5-Aminosalicylic Acid, A Weak Agonist for Aryl Hydrocarbon Receptor That Induces Splenic Regulatory T Cells

<b><i>Introduction:</i></b> 5-Aminosalicylic acid (5-ASA) is widely used as a key drug in inflammatory bowel disease. It has been recently reported that 5-ASA induces CD4 + Foxp3 + regulatory T cells (Tregs) in the colon via the aryl hydrocarbon receptor (AhR), a ligand-activated transcription factor that regulates inflammation. However, the role of 5-ASA as an AhR agonist that induces Tregs in the spleen remains unknown. <b><i>Methods:</i></b> In the present study, we investigated these themes using an AhR-mediated transactivation assay and flow cytometry analysis. The experiments were conducted by using DR-EcoScreen cells and C57BL/6 mice. <b><i>Results:</i></b> The DR-EcoScreen cell-based transactivation assay revealed that 5-ASA acted as a weak AhR agonist at concentrations of ≥300 μM (1.31–1.45-fold), and that a typical AhR agonist, 2,3,7,8-tetrachlorodibenzo-<i>p</i>-dioxin (TCDD), activated AhR at a concentration of 0.1 nM (22.8-fold). In addition, the treatment of mouse splenic cells with 300 μM 5-ASA in a primary culture assay significantly induced CD4+CD25 + Foxp3 + Tregs (control vs. 5-ASA: 9.0% vs. 12.65%, <i>p</i> &#x3c; 0.05), while 0.1 nM TCDD also showed significant induction of Tregs (control vs. TCDD: 9.0% vs. 14.1%, <i>p</i> &#x3c; 0.05). Interestingly, this induction was eliminated by co-treatment with an AhR antagonist, CH-223191. <b><i>Discussion:</i></b> These results suggest that 5-ASA is a weak agonist of AhR and thereby induces Tregs in spleen cells. Our findings may provide useful insights into the mechanism by which 5-ASA regulates inflammation.

TLR7 modulating B-cell immune responses in the spleen of C57BL/6 mice infected with Schistosoma japonicum

B cells played an important role in Schistosoma infection-induced diseases. TLR7 is an intracellular member of the innate immune receptor. The role of TLR7 on B cells mediated immune response is still unclear. Here, C57BL/6 mice were percutaneously infected by S. japonicum for 5–6 weeks. The percentages and numbers of B cells increased in the infected mice (p < 0.05), and many activation and function associated molecules were also changed on B cells. More splenic cells of the infected mice expressed TLR7, and B cells were served as the main cell population. Moreover, a lower level of soluble egg antigen (SEA) specific antibody and less activation associated molecules were found on the surface of splenic B cells from S. japonicum infected TLR7 gene knockout (TLR7 KO) mice compared to infected wild type (WT) mice (p < 0.05). Additionally, SEA showed a little higher ability in inducing the activation of B cells from naive WT mice than TLR7 KO mice (p < 0.05). Finally, the effects of TLR7 on B cells are dependent on the activation of NF-κB p65. Altogether, TLR7 was found modulating the splenic B cell responses in S. japonicum infected C57BL/6 mice.

Microlitter pollution in the marine environment and preliminary evidences of in vitro cytotoxic effects on two Mediterranean commercial fish species

Marine litter, which is composed mainly of plastics, is recognized as one of the most serious threats to marine ecosystems and a global environmental concern. Microplastics (MPs) densities were estimated in all environmental compartments: marine organisms are highly exposed to and ingest them, resulting in disruption of biological functions. Ecotoxicological approaches have also started elucidating the potential severity of MPs in controlled laboratory studies, but the commercially-available and pristine materials employed hardly reflect the actual composition of the environmental litter, which can be contaminated by chemical pollutants or biological agents. Building on the lack of research employing marine environmental MPs or microlitter as a whole, we characterized the quantity and quality of litter in the coastal epipelagic and in the digestive tract of two commercially-relevant fish species, and exposed primary cell cultures of mucosal and lymphoid organs to marine microlitter. A concentration of 0.30 ± 0.02 microlitter items m-3 was found in the water column of the Northern Tyrrhenian sea. μFT-IR analysis revealed that particles of plastic origin, namely polypropylene, HDP E and polyamide, were present in 100% and 83.3% of M. merluccius and M. barbatus stomachs, respectively, which overall ingested 14.67 ± 4.10 and 5.50 ± 1.97 items. Microlitter was confirmed as a vector of bacteria, fungi and flagellates. Lastly, and for the first time, the apical end-point of viability was significantly reduced in splenic cells exposed in vitro to two microlitter conditions. Considering the role of the spleen in the mounting of adaptive immune responses, our results warrant more in-depth investigations for clarifying the actual susceptibility of the biota to anthropogenic microliter.

Cell-Mediated Immunoreactivity of Poly(2-isopropenyl-2-oxazoline) as Promising Formulation for Immunomodulation

Poly(2-isopropenyl-2-oxazoline) (PIPOx) represents a functional polymer with high potential for drug delivery, tissue engineering, and immunomodulation. The immunomodulatory efficiency of the PIPOx formulation has been studied in vitro following splenic cells and RAW 264.7 macrophages exposition. The cell-specific immunomodulative effect on production of Th1, Th2, Th17, and Treg signature cytokines has been demonstrated. The impact on the functionality of PIPOx-sensitized RAW 264.7 macrophages was assessed by cell phagocytosis. Time- and concentration-dependent cell internalization and intracellular organelles colocalization of fluorescently labeled PIPOx has been examined. The in vitro results demonstrated the PIPOx bioavailability and the capability of triggering immune cell responses resulting in the induced production of cell-specific signature interleukins, important prerequisite properties for future potential biomedical applications.

Urequinona, a molecule from the root of Pentalinon andrieuxii Muell-Arg heals Leishmania mexicana ear’s infection in mice: This plant is widely used by the Mayan traditional medicine

In this work we tested both the in vitro and in vivo anti-Leishmania mexicana activity of a molecule we originally identified in the root of Pentalinon andrieuxii Muell-Arg, a plant that is widely used in Mayan traditional medicine. The chemical name of this molecule is 24-methylcholesta-4-24(28)-dien-3-one and for simplicity we assigned the short and trivial name of urequinona that will be used throughout this work. It induces necrosis and apoptosis of promastigotes cultured in vitro and extensive ultrastructural damage of both promastigotes and amastigotes. It also induces production of Interleukin (IL)-2 and interferon (IFN)-γ by splenic cells from infected and urequinona treated mice stimulated in vitro with parasite antigen (Ag) but inhibits production of IL-6 and IL-12p70 by bone marrow derived macrophages (BMM) infected in vitro and then treated with urequinona. It also induces activation of transcription factors such as NFkB and AP-1 (NFkB/AP-1) in RAW reporter cells. We also developed a novel pharmaceutical preparation of urequinona encapsulated in hydroxyethyl cellulose for dermal application that significantly reduced experimentally induced ear′s lesions of C57BL/6 mice. We conclude the preparation containing this molecule is a good candidate for a novel anti-leishmanial drug′s preparation.

Lepidium sativum and Its Biogenic Silver Nanoparticles Activate Immune Cells and Induce Apoptosis and Cell Cycle Arrest in HT-29 Colon Cancer Cells

There is an increased demand for plants with antioxidants and anticancer properties. Lepidium sativum L. is an edible plant with medical importance. In this study, we aimed to investigate the anticancer activity; antioxidant capacity and antibacterial impact of Lepidium sativum L. seed acetone extract (LSSAExt), alone and with its biogenic silver nanoparticles (AgNPs). LSSAExt-produced AgNPs were characterized using SEM, XRD and Vis/UV analysis. Biomolecules in LSSAExt and LSSAExt + AgNPs were explored utilizing FTIR. The ability of LSSAExt and LSSAExt + AgNPs to induce apoptosis and mitotic cell arrest in the HT-29 colon cancer cells, compared to normal and repeated cell division activated splenic cells was determined by florescent stains and flow cytometry. Antibacterial power was tested using well diffusion technique. LSSAExt and LSSAExt + AgNPs showed a good antibacterial impact. LSSAExt contains ROS, which could help in cancer cells apoptosis. LSSAExt and LSSAExt+AgNPs were not toxic to splenic cells and increased the rate of their cell division. LSSAExt and LSSAExt+AgNPs increased p53 expression and could arrest cell division of HT-29 colon cancer cells but not of normal fast dividing cells. LSSAExt and LSSAExt+AgNPs caused apoptosis in cancer cells rather than necrosis. In conclusion, acetone preparation of the edible plant L. sativum is a good antibacterial agent, good anticancer preparation at least against colon cancer as it is shown to be targeted, effective and can boost immune cells.

Spleno-adrenal fusion mimicking an adrenal metastasis of a renal cell carcinoma: A case report and embryological background

Foci of splenic tissue separated from the spleen can occur as a congenital anomaly. Isolated nodules of splenic tissue are called accessory spleens or spleniculli. However, nodules of splenic tissue can merge with other organs during embryonic development, in which case we speak of spleno-visceral fusions: most often, they merge with the tail of the pancreas (thus forming spleno-pancreatic fusion or an intrapancreatic accessory spleen), with the reproductive gland (i.e., spleno-gonadal fusion), or with the kidney (i.e., spleno-renal fusion). Our case report describes the fusion of heterotopic splenic tissue with the right adrenal gland, which was misinterpreted as a metastasis of a renal cell carcinoma. To the best of our knowledge, this is the first reported case of spleno-adrenal fusion. Spleno-visceral fusions usually represent asymptomatic conditions; their main clinical significance lies in the confusion they cause and its misinterpretation as tumors of other organs. We believe that the cause of retroperitoneal spleno-visceral fusions is the anomalous migration of splenic cells along the dorsal mesentery to the urogenital ridge, together with primitive germ cells, at the end of the fifth week and during the sixth week of embryonic age. This theory explains the possible origin of spleno-visceral fusions, their different frequency of occurrence, and the predominance of findings on the left side.

Majra Honey Abrogated the Normal and Cancer Cells Proliferation Inhibition by Juniperus procera Extract and Extract/Honey Generated AgNPs

Background: Juniperus procera and Majra honey are well-known as a folk medicine in many countries. Objectives: This work aimed to study the immunomodulatory effects after mixing Majra honey, J. procera water leaves extract and silver Nanoparticles (AgNPs) on immune or cancer cells. Methods: Juniperus procera water leaves extract and 20% Majra honey were prepared. Both the extract and honey were used separately to synthesize AgNPs. AgNPs were characterized using UV/Vis spectrophotometry and electron microscopy. Bioactive molecules in honey and the extract were explored using Fourier Transform Infrared (FT-IR) spectroscopy. Protein profile of honey was explored using Sodium Dodecyl Sulfate- Polyacrylamide Gel Electrophoresis (SDS-PAGE) and honey sugar content was determined using High- Performance Liquid Chromatography (HPLC). Biological activities of honey and the extract were tested. Results: The results demonstrated the ability of the extract/honey to produce AgNPs in a spherical shape. The extract/honey contained many functional groups. SDS-PAGE of Majra honey showed many protein bands. HPLC revealed honey is of good quality and no external additives are added to it. The extract and extract+ AgNPs inhibited the growth of normal rat splenic cells while honey stimulated it. The extract+honey turned stimulatory to the splenic cells’ growth and significantly diminished the inhibitory potential of the extract containing AgNPs. Both the extract and honey have antimicrobial activities, this potential increased in the presence of AgNPs. Honey and Honey+AgNPs inhibited HepG2 cancer cell proliferation while Hela cell growth inhibited only with honey+AgNPs. Conclusion: Both honey and the extract have antibacterial and immunomodulatory potentials as well as the power to produce AgNPs. Majra honey alone showed anticancer activity against HepGe2 cells, but not against Hela cells, and when contained AgNPs had anticancer activity on both cell lines. Mixing of Majra honey with J. procera extract showed characterized immunomodulatory potentials that can be described as immunostimulant.

Hydroxyapatite Nanostructure Doped by Lithium Iodide with Their Biological Activity

The nanostructure of biomaterial samples of Hydroxyapatite (HAp) was treated by microwave radiation treatment with different additives (1, 10, 20, 30 and 40 wt. in percent) of Lithium Iodide (LiI) using the known sol–gel process. The sample crystal structure was achieved through the analysis of X-ray diffraction and some associated parameters like that strain, grain size, and dislocation. The FTIR and Raman spectroscopy investigations identified effective functional groups and their modes. SEM conforms to the sample morphology's fine low-dimensional structure (10–28 nm). The various preparations were studied for their anti-proliferative/anticytotoxicity/stimulatory ability against normal and activated splenic cells of the mouse in vitro and for the lytic effects on red blood cells (RBCs). Results showed that various LiI additives have inhibitory effects on normal splenic cells of the mouse. The pure LiI and Li 10 had relaxing effects on splenic cells activated by the mouse while the other formulations (LiI 20, LiI 30 and LiI 40) displayed inhibitory/cytotoxic results besides that all preparation samples were safe effects to RBCs.