Surfactant-Dependent Bulk Scale Mechanochemical Synthesis of CsPbBr3 Nanocrystals for Plastic Scintillator-Based X-ray Imaging.

We report a facile, solvent-free surfactant-dependent mechanochemical synthesis of highly luminescent CsPbBr3 nanocrystals (NCs) and study their scintillation properties. A small amount of surfactant oleylamine (OAM) plays an important role in the two-step ball milling method to control the size and emission properties of the NCs. The solid-state synthesized perovskite NCs exhibit a high photoluminescence quantum yield (PLQY) of up to 88% with excellent stability. CsPbBr3 NCs capped with different amounts of surfactant were dispersed in toluene and mixed with polymethyl methacrylate (PMMA) polymer and cast into scintillator discs. With increasing concentration of OAM during synthesis, the PL yield of CsPbBr3/PMMA nanocomposite was increased, which is attributed to reduced NC aggregation and PL quenching. We also varied the perovskite loading concentration in the nanocomposite and studied the resulting emission properties. The most intense PL emission was observed from the 2% perovskite-loaded disc, while the 10% loaded disc exhibited the highest radioluminescence (RL) emission from 50 kV X-rays. The strong RL yield may be attributed to the deep penetration of X-rays into the composite, combined with the large interaction cross-section of the X-rays with the high-Z atoms within the NCs. The nanocomposite disc shows an intense RL emission peak centered at 536 nm and a fast RL decay time of 29.4 ns. Further, we have demonstrated the X-ray imaging performance of a 10% CsPbBr3 NC-loaded nanocomposite disc.

Formamidinium Lead Halide Perovskite Nanocomposite Scintillators.

While there is great demand for effective, affordable radiation detectors in various applications, many commonly used scintillators have major drawbacks. Conventional inorganic scintillators have a fixed emission wavelength and require expensive, high-temperature synthesis; plastic scintillators, while fast, inexpensive, and robust, have low atomic numbers, limiting their X-ray stopping power. Formamidinium lead halide perovskite nanocrystals show promise as scintillators due to their high X-ray attenuation coefficient and bright luminescence. Here, we used a room-temperature, solution-growth method to produce mixed-halide FAPbX3 (X = Cl, Br) nanocrystals with emission wavelengths that can be varied between 403 and 531 nm via adjustments to the halide ratio. The substitution of bromine for increasing amounts of chlorine resulted in violet emission with faster lifetimes, while larger proportions of bromine resulted in green emission with increased luminescence intensity. By loading FAPbBr3 nanocrystals into a PVT-based plastic scintillator matrix, we produced 1 mm-thick nanocomposite scintillators, which have brighter luminescence than the PVT-based plastic scintillator alone. While nanocomposites such as these are often opaque due to optical scattering from aggregates of the nanoparticles, we used a surface modification technique to improve transmission through the composites. A composite of FAPbBr3 nanocrystals encapsulated in inert PMMA produced even stronger luminescence, with intensity 3.8× greater than a comparative FAPbBr3/plastic scintillator composite. However, the luminescence decay time of the FAPbBr3/PMMA composite was more than 3× slower than that of the FAPbBr3/plastic scintillator composite. We also demonstrate the potential of these lead halide perovskite nanocomposite scintillators for low-cost X-ray imaging applications.

Recent advances in lead-free double perovskites for x-ray and photodetection.

Over the last decade, lead halide perovskites have attracted significant research attention in the field of photovoltaics, light-emitting devices, photodetection, ionizing radiation detection, etc, owing to their outstanding optoelectrical properties. However, the commercial applications of lead-based perovskite devices are restricted due to the poor ambient stability and toxicity of lead. The encapsulation of lead-based devices can reduce the possible leakage of lead. However, it is hard to ensure safety during large-scale production and long-term storage. Recently, considerable efforts have been made to design lead-free perovskites for different optoelectronic applications. Metal halide double perovskites with the general formula of A2MIMIIIX6or A2MIVX6could be potentially considered as green and stable alternatives for different optoelectronic applications. In this review article, we focus on the recent progress and findings on lead-free halide double perovskites for x-ray and UV-vis photodetection applications. Lead-free halide double perovskite has recently drawn a great deal of attention for superior x-ray detection due to its high absorption coefficient, large carrier mobility-lifetime product, and large bulk resistance. In addition, these materials exhibit good performance in photodetection in the UV-vis region due to high photocarrier generation and efficient carrier separation. In this review, first, we define the characteristics of lead-free double perovskite materials. The fundamental characteristics and beneficial properties of halide perovskites for direct and indirect x-ray detection are then discussed. We comprehensively review recent developments and efforts on lead-free double perovskite for x-ray detection and UV-vis photodetection. We bring out the current challenges and opportunities in the field and finally present the future outlook for developing lead-free double perovskite-based x-ray and UV-vis photodetectors for practical applications.

Understanding the interfacial charge transfer in the CVD grown Bi2O2Se/CsPbBr3 nanocrystal heterostructure and its exploitation in superior photodetection: experiment vs. theory.

Efficient charge transfer in a 2D semiconductor heterostructure plays a crucial role in high-performance photodetectors and energy harvesting devices. Non-van der Waals 2D Bi2O2Se has enormous potential for high-performance optoelectronics, though very little is known about the interfacial charge transport at the corresponding 2D heterojunction. Herein, we report a combined experimental and theoretical investigation of interfacial charge transfer in the Bi2O2Se/CsPbBr3 heterostructure through various microscopic and spectroscopic tools corroborated with density functional theory calculations. The CVD-grown few-layer Bi2O2Se nanosheet possesses high crystallinity and a high absorption coefficient in the visible-near IR region. We integrated the few-layer Bi2O2Se nanosheet possessing superior electron mobility and CsPbBr3 nanocrystals with high light-harvesting capability for efficient broadband photodetection. The band alignment reveals a type-I heterojunction, and the device under reverse bias reveals a fast response time of 12 µs/24 µs (rise time/fall time) and an improved responsivity in the 390 to 840 nm range due to the effective interfacial charge transfer and efficient interlayer coupling at the Bi2O2Se/CsPbBr3 interface. Notably, a photodetector with a better light on/off ratio and a peak responsivity of ∼103 A W-1 was achieved in the Bi2O2Se/CsPbBr3 heterostructure due to the synergistic effects in the heterostructure under ambient conditions. The DFT analysis of the density of states and charge density plots in the heterostructure revealed a net transfer of electrons/holes from perovskite nanocrystals to Bi2O2Se layers and additional density of states in Bi2O2Se. These results are significant for the development of non-van der Waals heterostructure based high-performance low-powered photodetectors.

Potential Anti-leishmanial Activity of a Semi-purified Fraction Isolated from the Leaves of Parthenium hysterophorus.

PURPOSE: In the present perspective, emergence of resistant strains of Leishmania donovani and severe side effects resulting from the use of conventional anti-leishmanial therapies present an urgent need for developing novel agents against this parasite. We have explored the effectiveness of secondary plant metabolites as alternative choices in the treatment for visceral leishmaniasis (vl). METHODS: The plant Parthenium hysterophorus L. (Asteraceae) was collected from the West Bengal State University Campus, Barasat, West Bengal, India. The leaves of this plant were extracted by different solvents, such as ethyl acetate, water, petroleum ether and hexane. Gas chromatography-mass spectrometry (GC-MS) analysis was also carried out for the identification of compounds in the hexane soluble fraction (PHFd) with substantial anti-leishmanial activities. The antipromastigote activity and cytotoxicity of this fraction were evaluated by the tetrazolium MTT assay. Other biochemical and physiological parameters were studied by microscopic observation and flow cytometric analyses. RESULTS: PHFd showed considerable activity against L. donovani promastigotes (IC50: 20 µg/ml). The PHFd also inhibited in vitro growth of L. major LV39 promastigotes dose dependently with an IC50 of 40 µg/ml. The GC-MS studies of this particular fraction revealed the presence of four major compounds with different retention times (RT) of 26.08, 33.11, 36.41, and 41.20 min. In this study, we also established that PHFd could induce DNA damage and subsequent apoptosis of L. donovani promastigotes with a concomitant increase in generations of reactive oxygen species (ROS) in a time-dependent manner. This fraction was also found to be effective in nitric oxide-mediated inhibition of intracellular amastigotes (IC50:12.5 µg/ml) without any noticeable cytotoxicity towards murine splenocytes in vitro. CONCLUSION: This study provides the basis for additional phytochemical and pharmacological studies on the antiprotozoal applications of P. hysterophorus.

Combination of Mycobacterium indicus pranii and Heat-Induced Promastigotes Cures Drug-Resistant Leishmania Infection: Critical Role of Interleukin-6-Producing Classical Dendritic Cells.

The major issues in available therapeutic modalities against leishmaniasis are cost, toxicity, and the emergence of drug resistance. The aim of this work was to develop a successful therapeutic adjuvant against drug-resistant Leishmania donovani infection by means of combining Mycobacterium indicus pranii with heat-induced promastigotes (HIP). One-month postinfected BALB/c mice were administered subcutaneously with M. indicus pranii (108 cells) and HIP (100 µg) for 5 days. Spleens were harvested for flow cytometric and reverse transcriptase PCR analysis. The antileishmanial effect of the combination strategy was associated with induction of a disease-resolving Th1 and Th17 response with simultaneous downregulation of CD4+ CD25+ Foxp3+ (nTreg) cells and CD4+ CD25- Foxp3- (Tr1) cells in the spleen. The significant expansion of CD4+ TCM (CD4+ CD44hi CD11ahi CD62Lhi) cells was a further interesting outcome of this therapeutic strategy in the context of long-term protection of hosts against secondary infection. Toll-like receptor 2 (TLR2) was also found instrumental in this antiparasitic therapy. Induced interleukin-6 (IL-6) production from expanded CD11c+ CD8α+ (cDC1) and CD11c+ CD11b+ (cDC2) dendritic cells (DCs) but not from the CD11b+ Ly6c+ inflammatory monocytes (iMOs), was found critical in the protective expansion of Th17 as evidenced by an in vivo IL-6 neutralization assay. It also promoted the hematopoietic conversion toward DC progenitors (pre-DCs) from common dendritic cell progenitors (CDPs), the immediate precursors, in bone marrow. This novel combinational strategy demonstrated that expansion of Th17 by IL-6 released from CD11c+ classical DCs is crucial, together with the conventional Th1 response, to control drug-resistant infection.

Origin and tunability of dual color emission in highly stable Mn doped CsPbCl3 nanocrystals grown by a solid-state process.

Herein, we report on a facile, bulk scale room temperature solid-state synthesis of highly stable and luminescent Mn-doped CsPbCl3 nanocrystal (NCs) with high Mn substitution, and investigate the origin and tunability of its dual-color emission. The structural and compositional analyses confirm the successful doping of Mn (1-40%) ion in CsPbCl3 NCs. The Mn-doped CsPbCl3 NCs exhibit distinct excitonic photoluminescence (PL) emission at ~412 nm (Iex) and Mn related emission at ~590 nm (IMn) with high PL quantum yield (up to 35%). Our study reveals that the intensity ratio IMn/Iex could be widely tuned by a factor of 64 and 23 by changing the Mn concentration and the measurement temperature, respectively. The stronger Mn emission at higher temperature is attributed to the higher rate of transfer of photoexcited carriers from the excitonic state of CsPbCl3 host to Mn related state. Further, excitation intensity-dependent PL along with time-resolved PL studies revealed important insights into the origin and tunability of Mn related orange-red PL in the dual color emitting Mn-doped CsPbCl3 NCs. The PL line shape analysis revealed additional PL peak in the range ~634-666 nm, which grows stronger with higher doping concentration and it is attributed, for the first time, to structural defects in the NCs. Remarkably, the Mn-doped CsPbCl3 NCs synthesized by our method exhibit about 10 times higher storage stability than those reported earlier due to the high Mn doping efficiencies achieved due to the strain induced enhanced doping process. Finally, white light emitting diodes (LEDs) were fabricated by employing blue-emitting CsPbCl1.5Br1.5 NCs, green-emitting CsPbBr3 NCs and orange-red emitting 10% Mn-doped CsPbCl3 NCs all grown by the same method. Our work demonstrates a low-cost synthesis strategy for high Mn doping in CsPbCl3 NCs with superior ambient stability and highly tunable emission.

Strong Cathodoluminescence and Fast Photoresponse from Embedded CH3NH3PbBr3 Nanoparticles Exhibiting High Ambient Stability.

This study presents a comprehensive analysis of the strong cathodoluminescence (CL), photoluminescence (PL), and photoresponse characteristics of CH3NH3PbBr3 nanoparticles (NPs) embedded in a mesoporous nanowire (NW) template. Our study revealed a direct correlation between the CL and PL emissions from the perovskite NPs (Per NPs), for the first time. Per NPs are fabricated by a simple spin-coating of a perovskite precursor on the surface of metal-assisted chemically etched mesoporous Si NW arrays. The Per NPs confined in the mesopores show blue-shifted and enhanced CL emission as compared to the bare perovskite film, while the PL intensity of Per NPs is dramatically high compared to that of their bulk counterpart. A systematic analysis of the CL/PL spectra reveals that the quantum confinement effect and ultralow defects in Per NPs are mainly responsible for the enhanced CL and PL emissions. Low-temperature PL and time-resolved PL analysis confirm the high exciton binding energy and radiative recombination in Per NPs. The room temperature PL quantum yield of the Per NP film on the NW template was found to be 40.5%, while that of Per film was 2.8%. The Per NPs show improved ambient air stability than the bare film due to the protection provided by the dense NW array, since a dense NW array can slow down the lateral diffusion of oxygen and water molecules in Per NPs. Interestingly, the Si NW/Per NP junction shows superior visible light photodetection and the prototype photodetector shows a high responsivity (0.223 A/W) with response speeds of 0.32 and 0.28 s of growth and decay in photocurrent, respectively, at 2 V applied bias, which is significantly better than the reported photodetectors based on CH3NH3PbBr3 nanostructures. This work demonstrates a low-cost fabrication of CH3NH3PbBr3 NPs on a novel porous NW template, which shows excellent photophysical and optoelectronic properties with superior ambient stability.

Multifunctional Ag nanoparticle decorated Si nanowires for sensing, photocatalysis and light emission applications.

We report on the fabrication of Ag nanoparticle (NP) decorated mesoporous Si nanowire (NW) heterostructure (HS) by a simple and low cost chemical process. The as-grown Si NWs are mesoporous in nature and the Ag NP decorated Si NWs (Ag@Si NWs) exhibit broadband light emission, ultralow reflectance, efficient photocatalytic degradation of organic dyes and excellent sensitivity for the detection of organic molecules over a wide range of concentration. The broadband white light photoluminescence emission from the bare Si NWs is explained on the basis of quantum confinement effect in Si NCs/NWs and the nonbridging oxygen hole center defects in the SiSiOx interface. High work function of the noble metal NPs facilitates the effective separation of the photoinduced electron-hole pairs in Si NWs, which enables the Ag@Si NWs to exhibit high photocatalytic efficiency for the degradation of organic dye. The Ag@Si NWs exhibited high potential and sensitivity for the selective and quantitative detection of different organic molecules at extremely low concentration down to 10-12 M by surface-enhanced Raman scattering and 10-11 M by fluorescence-based detection. These versatile properties of the Ag@Si NWs open up opportunities for a variety of energy and environmental applications, such as white light emission, solar cell, artificial photosynthesis, disposal of organic pollutant and bio-chemical sensors etc.

Selective in vitro inhibition of Leishmania donovani by a semi-purified fraction of wild mushroom Grifola frondosa.

The current study was designed to assess the anti-leishmanial effect of a semi-purified fraction of wild mushroom Grifola frondosa against Leishmania donovani, in vitro. A total of five extracts from three wild mushrooms [Grifola frondosa (family, Meripilaceae) Laetiporus sulphurous (family, Polyporaceae) and Meripilus giganteus (family, Meripilaceae) were explored for novel anti-leishmanial leads against promastigotes. The ethanol extract of G. frondosa was selected as the most efficient against L. donovani promastigotes (IC50: 93.9 µg/mL). A semi-purified fraction was obtained from an active ethanol extract of G. frondosa and found to inhibit the survival of promastigotes of L. donovani (MHOM/IN/83/AG83) significantly (IC50: 20.37 µg/mL) and it also had some effect against L. major LV39 (MRHO/Sv/59/P strain) and L. tropica WR683 (MHOM/SU/58/OD) strains at higher concentrations (IC50: 46.08 µg/mL and 53.79 µg/mL respectively). The semi-purified fraction also interfered in lipid biosynthesis, altered parasite morphology and induced apoptosis in L. donovani promastigotes. The semi-purified fraction was also effective against intracellular amastigotes in infected macrophages and enhanced the release of nitric oxide and pro-inflammatory cytokines, in vitro. Interestingly, the 50% inhibitory concentration of the semi-purified fraction against the intracellular amastigotes (IC50: 2.48 µg/mL) was much lower in comparison to promastigotes (IC50: 20.37 µg/mL). The semi-purified fraction was found to inhibit the intracellular amastigotes slightly more efficiently in comparison to conventional anti-leishmanial drugs; sodium antimony gluconate, amphotericin B, miltefosine and paromomycin and noticeably non-toxic towards host splenocytes. The findings of the present study established that G. frondosa might be a natural resource for development of a new anti-leishmanial lead.

A decoherence-free subspace in a charge quadrupole qubit.

Quantum computing promises significant speed-up for certain types of computational problems. However, robust implementations of semiconducting qubits must overcome the effects of charge noise that currently limit coherence during gate operations. Here we describe a scheme for protecting solid-state qubits from uniform electric field fluctuations by generalizing the concept of a decoherence-free subspace for spins, and we propose a specific physical implementation: a quadrupole charge qubit formed in a triple quantum dot. The unique design of the quadrupole qubit enables a particularly simple pulse sequence for suppressing the effects of noise during gate operations. Simulations yield gate fidelities 10-1,000 times better than traditional charge qubits, depending on the magnitude of the environmental noise. Our results suggest that any qubit scheme employing Coulomb interactions (for example, encoded spin qubits or two-qubit gates) could benefit from such a quadrupolar design.

Successful Therapy of Murine Visceral Leishmaniasis with Astrakurkurone, a Triterpene Isolated from the Mushroom Astraeus hygrometricus, Involves the Induction of Protective Cell-Mediated Immunity and TLR9.

In our previous report, we showed that astrakurkurone, a triterpene isolated from the Indian mushroom Astraeus hygrometricus (Pers.) Morgan, induced reactive oxygen species, leading to apoptosis in Leishmania donovani promastigotes, and also was effective in inhibiting intracellular amastigotes at the 50% inhibitory concentration of 2.5 µg/ml. The aim of the present study is to characterize the associated immunomodulatory potentials and cellular activation provided by astrakurkurone, leading to effective antileishmanial activity in vitro and in vivo Astrakurkurone-mediated antileishmanial activity was evaluated by real-time PCR and flow cytometry. The involvement of Toll-like receptor 9 (TLR9) was studied by in vitro assay in the presence of a TLR9 agonist and antagonist and by in silico modeling of a three-dimensional structure of the ectodomain of TLR9 and its interaction with astrakurkurone. Astrakurkurone caused a significant increase in TLR9 expression of L. donovani-infected macrophages along with the activation of proinflammatory responses. The involvement of TLR9 in astrakurkurone-mediated amastigote killing has been evidenced from the fact that a TLR9 agonist (CpG, ODN 1826) in combination with astrakurkurone enhanced the amastigote killing, while a TLR9 antagonist (bafilomycin A1) alone or in combination with astrakurkurone curbed the amastigote killing, which could be further justified by in silico evidence of docking between mouse TLR9 and astrakurkurone. Astrakurkurone was found to reduce the parasite burden in vivo by inducing protective cytokines, gamma interferon and interleukin 17. Moreover, astrakurkurone was nontoxic toward peripheral blood mononuclear cells of immunocompromised patients with visceral leishmaniasis. Astrakurkurone, a nontoxic antileishmanial, enhances the immune efficiency of host cells, leading to parasite clearance in vitro and in vivo.

Induction of apoptosis by zerumbone isolated from Zingiber zerumbet (L.) Smith in protozoan parasite Leishmania donovani due to oxidative stress

Abstract In the present context of emergence of resistance aligned with the conventional anti-leishmanial drugs and occasional treatment failure compelled us to continue the search for replaceable therapeutic leads against Leishmaniainfection. Various ginger spices of the Zingiberaceae family are widely used as spices, flavouring agents, and medicines in Southeast Asia because of their unique flavour as well as due to their medicinal properties. Zerumbone, a natural component of Zingiber zerumbet (L.) Smith, has been studied for its pharmacological potential as antiulcer, antioxidant, anticancer, and antimicrobial. In this study, we have shown that zerumbone could induce ROS mediated apoptosis in Leishmania donovani promastigotes and also found effective in reducing intracellular amastigotes in infected-macrophages. We emphasized the potential of zerumbone to be employed in the development of new therapeutic drugs against L. donovaniinfection and provided the basis for future research on the application of transitional medicinal plants.

Induction of apoptosis by zerumbone isolated from Zingiber zerumbet (L.) Smith in protozoan parasite Leishmania donovani due to oxidative stress.

In the present context of emergence of resistance aligned with the conventional anti-leishmanial drugs and occasional treatment failure compelled us to continue the search for replaceable therapeutic leads against Leishmania infection. Various ginger spices of the Zingiberaceae family are widely used as spices, flavouring agents, and medicines in Southeast Asia because of their unique flavour as well as due to their medicinal properties. Zerumbone, a natural component of Zingiber zerumbet (L.) Smith, has been studied for its pharmacological potential as antiulcer, antioxidant, anticancer, and antimicrobial. In this study, we have shown that zerumbone could induce ROS mediated apoptosis in Leishmania donovani promastigotes and also found effective in reducing intracellular amastigotes in infected-macrophages. We emphasized the potential of zerumbone to be employed in the development of new therapeutic drugs against L. donovani infection and provided the basis for future research on the application of transitional medicinal plants.

High-Fidelity Single-Shot Toffoli Gate via Quantum Control.

A single-shot Toffoli, or controlled-controlled-not, gate is desirable for classical and quantum information processing. The Toffoli gate alone is universal for reversible computing and, accompanied by the Hadamard gate, forms a universal gate set for quantum computing. The Toffoli gate is also a key ingredient for (nontopological) quantum error correction. Currently Toffoli gates are achieved by decomposing into sequentially implemented single- and two-qubit gates, which require much longer times and yields lower overall fidelities compared to a single-shot implementation. We develop a quantum-control procedure to construct a single-shot Toffoli gate for three nearest-neighbor-coupled superconducting transmon systems such that the fidelity is 99.9% and is as fast as an entangling two-qubit gate under the same realistic conditions. The gate is achieved by a nongreedy quantum control procedure using our enhanced version of the differential evolution algorithm.

Efficacy of liquid-based cytology versus conventional smears in FNA samples.

BACKGROUND: Liquid-based cytology (LBC) is fast becoming a useful method in evaluating both gynecological and non-gynecological preparations, including fine needle aspiration (FNA) cytology. Even distribution of cells, decreasing obscuring background elements like blood and mucus, well preserved nuclear and cytoplasmic details and rapid fixation helps in better visualization of cells. AIM: This study was conducted to asses the diagnostic accuracy of liquid-based cytology versus conventional smears in fine needle aspiration samples. STUDY DESIGN: In this prospective study, we had 110 cases, including 30 cases of breast, 40 of lymph node, 10 of salivary glands, 18 of thyroid and 12 of bone and soft tissue. In each case, two passes were performed. The first pass was for conventional preparation (CP) and the second pass yielded material for thin-prep (TP) preparation. Both CP and TP smears were compared for cellularity, background blood and necrotic cell debris, cell architecture, informative background, presence of a monolayer of cells and nuclear and cytoplasmic details by a semiquantitative scoring system. Wilcoxon's signed rank test on an SPSS program was used for statistical analysis. RESULTS: Diagnostic accuracy was better in LBC smears compared with CP smears due to lack of background debris and better cell morphology, which was performed according to Wilcoxon's signed rank test, yielding a P-value of <0.001. However, in some cases, because of a decrease in cell size, clustering and altered background in LBC, a support of CP was essential. CONCLUSION: LBC performed on FNA samples can be a simple and valuable technique. Only in few selected cases, where background factor is an essential diagnostic clue, a combination of both CP and TP is necessary.

Protective effect of Croton caudatus Geisel leaf extract against experimental visceral leishmaniasis induces proinflammatory cytokines in vitro and in vivo.

In the present state of overwhelming emergence of drug-unresponsive phenotypes of Leishmania donovani and persistent severe toxicity in conventional anti-leishmanial therapy, in search for novel leads, the aim of this study has been fixed to identify the active extract(s) of Croton caudatus Geisel. var. tomentosus Hook effective against the parasitic protozoans in vitro and in vivo. C. caudatus Geisel. is often used by Chakma and Hmar community, the local tribes of north-east India for medicinal and veterinary purposes. Among the five semi-purified extracts tested, C. caudatus leaves, extracted in hexane and subsequently semi-purified in a column packed with silica gel (70-130 µM; mesh size 60 A°) using ethyl acetate-hexane solvent (9:1), was found to be the most effective growth inhibitor (JDHex) against the Leishmania promastigotes and amastigotes. JDHex significantly altered the biochemical parameters (protein, lipid and carbohydrates) in promastigotes followed by the morphological changes, DNA condensation and subsequent apoptosis in L. donovani. In consequent steps, it has been also proved that JDHex reduced the replication of intracellular amastigotes with concomitant release of nitric oxide and pro-inflammatory cytokines, IL-12 and TNF-α in vitro. Significantly, the 50% inhibitory concentration of JDHex was estimated much lower against the intracellular amastigotes (2.5 µg/mL) in comparison to promastigotes (10 µg/mL). JDHex was also found efficient in reducing parasite burden in spleen and liver when treated in vivo and increased the intracellular IFN-γ and decreased the IL-10 in CD4+ T cells in splenocytes of orally treated animals. The results of this study support the importance in exploration of novel anti-leishmanial leads from C. caudatus Geisel. var. tomentosus Hook. against the L. donovani (MHOM/IN/83/AG83) infection. Partial chemical characterization of JDHex revealed the presence of terpenoids. However, the further chemical investigation of JDHex is warranted.

Selective inhibition of Leishmania donovani by active extracts of wild mushrooms used by the tribal population of India: An in vitro exploration for new leads against parasitic protozoans.

The study was intended at evaluating the anti-proliferating effect of mushrooms used in traditional folklore of Santal tribal population in India against Leishmania donovani (MHOM/IN/83/AG83). A total of eighteen extracts, three estracts from each mushroom [(80% ethanol extracted; Fa), (water-soluble polysaccharide fraction; Fb), (polyphenolic fraction; Fc)], from six wild mushrooms were obtained. These extracts were tested against the promastigotes and amastigotes for their antileishmanial capacity. Fa fractions (250 µg/mL) of Astraeus hygrometricus and Tricholoma giganteum significantly inhibited the growth of L. donovani promastigotes and interfered in lipid biosynthesis. Moreover, both fractions induced apoptosis in promastigotes. Water soluble Fb fractions of A. hygrometricus, Russula laurocerasi, Russula albonigra, Termitomyces eurhizus, Russula delica and polyphenolic Fc fraction of R. laurocerasi were found to inhibit the replication of intracellular amastigotes in macrophages dose dependently. Significantly, 50% inhibitory concentration of the active extracts against intracellular amastigotes induced release of nitric oxide and IL-12 in murine macrophages and dendritic cells assay and also found considerably non-toxic on murine splenocytes. Results of this study can be used as a basis for further phytochemical and pharmacological investigations in the effort for search of novel anti-leishmanial leads.

Synthesis of bioactive 28-hydroxy-3-oxolup-20(29)-en-30-al with antileukemic activity.

An easy and efficient route to partial synthesis of bioactive 28-hydroxy-3-oxolup-20(29)-en-30-al (1), starting from betulinic acid (2), has been developed (eight steps, 44% overall yield). Structures of all the compounds were determined by spectral studies (IR, (1)H, (13)C NMR, MS, NOESY, COSY, etc.). Compound 1 and the precursors (2, 3, 5, and 7) showed antiproliferative activities against human K562 leukemia, murine WEHI3 leukemia, and murine MEL erythroid progenitor.

Protective therapy with novel chromone derivative against Leishmania donovani infection induces Th1 response in vivo.

BACKGROUND: Visceral leishmaniasis is a chronic protozoan disease caused by Leishmania donovani, an obligatory intracellular parasite that resides and multiplies within macrophages of the reticuloendothelial system. The aim of this study was to evaluate the efficacy of nine novel synthetic chromone derivatives as antileishmanial molecules in experimental murine visceral leishmaniasis. METHODS: In vitro activity of the molecules (2, 5 and 10 µg/ml) was assessed against promastigotes of both pentavalent antimonial-responsive strain AG83 and pentavalent antimonial-resistant strain GE1F8R at days 2 (48 h), 4 (96 h) and 6 (144 h). The efficacy of the most efficient chromone derivative [C-(6-Methyl-4-oxo-4H-1-benzopyran-3-yl)-N-(p-tolyl) nitrone], designated here as NP1, was also tested against intracellular amastigotes in vitro and in vivo. RESULTS: NP1, 5 µg/ml, inhibited the growth of AG83 and GE1F8R promastigotes by 98.57% (day 4) and 75.75% (day 6), respectively, and also inhibited the growth of intracellular amastigotes by 85% (day 3), compared to DMSO control. Treatment of L. donovani-infected mice with NP1 resulted in a 70% significant decrease in parasite load in the spleen in the 7th week after infection (5 mice in each group), with associated induction of interferon-γ synthesis by dose 2 (37.5 mg/kg body weight) compared to DMSO control. Dose 2 was found efficient over dose 1 (25 mg/kg body weight). CONCLUSIONS: The novel synthetic chromone derivative is effective in the treatment of visceral leishmaniasis and induces the synthesis of interferon-γ in rodent models.