Curcumin complexation with cyclodextrins by the autoclave process: Method development and characterization of complex formation.

One approach to enhance curcumin (CUR) aqueous solubility is to use cyclodextrins (CDs) to form inclusion complexes where CUR is encapsulated as a guest molecule within the internal cavity of the water-soluble CD. Several methods have been reported for the complexation of CUR with CDs. Limited information, however, is available on the use of the autoclave process (AU) in complex formation.

Diabetes-Induced Reactive Oxygen Species: Mechanism of Their Generation and Role in Renal Injury.

Diabetes induces the onset and progression of renal injury through causing hemodynamic dysregulation along with abnormal morphological and functional nephron changes. The most important event that precedes renal injury is an increase in permeability of plasma proteins such as albumin through a damaged glomerular filtration barrier resulting in excessive urinary albumin excretion (UAE). Moreover, once enhanced UAE begins, it may advance renal injury from progression of abnormal renal hemodynamics, increased glomerular basement membrane (GBM) thickness, mesangial expansion, extracellular matrix accumulation, and glomerulosclerosis to eventual end-stage renal damage.

Dizziness: Approach to Evaluation and Management.

Dizziness is a common yet imprecise symptom. It was traditionally divided into four categories based on the patient's history: vertigo, presyncope, disequilibrium, and light-headedness. However, the distinction between these symptoms is of limited clinical usefulness.

Megakaryocyte expansion and macrophage infiltration in bone marrow of rats subchronically treated with MNX, N-nitroso environmental degradation product of munitions compound RDX (hexahydro-1,3,5-trinitro-1,3,5-triazine).

Hexahydro-1-nitroso-3,5-dinitro-1,3,5-triazine (MNX), environmental degradation product of munitions hexahydro-1,3,5-trinitro-1,3,5-triazine (RDX), causes seizures in rats with acute oral exposure like parent RDX. Our previous studies have additionally reported hematotoxicity with acute MNX exposure manifested as myelosuppression, anemia and splenic hemosiderosis. This study explored whether MNX administered subchronically continued to target bone marrow to elicit peripheral blood cytopenia.

Synthesis, characterization, and in-vitro antitumor activity of the polyethylene glycol (350 and 1000) succinate derivatives of the tocopherol and tocotrienol isomers of Vitamin E.

Vitamin E refers to a group of saturated tocopherol (T) isomers and the biologically more active unsaturated tocotrienol (T) isomers. PEGylated α-tocopherol, commercially known as Vitamin E TPGS, has been used as an emulsifier and therapeutic agent for children with vitamin E deficiency. Limited information, however, is available about the PEG conjugates of the tocotrienol isomers of vitamin E.

High-intensity interval training and athletic performance in Taekwondo athletes.

Background: The purpose of this study was to determine the effects of high-intensity interval training (HIIT) on athletic performance in Taekwondo athletes.

Methods: Thirty-three male and female collegiate Taekwondo athletes were randomly divided into a HIIT group (N.=16) or a high-intensity continuous running (HICR) group (N.

Prophage-mediated defence against viral attack and viral counter-defence.

Temperate phages are common, and prophages are abundant residents of sequenced bacterial genomes. Mycobacteriophages are viruses that infect mycobacterial hosts including Mycobacterium tuberculosis and Mycobacterium smegmatis, encompass substantial genetic diversity and are commonly temperate. Characterization of ten Cluster N temperate mycobacteriophages revealed at least five distinct prophage-expressed viral defence systems that interfere with the infection of lytic and temperate phages that are either closely related (homotypic defence) or unrelated (heterotypic defence) to the prophage.

Amylin Enhances Amyloid-β Peptide Brain to Blood Efflux Across the Blood-Brain Barrier.

Findings from Alzheimer's disease (AD) mouse models showed that amylin treatment improved AD pathology and enhanced amyloid-β (Aβ) brain to blood clearance; however, the mechanism was not investigated. Using the Tg2576 AD mouse model, a single intraperitoneal injection of amylin significantly increased Aβ serum levels, and the effect was abolished by AC253, an amylin receptor antagonist, suggesting that amylin effect could be mediated by its receptor. Subsequent mechanistic studies showed amylin enhanced Aβ transport across a cell-based model of the blood-brain barrier (BBB), an effect that was abolished when the amylin receptor was inhibited by two amylin antagonists and by siRNA knockdown of amylin receptor Ramp3.

The marine-derived pachycladin diterpenoids as novel inhibitors of wild-type and mutant EGFR.

Epidermal growth factor receptor (EGFR) is a key player in proliferation and metastasis of various cancers. Discovery of novel EGFR inhibitors is still an urgent clinical oncology unmet need. Pachycladins are eunicellin-based diterpenoids isolated from the soft coral Cladiella pachycladous species.

Role of Rac1/WAVE2 Signaling in Mediating the Inhibitory Effects of γ-Tocotrienol on Mammary Cancer Cell Migration and Invasion.

The majority of breast cancer deaths result from the progression of this disease to a metastatic phenotype. Rac1 and Cdc42 are Rho family members that together with their downstream effectors, Wiskott-Aldrich Syndrome protein-family verprolin-homologous protein 2 (WAVE2) and Arp2/3, play an important role in cytoskeletal reorganization and the formation of membrane protrusions that promote cancer cell migration and invasion. γ-Tocotrienol, is a natural isoform within the vitamin E family of compounds that inhibits breast cancer cell growth and progression by suppressing various signaling pathways involved in mitogenic signaling and metastatic progression.

Role of agents for reversing the effects of target-specific oral anticoagulants.

Purpose: The available clinical data on target-specific oral anticoagulant (TSOAC) reversal agents that are currently in development or have been approved by the Food and Drug Administration (FDA) are reviewed.

Summary: The development of TSOACs such as dabigatran, rivaroxaban, edoxaban, and apixaban has presented benefits and new challenges. One of the main challenges associated with the use of TSOACs is the lack of suitable agent-specific reversal agents.

Astaxanthin and Docosahexaenoic Acid Reverse the Toxicity of the Maxi-K (BK) Channel Antagonist Mycotoxin Penitrem A.

Penitrem A (PA) is a food mycotoxin produced by several terrestrial and few marine species. PA is a potent tremorgen through selective antagonism of the calcium-dependent potassium BK (Maxi-K) channels. Discovery of natural products that can prevent the toxic effects of PA is important for food safety.

Implementation of Problem-Based Learning by Faculty Members at 12 U.S. Medical and Dental Schools.

The aim of this study was to assess the perspectives of medical and dental faculty members regarding implementation of problem-based learning (PBL). A survey instrument was designed with demographic questions and two open-ended questions to investigate faculty members' perceptions of the most suitable subjects or courses in which to use PBL and examples of how they incorporated PBL into their instruction. The survey was sent to 12 U.

(1S,2E,4S,7E,11E)-2,7,11-Cembratriene-4,6-diol semisynthetic analogs as novel c-Met inhibitors for the control of c-Met-dependent breast malignancies.

(1S,2E,4S,6R,7E,11E)-2,7,11-Cembratriene-4,6-diol (1) and its 4-epi-analog (2) are the cembranoid precursors to several key flavor ingredients in most Nicotiana (tobacco) species. Nearly 40-60% of 1 and 2 are purposely degraded during the commercial tobacco fermentation. However, 1 and 2 display promising bioactivities, including anticancer.

Design of a doxorubicin-peptidomimetic conjugate that targets HER2-positive cancer cells.

Doxorubicin (DOX) belongs to the anthracycline class of drugs that are used in the treatment of various cancers. It has limited cystostatic effects in therapeutic doses, but higher doses can cause cardiotoxicity. In the current approach, we conjugated a peptidomimetic (Arg-aminonaphthylpropionic acid-Phe, compound 5) known to bind to HER2 protein to DOX via a glutaric anhydride linker.

Targeting of the epidermal growth factor receptor with mesoporphyrin IX-peptide conjugates.

The synthesis and evaluation of four mesoporphyrin IX-peptide conjugates designed to target EGFR, over-expressed in colorectal and other cancers, are reported. Two peptides with known affinity for EGFR, LARLLT () and GYHWYGYTPQNVI (), were conjugated to mesoporphyrin IX (MPIX, ) one or both the propionic side chains, directly (, ) or with a triethylene glycol spacer (, ). The conjugates were characterized using NMR, MS, CD, SPR, UV-vis and fluorescence spectroscopies.

Hindbrain A2 noradrenergic neuron adenosine 5'-monophosphate-activated protein kinase activation, upstream kinase/phosphorylase protein expression, and receptivity to hormone and fuel reporters of short-term food deprivation are regulated by estradiol.

Estradiol (E) mitigates acute and postacute adverse effects of 12 hr-food deprivation (FD) on energy balance. Hindbrain 5'-monophosphate-activated protein kinase (AMPK) regulates hyperphagic and hypothalamic metabolic neuropeptide and norepinephrine responses to FD in an E-dependent manner. Energy-state information from AMPK-expressing hindbrain A2 noradrenergic neurons shapes neural responses to metabolic imbalance.

Inhibition of glucosylceramide synthase eliminates the oncogenic function of p53 R273H mutant in the epithelial-mesenchymal transition and induced pluripotency of colon cancer cells.

Missense mutation of tumor suppressor p53, which exhibits oncogenic gain-of-function (GOF), not only promotes tumor progression, but also diminishes therapeutic efficacies of cancer treatments. However, it remains unclear how a p53 missense mutant contributes to induced pluripotency of cancer stem cells (CSCs) in tumors exposed to chemotherapeutic agents. More importantly, it may be possible to abrogate the GOF by restoring wild-type p53 activity, thereby overcoming the deleterious effects resulting from heterotetramer formation, which often compromises the efficacies of current approaches being used to reactivate p53 function.

Effect of mouse strain as a background for Alzheimer's disease models on the clearance of amyloid-β.

Novel animal models of Alzheimer's disease (AD) are relentlessly being developed and existing ones are being fine-tuned; however, these models face multiple challenges associated with the complexity of the disease where most of these models do not reproduce the full phenotypical disease spectrum. Moreover, different AD models express different phenotypes that could affect their validity to recapitulate disease pathogenesis and/or response to a drug. One of the most important and understudied differences between AD models is differences in the phenotypic characteristics of the background species.

Tropical Cyclone Diurnal Cycle as Observed by TRMM.

Previous work has indicated a clear, consistent diurnal cycle in rainfall and cold cloudiness coverage around tropical cyclones. This cycle may have important implications for structure and intensity changes of these storms and the forecasting of such changes. The goal of this paper is to use passive and active microwave measurements from the Tropical Rainfall Measuring Mission (TRMM) Microwave Imager (TMI) and Precipitation Radar (PR), respectively, to better understand the tropical cyclone diurnal cycle throughout a deep layer of a tropical cyclone's clouds.

Distributions of oxytocin and vasopressin 1a receptors in the Taiwan vole and their role in social monogamy.

Social monogamy is a mating strategy rarely employed by mammalian species. Laboratory studies in socially monogamous prairie voles () demonstrate that oxytocin and vasopressin act within the mesolimbic dopamine pathway to facilitate pair-bond formation. Species differences in oxytocin receptor (OTR) and vasopressin 1a receptor (V1aR) distribution in this pathway are associated with species differences in mating strategy.

Hepatic Overexpression of Annexin A1 and A2 in Thioacetamide-Primed Mice Protects Them Against Acetaminophen-Induced Liver Failure and Death.

Compensatory tissue repair (CTR) in thioacetamide (TA)-primed rats protects them against acetaminophen (APAP)-induced lethality. This study was aimed at investigating the mechanisms of CTR-mediated heteroprotection in mice. Male Swiss Webster mice received a priming dose of TA (40 mg/kg body weight [BW] in 10 mL distilled water [DW]/kg BW, intraperitoneally [IP]).

Transporters as Drug Targets in Neurological Diseases.

Membrane transport proteins have central physiological function in maintaining cerebral homeostasis. These transporters are expressed in almost all cerebral cells in which they regulate the movement of a wide range of solutes, including endogenous substrates, xenobiotic, and therapeutic drugs. Altered activity/expression of central nervous system (CNS) transporters has been implicated in the onset and progression of multiple neurological diseases.

Discovery and preliminary structure-activity relationship of the marine natural product manzamines as herpes simplex virus type-1 inhibitors.

Herpes simplex virus type-1 (HSV-1) is a member of alpha-herpesviridae family and is known to cause contagious human infections. The marine habitat is a rich source of structurally unique bioactive secondary metabolites. A small library of marine natural product classes 1-10 has been screened to discover a new hit entity active against HSV-1.

Cancer control potential of marine natural product scaffolds through inhibition of tumor cell migration and invasion.

The marine environment is a reliable source for the discovery of novel treatment options for numerous diseases. Past research efforts toward the discovery of marine-derived anticancer agents have resulted in several commercially available marine-based drugs. The pharmaceutical value of anticancer drugs from marine natural products (MNPs) ranges from US$563 billion to US$5.