Dietary n-3 fatty acids,curcumin and capsaicin lower the release of lysosomal enzymes and eicosanoids in rat peritoneal macrophages

Male Wistar rats (12 rats/group) were fed a diet containing 8 wt % coconut oil or groundnut oil or cod-liver oil for a total period of 8 weeks. The diets were also supplemented with 2 wt % groundnut oil for providing essential fatty acids. During the last 2 weeks, 6 rats form each group were additionally given curcumin (30 mg/kg body wt/day) or capsaicin (5 mg/kg body wt/day) in 1 ml groundnut oil. The peritoneal macrophages from rats fed cod-liver oil diet secreted lower levels of lysosomal enzymes collagenase, elastase and hyaluronidase as compared to those from rats fed coconut oil or groundnut oil diets. Curcumin and capsaicin significantly lowered the secretion of these lysosomal enzymes from macrophages in animals given coconut oil or groundnut oil diet. Macrophages from rats fed cod-liver oil secreted lower amounts of prostaglandin E₂, 6-keto PGF_1a, leukotrienes B₄and C₄and also incorporated lesser amounts of [^3H]-arachidonic acid as compared to those given coconut oil or groundnut oil diets. Curcumin and capsaicin lowered the secretion of these eicosanoids and decreased the incorporation of [³H]-arachidonic acid in macrophage lipids. However curcumin and capsaicin significantly increased the secretion of 6-keto PGF_1ain all the groups of animals. These studies indicated that dietary cod-liver oil (rich in n-3 fatty acids), and spice principles curcumin and capsaicin can lower the secretory functions of macrophages in a beneficial manner.     

Unexpected equivalent potency of a constrained chromene enantiomeric pair rationalized by co-crystal structures in complex with estrogen receptor alpha

Despite tremendous progress made in the understanding of the ERα signaling pathway and the approval of many therapeutic agents, ER+?breast cancer continues to be a leading cause of cancer death in women. We set out to discover compounds with a dual mechanism of action in which they not only compete with estradiol for binding with ERα, but also can induce the degradation of the ERα protein itself. We were attracted to the constrained chromenes containing a tetracyclic benzopyranobenzoxepine scaffold, which were reported as potent selective estrogen receptor modulators (SERMs). Incorporation of a fluoromethyl azetidine side chain yielded highly potent and efficacious selective estrogen receptor degraders (SERDs), such as 16aa and surprisingly, also its enantiomeric pair 16ab. Co-crystal structures of the enantiomeric pair 16aa and 16ab in complex with ERα revealed default (mimics the A-D rings of endogenous ligand estradiol) and core-flipped binding modes, rationalizing the equivalent potency observed for these enantiomers in the ERα degradation and MCF-7 anti-proliferation assays.     

Adamantinoma. A case report with aspiration cytology and differential diagnostic and immunohistochemical considerations.

Fine needle aspiration biopsy of bone lesions is routinely used in the metastatic workup of patients with radiographically suspicious areas. However, caution must be used when interpreting smears from aspirates performed on primary bone neoplasms. These tumors are often heterogeneous, and problems with sampling may be encountered. We report a case of a 25-year-old male who presented with a 3-cm lytic lesion in the tibia. A diagnosis of benign fibroosseous lesion was based on the clinical presentation, radiographic appearance and presence of numerous sheets and single cytologically bland spindle cells. Subsequent curettage of the specimen revealed an adamantinoma with a prominent fibrous component. Most of these rare, locally aggressive neoplasms are located in the tibia. They are characterized histologically as having a fibrous background with islands of basaloid, spindle or squamoid cells. Furthermore, a differentiated, regressing variant with an osteofibrous dysplasia-like appearance also exists. Smears consisting primarily of spindle cells or fibrous tissue may lead to an erroneous diagnosis of a fibrohistiocytic neoplasm, fibrous dysplasia, fibrous cortical defect or ossifying fibroma. Pertinent cytomorphologic features should aid in establishing the correct diagnosis of adamantinoma.     

The human immune response to saliva of Phlebotomus alexandri,the vector of visceral leishmaniasis in Iraq,and its relationship to sand fly exposure and infection

BackgroundSand fly saliva exposure plays an important role in immunity against leishmaniasis where it has mostly been associated with protection. Phlebotomus (Ph.) alexandri transmits Leishmania (L.) infantum, the causative agent of visceral leishmaniasis (VL), in Iraq. Our group recently demonstrated that 20% of Operation Iraqi Freedom (OIF) deployers had asymptomatic VL (AVL) indicative of prior infection by the parasite L. infantum. Little is known about Ph. alexandri saliva, and the human immune response to it has never been investigated. Here, we characterize the humoral and cellular immune response to vector saliva in OIF deployers naturally exposed to bites of Ph. alexandri and characterize their immunological profiles in association to AVL.Methodology/Principal findingsThe humoral response to Ph. alexandri salivary gland homogenate (SGH) showed that 64% of 200 OIF deployers developed an antibody response. To assess the cellular immune response to saliva, we selected a subcohort of subjects based on their post-travel (median 4 months; range 1–22 months) antibody response (SGH Antibody [Ab] positive or negative) as well as their AVL status; ten never-traveled controls were also included. Banked peripheral blood mononuclear cells (PBMC), collected ~10 years after end of deployment, were stimulated with SGH for 96 hours. The levels of IFN- γ, IL-6, IL-10, IL-13 and IL-17 were determined by ELISA. Our findings indicate that OIF deployers mounted a cellular response to SGH where the anti-SGH+ asymptomatic subjects developed the highest cytokine levels. Further, stimulation with SGH produced a mixture of pro-inflammatory and anti-inflammatory cytokines. Contrary to our hypothesis, we observed no correlation between the cellular immune response to Ph. alexandri SGH and prevention from asymptomatic infection with L. infantum.Conclusions/SignificanceAs we found, although all infected deployers demonstrated persistent disease control years after deployment, this did not correlate with anti-saliva systemic cellular response. More exposure to this vector may facilitate transmission of the L. infantum parasite. Since exposure to saliva of Ph. alexandri may alter the human immune response to bites of this vector, this parameter should be taken into consideration when considering the VL risk.     

Bioethanol from Macroalgal Biomass: Utilization of Marine Yeast for Production of the Same

The present study deals with the first systematic study on the isolation, characterization, and utilization of marine yeast for bioethanol production using seaweed biomass. The ability and efficiency of isolated marine yeast to grow and ferment sugar to ethanol in the presence of 2.5 % to 15 % salt concentration was validated by fermenting galactose in the presence of different salts at varied concentrations. Successively, this yeast was employed for fermentation of seaweed hydrolysate, containing high salt concentration, to ethanol. The hydrolysate having varying sugar as well as salt contents, from 2.7 % to 5.5 % and from 6.25 to 11.25 %, respectively, yielded 1.23–1.76 % ethanol. Through biochemical, fatty acid methyl ester analysis, and BioLog, the yeast was identified as Candida sp. The ability of this yeast to function at high salinity can be commercialized for its use to convert seaweed polysaccharide based hydrolysate, rich in salt, to ethanol without desalting process, ultimately making the process more efficient and economically viable. This is the first organized study for the utilization of marine yeast for converting Kappaphycus alvarezii, a red algal biomass, into ethanol as a byproduct, under highly saline condition.