Phenyllactic acid but not tropic acid is an intermediate in the biosynthesis of tropane alkaloids in Datura and Brugmansia transformed root cultures

(S)-(-)-Tropic acid is the acidic moiety of the tropane ester alkaloids, hyoscyamine and scopolamine (hyoscine). When tropic acid is fed to transformed root cultures of Datura stramonium L. or a Brugmansia (Datura) Candida x B. aurea hybrid, the formation of these alkaloids is inhibited. Phenyllactic acid, from which the tropoyl moiety is derived, is considerably less inhibitory. Label from (RS)-phenyl[1,3-¹³C₂]lactic acid is incorporated at high levels into apoatropine, littorine, aposcopolamine, hyoscyamine, 7-hydroxyapoatropine, scopolamine and 7-hydroxyhyoscyamine when fed to these cultures. The presence of an excess concentration of unlabelled tropic acid has little influence on the specific incorporation into these products. It is concluded that free tropic acid is not an intermediate in hyoscyamine biosynthesis but rather that the rearrangement of phenyllactic acid occurs subsequent to its esterification.Abbreviations FM fresh mass - NMR nuclear magnetic resonance spectroscopy We are grateful to Drs. N.J. Walton, A.J. Parr, M.J.C. Rhodes (Institue of Food Research, Norwich) and B. Dräger (Münster, Germany) for helpful and critical discussions. We also wish to thank Dr. P. Bachmann (Braunschweig, Germany) for suggesting the use of the DB-17 column to separate littorine from hyoscyamine and for the modified Excel programme used to calculate the specific incorporations, Yannick Ford (AFRC Co-operative Award Studentship, University of Oxford) and Abigael Peerless for their able assistance, Dr. I. Colquhoun for assistance with some of the NMR spectroscopy and Drs. K. Shimomura (Tsukuba, Japan) and T. Hashimoto (Kyoto, Japan) for pure samples of 7-hydroxyhyoscyamine. J.G.W, gratefully acknowledges support from the Nuffield Foundation under the Small Grants Scheme to promote collaborative experimentation and M.A. is grateful to the Ministry of Education, Iran for a research scholarship.     

Incorporation of the Tat cell‐penetrating peptide into nanofibers improves the respective antitumor immune response

A major challenge for the development of anticancer vaccines is the induction of a safe and effective immune response, particularly mediated by CD8+ T lymphocytes, in an adjuvant‐free manner. In this respect, we present a simple strategy to improve the specific CD8+ T cell responses using KFE8 nanofibers bearing a Class I (Kb)‐restricted peptide epitope (called E. nanofibers) without the use of adjuvant. We demonstrate that incorporation of Tat, a cell‐penetrating peptide (CPP) of the HIV transactivator protein, into E. nanofibers remarkably enhanced tumor‐specific CD8+ T cell responses. E. nanofibers containing 12.5% Tat peptide (E.Tat_12.5 nanofiber) increased antigen cross‐presentation by bone marrow‐derived dendritic cells as compared with E. nanofibers, or E. nanofibers containing 25 or 50% the Tat peptide. Uptake of KFE8.Tat_12.5 nanofibers by dendritic cells (DCs) was significantly increased compared with KFE8 nanofiber lacking Tat. Peritoneal and lymph node DCs of mice immunized with E.Tat_12.5 nanofibers exhibited increased presentation of the H2kb‐epitope (reminiscent for cross‐presentation) compared with DCs obtained from E. nanofiber vaccinated mice. Tetrameric and intracellular cytokine staining revealed that vaccination with E.Tat_12.5 triggered a robust and specific CD8+ T lymphocyte response, which was more pronounced than in mice vaccinated with E. nanofibers alone. Furthermore, E.Tat_12.5 nanofibers were more potent than E. nanofiber to induce antitumor immune response and tumor‐infiltrating IFN‐γ CD8 T lymphocyte. In terms of cancer vaccine development, we propose that harnessing the nanofiber‐based vaccine platform with incorporated Tat peptide could present a simple and promising strategy to induce highly effective antitumor immune response.     

Evaluation of serum level of substance P and tissue distribution of NK-1 receptor in colorectal cancer

Colorectal cancer (CRC) is known as the most common form of malignancies in the world and its occurrence is annually increasing. Due to the relatively high death rates in patients, finding better diagnostic and prognostic factors are required. Substance P (SP) belongs to the tachykinin family that acts as an immunomodulator by binding to the neurokinin-1 receptor (NK1R). The interaction of SP with NK1R might be involved in tumor cell proliferation, angiogenesis, and migration. Hence, this study was aimed to evaluate the serum SP level and tissue distribution of NK1Rs in CRC. Also, we assessed the relationship between tissue distribution of NK1R and some different tumor characteristics, including tumor size, and lymph node status. Recruiting 38 patients primarily diagnosed with CRC, the tissue distribution of NK1R was immunohistochemically evaluated in tumor tissues and their adjacent normal tissue. The serum level of SP was measured using an ELISA method in both cases and healthy control group. The SP value was significantly increased in the serum of patients in comparison with the healthy group (p?=?0.001). Tumor tissues expressed a higher number of NK1R than adjacent normal tissues (p?=?0.01) considering both the percentage of stained cells and intensity of staining. However, there was not any statistically significant relevance between NK1R distribution and tumor characteristics. The SP/NK1R system is involved in tumorigenesis of CRC, and might be suggested as a potent prognostic or diagnostic factor, or a new target in the treatment of CRC.

     

Sensitive Hemoglobin Concentration Sensor Based on Graphene-Plasmonic Nano-structures

Plasmonics - In this paper, half-cylindrical-shaped rods are arranged in a row in order to form hemoglobin concentration sensors. The proposed structures can effectively detect hemoglobin...     

Diagnostic biomarker and therapeutic target applications of miR-326 in cancers: A systematic review

MicroRNAs (miRNAs) are endogenous mediators of RNA interference and have key roles in the modulation of gene expression under healthy, inflamed, stimulated, carcinogenic, or other cells, and tissues of a pathological state. Many studies have proved the association between miRNAs and cancer. The role of miR-326 as a tumor suppressor miRNA in much human cancer confirmed. We will explain the history and the role of miRNAs changes, especially miR-326 in cancers and other pathological conditions. Attuned with these facts, this review highlights recent preclinical and clinical research performed on miRNAs as novel promising diagnostic biomarkers of patients at early stages, prediction of prognosis, and monitoring of the patients in response to treatment. All related publications retrieved from the PubMed database, with keywords such as epigenetic, miRNA, microRNA, miR-326, cancer, diagnostic biomarker, and therapeutic target similar terms from 1899 to 2018 with limitations in the English language. Recently, researchers have focused on the impacts of miRNAs and their association in inflammatory, autoinflammatory, and cancerous conditions. Recent studies have suggested a major pathogenic role in cancers and autoinflammatory diseases. Investigations have explained the role of miRNAs in cancers, autoimmunity, and autoinflammatory diseases, and so on. The miRNA-326 expression has an important role in cancer conditions and other diseases.     

Detection of Contracaecum multipapillatum (Nematoda: Anisakidae) in the indigenous killifish Aphanius hormuzensis (Teleostei; Aphaniidae) and its histopathological effects: A review of Iranian Aphanius species parasites

The present study reports the occurrence of Contracaecum multipapillatum (Nematoda: Anisakidae) in an indigenous small killifish, Aphanius hormuzensis Teimori, Esmaeili, Hamidan, Reichenbacher, 2018 from Southern Iran and shows its histopathology. A total of 110 A. hormuzensis specimens were collected from Shur (Naband) River, Hormuzgan basin in Southern Iran and examined for their possible parasitic infections. Third‐stage larva of C. multipapillatum was extracted for the first time from the body cavity of 19 fish specimens (one male and 18 female) and identified by molecular and morphological methods. In comparison with non‐infected fishes, the melanomacrophage centers were detected in the tissue sections from liver, kidney and spleen of all the parasite infected fishes. To date, 16 parasites belong to nine families have been recorded from six Aphanius species (out of 15 known species) in Iran. Among them, eight and four parasites have been identified from A. vladykovi, and A. hormuzensis respectively. Since Aphanius species are living in different environments, therefore, they seem to be good hosts for the different types of parasites, and more new parasites are expected to be found in these fishes.