Temperature dependent study of thermophysical properties of binary mixtures of 1,4-butanediol + picolines

The experimental values of densities (r) and speeds of sound (u) of (1,4-butanediol + α-, orβ- picoline) binary mixtures have been used to calculate the internal pressure (πi), free volume (Vf), enthalpy (H), entropy (Ts), excess internal pressure (πiE), excess free volume (VfE), excess enthalpy (HE), excess free energy (GE) and excess entropy (TsE) at temperatures 303.15, 308.15, 313.15 and 318.15K over the entire composition range. The results have been discussed in terms of molecular interactions due to physical, chemical and structural effects between the unlike molecules. It has been observed that the strength of intermolecular interaction between 1,4-butanediol and picoline molecules is in order ɑ-picoline>β-picoline

A novel nanomicellar combination of fenretinide and lenalidomide shows marked antitumor activity in a neuroblastoma xenograft model

Purpose: Currently >50% of high-risk neuroblastoma (NB) patients, despite intensive therapy and initial partial or complete response, develop recurrent NB due to the persistence of minimal residual disease (MRD) that is resistant to conventional antitumor drugs. Indeed, their low therapeutic index prevents drug-dose escalation and protracted administration schedules, as would be required for MRD treatment. Thus, more effective and less toxic therapies are urgently needed for the management of MRD. To address this aim, we evaluated a new combination of fenretinide and lenalidomide, both endowed with antitumor activity and low-toxicity profiles. New nanomicelles were prepared as carriers for this combination to maximize bioavailability and accumulation at the tumor site because of the enhanced permeability and retention (EPR) effect. Experimental design: New nanomicelles containing the fenretinide\u2013lenalidomide combination (FLnMs) were prepared by a one-step method, providing high drug encapsulation and micelle dimensions suitable for tumor accumulation. Their administration to mice bearing human NB xenografts allowed us to evaluate their efficacy in comparison with the nanomicelles containing fenretinide alone (FnMs). Results: Treatment by FLnMs significantly decreased the tumor growth of NB xenografts. FLnMs were more active than FnMs despite comparable fenretinide concentrations in tumors, and lenalidomide alone did not show cytotoxic activity in vitro against NB cells. The tumor mass at the end of treatment with FLnMs was predominantly necrotic, with a decreased Ki-67 proliferation index. Conclusion: FLnMs provided superior antitumor efficacy in NB xenografts compared to FnMs. The enhanced efficacy of the combination was likely due to the antiangiogenic effect of lenalidomide added to the cytotoxic effect of fenretinide. This new nanomicellar combination is characterized by a low-toxicity profile and offers a novel therapeutic option for the treatment of high-risk tumors where the persistence of MRD requires repeated administrations of therapeutic agents over long periods of time to avoid recurrent disease

MYCN (v-myc myelocytomatosis viral related oncogene, neuroblastoma derived (avian))

Review on MYCN (v-myc myelocytomatosis viral related oncogene, neuroblastoma derived (avian)), with data on DNA, on the protein encoded, and where the gene is implicated

Nanomicellar Lenalidomide-Fenretinide Combination Suppresses Tumor Growth in an MYCN Amplified Neuroblastoma Tumor

Purpose: In a previous study, we demonstrated that the combination of fenretinide with lenalidomide, administered by a novel nanomicellar formulation (FLM), provided a strong antitumor effect in a neuroblastoma TrkB-expressing tumor. In this study, we tested the nanomicellar combination in an MYCN amplified neuroblastoma xenograft to assess its efficacy in different tumor genotypes and evaluate the interactions of the nanomicelles with the tumor cells. Experimental Design: FLM was administered to mice bearing human NLF xenografts to evaluate its efficacy in comparison with the nanomicelles containing fenretinide alone (FM). Confocal laser-scanning fluorescence microscopy images of the NLF cells treated with FLM and FM allowed us to estimate the nanomicelle ability to transport the encapsulated drugs inside the tumor cells. Flow cytometric analysis of the cells from treated tumors was performed to assess the effect of treatment on GD2 expression and NK cell infiltration. Results: FLM and FM decreased the growth of NLF xenografts at comparable extents during the treatment period. Afterwards, FLM induced a progressive tumor regression without regrowth, while FM treatment was followed by regrowth within 15-20 days after the end of treatment. Both FLM and FM were able to penetrate the tumor cells transporting the encapsulated drugs. FLM transported higher amount of fenretinide inside the cells. Also, FLM treatment strongly increased GD2 expression in treated tumors and slightly decreased the NK infiltration compared to FM. Conclusion: FLM treatment induced a superior antitumor response than FM in NLF xenografts, presumably due to the combined effects of fenretinide cytotoxicity and lenalidomide antiangiogenic activity. The ability of FLM to penetrate tumor cells, transporting the encapsulated drugs, substantially improved the therapeutic efficiency of this system. Moreover, the enhancement of GD2 expression in FLM treated tumors offers the possibility to further increase the antitumor effect by the use of anti-GD2 CAR-T cells and anti-GD2 antibodies in combination with FLM in multimodal therapies

Evaluating the Immunogenicity of Protein Drugs by Applying In Vitro

The immune system has evolved to become highly specialized in recognizing and responding to pathogens and foreign molecules. Specifically, the function of HLA class II is to ensure that a sufficient sample of peptides derived from foreign molecules is presented to T cells. This leads to an important concern in human drug development as the possible immunogenicity of biopharmaceuticals, especially those intended for chronic administration, can lead to reduced efficacy and an undesired safety profile for biological therapeutics. As part of this review, we will highlight the molecular basis of antigen presentation as a key step in the induction of T cell responses, emphasizing the events associated with peptide binding to polymorphic and polygenic HLA class II molecules. We will further review methodologies that predict HLA class II binding peptides and candidate epitopes. We will focus on tools provided by the Immune Epitope Database and Analysis Resource, discussing the basic features of different prediction methods, the objective evaluation of prediction quality, and general guidelines for practical use of these tools. Finally the use, advantages, and limitations of the methodology will be demonstrated in a review of two previous studies investigating the immunogenicity of erythropoietin and timothy grass pollen

Potential yield losses caused by the adults of Schizonycha ruficollis on pomegranate (Punica granatum) flowers

Pomegranate is an important fruit crop that is capturing international attention for its rich antioxidants and nutraceutical value. The demand for the fruit is rapidly increasing in major national and international markets. Therefore, any serious pest is of great importance and here we report the severe incidence of adult beetles of Schizonycha ruficollis that resulted in potential yield loss due to its feeding on pomegranate flowers in Devanahalli, Karnataka. Usually June/July adult beetle emerge and feed on hosts like neem and Melia rubra which the farmers plant them as wind breaks along the borders. These attract the beetles into pomegranate field and the pomegranate flowers are then infested by the adult beetles. The pomegranate on an average possess 223 female flowers per tree, which when damaged fails to set fruits causing economic loss. A documentation study during 2023 was taken up to evaluate the crop loss caused by S. ruficollis in pomegranate resulted in potential seven percent yield loss accounting to ₹ 53215/acre at the farm gate price. This loss can be avoided by initiating a management practice at the first site of the beetles especially after the first monsoon rain. This study also helped us to alert pomegranate exporters and extension officials about the need of preventive measures to avoid the yield loss

Molecular interaction in binary mixtures of 1,4-butanediol+picolines: Viscometric approach

The viscosity (h) of {1,4-butanediol (i) + α-, or β-, or γ-picoline (j)}binary mixtures have been measured and reported at 303.15, 308.15, 313.15 and 318.15 K over the entire range of composition. Viscosity deviation (∆h) and excess Gibbs energy of activation of viscous flow (∆G*E) based on Eyring’s theory have been evaluated and the results fitted to the Redlich-Kister equation. The ∆h values are observed to be negative over the entire range of composition for (1,4-butanediol+α-picoline), (1,4-butanediol+β-picoline) and (1,4-butanediol+γ-picoline) systems. The experimental viscosity data have been compared with some well-known equations of Frenkel, modified Frenkel approach and predictive ones like McAllister, Grunberg-Nissan, Hind et al., Tamura Kurata and Katti-Chaudhri. The effects of molecular sizes and shapes of the component molecules on the molecular interactions present thereof in the mixtures have been discussed.

Anatomy and origin of authochthonous late Pleistocene forced regression deposits, east Coromandel inner shelf, New Zealand: implications for the development and definition of the regressive systems tract

High-resolution seismic reflection data from the east Coromandel coast, New Zealand, provide details of the sequence stratigraphy beneath an autochthonous, wave dominated inner shelf margin during the late Quaternary (0-140 ka). Since c. 1 Ma, the shelf has experienced limited subsidence and fluvial sediment input, producing a depositional regime characterised by extensive reworking of coastal and shelf sediments during glacio-eustatic sea-level fluctuations. It appears that only one complete fifth-order (c. 100 000 yr) depositional sequence is preserved beneath the inner shelf, the late Pleistocene Waihi Sequence, suggesting any earlier Quaternary sequences were mainly cannibalised into successively younger sequences. The predominantly Holocene-age Whangamata Sequence is also evident in seismic data and modern coastal deposits, and represents an incomplete depositional sequence in its early stages of formation. A prominent aspect of the sequence stratigraphy off parts of the east Coromandel coast is the presence of forced regressive deposits (FRDs) within the regressive systems tract (RST) of the late Pleistocene Waihi Sequence. The FRDs are interpreted to represent regressive barrier-shoreface sands that were sourced from erosion and onshore reworking of underlying Pleistocene sediments during the period of slow falling sea level from isotope stages 5 to 2 (c. 112-18 ka). The RST is volumetrically the most significant depositional component of the Waihi Sequence; the regressive deposits form a 15-20 m thick, sharp-based, tabular seismic unit that downsteps and progrades continuously across the inner shelf. The sequence boundary for the Waihi Sequence is placed at the most prominent, regionally correlative, and chronostratigraphically significant surface, namely an erosional unconformity characterised in many areas by large incised valleys that was generated above the RST. This unconformity is interpreted as a surface of maximum subaerial erosion generated during the last glacial lowstand (c. 18 ka). Although the base of the RST is associated with a prominent regressive surface of erosion, this is not used as the sequence boundary as it is highly diachronous and difficult to identify and correlate where FRDs are not developed. The previous highstand deposits are limited to subaerial barrier deposits preserved behind several modern Holocene barriers along the coast, while the transgressive systems tract is preserved locally as incised-valley fill deposits beneath the regressive surface of erosion at the base of the RST. Many documented late Pleistocene RSTs have been actively sourced from fluvial systems feeding the shelf and building basinward-thickening, often stacked wedges of FRDs, for which the name allochthonous FRDs is suggested. The Waihi Sequence RST is unusual in that it appears to have been sourced predominantly from reworking of underlying shelf sediments, and thus represents an autochthonous FRD. Autochthonous FRDs are also present on the Forster-Tuncurry shelf in southeast Australia, and may be a common feature in other shelf settings with low subsidence and low sediment supply rates, provided shelf gradients are not too steep, and an underlying source of unconsolidated shelf sediments is available to source FRDs. The preservation potential of such autochthonous FRDs in ancient deposits is probably low given that they are likely to be cannibalised during subsequent sea-level falls