A perspective on the impact of radiation therapy on the immune rheostat.

The advent and success of immune checkpoint inhibitors (ICIs) in cancer treatment has broadened the spectrum of tumours that might be considered "immunogenic" and susceptible to immunotherapeutic (IT) intervention. Not all cancer types are sensitive, and not all patients with any given type respond. Combination treatment of ICIs with an established cytotoxic modality such as radiation therapy (RT) is a logical step towards improvement. For one, RT alone has been shown to be genuinely immunomodulatory and secondly pre-clinical data generally support combined ICI-RT approaches. This new integrated therapy for cancer treatment holds much promise, although there is still a lot to be learned about how best to schedule the treatments, manage the toxicities and determine what biomarkers might predict response, as well as many other issues. This review examines how RT alters the immune rheostat and how it might best be positioned to fully exploit IT

Formulation and Evaluation of PH Triggered In Situ Gelling System of Levofloxacin

This research was to prepare ramipril loaded solid lipid nanoparticles for controlled release of drug and a trial to improve the bioavailability. Hot homogenization and ultrasound dispersion were employed to produce SLNs using biodegradable lipids and non ionic surfactants. The formulated SLNs were characterized for entrapment efficiency, particle size and in vitro release studies in phosphate buffer saline PH 7.4. The nanoparticle colloidal drug delivery system of ramipril prepared type of lipids and non ionic surfactants obtained better entrapment efficiency. The better entrapment efficiency of SLNs was obtained with more hydrophilic surfactants (poloxamer 188) about 85.36% due to the higher HLB value of the surfactant. The results revealed that the increase in the surfactant concentration increases the entrapment efficiency for all formulations and the percentage entrapment efficiency of various non ionic surfactants was observed in the order of Poloxamer 188 > Tween 80 > Span 20. The particle size of the formulated ramipril SLNs exhibited nanometer size range spherical shape particles. The in vitro release studies revealed that the SLN formulations showed a prolonged drug release. SEM analysis of the SLN dispersion showed the spherical shape of the nanoparticles. Stability studies indicated that the entrapment efficiency of the SLN was not affected significantly in the refrigerated storage temperature. However there may be a slight reduction in the entrapment efficiency of the SLN due to the drug expulsion from the crystal lattice. The results of the IR studies proved that no interactions between the drug, lipid and formulations. It is concluded that the hot homogenization and ultrasound dispersion method, is a useful method for the successful incorporation of poorly water soluble drug ramipril with high entrapment efficiency. The prolonged release of the drug from the solid lipid nanoparticles suggests that the frequency of administration may be reduced. Further it may be presumed that if the nanometer range particles are obtained, the bioavailability may be increased. Hence we can conclude that solid lipid nanoparticles provide controlled release of drug and these systems are used as drug carriers for lipophilic drugs to enhance the bioavailability of poorly water soluble drugs through nanoparticle as a drug delivery system

Mechanical model of the ultra-fast underwater trap of Utricularia

The underwater traps of the carnivorous plants of the Utricularia species catch their preys through the repetition of an "active slow deflation / passive fast suction" sequence. In this paper, we propose a mechanical model that describes both phases and strongly supports the hypothesis that the trap door acts as a flexible valve that buckles under the combined effects of pressure forces and the mechanical stimulation of trigger hairs, and not as a panel articulated on hinges. This model combines two different approaches, namely (i) the description of thin membranes as triangle meshes with strain and curvature energy, and (ii) the molecular dynamics approach, which consists in computing the time evolution of the position of each vertex of the mesh according to Langevin equations. The only free parameter in the expression of the elastic energy is the Young's modulus E of the membranes. The values for this parameter are unequivocally obtained by requiring that the trap model fires, like real traps, when the pressure difference between the outside and the inside of the trap reaches about 15 kPa. Among other results, our simulations show that, for a pressure difference slightly larger than the critical one, the door buckles, slides on the threshold and finally swings wide open, in excellent agreement with the sequence observed in high-speed videos.Comment: Accepted for publication in Physical Review

The Prevalence of Previously Undiagnosed Leprosy in the General Population of Northwest Bangladesh

In order to estimate the level of leprosy in an area with many leprosy patients, we determined the prevalence of previously undiagnosed leprosy in the general population and compared this with the registered (or known) number of leprosy patients. We also compared it with the known prevalence of leprosy in contacts of leprosy patients. We examined 20 randomly selected geographical clusters of 1,000 persons each in two districts of Bangladesh, with over 4 million population. Physical examination was performed on all individuals. The number of newly found leprosy cases among 17,862 people above 5 years of age from the clusters was 27, giving a rate of previously undiagnosed leprosy of 15.1 per 10,000. This rate is six times higher than the registered prevalence, but three times lower than the rate in the most distant subgroup of contacts (neighbour of neighbour and social contacts) of leprosy patients in the same area. We conclude that in areas where leprosy is common, it may be preferable to do full village or neighbourhood surveys when a new leprosy patient is found, rather than to limit contact surveys to close contacts only, such as household members

Synthesis and down conversion emission property of Eu3+ doped LaAlO3 CsAlO2 and LiLaO2 phosphors

[EN] LaAlO3:Eu3+, CsAlO2:Eu3+ and LiLaO2:Eu3+ phosphors with varying concen- trations of Eu3+ from 3 to 10 mol% were prepared by combustion synthesis method and the samples were further heated to 1,000ºC to improve the crystallinity of the materials. The structure and morphology of materials have been examined by X-ray diffraction and scan- ning electron microscopy. SEM images depicted that the morphology of crystallites have no uniform shapes and sizes. Small and coagulated particles of irregular shapes of different sizes are obtained. The characteristic emissions of Eu3+ were clearly observed at nearly 580, 592, 650, 682 to 709 (multiplet structure) nm for 5D - 7 Fn transitions where n = 0, 1, 3, 4 respectively, including the strongest emission peaks at 614 and 620 nm for 5 D0 - 7 F2 transitions in CsAlO2:Eu3+ and LiLaO2:Eu3+ host lattices. The intensity of emission peak corresponding to 5 D0 !→ 7 F1 transitions in LaAlO3 :Eu3+ material is comparable to that of 5D0 5D-7F2 transitions which is also a singlet. Photoluminescence intensity follows the order as in LiLaO2 > LaAlO3 > CsAlO2 lattices. Remarkable high photoluminescence intensity with 7 mol% doping of Eu3+ in LiLaO2 makes it a strong contender for red colored display applications.This work was supported by the European Commission through Nano CIS project (FP7-PEOPLE-2010-IRSES ref. 269279).Marí Soucase, B.; Singh, KC.; Moya Forero, MM.; Singh, I.; Om, H.; Chand, S. (2015). Synthesis and down conversion emission property of Eu3+ doped LaAlO3 CsAlO2 and LiLaO2 phosphors. Optical and Quantum Electronics. 47(7):1569-1578. https://doi.org/10.1007/s11082-014-9997-9S15691578477Abbattista, F., Vallino, M.: Remarks on the $$\text{La}_{2}\text{O}_{3}-\text{Li}_{2}\text{O}$$ La 2 O 3 - Li 2 O binary system between 750 and 1,000  $$^{\circ}$$ ∘ C. Ceram. 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Emodin Suppresses Migration and Invasion through the Modulation of CXCR4 Expression in an Orthotopic Model of Human Hepatocellular Carcinoma

10.1371/journal.pone.0057015PLoS ONE83

In vitro anti-HIV activity of some Indian medicinal plant extracts

Background Human Immunodeficiency Virus (HIV) persists to be a significant public health issue worldwide. The current strategy for the treatment of HIV infection, Highly Active Antiretroviral Therapy (HAART), has reduced deaths from AIDS related disease, but it can be an expensive regime for the underdeveloped and developing countries where the supply of drugs is scarce and often not well tolerated, especially in persons undergoing long term treatment. The present therapy also has limitations of development of multidrug resistance, thus there is a need for the discovery of novel anti-HIV compounds from plants as a potential alternative in combating HIV disease. Methods Ten Indian medicinal plants were tested for entry and replication inhibition against laboratory adapted strains HIV-1IIIB, HIV-1Ada5 and primary isolates HIV-1UG070, HIV-1VB59 in TZM-bl cell lines and primary isolates HIV-1UG070, HIV-1VB59 in PM1 cell lines. The plant extracts were further evaluated for toxicity in HEC-1A epithelial cell lines by transwell epithelial model. Results The methanolic extracts of Achyranthes aspera, Rosa centifolia and aqueous extract of Ficus benghalensis inhibited laboratory adapted HIV-1 strains (IC80 3.6–118 μg/ml) and primary isolates (IC80 4.8–156 μg/ml) in TZM-bl cells. Methanolic extract of Strychnos potatorum, aqueous extract of Ficus infectoria and hydroalcoholic extract of Annona squamosa inhibited laboratory adapted HIV-1 strains (IC80 4.24–125 μg/ml) and primary isolates (IC80 18–156 μg/ml) in TZM-bl cells. Methanolic extracts of Achyranthes aspera and Rosa centifolia, (IC801-9 μg/ml) further significantly inhibited HIV-1 primary isolates in PM1cells. Methanolic extracts of Tridax procumbens, Mallotus philippinensis, Annona reticulate, aqueous extract of Ficus benghalensis and hydroalcoholic extract of Albizzia lebbeck did not exhibit anti-HIV activity in all the tested strains. Methanolic extract of Rosa centifolia also demonstrated to be non-toxic to HEC-1A epithelial cells and maintained epithelial integrity (at 500 μg/ml) when tested in transwell dual-chamber. Conclusion These active methanolic extracts of Achyranthes aspera and Rosa centifolia, could be further subjected to chemical analysis to investigate the active moiety responsible for the anti-HIV activity. Methanolic extract of Rosa centifolia was found to be well tolerated maintaining the epithelial integrity of HEC-1A cells in vitro and thus has potential for investigating it further as candidate microbicide