Reassessing vascular endothelial growth factor (VEGF) in anti-angiogenic cancer therapy.

Vascularization is fundamental to the growth and spread of tumor cells to distant sites. As a consequence, angiogenesis, the sprouting of new blood vessels from existing ones, is a characteristic trait of cancer. In 1971, Judah Folkman postulated that tumour growth is angiogenesis dependent and that by cutting off blood supply, a neoplastic lesion could be potentially starved into remission. Decades of research have been devoted to understanding the role that vascular endothelial growth factor (VEGF) plays in tumor angiogenesis, and it has been identified as a significant pro-angiogenic factor that is frequently overexpressed within a tumor mass. Today, anti-VEGF drugs such as Sunitinib, Sorafenib, Axitinib, Tanibirumab, and Ramucirumab have been approved for the treatment of advanced and metastatic cancers. However, anti-angiogenic therapy has turned out to be more complex than originally thought. The failure of this therapeutic option calls for a reevaluation of VEGF as the major target in anti-angiogenic cancer therapy. The call for reassessment is based on two rationales: first, tumour blood vessels are abnormal, disorganized, and leaky; this not only prevents optimal drug delivery but it also promotes hypoxia and metastasis; secondly, tumour growth or regrowth might be blood vessel dependent and not angiogenesis dependent as tumour cells can acquire blood vessels via non-angiogenic mechanisms. Therefore, a critical assessment of VEGF, VEGFRs, and their inhibitors could glean newer options such as repurposing anti-VEGF drugs as vascular normalizing agents to enhance drug delivery of immune checkpoint inhibitors.

Fabrication, characterization and antifungal evaluation of polyphenolic extract activated keratin starch coating on infected tomato fruits.

In recent times, the application of protein-based bio-composite edible films in postharvest preservation of food and agricultural products is attracting increased attention due to their biodegradability, eco-friendliness and sustainability. In this study, an avocado pear peel polyphenolic extract enriched keratin-starch composite film was fabricated, characterized and evaluated for antimicrobial activity against fungal infected tomato fruits after 6 days of storage at room (25 ± 2 °C) temperature. The SEM/EDX and FTIR results revealed the successful film formation with high degree of compatibility and homogeneity. Following a 6-day post-coating loss in weight of the coated tomato fruits decreased significantly (p < 0.05) with increasing extract concentration while titratable acidity showed a significant (p < 0.05) increase with increasing extract load. Ascorbic acid and lycopene contents were significantly (p < 0.05) higher in the avocado pear peel polyphenolic extract-loaded films. No significant effect was observed in catechol oxidase activity of the tomato extract across the different treatment groups. In addition, fungal growth inhibition showed a dose dependent increase consistent with avocado pear peel polyphenolic load in coated tomato fruits compared to control. Results obtained in this study showed that polyphenolic activated keratin-starch coating was able to reduce spoilage-induce weight loss as well as conserve the overall quality (including titratable acid levels, lycopene and ascorbic acid contents) of fungal-infected tomato fruit and reduce microbial growth. Therefore polyphenolic activated keratin-starch coating could serve as a sustainable and ecofriendly postharvest preservation method to prolong the shelf life of tomato fruits.

Fabrication and characterization of keratin starch biocomposite film from chicken feather waste and ginger starch.

The disposal of chicken feather through burning or burying is not environmentally compliant due to the accompanying release of greenhouse gas and underground water contamination. Thus, the transformation of this bio-waste into a bio-composite film is considered not only a sustainable strategy for disposal of this solid wastes but also an attractive alternative to developing an efficient nanostructured biomaterial from renewable bio resource. In the present study keratin extracted from chicken feather waste in combination with ginger starch were fabricated into a bio-composite film. The fabricated bio-composite films were characterized, using different analytical techniques. The physicochemical characteristics of ginger starch showed a moisture content of 33.8%, pH of 6.21, amylose and amylopectin contents of 39.1% and 60.9%, respectively. The hydration capacity of the starch was 132.2% while its gelatinization temperature was 65.7 °C. Physical attributes of the bio-composite film, such as surface smoothness and tensile strength increased significantly (p < 0.05) with increasing keratin content, while its transparency and solubility showed significant (p < 0.05) decrease with increasing keratin level. The various blends of the bio-composite films decayed by over 50% of the original mass after 12 days of complete burial in soil. Based on the results obtained in this study, the addition of keratin to starch bio-composite showed remarkable improvement in mechanical properties, such as tensile strength and surface smoothness. The bio-composite film exhibited appropriate stability in water, although future study should be carried out to evaluate its thermal stability. Nonetheless, the fabricated keratin-starch bio-composite showed desirable characteristics that could be optimized for industrial applications.

Effects of co-administration of Ganoderma terpenoid extract with chloroquine on inflammatory markers and antioxidant status in Plasmodium berghei-infected mice.

OBJECTIVE: To understand the protective effects of Ganoderma terpenoid extract (GTE) against Plasmodium berghei-malarial infection in mice, the present study was carried out to evaluate the effects of GTE in combination with chloroquine disulphate (CQ) on erythrocyte-selected inflammatory markers and antioxidant defense status in P. berghei-infected mice. METHODS: P. berghei-infected mice were divided into six groups: infected control (IC) group, administered 1 mL Tween 20; GTE100 and GTE250 groups, administered 100 and 250 mg/kg GTE, respectively; GT100 + CQ and GT250 + CQ groups, co-administered 100 and 250 mg/kg GTE plus 30 mg/kg CQ, respectively; and CQ group, administered 30 mg/kg CQ. A separate group of non-infected mice were given 1 mL Tween 20, and served as a normal control group (NC). Extract and drug were dissolved in Tween 20 and administered orally once daily for 12 consecutive days. At the end of the treatment period, mice were anesthetized with chloroform and sacrificed by cervical dislocation. Plasma was prepared from blood obtained from each mouse. Parameters evaluated at the end of the treatment period include parasitemia, red blood cell count, hematocrit, malondialdehyde (MDA), glutathione (GSH), catalase (CAT), glutathione peroxidase (GPx), superoxide dismutase (SOD), tumor necrosis factor-α (TNF-α), and interleukin-10 (IL-10). RESULTS: Infected mice treated with a combination of GTE and CQ (GT100 + CQ and GT250 + CQ groups) showed significantly reduced parasitemia levels (P < 0.05) compared to those administered GTE alone as well as IC. Significant improvement in body weight (P < 0.05) was also observed in infected mice treated with a combination of GTE and CQ (GT100 + CQ and GT250 + CQ groups), compared to mice receiving GTE alone (GTE100 and GTE250 groups). Plasma MDA and TNF-α concentrations were significantly lowered, and IL-10 concentration was significantly increased in GT100 + CQ and GT250 + CQ groups, relative to the IC group (P < 0.05). GSH concentration and SOD, CAT and GPx activities were significantly higher in GT100 + CQ and GT250 + CQ groups compared to the GTE100, GTE250, IC and NC groups (P < 0.05). CONCLUSION: Data generated in this study showed that GTE enhanced the anti-plasmodial action of CQ in mice through its anti-inflammatory and antioxidant activities.

Effects of Talinum triangulare leaf flavonoid extract on streptozotocin-induced hyperglycemia and associated complications in rats.

Talinum triangulare leaf flavonoid extract (TTFE) was evaluated for its effects on streptozotocin-hyperglycemia and associated complications especially as it relates to dyslipidemia, lipid peroxidation, and renal dysfunction in rats. Two normoglycemic rat groups designated: control (administered distilled water) and control + TTFE (administered 10 mg/kg b.w. TTFE) and two streptozotocin-induced (STZ) diabetic rat groups designated: STZ-control (administered distilled water) and STZ + TTFE (administered 10 mg/kg TTFE). The treatment was given orally once daily for 21 consecutive days. Body weight and insulin concentration showed significant improvement while blood glucose, uric acid, creatinine, and total bilirubin concentrations were significantly reduced in diabetic rats administered TTFE compared to diabetic untreated rats. Furthermore, triglycerides, total cholesterol, LDL-cholesterol, and malondialdehyde concentrations were significantly lowered in diabetic rats administered TTFE compared with diabetic untreated rats. Key enzymes involved in carbohydrate breakdown and cholesterol synthesis, α-amylase and 3-hydroxy-3-methylglutaryl-CoA (HMG-CoA) reductase, respectively, were significantly inhibited in TTFE-treated diabetic rats compared to diabetic control. Results presented in this study suggest that administration of TTFE for 21 days normalized STZ-induced hyperglycemia and its associated dyslipidemia by a mechanism involving inhibition of α-amylase and HMG-CoA reductase activities, respectively, in rats.

Ganoderma terpenoid extract exhibited anti-plasmodial activity by a mechanism involving reduction in erythrocyte and hepatic lipids in Plasmodium berghei infected mice.

Bioactive components of Ganoderma lucidum has recently gained intense research attention due to their acclaimed nutritional and medicinal properties. Thus, the terpenoid extract from the fruit bodies of G. lucidum (GT) was evaluated for activity against Plasmodium berghei in mice in two separate experiments. In addition, the effects of the extract on erythrocyte and hepatic lipids as well as liver HMG-CoA reductase activity before and after the treatments were also assessed. Mice with established infection were administered 100 and 250 mg/kg/day GT alone and in combination with chloroquine (CQ), in either case two separate controls designated: CQ (30 mg/kg chloroquine) and INF-CTR (1 mL DMSO) were also included. Treatment was administered orally for 12 days and parasitemia determined every three days. Percentage survival was significantly increased to 87% from 66% due to combination of GT100 with CQ compared to GT100 alone and to 75% from 62% when GT250 was administered with CQ compared to GT250 alone. Erythrocyte triglycerides, total cholesterol (TC), LDL and phospholipids contents were significantly lower in GT + CQ-treated mice compared to CQ alone and INF-CTR. Similarly, hepatic TC and phospholipid levels were significantly lower in the GT + CQ-treated mice compared to CQ alone and INF-CTR and HMG-CoA reductase activity in the liver was significantly inhibited due to administration of GT + CQ. Data from this study suggest that the anti-plasmodial action of GT could involve mechanisms associated with its hypolipidemic activity. It was also demonstrated that chloroquine, when administered in combination with GT, potentiates its curative effect in P. berghei-infected mice.

Nutritional composition and glycemic index analyses of vitamin A-biofortified maize in healthy subjects.

Besides being a veritable tool for easing the problem of vitamin A deficiency (VAD), this study sought to explore another potential health benefit of vitamin A-biofortified maize (VABM). In the present study, the nutritional composition and glycemic index (GI) of tuwo masara (a nonfermented maize-based dumpling), made from VABM and the indigenous white maize (IWM) genotype, were evaluated. VABM showed significantly (p < 0.05) lower fat (4.38 ± 0.46%) and crude protein (6.58 ± 0.13%) but higher crude fiber (5.29 ± 0.0%) contents compared to 5.22 ± 0.25% crude fat, 7.28 ± 0.11% crude protein, and 4.69 ± 0.00% crude fiber in the IWM. The phytic acid content in the IWM (2.77 mg/100 g) was 39% higher than the level (2.0 ± 0.04 mg/100 g) in VABM. The major provitamin A carotenoid in the VABM were lutein (7.37 ± 0.52 µg/g), zeaxanthin (1.65 ± 0.01 µg/g), cryptoxanthin (1.29 ± 0.02 µg/g), and all-trans-ß-carotene (0.83 ± 0.02 µg/g), while the IWM contained only lutein (1.52 ± 0.32 µg/g). The total carotene concentration, 12.74 ± 1.13 µg/g dry weight in the VABM, was over eight times higher than that observed for the IWM, 1.52 ± 0.32 µg/g dry weight. The VABM tuwo masara showed a significantly lower GI value (70.3%) compared to the IWM tuwo masara (87.7%). Data obtained from the study further attest to the positive nutritional and health benefits of VABM.

Chicken feather hydrolysate as alternative peptone source for microbial cultivation.

Background: Commercially available conventional growth medium for the culture of microbes are expensive, hence the need for alternative cheaper sources. Poultry waste, in the form of feather and blood, are of value in biotechnology because of their high protein content. Hence the primary aim of this study was to produce a cheaper peptone alternative from chicken feather protein hydrolysate (CFPH) and blood meal (BM). Methods: We monitored the growth of selected bacteria and fungi in different concentrations of medium produced from varying combination of peptone, CFPH and BM in order to determine the combination that produced maximum growth. Five different media, namely 100% peptone (control), 100% BM, 40% peptone + 60% CFPH, 40% BM + 60% CFPH and 20% peptone + 20% BM + 60% CFPH were prepared and used for the study. The different media were inoculated with 1 ml of each test organism ( Escherichia coli, Klebsiella pneumoniae, Proteus mirabilis, Staphylococcus aureus, Pseudomonas aeruginosa, Candida carpophila, Candida tropicalis and Pichia kundriavzevii) and their growth monitored for 10 h. Results:Pseudomonas aeruginosa, Proteus mirabilis and Staphylococcus aureus grew best in the 100% peptone, Klebsiella pneumoniae grew best in 100 BM. The fungi species were observed to grow best in 100% peptone. The 60% CFPH + 40% peptone combination (CFPH obtained with precipitate of TCA, HCl, and HNO 3 gave the best growth of E. coli.  The 60% CFPH + 40% peptone combination (CFPH obtained with precipitate of TCA) also gave the best growth of C. tropicalis and Klebsiella pneumoniae respectively. Conclusions: Overall, the 60% CFPH + 40% peptone combination showed the most potential as an alternative to peptone, especially for E. coli.

Modulatory effect of crude aqueous extract of Lingzhi or Reishi Medicinal Mushroom, Ganoderma lucidum (Higher Basidiomycetes), on hematological and antioxidant indices in Plasmodium berghei-infected mice.

Hematological and antioxidant effects of the aqueous extract of fruiting bodies of Ganoderma lucidum were evaluated in Plasmodium berghei-infected mice. Extract was administered at doses of 100, 250, and 500 mg/kg body weight by an intragastric tube once daily for 14 d starting from the fourth day after parasite inoculation. At the end of treatment period, mice in each group were sacrificed and blood was collected for hematological and biochemical analyses. A significant (P<0.05) decrease was observed in serum malondialdehyde content with a corresponding significant (P<0.05) increase in superoxide dismutase, glutathione peroxidase, glutathione S-transferase, and glucose 6-phosphate dehydrogenase activities in the extract-treated groups compared to the infected but untreated group. The results obtained suggest that crude aqueous extract of G. lucidum fruiting bodies possesses potent antioxidant activity that protects hemoglobin against Plasmodium-induced oxidative damage. These findings seem to justify the use of the plant in traditional African and Chinese medicine as an anti-inflammatory and antimicrobial agent.

Modulation of Lipoprotein Cholesterol Levels in Plasmodium berghei Malarial Infection by Crude Aqueous Extract of Ganoderma lucidum.

In this study, attempt is made to establish changes in serum and liver lipoprotein cholesterols accompanying Plasmodium berghei malarial infection in mice treated with aqueous extract of Ganoderma lucidum at 100, 250, and 500 mg/kg body weight in comparison with 15 mg/kg chloroquine (CQ). Significant increases in all the lipoprotein fractions were observed in infected untreated mice compared with normal control mice. Treatment with 100 and 250 mg/kg G. lucidum extract produced significant reduction in serum total cholesterol (TC) and low-density cholesterol (LDL-C) contents compared with 500 mg/kg G. lucidum and CQ. Treatment with CQ, however, produced significant reduction in hepatic TC and LDL-C compared with the extract. A dose-dependent significant increase in serum high-density lipoprotein cholesterol (HDL-C) was observed in the G. lucidum treated mice compared with normal control but significantly lower compared with CQ-treated mice. Liver HDL-C level was significantly higher in CQ-treated mice compared with normal control and significantly lower compared with G. lucidum-treated and infected untreated mice. A dose-dependent effect of the extract was observed in both serum and liver very-low density lipoprotein cholesterol (VLDL-C). The implication of these results is discussed with respect to the parasite survival and proliferation in the serum and liver.

Antimalarial and hepatoprotective effects of crude ethanolic extract of Lingzhi or Reishi medicinal mushroom, Ganoderma lucidum (W.Curt.:Fr.)P.Karst. (higher Basidiomycetes), in Plasmodium berghei-infected mice.

This study was aimed at investigating the in vivo antimalarial activity (using some biochemical indices) of crude aqueous extracts of the fruiting bodies of Ganoderma lucidum, a mushroom with well-established medicinal properties. A rodent malaria parasite, Plasmodium berghei (1 × 107), was inoculated intraperitoneally into Swiss albino mice. The test groups were administered G. lucidum extract and chloroquine (CQ, as standard drug), while the control groups were administered the same amount of distilled water by an intragastric tube once daily. The antimalarial activity of the extract was investigated from the suppressive, curative, and prophylactic effects of the extract on parasite growth. Serum aminotransferases (AST and ALT), alkaline phosphatase (ALP), and gamma glutamine transpeptidase (γ-GT) levels monitored following the 4-day suppressive test were significantly reduced, with a corresponding significant increase in the livers of mice treated with the extract compared with infected untreated mice. The results obtained from this study provide scientific justification in an animal model of malaria that an ethanolic extract of G. lucidum possesses potent antimalarial activity and also could help ameliorate the attendant Plasmodium-induced liver damage due to malarial infection.