Retroperitoneal lymphangiomyomatosis diagnosed by fine needle aspiration: a case report

BACKGROUND: Lymphangiomyomatosis is a rare condition affecting women of childbearing age. It is characterized by an abnormal proliferation of smooth muscle cells around lymphatics, giving rise to blockage of the large lymphatics, including the thoracic duct, and resulting in chylothorax and/or chyloascitis. The lung is the most common site of involvement. Retroperitoneum and lymph nodes can be also involved. CASE: A 40-year-old woman presented with lower urinary tract symptoms after a history of trauma and was found to have a retroperitoneal mass. Fine needle aspiration cytologic examination of the milky fluid aspirated from the mass revealed a few cohesive, 3-dimensional clusters of medium-sized cells with scanty cytoplasm, and ovoid and hyperchromatic nuclei. The background contained numerous mature lymphocytes. Laparoscopy revealed a multicystic mass filled with milky fluid. Histologic examination confirmed the cytologic diagnosis of lymphangiomyomatosis. CONCLUSION: Fine needle aspiration of lymphangiomyomatosis can be performed if cohesive clusters and a lymphoid background are present in chylous-type fluid and provided that adequate clinical information is available.     

The cyclobutane dimers of 5-methylcytosine and their deamination products.

The photochemical reactions of 5-methylcytosine (m(5)C), a minor component of mammalian DNA, have been studied at a concentration of 2 mM in frozen 10 mM aqueous NaCl solution at dry ice temperature (194.5 K). For these studies, low-pressure lamps emitting mainly UVB radiation were used. We have isolated and characterized three cyclobutane dimers, namely the cis-anti(c,a) the cis-syn(c,s) and the trans-syn(t,s) forms. While the c,a and the t,s cyclobutane dimers are relatively stable towards deamination upon standing in solution at 277 K, the c,s isomer is gradually converted into the corresponding c,s m(5)C-thymine (Thy) mixed dimer; this latter reaction occurs considerably faster at 310 K. The t,s cyclobutane dimer is converted into the corresponding m(5)C-Thy mixed dimer upon incubation at 373 K, while the c,a dimer is converted into a mixture of m(5)C and c,a mixed dimer when incubated at 310 K. Irradiation of equimolar mixtures of Thy (1 mM) and m(5)C (1 mM) under similar conditions yields each of the three m(5)C cyclobutane dimers, as well as significant amounts of c,a, c,s and t,s m(5)C-Thy mixed cyclobutane dimers. These m(5)C-Thy dimers undergo decompositions similar in nature to the processes undergone by m(5)C cyclobutane dimers. Pseudo-first order rate constants for deamination of the c,s m(5)C homodimer and c,s m(5)C-Thy heterodimer at various temperatures and at pH 7.7 have been measured and the enthalpies and entropies of activation have been evaluated for the deamination processes for these two compounds. The two dimers have half-lives of about 14 and 22 h, respectively, at 310 K; however, at 273 K, the corresponding half-lives can be evaluated as being around 30 and 36 days, respectively.     

Mesenchymal stem cell: Basic research and potential applications in cattle and buffalo

Characteristic features like self-renewal, multilineage differentiation potential, and immune-modulatory/anti-inflammatory properties, besides the ability to mobilize and home distant tissues make stem cells (SCs) a lifeline for an individual. Stem cells (SCs) if could be harvested and expanded without any abnormal change may be utilized as an all-in-one solution to numerous clinical ailments. However, slender understanding of their basic physiological properties, including expression potential, behavioral alternations during culture, and the effect of niche/microenvironment has currently restricted the clinical application of SCs. Among various types of SCs, mesenchymal stem cells (MSCs) are extensively studied due to their easy availability, straightforward harvesting, and culturing procedures, besides, their less likelihood to produce teratogens. Large ruminant MSCs have been harvested from various adult tissues and fetal membranes and are well characterized under in vitro conditions but unlike human or other domestic animals in vivo studies on cattle/buffalo MSCs have mostly been aimed at improving the animals’ production potential. In this document, we focused on the status and potential application of MSCs in cattle and buffalo.     

NMR structure of the full-length linear dimer of stem-loop-1 RNA in the HIV-1 dimer initiation site

The packaging signal of HIV-1 RNA contains a stem-loop structure, SL1, which serves as the dimerization initiation site for two identical copies of the genome and is important for packaging of the RNA genome into the budding virion and for overall infectivity. SL1 spontaneously dimerizes via a palindromic hexanucleotide sequence in its apical loop, forming a metastable kissing dimer form. Incubation with nucleocapsid protein causes this form to refold to a thermodynamically stable mature linear dimer. Here, we present an NMR structure of the latter form of the full-length SL1 sequence of the Lai HIV-1 isolate. The structure was refined using nuclear Overhauser effect and residual dipolar coupling data. The structure presents a symmetric homodimer of two RNA strands of 35 nucleotides each; it includes five stems separated by four internal loops. The central palindromic stem is surrounded by two symmetric adenine-rich 1-2 internal loops, A-bulges. All three adenines in each A-bulge are stacked inside the helix, consistent with the solution structures of shorter SL1 constructs determined previously. The outer 4-base pair stems and, proximal to them, purine-rich 1-3 internal loops, or G-bulges, are the least stable parts of the molecule. The G-bulges display high conformational variability in the refined ensemble of structures, despite the availability of many structural restraints for this region. Nevertheless, most conformations share a similar structural motif: a guanine and an adenine from opposite strands form a GA mismatch stacked on the top of the neighboring stem. The two remaining guanines are exposed, one in the minor groove and another in the major groove side of the helix, consistent with secondary structure probing data for SL1. These guanines may be recognized by the nucleocapsid protein, which binds tightly to the G-bulge in vitro.     

Virulence variation of Puccinia striiformis Westend. f. sp. tritici in Pakistan

Yellow rust populations of Pakistan were characterised for their virulence pathotypes/races and pathogenetic variation using seedling evaluation of differential genotypes under glasshouse conditions in Murree (6000 feet above sea level). Differential genotypes comprised a world set, an European set, near isogenic lines and the universally susceptible bread wheat cultivar “Morocco”. Over the two-year study a total of 18 race groups were identified. Out of these 18 race groups, several (68E0, 64E0, 66E0, 70E0, 6E0, 71E0, 6E0, 2E0, 67E0, and 68E16) were found previously. The new race group 70E32 found probably evolved because of mutation from the previously existing 70E16. Virulence frequencies of yellow rust (Yr) resistance genes were also determined on near isogenic lines. The highest virulence frequencies (%) were found for Yr7 (88%), Yr9 (57%), Yr18 (70%), and Yr24 (69%). Virulence frequencies were low for Yr 1 (4%), Yr5 (7%), Yr10 (10%) and Yr15 (4%). Our studies indicated that virulence existed for almost all yr genes, necessitating regular monitoring of the yellow rust populations and intensifying efforts to identify new sources of resistance to this pathogen.     

NMR structure of the mature dimer initiation complex of HIV-1 genomic RNA

The two identical genomic RNA strands inside each HIV-1 viral particle are linked through homodimerization of an RNA stem-loop, termed SL1, near their 5' ends. SL1 first dimerizes through a palindromic sequence in its loop, forming a transient kissing-loop complex which then refolds to a mature, linear duplex. We previously reported the NMR structure of a 23-base truncate of SLI in kissing-dimer form, and here report the high-resolution structure of its linear isoform. This structure comprises three short duplex regions--derived from the central palindrome and two stem regions of each strand, respectively--separated by two bulges that each encompass three unpaired adenines flanking the palindromes. The stacking pattern of these adenines differs from that seen in the kissing-loop complex, and leads to greater colinear base stacking overall. Moreover, the mechanical distortion of the palindrome helix is reduced, and base pairs ruptured during formation of the kissing-loop complex are re-established, so that all potential Watson-Crick pairs are intact. These features together likely account for the greater thermodynamic stability of the mature dimer as compared to its kissing-loop precursor.     

Biological effects of amphiphilic copolymer nanoparticle-encapsulated multi-target chemotherapeutic drugs on MCF-7 human breast cancer cells

Introduction

Amphiphilic copolymer nanoparticle-encapsulated multi-target chemotherapeutic drugs have attracted considerable attention due to their favorable drug efficiency and potential application prospect. Studies have shown that an amphiphilic copolymer, methoxypoly(ethylene glycol)-poly(lactide-co-glycolide) modified with ε-polylysine, and encapsulated with hydrophilic doxorubicin, hydrophobic paclitaxel and survivin siRNA profoundly improved the therapeutic effect both in vitro and in vivo.

Objectives

To investigate how MCF-7 cells would response to the exposure of these nanoparticles over with time and assess the biological effects of these nanoparticles and their encapsulated drugs in a holistic manner.

Methods

MCF-7 cells were treated with PBS, nanocarrier and three encapsulated drugs, respectively. Metabolic alterations associated with nano-drugs exposure were investigated by performing untargeted NMR metabolomics with combination of targeted fatty acids analysis by GC-MS on cell extracts. Altered metabolic pathways were further validated by qRT-PCR approach.

Results

Copolymers showed great biocompatibility with cells as it induced transit metabolic disruptions without affecting cell survival rate. The rapid release of encapsulated doxorubicin resulted in inhibition of glycolysis and DNA synthesis, active proteolysis; these metabolic alternations were recovered after 10 h exposure. However, the combination use of multiple drugs consistently induced cell cycle arrest and apoptosis evidenced by reduction in glycolysis, active proteolysis, stimulated O-GlcNAcylation, reduced the PC:GPC ratio and fatty acids accumulation. Prolonged exposure to encapsulated-multiple-drugs also induced oxidative stress to cells.

Conclusion

These findings provide important insight into the biological effects of nanoparticles and their encapsulated drugs while demonstrate that metabolomics is a powerful approach to evaluate the biological effects of nano-drugs.

     

ZnCl2 catalyzed new coumarinyl-chalcones as cytotoxic agents

A new series of coumarin-yl-chalcone derivatives (3a-m) had been designed and synthesized through different reactions such as aromatic addition, cyclization and Claisen-Schmidt reactions in good yields (54–78%). 5-acetyl-4-(2-hydroxyphenyl) -6-methyl-3, 4-dihydropyrimidin-2(1H) -one (1) has been synthesized by multi-component one pot reaction of salicylaldehyde, methyl acetoacetate and urea, which was further reacted with malonic acid employing ZnCl₂ catalyst to yield 5-acetyl-4-(4-hydroxy-2-oxo-2H-chromen-8-yl) -6-methyl-3, 4-dihydropyrimidin-2(1H) -one (2). The title compounds (3a-m) were synthesised by reacting 5-acetyl-4-(4-hydroxy-2-oxo-2H-chromen-8-yl) -6-methyl-3, 4-dihydropyrimidin-2(1H)-one (2) with different aromatic aldehydes in the presence of potassium hydroxide. In silico studies, a preliminary screening method for predicting the anti-cancer activity was performed for the synthesized compounds (3a-m) against Src, Alb tyrosine kinase and homology model protein (PDB ID: 4csv). The derivatives 3h and 3m showed moderate binding energies. The in vitro cytotoxic activity was evaluated for the compounds 3h and 3m by using human cancer cell-line morphology and MTT assay against three human cell-lines A549 (Lung), Jurkat (Leukemia) and MCF-7 (Breast). The results indicate that the derivatives 3h and 3m display significant anti-cancer activity, however it was found to be less cytotoxic when compared to the standard used i.e. Imatinib.     

Balanced Carrier Mobilities: Not a Necessary Condition for High‐Efficiency Thin Organic Solar Cells as Determined by MIS‐CELIV

A novel technique based upon injection‐charge extraction by linearly increasing voltage (i‐CELIV) in a metal‐insulator‐semiconductor (MIS) diode structure is described for studying charge transport in organic semiconductors. The technique (MIS‐CELIV) allows selective measurement of both electron and hole mobilities of organic solar cells with active layers thicknesses representative of operational devices. The method is used to study the model high efficiency bulk heterojunction combination poly[N‐9′′‐heptadecanyl‐2,7‐carbazole‐alt‐5,5‐(4′,7′‐di‐2‐thienyl‐2′,1′,3′‐benzothiadiazole)] (PCDTBT) and [6,6]‐phenyl C70‐butyric acid methyl ester (PC70BM) at various blend ratios. The absence of bipolar transport in PCDTBT‐and‐PC70BM‐only diodes is shown and strongly imbalanced carrier mobility is found in the most efficient “optimized” blend ratios. The mobility measurements are correlated with overall device performance and it is found that balanced and high charge carrier mobility are not necessarily required for high efficiencies in thin film organic solar cells.