Combination of sulfamethoxazole and selenium in anticancer therapy: a novel approach

Sulfonamides have been reported to possess substantial antitumor activity as they act as carbonic anhydrase inhibitors. In addition, selenium appears to have a protective effect at various stages of cancer due to its antioxidant property, enhanced carcinogen detoxification, inhibition of cell invasion, and by inhibiting angiogenesis. Here, in the present study we aimed to evaluate and synergize the cytotoxic activity of sulfonamide and selenium (SM+SE) as effective therapy in the treatment of DENA-induced HCC. Hepatocarcinogeneis was induced by a single intraperitoneal injection of diethylnitrosamine (DENA) (200 mg/kg) in phosphate buffer. 30 Male Wistar rats used in this study were divided randomly into five equal groups (n = 6). DENA-administered animals showed significant alteration (p < 0.001) in liver-specific enzymes—glutamate oxaloacetate transaminase (SGOT), serum glutamate pyruvate transaminase (SGPT), alkaline phosphatase (ALP), and Alpha fetoproteins (AFP), and also induced severe histopathological changes in the hepatic tissues. Interestingly, treatment with (SE+SE) (SM 30 mg/kg + SE 3 mg/kg) significantly reduced (P < 0.001, P < 0.001, P < 0.001, P < 0.001) the elevated AFP, SGOT, SGPT, and ALP levels, respectively, suggesting that combination therapy of SM+SE has a potential to treat DENA-induced liver damage.     

Turbulence Model Selection for Low Reynolds Number Flows

One of the major flow phenomena associated with low Reynolds number flow is the formation of separation bubbles on an airfoil’s surface. NACA4415 airfoil is commonly used in wind turbines and UAV applications. The stall characteristics are gradual compared to thin airfoils. The primary criterion set for this work is the capture of laminar separation bubble. Flow is simulated for a Reynolds number of 120,000. The numerical analysis carried out shows the advantages and disadvantages of a few turbulence models. The turbulence models tested were: one equation Spallart Allmars (S-A), two equation SST K-ω, three equation Intermittency (γ) SST, k-kl-ω and finally, the four equation transition γ-Re_θ SST. However, the variation in flow physics differs between these turbulence models. Procedure to establish the accuracy of the simulation, in accord with previous experimental results, has been discussed in detail.     

Human NOC3 is essential for DNA replication licensing in human cells

Noc3p (Nucleolar Complex-associated protein) is an essential protein in budding yeast DNA replication licensing. Noc3p mediates the loading of Cdc6p and MCM proteins onto replication origins during the M-to-G₁ transition by interacting with ORC (Origin Recognition Complex) and MCM (Minichromosome Maintenance) proteins. FAD24 (Factor for Adipocyte Differentiation, clone number 24), the human homolog of Noc3p (hNOC3), was previously reported to play roles in the regulation of DNA replication and proliferation in human cells. However, the role of hNOC3 in replication licensing was unclear. Here we report that hNOC3 physically interacts with multiple human pre-replicative complex (pre-RC) proteins and associates with known replication origins throughout the cell cycle. Moreover, knockdown of hNOC3 in HeLa cells abrogates the chromatin association of other pre-RC proteins including hCDC6 and hMCM, leading to DNA replication defects and eventual apoptosis in an abortive S-phase. In comparison, specific inhibition of the ribosome biogenesis pathway by preventing pre-rRNA synthesis, does not lead to any cell cycle or DNA replication defect or apoptosis in the same timeframe as the hNOC3 knockdown experiments. Our findings strongly suggest that hNOC3 plays an essential role in pre-RC formation and the initiation of DNA replication independent of its potential role in ribosome biogenesis in human cells.     

Selection of suitable reference genes for quantitative real-time PCR gene expression analysis in Mulberry (Morus alba L.) under different abiotic stresses

Molecular Biology Reports - Mulberry (Morus alba L.) is the sole food source for the mulberry silkworm, Bombyx mori and therefore important for sericulture industry. Different abiotic stress...     

Selective Cu2+ binding, redox silencing, and cytoprotective effects of the small heat shock proteins alphaA- and alphaB-crystallin

Oxidative stress and Cu²⁺ have been implicated in several neurodegenerative diseases and in cataract. Oxidative stress, as well as Cu²⁺, is also known to induce the expression of the small heat shock proteins α-crystallins. However, the role of α-crystallins in oxidative stress and in Cu²⁺-mediated processes is not clearly understood. We demonstrate using fluorescence and isothermal titration calorimetry that α-crystallins (αA- and αB-crystallin and its phosphorylation mimic, 3DαB-crystallin) bind Cu²⁺ with close to picomolar range affinity. The presence of other tested divalent cations such as Zn²⁺, Mg²⁺, and Ca²⁺ does not affect Cu²⁺ binding, indicating selectivity of the Cu²⁺-binding site(s) in α-crystallins. Cu²⁺ binding induces structural changes and increase in the hydrodynamic radii of α-crystallins. Cu²⁺ binding increases the stability of α-crystallins towards guanidinium chloride-induced unfolding. Chaperone activity of αA-crystallin increases significantly upon Cu²⁺ binding. α-Crystallins rescue amyloid beta peptide, Aβ_1-40, from Cu²⁺-induced aggregation in vitro. α-Crystallins inhibit Cu²⁺-induced oxidation of ascorbate and, hence, prevent the generation of reactive oxygen species. Interestingly, α-synuclein, a Cu²⁺-binding protein, does not inhibit this oxidation process significantly. We find that the Cu²⁺-sequestering (or redox-silencing) property of α-crystallins confers cytoprotection. To the best of our knowledge, this is the first study to reveal high affinity (close to picomolar) for Cu²⁺ binding and redox silencing of Cu²⁺ by any heat shock protein. Thus, our study ascribes a novel functional role to α-crystallins in Cu²⁺ homeostasis and helps in understanding their protective role in neurodegenerative diseases and cataract.