Therapeutic Effects In Humans Research Articles

Conjugation of Doxorubicin and Carbon-based-nanostructures for Drug Delivery against HT-29 Colon Cancer Cells.

A drug delivery system is the method or process of administering a pharmaceutical compound to achieve a therapeutic effect in humans or animals. Such systems release the drugs at specific amounts in a specific site. The carbon based-nanomaterials have been actively used as drug carriers to treat various cancer. This study aimed to evaluate the cytotoxic effects of DOX-GO, DOX-OMC and DOXCNT in colon cancer cells (HT29). We reported platforms based on graphene oxide (GO), ordered mesoporous carbon (OMC) and carbon nanotubes (CNT) to conjugate with doxorubicin (DOX). The conjugation of DOX with carbon nanomaterial was investigated by UV-Vis spectroscopy, field emission scanning electron microscope (FE-SEM) and cyclic voltammetry (CV) methods. We showed that graphene oxide was a highly efficient matrix. Efficient loading of DOX, 89%, 78%, and 73.5% at pH 7.0 was seen onto GO, OMC and CNT, respectively. Upon pH 4. 0 after 15 h, 69%, 61% and 61% of DOX could be released from the DOX-GO, DOX-OMC and DOX-CNT, respectively, which illustrated the significant benefits of the developed approach for carbon nanomaterial applications. In vitro cytotoxicity analysis showed greater cytotoxicity of DOX/GO, DOX/OMC and DOX/CNT in comparison with GO, OMC and CNT against HT29 colon cancer cells with cell viability of 22%, 40% and 44% after 48 h for DOX-GO, DOX-OMC and DOX-CNT, respectively. The nanohybrids based on DOX-carbon nanomaterial, because of their unique physical and chemical properties, will remarkably enhance the anti-cancer activity.

Oral Health and Nutraceutical Agents.

Oral health is essential for both overall health and quality of life. The mouth is a window into the body's health, and nutrition can strongly impact the state of general and oral health. A healthy diet involves the synergistic effect of various nutraceutical agents, potentially capable of conferring protective actions against some inflammatory and chronic-degenerative disorders. Nutraceuticals, mostly present in plant-derived products, present multiple potential clinical, preventive, and therapeutic benefits. Accordingly, preclinical and epidemiological studies suggested a protective role for these compounds, but their real preventive and therapeutic effects in humans still await confirmation. Available evidence suggests that plant extracts are more effective than individual constituents because they contain different phytochemicals with multiple pharmacological targets and additive/synergistic effects, maximizing the benefits for oral health. Moreover, nutritional recommendations for oral health should be personalized and aligned with valid suggestions for overall health. This review is aimed to: introduce the basic concepts of nutraceuticals, including their main food sources; examine the logic that supports their relationship with oral health, and summarize and critically discuss clinical trials testing the utility of nutraceuticals in the prevention and treatment of oral diseases.

The effect of orally consumed Lactuca sativa syrup on human milk volume and weight gain in the preterm infant: a randomized controlled clinical trial

Human milk feeding can support premature infants to thrive. Yet those with premature infants can be challenged in human milk production. Considering this, and the use of potentially harmful human milk enhancers, the present study was conducted with the aim of determining the effect of orally consumed Lactuca sativa (L. sativa) syrup (lettuce extract) on human milk volume and subsequent weight gain in the preterm infant. Extracts from lettuce and other plants such as silymarin are already evidenced to be safe for use during lactation and have other therapeutic effects in humans. Yet this is the first study of its kind. This parallel randomized clinical trial included lactating participants with their preterm infants who were born at < 32 weeks' gestation and admitted to an intensive care unit. Convenience sampling was used to recruit participants. Eligible participants were allocated to groups randomly: intervention (n = 47), placebo (n = 46), and control (n = 47). The intervention group received one tablespoon of Lactuca sativa (L. sativa) syrup, and the placebo group received one tablespoon of placebo syrup 3 times a day for 1 week. Those in the control group did not receive any herbal or chemical milk-enhancing compounds. Routine care was provided to all three groups. Participants recorded their milk volume for 7 days in a daily information recorder form. Infant weight was measured prior to the intervention, and on the third, fifth and seventh days of the intervention period. There was a statistically significant difference observed in the adjusted mean volume of milk on the fourth and fifth days between the intervention, placebo, and control groups (P < 0.05). The adjusted mean milk volume of those in the intervention group on the first day was significantly higher than those in the control group and those in the placebo group. On the second day, the adjusted mean milk volume of those in the intervention group was higher than in those from the control group; and on the fourth day it was higher than in those from both the control and placebo groups; on the fifth day it was higher than in those in the placebo group; on the sixth day it was higher than in those in the control group and on the seventh day it was higher than in those in the control group (P < 0.05). There was no statistically significant difference in terms of the mean changes (with or without adjustment) in the weight of preterm infants between any of the groups. Lactuca sativa (L. sativa) syrup increases the volume of human milk production and no specific side effects have been reported in its use. Therefore, Lactuca sativa syrup can be recommended for use as one of the compounds that increase human milk volume.

Deciphering the binding mechanism of an anti-cancer phytochemical plumbagin with calf thymus DNA using biophysical and in silico techniques.

Plumbagin (PLM), a plant derivative, is well known for a wide range of therapeutic effects in humans including anti-cancer, anti-inflammatory, anti-oxidant, and anti-microbial. Cytotoxic and genotoxic potential of this phytochemical has been studied which demands further insight. DNA being a major target for several drugs was taken to study against PLM to understand its effects on the cellular system. UV-Vis spectroscopy has indicated the binding of PLM to ctDNA and dye displacement assays have confirmed the formation of PLM-ctDNA complex. The insignificant changes in circular dichroism spectra suggested that PLM is not affecting the structural makeup of the ctDNA, hence the binding could be peripheral and not intercalating. Further, the relative viscosity and minimal change in melting temperature upon the complex formation supported this finding and confirmed the groove binding of PLM. Molecular docking analysis and simulation studies also show PLM as a minor groove binder to DNA and provide details on the interaction dynamics of PLM-DNA complex. Docking followed by a 100ns simulation reveals the negative Gibbs free energy change (∆G = -6.6kcalmol-1), and the formation of a stable complex. The PLM- DNA complex with stable dynamics was further supported by different parameters including RMSD, RMSF, SASA, Rg, and the energy profile of interaction. This study provides an insight into the cytotoxic and genotoxic mechanism of PLM which can be a crucial step forward to exploit its therapeutic potential against several diseases including cancer.

Quantum Dots in Drug Delivery: The Artificial Atom

Drug delivery is the process of administering a pharmaceutical compound to achieve a therapeutic effect in humans or animals. Quantum dots (QDs), nano-sized semiconductors, are one of the most important materials that create a bridge between nanotechnology, and drug assay. Large-scale particles in drug delivery suffer from some major drawbacks. Thus arises the need for quantum dots. The following properties of quantum dots (especially carbon-based quantum dots) makes them promising candidates for drug delivery; their great aqueous stability, ability to cross cell membranes easily, high specific surface area which provides multiple attachment sites for drug targeting. Graphene quantum dots can load drugs through hydrophobic or noncovalent pi-pi stacking interactions or hydrogen bonding.

A Comprehensive Review on Targeted Drug Delivery System

Drug delivery is the method or process of administering a pharmaceutical compound to achieve a therapeutic effect in humans or animals. For the treatment of human diseases, nasal and pulmonary routes of drug delivery are gaining increasing importance. These routes provide promising alternatives to parenteral drug delivery particularly for peptide and protein therapeutics. For this purpose, several drug delivery systems have been formulated and are being investigated for nasal and pulmonary delivery. These include liposomes, proliposomes, microspheres, gels, prodrugs, and cyclodextrins, among others. Nanoparticles composed of biodegradable polymers show assurance in fulfilling the stringent requirements placed on these delivery systems, such as ability to be transferred into an aerosol, stability against forces generated during aerosolization, biocompatibility, targeting of specific sites or cell populations in the lung, release of the drug in a predetermined manner, and degradation within an acceptable period of time.

Rg3 and Rh2 ginsenosides suppress embryoid body formation by inhibiting the epithelial-mesenchymal transition

Numerous active compounds derived from ginseng exhibit various pharmacological and therapeutic effects in humans. Despite the benefits of ginsenosides, little is known about their influence on embryonic development, especially in human embryonic models. In this study, we evaluated the effect of two ginsenosides (Rg3 and Rh2) on human embryonic development, using embryoid bodies and three-dimensional (3D) aggregates of pluripotent stem cells. We exposed embryoid bodies to varying concentrations of Rg3 and Rh2 (5, 10, and 25μg/mL), and their embryotoxicity was evaluated by measuring the size of the embryoid body and the expression of epithelial-mesenchymal transition (EMT) markers. The growth rates of embryoid bodies were reduced upon treatment with a high concentration (25μg/mL) of Rg3 and Rh2. In addition, Rg3 induced E-cadherin expression while inhibiting N-cadherin and vimentin expression, which implies the inhibition of EMT. Such a change in E-cadherin expression was not observed after Rh2 treatment, but the inhibition of N-cadherin and vimentin expression was observed to be consistent with that observed on treatment with Rg3. Taken together, using the human embryoid model, we found that the two active ginsenosides, Rg3 and Rh2, induce aberrant embryoid body formation and ablate normal EMT.

Preventing and Treating Neurological Disorders with the Flavonol Fisetin

Neurological disorders, including neurodegenerative diseases, have a significant negative impact on both patients and society at large. Since the prevalence of most of these disorders increases with age, the consequences for our aging population are only going to grow. It is now acknowledged that neurological disorders are multi-factorial involving disruptions in multiple cellular systems. While each disorder has specific initiating mechanisms and pathologies, certain common pathways appear to be involved in most, if not all, neurological disorders. Thus, it is becoming increasingly important to identify compounds that can modulate the multiple pathways that contribute to disease development or progression. One of these compounds is the flavonol fisetin. Fisetin has now been shown in preclinical models to be effective at preventing the development and/or progression of multiple neurological disorders including Alzheimer’s disease, Parkinson’s disease, Huntington’s disease, amyotrophic lateral sclerosis, stroke (both ischemic and hemorrhagic) and traumatic brain injury as well as to reduce age-associated changes in the brain. These beneficial effects stem from its actions on multiple pathways associated with the different neurological disorders. These actions include its well characterized anti-inflammatory and anti-oxidant effects as well as more recently described effects on the regulated cell death oxytosis/ferroptosis pathway, the gut microbiome and its senolytic activity. Therefore, the growing body of pre-clinical data, along with fisetin’s ability to modulate a large number of pathways associated with brain dysfunction, strongly suggest that it would be worthwhile to pursue its therapeutic effects in humans.

Genetic Engineering Of Mesenchymal Stem Cells To Improve Therapeutic Effects

Based on the therapeutic potential of MSCs, including homing to damaged sites, trans-differentiation, secretion of trophic factors, and immunomodulation, approximately 1,100 clinical studies have been registered in the ClinicalTrials.Gov, and several drugs using MSCs have been approved worldwide. However, despite their therapeutic potential, MSCs have not yet shown sufficient therapeutic effects in humans. Therefore, in order to increase the therapeutic potential of MSCs, methods such as MSC priming, genetic modification, Three-Dimensional (3-D) culture, and MSC-derived exosomes are being studied intensively. Among them, genetic modification increases the expression of therapeutic genes, leading to increased homing of MSCs to the damaged sites, increased engraftment rates, and increased survival durations of transplanted MSCs.

Stepwise mass spectrometry-based approach for confirming the presence of benzoxazinoids in herbs and vegetables.

Benzoxazinoids (BXs) are plant phytochemicals that have both defensive properties in plants and therapeutic effects in humans. The presence of BXs has been largely studied in the Poaceae family (monocots). To study the presence or absence of BXs in dicotyledons and monocotyledons outside the Poaceae family, parts of 24 plant species at several growth stages were selected for analysis, some of which were already known to contain BXs. To devise a stepwise mass spectrometry-based approach for confirming the presence of BXs in plant samples, and to use the method to explore the status of BXs in selected plant species. Plant samples were extracted using accelerated solvent extraction and analysed using triple-quadrupole liquid chromatography-mass spectrometry. The use of different columns, double mass transitions, and ion ratios proved to be a robust tool for confirming the presence of BXs in different plant species. By this method, the presence of BXs was confirmed in three of the 24 species. Double-hexose forms of BXs, which have not been reported before in dicotyledons, were confirmed to be present in the dicotyledon plants Acanthus mollis and Lamium galeobdolon, and the presence of BXs in the seeds of Consolida orientalis is reported for the first time here. High concentrations of BXs were found in the aerial parts of Acanthus mollis and Lamium galeobdolon, at 20 and 32 μmol/g plant dry weight, respectively. The stepwise approach described in this work confirmed the presence of BXs in new samples.

Targeted Local Drug Delivery – A Possible Approach in Dentistry

Drug delivery is a method of administering a pharmaceutical compound to achieve a therapeutic effectin humans and animals. Conventional therapy is a classical method of achieving drug delivery. Where,it provides drug release immediately and causes fluctuation of drug level in in blood depending on thedosage forms compared to conventional, which improves the drug potency, controlled drug release to give asustained therapeutic effect, provide greater safety and target a drug specifically to a desired tissue. It mainlyincludes targeted, controlled and modulated drug delivery systems. Hence, there is an increased interesttowards the application of targeted therapies in medicine and dentistry and has proven to be successful inprevention and treatment of various oro-dental disorders.

Abstract PR09: ADU-S100 (MIW815) synergizes with checkpoint blockade to elicit an antitumor CD8+ T-cell response to control distal tumors

Abstract Stimulator of interferon genes (STING) is a critical component of an innate immune pathway that activates robust antiviral and antitumor responses in mouse models. Activation of the STING pathway by intratumoral (IT) injection of synthetic cyclic dinucleotides (CDNs) is being explored as a cancer therapy and has shown potent antitumor activity in preclinical models. Here we assessed the benefit of combining immune checkpoint blockade with ADU-S100 (MIW815), a CDN under clinical evaluation, in different syngeneic mouse tumor models. In mice bearing dual flank 4T1 mammary carcinoma tumors resistant to anti-PD-1 treatment, adding a single dose of ADU-S100 with anti-PD-1 induced eradication of both injected and noninjected tumors, leading to near-complete responses, demonstrating that ADU-S100 potentiates the activity of checkpoint blockade. Tumor control was CD8+ T cell-dependent and correlated with an enhanced CD8+ T-cell effector profile in both the periphery and in noninjected tumors. Combining a single injection of ADU-S100 with anti-PD-1 also elicited enhanced tumor control in the dual flank MC-38 colon carcinoma model compared to ADU-S100 or anti-PD-1 treatment alone. Those mice cured by combination treatment were also protected from tumor rechallenge. Moreover, in the poorly immunogenic B16.F10 model, adding ADU-S100 to the ineffective combination therapy of anti-PD-1 and anti-CTLA-4 induced tumor-specific CD8+ T-cell responses and tumor control, leading to multiple complete responses and durable immunity in surviving animals. Together, these results highlight the immune correlates of STING-mediated antitumor efficacy and illustrate the potential of combining ADU-S100 with checkpoint inhibitors for the treatment of human cancer. Clinical trials of ADU-S100 in combination with anti-PD-1 or with anti-CTLA-4 are ongoing and could further elucidate the immunologic mechanism of action and therapeutic effect in humans. This abstract is also being presented as Poster B47. Citation Format: Weiwen Deng, Anthony L. Desbien, Kelsey Sivick Gauthier, Gabrielle Reiner, Leticia Corrales, Tamara Schroeder, Laura Hix Glickman, Natalie H. Surh, Brian Francica, Justin J. Leong, Ken Metchette, Lianxing Zheng, Charles Cho, Yan Feng, Jeffery M. McKenna, Steven L. Bender, Chudi Ndubaku, Meredith L. Leong, Andrea van Elsas, Sarah M. McWhirter. ADU-S100 (MIW815) synergizes with checkpoint blockade to elicit an antitumor CD8+ T-cell response to control distal tumors [abstract]. In: Proceedings of the AACR Special Conference on Tumor Immunology and Immunotherapy; 2018 Nov 27-30; Miami Beach, FL. Philadelphia (PA): AACR; Cancer Immunol Res 2020;8(4 Suppl):Abstract nr PR09.

Nonsteroidal Anti-Inflammatory Drugs and Their Neuroprotective Role After an Acute Spinal Cord Injury: A Systematic Review of Animal Models.

Study Design:Systematic review.Objective:Spinal cord injuries (SCIs) resulting in motor deficits can be devastating injuries resulting in millions of health care dollars spent per incident. Nonsteroidal anti-inflammatory drugs (NSAIDs) are a potential class of drugs that could improve motor function after an SCI. This systematic review utilizes PRISMA guidelines to evaluate the effectiveness of NSAIDs for SCI.Methods:PubMed/MEDLINE, CINAHL, PsycINFO, Embase, and Scopus were reviewed linking the keywords of “ibuprofen,” “meloxicam,” “naproxen,” “ketorolac,” “indomethacin,” “celecoxib,” “ATB-346,” “NSAID,” and “nonsteroidal anti-inflammatory drug” with “spinal.” Results were reviewed for relevance and included if they met inclusion criteria. The SYRCLE checklist was used to assess sources of bias.Results:A total of 2960 studies were identified in the PubMed/MEDLINE database using the above-mentioned search criteria. A total of 461 abstracts were reviewed in Scopus, 340 in CINAHL, 179 in PsycINFO, and 7632 in Embase. A total of 15 articles met the inclusion criteria.Conclusions:NSAIDs’ effectiveness after SCI is largely determined by its ability to inhibit Rho-A. NSAIDs are a promising therapeutic option in acute SCI patients because they appear to decrease cord edema and inflammation, increase axonal sprouting, and improve motor function with minimal side effects. Studies are limited by heterogeneity, small sample size, and the use of animal models, which might not replicate the therapeutic effects in humans. There are no published human studies evaluating the safety and efficacy of these drugs after a traumatic cord injury. There is a need for well-designed prospective studies evaluating ibuprofen or indomethacin after adult spinal cord injuries.

Validity and reliability of test strips for the measurement of salivary nitrite concentration with and without the use of mouthwash in healthy adults

The nitrate (NO3−)-nitrite (NO2−)-nitric oxide (NO) pathway has received considerable interest in recent years as a potential target for nutritional interventions designed to increase NO production, and elicit therapeutic effects in humans. In particular, studies have evaluated the effects of supplemental dietary NO3−, which serves as a ‘substrate’ for this pathway, on numerous different health outcomes. One challenge has been to evaluate compliance with the NO3− interventions. A recent advance in this field has been the development of a non-invasive, simple and rapid method to measure nitrite concentrations in saliva using small test salivary strips.In the present study, ten healthy adults were recruited to a randomised, crossover study and received an acute dose of NO3−-rich beetroot juice (BJ) after rinsing their mouth with either water or commercially available antibacterial mouthwash. Salivary NO3− and NO2− concentrations were measured at baseline and up to 5 h after BJ consumption using the gold-standard chemiluminescence and a colorimetric Griess assay. In addition, two salivary test strips (Berkeley Test strips, CA, USA) were used to measure NO2−concentrations at the same time points. Five observers read the strips and inter- and intra-observer reliability was measured. The Bland-Altman method was used to provide a visual representation of the agreement between the methods used to evaluate salivary NO3−/NO2−concentration. Sialin concentrations were measured at baseline and up to 5 h after BJ consumption.BJ elevated salivary NO3− and NO2− concentrations when the mouth was rinsed with water (both P < 0.01), as assessed via both chemiluminescence and Griess methods. Rinsing the mouth with antibacterial mouthwash attenuated markedly the increase in NO2− (P < 0.001), while NO3−concentrations were unaffected (P > 0.05). The Intra-Class Coefficients of Correlation (ICC) showed a high inter- and intra-observer reliability (r > 0.8). A significant positive correlation was found between absolute salivary NO2− concentrations measured by strips and Griess and chemiluminescence methods (rho = 0.83 and 0.77, respectively) and also when expressed as changes in salivary NO2− concentrations (rho = 0.80 and 0.79, respectively). Bland Altman analysis indicated a poor agreement for absolute NO2− concentrations between salivary strips and the chemiluminescence and Griess methods. A small significant negative correlation was found between changes in salivary sialin and salivary NO2ˉ concentrations (r = −0.20, P = 0.04). A non-significant positive correlation was observed between the change in salivary sialin and salivary NO3ˉ concentrations (r = 0.18, P = 0.06).This study suggests that commercially available salivary NO2− test strips provide a reasonable surrogate marker for monitoring changes in salivary NO2− concentrations in humans. However, the strips do not provide accurate estimates of absolute NO2− concentrations.

1161-P: SCO-267, a GPR40 Full Agonist, Improves Glycemic and Body Weight Control More Than That by Fasiglifam in Rat Models of Diabetes and Obesity

GPR40/FFAR1 is a G-protein-coupled receptor expressed in pancreatic islets and enteroendocrine cells. SCO-267 is a novel full agonist of GPR40 being developed as a treatment for type 2 diabetes and obesity. The efficacy of SCO-267 was investigated in cells and animal models of diabetes and obesity. In animal studies, the efficacy of SCO-267 was compared with that of fasiglifam, a clinically effective GPR40 agonist. SCO-267 treatment activated Gq signaling in both high and low GPR40-expressing CHO cells, stimulated insulin secretion in MIN6 cells, and induced GLP-1 release in GLUTag cells. In rats, SCO-267 increased insulin, glucagon, GLP-1, GIP, and PYY secretion, without hypoglycemia. In the neonatal streptozotocin (N-STZ)-1.5 rat, a diabetic model with impaired beta-cell function, compared to fasiglifam, SCO-267 was more effective in stimulating insulin and GLP-1 secretion, and improving glucose tolerance. In a single dose study using N-STZ-1.5 rats, 0.3 mg/kg SCO-267 (Cmax 0.023 μg/mL) and 3 mg/kg fasiglifam (Cmax 6.2 μg/mL) exhibited similar glucose-lowering efficacies. In a two-week dosing study of N-STZ-1.5 rats, glucose tolerance was more effectively improved by 1 mg/kg SCO-267 (Cmax, 0.139 μg/mL; AUC0-24hr, 0.626 μg h/mL) than by 10 mg/kg fasiglifam (Cmax, 39.8 μg/mL; AUC0-24hr, 254.6 μg h/mL). Diet-induced obese rats treated with SCO-267 for 2 weeks showed elevated plasma GLP-1 and PYY, reduced food intake, and decreased body weight, whereas fasiglifam-treated rats were weight-neutral. The reduction in body weight by SCO-267 was abolished in GPR40 knockout mice. Plasma protein binding of SCO-267 was similar across species (99.6-99.7%), indicating that similar compound exposure may induce therapeutic effects in humans. SCO-267 showed good pharmacokinetic and safety profiles in preclinical studies. These results suggest that SCO-267 treatment may result in effective glycemic and body weight control in patients. Disclosure Y. Moritoh: Employee; Self; SCOHIA PHARMA, Inc. H. Ueno: Employee; Self; Takeda Pharmaceutical Company Limited. R. Ito: Employee; Self; Takeda Pharmaceutical Company Limited. S. Abe: Employee; Self; SCOHIA PHARMA, Inc. H. Miyashita: Employee; Self; Takeda Pharmaceutical Company Limited. H. Ogino: Employee; Self; Takeda Pharmaceutical Company Limited. M. Ookawara: Employee; Self; SCOHIA PHARMA, Inc. Y. Ishimura: Employee; Self; Takeda Pharmaceutical Company Limited. Y. Miyamoto: None. T. Yoshihara: Employee; Self; Takeda Pharmaceutical Company Limited. Employee; Spouse/Partner; Takeda Pharmaceutical Company Limited. Y. Tsujihata: Employee; Self; Takeda Pharmaceutical Company Limited. K. Takeuchi: Employee; Self; Takeda Pharmaceutical Company Limited. N. Nishigaki: Employee; Self; Takeda Pharmaceutical Company Limited. Y. Yamada: Board Member; Self; SCOHIA PHARMA, Inc. M. Watanabe: Employee; Self; SCOHIA PHARMA, Inc. Funding Takeda Pharmaceutical Company Limited; SCOHIA PHARMA, Inc.

Clinical management of herpes simplex virus infections: past, present, and future.

Infection with herpes simplex virus (HSV) types 1 and 2 is ubiquitous in the human population. Most commonly, virus replication is limited to the epithelia and establishes latency in enervating sensory neurons, reactivating periodically to produce localized recurrent lesions. However, these viruses can also cause severe disease such as recurrent keratitis leading potentially to blindness, as well as encephalitis, and systemic disease in neonates and immunocompromised patients. Although antiviral therapy has allowed continual and substantial improvement in the management of both primary and recurrent infections, resistance to currently available drugs and long-term toxicity pose a current and future threat that should be addressed through the development of new antiviral compounds directed against new targets. The development of several promising HSV vaccines has been terminated recently because of modest or controversial therapeutic effects in humans. Nevertheless, several exciting vaccine candidates remain in the pipeline and are effective in animal models; these must also be tested in humans for sufficient therapeutic effects to warrant continued development. Approaches using compounds that modulate the chromatin state of the viral genome to suppress infection and reactivation or induce enhanced antiviral immunity have potential. In addition, technologies such as CRISPR/Cas9 have the potential to edit latent viral DNA in sensory neurons, potentially curing the neuron and patient of latent infection. It is hoped that development on all three fronts—antivirals, vaccines, and gene editing—will lead to substantially less HSV morbidity in the future.

Honey reduces the metastatic characteristics of prostate cancer cell lines by promoting a loss of adhesion.

Honey has been shown to have a range of therapeutic effects in humans, with anti-inflammatory and anti-bacterial effects among those previously characterised. Here, we examine the possibility of New Zealand thyme, manuka and honeydew honeys, and their major sugar and phenolic components, reducing the development of metastatic cancer. Their activity was examined in vitro, in PC3 and DU145 prostate cancer cell lines, through measuring the compounds’ effects on the metastatic characteristics of migration, invasion and adhesion. First, the phenolic compounds gallic acid, caffeic acid, quercetin, kaempferol and chrysin were quantified in the honeys using high performance liquid chromatography, and found in nanomolar concentrations. In a Boyden chamber-based migration assay, non-toxic concentrations of thyme and honeydew honeys reduced cell migration by 20%, and all phenolic compounds except caffeic acid also lowered migration, although a mixture of only the sugars found in honey had no effect. All of the honeys, phenolics and the sugar-only mixture reduced invasive movement of cells through extracellular matrix by up to 75%. Most notably, each of the three honeys and the sugar-only mixture reduced cell adhesion to collagen I by 90%. With the exception of quercetin, phenolic compounds did not reduce adhesion. Therefore, honey and its sugar and phenolic components can lower the metastatic properties of cancer cells, and may do this by preventing effective cell adhesion to the extracellular matrix. The sugars and phenol compounds of honey are much more effective in combination than individually.

Consumer Acceptance of Bars and Gummies with Unencapsulated and Encapsulated Resveratrol.

The addition of resveratrol, a polyphenol found in red wine and peanuts, to food products would help to provide the health benefits associated with the compound to the consumer in a wide array of food matrices. The bitterness of resveratrol and instability of its bioactive form in light are 2 major challenges with the incorporation of the compound into food products. Microencapsulation in a sodium caseinate matrix was utilized as a strategy to overcome these challenges. The objective of this research was to show the application of the resveratrol microcapsules in easy-to-consume foods. Consumer acceptance was evaluated for gummies and bars with encapsulated resveratrol in comparison to the controls. Four different controls were used: 1) without any resveratrol OR protein (Plain), 2) unencapsulated resveratrol (Resv), 3) sodium caseinate and unencapsulated resveratrol just mixed without encapsulation (P + R), and 4) sodium caseinate only (PRO). Two concentrations of resveratrol that have been shown to offer therapeutic effects in humans were tested (10 and 40 mg/d). The overall liking, evaluated using a 9-point scale, of bars with 10 mg of encapsulated resveratrol did not differ significantly from the control without any added resveratrol and protein (Plain) or from the controls with equivalent protein and/or resveratrol concentrations. For gummies, the samples with the resveratrol microcapsules had a significantly lower overall liking than the controls with the same protein and/or resveratrol content. This research demonstrated application of resveratrol microcapsules into easy-to-consume food products in order to deliver the health benefits to the consumer.

Genetic Variants of Cytochrome CYP2D6 in Two Mixed Chilean Populations

Objectives: It is known that the interindividual and interethnic variability of the genetic polymorphisms of CYP2D6 plays an important role in the presentation of adverse drug reactions and concerning lack of therapeutic effects in humans. However, there are few data available from mixed populations of Latin America, including the Chilean. The aim of this study was therefore to estimate the frequencies of CYP2D6 variants in two samples of hospitals from the northern (Hospital San José, HSJ) and eastern (Clínica Las Condes, CLC) parts of Santiago, Chile, with different degrees of Amerindian admixture (HSJ: 34.5%; CLC: 15.9%). Methods: We used polymerase chain reaction followed by restriction endonuclease digestion (PCR-RFLP) to genotype 7 CYP2D6 alleles in 250 healthy unrelated individuals of Chilean Mestizo background. The detection of allele CYP2D6*5 and the duplication of this gene was performed by long-PCR. Results: The degrees of Amerindian admixture are reflected in the observed frequencies of the CYP2D6*1 (HSJ: 58.26%; CLC: 41.06%), CYP2D6*2 (HSJ: 28.10%; CLC: 40.65%), and CYP2D6*4 (HSJ: 8.26%; CLC: 12.60%) alleles; the frequencies of CYP2D6*1 (p = 0.0002) and CYP2D6*2 (p = 0.0036) are significantly different between the samples. Four individuals (CLC: 0.41%; HSJ: 1.24%) could not be assigned to a genotype. We identified 3.25% of the genotypes which predict a poor metabolizer phenotype in CLC and 1.65% in HSJ. Conclusion: Our data indicate ethnic group-dependent genetic differences in the vulnerability to treatment with the large variety of drugs metabolized by the enzyme CYP2D6.

Phytochemical composition of some common coastal halophytes of the United Arab Emirates

Halophyte species of United Arab Emirates are a source of unique active phytochemicals, potentially due to the extreme environmental conditions under which the plants grow in the UAE. These phytochemicals make the native halophytes possibly interesting crops for biorefining, where biofuel production is combined with the production of value added chemicals, improving the economic feasibility of both process. Phytochemicals found in these species are widely recognized and researched as potential pharmaceutical and nutraceutical products. We reviewed the literature for secondary metabolites from species from the following halophyte families: Aizoaceae, Amaranthaceae (incl. Chenopodiaceae), Avicenniaceae, Zygophyllaceae. The review revealed that plant species belonging to these families contain valuable phytochemicals, such as fatty acids, terpenoids, flavonoids, alkaloids, steroids, tannins, saponins, quinones and coumarins, many of which have been reported to have therapeutic effects in humans.