway Is Required for Phytic Acid-Chitosan-Iron Oxide Nanocomposite (Phy-CS-MNP) to Induce G₀/G₁ Cell Cycle Arrest and Apoptosis in the Human Colorectal Cancer (HT-29) Cell Line

Tan BL, Norhaizan ME, Chan LC

Pharmaceutics, 2018 Oct 23;10(4).
PMID: 30360519 DOI: 10.3390/pharmaceutics10040198

Magnetic iron oxide nanoparticles are among the most useful metal nanoparticles in biomedical applications. A previous study had confirmed that phytic acid-chitosan-iron oxide nanocomposite (Phy-CS-MNP) exhibited antiproliferative activity towards human colorectal cancer (HT-29) cells. Hence, in this work, we explored the in vitro cytotoxicity activity and mechanistic action of Phy-CS-MNP nanocomposite in modulating gene and protein expression profiles in HT-29 cell lines. Cell cycle arrest and apoptosis were evaluated by NovoCyte Flow Cytometer. The mRNA changes (cyclin-dependent kinase 4 (Cdk4), vascular endothelial growth factor A (VEGFA), c-Jun N-terminal kinase 1 (JNK1), inducible nitric oxide synthase (iNOS), and matrix metallopeptidase 9 (MMP9)) and protein expression (nuclear factor-kappa B (NF-κB) and cytochrome c) were assessed by quantitative real-time polymerase chain reaction (PCR) and western blotting, respectively. The data from our study demonstrated that treatment with Phy-CS-MNP nanocomposite triggered apoptosis and G₀/G₁ cell cycle arrest. The transcriptional activity of JNK1 and iNOS was upregulated after treatment with 90 μg/mL Phy-CS-MNP nanocomposite. Our results suggested that Phy-CS-MNP nanocomposite induced apoptosis and cell cycle arrest via an intrinsic mitochondrial pathway through modulation of Bax and Bcl-2 and the release of cytochrome c from the mitochondria into the cytosol.

Matched MeSH terms: Vascular Endothelial Growth Factor A
Fulltext Manilkara zapota (L.) P. Royen Leaf Water Extract Induces Apoptosis in Human Hepatocellular Carcinoma (HepG2) Cells via ERK1/2/Akt1/JNK1 Signaling Pathways

Tan BL, Norhaizan ME, Chan LC

Evid Based Complement Alternat Med, 2018;2018:7826576.
PMID: 30519270 DOI: 10.1155/2018/7826576

Manilkara zapota (L.) P. Royen, called sapodilla, or locally known as ciku, belongs to the family Sapotaceae. We found that Manilkara zapota leaf water extract has cytotoxic effect against human hepatocellular carcinoma (HepG2) cell line in our earlier study. Therefore, this study aimed to explore the anticancer properties of Manilkara zapota leaf water extract in HepG2 cells. We also aimed to unravel yet undiscovered mechanisms and identified several expressed genes whose functions in cytotoxicity activity of Manilkara zapota leaf water extract in HepG2 cells have not been well-studied. The apoptosis and intracellular reactive oxygen species (ROS) activities were analyzed using Annexin V-propidium iodide staining and dichlorodihydrofluorescein diacetate, respectively, by NovoCyte Flow Cytometer. Bax and Bcl-2 expression were assessed using Enzyme-Linked Immunosorbent Assay. The associated molecular pathways were evaluated by quantitative real-time PCR. Overall analyses revealed that Manilkara zapota leaf water extract can increase percentage of early apoptotic cells, induce the formation of ROS, upregulate c-Jun N-terminal kinase 1 (JNK1) and inducible nitric oxide synthase (iNOS), and reduce Akt1 and vascular endothelial growth factor A (VEGFA) transcriptional activities. Our data suggest that Manilkara zapota leaf water extract can suppress the growth of HepG2 cells via modulation of ERK1/2/Akt1/JNK1 transcriptional expression.

Matched MeSH terms: Vascular Endothelial Growth Factor A
Scopoletin, an active principle of tree tobacco (Nicotiana glauca) inhibits human tumor vascularization in xenograft models and modulates ERK1, VEGF-A, and FGF-2 in computer model

Tabana YM, Hassan LE, Ahamed MB, Dahham SS, Iqbal MA, Saeed MA, et al.

Microvasc Res, 2016 09;107:17-33.
PMID: 27133199 DOI: 10.1016/j.mvr.2016.04.009

We recently reported the antineovascularization effect of scopoletin on rat aorta and identified its potential anti-angiogenic activity. Scopoletin could be useful as a systemic chemotherapeutic agent against angiogenesis-dependent malignancies if its antitumorigenic activity is investigated and scientifically proven using a suitable human tumor xenograft model. In the present study, bioassay-guided (anti-angiogenesis) phytochemical investigation was conducted on Nicotiana glauca extract which led to the isolation of scopoletin. Further, anti-angiogenic activity of scopoletin was characterized using ex vivo, in vivo and in silico angiogenesis models. Finally, the antitumorigenic efficacy of scopoletin was studied in human colorectal tumor xenograft model using athymic nude mice. For the first time, an in vivo anticancer activity of scopoletin was reported and characterized using xenograft models. Scopoletin caused significant suppression of sprouting of microvessels in rat aortic explants with IC50 (median inhibitory concentration) 0.06μM. Scopoletin (100 and 200mg/kg) strongly inhibited (59.72 and 89.4%, respectively) vascularization in matrigel plugs implanted in nude mice. In the tumor xenograft model, scopoletin showed remarkable inhibition on tumor growth (34.2 and 94.7% at 100 and 200mg/kg, respectively). Tumor histology revealed drastic reduction of the extent of vascularization. Further, immunostaining of CD31 and NG2 receptors in the histological sections confirmed the antivascular effect of scopoletin in tumor vasculature. In computer modeling, scopoletin showed strong ligand affinity and binding energies toward the following angiogenic factors: protein kinase (ERK1), vascular endothelial growth factor A (VEGF-A), and fibroblast growth factor 2 (FGF-2). These results suggest that the antitumor activity of scopoletin may be due to its strong anti-angiogenic effect, which may be mediated by its effective inhibition of ERK1, VEGF-A, and FGF-2.

Matched MeSH terms: Vascular Endothelial Growth Factor A/metabolism*; Vascular Endothelial Growth Factor A/chemistry
Fulltext Ophthalmic Intervention of Naringenin Decreases Vascular Endothelial Growth Factor by Counteracting Oxidative Stress and Cellular Damage in In Vivo Zebrafish

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
Intravitreal bevacizumab for radiation-induced cystoid macular oedema in patients with nasopharyngeal carcinoma: a clinical series

Subrayan V, Khaw KW, Peyman M, Koay AC, Tajunisah I

Ophthalmologica, 2013;229(4):208-11.
PMID: 23548379 DOI: 10.1159/000348630

To evaluate the outcome of intravitreal bevacizumab in the treatment of radiation-induced cystoid macular oedema among patients who underwent external beam radiotherapy for nasopharyngeal carcinoma.

Matched MeSH terms: Vascular Endothelial Growth Factor A/antagonists & inhibitors
Recurrence of SRF Post Intravitreal Ranibizumab for Pediatric Choroidal Neovascularisation Secondary to Best Disease

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
Associations between Aging and Vitamin D Status with Whole-Body Nitric Oxide Production and Markers of Endothelial Function

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
Fulltext Osteoblasts growth behaviour on bio-based calcium carbonate aragonite nanocrystal

Shafiu Kamba A, Zakaria ZA

Biomed Res Int, 2014;2014:215097.
PMID: 24734228 DOI: 10.1155/2014/215097

Calcium carbonate (CaCO3) nanocrystals derived from cockle shells emerge to present a good concert in bone tissue engineering because of their potential to mimic the composition, structure, and properties of native bone. The aim of this study was to evaluate the biological response of CaCO3 nanocrystals on hFOB 1.19 and MC3T3 E-1 osteoblast cells in vitro. Cell viability and proliferation were assessed by MTT and BrdU assays, and LDH was measured to determine the effect of CaCO3 nanocrystals on cell membrane integrity. Cellular morphology was examined by SEM and fluorescence microscopy. The results showed that CaCO3 nanocrystals had no toxic effects to some extent. Cell proliferation, alkaline phosphatase activity, and protein synthesis were enhanced by the nanocrystals when compared to the control. Cellular interactions were improved, as indicated by SEM and fluorescent microscopy. The production of VEGF and TGF-1 was also affected by the CaCO3 nanocrystals. Therefore, bio-based CaCO3 nanocrystals were shown to stimulate osteoblast differentiation and improve the osteointegration process.

Matched MeSH terms: Vascular Endothelial Growth Factor A/metabolism
Fulltext PI3K/Akt activity has variable cell-specific effects on expression of HIF target genes, CA9 and VEGF, in human cancer cell lines

Shafee N, Kaluz S, Ru N, Stanbridge EJ

Cancer Lett, 2009 Sep 8;282(1):109-15.
PMID: 19342157 DOI: 10.1016/j.canlet.2009.03.004

The phosphatidylinositol 3-kinase/Akt (PI3K) pathway regulates hypoxia-inducible factor (HIF) activity. Higher expression of HIF-1alpha and carbonic anhydrase IX (CAIX), a hypoxia-inducible gene, in HT10806TG fibrosarcoma cells (mutant N-ras allele), compared to derivative MCH603 cells (deleted mutant N-ras allele), correlated with increased PI3K activity. Constitutive activation of the PI3K pathway in MCH603/PI3K(act) cells increased HIF-1alpha but, surprisingly, decreased CAIX levels. The cell-type specific inhibitory effect on CAIX was confirmed at the transcriptional level whereas epigenetic modifications of CA9 were ruled out. In summary, our data do not substantiate the generalization that PI3K upregulation leads to increased HIF activity.

Matched MeSH terms: Vascular Endothelial Growth Factor A/metabolism*
Fulltext HLA-DRB1*04 as a Risk Allele to Systemic Lupus Erythematosus and Lupus Nephritis in the Malay Population of Malaysia

Selvaraja M, Chin VK, Abdullah M, Arip M, Amin-Nordin S

Front Med (Lausanne), 2020;7:598665.
PMID: 33644084 DOI: 10.3389/fmed.2020.598665

Systemic lupus erythematosus (SLE) is a chronic autoimmune disease afflicting multiple organs. Lupus nephritis (LN) is a serious complication of SLE and remains a major cause of mortality and morbidity. Curative therapy remains unavailable as etiology from genetic and environmental factors is still unclear. The present study was conducted to elucidate the link between HLA-DRB1 gene polymorphisms with SLE and LN through clinical and laboratory/biological presentations in a population of Malaysian Malay females with SLE. A total of 100 Malay female SLE patients inclusive of 70 SLE patients without LN and 30 patients with LN were included in this study. HLA-DRB1 allele examination in SLE patients was performed using PCR-SSO, and the alleles' frequencies were compared with 951 publicly available datasets representing Malay healthy controls in Malaysia. Cytokines and free radical levels were detected by ELISA and bead-based multiplexed Luminex assays. The association between HLA-DRB1 alleles with clinical and serological manifestations and immune mediators was analyzed using different statistical approaches whenever applicable. Our study showed that HLA-DRB1*0405, HLA-DRB1*1502, and HLA-DRB1*1602 were associated with the increased risk of SLE while HLA-DRB1*1201 and HLADRB1*1202 alleles were associated with a lower risk of SLE development. Furthermore, HLA-DRB1*04 showed significant association to LN and arthritis while HLA-DRB1*15 was significantly associated with oral ulcer in Malay SLE patients. Association analysis of HLA-DRB1*04 with clinical and biological factors revealed that HLA-DRB1*04 was significantly associated with Systemic Lupus Erythematosus Disease Activity Index (SLEDAI) scores, anti-nuclear antibody (ANA), C-reactive protein (CRP) in the blood, and total protein in the urine. SLE carriers with the HLA-DRB1*04 allele were significantly correlated to the increased levels of cytokines (IFN-y, GM-CSF, IL-17F, IL-18, IL-21, and VEGF) and were significantly showing negative correlation to IL-5 and free radicals (LPO and catalase enzyme) levels compared to SLE carriers without HLA-DRB1*04 allele. The results suggested that disease severity in SLE may be determined by HLA-DRB1 alleles. The risk of HLA-DRB1*04 allele with LN was supported by the demonstration of an intense inflammatory response in Malay SLE patients in Malaysia. More studies inclusive of a larger and multiple SLE cohorts in the future are warranted to validate these findings.

Matched MeSH terms: Vascular Endothelial Growth Factor A
A Case of Polypoidal Choroidal Vasculopathy Associated With Optic Disc Drusen

Sarojini K, Ling KP, Teh WM, Ali H, Zunaina E

Cureus, 2020 Sep 07;12(9):e10297.
PMID: 33047087 DOI: 10.7759/cureus.10297

We report a case of optic disc drusen (ODD) associated with peripapillary polypoidal choroidal vasculopathy (PCV). A 62-year-old Malay lady presented with both eye ODD and the left eye associated with peripapillary subretinal hemorrhage. Ultrasound B-scan and red-free photography confirmed the optic nerve head drusen findings bilaterally. Optical coherence tomography (OCT) of the left eye showed sharply elevated peripapillary pigment epithelial detachment with subretinal fluid. The presence of peripapillary polyps with branching vascular network in indocyanine green angiography of the left eye further confirmed the diagnosis of PCV and excluded choroidal neovascularization (CNV) secondary to ODD. Subsequently, the patient was treated with a combination of verteporfin photodynamic therapy with three monthly intravitreal ranibizumab injections. Three months after the combined treatment, OCT showed completely resolved subretinal fluid. ODD can cause compression of the subretinal vessels at the optic disc that results in retinal ischemia and release of vascular endothelial growth factor, which may trigger the development of CNV or PCV. The rarity of this combination makes it interesting to study more cases of ODD with PCV. Importantly, a thorough evaluation in distinguishing the PCV from the CNV that mimics it is crucial for early detection and prompt intervention. In this case, indocyanine green angiography (ICGA) is the diagnostic method to differentiate the PCV from CNV secondary to ODD.

Matched MeSH terms: Vascular Endothelial Growth Factor A
Fulltext Impact on visual acuity and psychological outcomes of ranibizumab and subsequent treatment for diabetic macular oedema in Japan (MERCURY)

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
Fulltext Protective Effect of Palm Oil-Derived Tocotrienol-Rich Fraction Against Retinal Neurodegenerative Changes in Rats with Streptozotocin-Induced Diabetic Retinopathy

Sadikan MZ, Nasir NAA, Agarwal R, Ismail NM

Biomolecules, 2020 04 05;10(4).
PMID: 32260544 DOI: 10.3390/biom10040556

: Oxidative stress plays an important role in retinal neurodegeneration and angiogenesis associated with diabetes. In this study, we investigated the effect of the tocotrienol-rich fraction (TRF), a potent antioxidant, against diabetes-induced changes in retinal layer thickness (RLT), retinal cell count (RCC), retinal cell apoptosis, and retinal expression of vascular endothelial growth factor (VEGF) in rats. Additionally, the efficacy of TRF after administration by two different routes was compared. The diabetes was induced in Sprague-Dawley rats by intraperitoneal injection of streptozotocin. Subsequently, diabetic rats received either oral or topical treatment with vehicle or TRF. Additionally, a group of non-diabetic rats was included with either oral or topical treatment with a vehicle. After 12 weeks of the treatment period, rats were euthanized, and retinas were collected for measurement of RLT, RCC, retinal cell apoptosis, and VEGF expression. RLT and RCC in the ganglion cell layer were reduced in all diabetic groups compared to control groups (p < 0.01). However, at the end of the experimental period, oral TRF-treated rats showed a significantly greater RLT compared to topical TRF-treated rats. A similar observation was made for retinal cell apoptosis and VEGF expression. In conclusion, oral TRF supplementation protects against retinal degenerative changes and an increase in VEGF expression in rats with streptozotocin-induced diabetic retinopathy. Similar effects were not observed after topical administration of TRF.

Matched MeSH terms: Vascular Endothelial Growth Factor A/metabolism
In-vivo evaluation of Alginate-Pectin hydrogel film loaded with Simvastatin for diabetic wound healing in Streptozotocin-induced diabetic rats

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
Novel Fish Oil-based Bigel System for Controlled Drug Delivery and its Influence on Immunomodulatory Activity of Imiquimod Against Skin Cancer

Rehman K, Zulfakar MH

Pharm Res, 2017 01;34(1):36-48.
PMID: 27620176 DOI: 10.1007/s11095-016-2036-8

PURPOSE: To characterize bigel system as a topical drug delivery vehicle and to establish the immunomodulatory role of imiquimod-fish oil combination against skin cancer and inflammation resulting from chemical carcinogenesis.
METHODS: Imiquimod-loaded fish oil bigel colloidal system was prepared using a blend of carbopol hydrogel and fish oil oleogel. Bigels were first characterized for their mechanical properties and compared to conventional gel systems. Ex vivo permeation studies were performed on murine skin to analyze the ability of the bigels to transport drug across skin and to predict the release mechanism via mathematical modelling. Furthermore, to analyze pharmacological effectiveness in skin cancer and controlling imiquimod-induced inflammatory side effects, imiquimod-fish oil combination was tested in vitro on epidermoid carcinoma cells and in vivo in Swiss albino mice cancer model.
RESULTS: Imiquimod-loaded fish oil bigels exhibited higher drug availability inside the skin as compared to individual imiquimod hydrogel and oleogel controls through quasi-Fickian diffusion mechanism. Imiquimod-fish oil combination in bigel enhanced the antitumor effects and significantly reduced serum pro-inflammatory cytokine levels such as tumor necrosis factor-alpha and interleukin-6, and reducing tumor progression via inhibition of vascular endothelial growth factor. Imiquimod-fish oil combination also resulted in increased expression of interleukin-10, an anti-inflammatory cytokine, which could also aid anti-tumor activity against skin cancer.
CONCLUSION: Imiquimod administration through a bigel vehicle along with fish oil could be beneficial for controlling imiquimod-induced inflammatory side effects and in the treatment of skin cancer.

Matched MeSH terms: Vascular Endothelial Growth Factor A/metabolism
Fulltext Exudative retinal detachment and macular hole as a rare sequelae of central vein occlusion

Rathna, R., Mushawiahti, M., Bastion, M.L.C., Masdar, A., Ropilah, A.R.

Medicine & Health, 2018;13(1):243-250.
MyJurnal

Central retinal vein occlusion (CRVO) is uncommon among young patients. Among the young adults, CRVO tends to be more benign with good visual prognosis. Macular oedema secondary to retinal vein occlusion is a relatively common complication that is currently being treated with intravitreal anti vascular endothelial growth factor with good outcomes. Other complications include lamellar hole, vitreous hemorrhage and neovascular glaucoma. We report a case of central retinal vein occlusion in a young female who presented to us with the complaint of blurring of vision in the left eye for four months. Fundus examination showed hyperemic optic disc, dilated tortuous vein, extensive retinal hemorrhages with macular oedema and an inferior shallow exudative retinal detachment. One month later, intravitreal ranibizumab injection for her macular oedema, a full thickness macular hole developed with reduction of macular oedema. Four months later, the hole spontaneously closed but her macular oedema persisted. The possibility of rare complications like exudative retinal detachment and full thickness macular hole must be kept in mind to ensure early detection and effective management is provided to preserve vision.

Matched MeSH terms: Vascular Endothelial Growth Factor A
Fulltext Cytokine expression profile of dengue patients at different phases of illness

Rathakrishnan A, Wang SM, Hu Y, Khan AM, Ponnampalavanar S, Lum LC, et al.

PLoS One, 2012;7(12):e52215.
PMID: 23284941 DOI: 10.1371/journal.pone.0052215

BACKGROUND: Dengue is an important medical problem, with symptoms ranging from mild dengue fever to severe forms of the disease, where vascular leakage leads to hypovolemic shock. Cytokines have been implicated to play a role in the progression of severe dengue disease; however, their profile in dengue patients and the synergy that leads to continued plasma leakage is not clearly understood. Herein, we investigated the cytokine kinetics and profiles of dengue patients at different phases of illness to further understand the role of cytokines in dengue disease.
METHODS AND FINDINGS: Circulating levels of 29 different types of cytokines were assessed by bead-based ELISA method in dengue patients at the 3 different phases of illness. The association between significant changes in the levels of cytokines and clinical parameters were analyzed. At the febrile phase, IP-10 was significant in dengue patients with and without warning signs. However, MIP-1β was found to be significant in only patients with warning signs at this phase. IP-10 was also significant in both with and without warning signs patients during defervescence. At this phase, MIP-1β and G-CSF were significant in patients without warning signs, whereas MCP-1 was noted to be elevated significantly in patients with warning signs. Significant correlations between the levels of VEGF, RANTES, IL-7, IL-12, PDGF and IL-5 with platelets; VEGF with lymphocytes and neutrophils; G-CSF and IP-10 with atypical lymphocytes and various other cytokines with the liver enzymes were observed in this study.
CONCLUSIONS: The cytokine profile patterns discovered between the different phases of illness indicate an essential role in dengue pathogenesis and with further studies may serve as predictive markers for progression to dengue with warning signs.

Matched MeSH terms: Vascular Endothelial Growth Factor A/blood
Fulltext Basic fibroblast growth factor modulates cell cycle of human umbilical cord-derived mesenchymal stem cells

Ramasamy R, Tong CK, Yip WK, Vellasamy S, Tan BC, Seow HF

Cell Prolif, 2012 Apr;45(2):132-9.
PMID: 22309282 DOI: 10.1111/j.1365-2184.2012.00808.x

BACKGROUND: Mesenchymal stem cells (MSC) have great potential in regenerative medicine, immunotherapy and gene therapy due to their unique properties of self-renewal, high plasticity, immune modulation and ease for genetic modification. However, production of MSC at sufficient clinical scale remains an issue as in vitro generation of MSC inadequately fulfils the demand with respect to patients.
OBJECTIVES: This study has aimed to establish optimum conditions to generate and characterize MSC from human umbilical cord (UC-MSC).
MATERIALS AND METHODS: To optimize MSC population growth, basic fibroblast growth factor (bFGF) was utilized in culture media. Effects of bFGF on expansion kinetics, cell cycle, survival of UC-MSC, cytokine secretion, expression of early stem-cell markers and immunomodulation were investigated.
RESULTS: bFGF supplementation profoundly enhanced UC-MSC proliferation by reducing population doubling time without altering immunophenotype and immunomodulatory function of UC-MSC. However, cell cycle studies revealed that bFGF drove the cells into the cell cycle, as a higher proportion of cells resided in S phase and progressed into M phase. Consistent with this, bFGF was shown to promote expression of cyclin D proteins and their relevant kinases to drive UC-MSC to transverse cell cycle check points, thus, committing the cells to DNA synthesis. Furthermore, supplementation with bFGF changed the cytokine profiles of the cells and reduced their apoptotic level.
CONCLUSION: Our study showed that bFGF supplementation of UC-MSC culture enhanced the cells' growth kinetics without compromising their nature.

Matched MeSH terms: Vascular Endothelial Growth Factor A/metabolism
Fulltext An Overview of In Vitro, In Vivo, and Computational Techniques for Cancer-Associated Angiogenesis Studies

Rahman HS, Tan BL, Othman HH, Chartrand MS, Pathak Y, Mohan S, et al.

Biomed Res Int, 2020;2020:8857428.
PMID: 33381591 DOI: 10.1155/2020/8857428

Angiogenesis is a crucial area in scientific research because it involves many important physiological and pathological processes. Indeed, angiogenesis is critical for normal physiological processes, including wound healing and embryonic development, as well as being a component of many disorders, such as rheumatoid arthritis, obesity, and diabetic retinopathies. Investigations of angiogenic mechanisms require assays that can activate the critical steps of angiogenesis as well as provide a tool for assessing the efficacy of therapeutic agents. Thus, angiogenesis assays are key tools for studying the mechanisms of angiogenesis and identifying the potential therapeutic strategies to modulate neovascularization. However, the regulation of angiogenesis is highly complex and not fully understood. Difficulties in assessing the regulators of angiogenic response have necessitated the development of an alternative approach. In this paper, we review the standard models for the study of tumor angiogenesis on the macroscopic scale that include in vitro, in vivo, and computational models. We also highlight the differences in several modeling approaches and describe key advances in understanding the computational models that contributed to the knowledge base of the field.

Matched MeSH terms: Vascular Endothelial Growth Factor A/metabolism
Human tuberculosis brain promotes neuronal apoptosis but not in astrocytes with high expression of vascular endothelial growth factor

Othman FN, Muthuraju S, Noor SSM, Abdullah S, Mohd Yusoff AA, Tharakan J, et al.

Tuberculosis (Edinb), 2018 09;112:45-51.
PMID: 30205968 DOI: 10.1016/j.tube.2018.07.007

The present study aimed to investigate the involvement of the angiogenic marker vascular endothelia growth factor (VEGF) and apoptotic markers of Bcl-2 and Bax in the neurons and astrocytes in the brain infected by Mycobacterium tuberculosis. The immunohistochemistry staining was performed to analyze the expression of the VEGF, Bcl-2 and Bax in the astrocytes and neurons. The expression of VEGF was high in neurons and astrocytes in both the infected brain and control tissues with no difference of angiogenic activity (p = 0.40). Higher Bcl-2 expression was seen in astrocytes of infected brain tissues compared to the control tissues (p = 0.004) promoted a higher anti-apoptotic activity in astrocytes. The neurons expressed strong Bax expression in the infected brain tissues compared to the control tissues (p 

Matched MeSH terms: Vascular Endothelial Growth Factor A/metabolism*

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