Biosorption of Cr(VI) by Ceratocystis paradoxa MSR2 Using Isotherm Modelling,Kinetic Study and Optimization of Batch Parameters Using Response Surface Methodology

This study is focused on the possible use of Ceratocystis paradoxa MSR2 native biomass for Cr(VI) biosorption. The influence of experimental parameters such as initial pH, temperature, biomass dosage, initial Cr(VI) concentration and contact time were optimized using batch systems as well as response surface methodology (RSM). Maximum Cr(VI) removal of 68.72% was achieved, at an optimal condition of biomass dosage 2g L⁻¹, initial Cr(VI) concentration of 62.5 mg L⁻¹ and contact time of 60 min. The closeness of the experimental and the predicted values exhibit the success of RSM. The biosorption mechanism of MSR2 biosorbent was well described by Langmuir isotherm and a pseudo second order kinetic model, with a high regression coefficient. The thermodynamic study also revealed the spontaneity and exothermic nature of the process. The surface characterization using FT-IR analysis revealed the involvement of amine, carbonyl and carboxyl groups in the biosorption process. Additionally, desorption efficiency of 92% was found with 0.1 M HNO₃. The Cr(VI) removal efficiency, increased with increase in metal ion concentration, biomass concentration, temperature but with a decrease in pH. The size of the MSR2 biosorbent material was found to be 80 μm using particle size analyzer. Atomic force microscopy (AFM) visualizes the distribution of Cr(VI) on the biosorbent binding sites with alterations in the MSR2 surface structure. The SEM-EDAX analysis was also used to evaluate the binding characteristics of MSR2 strain with Cr(VI) metals. The mechanism of Cr(VI) removal of MSR2 biomass has also been proposed.     

An Age-Wise Comparison of Human Airway Smooth Muscle Proliferative Capacity

We compared the proliferation of neonatal and adult airway smooth muscle cells (ASMC) with no/moderate lung disease, in glucose- (energy production by glycolysis) or glucose-free medium (ATP production from mitochondrial oxidative phosphorylations only), in response to 10% fetal calf serum (FCS) and PDGF-AA. In the presence of glucose, cell counts were significantly greater in neonatal vs. adult ASMC. Similarly, neonatal ASMC DNA synthesis in 10% FCS and PDGF-AA, and [Ca²⁺]i responses in the presence of histamine were significantly enhanced vs. adults. In glucose-free medium, cell proliferation was preserved in neonatal cells, unlike in adult cells, with concomitant increased porin (an indicator of mitochondrial activity) protein expression. Compared to adults, stimulated neonatal human ASMC are in a rapid and robust proliferative phase and have the capacity to respond disproportionately under abnormal environmental conditions, through increased mitochondrial biogenesis and altered calcium homeostasis.     

NSC666715 and Its Analogs Inhibit Strand-Displacement Activity of DNA Polymerase β and Potentiate Temozolomide-Induced DNA Damage,Senescence and Apoptosis in Colorectal Cancer Cells

Recently approved chemotherapeutic agents to treat colorectal cancer (CRC) have made some impact; however, there is an urgent need for newer targeted agents and strategies to circumvent CRC growth and metastasis. CRC frequently exhibits natural resistance to chemotherapy and those who do respond initially later acquire drug resistance. A mechanism to potentially sensitize CRC cells is by blocking the DNA polymerase β (Pol-β) activity. Temozolomide (TMZ), an alkylating agent, and other DNA-interacting agents exert DNA damage primarily repaired by a Pol-β-directed base excision repair (BER) pathway. In previous studies, we used structure-based molecular docking of Pol-β and identified a potent small molecule inhibitor (NSC666715). In the present study, we have determined the mechanism by which NSC666715 and its analogs block Fen1-induced strand-displacement activity of Pol-β-directed LP-BER, cause apurinic/apyrimidinic (AP) site accumulation and induce S-phase cell cycle arrest. Induction of S-phase cell cycle arrest leads to senescence and apoptosis of CRC cells through the p53/p21 pathway. Our initial findings also show a 10-fold reduction of the IC₅₀ of TMZ when combined with NSC666715. These results provide a guide for the development of a target-defined strategy for CRC chemotherapy that will be based on the mechanisms of action of NSC666715 and TMZ. This combination strategy can be used as a framework to further reduce the TMZ dosages and resistance in CRC patients.     

Subgroups of Paediatric Acute Lymphoblastic Leukaemia Might Differ Significantly in Genetic Predisposition to Asparaginase Hypersensitivity

L-asparaginase (ASP) is a key element in the treatment of paediatric acute lymphoblastic leukaemia (ALL). However, hypersensitivity reactions (HSRs) to ASP are major challenges in paediatric patients. Our aim was to investigate genetic variants that may influence the risk to Escherichia coli-derived ASP hypersensitivity. Sample and clinical data collection was carried out from 576 paediatric ALL patients who were treated according to protocols from the Berlin—Frankfurt—Münster Study Group. A total of 20 single nucleotide polymorphisms (SNPs) in GRIA1 and GALNT10 genes were genotyped. Patients with GRIA1 rs4958351 AA/AG genotype showed significantly reduced risk to ASP hypersensitivity compared to patients with GG genotype in the T-cell ALL subgroup (OR = 0.05 (0.01–0.26); p = 4.70E-04), while no such association was found in pre-B-cell ALL. In the medium risk group two SNPs of GRIA1 (rs2055083 and rs707176) were associated significantly with the occurrence of ASP hypersensitivity (OR = 0.21 (0.09–0.53); p = 8.48E-04 and OR = 3.02 (1.36–6.73); p = 6.76E-03, respectively). Evaluating the genders separately, however, the association of rs707176 with ASP HSRs was confined only to females. Our results suggest that genetic variants of GRIA1 might influence the risk to ASP hypersensitivity, but subgroups of patients can differ significantly in this respect.     

Does the Neighborhood Area of Residence Influence Non-Attendance in an Urban Mammography Screening Program? A Multilevel Study in a Swedish City

MethodsWe analyze all women invited to mammography screening in 2005–09, residing in the city of Malmö, Sweden. Information regarding mammography screening attendance was linked to data on area of residence, demographic and socioeconomic characteristics available from Statistics Sweden. The influence of individual and neighborhood factors was assessed by multilevel logistic regression analysis with 29,901 women nested within 212 neighborhoods.ResultsThe prevalence of non-attendance among women was 18.3%. After adjusting for individual characteristics, the prevalence in the 212 neighborhoods was 3.6%. Neighborhood of residence had little influence on non-attendance. The multilevel analysis indicates that 8.4% of the total individual differences in the propensity of non-attendance were at the neighborhood level. However, when adjusting for specific individual characteristics this general contextual effect decreased to 1.8%. This minor effect was explained by the sociodemographic characteristic of the neighborhoods. The discriminatory accuracy of classifying women according to their non-attendance was 0.747 when considering only individual level variables, and 0.760 after including neighborhood level as a random effect.ConclusionOur results suggest that neighborhoods of residence in Malmö, Sweden (as defined by small-area market statistics (SAMS) areas) do not condition women’s participation in population based mammography screening. Thus, interventions should be directed to the whole city and target women with a higher risk of non-attendance.     

In Vitro and Sensory Evaluation of Capsaicin-Loaded Nanoformulations

Capsaicin has known health beneficial and therapeutic properties. It is also able to enhance the permeability of drugs across epithelial tissues. Unfortunately, due to its pungency the oral administration of capsaicin is limited. To this end, we assessed the effect of nanoencapsulation of capsaicin, under the hypothesis that this would reduce its pungency. Core-shell nanocapsules with an oily core and stabilized with phospholipids were used. This system was used with or without chitosan coating. In this work, we investigated the in vitro release behavior of capsaicin-loaded formulations in different physiological media (including simulated saliva fluid). We also evaluated the influence of encapsulation of capsaicin on the cell viability of buccal cells (TR146). To study the changes in pungency after encapsulation we carried out a sensory analysis with a trained panel of 24 students. The in vitro release study showed that the systems discharged capsaicin slowly in a monotonic manner and that the chitosan coating had an effect on the release profile. The cytotoxic response of TR146 cells to capsaicin at a concentration of 500 μM, which was evident for the free compound, was reduced following its encapsulation. The sensory study revealed that a chitosan coating results in a lower threshold of perception of the formulation. The nanoencapsulation of capsaicin resulted in attenuation of the sensation of pungency significantly. However, the presence of a chitosan shell around the nanoformulations did not mask the pungency, when compared with uncoated systems.