Evaluation of plant phenolic metabolites as a source of Alzheimer's drug leads.

Epidemiological studies have proven an association between consumption of polyphenols and prevention of Alzheimer's disease, the most common form of dementia characterized by extracellular deposition of amyloid beta plaques. The aim of this study is pharmacological screening of the aqueous alcohol extract of Markhamia platycalyx leaves, Schotia brachypetala leaves and stalks, and piceatannol compared to aqueous alcohol extract of Camellia sinensis leaves as potential Alzheimer's disease drugs. LC-HRESI(-ve)-MS(n) was performed to identify phenolics' profile of Schotia brachypetala stalks aqueous alcohol extract and revealed ten phenolic compounds as first report: daidzein, naringin, procyanidin isomers, procyanidin dimer gallate, quercetin 3-O-rhamnoside, quercetin 3-O-glucuronide, quercetin hexose gallic acid, quercetin hexose protocatechuic acid, and ellagic acid.

The accuracy of computer-assisted primary mandibular reconstruction with vascularized bone flaps: iliac crest bone flap versus osteomyocutaneous fibula flap.

Background: The intention of mandibular reconstruction is to restore the complex anatomy with maximum possible functionality and high accuracy. The aim of this study was to evaluate the accuracy of computer-assisted surgery in primary mandibular reconstruction with an iliac crest bone flap compared with an osteomyocutaneous fibula flap.

Materials And Methods: Preoperative computed tomography data of the mandible and the iliac crest or fibula donor site were imported into a specific surgical planning software program.

Computer-Aided Mandibular Reconstruction With Vascularized Iliac Crest Bone Flap and Simultaneous Implant Surgery.

The intention of oral rehabilitation in patients with mandibular defects is an early prosthetic treatment with maximum possible functionality and high accuracy. The present study describes a new computer-aided technique for mandibular reconstruction using a free vascularized iliac flap and simultaneous insertion of dental implants into the flap while it is still pedicled at the donor site. Based on preoperative computerized tomography data of the facial skeleton and the iliac crest donor site, a surgical guide transferred the virtual plan including information on the transplant dimensions and shape as well as the position of the dental implants into real-time surgery.

Dramatic expansion of the black widow toxin arsenal uncovered by multi-tissue transcriptomics and venom proteomics.

Background: Animal venoms attract enormous interest given their potential for pharmacological discovery and understanding the evolution of natural chemistries. Next-generation transcriptomics and proteomics provide unparalleled, but underexploited, capabilities for venom characterization. We combined multi-tissue RNA-Seq with mass spectrometry and bioinformatic analyses to determine venom gland specific transcripts and venom proteins from the Western black widow spider (Latrodectus hesperus) and investigated their evolution.

Multi-tissue transcriptomics of the black widow spider reveals expansions, co-options, and functional processes of the silk gland gene toolkit.

Background: Spiders (Order Araneae) are essential predators in every terrestrial ecosystem largely because they have evolved potent arsenals of silk and venom. Spider silks are high performance materials made almost entirely of proteins, and thus represent an ideal system for investigating genome level evolution of novel protein functions. However, genomic level resources remain limited for spiders.

Olive phenolics as c-Met inhibitors: (-)-Oleocanthal attenuates cell proliferation, invasiveness, and tumor growth in breast cancer models.

Dysregulation of the Hepatocyte growth factor (HGF)/c-Met signaling axis upregulates diverse tumor cell functions, including cell proliferation, survival, scattering and motility, epithelial-to-mesenchymal transition (EMT), angiogenesis, invasion, and metastasis. (-)-Oleocanthal is a naturally occurring secoiridoid from extra-virgin olive oil, which showed antiproliferative and antimigratory activity against different cancer cell lines. The aim of this study was to characterize the intracellular mechanisms involved in mediating the anticancer effects of (-)-oleocanthal treatment and the potential involvement of c-Met receptor signaling components in breast cancer.

Entrapment into nanoemulsions potentiates the anticancer activity of tocotrienols against the highly malignant (+SA) mouse mammary epithelial cells.

The highly malignant +SA mouse mammary epithelial cells were used as the model cell line over the years to establish the anticancer activity of tocotrienols. Tocotrienols, however, have poor oral bioavailability and were therefore entrapped into parenteral nanoemulsions for parenteral administration. The objective of this work was to test whether the activity of tocotrienols in lipid nanoemulsions against the +SA cells was retained.

KDM4C (GASC1) lysine demethylase is associated with mitotic chromatin and regulates chromosome segregation during mitosis.

Various types of human cancers exhibit amplification or deletion of KDM4A-D members, which selectively demethylate H3K9 and H3K36, thus implicating their activity in promoting carcinogenesis. On this basis, it was hypothesized that dysregulated expression of KDM4A-D family promotes chromosomal instabilities by largely unknown mechanisms. Here, we show that unlike KDM4A-B, KDM4C is associated with chromatin during mitosis.

Evaluation of computer-assisted mandibular reconstruction with vascularized iliac crest bone graft compared to conventional surgery: a randomized prospective clinical trial.

Background: Computer-assisted surgery plays an increasingly important role in mandibular reconstruction, ensuring the best possible masticatory function and aesthetic outcome.

Methods: Twenty patients were randomly assigned to computer-assisted or conventional mandibular reconstruction with vascularized iliac crest bone graft in a prospective study design.Virtual surgical planning was based on preoperative CT-data using specific surgical planning software.

Three-dimensional evaluation of the different donor sites of the mandible for autologous bone grafts.

Objectives: For effective placement of endosseous implants, a sufficient volume of bone is required at the recipient site. The aim of this study is to evaluate the density and maximum amount of harvestable bone graft required from the mandible symphysis, coronoid process, and ascending ramus, depending on dentition.

Materials And Methods: CT data from 42 patients (13 females and 29 males) in DICOM format were read using special planning software.

Tumor cell transformation using antisense oligonucleotide.

Major histocompatibility complex (MHC) Class II-positive, invariant chain (Ii)-suppressed tumor cells induce both T helper and cytotoxic T lymphocytes' responses. Genetically controlled immunotherapy could be utilized for prophylactic vaccination of tumor-free individuals who are at high risk of developing tumor and can be therapeutic for treating established tumors that are nonresponsive to existing therapies. In this chapter, we provide practical methods to create a potent in vivo tumor cell vaccine by inducing MHC Class II and Ii using MHC Class II transactivator (CIITA) or interferon-gamma (IFN-γ) and subsequently inhibiting Ii by antisense oligonucleotides.

Intragenic homogenization and multiple copies of prey-wrapping silk genes in Argiope garden spiders.

Background: Spider silks are spectacular examples of phenotypic diversity arising from adaptive molecular evolution. An individual spider can produce an array of specialized silks, with the majority of constituent silk proteins encoded by members of the spidroin gene family. Spidroins are dominated by tandem repeats flanked by short, non-repetitive N- and C-terminal coding regions.

PARP1-dependent recruitment of KDM4D histone demethylase to DNA damage sites promotes double-strand break repair.

Members of the lysine (K)-specific demethylase 4 (KDM4) A-D family of histone demethylases are dysregulated in several types of cancer. Here, we reveal a previously unrecognized role of KDM4D in the DNA damage response (DDR). We show that the C-terminal region of KDM4D mediates its rapid recruitment to DNA damage sites.

Computer-assisted zygoma reconstruction with vascularized iliac crest bone graft.

Background: The reconstruction of zygoma is a challenge with regard to aesthetic and reconstructive demands.

Methods: Pre-operative CT data were imported into specific surgical planning software. The mirror-imaging technique was used.

Complex gene expression in the dragline silk producing glands of the Western black widow (Latrodectus hesperus).

Background: Orb-web and cob-web weaving spiders spin dragline silk fibers that are among the strongest materials known. Draglines are primarily composed of MaSp1 and MaSp2, two spidroins (spider fibrous proteins) expressed in the major ampullate (MA) silk glands. Prior genetic studies of dragline silk have focused mostly on determining the sequence of these spidroins, leaving other genetic aspects of silk synthesis largely uncharacterized.

Indole diterpene alkaloids as novel inhibitors of the Wnt/β-catenin pathway in breast cancer cells.

Penitrems are indole diterpene alkaloids best known for their BK channel inhibition and tremorgenic effects in mammals. In a previous study, penitrems A-F (1-5), their biosynthetic precursors, paspaline (6) and emindole SB (7), and two brominated penitrem analogs 8 and 9 demonstrated promising in vitro antiproliferative, antimigratory, and anti-invasive effects in the MTT (MCF-7 and MDA-MB-231), wound-healing, and Cultrex BME cell invasion (MDA-MB-231) assays, respectively. The study herein reports the novel ability of penitrem A to suppress total β-catenin levels in MDA-MB-231 mammary cancer cells.

An audit on public awareness of depression symptoms in Jordan.

Objectives: Depression is a common mental health disorder. The aim of this study is to determine the level of public awareness regarding this illness, its symptoms, associated factors, available forms of treatment, and the attitude towards depressed people.

Methods: A self administered questionnaire was filled in by approximately 5000 individuals selected from various regions of Jordan.

Combined γ-tocotrienol and Met inhibitor treatment suppresses mammary cancer cell proliferation, epithelial-to-mesenchymal transition and migration.

Objectives: Dysregulation of Met signalling is associated with malignant transformation. Combined treatment has been shown to reduce Met activation and mammary tumour cell proliferation. Experiments here, were conducted to determine mechanisms involved in mediating anti-cancer effects of combined γ-tocotrienol and SU11274 (Met inhibitor) treatment in various mammary cancer cell lines.

A cancer-associated BRCA2 mutation reveals masked nuclear export signals controlling localization.

Germline missense mutations affecting a single BRCA2 allele predispose humans to cancer. Here we identify a protein-targeting mechanism that is disrupted by the cancer-associated mutation, BRCA2(D2723H), and that controls the nuclear localization of BRCA2 and its cargo, the recombination enzyme RAD51. A nuclear export signal (NES) in BRCA2 is masked by its interaction with a partner protein, DSS1, such that point mutations impairing BRCA2-DSS1 binding render BRCA2 cytoplasmic.

Potential role of tocotrienols in the treatment and prevention of breast cancer.

Vitamin E is a generic term that refers to a family of compounds that is further divided into two subgroups called tocopherols and tocotrienols. Although all natural forms of vitamin E display potent antioxidant activity, tocotrienols are significantly more potent than tocopherols in inhibiting tumor cell growth and viability, and anticancer activity of tocotrienols is mediated independently of their antioxidant activity. In addition, the anticancer effects of tocotrienols are observed using treatment doses that have little or no effect on normal cell function or viability.

Hemocyanin gene family evolution in spiders (Araneae), with implications for phylogenetic relationships and divergence times in the infraorder Mygalomorphae.

Hemocyanins are multimeric copper-containing hemolymph proteins involved in oxygen binding and transport in all major arthropod lineages. Most arachnids have seven primary subunits (encoded by paralogous genes a-g), which combine to form a 24-mer (4×6) quaternary structure. Within some spider lineages, however, hemocyanin evolution has been a dynamic process with extensive paralog duplication and loss.

Heat shock protein 90 (Hsp90) selectively regulates the stability of KDM4B/JMJD2B histone demethylase.

The family of KDM4A-D histone demethylases selectively demethylates H3K9 and H3K36 and is implicated in key cellular processes including DNA damage response, transcription, cell cycle regulation, cellular differentiation, senescence, and carcinogenesis. Various human cancers exhibit elevated protein levels of KDM4A-D members, and their depletion impairs tumor formation, suggesting that their enhanced activity promotes carcinogenesis. However, the mechanisms regulating the KDM4 protein stability remain largely unknown.

Tocotrienols target PI3K/Akt signaling in anti-breast cancer therapy.

The PI3K/Akt signaling pathway mediates mitogen-dependent growth and survival in various types of cancer cells, and inhibition of this pathway results in tumor cell growth arrest and apoptosis. Tocotrienols are natural forms of vitamin E that displays potent anticancer activity at treatment doses that had little or no effect on normal cell viability. Mechanistic studies revealed that the anticancer effects of γ-tocotrienol were associated with a suppression in PI3K/Akt signaling.

Sesamin synergistically potentiates the anticancer effects of γ-tocotrienol in mammary cancer cell lines.

γ-Tocotrienol and sesamin are phytochemicals that display potent anticancer activity. Since sesamin inhibits the metabolic degradation of tocotrienols, studies were conducted to determine if combined treatment with sesamin potentiates the antiproliferative effects of γ-tocotrienol on neoplastic mouse (+SA) and human (MCF-7 and MDA-MB-231) mammary cancer cells. Results showed that treatment with γ-tocotrienol or sesamin alone induced a significant dose-responsive growth inhibition, whereas combination treatment with these agents synergistically inhibited the growth of +SA, MCF-7 and MDA-MB-231 mammary cancer cells, while similar treatment doses were found to have little or no effect on normal (mouse CL-S1 and human MCF-10A) mammary epithelial cell growth or viability.

Management of recurrent hepatocellular carcinoma in liver transplant recipients: a systematic review.

Hepatocellular carcinoma is the most common form of liver cancer, representing 70% to 85% of primary hepatic malignancies in adults. Liver transplant is an optimal treatment for patients with hepatocellular carcinoma because it eliminates the malignancy as well as the often-underlying liver cirrhosis and restores normal liver function. Since the development of strict selection criteria in hepatocellular carcinoma patients undergoing liver transplant with the implementation of the Milan criteria, patient survival and recurrence rates after liver transplant have dramatically improved.