Enantiopure ethyl 2,3-dibromopropionate: Enantioselective synthesis vs preparative HPLC enantioseparation of racemate on multigram scale

Racemic ethyl 2,3-dibromopropionate, commercially available at low price, is a key intermediate used in the synthesis of several heterocycle fragments, which are present in many biologically active compounds. Surprisingly, the enantiomers are not commercially available and have never been described in the literature. In this work, we undertook two different strategies to obtain these enantiomers, which are enantioselective synthesis and preparative HPLC enantioseparation of commercially available racemate on multigram scale. The first strategy has proved inadequate because racemization occurred during the synthesis (ee ≈ 9-50%). Conversely, the second strategy produced a very good enantioseparation of commercially available racemate (ee > 99.5% for both enantiomers) on multigram scale.     

Design,synthesis and molecular docking of novel diarylcyclohexenone and diarylindazole derivatives as tubulin polymerization inhibitors

New target compounds were designed as inhibitors of tubulin polymerization relying on using two types of ring B models (cyclohexenone and indazole) to replace the central ring in colchicine. Different functional groups (R¹) were attached to manipulate their physicochemical properties and/or their biological activity. The designed compounds were assessed for their antitumor activity on HCT-116 and MCF-7 cancer cell lines. Compounds 4b, 5e and 5f exhibited comparable or higher potency than colchicine against colon HCT-116 and MCF-7 tumor cells. The mechanism of the antitumor activity was investigated through evaluating the tubulin inhibition potential of the active compounds. Compounds 4b, 5e and 5f showed percentage inhibition of tubulin in both cell line homogenates ranging from 79.72% to 89.31%. Cell cycle analysis of compounds 4b, 5e and 5f revealed cell cycle arrest at G₂/M phase. Molecular docking revealed the binding mode of these new compounds into the colchicine binding site of tubulin.     

Influence of three rates of salinity on okra plants (Abelmoschus esculentus L.) infected with root-knot nematode in vivo

A greenhouse experiment was carried-out to evaluate the effect of three rates of salinity as abiotic stress on okra plants (Abelmoschus esculentus) infected with the root-knot nematode (Meloidogyne incognita) as biotic stress. Plant lengths and weights were significantly (p?≤?0.05) reduced except root weight and there was a positive correlation between increasing the salinity concentration from 0.1 to 0.3% and increasing the rate of reduction in plant criteria. The number of J2 in soil, galls, and eggmasses were decreased linked to increased salinity rate as compared to nematode control treatment. However, peroxidase and catalase activities were significantly reduced linked to increasing the salinity concentration from 0.1 to 0.3%. There was no significant difference between total phenols at all treatments. Meanwhile, there was no significant improvement in N, P, and K contents whereas photosynthetic pigments (a, b) and carotene were significantly (p?≤?0.05) reduced by nematode infection and increasing the salinity rate from 0.1 to 0.3%.     

Pneumocystis stimulates MCP-1 production by alveolar epithelial cells through a JNK-dependent mechanism

Pneumocystis carinii is an opportunistic fungal pathogen that causes pneumonia (PCP) in immunocompromised individuals. Recent studies have demonstrated that the host's immune response is clearly responsible for the majority of the pathophysiological changes associated with PCP. P. carinii interacts closely with alveolar epithelial cells (AECs); however, the nature and pathological consequences of the epithelial response remain poorly defined. Monocyte chemotactic protein-1 (MCP-1) is involved in lung inflammation, immunity, and epithelial repair and is upregulated during PCP. To determine whether AECs are an important source of MCP-1 in the P. carinii-infected lung, in vivo and in vitro studies were performed. In situ hybridization showed that MCP-1 mRNA was localized to cells with morphological characteristics of AECs in the lungs of infected mice. In vitro studies demonstrated that P. carinii stimulated a time- and dose-dependent MCP-1 response in primary murine type II cells that was preceded by JNK activation. Pharmacological inhibition of JNK nearly abolished P. carinii-stimulated MCP-1 production, while ERK, p38 MAPK, and TNF receptor signaling were not required. Furthermore, delivery of a JNK inhibitory peptide specifically to pulmonary epithelial cells using a recombinant adenovirus vector blocked the early lung MCP-1 response following intratracheal instillation of infectious P. carinii. JNK inhibition did not affect P. carinii-stimulated production of macrophage inflammatory protein-2 in vitro or in vivo, indicating that multiple signaling pathways are activated in P. carinii-stimulated AECs. These data demonstrate that AECs respond to P. carinii in a proinflammatory manner that may contribute to the generation of immune-mediated lung injury.     

Structural characterization and study of immunoenhancing and antioxidant property of a novel polysaccharide isolated from the aqueous extract of a somatic hybrid mushroom of Pleurotus florida and Calocybe indica variety APK2

A water-soluble polysaccharide was isolated from the aqueous extract of the fruit bodies of somatic hybrid PCH9FB, obtained through intergeneric protoplast fusion between the strains Pleurotus florida and Calocybe indica var. On the basis of total acid hydrolysis, the polysaccharide was found to contain galactose, fucose, and glucose in a molar ratio of nearly 2:1:2. Methylation analysis and NMR experiments ((1)H, (13)C, DEPT-135, DQF-COSY, TOCSY, NOESY, ROESY, HMQC, and HMBC) showed that the structure of the repeating unit present in the polysaccharide was This molecule showed macrophage, splenocyte, thymocyte activation as well as antioxidant property.     

Relationship between Obesity and Massive Transfusion Needs in Trauma Patients,and Validation of TASH Score in Obese Population: A Retrospective Study on 910 Trauma Patients

Background

Prediction of massive transfusion (MT) is challenging in management of trauma patients. However, MT and its prediction were poorly studied in obese patients. The main objective was to assess the relationship between obesity and MT needs in trauma patients. The secondary objectives were to validate the Trauma Associated Severe Hemorrhage (TASH) score in predicting MT in obese patients and to use a grey zone approach to optimize its ability to predict MT.

Methods and Findings

An observational retrospective study was conducted in a Level I Regional Trauma Center Trauma in obese and non-obese patients. MT was defined as ≥10U of packed red blood cells in the first 24h and obesity as a BMI≥30kg/m². Between January 2008 and December 2012, 119 obese and 791 non-obese trauma patients were included. The rate of MT was 10% (94/910) in the whole population. The MT rate tended to be higher in obese patients than in non-obese patients: 15% (18/119, 95%CI 9‒23%) versus 10% (76/791, 95%CI 8‒12%), OR, 1.68 [95%CI 0.97‒2.92], p = 0.07. After adjusting for Injury Severity Score (ISS), obesity was significantly associated with MT rate (OR, 1.79[95%CI 1.00‒3.21], p = 0.049). The TASH score was higher in the obese group than in the non-obese group: 7(4–11) versus 5(2–10)(p<0.001). The area under the ROC curves of the TASH score in predicting MT was very high and comparable between the obese and non-obese groups: 0.93 (95%CI, 0.89‒0.98) and 0.94 (95%CI, 0.92‒0.96), respectively (p = 0.80). The grey zone ranged respectively from 10 to 13 and from 9 to 12 in obese and non obese patients, and allowed separating patients at low, intermediate or high risk of MT using the TASH score.

Conclusions

Obesity was associated with a higher rate of MT in trauma patients. The predictive performance of the TASH score and the grey zones were robust and comparable between obese and non-obese patients.     

Comparison of the radial forearm flap and the thinned anterolateral thigh cutaneous flap for reconstruction of tongue defects: an evaluation of donor-site morbidity

The radial forearm flap is commonly used for reconstruction of tongue defects following tumor extirpation. This flap is easy to harvest and offers thin tissue with large-caliber vessels. However, its use leaves behind a conspicuous aesthetic deformity in the forearm and requires the sacrifice of a major artery of that limb, the radial artery. The anterolateral thigh cutaneous flap has found clinical applications in the reconstruction of soft-tissue defects requiring thin tissue. More recently, in a thinned form, the anterolateral thigh flap has been used for reconstructing defects of the tongue with functional results equivalent to that of the radial forearm flap. For the reconstruction of tongue defects, these two flaps could provide similar soft-tissue coverage, but they seem to result in different donor-site appearances. The donor site is closed primarily, leaving only a linear scar that is inconspicuous with normal clothing, and no functional deficit is left behind in the thigh. Thus, for the supply of flaps for tongue defects, a comparison between the radial forearm flap and the anterolateral thigh flap donor sites is provided in this study. Between December of 2000 and August of 2002, 41 patients who underwent reconstruction of defects of the tongue using either a radial forearm flap or an anterolateral thigh flap were evaluated. The focus was on the evaluation of the functional and aesthetic outcome of the donor site after harvesting these flaps for the purpose of reconstructing either total or partial tongue defects. Finally, a comparison was performed between the donor sites of the two flaps. The disadvantages of the radial forearm flap include the conspicuous unattractive scar in the forearm region, pain, numbness, and the sacrifice of a major artery of the limb. In some patients, the donor-site scar of the forearm acted as a social stigma, preventing these patients from leading a normal life. In contrast, the anterolateral thigh cutaneous flap, after thinning, achieved the same results in reconstructing defects of the tongue without the associated donor-site morbidity. Most importantly, the donor site in the thigh could be closed primarily in almost all patients without any functional deficit. The thinned anterolateral thigh cutaneous flap is a viable substitute for the radial forearm flap when reconstructing defects of the tongue. The results achieved are similar to those of the radial forearm flap, and the donor-site morbidity is significantly decreased.     

Cloning and Sequencing of an Original Gene Encoding a Maltogenic Amylase from <Emphasis Type="Italic">Bacillus</Emphasis> sp. US149 Strain and Characterization of the Recombinant Activity

A gene encoding maltogenic amylase from acidic Bacillus sp. US149 (maUS149) was cloned, sequenced and over-expressed in Escherichia coli. The nucleotide sequence analysis revealed an open reading frame (ORF) of 1749 bp encoding a protein of 582 residues. The alignment of deduced amino acid sequence revealed a relatively low homology with the already reported maltogenic amylases. In fact, its highest identity, of only 60%, was found with the maltogenic amylase of Thermus sp. IM6501. The recombinant enzyme (MAUS149) was found to be intracellular and was purified to homogeneity from the cell crude extract with a yield of 23%. According to PAGE analysis, under reducing and non-reducing conditions, the recombinant enzyme has an apparent molecular weight of 135 kDa and is composed of two identical subunits of 67.5 kDa each. The maximum activity was obtained at 40°C and pH 6.5. MAUS149 could be classified as a maltogenic amylase since it produces mainly maltose from starch, maltose and glucose from β-cyclodextrin, and panose from pullulan.     

New costimulatory families: signaling lymphocytic activation molecule in adaptive allergic responses

The generation of an allergic immune response requires at least two signals for complete activation of T cells. Costimulatory molecules are integral to the second signal. In this review, we analyze the costimulatory molecule signaling lymphocytic activation molecule (SLAM) and other recently described SLAM family members. We highlight recent findings that position SLAM as critical for allergic inflammation and its role in modulation of cytokine secretion. Furthermore, a possible role of SLAM as a link between the adaptive and innate immune response is also discussed. Understanding the role of costimulatory molecules, including SLAM and SLAM family members, may elucidate mechanisms involved in the allergic immune response, and suggest potential therapeutic opportunities.