Glioblastoma multiforme is the most invasive and aggressive brain tumor in humans, and despite the latest chemical and radiative therapeutic approaches, it is still scarcely sensitive to these treatments and is generally considered an incurable disease. This paper will focus on the latest approaches to the treatment of this cancer, including the new chemicals such as proautophagic drugs and kinases inhibitors, and di ff erentiating agents. In this field, there have been opening new perspectives as the discovery of possible specific targets such as the EGFRvIII, a truncated form of the EGF receptor. Antibodies against these targets can be used as proapoptotic agents and as possible carriers for chemicals, drugs, radioisotopes, and toxins. In this paper, we review the possible mechanism of action of these therapies, with particular attention to the combined use of toxic substances (for example, immunotoxins) and antiproliferative/di ff erentiating compounds (i.e., ATRA, PPAR γ agonists). All these aspects will be discussed in the view of progress clinical trials and of possible new approaches for directed drug formulations.
The transforming growth factor-beta (TGFβ) superfamily encompasses widespread and evolutionarily conserved polypeptide growth factors that regulate and orchestrate growth and differentiation in all cell types and tissues. While they regulate asymmetric cell division and cell fate determination during early development and embryogenesis, TGFβ family members play a major regulatory role in hormonal and immune responses, cell growth, cell death and cell immortalization, bone formation, tissue remodeling and repair, and erythropoiesis throughout adult life. The biological and physiological functions of TGFβ, the founding member of this family, and its receptors are of central importance to human diseases, particularly cancer. By regulating cell growth, death, and immortalization, TGFβ signaling pathways exert tumor suppressor effects in normal cells and early carcinomas. Thus, it is not surprising that a high number of human tumors arise due to mutations or deletions in the genes coding for the various TGFβ signaling components. As tumors develop and progress, these protective and cytostatic effects of TGFβ are often lost. TGFβ signaling then switches to promote cancer progression, invasion, and tumor metastasis. The molecular mechanisms underlying this dual role of TGFβ in human cancer will be discussed in depth in this paper, and it will highlight the challenge and importance of developing novel therapeutic strategies specifically aimed at blocking the prometastatic arm of the TGFβ signaling pathway without affecting its tumor suppressive effects.
Microbial xylanase and pectinase are two extremely valuable enzymes, which have captivated much attention. This can be seen from the increased demand for these enzymes by many industrial sectors. This study investigates the isolation and screening of extracellular xylanopectinolytic enzymes-producing bacteria in a submerged fermentation (SmF). Samples are collected from the compost of empty fruit bunch (EFB) at Biocompost Pilot Plant, located at Biorefinery Plant, Universiti Putra Malaysia. From the experiment, out of 20 isolates, 11 isolates show xylanase or/and pectinase activity, and only one isolate (EFB-11) shows the concurrent activities of xylanase and pectinase. These activities are selected for enzyme production under submerged fermentation (quantitative screening). At the 72nd hour of incubation, xylanase and pectinase show the highest production, which ranges about 42.33 U/mL and 62.17 U/mL (with low amount of cellulase present), supplemented with 2% (w/v) of rice bran as carbon source at incubation temperature level, which is 30°C. Meanwhile, the pH of media is shifted to 8.42, which indicates that EFB-11 isolate is alkalotolerant bacteria and identified as Bacillus subtilis ADI1. This strain proves to have potential in agroindustrial bioconversion and has a promising ability to scale up to an industrial scale.
Thein vivodynamics of HIV infection, the infection mechanism, the cell types infected, and the role played by the cytotoxic cells are poorly understood. This paper uses mathematical modelling as a tool to investigate and analyze the immune system dynamics in the presence of HIV infection. We formulate a six-dimensional model of nonlinear ordinary differential equations derived from known biological interaction mechanisms between the immune cells and the HIV virions. The existence and uniqueness as well as positivity and boundedness of the solutions to the differential equations are proved. Furthermore, the disease-free reproduction number is derived and the local asymptotic stability of the model investigated. In addition, numerical analysis is carried out to illustrate the importance of havingR0<1. Lastly, the biological dynamics of HIVin vivoinfection are graphically represented. The results indicate that, at acute infection, the cytotoxic T-cells play a paramount role in reducing HIV viral replication. In addition, the results emphasize the importance of developing controls, interventions, and management policies that when implemented would lead to viral suppression during acute infection.
[This corrects the article DOI: 10.1155/2013/139273.].
Dyslipidemia is a common metabolic disorder especially in diabetes mellitus (DM). In this study, the ability of Sapium ellipticum (SE) leaf extract to restore lipid homeostasis in streptozotocin-induced diabetes was examined. DM was induced in experimental rats (Wistar strains) using single intraperitoneal dose (55 mg/kg body weight {BW}) of streptozotocin (STZ). Treatment of diabetic rats with SE was oral (p.o), at doses of 400 and 800 mg kg −1 BW, twice daily at 8 h interval for 21 days. Lipid parameters were analyzed in the serum of rats using test kits. SE caused a significant ( P ≤ 0.05) reduction in STZ-induced hypercholesterolemia in a dose dependent pattern (13.7 and 17.89%). These effects were comparable to that provided by metformin (15.45%), a standard antidiabetic drug. Similar pattern was noted with serum triglycerides (TG) (10.63 and 19.06%) and LDL (31.47 and 25.97%). Adipose tissue TG level was improved to near normal. Besides, the cardiovascular risk predictors in terms of atherogenic index of plasma (AIP) and LDL/HDL ratio were lowered by 57.85 and 44.12%, respectively. However, the extract failed to significantly reverse the STZ-induced decline in serum HDL. Overall, with AIP value of 0.28 and LDL/HDL ratio of 0.91, SE demonstrated the potential to maintain lipid homeostasis in the diabetics.
BACKGROUND:Bullous pemphigoid (BP) is an autoimmune subepidermal blistering skin disorder which occurs mostly in the elderly. Several studies have reported an association between BP and neurological disorders (ND).OBJECTIVE:The purpose of this study was to evaluate the association between BP and neurological disorders in Iranian patients.METHODS:In this cross-sectional study, 87 patients with BP were enrolled. They were compared to 184 controls. Statistical analysis was done by SPSS statistical software version 19.RESULTS:Out of 87 patients with BP, 17 (19.5%) had at least one neurological disease. Cerebrovascular accident (CVA) was the most common neurological disease that was seen in 7 patients (8.0%) in the case group and 4 (2.1%) in the control group. The incidence of CVA was significantly different between BP patients and the control group (P = 0.022). Dementia was observed in 6 patients in the case group (16.8%) and 2 (1.0%) in the control group. The incidence of dementia was significantly different between BP patients and the control group (P = 0.008). In this study, the incidences of Parkinson's disease (P = 0.830), epilepsy (P = 0.067), and multiple sclerosis (P = 0.326) were not statistically significant between the two groups.CONCLUSION:The incidence of CVA and dementia in patients with BP compared to the control group was significantly higher.
We investigated the antioxidant and anti-inflammatory effects of a 70% v/v ethanol extract of the stem bark of Antrocaryon micraster on murine models of carrageenan-induced pleurisy and paw oedema. Rat pleural fluid was analysed for volume, protein content, and leucocytes, while lung histology was assessed for damage. Lung tissue homogenates were assayed for glutathione (GSH), superoxide dismutase (SOD), catalase (CAT), malondialdehyde (MDA), and myeloperoxidase (MPO). Phytochemical analysis was carried out on the stem bark. Acute toxicity studies were conducted in rats. In the pleurisy model the extract (30–300 mg/kg) significantly reduced the volume and amount of proteins and leucocytes in the exudate and also protected against lung injury. Tissue level of GSH and SOD and CAT expression were increased while MDA level and MPO activity were reduced. The peak and total oedema responses were significantly suppressed when given both preemptively and curatively in the mice paw oedema test. Saponins, alkaloids, triterpenoids, and tannins were present in the stem bark. A. micraster extract exhibited no apparent acute toxicity. We conclude that the ethanolic stem-bark extract of A. micraster has antioxidant action and exhibits significant anti-inflammatory activity through suppression of pleurisy and paw oedema induced with carrageenan.
Inconsistency in prognostic scores occurs where two different risk categories are applied to the same chronic myeloid leukemia (CML) patient. This study evaluated common scoring systems for identifying risk groups based on patients' molecular responses to select the best prognostic score when conflict prognoses are obtained from patient profiles. We analyzed 104 patients diagnosed with CML and treated at King Abdulaziz Medical City, Saudi Arabia, who were monitored for major molecular response (achieving a BCR-ABL1 transcript level equal to or less than 0.1%) by Real-Time Quantitative Polymerase Chain Reaction (RQ-PCR), and their risk profiles were identified using Sokal, Hasford, EUTOS, and ELTS scores based on the patients' clinical and hematological parameters at diagnosis. Our results found that the Hasford score outperformed other scores in identifying risk categories for conflict groups, with an accuracy of 63%.
The physicochemical and phytochemical analyses of honeys ( n = 50) from Sudanese, Sudano-Guinean, and Guinean areas of Benin were investigated. Results showed that dark amber is the dominant color. Moisture content ranged from 15.50% to 23.50%, and 72% of honeys respected the Codex Alimentarius recommendation. pH varied between 2.87 and 6.15, and free acidity ranged from 9.00 to 39.00 meq/kg. Electrical conductivity varied from 0.37 to 1.43 mS/cm. The content in fructose varied from 21.67% to 94.21%, and proline content ranged between 306.31 and 1187.93 mg/kg. All physicochemical characteristics varied with the areas. A negative correlation was found between pH and moisture content ( r = −0.55; p < 0.01). A positive correlation was established between pH and conductivity ( r = 0.79; p < 0.01) and between proline and color ( r = 0.44; p < 0.01). Total phenolic content varied between 55.97 and 224.99 mg GAE/100 g, and flavonoid content ranged between 1.43 and 29.81 mg CAE/100 g. Flavonoid was positively correlated with color ( r = 0.78; p < 0.01) and proline ( r = 0.47; p < 0.01). Tukey’s test revealed differences between total phenolic and flavonoid contents of honeys from five areas ( p < 0.01). In general, Sudanese and Sudano-Guinean honeys showed potential toward therapeutic applications because of their high phenolic contents.
