Revisiting anti-Hu paraneoplastic autoimmunity: phenotypic characterization and cancer diagnosis.

Anti-Hu are the most frequent antibodies in paraneoplastic neurological syndromes, mainly associated with an often limited stage small cell lung cancer. The clinical presentation is pleomorphic, frequently multifocal. Although the predominant phenotypes are well characterized, how different neurological syndromes associate is unclear. Likewise, no specific study assessed the performance of new-generation CT and PET scanners for cancer screening in these patients. Herein, we aimed to describe the clinical pattern and cancer screening in a retrospective cohort of 466 patients with anti-Hu autoimmunity from the French Reference Centre on Paraneoplastic Neurological Syndromes registry. Clinical presentation, cancer screening and diagnosis were analysed. Among the 466 patients, 220 (54%) had multifocal neurological involvement. A hierarchical cluster analysis grouped the patients into (i) mainly limbic encephalitis, (ii) predominantly peripheral neuropathy and (iii) broad involvement of the nervous system (mixed group). Compared with limbic encephalitis and mixed groups, patients in the neuropathy group more frequently had a chronic onset of symptoms (29 versus 13 and 17%), elevated CSF proteins (83 versus 47 and 67%) and died from cancer progression (67 versus 15 and 28%; all P < 0.05). No significant difference in overall survival was observed between groups. Dysautonomia and brainstem signs were associated with a higher risk of death from the neurological cause; cancer diagnosis was the main predictor of all-cause death, especially when diagnosed within 2 years from clinical onset (all P < 0.05). Three hundred and forty-nine (75%) patients had cancer: in 295 (84%) neurological symptoms preceded tumour diagnosis, being lung cancer in 262 (89%), thereof small cell lung cancer in 227 (87%). First CT scan revealed lung cancer in 205/241 (85%), and PET scan shortened the interval to diagnosis when the initial CT scan was negative [7 months (1-66) in 27 patients versus 14 months (2-45) in 6; P < 0.001]. Although cancer diagnosis mostly occurred within 2 years from clinical onset, 13/295 (4%) patients exceeded that threshold. Conversely, 33 patients (7%) were 'cancer-free' after 2 years of follow-up. However, 13/33 (39%) had initial suspicious imaging findings that spontaneously regressed. In conclusion, although anti-Hu autoimmunity clinical presentation is mostly multifocal, we observed patients with a predominant limbic syndrome or isolated sensory neuropathy. Early implementation of PET scan shortens the interval to cancer diagnosis, which was the strongest predictor of death, especially if diagnosed ≤2 years from clinical onset. As cancer was diagnosed >2 years after clinical onset in few patients, screening should be extended up to 5 years. In addition, tumour regression was suspected in a substantial proportion of 'cancer-free' patients.

Phytochemical Characterization of Purple Coneflower Roots (Echinacea purpurea (L.) Moench.) and Their Extracts.

Echinacea purpurea is a perennial plant that belongs to the Asteraceae family. It has a wide range of applications mainly in the treatment and prevention of inflammations in the respiratory system. The current study aimed to perform a phytochemical characterization of purple coneflower (Echinacea purpurea) roots and their extracts (water, 40%, 50%, 60% ethanol, and 60% glycerol). Phytochemical characterization was carried out by gravimetric, spectrophotometric, and chromatographic methods. Echinacea roots were characterized by a low lipid (0.8%) content. In contrast, carbohydrates (45%) and proteins (20%) occupied a large part of the dry matter. Amongst the extracts, the highest yield was obtained using water as a solvent (53%). Water extract was rich in protein and carbohydrates as fructans (inulin) were the most abundant carbohydrate constituent. The most exhaustive recovery of the phenolic components was conducted by extraction with 40% ethanol and 60% glycerol. It was found that water is the most suitable extractant for obtaining a polysaccharide-containing complex (PSC) (8.87%). PSC was composed mainly of fructans (inulin) and proteins with different molecular weight distributions. The yield of PSC decreased with an increasing ethanol concentration (40% > 50% > 60%) but the lowest yield was obtained from 60% glycerol extract. The obtained results showed that Echinacea roots contained a large amount of biologically active substances-phenolic components and polysaccharides and that glycerol was equally efficient to ethanol in extracting caffeic acid derivatives from purple coneflower roots. The data can be used for the preparation of extracts having different compositions and thus easily be incorporated into commercial products.

Subcritical Water Extraction of Rosmarinic Acid from Lemon Balm (Melissa officinalis L.) and Its Effect on Plant Cell Wall Constituents.

Rosmarinic acid (RA), an ester of caffeic acid and 3,4-dihydroxyphenyllactic acid, is a potent radical scavenger, a chelator of prooxidant ions, and an inhibitor of lipid peroxidation. RA-containing extracts are widely used natural antioxidants in food products, and many herbal preparations and food supplements, containing RA, are marketed with claims of beneficial health effects. The current study investigated the effectiveness of subcritical water extraction (SWE) for the recovery of RA from lemon balm (Melissa officinalis), as a "green" alternative to conventional hydro-alcoholic extraction. Different durations (10 min and 20 min) and extraction temperatures (100 °C and 150 °C) were applied. Subcritical water applied at a temperature of 100 °C was equally efficient as 50% ethanol in extracting RA. However, the further elevation of temperature to 150 °C decreased RA content by up to 20% due to thermal degradation. The content of RA in dried extracts was between 2.36% and 5.55% and the higher temperature of SWE increased extract yield by up to 41%. The higher extraction yield resulted from the degradation of plant material by subcritical water as evidenced by the increased extraction and degradation of proteins, pectin, and cellulose. These results reveal that SWE is an efficient technology for the extraction of RA and other antioxidants from lemon balm at reduced extraction time and without the use of toxic organic solvents. Furthermore, by modification of SWE conditions, dry extracts with different purity and content of RA are obtained. These extracts could be used in the food industry as food antioxidants, or in the development of food supplements and functional foods.

Chemical characterization and biological effect of exopolysaccharides synthesized by Antarctic yeasts Cystobasidium ongulense AL101 and Leucosporidium yakuticum AL102 on murine innate immune cells.

The current study aimed to investigate exopolysaccharides (EPSs) produced by two Antarctic yeasts isolated from soil and penguin feathers samples collected on Livingston Island (Antarctica). The strains were identified as belonging to the species Leucosporidium yakuticum (LY) and Cystobasidium ongulense (CO) based on molecular genetic analysis. The EPS production was investigated using submerged cultivation. Different chemical, chromatographic, and spectral analyses were employed to characterize EPSs. LY accumulated 5.5 g/L biomass and 4.0 g/L EPS after 120 h of cultivation, while CO synthesized 2.1 g/L EPS at the end of cultivation, and the biomass amount reached 5.5 g/L. LY-EPS was characterized by a higher total carbohydrate content (80%) and a lower protein content (18%) by comparison with CO-EPS (62%, 30%). The LY-EPS mainly consisted of mannose (90 mol%), whereas CO-EPS had also glucose, galactose, and small amounts of uronic acids (8-5 mol%). Spectral analyses (FT-IR and 1D, 2D NMR) revealed that LY-EPS comprised a typical ß-(1 → 4)-mannan. Branched (hetero)mannan, together with ß/α-glucans constituted the majority of CO-EPS. Unlike LY-EPS, which had a high percentage of high molecular weight populations, CO-EPS displayed a large quantity of lower molecular weight fractions and a higher degree of heterogeneity. LY-EPS (100 ng/mL) elevated significantly interferon gamma (IFN-γ) production in splenic murine macrophages and natural killer (NK) cells. The results indicated that newly identified EPSs might affect IFN-γ signaling and in turn, might enhance anti-infectious responses. The data obtained also revealed the potential of EPSs and yeasts for practical application in biochemical engineering and biotechnology.

Addition of Medicinal Plants Increases Antioxidant Activity, Color, and Anthocyanin Stability of Black Chokeberry (Aronia melanocarpa) Functional Beverages.

The present study investigates the effect of the addition of medicinal plants, such as lady's mantle, lavender, rosehip, and meadowsweet, on the chemical composition, antioxidant activity, and color intensity of ready-to-drink aronia nectar during pasteurization and long-term storage. Pasteurization caused a significant decrease in anthocyanin content of aronia nectar, which reduced to 20% of the initial value after four months of storage. Herbs provided different protection to aronia anthocyanins that degraded more slowly during the four-month storage compared to pasteurized control without herbs. The addition of medicinal plants enriched aronia nectar with phenolic compounds and increased its antioxidant activity by up to 52% in meadowsweet-aronia nectar. Moreover, it was accompanied by a color intensity magnification due to co-pigmentation of aronia anthocyanins and herbal phenolics. In contrast to anthocyanins, which constantly degraded during the whole period, color intensity began to stabilize after 30 days, demonstrating that co-pigmentation was progressively established during the time and rosehip provided the best stabilization of aronia nectar color. Current research demonstrates for the first time that medicinal plants such as lady's mantle, rosehip, and especially meadowsweet can be used to increase antioxidant activity, color, and anthocyanin stability of black chokeberry functional beverages.