Application of Next-Generation Sequencing for the Genomic Characterization of Patients with Smoldering Myeloma.

Genomic analysis could contribute to a better understanding of the biological determinants of the evolution of multiple myeloma (MM) precursor disease and an improved definition of high-risk patients. To assess the feasibility and value of next-generation sequencing approaches in an asymptomatic setting, we performed a targeted gene mutation analysis and a genome-wide assessment of copy number alterations (CNAs) by ultra-low-pass whole genome sequencing (ULP-WGS) in six patients with monoclonal gammopathy of undetermined significance and 25 patients with smoldering MM (SMM). Our comprehensive genomic characterization highlighted heterogeneous but substantial values of the tumor fraction, especially in SMM; a rather high degree of genomic complexity, in terms of both mutations and CNAs, and inter-patient variability; a higher incidence of gene mutations and CNAs in SMM, confirming ongoing evolution; intraclonal heterogeneity; and instances of convergent evolution.

Expression Pattern and Biological Significance of the lncRNA ST3GAL6-AS1 in Multiple Myeloma.

The biological impact of long non-coding RNAs (lncRNAs) in multiple myeloma (MM) is becoming an important aspect of investigation, which may contribute to the understanding of the complex pathobiology of the disease whilst also providing novel potential therapeutic targets. Herein, we investigated the expression pattern and the biological significance of the lncRNA ST3 beta-galactoside alpha-2,3 sialyltransferase 6 antisense RNA 1 (ST3GAL6-AS1) in MM. We documented a high ST3GAL6-AS1 expression level in MM compared to normal plasma cells (PCs) or other hematological malignancies.

Influence of weight gain, according to Institute of Medicine 2009 recommendation, on spontaneous preterm delivery in twin pregnancies.

Backgrounds: Maternal total weight gain during pregnancy influences adverse obstetric outcomes in singleton pregnancies. However, its impact in twin gestation is less understood. Our objective was to estimate the influence of total maternal weight gain on preterm delivery in twin pregnancies.

Development of biocatalysts carrying naphthalene dioxygenase and dihydrodiol dehydrogenase genes inducible in aerobic and anaerobic conditions.

We developed biocatalysts carrying naphthalene dioxygenase and dihydrodiol dehydrogenase genes cloned from plasmid pN3 of Pseudomonas fluoresceins N3 involved in naphthalene degradation, as an alternative approach to the production of hydroxylated compounds by chemical synthesis. Naphthalene dioxygenase is responsible for hydroxylation of the hydrocarbon into the corresponding 1,2-dihydro-1,2-dihydroxy derivative and dihydrodiol dehydrogenase is involved in the subsequent transformation into the 1,2-dihydroxy derivative. The first reaction strictly requires the presence of oxygen, essential for the dioxygenation reaction, while the second one can also be performed in anaerobic conditions that are optimal to avoid the easy oxidation of bioconversion products.

Polyphenolic glycosides from african proteaceae.

The phytochemical investigation of members of the genus Protea afforded a series of polyphenolic compounds (1-5) that were identified by 1D and 2D NMR experiments. Of these, 2-5 are new compounds. Chemical syntheses of 1-3 were performed in order to confirm the structures and to prepare additional material for biological evaluation.

A new biocatalyst for production of optically pure aryl epoxides by styrene monooxygenase from Pseudomonas fluorescens ST.

We developed a biocatalyst by cloning the styrene monooxygenase genes (styA and styB) from Pseudomonas fluorescens ST responsible for the oxidation of styrene to its corresponding epoxide. Recombinant Escherichia coli was able to oxidize different aryl vinyl and aryl ethenyl compounds to their corresponding optically pure epoxides. The results of bioconversions indicate the broad substrate preference of styrene monooxygenase and its potential for the production of several fine chemicals.

Isolation, synthesis, and antiplatelet aggregation activity of resveratrol 3-O-beta-D-glucopyranoside and related compounds.

Resveratrol 3-O-beta-D-glucopyranoside (1) has been isolated from the seeds of Erythrophleum lasianthum (Caesalpinioidae, Leguminosae), a South African plant used in traditional medicine, and has shown antiplatelet aggregation activity. The synthesis of 1, related hydroxystilbenes, and their glucosides has been undertaken to provide larger quantities, for further biological evaluation, and has been accomplished via Wittig reactions followed by glucosylation under phase transfer catalysis.

Synthesis of biologically active polyphenolic glycosides (combretastatin and resveratrol series).

(E)-3-(beta-D-Glucopyranosyloxy)-4',5-dihydroxystilbene (resveratrol 3-beta-D-glucoside, piceid), (Z)-2',3'-dihydroxy-3,4,4',5-tetramethoxystilbene (combretastatin A-1), (Z)-3'-hydroxy-3,4,4',5-tetramethoxystilbene (combretastatin A-4), (Z)-2'-hydroxy-3-4-4'-5-tetramethoxystilbene (combretastatin iso-A-4), alpha, beta-dihydro-2',3'-dihydro-2',3'-dihydroxy-3,4,4',5-tetramethoxystilb ene (combretastatin B-1), the corresponding glucosides, and related compounds have been synthesized via Wittig reactions followed by glucosylation under phase-transfer catalysis. Most of the compounds synthesized have been tested with respect to biological activity (cytostatic, cytotoxic, antimitotic, neurotoxic, antiplatelet, aggregation activity).

Production of substituted naphthalene dihydrodiols by engineered Escherichia coli containing the cloned naphthalene 1,2-dioxygenase gene from Pseudomonas fluorescens N3.

Naphthalene dioxygenase, a key enzyme in the dihydroxylation of naphthalene, is encoded by the plasmid pN3, responsible for naphthalene metabolism in Pseudomonas fluorescens N3. The naphthalene dioxygenase, including all the sequences for its expression and the regulatory region, has been localized on the 4.3-kb HindIII-ClaI fragment and on the 3.

A novel K+ channel blocker isolated from 'hiccup nut' toxin.

Combretastatin B1, a polyhydroxybibenzyl compound extracted from the fruit of Combretum kraussii, known to contain 'hiccup nut' toxin, reversibly increased the duration, but not the peak or the rate of rise, of the action potential in rat sensory neurones by approximately 300%. This effect was only seen when it was applied to the extracellular side of the membrane. No effects on the resting potential were observed.

Prevention of cytokine-induced hypotension in cancer patients by the pineal hormone melatonin.

Hypotension is a frequent side-effect of cancer biotherapies with cytokines. Cytokine-induced hypotension would mainly depend on the stimulation of nitric oxide (NO) production, which represents the most effective endogenous vasodilator. Moreover, it has been proven that both biological activity and toxicity of cytokines are influenced by the psychoneuroendocrine system, in particular by the pineal hormone melatonin.

Immunomodulatory properties of a pineal indole hormone other than melatonin, the 5-methoxytryptophol.

Several experiments have suggested that the pineal gland has an antitumor immunomodulatory action. Melatonin (MLT), the best known pineal hormone, has been shown to stimulate anticancer immune defenses during the night, corresponding to the period of its maximum blood levels, whereas it has no effect during the light phase of the day. At present, no study has been performed to investigate possible immunomodulating properties of other pineal indoles, such as 5-methoxytryptophol (5-MTL), whose circadian secretion would be opposite with respect to that of MLT, since it reaches its highest levels during the light phase of the day.

Cycloartane triterpene glycosides from Astragalus trigonus.

Three new cycloartane glycosides, trigonoside I, II and III, and the known astragalosides I and II were isolated from the roots of Astragalus trigonus. The structures of the new glycosides were totally elucidated by high field (600 MHz) NMR analyses as cycloastragenol-6-O-beta-xylopyranoside, cycloastragenol-3-O-[alpha-L-arabinopyranosyl(1-->2)-beta-D- xylopyranosyl]- 6-O-beta-D-xylopyranoside and cycloastragenol-3-O-[alpha-L-arabinopyranosyl (1-->2)-beta-D-(3-O-acetyl)-xylopyranosyl]-6-O-beta-D-xylopyranoside.

Study of the resolution of amino acids and aminoalcohols in organic solvents.

The enzymatic resolution of racemic phenylglycine, phenylglycinol and phenylalaninol has been studied in organic solvents under a variety of experimental conditions. Subtilisin in 3-methyl-3-pentanol was effective for the resolution of phenylglycine esters, via N-acylation with trifluoroethyl butyrate. Porcine pancreatic lipase in ethyl acetate gave satisfactory results in the resolution of phenylglycinol and phenylalaninol; theα orβ position of the phenyl group was found to influence both the rate and the chemioselectivity of the reaction.

Enhanced secretion of tumour necrosis factor in patients with myocardial infarction.

Objectives: Recent evidence suggests that leukocyte infiltration of myocardial tissue may extend the area of necrosis during the acute phase of myocardial infarction. Since the activation of leukocytes depends on the action of cytokines, mainly tumour necrosis factor (TNF), we evaluated TNF secretion during myocardial infarction.

Methods: The study included 12 patients with acute myocardial infarction as diagnosed on the basis of enzymatic and ECG criteria.

[Cardioangioimmunology: the immune implications in the principle cardiovascular pathologies].

At present, it is known that the immune system acts through the release of protein factors, so-called cytokines. In addition to their immunomodulating and endocrinometabolic effects, cytokines have appeared to be able to have an influence on the cardiovascular system by inducing important haemodynamic changes. Cytokines cause hypotension, particularly IL-2 and TNF, due at least in part to a production of nitric oxide by endothelial cells.

Saponins from Albizzia lucida.

Three main saponins were isolated from the seeds of Albizzia lucida. Their structures were established by spectral analyses and chemical and enzymatic transformations as 3-O-[beta-D-xylopyranosyl(1----2)-alpha-L-arabinopyranosyl (1----6)] [beta-D-glucopyranosyl (1----2)] beta-D-glucopyranosyl echinocystic acid; 3-O-[alpha-L-arabinopyranosyl (1----6)] [beta-D-glucopyranosyl (1----2)]-beta-D-glucopyranosyl echinocystic acid and 3-O-[beta-D-xylopyranosyl (1----2)-beta-D-fucopyranosyl (1----6)-2-acetamido-2-deoxy-beta-D-glucopyranosyl echinocystic acid, characterized as its methyl ester.

Melatonin response to atrial natriuretic peptide administration in healthy volunteers.

Recent observations have demonstrated that the pineal hormone melatonin (MLT) plays a role in the neuroendocrine control of the cardiovascular system. On the other hand, it has been observed that the cardiac hormone alpha-atrial natriuretic peptide (ANP) may regulate the neuroendocrine functions. The present study was carried out to investigate the possible relationship between cardiac and pineal endocrine functions.

Pineal gland and tumor cell kinetics: serum levels of melatonin in relation to Ki-67 labeling rate in breast cancer.

Recent observations showed that host may regulate either endocrinologically or immunologically tumor growth and differentiation, perhaps by modulating oncogene expression. Within the endocrine system, the pineal hormone, melatonin, seems to play an important antineoplastic role. To investigate its secretion in relation to tumor growth, we have evaluated the daily serum levels of melatonin in a group of 25 untreated breast cancer patients with a locally limited disease.

A study of heart-pineal interactions: atrial natriuretic peptide response to melatonin administration in healthy humans.

It is known that the pineal hormone melatonin plays a role in the regulation of several biological functions. In an attempt to investigate interactions between the pineal and the cardiac endocrine activity, in this preliminary study we have evaluated the effect of melatonin on the secretion of the cardiac hormone, atrial natriuretic peptide (ANP). The study included five healthy volunteers, and melatonin was given orally at a dose of 30 mg at 17:00.