A 2x folic acid treatment affects epigenetics and dendritic spine densities in SHSY5Y cells.

Many diseases are now associated with aberrant epigenetics and gene expression changes. Epigenetics can be modified by factors like diet. One dietary factor, folic acid, is consumed in various forms including supplements, energy drinks, and fortified grains. It was hypothesized high levels of folic acid would affect gene expression and enzyme activity of chromatin modifying enzymes as well as dendritic spine densities in a commonly utilized neuron model, the SHSY5Y cell. Decreased MBD2 and MECP2 were discovered upon treatment of SHSY5Y cells with a 2x folic acid dose. Corresponding decreases in dendritic spines were apparent in the 2x folic acid treated cells as well. Activity of DNMTs and H3K4 HMTs was altered. Further, H3K4me1, H3K4me3, H3K9Ac, and global DNA methylation were decreased in the 2x folic acid treated cells. Further studies are warranted to determine if the effects of excess folic acid are detrimental to organismal physiology.

The ReFRAME library as a comprehensive drug repurposing library and its application to the treatment of cryptosporidiosis.

The chemical diversity and known safety profiles of drugs previously tested in humans make them a valuable set of compounds to explore potential therapeutic utility in indications outside those originally targeted, especially neglected tropical diseases. This practice of "drug repurposing" has become commonplace in academic and other nonprofit drug-discovery efforts, with the appeal that significantly less time and resources are required to advance a candidate into the clinic. Here, we report a comprehensive open-access, drug repositioning screening set of 12,000 compounds (termed ReFRAME; Repurposing, Focused Rescue, and Accelerated Medchem) that was assembled by combining three widely used commercial drug competitive intelligence databases (Clarivate Integrity, GVK Excelra GoStar, and Citeline Pharmaprojects), together with extensive patent mining of small molecules that have been dosed in humans. To date, 12,000 compounds (∼80% of compounds identified from data mining) have been purchased or synthesized and subsequently plated for screening. To exemplify its utility, this collection was screened against Cryptosporidium spp., a major cause of childhood diarrhea in the developing world, and two active compounds previously tested in humans for other therapeutic indications were identified. Both compounds, VB-201 and a structurally related analog of ASP-7962, were subsequently shown to be efficacious in animal models of Cryptosporidium infection at clinically relevant doses, based on available human doses. In addition, an open-access data portal (https://reframedb.org) has been developed to share ReFRAME screen hits to encourage additional follow-up and maximize the impact of the ReFRAME screening collection.

Vitamin D Increases Aß140 Plasma Levels and Protects Lymphocytes from Oxidative Death in Mild Cognitive Impairment Patients.

BACKGROUND: Mild cognitive impairment (MCI) has an increased rate of progression to dementia. Alterations of some metabolic factors, such as deficiency of vitamin D, are a risk factor for cognitive deterioration. Vitamin D is involved in the clearance of ß-amyloid (Aß) from the brain. We have reported that lymphocytes from Alzheimer's disease (AD) patients have an increased susceptibility to oxidative death by H2O2 exposure, but currently it is unknown if this characteristic is modifiable in vivo. OBJECTIVE: To determine if correction of low vitamin D levels protects lymphocytes from oxidative death and increases Aß1-40 plasma levels in MCI and very early AD (VEAD) patients. METHOD: Sixteen MCI, 11 VEAD and 25 healthy control (HC) voluntaries were evaluated with the Clinical Dementia Rating (CDR), Montreal Cognitive assessment (MoCA), and Memory Index score (MIS). Lymphocyte death was measured by flow cytometry after 20h exposure to H2O2. In patients with low levels of vitamin D -11 MCI, 9 VEAD and 20 HC- lymphocyte H2O2-death, plasma Aß1-40 levels and cognitive status were evaluated pre- and post-vitamin D supplementation for 6 months. RESULTS: Lymphocytes from MCI and VEAD patients showed increased susceptibility to oxidative death at study entry. In MCI, but not VEAD patients, lymphocyte susceptibility to death and Aß1-40 levels plasma levels improved after 6 months of vitamin D supplementation. In addition, cognitive status on follow-up (18 months) improved in MCI patients after vitamin D supplementation. CONCLUSION: Vitamin D supplementation may be beneficial in MCI. The lack of effect in VEAD may be due to a more advanced stage or different characteristics of the neurodegenerative process.

A Novel Multi-Targeting Approach to Treating Hair Loss, Using Standardized Nutraceuticals.

Hair loss is a complicated problem that causes significant concern for those who are affected. Patients seeking medical treatment have limited options that include topical minoxidil and oral finasteride. While these treatments are backed by long term clinical use and research outcomes, many patients find topical minoxidil difficult to incorporate into their daily routine and some are concerned with the side effects associated with finasteride. In the office setting, patients may be treated with more invasive procedures such as platelet-rich plasma injections (PRP) and hair transplantation, treatments that often must be repeated and can lead to a costly investment. Consumers are increasingly interested in natural treatments for hair loss. Many turn to basic supplements only to be disappointed when they fail to deliver due to lack of standardization and efficacy. In this paper we review the benefits of a nutraceutical containing a specific blend of highly purified, standardized, bio-optimized, and bioavailable botanical extracts to treat hair loss. These phytoactives were selected because of their diverse multi-modal biologic activity against inflammation, DHT, stress mediators, oxidative damage, and intermediary signaling cascades. This supplement represents a paradigm shift as it addresses not only the factors that trigger hair loss but the downstream mediators of inflammation as well. Multi-center clinical studies are currently underway to confirm the efficacy and benefits of this unique nutraceutical.

J Drugs Dermatol. 2017;16(11 Suppl):s141-148.

Hair Transplantation Controversies.

BACKGROUND: Hair transplant surgery creates consistently natural appearing transplanted hair for men. It is increasingly popular procedure to restore natural growing hair for men with hair loss. OBJECTIVE: To review some current controversies in hair transplant surgery. MATERIALS AND METHODS: Review of the English PubMed literature and specialty literature in hair transplant surgery. RESULTS: Some of the controversies in hair transplant surgery include appropriate donor harvesting technique including elliptical donor harvesting versus follicular unit extraction whether manual versus robotic, the role of platelet-rich plasma and low-level light surgery in hair transplant surgery. CONCLUSION: Hair transplant surgery creates consistently natural appearing hair. As with all techniques, there are controversies regarding the optimal method for performing the procedure. Some of the current controversies in hair transplant surgery include optimal donor harvesting techniques, elliptical donor harvesting versus follicular unit extraction, the role of low-level light therapy and the platelet-rich plasma therapy in the procedure. Future studies will further clarify their role in the procedure.

Effects of 12 Weeks of Tai Chi Chuan Training on Balance and Functional Fitness in Older Japanese Adults.

The purpose of this study was to determine the effects of Tai Chi Chuan on static and dynamic balance, and functional fitness in older adults. Forty-nine volunteers were divided into an exercise group (EX: 9 men and 16 women, average age 72 ± 5 years) and control group (13 men and 11 women, average age 73 ± 6 years). The EX participated in a 12-week supervised exercise program (60 min/day, 2 days/week) that consisted of 10-min warm-up and stretching, 40-min Tai Chi Chuan exercise (long-form Yang style with 108 movements), and 10-min cool-down/relaxation exercises. The control group was asked to not change their physical activity habits. Static (sway velocity standing on firm or foam surfaces with eyes open or closed) and dynamic balance (limits of stability (LOS)), as well as functional fitness measures of body mass; upper- and lower-body strength; and flexibility, mobility, and aerobic fitness were taken before and after the intervention. After the 12-week Tai Chi Chuan exercise program, there were no improvements in any functional fitness or balance variable although components of LOS tended to increase (13.1%, p = 0.052). These results indicate that 12 weeks of Tai Chi Chuan exercise has no significant effect on balance and functional fitness parameters in older Japanese adults.

Metabolic Benefit of Chronic Caloric Restriction and Activation of Hypothalamic AGRP/NPY Neurons in Male Mice Is Independent of Ghrelin.

Aging is associated with attenuated ghrelin signaling. During aging, chronic caloric restriction (CR) produces health benefits accompanied by enhanced ghrelin production. Ghrelin receptor (GH secretagogue receptor 1a) agonists administered to aging rodents and humans restore the young adult phenotype; therefore, we tested the hypothesis that the metabolic benefits of CR are mediated by endogenous ghrelin. Three month-old male mice lacking ghrelin (Ghrelin-/-) or ghrelin receptor (Ghsr-/-), and their wild-type (WT) littermates were randomly assigned to 2 groups: ad libitum (AL) fed and CR, where 40% food restriction was introduced gradually to allow Ghrelin-/- and Ghsr-/- mice to metabolically adapt and avoid severe hypoglycemia. Twelve months later, plasma ghrelin, metabolic parameters, ambulatory activity, hypothalamic and liver gene expression, as well as body composition were measured. CR increased plasma ghrelin and des-acyl ghrelin concentrations in WT and Ghsr-/- mice. CR of WT, Ghsr-/-, and Ghrelin-/- mice markedly improved metabolic flexibility, enhanced ambulatory activity, and reduced adiposity. Inactivation of Ghrelin or Ghsr had no effect on AL food intake or food anticipatory behavior. In contrast to the widely held belief that endogenous ghrelin regulates food intake, CR increased expression of hypothalamic Agrp and Npy, with reduced expression of Pomc across genotypes. In the AL context, ablation of ghrelin signaling markedly inhibited liver steatosis, which correlated with reduced Pparγ expression and enhanced Irs2 expression. Although CR and administration of GH secretagogue receptor 1a agonists both benefit the aging phenotype, we conclude the benefits of chronic CR are a consequence of enhanced metabolic flexibility independent of endogenous ghrelin or des-acyl ghrelin signaling.

Contemporary hair transplantation.

BACKGROUND: The field of hair transplantation has evolved considerably over the last quarter century. Performed correctly, the cosmetic results of contemporary hair transplantation are virtually undetectable in women and men. Large, pluggy "punch grafts" have been replaced with natural-appearing follicular unit grafts, which maintain their existing anatomy and with proper technique can match the orientation of surrounding hair follicles. OBJECTIVE: To review all of the steps involved in hair transplantation surgery and to provide an overview of medications used in conjunction with transplantation to help prevent hair loss. MATERIALS, METHODS, AND RESULTS: The authors review key aspects of the consultation, physical examination, selection of appropriate candidates, excision of donor area, hairline design, graft creation and placement, and postoperative instructions. The role of medications such as minoxidil and finasteride in preventing ongoing hair loss is an essential part of the treatment plan. For nonsurgical candidates, other treatments such as wigs, hairpieces, and camouflages are reviewed. Future trends may involve the use of low-level laser light therapy, dutasteride, and cloning of follicles. CONCLUSION: Patients and physicians alike are pleased with the results of contemporary hair transplantation, and physicians can now recommend the procedure without reservation. The authors have indicated no significant interest with commercial supporters.

The use of low-level light for hair growth: part I.

BACKGROUND AND OBJECTIVE: Low-level laser therapy (LLLT) is a new therapy for the treatment of hair loss. It has received enormous media attention and tremendous marketing budgets from companies that sell the devices, but no independent, peer-reviewed studies have demonstrated its efficacy in this application. Here we investigate the efficacy of LLLT in enhancing hair growth. METHODS: A total of seven patients were exposed to LLLT twice weekly for 20 minutes each time over a period of 3-6 months. Five patients were treated for a total of 3 months and two were treated for 6 months. Videomicroscopic images were taken at baseline, 3 months, and 6 months, and analyzed for changes in vellus hair counts, terminal hair counts, and shaft diameter. Both videomicroscopic and global images underwent blinded review for evidence of subjective improvement. Patients also answered questionnaires assessing hair growth throughout the study. Neither patients nor physicians conducting the study received any financial compensation. RESULTS: The results indicate that on average patients had a decrease in the number of vellus hairs, an increase in the number of terminal hairs, and an increase in shaft diameter. However, paired i-testing indicated that none of these changes was statistically significant. Also, blinded evaluation of global images did not support an improvement in hair density or caliber. CONCLUSIONS: LLLT may be a promising treatment option for patients who do not respond to either finasteride or minoxidil, and who do not want to undergo hair transplantation. This technology appears to work better for some people than for others. Factors predicting who will most benefit are yet to be determined. Larger, longer-term placebo-controlled studies are needed to confirm these findings, and demonstrate statistical significance, or refute them altogether.

Medical treatments for male and female pattern hair loss.

UNLABELLED: Male and female pattern hair loss affects a large percentage of the population, and patients frequently present for treatment of this to their dermatologist. Here we review the many treatments available for hair loss. We review the evidence for each, and outline the most effective treatment strategies for both men and women. LEARNING OBJECTIVE: At the conclusion of this article, the reader should be able to describe the most effective treatments for hair loss, understand their mechanism(s) of action, and explain which treatments are the best in different settings.

Hair transplantation for men.

Men throughout history have suffered from various degrees of hair loss. Modern techniques for hair transplantation give rise to natural and long-lasting results. In this paper we provide an overview of the procedure, including the harvesting of donor hair in the occipital scalp, and its redistribution along the frontal- and mid-scalp areas. Special consideration must be made to choosing the candidates carefully and to performing their surgery in a manner that looks appropriate for all ages. We describe the role of medications for male pattern hair loss and with hair transplantation.

Functional fitness gain varies in older adults depending on exercise mode.

UNLABELLED: Various exercise modes are available to improve functional fitness (FF) in older adults. However, information on the comparative capability of different exercise modes to improve FF is insufficient. PURPOSE: To compare the effects of aerobic, resistance, flexibility, balance, and Tai Chi programs on FF in Japanese older adults. METHODS: FF was evaluated using a chair stand, arm curl, up and go, sit and reach, back scratch, functional reach, and 12-min walk. One hundred thirteen older adults (73 +/- 6 yr, 64 men, 49 women) volunteered for one of five exercise groups: aerobic (AER), resistance (RES), balance (BAL), flexibility (FLEX), and Tai Chi (T-CHI), or they were assigned to the wait-list control group (CON). Programs were performed for 12 wk, 2 d x wk(-1) (RES, BAL, FLEX, T-CHI) or 3 d x wk(-1) (AER), and 90 min x d(-1). RESULTS: Improvement in cardiorespiratory fitness was limited to AER (16%). Improvements in upper- and lower-body strength and balance/agility were outcomes of RES, BAL, and T-CHI. RES elicited the greatest upper-body strength improvement (31%), whereas BAL produced the greatest improvement in lower-body strength (40%). Improvements in balance/agility were similar across RES (10%), BAL (10%), and T-CHI (10%). Functional reach improved similarly in AER (13%), BAL (16%), and RES (15%). There were no improvements in flexibility. CONCLUSION: Results suggest that a single mode with crossover effects could address multiple components of fitness. Therefore, a well-rounded exercise program may only need to consist of two types of exercise to improve the components of functional fitness. One type should be aerobic exercise, and the second type could be chosen from RES, BAL, and T-CHI.